Bio

Bio


Dr. Nguyen is a clinician investigator. She has a large and comprehensive practice of general liver as well as liver transplant patients at Stanford University Medical Center and 3 outreach clinics in the San Jose and Los Gatos areas. Her research areas include epidemiology, clinical outcomes, and therapeutic clinical trials for chronic hepatitis B, chronic hepatitis C, liver cancer/tumors, other chronic liver diseases as cause of liver cancer such as nonalcoholic fatty liver disease and liver transplant-related issues. Her research lab includes trainees who are undergraduate students, medical students, graduate students in the Masters' in Epidemiology Program, interns/residents, and gastroenterology/hepatology fellows.

She is active in community outreach efforts locally and nationally including service as executive board of director for nonprofit organizations. She also serves in the Education and Hepatology Associate Committees for the American Association for the Study of Liver Diseases (AASLD), as member of the Steering Committee for the Hepatobiliary Neoplasia Special Interest Group at AASLD, and as member of the Editorial Board for various journals including Gastroenterology.

Clinical Focus


  • Evaluation of abnormal liver tests
  • End-stage liver disease
  • Cirrhosis
  • Chronic hepatitis B and C
  • Liver cancer and tumors
  • Community Outreach
  • Liver tumors
  • Hepatology and Liver Transplantation
  • Gastroenterology

Academic Appointments


Administrative Appointments


  • Liver Section Editor, Journal of Clinical Gastroenterology (2013 - Present)
  • Steering Committee, Hepatobiliary Neoplasia Special Interest Group, American Association for the Study of Liver Diseases (AASLD) (2014 - 2016)
  • Hepatology Associates Committee , MD Liaison, American Association for the Study of Liver Diseases (AASLD) (2013 - 2016)
  • Education Committee, American Association for the Study of Liver Diseases (AASLD) (2013 - 2016)
  • Committee Chair, Abstract Review for Chronic Hepatitis B, American Association for the Study of Liver Diseases (AASLD) (2013 - Present)
  • Executive Board of Director, Asian Health Foundation (2013 - Present)
  • Medical Advisory Board, American Liver Foundation (2013 - Present)
  • Editorial Board, Gastroenterology (2011 - 2014)
  • Abstract review member for the Hepatitis B : Epidemiology/Prevention/Control review group, American Association for the Study of Liver Diseases (AASLD) (2011 - 2013)
  • Director of Clinical Research, Pacific Health Foundation (2004 - Present)
  • Director of Continuing Medical Education, Pacific Health Foundation (2005 - 2012)
  • Editorial Board, Digestive Diseases and Sciences (2008 - Present)
  • Training and Workforce Committee, Member, American Association for the Study of Liver Diseases (AASLD) (2002 - 2004)

Honors & Awards


  • Pacific Free Clinic Physician Service Award, Cardinal Free Clinics, Stanford University School of Medicine (April 2013)
  • The Franklin Edbaugh Advising Award for Faculty, Stanford University School of Medicine (May 2013)
  • Phi Beta Kappa, University of California, Irvine (1985)
  • Magna Cum Laude, University of California, Irvine (1988)
  • Excellence in Teaching Award, University of California, San Diego, School of Medicine (1996)
  • Chief Resident, University of California, San Diego Medical Center (1996)
  • Advanced Hepatology Research Fellow Award, American Association for the Study of Liver Diseases (2001)
  • Chief Fellow in Gastroenterology and Hepatology, Stanford University Medical Center (2002)

Boards, Advisory Committees, Professional Organizations


  • See Administrative Appointment Section above, See above (2013 - Present)

Professional Education


  • Medical Education:UCSD School of Medicine (1992) CA
  • B.S., University of California, Irvine, Biological Sciences (1988)
  • M.D., Univ. of California, San Diego, Medicine (1992)
  • M.A.S., Univ. of Calif., San Francisco, Masters of Advanced Studies in Clinical Research (2004)
  • Internship:UCSD Medical Center (1995) CA
  • Residency:UCSD Medical Center (1996) CA
  • Fellowship:Stanford University School of Medicine (2002) CA
  • Board Certification: Transplant Hepatology, American Board of Internal Medicine (2010)

Community and International Work


  • Pacific Free Clinic

    Topic

    Hepatology Clinic

    Location

    Bay Area

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Outreach Liver Clinics, San Jose and Los Gatos, San Jose, Los Gatos

    Populations Served

    Patients with liver disease

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • Community education, outreach service, and research, San Jose

    Partnering Organization(s)

    Pacific Health Foundation

    Populations Served

    Understudied populations

    Location

    Bay Area

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Epidemiology and treatment outcomes of Asian patients with chronic hepatitis B and C, San Jose, Southern California, Texas

    Topic

    Ethnic differences of disease activities, treatment, and outcomes in Asian Americans

    Partnering Organization(s)

    Pacific Health Foundation

    Populations Served

    Asian Americans

    Location

    US

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Colon cancer screening in Asian Americans, San Jose

    Partnering Organization(s)

    Pacific Health Foundation

    Populations Served

    Asian Americans

    Location

    Bay Area

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Updates in Hepatology, Vietnam

    Partnering Organization(s)

    University of Michigan and Vietnamese Association for the Study of Liver Diseases

    Populations Served

    Vietnamese Hepatologists

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


For more information, please contact my lab at 650-498-5691 or liverresearch@stanford.edu.

Clinical Trials


  • Transarterial Chemoembolization vs CyberKnife for Recurrent Hepatocellular Carcinoma Not Recruiting

    Primary Objective: To compare the efficacy of TACE vs. CyberKnife SBRT in the treatment of locally recurrent HCC after initial TACE. Secondary Objectives: 1. To determine the progression-free survival of TACE vs. CyberKnife SBRT 2. To determine the overall survival of TACE vs. CyberKnife SBRT for locally recurrent HCC 3. To determine the toxicities associated with TACE or CyberKnife SBRT for the treatment of recurrent HCC.

    Stanford is currently not accepting patients for this trial. For more information, please contact Laurie Ann Columbo, (650) 736 - 0792.

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  • GS-5885 Alone or in Combination With GS-9451 With Peginterferon Alfa 2a and Ribavirin in Treatment Chronic Genotype 1 Hepatitis C Virus Not Recruiting

    This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy with GS-5885 Alone or in Combination with GS-9451 with Peginterferon Alfa 2a and Ribavirin in Treatment Nave Subjects with Chronic Genotype 1 Hepatitis C Virus Infection.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H. Nguyen, MD, 650-498-7878.

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  • Evaluation of Stereotactic Radiosurgery For Liver Malignancies Not Recruiting

    This study is intended to establish the practicality of treating cancer in the liver with precisely administered single fractions of high-energy radiation using a radiosurgical (cross-firing) technique. A second purpose is to establish a safe dose for such therapy. Finally, the efficacy of radiosurgical ablation of liver tumors, in terms of radiographic response, will be measured.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jeff Kim, (650) 498 - 7703.

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  • Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate for Treatment of Hepatitis B e Antigen-Negative Hepatitis B Recruiting

    The purpose of this study is to evaluate the safety and efficacy of tenofovir alafenamide (TAF) compared to that of tenofovir disoproxil fumarate (TDF) in treatment naive and experienced adult subjects with chronic hepatitis B virus (HBV) infection, as determined by the achievement of HBV DNA < 29 IU/mL at Week 48.

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  • Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) Ribavirin in HCV Genotype 1 Subjects Not Recruiting

    This study is to evaluate the safety, tolerability and antiviral efficacy of ledipasvir (formerly GS-5885)/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV) administered for 8 or 12 weeks of treatment in participants with chronic genotype 1 hepatitis C virus (HCV) infection who are treatment-naive and for 12 weeks in participants who had previously received a regimen containing a protease inhibitor for the treatment of HCV.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H Nguyen, 650-498-7878.

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  • Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C Not Recruiting

    This study will assess the rates of Sustained Virological Response following anti-viral therapy with Peg-Interferon plus Ribavirin in patients that have been liver transplanted with recurrent Hepatitis C and treated with Neoral or tacrolimus.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mindie Nguyen, MD, 650-498-7878.

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  • Study to Evaluate the Efficacy and Safety of Tenofovir Disoproxil Fumarate (TDF) in Combination With Peginterferon ?-2a vs Standard of Care Tenofovir Disoproxil Fumarate Monotherapy or Peginterferon ?-2a Monotherapy for 48 Weeks in Chronic Hepatitis B(CHB). Not Recruiting

    The purpose of this study is to evaluate the safety and efficacy of Tenofovir Disoproxil Fumarate (TDF) plus Peginterferon ?-2a (PEG) combination therapy versus standard of care TDF monotherapy or PEG monotherapy in non-cirrhotic CHB subjects as determined by loss of HBsAg.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mindie Nguyen, MD, 650-498-7878.

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  • Gilead Sustained Virologic Response (SVR) Registry Recruiting

    This Registry is designed to provide long term clinical and virologic follow up in subjects who have achieved sustained virologic response (SVR) while participating in a previous Gilead sponsored Hepatitis C Virus (HCV) study. This long term follow up study is observational and no treatment is provided for HCV.

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  • Safety and Efficacy Study in Subjects With Chronic HCV and Underlying Hemophilia Not Recruiting

    The primary objective for this study is to evaluate the proportion of subjects who achieve SVR12 (HCV RNA < LLOQ (target not detected) at post-treatment follow-up Week 12 in subjects with Genotype(GT)-1b, -4 and GT-2, -3

    Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H. Nguyen, MD, 650-498-7878.

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  • A Gilead Sequence Registry of Subjects Who Did Not Achieve Sustained Virologic Response Recruiting

    This Registry is designed to obtain long term data on subject who have failed to achieve sustained virologic response (SVR) while receiving at least one Gilead oral antiviral agent (OAV) in a previous Gilead-sponsored hepatitis C study.

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  • IDX719 in Combinations With Simeprevir and/or TMC647055/Ritonavir With or Without Ribavirin for 12 Weeks in Subjects With Chronic Hepatitis C Infection Recruiting

    Parts A and B of this study are designed to evaluate the safety, tolerability, efficacy and pharmacokinetic profiles of IDX719 and simeprevir when administered in combination with ribavirin (RBV) for 12 weeks in treatment-nave, Genotype 1b, 4 and 6 HCV-infected subjects. Part C of this study is designed to evaluate the safety, tolerability, efficacy and pharmacokinetic profiles of IDX719, simeprevir, TMC647055 and ritonavir (RTV) when administered in combinations with or without RBV for 12 weeks in treatment-nave or interferon/RBV-treatment relapsed, Genotype 1a and 1b HCV-infected subjects.

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  • GS 5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) in Chronic Genotype 1 Hepatitis C Virus (HCV) Infection Not Recruiting

    The purpose of this phase 2 study is to determine whether 30 mg or 90 mg of GS-5885 when given with GS-9451, Tegobuvir and Ribavirin (RBV) for 12 or 24 weeks is effective, safe and tolerable in the treatment of Chronic Genotype 1 HCV Infection.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H Nguyen, MD, 650-498-7878.

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  • Hepatitis B Virus (HBV) Viral Suppression by Entecavir in Adefovir Partial Responders Not Recruiting

    We propose a largely retrospective study with short-term prospective follow-up in a subgroup of patients who have not yet been treated with 48 weeks of entecavir following partial response to adefovir. The aim of the study is to describe sequential virologic response to adefovir and entecavir.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H. Nguyen, MD, 650-498-7878.

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  • Safety and Efficacy of Sofosbuvir/Ledipasvir Fixed-Dose Combination (FDC) With and Without Ribavirin for the Treatment of HCV Recruiting

    The purpose of this study is to evaluate the safety, tolerability and antiviral efficacy of sofosbuvir (SOF)/ledipasvir (LDV) fixed dose combination (FDC) tablets with or without ribavirin (RBV) administered for 12 and 24 weeks in treatment-naive subjects with chronic genotype 1 HCV infection.

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  • Safety and Efficacy of GS-5885/Sofosbuvir Fixed-Dose Combination Ribavirin for the Treatment of HCV Not Recruiting

    This study is to evaluate the safety, tolerability, and antiviral efficacy of GS-5885/sofosbuvir fixed dose combination (FDC) with or without ribavirin (RBV) administered for 12 or 24 weeks in treatment-experienced subjects with chronic genotype 1 hepatitis C virus (HCV) infection.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mindie H. Nguyen, MD, 650-498-7878.

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  • Registry Study for Patients With Chronic HBV Receiving Nucleotide Therapy Recruiting

    This registry will remain open for approximately 5 years. Subjects will be followed until Orthotopic Liver Transplant (OLT), resolution of liver decompensation, death, or conclusion of the registry.

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  • Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate for Treatment of Hepatitis B e Antigen-Positive Hepatitis B Recruiting

    The purpose of this study is to evaluate the safety and efficacy of tenofovir alafenamide (TAF) compared to that of tenofovir disoproxil fumarate (TDF) in treatment naive and experienced adult subjects with chronic hepatitis B virus (HBV) infection, as determined by the achievement of HBV DNA < 29 IU/mL at Week 48.

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  • Risk Factors and Molecular Genomics of U.S. Patients With Chronic Liver Disease &Hepatocellular CA Not Recruiting

    To identify risk factors for the development and diagnosis of hepatocellular CA in patients with chronic hepatitis C and to use the data to ultimately develop an effective screening program.

    Stanford is currently not accepting patients for this trial. For more information, please contact Andrea Linder, (650) 725 - 4047.

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Teaching

2013-14 Courses


Graduate and Fellowship Programs


  • Gastroenterology & Hepatology (Fellowship Program)

Publications

Journal Articles


  • Systematic review with meta-analysis: the proportion of chronic hepatitis B patients with normal alanine transaminase <= 40 IU/L and significant hepatic fibrosis ALIMENTARY PHARMACOLOGY & THERAPEUTICS Chao, D. T., Lim, J. K., Ayoub, W. S., Nguyen, L. H., Nguyen, M. H. 2014; 39 (4): 349-358

    Abstract

    Chronic hepatitis B (CHB) may lead to cirrhosis, hepatocellular carcinoma and premature death. Elevated alanine transaminase (ALT) levels ? the upper limit of normal (ULN) are a major determinant for initiating anti-viral therapy; however, ALT levels alone may not be predictive of hepatic fibrosis.To determine the proportion of CHB patients with ALT ?40IU/L and liver fibrosis stage ?2. Secondary goals include subgroup analysis by hepatitis B e antigen (HBeAg) status, high hepatitis B virus (HBV) DNA levels, Asian ethnicity, lower ULN of ?30IU/L (males) and 19IU/L (females), and advanced age.Studies identified in EMBASE and MEDLINE (1/1990-6/2012) using the search criteria: "Hepatitis B"[Mesh] OR "Hepatitis B virus"[Mesh] OR "Hepatitis B, Chronic"[Mesh])) AND "Alanine Transaminase"[Mesh]) and abstracts containing the term 'hepatitis' from recent major U.S. gastroenterology and liver society meetings were considered.Among nine studies (N=830 patients), a significant proportion (20.7%; 95% CI: 16.2-26.0%) of CHB patients with ALT levels ?40IU/L had significant fibrosis irrespective of HBeAg status, high HBV DNA levels, ethnicity or age, although this proportion may be higher in patients older than 30-40years old. The corresponding proportion was 27.8% even when the newer ULN of 30IU/L (males) and 19IU/L (females) was applied.Approximately one fifth of CHB patients with ALT ?40IU/L may have significant hepatic fibrosis. The approach to such patients should be individualised, as further evaluation and treatment may be appropriate.

    View details for DOI 10.1111/apt.12590

    View details for Web of Science ID 000329932800001

    View details for PubMedID 24387289

  • Primary surgical resection versus liver transplantation for transplant-eligible hepatocellular carcinoma patients. Digestive diseases and sciences Wong, R. J., Wantuck, J., Valenzuela, A., Ahmed, A., Bonham, C., Gallo, A., Melcher, M. L., Lutchman, G., Concepcion, W., Esquivel, C., Garcia, G., Daugherty, T., Nguyen, M. H. 2014; 59 (1): 183-191

    Abstract

    Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Existing studies comparing outcomes after liver transplantation (LT) versus surgical resection among transplant-eligible patients are conflicting.The purpose of this study was to compare long-term survival between consecutive transplant-eligible HCC patients treated with resection versus LT.The present retrospective matched case cohort study compares long-term survival outcomes between consecutive transplant-eligible HCC patients treated with resection versus LT using intention-to-treat (ITT) and as-treated models. Resection patients were matched to LT patients by age, sex, and etiology of HCC in a 1:2 ratio.The study included 171 patients (57 resection and 114 LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs. 12.9%, p<0.001) compared to LT patients. In the as-treated model of the pre-model for end stage liver disease (MELD) era, LT patients had significantly better 5-year survival compared to resection patients (100 vs. 69.5%, p=0.04), but no difference was seen in the ITT model. In the multivariate Cox proportional hazards model, inclusive of age, sex, ethnicity, tumor stage, and MELD era (pre-MELD vs. post-MELD), treatment with resection was an independent predictor of poorer survival (HR 2.72; 95% CI, 1.08-6.86).Transplant-eligible HCC patients who received LT had significantly better survival than those treated with resection, suggesting that patients who can successfully remain on LT listing and actually undergo LT have better outcomes.

    View details for DOI 10.1007/s10620-013-2947-8

    View details for PubMedID 24282054

  • Isoniazid Hepatotoxicity Requiring Liver Transplantation. Digestive diseases and sciences Sheen, E., Huang, R. J., Uribe, L. A., Nguyen, M. H. 2014

    View details for DOI 10.1007/s10620-014-3072-z

    View details for PubMedID 24573717

  • Approximately one-half of patients with early-stage hepatocellular carcinoma meeting Milan criteria did not receive local tumor destructive or curative surgery in the post-MELD exception era. Cancer Devaki, P., Wong, R. J., Marupakula, V., Nangia, S., Nguyen, L., Ditah, I. C., Ehrinpreis, M. N., Nguyen, M. H. 2014

    Abstract

    Since 2002, priority Model for End-stage Liver Disease (MELD) exception status has been given to patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. Since then, the number of liver transplantations performed in patients with HCC has increased, but to the authors' knowledge, few studies to date have examined the effect of MELD exception recommendations on therapy use and survival rates in a nationwide sample. The current study examines therapy use and long-term survival rates among patients with HCC tumors meeting the Milan criteria in the post-MELD exception era.The current study is a retrospective cohort study of 2179 patients with localized HCC meeting the Milan criteria who were registered between 2004 and 2007 in the Surveillance, Epidemiology, and End Results database.A total of 43% of patients did not receive any specific therapy. Overall, the 5-year relative survival rate for patients receiving only supportive care was dismal at 24% (95% confidence interval [95% CI], 21%-27%), whereas that for patients undergoing liver transplantation was 77% (95% CI, 71%-82%). Long-term survival was found to be dependent on age, race/ethnicity, and type of therapy received. A multivariate Cox proportional hazards model adjusted for age, race/ethnicity, and type of therapy received demonstrated that, compared with white patients, black patients had significantly poorer survival outcomes (hazards ratio, 1.23; 95% CI, 1.03-1.47 [P?=?.02]), whereas Asian/Pacific Islander patients had significantly better survival rates when compared with white patients (HR, 0.66; 95% CI, 0.57-0.77 [P?

    View details for DOI 10.1002/cncr.28639

    View details for PubMedID 24590359

  • Tenofovir is superior to entecavir for achieving complete viral suppression in HBeAg-positive chronic hepatitis B patients with high HBV DNA. Alimentary pharmacology & therapeutics Gao, L., Trinh, H. N., Li, J., Nguyen, M. H. 2014

    Abstract

    Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the two first-line anti-viral therapies for chronic hepatitis B (CHB); however, there are limited studies directly comparing their effectiveness.To compare the effectiveness of ETV and TDF in nucleos(t)ide-nave CHB patients with high hepatitis B virus (HBV) DNA levels, defined as serum HBV DNA greater than 6 log10 IU/mL.We performed a retrospective multicentre cohort study of adult CHB patients who were seen between 2009 and 2012 at four Northern California community gastroenterology and hepatology clinics.We identified 59 consecutive patients treated with TDF and 216 patients treated with ETV. Pre-treatment characteristics were similar between the two groups. Among HBeAg-negative patients, there was no significant difference in viral suppression rates between ETV and TDF (P=0.72). In contrast, among HBeAg-positive patients, those treated with TDF achieved viral suppression significantly more rapidly than those treated with ETV (P<0.0001); the Kaplan-Meier estimated probability of complete suppression was 18% vs. 11% at 6months, 51% vs. 28% at 12months and 72% vs. 39% at 18months respectively. Multivariate Cox proportional hazards analysis indicated that treatment with TDF compared to ETV was a significant predictor of viral suppression, but only for HBeAg-positive patients (HR=2.59; 95% CI 1.58-4.22; P<0.001).Tenofovir is significantly more effective than entecavir for achieving complete viral suppression in HBeAg-positive, nucleos(t)ide-nave chronic hepatitis B patients with HBV DNA greater than 6 log10 IU/mL.

    View details for DOI 10.1111/apt.12629

    View details for PubMedID 24467455

  • Similar Response to Entecavir 0.5 and 1.0 Mg in Treatment-Na < ve Chronic Hepatitis B Patients: A Case-Control Study DIGESTIVE DISEASES AND SCIENCES Ha, N. B., Ha, N. B., Chaung, K. T., Trinh, H. N., Nguyen, H. A., Nguyen, K. K., Nguyen, M. H. 2014; 59 (1): 168-173

    Abstract

    The dose recommendation for entecavir (ETV) is 0.5mg daily for treatment-nave chronic hepatitis B (CHB) patients and 1.0mg daily for lamivudine-refractory patients; however, few data are available for the efficacy of a 1.0-mg daily dose in treatment-nave CHB patients. Our goal is to examine the treatment outcome of treatment-nave patients placed on ETV 0.5mg or ETV 1.0mg daily through week 48.Cases were 40 consecutive hepatitis B e antigen (HBeAg)-positive CHB patients treated with ETV 1.0mg daily between January 2005 and September 2010, and controls were 40 consecutive CHB patients treated with ETV 0.5mg daily between January 2005 and September 2010 at three US gastroenterology/liver clinics. Controls were matched for age (5years), sex, HBeAg, and baseline hepatitis B virus (HBV) DNA (0.5 log10 IU/ml). Complete viral suppression was defined as undetectable HBV DNA by polymerase chain reaction (<100IU/ml).Both groups had similar distributions of age (3811years), male patients (55%), and mean HBV DNA (7.71.1 log10 IU/ml). The complete viral suppression rate was similar in both cases and controls through week 24 (15 vs. 15%, p=1.00) and week 48 (22 vs. 36%, p=0.17). Non-adherence was reported in three patients in the ETV 1.0mg daily cohort at week 48.There were no significant differences in the proportion of patients with complete viral suppression in patients treated with ETV 0.5mg daily or the higher daily dose of 1.0mg.

    View details for DOI 10.1007/s10620-013-2940-2

    View details for Web of Science ID 000330585500027

    View details for PubMedID 24248420

  • Review article: the epidemiology and therapy of chronic hepatitis C genotypes 4, 5 and 6 ALIMENTARY PHARMACOLOGY & THERAPEUTICS Wantuck, J. M., Ahmed, A., Nguyen, M. H. 2014; 39 (2): 137-147

    Abstract

    The global burden of hepatitis C (HCV) infection is mostly found in Africa, the Middle East and Asia, where HCV genotypes 4, 5 and 6 are common. The literature on these genotypes is sparse and this synopsis will review characteristics of patients infected with these genotypes.To review characteristics of patients infected with HCV genotypes 4, 5 and 6.PubMed search for 'hepatitis C' AND 'genotype 4', 'hepatitis C' AND 'genotype 5', and 'hepatitis C' AND 'genotype 6' was conducted and relevant articles were reviewed.Intravenous drug use is generally responsible for HCV genotype 4 infection in developed countries, but unsafe medical practices cause most cases of HCV genotypes 4, 5 and 6 in endemic countries. The sustained virological response (SVR) rate for patients with HCV genotype 4 who receive pegylated interferon and ribavirin for 48weeks ranges from 40% to 70% in various small studies. The SVR rate is in the 60-70% range for HCV genotype 5 and 70-80% range for HCV genotype 6 following 48 weeks with pegylated interferon and ribavirin. Preliminary data suggest that a shorter course of 24weeks of pegylated interferon and ribavirin may be acceptable for HCV genotype 6, with an SVR rate of approximately 70%.The current standard-of-care therapy for HCV genotypes 4, 5 and 6 is pegylated interferon and ribavirin for 48weeks. A shorter course with 24weeks of therapy may be considered for patients with genotype 6. Newer and much more effective therapies may be forthcoming in the next few years.

    View details for DOI 10.1111/apt.12551

    View details for Web of Science ID 000328283900003

    View details for PubMedID 24251930

  • Clinical Presentation and Survival of Asian and Non-Asian Patients with HCV-Related Hepatocellular Carcinoma DIGESTIVE DISEASES AND SCIENCES Yip, B., Wantuck, J. M., Kim, L. H., Wong, R. J., Ahmed, A., Garcia, G., Nguyen, M. H. 2014; 59 (1): 192-200

    Abstract

    Hepatitis C virus (HCV) is an important cause of hepatocellular carcinoma (HCC) in Asians; however, it is often overlooked due to the high prevalence of hepatitis B virus in Asians. This study examines HCV-related HCC in Asians.We conducted a retrospective cohort study of 792 consecutive Asian (n=220) and non-Asian (n=572) patients with HCV-related HCC identified at Stanford University Medical Center using International Classification of Diseases-9 diagnosis between July 1996 and June 2012.Asian patients were much older [66 (38-88) vs. 56 (31-87) years, P<0.0001] and more likely to be female (33 vs. 19%, P<0.0001). A larger proportion of Asians were diagnosed with HCC within 2years of HCV diagnosis (35 vs. 20%, P=0.001). Asian patients were more likely to undergo palliative therapy (46 vs. 28%) and less likely to be listed for liver transplantation (20 vs. 48%, P<0.001), despite similar rates of meeting Milan criteria (52 vs. 58%, P=0.16). Overall, there was a trend for higher median survival rates in Asians (30 vs. 21months, P=0.091). Asians had higher long-term survival with palliative therapy only (5-year survival: 28 vs. 10%, P<0.0001); however, survival was similar among patients listed for liver transplantation.There were distinct differences in clinical presentations of Asian and non-Asian patients with HCV-related HCC. Asians with HCV-related HCC are less likely to undergo liver transplantation and more likely to have delayed HCV diagnosis. Improved strategies in HCV screening in Asians are needed, as it may lead to earlier diagnosis and treatment of HCV infection and possible prevention of HCC development.

    View details for DOI 10.1007/s10620-013-2948-7

    View details for Web of Science ID 000330585500030

    View details for PubMedID 24282055

  • Ethnic disparities and liver transplantation rates in hepatocellular carcinoma patients in the recent era: Results from the SEER registry. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Wong, R. J., Devaki, P., Nguyen, L., Cheung, R., Nguyen, M. H. 2014

    Abstract

    Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality. Following implementation of the model for end stage liver disease (MELD) system, rates of liver transplantation (LT) for HCC patients increased. However, it is not clear if this trend continued into the recent time period. Utilizing the Surveillance, Epidemiology, and End Results 1998-2010 registry, we retrospectively analyzed trends in LT among HCC patients using three time periods: 1998-2003, 2004-2008, and 2009-2010). A total of 60,772 HCC patients were identified. With more recent time periods, the proportion of localized stage HCC increased (45.0% in 1998-2003 vs. 50.4% in 2004-2008 vs. 51.7% in 2009-2010, p<0.001). While the proportion of HCC patients within Milan criteria also increased with time (22.8% vs. 31.8% vs. 37.1%, p<0.001), the proportion of these patients receiving LT increased from 1998-2003 to 2004-2008, but decreased in 2009-2010. However, the actual frequency of LT was similar in 2004-2008 (208.2/year) and 2009-2010 (201.5/year). Multivariate logistic regression, inclusive of sex, age, ethnicity, Milan criteria, tumor stage, tumor size and number, and time periods, demonstrated a lower likelihood of LT in 2009-2010 compared to 1998-2003 (OR 0.63, 95% CI 0.57-0.71). Blacks (OR 0.48, 95% CI 0.41-0.56), Asians (OR 0.65, 95% CI 0.57-0.73), and Hispanics (OR 0.76, 95% CI 0.68-0.85) were all less likely to receive LT compared to non-Hispanic whites. Despite increasing proportion of earlier staged HCC diagnosed, LT rates are declining in the recent era. In addition, ethnic minorities were significantly less likely to receive LT. The growing imbalance between the number of transplant-eligible HCC patients and the shortage of donor livers emphasizes the need to improve donor availability and curative alternatives to LT. Liver Transpl , 2014. 2014 AASLD.

    View details for DOI 10.1002/lt.23820

    View details for PubMedID 24415542

  • Chronic Hepatitis B Management Based on Standard Guidelines in Community Primary Care and Specialty Clinics DIGESTIVE DISEASES AND SCIENCES Ku, K. C., Li, J., Ha, N. B., Martin, M., Nguyen, V. G., Nguyen, M. H. 2013; 58 (12): 3626-3633

    Abstract

    Prior studies have underlined the need for increased screening and awareness of chronic hepatitis B (CHB), especially in certain high-risk populations. However, few studies have examined the patterns of evaluation and management of CHB between primary care physicians (PCP) and specialists according to commonly-used professional guidelines. Our goal was to examine whether necessary laboratory parameters used to determine disease status and eligibility for antiviral therapy were performed by PCPs and specialists.We conducted a retrospective study of 253 treatment-nave CHB patients who were evaluated by PCP only (n=63) or by specialists (n=190) for CHB at a community multispecialty medical center between March 2007 and June 2009. Criteria for CHB management and treatment eligibility were based on the American Association for the Study of Liver Diseases 2007 guideline and the US Panel 2006 algorithm. Required parameters for optimal evaluation for CHB included hepatitis B e antigen (HBeAg), HBV DNA, and alanine aminotransferase (ALT). Preferred antiviral agents for CHB included pegylated interferon, adefovir, and entecavir.The majority of patients were Asians (90%) and male (54%) with a mean age of 4311.6years. Compared to PCPs, specialists were more likely to order laboratory testing for ALT (94 vs. 86%, P=0.05), HBeAg (67 vs. 41%, P<0.0001) and HBV DNA (83 vs. 52%, P<0.0001). The proportion of patients having all three laboratory parameters was significantly higher among those evaluated by specialists compared to PCP (62 vs. 33%, P<0.0001). A total of 55 patients were initiated on antiviral treatment (n=47 by specialists and n=6 by PCPs). Lamivudine was prescribed more often by PCPs than specialists (33 vs. 2%, P=0.05). Preferred agents were used 96% of the time by specialists compared to 67% of those treated by PCPs (P=0.05).Patients evaluated by specialists for CHB are more likely to undergo more complete laboratory evaluation and, if eligible, are also more likely to be treated with preferred longer-term agents for CHB compared to those evaluated by PCPs only. A collaborative model of care involving both PCP and specialists may further optimize management of patients with CHB.

    View details for DOI 10.1007/s10620-013-2889-1

    View details for Web of Science ID 000327456500033

    View details for PubMedID 24122622

  • Both HCV and HBV are Major Causes of Liver Cancer in Southeast Asians. Journal of immigrant and minority health Lin, H., Ha, N. B., Ahmed, A., Ayoub, W., Daugherty, T. J., Lutchman, G. A., Garcia, G., Nguyen, M. H. 2013; 15 (6): 1023-1029

    Abstract

    The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians.

    View details for DOI 10.1007/s10903-013-9871-z

    View details for PubMedID 23864445

  • Less-established risk factors are common in asian americans with hepatitis C virus: a case-controlled study. Digestive diseases and sciences Kin, K. C., Lin, B., Chaung, K. T., Ha, N. B., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Nguyen, K. K., Levitt, B. S., Da Silveira, E. B., Nguyen, M. H. 2013; 58 (11): 3342-3347

    Abstract

    The Centers for Disease Control and Prevention recommend screening for hepatitis C virus (HCV) in patients with injection drug use, blood transfusion before 1992, stigmata of liver disease, or born between 1945 and 1965. The purpose of this study was to examine risk factors for HCV acquisition in Asian Americans.This was a case-controlled study, with 471 consecutive patients testing positive for anti-HCV between January 2001 and December 2008. Controls included 471 patients with negative HCV matched at a one-to-one ratio for sex, age (5years), and ethnicity.For Asian patients, the most common risk factors were blood transfusion and acupuncture or exposure to dirty needles (27 and 20%, respectively). On multiple logistic regression, potential predictors for a positive anti-HCV test in Asians were acupuncture or exposure to dirty needles (OR=12.9, P<0.0001), body tattoo (OR=12.0, P=0.001), and history of blood transfusion (OR=5.7, P<0.0001).Acupuncture and exposure to dirty needles are independent risk factors of HCV infection. Asians coming from endemic areas should be screened for HCV even when commonly-known risk factors for Western patients are not present.

    View details for DOI 10.1007/s10620-013-2884-6

    View details for PubMedID 24081641

  • Prevalence, Risk Factors, and Disease Knowledge of Chronic Hepatitis B Infection in Vietnamese Americans in California JOURNAL OF CANCER EDUCATION Ha, N. B., Trinh, H. N., Nguyen, T. T., Leduc, T., Bui, C., Ha, N. B., Wong, C. R., Anh Thu Tran, A. T., Nguyen, M. H. 2013; 28 (2): 319-324

    Abstract

    Our goal is to examine the prevalence, risk factors, and disease knowledge of chronic hepatitis B (CHB) among Vietnamese Americans in California. We also examined treatment eligibility and linkage to care among patients who tested positive for CHB. We enrolled 717 subjects from ten different hepatitis B virus (HBV) screening events in five locations from January 2009 to June 2010 in California. HBV status was determined by hepatitis B surface antigen (HBsAg) and antibody. Data were collected by a 36-question survey. A total of 99 patients (13.8%) had positive HBsAg, especially those aged 31-40years (23.6%), and 177 (24.7%) were still susceptible to HBV infection. A significant proportion of those who were HBsAg positive or still susceptible reported a history of HBV vaccination (10 and 20%, respectively). Following adjustments for age and sex, significant predictors for HBsAg positivity were lack of healthcare coverage (OR?=?2.4, p?=?0.004), having a family history of CHB (OR?=?2.1, p?=?0.009), and prior occupational exposure (OR?=?3.0, p?=?0.007). Of those who tested positive, 13.3% met criteria for antiviral therapy, but none had been initiated on treatment. HBV prevalence in Vietnamese Americans in California was high (13.8%), especially in those between 31 and 40years of age. Patient disease and treatment knowledge was poor, as were follow-up and management of those found to have CHB and/or have indication for antiviral therapy.

    View details for DOI 10.1007/s13187-013-0466-0

    View details for Web of Science ID 000319473500017

  • Treatment eligibility of patients with chronic hepatitis B initially ineligible for therapy. Clinical gastroenterology and hepatology Nguyen, N. H., Nguyen, V., Trinh, H. N., Lin, B., Nguyen, M. H. 2013; 11 (5): 565-571

    Abstract

    Chronic hepatitis B (CHB) is a dynamic disease, therefore patients initially ineligible for treatment, based on current guidelines, often become eligible at some point during their follow-up evaluation. We investigated the reasons for this change and developed a timeline for treatment eligibility for this population.We performed a retrospective cohort study of 245 consecutive treatment-naive, community-based patients with CHB who were not eligible for treatment when they first presented, from March 2007 through June 2010 (mean age, 44 y, almost all Asian). The patients were followed up for a median period of 26 months, receiving standard laboratory tests. They were treated according to US panel 2008 and American Association for Liver Disease (AASLD) 2009 guidelines.Fifty-four patients (22%) became eligible for treatment during the follow-up period; most of these (n = 47; 87%) were based on only the US Panel algorithm and the rest were based on AASLD guidelines (n = 7; 13%). Six percent of patients met the treatment criteria at 1 year, 18% at 2 years, and 29% at 3 years. Among hepatitis B e antigen-positive patients with levels of hepatitis B virus (HBV) DNA greater than 3 log IU/mL at baseline, 11% met treatment criteria at 1 year, 52% at 2 years, and 80% at 3 years. Based on Cox multivariate analysis, which included age; sex; and levels of hepatitis B e antigen, alanine aminotransferase, and HBV DNA, an increase in HBV DNA level was the only factor from the US panel associated with treatment eligibility (hazard ratio, 1.43; P < .001), and an increase in alanine aminotransferase was the only factor associated with treatment eligibility from the AASLD guidelines (hazard ratio, 1.03; P = .001).Although most patients with CHB who initially are not eligible for treatment remain ineligible, almost 30% become eligible within 3 years. These findings indicate the importance of carefully following disease status in patients with CHB.

    View details for DOI 10.1016/j.cgh.2012.12.028

    View details for PubMedID 23333662

  • Systematic review: Asian patients with chronic hepatitis C infection. Alimentary pharmacology & therapeutics Nguyen, L. H., Nguyen, M. H. 2013; 37 (10): 921-936

    Abstract

    Chronic hepatitis C (CHC) infection is a risk factor for both the development of end-stage liver disease and hepatocellular carcinoma (HCC). Globally, approximately 170 million people are chronically infected with the hepatitis C virus (HCV), and the majority of these individuals come from the western Pacific and Southeast Asia regions (94.6 million persons combined). CHC is an understudied and underappreciated health problem in many Asian countries and in the US, where Asians represent one of the fastest growing groups of new Americans.To perform a systematic review of the current literature on the epidemiology, diagnosis and screening, clinical characteristics and response to anti-viral therapy of Asians with CHC.Using a PubMed search of 'hepatitis C' and 'Asia,' 341 original manuscripts published in peer-reviewed journals were identified, and 99 were selected based on their relevance.Many Asian CHC patients do not have easily identifiable risk factors and may be underdiagnosed. Rates of HCV infection in Asians on community screening in the US are unexpectedly high, and there is a high prevalence of HCV genotype 6 in Southeast Asia and Southern China. HCV-infected Asians tend to present at older age and may have higher risk of HCC; however, they respond better to anti-viral therapy than non-Asians across all HCV genotypes.Given the high HCV endemicity in Asia, lack of identifiable risk factors and favourable treatment response rates in Asians, we advocate the screening for HCV infection of all Asians who come from areas where HCV prevalence is ?2%.

    View details for DOI 10.1111/apt.12300

    View details for PubMedID 23557103

  • Low incidence of hepatitis B e antigen seroconversion in patients treated with oral nucleos(t)ides in routine practice. Journal of gastroenterology and hepatology Lin, B., Ha, N. B., Liu, A., Trinh, H. N., Nguyen, H. A., Nguyen, K. K., Ahmed, A., Keeffe, E. B., Garcia, R. T., Garcia, G., Nguyen, M. H. 2013; 28 (5): 855-860

    Abstract

    Treatment end-point of therapy for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) includes HBeAg seroconversion, which ranges from 15% to 22% after 1 year of oral nucleos(t)ides according to clinical trials. Our goal was to determine the incidence and predictors of HBeAg seroconversion in such patients in routine clinical practice because they may differ than reported rates.We conducted a retrospective cohort study of 333 consecutive treatment-nave HBeAg-positive patients who were treated for CHB between 1/2000 and 6/2010 at three gastroenterology and liver clinics in the USA. Primary study end-point was HBeAg seroconversion-loss of HBeAg and antibody to HBeAg (anti-HBe) development.The majority of patients were Asian (96%). Median treatment duration prior to HBeAg seroconversion was 50 (range 26-52) weeks. Of the 333 study patients, 25% received lamivudine, 16% adefovir, 51% entecavir, and 8% tenofovir. HBeAg seroconversion at month 12 was 8.2%. On multivariate analysis inclusive of age, gender, and antiviral agents, independent predictors for HBeAg seroconversion at month 12 were hepatitis B virus DNA ?1.5??upper normal limit (HR?=?2.86 [1.05-7.81], P?=?0.040), but not the choice of nucleos(t)ides.The HBeAg seroconversion rate seen in clinical settings for oral nucleos(t)ides appears much lower than those reported in pivotal trials, especially in patients with lower ALT and higher HBV DNA levels. HBeAg-positive patients should be counseled about the high possibility of the long treatment duration required to achieve recommended treatment end-points.

    View details for DOI 10.1111/jgh.12108

    View details for PubMedID 23278507

  • Response to Higher Dose of Entecavir 1.0 mg Daily in Patients With Partial Response to Entecavir 0.5 mg Daily JOURNAL OF CLINICAL GASTROENTEROLOGY Ha, N. B., Ha, N. B., Trinh, H. N., Nguyen, H. A., Nguyen, K. K., Nguyen, M. H. 2013; 47 (5): 461-465

    Abstract

    Despite its high potency against hepatitis B virus (HBV), entecavir (ETV) 0.5 mg daily may not be sufficient to induce complete viral suppression in some patients with very high pretreatment viremia. It is not clear whether ETV 1.0 mg daily would have additive effect in such patients.Our goal was to examine virologic outcome of ETV 1.0 mg daily in patients with partial response to ETV 0.5 mg daily.We retrospectively studied 31 consecutive treatment-naive patients who were switched to ETV 1.0 mg daily after partial response [reduction of HBV DNA ?2 log10 IU/mL but with detectable HBV DNA levels (>100 IU/mL) after 24 weeks of therapy or longer] with ETV 0.5 mg daily from January 2005 to January 2010 at 2 clinics.All patients were Asians and 90% had positive hepatitis B e antigen. Mean HBV DNA was 8.040.65 log10 IU/mL before therapy and 3.640.91 log10 IU/mL at the time of switch. Overall rate of complete viral suppression were 29% (n=9/31) after 24 weeks of ETV 1.0 mg daily and 22% (n=5/23) after 48 weeks. Complete viral suppression after 24 weeks with ETV 1.0 mg daily was significantly higher in patients with lower HBV DNA (<3 log10 IU/mL) at time of switch: 75% versus 5%, P<0.0001.The majority of patients with partial response to ETV 0.5 mg daily did not achieve complete viral suppression with the higher dose of ETV 1.0 mg daily except those with minimal residual viremia (HBV DNA <3 log10 IU/mL).

    View details for DOI 10.1097/MCG.0b013e318266fd31

    View details for Web of Science ID 000317477400021

    View details for PubMedID 23090046

  • High Proportion of Hepatitis C Virus in Community Asian American Patients With Non-Liver-related Complaints JOURNAL OF CLINICAL GASTROENTEROLOGY Kin, K. C., Lin, B., Ha, N. B., Chaung, K. T., Trinh, H. N., Garcia, R. T., Nguyen, K. K., Nguyen, H. A., Da Silveira, E. B., Levitt, B. S., Nguyen, M. H. 2013; 47 (4): 367-371

    Abstract

    Besides United States population born between 1945 and 1965, screening for hepatitis C virus (HCV) is not recommended for the general US population. However, HCV may be more prevalent in certain subgroups and screening may be warranted. The goal of this study was to examine the proportion of HCV in a large sample of community Asian American patients presenting for non-liver-related complaints.We conducted a cross-sectional study of 1246 patients tested for hepatitis C virus antibodies (anti-HCV) referred to 2 gastroenterology clinics for non-liver-related gastrointestinal reasons between January 2001 and February 2011. We determined HCV status and patient history via electronic medical record review.Of the 1246 study patients tested for anti-HCV, the majority were Asian (81.4%) and 29 Asian patients (2.9%) had positive anti-HCV. HCV proportion in the remaining 232 non-Asians (non-Hispanic whites and Hispanics) was 1.7%. Asians with positive anti-HCV were more likely to have had blood transfusions (31.0% vs. 6.6%, P<0.0001) or acupuncture (10.3% vs. 1.5%, P<0.0001). Of the 976 Asian patients with hepatitis B surface antigen testing, 38 (3.9%) also had detectable hepatitis B surface antigen.Among patients seen at community gastroenterology clinics for non-liver-related reasons, HCV proportion was 1.7% for non-Asians and 2.9% for Asians. Screening for HCV should be offered to high-risk patients presenting to gastroenterology clinics with unrelated gastrointestinal complaints.

    View details for DOI 10.1097/MCG.0b013e3182688b3e

    View details for Web of Science ID 000316111800014

    View details for PubMedID 23090039

  • Low hepatitis B envelope antigen seroconversion rate in chronic hepatitis B patients on long-term entecavir 0.5 mg daily in routine clinical practice EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY Liu, A., Ha, N. B., Lin, B., Yip, B., Trinh, H. N., Nguyen, H. A., Nguyen, K. K., Ahmed, A., Garcia, G., Nguyen, M. H. 2013; 25 (3): 338-343

    Abstract

    Data from registration trials with highly selective patients have shown that hepatitis B envelope antigen (HBeAg)-positive patients with chronic hepatitis B respond well to entecavir (ETV) 0.5 mg daily, with an HBeAg seroconversion rate of 21% at 12 months. However, there are varying data on the treatment outcomes of ETV 0.5 mg daily in routine clinical settings, with seroconversion rates at 12 months ranging from 8 to 48% in studies limited to 44-90 patients from centers in Asia, Europe, and South America.In the present study, we examined long-term treatment efficacy and tolerability in 136 consecutive treatment-naive HBeAg-positive chronic hepatitis B patients treated between January 2005 and January 2011 with ETV 0.5 mg daily at community clinics and tertiary centers in the USA. The primary study end point was HBeAg seroconversion.Sixty-one percent of HBeAg-positive patients were men, mean age 39 12 years, median hepatitis B virus DNA 7.48 (3.7-9.8) log10 IU/ml, median alanine aminotransferase 67 (14-1077) U/l, and median treatment duration 18 (6-60) months. At months 12, 24, and 36, complete viral suppression rates were 41, 66, and 85% and HBeAg seroconversion rates were 4.8, 20, and 30%, respectively. No patients experienced adverse events or developed genotypic resistance to ETV.In clinical settings, ETV is highly tolerable and potent at suppressing hepatitis B viremia; however, the rates of HBeAg seroconversion appear to be much lower than those reported, highlighting the importance of appropriate counseling and planning for long-term therapy.

    View details for DOI 10.1097/MEG.0b013e32835b3677

    View details for Web of Science ID 000314633700011

    View details for PubMedID 23169311

  • Precore and basal core promoter mutations in Asian American patients with hepatitis B e antigen-positive chronic hepatitis B ALIMENTARY PHARMACOLOGY & THERAPEUTICS VuTien, P., Trinh, H. N., Nguyen, K., Garcia, R. T., Nguyen, H. A., Levitt, B. S., Nguyen, L., Ha, N. B., Ahmed, A., Daugherty, T., Garcia, G., Nguyen, M. H. 2013; 37 (4): 464-472

    Abstract

    Prior studies have shown that precore mutations abolish and basal core promoter (BCP) mutations down-regulate hepatitis B e antigen (HBeAg) production. Thus, the presence of precore and BCP mutations in HBeAg-positive patients indicates an infection with a mixed viral population of wild-type and precore and/or BCP mutant hepatitis B virus (HBV). To date, there has been limited study of the prevalence and clinical significance of precore and BCP mutations in patients with HBeAg-positive chronic hepatitis B.To determine the prevalence, predictors and clinical characteristics of mixed wild-type and precore/BCP HBV infection, through a cross-sectional study, in a US cohort of patients with chronic hepatitis B.We conducted a retrospective study of 828 chronic hepatitis B patients with HBV genotype and mutation panel testing seen at three US gastroenterology and liver clinics from June 2005 to September 2009.A majority of our patients (92.3%) were either Vietnamese or Chinese American. In the HBeAg-positive cohort, 17% of patients had precore mutations only, 28% had BCP mutations only and 5% had both BCP and precore mutations. On multivariate analyses, HBV genotype C, increasing age, lower HBV DNA level and an ALT quotient >2 were independent predictors for the presence of precore and/or BCP mutations.The current distinction and management recommendations for HBeAg-positive vs. HBeAg-negative patients with chronic hepatitis B should be reassessed. Additional biomarkers and treatment endpoints should be studied for their usefulness in predicting continued viral suppression after treatment discontinuation.

    View details for DOI 10.1111/apt.12193

    View details for Web of Science ID 000313891900011

    View details for PubMedID 23278246

  • Hepatocellular Carcinoma Incidence in Noncirrhotic Patients With Chronic Hepatitis B and Patients With Cirrhosis of All Etiologies. Journal of clinical gastroenterology Do, A. L., Wong, C. R., Nguyen, L. H., Nguyen, V. G., Trinh, H., Nguyen, M. H. 2013

    Abstract

    Hepatocellular carcinoma (HCC) causes approximately a half million deaths annually with the majority related to chronic hepatitis B (CHB) and cirrhosis. Results on HCC incidence in CHB patients without cirrhosis are conflicting.This study aimed to examine HCC incidence in 2 high-risk groups: (1) patients with noncirrhotic CHB and 45 years of age or older; and (2) patients with cirrhosis of all etiologies and any age.Through electronic query using ICD-9 diagnosis codes for CHB and cirrhosis (070.32 and 571.5, respectively) between January 2001 and January 2008, a total of 949 patients with 12 months of follow-up or longer were identified and reviewed. Over 4231.5 person-years of observation, HCC developed in 15 of the 741 noncirrhotic CHB patients and 30 of the 208 cirrhotic patients. Male and female noncirrhotic CHB patients had significantly lower annual HCC incidences than those found in male and female patients with cirrhosis regardless of etiologies (0.7% vs. 4.1%, P<0.0001 and 0.1% vs. 2.7%, P<0.0001). Annual HCC incidence increased significantly with age in both sexes of noncirrhotic CHB patients. In noncirrhotic CHB patients, annual HCC incidence was very low in young females, but increased to 0.3% to 0.4% in females 55 years of age or older. An HCC incidence rate of 1.1% per year was seen in noncirrhotic CHB men aged 55 or older.Although annual HCC incidence in cirrhotic patients did not differ significantly among different age groups, rates among noncirrhotic patients were significantly higher in older patients and up to 1.1% in males above 55 years.

    View details for DOI 10.1097/MCG.0000000000000015

    View details for PubMedID 24201999

  • Prevention of Mother-to-Child Transmission of Hepatitis B Virus: Is Elective Cesarean Section in Highly Viremic Mothers an Appropriate Adjunct to Immunoprophylaxis? Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Nguyen, L. H., Nguyen, M. H. 2013

    View details for PubMedID 23639607

  • Histologic Changes in Liver Tissues from Patients with Chronic Hepatitis B and Minimal Increases in Levels of Alanine Aminotransferase: a Meta-analysis and Systematic Review. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Nguyen, L. H., Chao, D., Lim, J. K., Ayoub, W., Nguyen, M. H. 2013

    Abstract

    Level of alanine aminotransferase (ALT) is a marker of hepatitis B severity and response to treatment. However, measurements ALT level may be of limited utility during the immune clearance phase of chronic hepatitis B (CHB), and can be affected by age, weight, and concomitant liver disease. We performed a literature review to determine the proportion of CHB patients with levels of ALT 1-2-fold the upper limit of normal who also had significant underlying liver fibrosis (stage ? 2).We performed Medline search of original manuscripts published before June 2012, their references; we also searched abstracts from the 2010 and 2011 Annual Meetings of the AASLD and 2011 and 2012 Digestive Disease Weeks. Studies were included that had ?20 consecutive treatment-nave CHB patients with ?6 months follow up, histologic data, and levels of ALT 1-2-fold the upper limit of normal. Study heterogeneity was assessed by Forest plot and Q and I2 analyses. Sensitivity was measured using 1-study removed analysis.Our analysis included 8 manuscripts and 1 abstract, comprising 683 patients. Based on random-effects modeling, 48% of patients had stage ? 2 fibrosis (95% confidence interval, 36%-61%). Upon sensitivity analysis, exclusion of the study that caused the greatest deflection of the pooled estimate produced a revised estimate of 43%. A subgroup of hepatitis B e-antigen-positive and -negative patients (n=168 and 170, respectively) revealed similar rates of fibrosis (41% vs 47%, P=non-significant).Despite heterogeneity in the literature, a substantial proportion of patients with slight increases in level of ALT have significant fibrosis. Given the possibility of advanced liver disease, the threshold for antiviral treatment must be individualized. Further studies are needed to investigate patients with modest increases in ALT.

    View details for DOI 10.1016/j.cgh.2013.11.038

    View details for PubMedID 24361419

  • Mutations in HBV DNA Polymerase Associated with Nucleos(t)ide resistance are Rare in Treatment-nave Patients. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Vutien, P., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Levitt, B. S., Nguyen, K., da Silveira, E., Daugherty, T., Ahmed, A., Garcia, G., Lutchman, G. A., Nguyen, M. H. 2013

    Abstract

    Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment nave patients. However, most of these studies used either direct PCR sequencing, which detects these mutations with low levels of sensitivity, or patient cohorts that were not well characterized. We investigated the prevalence of HBV mutations in DNA polymerase using a line probe assay.In a prospective, cross-sectional study, we enrolled 198 treatment-nave patients with chronic hepatitis B (52.5% male, mean age 41 y), from February 2009 through May 2011, from 3 gastroenterology and liver clinics in Northern California. Exclusion criteria included infection with hepatitis C or D viruses or HIV. All patients completed a questionnaire (to determine demographics, history of liver disease, prior treatments, family medical history, drug and alcohol use, and environmental risk factors for hepatitis) that was administered by a research coordinator; mutations in HBV DNA polymerase were detected using the INNO-LiPA HBV DR v.3 assay.Most patients were Vietnamese (48.5%) or Chinese (36.4%), and were infected with HBV genotypes B (67.5%) or C (24.2%). Mutations in HBV DNA polymerase were found in 2 patients (1%): rtI233V (n = 1) and rtM250M/L (n = 1).In a multicenter prospective study of treatment-nave patients with chronic hepatitis B, we detected mutations in HBV DNA polymerase in only 1%. Given the low prevalence of these mutations and the uncertain clinical significance of such quasi-species, routine HBV DNA polymerase mutation analysis cannot be recommended before initiation of antiviral therapy for treatment-nave patients with chronic hepatitis B. The analysis requires further molecular and clinical studies.

    View details for DOI 10.1016/j.cgh.2013.11.036

    View details for PubMedID 24342744

  • Increased Long-Term Survival Among Patients with Hepatocellular Carcinoma After Implementation of Model for End-Stage Liver Disease Score. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Wong, R. J., Devaki, P., Nguyen, L., Cheung, R., Cho-Phan, C., Nguyen, M. H. 2013

    Abstract

    Assignment of model for end-stage liver disease (MELD) exception points to patients with hepatocellular carcinoma (HCC) who fall within Milan criteria, which began in 2003, increases their priority on liver transplantation waitlists. However, little is known about how this change affected survival of all patients with HCC (transplant eligible and ineligible). We compared long-term survival of HCC patients before and after this change.We performed a large population-based cohort study using the Surveillance, Epidemiology, and End Results cancer registry to investigate survival times of patients with HCC before those who met the Milan criteria were given MELD exception points (1998-2003) and afterward (2004-2010), using Kaplan Meier methods. Multivariate Cox proportional hazards models evaluated independent predictors of survival.During 2004-2010, a significantly higher percentage of patients with HCC survived for 5 years compared to 1998-2003 (21.9% vs 13.0%, P<.001). This difference remained significant among all treatment groups (no therapy: 15.2% vs 10.2%, P<0.001; local tumor destruction: 37.6% vs 22.1%, P<0.001; resection: 55.5% vs 39.2%, P<0.001; transplantation: 77.2% vs 73.1%, P =0.12). Multivariate Cox proportional hazards models, inclusive of sex, age, ethnicity, Milan criteria, number and stage of tumor, and time period, showed increased survival of patients during 2004-2010 (hazard ratio [HR], 0.87; 95% confidence interval, 0.83-0.91; P<.001). Compared to non-Hispanic whites, Asians (HR, 0.81; 95% CI, 0.77-0.86; P<.001) and Hispanics (HR, 0.89, 95% CI, 0.84-0.95; P<.001) had longer survival times, whereas blacks had a trend toward shorter survival times (HR, 1.05; 95% CI 0.98-1.13; P=.16).Patients with HCC who met Milan criteria had significantly longer survival times after implementation of the MELD exception points, regardless of sex or ethnicity. Blacks continued to have the lowest rates of 5 year survival.

    View details for DOI 10.1016/j.cgh.2013.12.008

    View details for PubMedID 24361414

  • Incidence of Hepatocellular Carcinoma Among US Patients With Cirrhosis of Viral or Nonviral Etiologies CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Mair, R. D., Valenzuela, A., Ha, N. B., Ayoub, W. S., Daugherty, T., Lutchman, G. A., Garcia, G., Ahmed, A., Nguyen, M. H. 2012; 10 (12): 1412-1417

    Abstract

    We aimed to identify risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis in the United States. We performed a prospective study to identify associations between etiologies of cirrhosis and ethnicity with HCC incidence.We used convenience sampling to select a cohort of 379 patients with cirrhosis who visited the liver clinic at the Stanford University Medical Center from 2001 to 2009 (65% male, 75% white or Hispanic, and 20% Asian). Study end points were HCC diagnosis by histology or noninvasive criteria, liver transplantation, or last screening without HCC. Patients were followed up, with ultrasound or computed tomographic imaging analyses and measurements of serum levels of ?-fetoprotein, approximately every 6 months, for a median time of 34 months (range, 6-99 mo).The etiologies of cirrhosis in the cohort were 68% hepatitis C, 7% hepatitis B, and 25% nonviral. Forty-four patients (12%) were diagnosed with HCC during the follow-up period. Patients with cirrhosis related to viral hepatitis had a statistically significantly higher incidence of HCC than those with nonviral diseases in Kaplan-Meier analysis (P = .04). There was no statistically significant difference in HCC incidence between Asian and non-Asian patients. In a multivariate Cox proportional hazards model that included age, sex, ethnicity, etiology, and Child-Pugh-Turcotte score, viral cirrhosis was associated significantly with HCC, compared with nonviral cirrhosis (hazard ratio, 3.6; 95% confidence interval, 1.3-10.1; P = .02) but Asian ethnicity was not.In a diverse cohort of patients in the United States with cirrhosis, a viral etiology of cirrhosis was associated with increased incidence of HCC, but Asian ethnicity was not. These findings indicate the importance of cirrhosis etiology in determining risk for HCC.

    View details for DOI 10.1016/j.cgh.2012.08.011

    View details for Web of Science ID 000312265900021

    View details for PubMedID 22902757

  • High Frequency of Recurrent Viremia After Hepatitis B e Antigen Seroconversion and Consolidation Therapy JOURNAL OF CLINICAL GASTROENTEROLOGY Chaung, K. T., Ha, N. B., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Nguyen, K. K., Garcia, G., Ahmed, A., Keeffe, E. B., Nguyen, M. H. 2012; 46 (10): 865-870

    Abstract

    The primary treatment endpoint for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is HBeAg seroconversion; however, data on the durability of response are inconsistent.Our goal was to investigate the rate of recurrent viremia after HBeAg seroconversion and subsequent discontinuation of therapy.We retrospectively studied 88 consecutive Asian American patients who achieved HBeAg seroconversion [loss of HBeAg and development of antibody to HBeAg (anti-HBe)] among 458 HBeAg-positive patients who received oral antiviral therapy at 3 US clinics between March 1998 and November 2010. Recurrent viremia was defined as reappearance of detectable serum hepatitis B virus DNA (>100 IU/mL) on 2 consecutive laboratory tests from previously undetectable levels.Antiviral medications used at the time of HBeAg seroconversion included: lamivudine (23%), adefovir (34%), entecavir (36%), tenofovir (4%), and combination therapy (3%). Antiviral therapy was continued after HBeAg seroconversion in 49 patients (group I) and discontinued in the other 39 patients after consolidation therapy [median=12 months (range, 1 to 55 mo)] (group II). No patients in group I experienced recurrent viremia, whereas 90% in group II did. Elevated alanine aminotransferase also occurred in 38% of group II patients [median peak alanine aminotransferase 249 IU/mL (range, 93 to 1070 IU/mL)].Despite consolidation therapy, almost all patients who discontinued therapy after achieving HBeAg seroconversion and complete viral suppression experienced recurrent viremia, and close to half also experienced biochemical flares. HBeAg seroconversion does not seem to be a durable treatment endpoint for many patients, and they should be monitored carefully for virologic relapse and biochemical flares if antiviral therapy is withdrawn.

    View details for DOI 10.1097/MCG.0b013e31825ceed9

    View details for Web of Science ID 000312953400018

    View details for PubMedID 22941429

  • Tenofovir Monotherapy and Tenofovir Plus Entecavir Combination as Rescue Therapy for Entecavir Partial Responders DIGESTIVE DISEASES AND SCIENCES Yip, B., Chaung, K., Wong, C. R., Trinh, H. N., Nguyen, H. A., Ahmed, A., Cheung, R., Nguyen, M. H. 2012; 57 (11): 3011-3016

    Abstract

    Despite high potency, a significant proportion of patients treated with entecavir achieve only partial viral suppression. Our goal was to examine the complete viral suppression rate (undetectable HBV DNA PCR levels) with alternative therapies in such patients.We retrospectively studied 42 consecutive patients with partial response to entecavir (detectable HBV DNA at ?12 months of therapy) who were treated at three clinics with rescue therapies: entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n = 31). Antiviral resistance was excluded by negative mutation analysis and/or absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir).All patients were Asian and 57 % were male with a median age of 36 (22-64) years. Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %). Almost all patients (95 %) had positive HBeAg. Overall, the complete viral suppression rate was 79 %, and the alanine aminotransferase normalization rate was 83 % in entecavir partial responders after 6 months on rescue therapies. Cumulative complete viral suppression rates were significantly different (P = 0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20 vs. 100 vs. 97 %). All three patients without complete viral suppression on entecavir + adefovir became aviremic 6 months after switching to entecavir + tenofovir.Virologic response to entecavir + tenofovir combination therapy and tenofovir monotherapy appeared to be similar in most patients, but not with the entecavir + adefovir combination.

    View details for DOI 10.1007/s10620-012-2402-2

    View details for Web of Science ID 000309867800051

    View details for PubMedID 23010744

  • Undertreatment of Asian Chronic Hepatitis B Patients on the Basis of Standard Guidelines: A Community-Based Study DIGESTIVE DISEASES AND SCIENCES Zhang, S., Ristau, J. T., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Nguyen, M. H. 2012; 57 (5): 1373-1383

    Abstract

    Previous studies have found that a major proportion of patients with chronic hepatitis B (CHB) do not receive antiviral therapy. The objective of this study was to characterize treatment eligibility on the basis of current guidelines, determine whether eligible patients actually receive treatment, and examine associated predictors.We conducted a retrospective study of patients who were evaluated for CHB at two community gastroenterology clinics between April 2007 and February 2009. Using criteria published by the American Association for the Study of Liver Diseases (AASLD) in 2007-2009 and by a panel of US hepatologists (US Panel) in 2006-2008, treatment eligibility was determined for the patients.Of 612 consecutive CHB patients included, mean age was 4413years, 54% were male, and 99% were Asian. Half (51%) were eligible for treatment on the basis of the US Panel algorithm and 47% of these patients also met AASLD treatment criteria. Overall, antiviral therapy was initiated for 50% of eligible patients: 72% of AASLD-eligible patients and 29% of patients who were US Panel-eligible only. Independent predictors for actual treatment initiation were higher ALT for AASLD-eligible patients and higher ALT and older age for patients who were US Panel-eligible only. The leading reasons for nontreatment were further observation recommended by the physician, followed by loss of follow-up and patient refusal.Approximately half of the CHB patients evaluated at community referral clinics met treatment criteria of at least one guideline; however, only about half received antiviral therapy within 12months of presentation. Further studies are needed to optimize treatment of eligible CHB patients.

    View details for DOI 10.1007/s10620-012-2137-0

    View details for Web of Science ID 000303385100034

    View details for PubMedID 22466077

  • Risk factors for hepatocellular carcinoma in patients with chronic liver disease: a case-control study CANCER CAUSES & CONTROL Ha, N. B., Ha, N. B., Ahmed, A., Ayoub, W., Daugherty, T. J., Chang, E. T., Lutchman, G. A., Garcia, G., Cooper, A. D., Keeffe, E. B., Nguyen, M. H. 2012; 23 (3): 455-462

    Abstract

    The majority of data on risk factors (RFs) for hepatocellular carcinoma (HCC) comes from studies involving populations without underlying liver disease. It is important to evaluate RFs for HCC in patients with chronic liver disease since HCC rarely occurs in those without underlying liver disease. We conducted a hospital-based case-control study of 259 incident HCC cases and 781 controls by convenience sampling between 02/2001 and 12/2009 from the liver clinic at Stanford University Medical Center. The study population was 41% White, 14% Hispanic, 3% African American, 40% Asian American, and 2% other race/ethnicity. RFs were examined through medical records and an in-person questionnaire. Alcohol and tobacco use was calculated by cumulative grams of alcohol or cumulative pack(s) of cigarette consumed over one's lifetime. Diabetes mellitus (DM) was defined by random glucose level of ?200mg/dL. RFs were evaluated using multivariate logistic regression. Independent predictors of HCC risk, after mutual adjustment and additional control for alcohol use, etiology of liver diseases, and DM, included age >40 (OR=8.5 [2.6-28.3]), male gender (OR=3.5 [2.2-5.8]), presence of cirrhosis (OR=2.8 [1.6-4.9]), Asian ethnicity (OR=2.8 [1.8-4.6]), AFP>50 (OR=4.2 [2.6-6.8]), and cumulative lifetime tobacco use of >11,000 packs (OR=1.7 [1.0-2.9]). Heavy prolonged cigarette smoking, but not alcohol use, was a significant independent predictor for HCC in patients with underlying liver disease. Besides older age, male gender, presence of cirrhosis, and elevated AFP, Asian ethnicity and heavy cumulative tobacco use are strong independent predictors of HCC.

    View details for DOI 10.1007/s10552-012-9895-z

    View details for Web of Science ID 000300891100006

    View details for PubMedID 22258434

  • Prospective study of risk factors for hepatitis C virus acquisition by Caucasian, Hispanic, and Asian American patients JOURNAL OF VIRAL HEPATITIS Ho, E. Y., Ha, N. B., Ahmed, A., Ayoub, W., Daugherty, T., Garcia, G., Cooper, A., Keeffe, E. B., Nguyen, M. H. 2012; 19 (2): E105-E111

    Abstract

    Commonly known risk factors for infection with hepatitis C virus (HCV) include blood transfusion, injection drug use, intranasal cocaine use, and body tattoos. We hypothesized that Asian Americans infected with HCV may not identify with these established risk factors present in Caucasians and Hispanics, and our aim was to conduct a survey of risk factors in HCV-infected patients in these ethnic groups. In this prospective study, 494 patients infected with HCV completed a detailed risk assessment questionnaire at a liver centre in Northern California from 2001 to 2008. Among subjects participating in this study, 55% identified themselves as Caucasian, 20% as Hispanic, and 25% as Asian. Asian Americans were older, less likely to smoke or consume alcohol, and have a family history of cancer compared with Caucasians and Hispanics. The laboratory profiles were similar, and genotype 1 was the most common infection in all groups (74-75%). The great majority of Caucasians (94%) and Hispanics (86%) identified with commonly known risk factors, which was in contrast to 67% of Asians (P < 0.0001). The most common risk factors in Asians were blood transfusions (50%) and acupuncture (50%). Furthermore, 74% of Caucasians and 66% of Hispanics identified more than one major risk factor, while only 20% of Asians reported having more than one risk factor (P < 0.0001). Survey for established risk factors for acquisition of HCV may be more appropriate for risk assessment of Caucasians and Hispanics, but not for Asian Americans. These findings may guide the development of HCV screening in our increasingly diverse population.

    View details for DOI 10.1111/j.1365-2893.2011.01513.x

    View details for Web of Science ID 000299097400014

    View details for PubMedID 22239506

  • Ethnic differences in viral dominance patterns in patients with hepatitis B virus and hepatitis C virus dual infection Hepatology Nguyen LH, Nguyen MH 2012; 55: 1640
  • High Rate of Complete Viral Suppression With Combination Therapy in Patients With Chronic Hepatitis B and Prior Treatment Failure JOURNAL OF CLINICAL GASTROENTEROLOGY Wong, C. R., Trinh, H. N., Yip, B., Nguyen, H. A., Garcia, R. T., Ahmed, A., Keeffe, E. B., Nguyen, M. H. 2011; 45 (10): 900-905

    Abstract

    Combination therapy for chronic hepatitis B virus (HBV) infection is recommended for patients with antiviral resistance (AVR) or partial response (PR) to earlier antiviral therapy; however, data on outcomes are limited.To determine the rate of complete viral suppression (CVS) with combination therapy and to compare CVS among different indications and treatment regimens.A cohort of 109 consecutive patients with chronic hepatitis B from 3 liver clinics in Northern California was retrospectively studied. All patients started combination therapy between April 2004 and August 2009 for the following indications: AVR (n = 29), PR (n = 60), or others (n = 20). Combination treatments included lamivudine (LAM), adefovir (ADV), telbivudine (LdT), entecavir (ETV), tenofovir (TDF), and emtricitabine (FTC). CVS was defined as undetectable serum HBV DNA <100 IU/mL.Among the patients, who were nearly all Asian (99%), 73% had ? 2 prior treatments and 82% had treatment failure (AVR or PR). Median treatment duration of combination therapy was 21 months (range, 6 to 50 mo). The majority (77%) achieved CVS after 6 months of various combination regimens: 80% for ETV+TDF, 76% for TDF+LAM or FTC or LdT, 75% for ETV+ADV, and 69% for ADV+LAM or LdT (P = 0.86). After 6 months of therapy, CVS was observed in a similar proportion of patients treated for PR and AVR (72% and 74%, respectively).Although the majority of 109 treatment-experienced patients had prior treatment failure, high rates of CVS were rapidly achieved and did not significantly differ between indications of AVR and PR or between ETV-based and TDF-based regimens.

    View details for DOI 10.1097/MCG.0b013e318224d64f

    View details for Web of Science ID 000296144000014

    View details for PubMedID 21778896

  • The efficacy of entecavir therapy in chronic hepatitis B patients with suboptimal response to adevofir ALIMENTARY PHARMACOLOGY & THERAPEUTICS SHEEN, E., Trinh, H. N., Nguyen, T. T., Do, S. T., Tran, P., Nguyen, H. A., Nguyen, K. K., Garcia, R. T., Nguyen, M. H. 2011; 34 (7): 767-774

    Abstract

    An increasing number of patients with chronic hepatitis B (CHB) have experienced treatment failure to adefovir (ADV) and their management poses a growing challenge. Very limited data are available on the efficacy of entecavir (ETV) in patients previously treated with ADV.To examine the effect of ETV monotherapy on HBV DNA and ALT levels in CHB patients previously treated with ADV, but switched to ETV due to suboptimal response.Study candidates were enrolled from five community gastroenterology clinics in the U.S. Each completed at least 12 months of ETV treatment after being previously treated with ADV and experiencing suboptimal response. Primary and secondary outcome measurements were complete viral suppression (CVS, HBV DNA <100 IU/mL) and biochemical response (BR, ALT < 40 U/L), respectively.A total of 60 patients were included in this analysis. Twelve were lamivudine (LAM)-experienced and none were LAM-resistant. At time of switch to ETV, no patients had experienced CVS. The CVS rate was 68% after 12 months of ETV therapy. The BR rate was 67% at switch to ETV and 80% after 12 months. There was no significant difference in response rates between LAM-experienced and nave patients. Among the eight patients with ADV resistance, each achieved CVS after 12 months of ETV therapy and seven achieved BR.In patients with suboptimal response to adefovir, complete viral suppression and biochemical response can be achieved in the majority by 12 months after switching to entecavir, including patients with prior exposure to lamivudine and those with adefovir resistance.

    View details for DOI 10.1111/j.1365-2036.2011.04785.x

    View details for Web of Science ID 000294571200008

    View details for PubMedID 21806648

  • Systematic review: epidemiology of hepatitis C genotype 6 and its management ALIMENTARY PHARMACOLOGY & THERAPEUTICS Chao, D. T., Abe, K., Nguyen, M. H. 2011; 34 (3): 286-296

    Abstract

    Hepatitis C virus (HCV) genotype 6 is common among patients from Southeast Asia and the surrounding regions, where HCV prevalence is also high. HCV genotype 6 has great genetic diversity and different response to antiviral therapy compared with the more commonly known genotype 1.Our goal was to provide a systematic review of the current literature on the epidemiology, classification and treatment of HCV genotype 6.A search using PubMed for 'hepatitis C' AND 'genotype 6' produced a total of 47 articles, of which 33 articles were found to be relevant and included in this review. Additional articles were identified using the reference lists of these 33 primary articles.The prevalence of HCV genotype 6 is estimated to be as high as 50% in some regions of Southeast Asia with demonstrated significance among intravenous drug users and thalassemia major patients. Although previous line probe assays may have misclassified HCV genotype 6 as genotype 1, newer line probe assays can more accurately and reliably determine HCV genotype. Patients infected with HCV genotype 6 respond better to interferon-based therapy compared with those infected with genotype 1, although patient baseline clinical characteristics and side effect profiles are similar between HCV genotype 6 and other HCV genotypes.Future studies should seek to clarify issues regarding early predictors for treatment response in patients with HCV genotype 6, and the impact of ethnic and genotypic factors to treatment response in HCV genotype 6 patients.

    View details for DOI 10.1111/j.1365-2036.2011.04714.x

    View details for Web of Science ID 000292394800003

    View details for PubMedID 21623850

  • Medication Nonadherence with Long-Term Management of Patients with Hepatitis B e antigen-Negative Chronic Hepatitis B DIGESTIVE DISEASES AND SCIENCES Ha, N. B., Ha, N. B., Garcia, R. T., Trinh, H. N., Chaung, K. T., Nguyen, H. A., Nguyen, K. K., Levitt, B. S., Nguyen, M. H. 2011; 56 (8): 2423-2431

    Abstract

    Antiviral treatment responses for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are well-defined by data from registration trials but may differ from patients seen in community settings where medical adherence is usually not as strictly monitored. The goal of this study was to examine the long-term outcomes of HBeAg-negative patients in a community clinical setting.We performed a cohort study of 189 consecutive treatment-nave patients with CHB who were treated with either entecavir (ETV) 0.5 mg daily (n=107) or adefovir dipivoxil (ADV) 10 mg daily (n=82) from 2002 to 2009 at two community clinics.All patients were Asians. Both ETV and ADV cohorts had similar median baseline ALT and HBV DNA levels. By year 4, a similar proportion of ETV and ADV patients who remained on monotherapy achieved complete viral suppression (91-96%); however, more patients in the ADV cohort required alternative therapy (27 vs. 5%). No patients in the ETV cohort developed resistance while 18% of the ADV cohort did. Cumulative nonadherence rates were 10 and 12% in ADV and ETV cohorts, respectively.Failure to monotherapy in a community clinical setting is due to both antiviral resistance and patient nonadherence. Medication nonadherence is likely to be a more important contributor to treatment failure than antiviral resistance, especially with new anti-HBV agents such as ETV and tenofovir.

    View details for DOI 10.1007/s10620-011-1610-5

    View details for Web of Science ID 000293296100032

    View details for PubMedID 21327918

  • Ethnic Differences in Viral Dominance Patterns in Patients with Hepatitis B Virus and Hepatitis C Virus Dual Infection HEPATOLOGY Nguyen, L. H., Ko, S., Wong, S. S., Tran, P. S., Trinh, H. N., Garcia, R. T., Ahmed, A., Lutchman, G. A., Keeffe, E. B., Nguyen, M. H. 2011; 53 (6): 1839-1845

    Abstract

    Studies of hepatitis B virus (HBV)/hepatitis C virus (HCV) dual infection are limited. Most are small, conducted outside the United States, and compare dual infection with HCV monoinfection. The goal of this study was to characterize HBV/HCV dual infection in a large multiethnic, matched, case-control study of dual-infected and HBV-monoinfected patients at two United States centers. Using an International Classification of Disease Version 9 electronic query and chart review, we identified 115 HBV/HCV dual-infected patients with serial HBV DNA, HCV RNA, and alanine aminotransferase (ALT) levels. As a control, 115 HBV-monoinfected patients were chosen randomly and matched with cases by age 10 years, sex, Asian versus non-Asian ethnicity, and study site. Both groups had similar sex, ethnic, and age distributions (68% male, 83% Asian, age 52 14 years). The median follow-up times were 33 and 38 months for the dual-infected and monoinfected groups, respectively. More monoinfected patients received HBV antiviral therapy than dual-infected patients (43% versus 24%; P = 0.002). No significant difference was detected between the proportion of monoinfected versus dual-infected patients with ALT above 40 U/L at presentation or during follow-up. Dual infection patients exhibited very little HBV/HCV codominance at baseline and throughout follow-up: patients had either HBV viremia with low or absent HCV RNA or detectable HCV RNA with low or absent HBV DNA. Asian ethnicity was predictive of HBV dominance after adjusting for sex, age, and baseline ALT elevation (odds ratio 7.35; P = 0.01).HBV/HCV dual-infected and HBV-monoinfected patients had similar clinical characteristics. Asian ethnicity is a major independent predictor of HBV-dominant disease, and HCV dominance with undetectable HBV DNA is more common in non-Asian individuals. Larger studies are needed to further characterize the natural history of HBV/HCV dual infection in Asian and non-Asian individuals.

    View details for DOI 10.1002/hep.24308

    View details for Web of Science ID 000291307300009

    View details for PubMedID 21425314

  • Relationship between HBsAg seroconversion and hepatocellular carcinoma J Clin Gastroenterol Lutchman G, Nguyen MH 2011; 45: 64-68
  • Early virologic response in HCV genotype 6 Hepatology Lam KD, Nguyen MH 2011; 53: 1403
  • The role of steatosis in HBV infection Curr Hepat Rep Lim JK, Nguyen MH 2011; 10: 134-141
  • Hepatitis B virus reverse transcriptase sequence variant database for sequence analysis and mutation discovery ANTIVIRAL RESEARCH Rhee, S., Margeridon-Thermet, S., Nguyen, M. H., Liu, T. F., Kagan, R. M., Beggel, B., Verheyen, J., Kaiser, R., Shafer, R. W. 2010; 88 (3): 269-275

    Abstract

    Drug resistance resulting from reverse transcriptase (RT) mutations is one of the main obstacles to successful hepatitis B virus (HBV) therapy. Indeed, HBV treatment guidelines recommend HBV genotypic resistance testing for patients receiving nucleos(t)ide RT inhibitors (N(t)RTIs) who develop virological failure. N(t)RTI-resistance mutations at 10 RT positions have been well characterized in phenotypic studies, however, data are lacking on the relative frequency of these mutations in N(t)RTI-treated and untreated individuals. There are also few published data on the extent of amino acid variation at most of the 344 positions of HBV RT and the extent to which this variation is influenced by N(t)RTI treatment. We retrieved 23,871 HBV RT sequences from GenBank and reviewed the published reports of these sequences to ascertain the number of individuals from whom the sequences were obtained, the N(t)RTI treatments of these individuals, and the year and region of virus sampling. We then used these data to populate a relational database we named HBVrtDB. As of July 2010, HBVrtDB contained 6811 sequences from 3869 individuals reported in 281 references. Among these 3869 individuals, 73% were N(t)RTI-nave and 27% received one or more N(t)RTIs. Among the 10 well-characterized N(t)RTI-resistance mutations, L80I/V, V173L, L180M, A181T, T184S, S202G and M204I/V were significantly associated with treatment with lamivudine, an l-nucleoside analog, and A181S/T/V and N236T were significantly associated with treatment with adefovir, an acyclic nucleoside phosphonate. A similar analysis of ten additional less well-characterized resistance mutations demonstrated a significant association with N(t)RTI treatment for four of the mutations: L82M, S85A, A200V, and Q215S. We also created an interactive program, HBVseq, to enable users to identify mutations in submitted sequences and retrieve the prevalence of these mutations in HBVrtDB according to genotype and N(t)RTI treatment. HBVrtDB and HBVseq are available at http://hivdb.stanford.edu/HBV/releaseNotes/.

    View details for DOI 10.1016/j.antiviral.2010.09.012

    View details for Web of Science ID 000285660300004

    View details for PubMedID 20875460

  • Randomized Controlled Trial of Pegylated Interferon-Alfa 2a and Ribavirin in Treatment-Naive Chronic Hepatitis C Genotype 6 HEPATOLOGY Lam, K. D., Trinh, H. N., Do, S. T., Nguyen, T. T., Garcia, R. T., Nguyen, T., Phan, Q. Q., Nguyen, H. A., Nguyen, K. K., Nguyen, L. H., Nguyen, M. H. 2010; 52 (5): 1573-1580

    Abstract

    Hepatitis C virus (HCV) genotype is an important criteria in determining duration of therapy and predictor of sustained virologic response (SVR) to pegylated interferon (PEG IFN) and ribavirin (RBV) therapy. Optimal duration of therapy for patients with HCV genotype 6 is not known. We conducted a multicenter, open-label randomized controlled trial of patients with HCV genotype 6 at five gastroenterology clinics in the western U.S. Patients were stratified by viral load and histologic stage and assigned to receive PEG IFN-?2a 180 ?g subcutaneously weekly and weight-based oral RBV 800 to 1,200 mg daily for 24 or 48 weeks. Primary outcome measurement was SVR rate by intention-to-treat analysis. From February 2005 to October 2007 a total of 60 patients (age 51 10 years, 47% male, log HCVRNA 6.3 1.1 IU/mL) were enrolled: 27 patients to 24 weeks and 33 patients to 48 weeks of therapy. In the 24-week and 48-week groups, 96% and 97% achieved early virologic response (P = 0.90); 89% versus 94% achieved end of therapy virologic response (P = 0.48). SVR was achieved in 70% versus 79% of patients assigned to 24 weeks versus 48 weeks (P = 0.45). Rapid virologic response (RVR) was a significant predictor of SVR in the 48-week group and trending towards significance in the 24-week group: 82% and 83% of those with RVR achieved SVR versus 33% and 29% for the 24-week and 48-week groups, respectively (P = 0.07 and P = 0.02).There was no significant difference in SVR rates in patients with HCV genotype 6 treated with PEG IFN-?2a and RBV for 24 versus 48 weeks.

    View details for DOI 10.1002/hep.23889

    View details for Web of Science ID 000283764800007

    View details for PubMedID 21038410

  • Response to pegylated interferon and ribavirin in Asian American patients with Chronic hepatitis C genotypes 1 vs 2/3 vs 6 JOURNAL OF VIRAL HEPATITIS Nguyen, N. H., VuTien, P., Garcia, R. T., Trinh, H., Nguyen, H., Nguyen, K., Levitt, B., Nguyen, M. H. 2010; 17 (10): 691-697

    Abstract

    Chronic hepatitis C is generally underappreciated in Asian Americans, and most pivotal studies were conducted in western countries and only included a small numbers of Asian patients. Our goal was to examine and compare treatment outcomes in these patients with genotypes 1 vs 2/3 vs 6. We performed a retrospective cohort study of 167 consecutive treatment-nave Asian American patients treated with pegylated interferon (PEG IFN) plus ribavirin (RBV) at two community clinics in Northern California from 12/00 to 1/08. Primary outcome was sustained virological response rate by intention-to-treat analysis. The overall completion rate was 76%, and treatment adherence (completion of ? 75-80% PEG IFN + RBV dose for ? 75-80% of intended duration) was 74%. Significant depression was noted in only 4% of patients. Sustained virologic response in patients with genotype 6 treated for 48 weeks was similar to that seen in those with genotype 2/3 (74%vs 75%, P = 0.89) and significantly higher than those with genotype 1 (74%vs 49%, P = 0.016). On multivariate analysis inclusive of sex, age, body mass index (? 25 vs > 25) and viral load, only treatment adherence and genotype (2/3 and 6 treated for 48 weeks) were found to be significant predictors of sustained virologic response. We conclude that significant depression is rare in Asian American patients (4%). Patients with genotype 6 treated for 48 weeks appear to have a similar treatment response rate as patients with genotype 2/3 and a significantly higher response rate than those with genotype 1.

    View details for DOI 10.1111/j.1365-2893.2009.01226.x

    View details for Web of Science ID 000281829900003

    View details for PubMedID 20002562

  • Risk factors, genotype 6 prevalence, and clinical characteristics of chronic hepatitis C in Southeast Asian Americans HEPATOLOGY INTERNATIONAL Nguyen, N. H., Vutien, P., Trinh, H. N., Garcia, R. T., Nguyen, L. H., Nguyen, H. A., Nguyen, K. K., Nguyen, M. H. 2010; 4 (2): 523-529

    Abstract

    Although infection with hepatitis C virus (HCV) affects 32 million individuals from Southeast Asia, little is known about the mode of HCV acquisition and the epidemiology of chronic hepatitis C (CHC) in these individuals. Our goal was to examine risk factors for HCV acquisition, prevalence, and clinical characteristics of HCV genotype 6 compared with genotypes 1 and 2/3 in Southeast Asian (SEA) patients.We performed a cross-sectional study of 308 consecutive SEA Americans with CHC evaluated by five gastroenterologists from January 2000 to December 2008 at two community clinics in northern California via medical record review, using a case report form.A significant proportion of patients (41%) could not recall any specific risk factors for HCV acquisition. The most commonly reported risk factor in patients who reported at least one risk factor was history of surgeries (34%), followed by blood transfusion (25%) and acupuncture (13%). Among patients with core sequence testing for HCV genotype (n=181), the most common HCV genotypes were genotype 1 (42%) and genotype 6 (41%), followed by genotype 2/3 (17%). There were no major differences in the clinical and virological characteristics between the different genotype groups (1 vs. 2/3 vs. 6).HCV genotype 6 is as common as genotype 1 in SEAs. Commonly known risk factors for HCV acquisition were not readily identifiable in a large proportion of SEA Americans (41%) and may not be useful in identifying at-risk individuals for HCV screening in this population.

    View details for DOI 10.1007/s12072-010-9181-7

    View details for Web of Science ID 000279503500008

    View details for PubMedID 20827411

  • Similar Treatment Response to Peginterferon and Ribavirin in Asian and Caucasian Patients With Chronic Hepatitis C AMERICAN JOURNAL OF GASTROENTEROLOGY Vutien, P., Nguyen, N. H., Trinh, H. N., Li, J., Garcia, R. T., Garcia, G., Nguyen, K. K., Nguyen, H. A., Levitt, B. S., Keeffe, E. B., Nguyen, M. H. 2010; 105 (5): 1110-1115

    Abstract

    Previous studies have found ethnicity to be an important predictor of outcomes of treatment with peginterferon (PEG-IFN) and ribavirin (RBV) in chronic hepatitis C. Although the expected sustained virological response (SVR) rates of Hispanics and African Americans are lower than those of Caucasians, SVR rates in Asians appear to be more favorable. However, in some of these studies, hepatitis C virus (HCV) genotype was identified by INNO-LiPA assay, which can mistype the easier-to-treat HCV genotype 6 as genotype 1. Our goal was to compare SVR rates among Caucasian and Asian-American patients with genotype 1 and 2/3 infection whose HCV genotypes were accurately classified by core sequencing testing.A cohort of 269 consecutive treatment-naive HCV-infected patients with genotype 1 or 2/3 (157 Caucasians and 112 Asians) treated with PEG-IFN+RBV from January 2001 to November 2007 at four community-based gastroenterology clinics in Northern California were studied. The analysis of data was by intention-to-treat.The SVR rates for patients with genotype 1 were 45% for Caucasians and 52% for Asians (P=0.37). The SVR rates for patients with genotype 2/3 infection was 77% for Asians and 74% for Caucasians (P=0.7). On multivariate logistic regression analyses adjusting for age, alanine aminotransferase (ALT), baseline viral load, HCV genotype, and treatment adherence, we did not find Asian ethnicity to predict SVR. On a separate analysis, we found that Asians who had HCV genotype 1 or 1b by the less accurate INNO-LiPA assay had significantly higher SVR rates than Caucasians with genotype 1 (64% vs. 45%, respectively, P=0.03).SVR rates were similar in Asian Americans and Caucasians infected with HCV genotype 1 or 2/3 when HCV genotype classification was accurately determined.

    View details for DOI 10.1038/ajg.2009.635

    View details for Web of Science ID 000277440100019

    View details for PubMedID 19904247

  • Histologic Disease in Patients with Chronic Hepatitis B, HIgh HBV DNA, and Normal Alanine Aminotransferase Levels Curr Hepat Rep Lim JK, Ayoub WS, Nguyen MH 2010; 9: 65-74
  • Adherence to Screening for Hepatocellular Carcinoma Among Patients with Cirrhosis or Chronic Hepatitis B in a Community Setting DIGESTIVE DISEASES AND SCIENCES Wong, C. R., Garcia, R. T., Trinh, H. N., Lam, K. D., Ha, N. B., Nguyen, H. A., Nguyen, K. K., Levitt, B. S., Nguyen, M. H. 2009; 54 (12): 2712-2721

    Abstract

    Screening for hepatocellular carcinoma (HCC) has been shown to improve survival via earlier cancer detection. Although HCC screening is considered standard of care in the USA, little is known of the adherence to this practice, especially in a community setting.Our primary goal was to evaluate adherence to HCC screening and to find predictors of screening adherence in a community setting. Our secondary objective was to determine the impact of screening on survival.We studied a cohort of 557 consecutive patients at high risk for HCC: patients with cirrhosis and older chronic hepatitis B (CHB) patients without cirrhosis (?45 years old). Patients initiated screening 1/2001-1/2005 and were monitored ?12 months to 12/2008 in two community gastroenterology clinics in Northern California. HCC screening was categorized into four groups based on combined frequency of serum alpha-fetoprotein and imaging: optimal, suboptimal, poor, and no screening.About 40.6% of our cohort received poor or no screening. Noncirrhotic CHB patients had worse screening than cirrhotic patients. Multivariate analysis revealed that patients with a greater number of clinical visits per year were 3.4 times more likely to have regular screening than patients with fewer clinical visits per year (P<0.001). There was a trend for association between HCC screening and greater access to curative treatment.Since more frequent clinic visits is a strong independent predictor of improved screening adherence, regular routine clinic visits may help improve adherence to HCC screening, which may also lead to improved clinical outcomes.

    View details for DOI 10.1007/s10620-009-1015-x

    View details for Web of Science ID 000271923300025

    View details for PubMedID 19876735

  • Prevalence of hepatitis B virus DNA polymerase mutations in treatment-naive patients with chronic hepatitis B ALIMENTARY PHARMACOLOGY & THERAPEUTICS Nguyen, M. H., Garcia, R. T., Trinh, H. N., Nguyen, H. A., Nguyen, K. K., Nguyen, L. H., Levitt, B. 2009; 30 (11-12): 1150-1158

    Abstract

    One of the most important factors in treatment failure using nucleos(t)ide analogues in chronic hepatitis B is anti-viral resistance. Primary drug resistance refers to amino acid changes in the hepatitis B virus polymerase/reverse transcriptase (rt) that result in reduced susceptibility to anti-viral agents. Pre-existing drug resistance mutations may occur in untreated patients and may affect their treatment outcomes.To determine the prevalence of hepatitis B DNA polymerase mutations in treatment-nave patients.We used a direct PCR sequencing test to detect DNA polymerase mutations in 472 consecutive treatment-nave patients at two community gastroenterology clinics in Northern California.A majority of patients were Asians (>95%), had either genotype B or C (95%) and had no evidence of cirrhosis or liver cancer (94%). Mean age was 45 +/- 13 and mean hepatitis B virus DNA was 5.3 +/- 1.8 log(10) IU/mL. Most patients did not have any detectable mutations (82.4%). Some (16.7%) had mutations of unknown clinical significance (rtV207M/L/I) and only 4 patients had rtA181A/S, rtA194S or M250I.No rtM204V/I or rtN236T mutations were observed in our study. Less than 1% of our patients had mutations that can be associated with primary resistance to existing anti-viral therapies for hepatitis B virus.

    View details for DOI 10.1111/j.1365-2036.2009.04151.x

    View details for Web of Science ID 000271465300007

    View details for PubMedID 19785624

  • Combination of pharmacologic and endoscopic therapy for the secondary prevention of esophageal variceal bleeding GASTROINTESTINAL ENDOSCOPY Ayoub, W. S., Nguyen, M. H. 2009; 70 (4): 665-667

    View details for DOI 10.1016/j.gie.2009.05.035

    View details for Web of Science ID 000270527300011

    View details for PubMedID 19788982

  • Histological Disease in Asian-Americans With Chronic Hepatitis B, High Hepatitis B Virus DNA, and Normal Alanine Aminotransferase Levels AMERICAN JOURNAL OF GASTROENTEROLOGY Nguyen, M. H., Garcia, R. T., Trinh, H. N., Lam, K. D., Weiss, G., Nguyen, H. A., Nguyen, K. K., Keeffe, E. B. 2009; 104 (9): 2206-2213

    Abstract

    At present there is no clear consensus on how patients with chronic hepatitis B (CHB), high serum hepatitis B virus (HBV) DNA, and normal alanine aminotransferase (NLALT) levels should be managed. This study hypothesizes that a significant proportion of such patients may have histological disease.We carried out a retrospective study of 101 consecutive treatment-naive patients with CHB who underwent liver biopsies at a community gastroenterology clinic and had high HBV DNA and NLALT (< or = 40 U/l) levels at the time of biopsy. All patients were Asians. ALT levels were observed for a period of time before liver biopsy and were used to classify patients into two groups, namely those with only NLALT levels and those with fluctuating ALT (FLALT) levels. All patients had at least two ALT measurements during this period of time. Significant histology was defined as stage > or = 2 fibrosis or stage 1 fibrosis plus grade > or = 2 inflammation using the Batts-Ludwig scoring system.In patients with NLALT levels, the proportions of those with significant histology were 0, 22, and 45% for age < or = 35, 36-50, and >50 years, respectively (n=11, n=27, n=19; P=0.033). In patients who had FLALT levels, the corresponding proportions were 22, 42, and 69% (n=9, n=22, n=13; P=0.091). After adjustments for gender, hepatitis B e antigen (HBeAg) status, and mean pre-biopsy HBV DNA levels, significant predictors of histological disease were older age (odds ratio (OR)=6.2 for age 36-50 years and OR=17.6 for age >50 years compared with age < or = 35 years, P=0.041 and P=0.003, respectively) and FLALT levels (OR=3.6, P=0.008). Sub-analysis of patients with NLALT levels using lower cutoffs (30 U/l for men and 19 U/l for women) showed similar trends.Patients with CHB, high HBV DNA, and NLALT levels and aged more than 35 years or those with FLALT levels may have significant histological disease (22-70%).

    View details for DOI 10.1038/ajg.2009.248

    View details for Web of Science ID 000270024800014

    View details for PubMedID 19491836

  • Renal Dysfunction in Chronic Hepatitis B Patients Treated with Adefovir Dipivoxil HEPATOLOGY Ha, N. B., Ha, N. B., Garcia, R. T., Trinh, H. N., Vu, A. A., Nguyen, H. A., Nguyen, K. K., Levitt, B. S., Nguyen, M. H. 2009; 50 (3): 727-734

    Abstract

    Renal dysfunction has been reported in patients treated with adefovir dipivoxil (ADV); however, its incidence and clinical importance may be underappreciated given the lack of long-term follow-up and data outside of a clinical trial setting. Our goal was to examine the severity and incidence of renal dysfunction in a real-life setting for patients treated with ADV and whose baseline estimated glomerular filtration rate (eGFR) was >50 mL/minute. We performed a cohort study of 290 chronic hepatitis B patients: 145 patients treated with 10 mg ADV and 145 patients unexposed to ADV at two community clinics, who were matched for age (+/-10 years), sex, and baseline eGFR. The exposed and unexposed populations were well-matched with a similar mean age (46-47 years), proportion of male patients (76.5%), baseline serum creatinine (0.97-0.99 mg/dL), and baseline creatinine clearance (85.0-85.4 mL/minute). The incidence density for renal dysfunction defined by treatment termination and/or development of eGFR < or =50 mL/minute was five cases per 100 patient-years in the exposed group compared with 1.36 cases per 100 patient-years in the unexposed group (P = 0.02). The relative risk of exposed to unexposed was 3.68 (95% confidence interval 1.1-19.3). On Cox proportional hazard analysis also inclusive of sex, ADV was a significant predictor of significant renal dysfunction (hazard ratio [HR] 3.94, P = 0.03). There were also significant trends for age >50 years (HR 3.49, P = 0.087), mild renal impairment at baseline (HR 4.49, P = 0.073), and hypertension and/or diabetes mellitus (HR 2.36, P = 0.074). Conclusion: ADV is an independent predictor for significant deterioration of renal function. Patients on ADV should be monitored, especially patients who are older, have baseline renal insufficiency, or have hypertension and/or diabetes mellitus.

    View details for DOI 10.1002/hep.23044

    View details for Web of Science ID 000269551100011

    View details for PubMedID 19517525

  • Prevalence of hepatitis B virus genotype B in Vietnamese patients with chronic hepatitis B HEPATOLOGY INTERNATIONAL Nguyen, L. H., Ha, N. B., Vutien, P., Ha, N. B., Garcia, R. T., Trinh, H. N., Levitt, B. S., Nguyen, H. A., Nguyen, K. K., Keeffe, E. B., Nguyen, M. H. 2009; 3 (3): 461-467

    Abstract

    Hepatitis B virus (HBV) genotypes can affect treatment response to interferon-based therapy and disease outcomes in patients with chronic hepatitis B (CHB). Little data exist to characterize HBV genotypes in Vietnamese, one of the largest minority groups in the United States and also one with one of the highest CHB and liver cancer disease burdens. The goal of this study was to compare the distribution of HBV genotypes in Vietnamese and Chinese patients.We performed a cross-sectional study of 567 consecutive patients of Vietnamese (n=478) or Chinese (n=89) descent, with HBV genotype mutation analysis performed between 7/2,005 and 6/2,008 at a community gastroenterology clinic and a university-affiliated liver clinic in the United States.There were no significant differences between the Vietnamese and Chinese groups in mean age (45 and 44years), gender (58% and 61% male), HBeAg status (64% and 65% negative), median alanine aminotransferase (33 and 41 U/L), and log(10) HBV DNA (4.9 and 5.0 log(10)IU/ml), or the prevalence of precore/basic core promoter mutations (72% and 71%), respectively. Vietnamese patients had a much higher prevalence of HBV genotype B and a lower prevalence of genotype C than Chinese patients: 74% and 25% vs. 55% and 43% (P=0.001).Chinese patients with CHB often carry either B or C genotype. Vietnamese patients with CHB mostly have HBV genotype B. Additional studies are needed to further characterize the clinical significance of HBV genotype in the natural history and treatment outcomes of CHB in Vietnamese patients.

    View details for DOI 10.1007/s12072-009-9141-2

    View details for Web of Science ID 000268872300006

    View details for PubMedID 19669244

  • alpha-Fetoprotein, Des-gamma Carboxyprothrombin, and Lectin-Bound alpha-Fetoprotein in Early Hepatocellular Carcinoma GASTROENTEROLOGY Marrero, J. A., Feng, Z., Wang, Y., Nguyen, M. H., Befeler, A. S., Roberts, L. R., Reddy, K. R., Harnois, D., Llovet, J. M., Normolle, D., Dalhgren, J., Chia, D., Lok, A. S., Wagner, P. D., Srivastava, S., Schwartz, M. 2009; 137 (1): 110-118

    Abstract

    Alpha-fetoprotein (AFP) is widely used as a surveillance test for hepatocellular carcinoma (HCC) among patients with cirrhosis. Des-gamma carboxy-prothrombin (DCP) and lectin-bound AFP (AFP-L3%) are potential surveillance tests for HCC. The aims of this study were to determine performance of DCP and AFP-L3% for the diagnosis of early HCC; whether they complement AFP; and what factors affect DCP, AFP-L3%, or AFP levels.We conducted a large phase 2 biomarker case-control study in 7 academic medical centers in the United States. Controls were patients with compensated cirrhosis and cases were patients with HCC. AFP, DCP, and AFP-L3% levels were measured blinded to clinical data in a central reference laboratory.A total of 836 patients were enrolled: 417 (50%) were cirrhosis controls and 419 (50%) were HCC cases, of which 208 (49.6%) had early stage HCC (n = 77 very early, n = 131 early). AFP had the best area under the receiver operating characteristic curve (0.80, 95% confidence interval [CI]: 0.77-0.84), followed by DCP (0.72, 95% CI: 0.68-0.77) and AFP-L3% (0.66, 95% CI: 0.62-0.70) for early stage HCC. The optimal AFP cutoff value was 10.9 ng/mL leading to a sensitivity of 66%. When only those with very early HCC were evaluated, the area under the receiver operating characteristic curve for AFP was 0.78 (95% CI: 0.72-0.85) leading to a sensitivity of 65% at the same cutoff.AFP was more sensitive than DCP and AFP-L3% for the diagnosis of early and very early stage HCC at a new cutoff of 10.9 ng/mL.

    View details for DOI 10.1053/j.gastro.2009.04.005

    View details for Web of Science ID 000267410100021

    View details for PubMedID 19362088

  • Transarterial Chemoinfusion for Hepatocellular Carcinoma as Downstaging Therapy and a Bridge toward Liver Transplantation AMERICAN JOURNAL OF TRANSPLANTATION De Luna, W., Sze, D. Y., Ahmed, A., Ha, B. Y., Ayoub, W., Keeffe, E. B., Cooper, A., Esquivel, C., Nguyen, M. H. 2009; 9 (5): 1158-1168

    Abstract

    Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria.

    View details for DOI 10.1111/j.1600-6143.2009.02576.x

    View details for Web of Science ID 000265222200023

    View details for PubMedID 19344435

  • Clinical course of hepatitis B virus infection during pregnancy ALIMENTARY PHARMACOLOGY & THERAPEUTICS Nguyen, G., Garcia, R. T., Nguyen, N., Trinh, H., Keeffe, E. B., Nguyen, M. H. 2009; 29 (7): 755-764

    Abstract

    For women with hepatitis B virus (HBV) infection, little is known about the natural progression of the disease during pregnancy or its impact on pregnancy outcomes.To investigate the natural progression of HBV infection during pregnancy or its impact on pregnancy outcomes.In this retrospective cohort study, we reviewed medical records of all patients who were pregnant and presented with HBsAg-positivity between 2000 and 2008 at a community gastroenterology practice and a university hepatology clinic. Maternal characteristics were analysed according to maternal and perinatal outcomes.A total of 29 cases with at least 2 measurements of either HBV DNA or alanine aminotransferase (ALT) levels were included. Older age was the only predictor of a trend towards higher risk of an adverse clinical outcome [OR = 1.21 (0.97-1.51), P = 0.089], defined as either a negative foetal outcome (premature delivery, spontaneous abortion), or a negative maternal outcomes (gestational diabetes mellitus, pre-eclampsia, hepatic flare, liver failure). This trend for age remained even after adjusting for baseline ALT. Baseline serum HBV DNA, ALT, hepatitis B e antigen status, gravida and parity were not significant predictors for adverse clinical outcomes. Four patients developed liver failure.Maternal and neonatal outcomes are highly variable in this clinic-based patient cohort. Severe complications due to HBV infection can occur during pregnancy in previously asymptomatic patients. It is unclear how generalizable the results observed in this cohort would be to the general population; therefore, further studies are needed to identify reliable predictors for significant adverse outcomes and until more data are available, pregnant patients with HBV infection should be monitored with periodic serum HBV DNA and ALT levels.

    View details for DOI 10.1111/j.1365-2036.2009.03932.x

    View details for Web of Science ID 000263908900006

    View details for PubMedID 19183158

  • Chronic hepatitis B: early viral suppression and long-term outcomes of therapy with oral nucleos(t)ides JOURNAL OF VIRAL HEPATITIS Nguyen, M. H., Keeffe, E. B. 2009; 16 (3): 149-155

    Abstract

    Chronic hepatitis B is a serious health problem worldwide with a substantial minority of patients experiencing premature death due to end-stage liver disease and/or hepatocellular carcinoma. Antiviral therapy may help prevent complications of chronic hepatitis B, and seven agents are currently approved in many countries. Of these agents, five are nucleos(t)ide analogs that all have a risk of antiviral drug resistance with long-term use. Efforts have been made in the recent years to prevent or to reduce the risk of viral resistance in patients treated with oral nucleos(t)ides as the majority of these patients will require therapy for 3-5 years or longer. One approach is to identify patients who would most likely develop antiviral resistance on long-term therapy using predictors obtainable early in the course of treatment, when intervention with new or additional therapy can be instituted. The most important predictors of treatment outcomes are serum HBV DNA levels at baseline and during the first 6 months of therapy. The purpose of this synopsis is to review the recent literature regarding the importance of serum HBV DNA levels in association with treatment outcomes in chronic hepatitis B, particularly the association of complete viral suppression early in the course of oral therapy with long-term treatment outcomes, particularly the incidence of antiviral drug resistance.

    View details for DOI 10.1111/j.1365-2893.2009.01078.x

    View details for Web of Science ID 000263302200001

    View details for PubMedID 19236641

  • Hepatitis C virus and cancers: How strong are the relationships? Curr Hepat Rep Lutchman G, Nguyen MH 2009; 8: 141-147
  • Prevalence of Colorectal Neoplasms in Asian Americans DIGESTIVE DISEASES AND SCIENCES Lam, K. D., Garcia, R. T., Nguyen, L. H., Trinh, H., Triadafilopoulos, G., Phan, J. T., Nguyen, K., Nguyen, H., Ahmed, A., Nguyen, M. H. 2009; 54 (1): 160-167

    Abstract

    To determine the yield of colonoscopy in a predominantly Asian American gastroenterology practice in California from 8/2003 to 2/2005.A total 2,723 subjects were included: 87% were Asian and 13% were non-Asian. Advanced neoplasia prevalence was 12% in Asian men and 9% in non-Asian men (P = 0.21), and 8% and 7% in women (P = 0.62). Similar results were found in asymptomatic patients (13% and 13%, P = 0.99, for men; 8% and 6%, P = 0.46, for women). Factors associated with presence of advanced neoplasia were total number of polyps and presence of right-sided lesions. Asian men were more likely to have neoplasia overall compared with non-Asian men with odds ratio (OR) of 2.14 (1.23-3.72); however, there were no significant differences in the prevalences of advanced neoplasia in the two groups.Colorectal neoplasia is as prevalent in Asian Americans and preventive guidelines for colorectal cancer should also be advocated for this ethnic group.

    View details for DOI 10.1007/s10620-008-0499-0

    View details for Web of Science ID 000261653400026

    View details for PubMedID 18975084

  • Are Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B and HBeAg-Negative Chronic Hepatitis B Distinct Diseases? CLINICAL INFECTIOUS DISEASES Nguyen, M. H., Keeffe, E. B. 2008; 47 (10): 1312-1314

    View details for DOI 10.1086/592571

    View details for Web of Science ID 000260078800010

    View details for PubMedID 18840075

  • Low proportion of Barrett's esophagus in Asian Americans AMERICAN JOURNAL OF GASTROENTEROLOGY Lam, K. D., Phan, J. T., Garcia, R. T., Trinh, H., Nguyen, H., Nguyen, K., Triadafilopoulos, G., Vutien, P., Nguyen, L., Nguyen, M. H. 2008; 103 (7): 1625-1630

    Abstract

    To determine the proportion of Barrett's esophagus (BE) in Asians versus non-Asians and the predictors of BE in patients with upper gastrointestinal (GI) symptoms.We performed a cross-sectional study to determine the proportion of BE from all consecutive patients who underwent esophagogastroduodenoscopy (EGD) for various indications at an outpatient, community-based gastroenterology practice in northern California from February 2000 to September 2006. BE was defined as endoscopically recognized presence of salmon-pink mucosa in the distal esophagus and intestinal metaplasia on biopsy. We also performed a nested case-control study to determine potential predictors of BE.In total, 5,293 patients were reviewed. BE was more common in non-Asians (31/1464, 2.1%) than Asians (29/3829, 0.76%) (P < 0.001). In multivariate analysis controlling for increasing age, male gender, ethnicity, smoking, and alcohol, the strongest predictor of the presence of BE was non-Asian ethnicity (odds ratio [OR] 3.55, 95% confidence interval [CI] 1.85-6.85), followed by male gender (OR 2.68, 95% CI 1.32-5.45).BE is uncommon in Asian Americans; non-Asian ethnicity and male gender are significant independent predictors of BE.

    View details for DOI 10.1111/j.1572-0241.2008.01891.x

    View details for Web of Science ID 000257693900008

    View details for PubMedID 18557711

  • Higher rate of sustained virologic response in chronic hepatitis C genotype 6 treated with 48 weeks versus 24 weeks of peginterferon plus ribavirin AMERICAN JOURNAL OF GASTROENTEROLOGY Nguyen, M. H., Trinh, H. N., Garcia, R., Nguyen, G., Lam, K. D., Keeffe, E. B. 2008; 103 (5): 1131-1135

    Abstract

    Infection with hepatitis C virus (HCV) genotype 6 is common in patients from parts of China and Southeast Asia. No study to date has examined the treatment response to peginterferon and ribavirin (PEG IFN + RBV) in these patients, or the effects of treatment duration on sustained virologic response (SVR) rates.We performed a retrospective study of 190 consecutive Asian-American patients who were diagnosed with HCV genotype 6 at a gastroenterology clinic in northern California between 2001 and 2004, 66 of whom were treatment-nave and subsequently completed 24 wk of IFN + RBV or PEG IFN + RBV or 48 wk of PEG IFN + RBV therapy. The primary outcome was SVR.There was no statistical difference in SVR of 31 patients treated with 24 wk of IFN + RBV and in 23 patients treated with 24 wk of PEG IFN + RBV (51.6%vs 39%, P= 0.363). The SVR in 12 patients treated with 48 wk of PEG IFN + RBV was significantly higher than that in those treated for only 24 wk (75%vs 39%, P= 0.044).Treatment-eligible patients with HCV genotype 6 should be treated with a full course of 48 wk as tolerated. Larger prospective studies of patients with HCV genotype 6 are needed to confirm the optimal treatment duration with PEG IFN + RBV.

    View details for DOI 10.1111/j.1572-0241.2008.01793.x

    View details for Web of Science ID 000255750000010

    View details for PubMedID 18477343

  • Significant prevalence of histologic disease in patients with chronic hepatitis B and mildly elevated serum alanine aminotransferase levels CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Tsang, P. S., Trinh, H., Garcia, R. T., Phan, J. T., Ha, N. B., Nguyen, H., Nguyen, K., Keeffe, E. B., Nguyen, M. H. 2008; 6 (5): 569-574

    Abstract

    Serum ALT remains the most accessible test available to clinicians for monitoring chronic hepatitis B virus infection, but appropriate action when ALT levels are only mildly elevated is ambiguous in standard guidelines.A retrospective study was conducted to investigate the prevalence of significant histology in a patient population with mildly elevated serum ALT levels. A total of 193 consecutive patients were selected and divided into 2 groups according to HBeAg status. Patients were further divided into cohorts on the basis of their highest ALT elevation during follow-up and whether it was 1-1.5 times the upper limit of normal (ULN), 1.5-2 times the ULN, or greater than twice the ULN. The ULN that was used is 30 U/L for men and 19 U/L for women.In all cohorts there was a substantial fraction of patients with histologic disease as evaluated by liver biopsy. HBeAg-negative patients were older, had lower viral load, and had a higher prevalence of disease. After adjustments for age, HBeAg status and HBV DNA viral load were not predictors of significant histology. Age >35 years, male gender, and increasing ALT levels were predictors for significant histology on multivariate analysis.A substantial proportion of patients with mildly elevated ALT levels have significant histologic disease. The prevalence increased with the higher ALT levels and age.

    View details for DOI 10.1016/j.cgh.2008.02.037

    View details for Web of Science ID 000255806200018

    View details for PubMedID 18455697

  • Long-term survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoinfusion ALIMENTARY PHARMACOLOGY & THERAPEUTICS Ha, B. Y., Ahmed, A., Sze, D. Y., Razavi, M. K., Simpson, N., Keeffe, E. B., Nguyen, M. H. 2007; 26 (6): 839-846

    Abstract

    Transcatheter arterial chemoembolization (TACE) has become one of the most common treatments for unresectable hepatocellular carcinoma. Published studies of TACE report a 5-16% risk of serious complications. Compared with TACE, transcatheter arterial chemoinfusion (TACI) may have similar efficacy and fewer side effects.To examine the clinical outcomes of TACI.We performed a retrospective cohort study of 345 consecutive TACI cases in 165 patients performed at a single United States medical center between 1998 and 2002. Primary outcomes were tumour response and survival rates.Only seven patients were hospitalized for more than 24 h after the procedure, and only three patients had worsening of liver function within 30 days of TACI. Survival was significantly poorer for patients with tumour-node-metastasis (TNM) IV compared to those with TNM I-III and also for patients with Child's class B/C vs. A. Following adjustment for age, gender, ethnicity and aetiology of liver diseases, independent predictors of poor survival were Child's class B/C [Hazard Ratio (HR) = 1.69, P = 0.024] and TNM IV staging (HR = 1.63, P = 0.014).TACI appears to be safe and effective for unresectable hepatocellular carcinoma with TNM stage I-III; randomized controlled trials are needed to compare TACI to TACE.

    View details for DOI 10.1111/j.1365-2036.2007.03424.x

    View details for Web of Science ID 000249130100008

    View details for PubMedID 17767468

  • Chronic HBV infection and normal ALT levels: Underlying histological disease Curr Hepat Rep Hoda K, Nguyen MH 2007; 6: 24-29
  • Prevalence and treatment of hepatitis C virus genotypes 4, 5, and 6. Clinical gastroenterology and hepatology Nguyen, M. H., Keeffe, E. B. 2005; 3 (10): S97-S101

    Abstract

    Infection with hepatitis C virus (HCV) genotypes 4-6 (with the previously named genotypes 7-9 included as subtypes of genotype 6) is distributed and studied less widely than genotypes 1-3. However, genotypes 4-6 are very common in geographic areas where chronic hepatitis C is highly prevalent. In fact, the majority (87%) of the 169.7 million HCV-infected individuals worldwide are from western Pacific countries (62.2 million), southeast Asia (32.3 million), Africa (31.9 million), and eastern Mediterranean countries (21.3 million). It is among this large population outside of the Americas and Europe that these less well known genotypes are found: genotype 4 in Egypt and Africa, genotype 5 in South Africa, and genotype 6 in southeast Asia. The existing literature, although limited, suggests that patients with chronic hepatitis C genotypes 4-6 may exhibit different clinical courses and treatment outcomes. Ethnicity-related factors may contribute to the presence of more advanced disease in patients with genotype 4, who also tend to have a poor response to interferon-based therapy. HCV genotype 5 appears to be an easy-to-treat virus with response rates similar to those of genotypes 2 and 3 after a 48-week course of therapy. Response to treatment in patients with HCV genotype 6 may be at an intermediate level between that seen with genotype 1 and genotype 2 or 3. The optimal duration of treatment (24 vs 48 wk) for HCV genotype 6 is unclear and currently is under investigation.

    View details for PubMedID 16234071

  • Chronic hepatitis C: genotypes 4 to 9. Clinics in liver disease Nguyen, M. H., Keeffe, E. B. 2005; 9 (3): 411-?

    Abstract

    Infection with hepatitis C virus (HCV) genotypes 1, 2, or 3 is widely distributed throughout the world and has been the focus of the majority of studies on the epidemiology and treatment of chronic hepatitis C. Infection with HCV genotypes 4 through 9 is prevalent in some geographic areas where the disease burden of chronic hepatitis C approaches endemic levels (eg, HCV genotype 4 in Egypt where there is an HCV infection prevalence of approximately 18%). This article reviews the existing literature, which suggests that chronic hepatitis C with genotypes 4 through 9 may exhibit epidemiologic, clinical, and treatment outcome differences from infection with genotypes 1, 2, or 3.

    View details for PubMedID 16023974

  • The diagnosis and management of benign hepatic tumors JOURNAL OF CLINICAL GASTROENTEROLOGY Choi, B. Y., Nguyen, M. H. 2005; 39 (5): 401-412

    Abstract

    Benign hepatic tumors include a broad spectrum of regenerative and true neoplastic processes. Because of advances in imaging studies such as computed tomography (CT) and magnetic resonance imaging (MRI) as well as progress in immunohistochemistry, accurate diagnosis can now be made in a large percentage of patients without surgical laparotomy or resection. This article will focus on the pathogenesis, diagnosis, and management of focal benign lesions of the liver. Many of these tumors present with typical features in various imaging studies. On occasions, biopsies are required and/or surgical removal is needed. The most common benign hepatic tumors include cavernous hemangioma, focal nodular hyperplasia, hepatic adenoma, and nodular regenerative hyperplasia. In the majority of cases of benign hepatic tumors, patients are asymptomatic, and no treatment is indicated. The main indication for treatment is the presence of significant clinical symptoms or suspicion of malignancy or fear of malignant transformation.

    View details for Web of Science ID 000228498000012

    View details for PubMedID 15815209

  • General management BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY Nguyen, M. H., Keeffe, E. B. 2005; 19 (1): 161-174

    Abstract

    Hepatocellular carcinoma is one of the most common malignancies worldwide. The general management of hepatocellular carcinoma begins with an accurate diagnosis. With advances in imaging studies, noninvasive diagnosis has become an accepted standard of care for hepatocellular carcinoma, though pathologic examination is still required in selected cases. Following diagnosis, accurate staging is the next most important step in selecting the most appropriate treatment modality. Patients with localised tumor and compensated liver disease should be considered for partial hepatectomy, and patients with poor hepatic function but early tumor stage are candidates for liver transplantation. Patients who do not qualify for either of these curative treatments may be evaluated for palliative therapy, of which transarterial chemoembolisation is most widely used. This review will discuss the role of biopsy, the pros and cons of noninvasive and pathologic tissue diagnosis as well as the general approach to choose the most appropriate treatment for patients with hepatocellular carcinoma.

    View details for Web of Science ID 000227994200011

    View details for PubMedID 15757811

  • Benign tumors and evaluation of liver masses In: Al Knawy B, Schiffman ML, and Wiesner R, eds. Hepatology: A Practical Approach, 1st ed. Amsterdam: Elsevier Science BV. Nguyen MH, Keeffe EB 2005
  • Role of Ethnicity in Risk for Hepatocellular Carcinoma in Patients With Chronic Hepatitis C and Cirrhosis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Nguyen, M. H., Whittemore, A. S., Garcia, R. T., Tawfeek, S. A., Ning, J., Lam, S., Wright, T. L., Keeffe, E. B. 2004; 2 (9): 820-824

    Abstract

    In the United States, hepatocellular carcinoma (HCC) is more common among Asians and African Americans than Caucasians, with chronic hepatitis C virus (HCV) infection accounting for up to half of the patients. Our study examined ethnicity as a potential risk factor for HCC among patients with chronic hepatitis C.We conducted a case-control study of 464 patients with chronic hepatitis C and cirrhosis (207 cancer patients and 257 controls) using medical records and pathology records at 4 medical centers. We estimated odds ratios with 95% confidence intervals by using conditional logistic regression on case-control sets, matched within study centers and study period on sex and age groups (< or =45, 46-55, 56-65, >65 yr). To control for potential confounding caused by severity of cirrhosis and residual confounding caused by age, we also included Child-Turcotte-Pugh (CTP) scores and age (continuous variable) in all regression analyses.Compared with Caucasians, the cancer risk was increased significantly among Asians (adjusted odds ratio, 4.3; 95% confidence interval, 2.1-9.0 for men, and 4.6; 1.2-18.5 for women) and somewhat increased among African-American men (adjusted odds ratio, 2.4; 95% confidence interval, 0.9-6.3).This study suggests that, among patients with chronic hepatitis C and cirrhosis, liver cancer risk is increased 4-fold in Asians and may be doubled in African-American men, compared with Caucasians. These results need confirmation in larger studies from racially diverse populations, but, if confirmed, these results point to high-risk populations that should be targeted for screening and preventive efforts.

    View details for DOI 10.1053/S1542-3565(04)00353-2

    View details for Web of Science ID 000208072100013

    View details for PubMedID 15354283

  • Use of endoclips in the treatment of massive colonic diverticular bleeding GASTROINTESTINAL ENDOSCOPY Simpson, P. W., Nguyen, M. H., Lim, J. K., Soetikno, R. M. 2004; 59 (3): 433-437

    View details for Web of Science ID 000220179200024

    View details for PubMedID 14997150

  • Epidemiology and treatment outcomes of patients with chronic hepatitis C and genotypes 4 to 9. Reviews in gastroenterological disorders Nguyen, M. H., Keeffe, E. B. 2004; 4: S14-21

    Abstract

    Pivotal clinical trials of antiviral therapy for chronic hepatitis C have been conducted predominantly in Europe and the United States, where most patients are infected with genotypes 1, 2, or 3. As a result, published data on the outcomes of therapy in patients infected with genotypes 4, 5, and 6 to 9 are limited. However, a major proportion of patients with chronic hepatitis C worldwide reside in geographic areas where genotypes 4 (Africa and the Middle East), 5 (South Africa), or 6 to 9 (southern China and Southeast Asia) are prevalent or even the most common genotypes. The epidemiology of hepatitis C virus genotypes 4 to 9 is reviewed, and the studies reporting the results of antiviral therapy of these genotypes are summarized. The limited data on antiviral therapy in patients with genotypes 4 to 9 highlight the need for further and controlled treatment trials in these populations.

    View details for PubMedID 15184820

  • Unsedated ultrathin EGD is well accepted when compared with conventional sedated EGD: A multicenter randomized trial GASTROENTEROLOGY Garcia, R. T., Cello, J. P., Nguyen, M. H., Rogers, S. J., Rodas, A., Trinh, H. N., Stollman, N. H., Schlueck, G., McQuaid, K. R. 2003; 125 (6): 1606-1612

    Abstract

    In the United States, upper gastrointestinal endoscopy is usually performed using intravenous sedation. Sedation increases the rate of both complications and costs of endoscopy. Unsedated esophagogastroduodenoscopy (EGD) using conventional 8-11-mm endoscopes is an alternative to sedated endoscopy but is generally perceived as unacceptable to many American patients. Unsedated EGD using ultrathin 5-6-mm endoscopes is better tolerated. A randomized trial comparing unsedated ultrathin EGD (UT-EGD) with sedated conventional EGD (C-EGD) in a diverse American population is needed.In this multicenter, randomized, controlled trial, 80 patients scheduled to undergo elective outpatient EGD were randomized to unsedated UT-EGD or sedated C-EGD. The study was carried out at San Francisco General Hospital, San Francisco Veterans Affairs Medical Center, and the Liver and Digestive Health Medical Clinic, San Jose.Baseline characteristics of patients randomized to unsedated UT-EGD and sedated C-EGD were similar. Moreover, there were no significant differences in overall patient satisfaction and willingness to repeat endoscopy in the same manner among the 2 study groups. There was, however, a significant difference in median total procedure time between the 2 study groups of 1.5 hours (P < 0.0001). The mean (+/- SD) total procedure cost was 512.4 US dollars (+/- 100.8 US dollars) for sedated C-EGD and 328.6 US dollars (+/- 70.3 US dollars) for unsedated UT-EGD (P < 0.0001).Patients undergoing unsedated UT-EGD are as satisfied as patients undergoing sedated C-EGD and are just as willing to repeat an unsedated UT-EGD. Unsedated UT-EGD was also faster, less costly, and may allow greater accessibility to this procedure.

    View details for DOI 10.1053/S0016-5085(03)01524-5

    View details for Web of Science ID 000187177600011

    View details for PubMedID 14724812

  • Prophylactic clip application GASTROINTESTINAL ENDOSCOPY Nguyen, M. H., Soetikno, R. 2003; 58 (6): 941-941

    View details for Web of Science ID 000187160200033

    View details for PubMedID 14682305

  • Prophylaxis against chemotherapy-induced reactivation of hepatitis B virus infection with lamivudine JOURNAL OF CLINICAL GASTROENTEROLOGY Simpson, N. D., Simpson, P. W., Ahmed, A. M., Nguyen, M. H., Garcia, G., Keeffe, E. B., Ahmed, A. 2003; 37 (1): 68-71

    Abstract

    The results of lamivudine therapy in 4 patients with chemotherapy-induced hepatitis B virus (HBV) reactivation are reported. Cancer chemotherapy-induced reactivation is a known complication in patients with chronic HBV infection or history of HBV infection with recovery. Reactivation of HBV infection has a broad spectrum of manifestations ranging from mild elevation of aminotransferase levels to fatal fulminant hepatitis. Lamivudine is a nucleoside analogue and a potent inhibitor of HBV reverse transcription. The 4 patients treated with lamivudine included 1 woman with breast cancer and 3 men with non-Hodgkin lymphoma, ranging from 41 to 63 years of age. All 4 patients were undergoing standard, multi-agent chemotherapy when they presented with HBV reactivation manifested by sudden onset of fatigue, jaundice, and HBV serology consistent with active HBV infection (detectable serum HBV DNA) in the absence of other known causes of acute hepatitis. Lamivudine therapy (100 mg/d in 3 patients and 150 mg/d in 1 patient) was initiated from 1 to 18 days following the diagnosis of HBV reactivation. All 4 patients showed rapid decrease in aminotransferase levels within 2 weeks after initiating lamivudine therapy. Unfortunately, hepatic synthetic function failed to improve in 2 patients, who both died. The remaining 2 patients had suppression of HBV DNA to undetectable levels after 1 and 4 months of treatment and had biochemical and clinical improvement. The 2 patients who died received lamivudine therapy for 8 days and for 3 weeks. There have been no randomized clinical trials to study the role of lamivudine for prophylaxis or treatment of HBV reactivation associated with chemotherapy. However, based on our limited experience, lamivudine may be efficacious in suppressing potentially fatal HBV reactivation secondary to chemotherapy in patients with chronic HBV infection or prior infection with recovery. Patients who undergo chemotherapy should be screened for the presence of markers of chronic hepatitis B infection or previous HBV infection. We recommend that patients with chronic HBV infection (positive HBV DNA and/or positive HBsAg) or history of HBV infection with recovery (positive hepatitis B core antibody with or without HBsAb) be considered for prophylactic lamivudine use to prevent chemotherapy-induced HBV reactivation.

    View details for Web of Science ID 000183597500016

    View details for PubMedID 12811213

  • Chronic hepatitis B and hepatitis C in Asian Americans. Reviews in gastroenterological disorders Nguyen, M. H., Keeffe, E. B. 2003; 3 (3): 125-134

    Abstract

    Both chronic hepatitis B and hepatitis C are prevalent among the 12 million Asians and Pacific Islanders living in the United States. Significant epidemiological and clinical differences exist between Asian Americans and the general U.S. population, most notably the higher rate of primary liver cancer and the differential response to various antiviral therapies. Perinatal and childhood transmission is common for hepatitis B virus. Transmission of hepatitis C virus probably also occurs early in life and results from nosocomial transmission and person-to-person spread. Asian patients with chronic hepatitis B commonly have hepatitis B e antigen-negative hepatitis B with either the precore or core-promoter mutant hepatitis B virus, which may require long-term antiviral viral therapy because of high rates of relapse following therapy. Asian patients with chronic hepatitis C may have a substantially higher risk of liver cancer but a better response to interferon-based therapy, both in terms of sustained virological response and reduced future incidence of liver cancer. Understanding these differences will lead to improved care for Asian Americans with viral hepatitis and better disease control for hepatitis B and hepatitis C for the entire U.S. population. This review briefly summarizes the major issues in the clinical care of patients with chronic viral hepatitis and focuses on pertinent epidemiological and clinical differences between Asian-American and Caucasian patients.

    View details for PubMedID 14502116

  • Treatment of Hepatocellular Carcinoma Rustgi AK and Crawford J, eds. Gastrointestinal Cancer: A companion to Sleisenger & Fordtran?s GI and liver diseases. Philadelphia: WB Saunders Nguyen MH, Keeffe EB 2003; 1st ed: 605-622
  • Screening for hepatocellular carcinoma JOURNAL OF CLINICAL GASTROENTEROLOGY Nguyen, M. H., Keeffe, E. B. 2002; 35 (5): S86-S91

    Abstract

    Hepatocellular carcinoma (HCC) is common throughout the world and most often develops as a late complication of chronic viral hepatitis or cirrhosis of any cause. As a result of the high prevalence rate of chronic hepatitis C, the incidence of HCC is rising in the United States, as well as in European and Asian countries. The overall survival rate of HCC is poor, and surgical resection and liver transplantation are the only curative treatment options. Screening for HCC offers the best hope for early detection, eligibility for treatment, and improved survival. Most physicians routinely screen at-risk patients with chronic viral hepatitis and cirrhosis for HCC, despite the lack of official guidelines. The current consensus recommendations are to screen healthy hepatitis B virus carriers with annual or semiannual serum alpha-fetoprotein; carriers with chronic hepatitis or cirrhosis and patients with cirrhosis of any etiology are surveyed with twice yearly serum alpha-fetoprotein and liver ultrasound. This article will review the current recommendations for HCC screening, the rationale that led to these recommendations, and the challenges of cost-effectiveness research in this area.

    View details for Web of Science ID 000179165200004

    View details for PubMedID 12394211

  • Racial differences in effectiveness of alpha-fetoprotein for diagnosis of hepatocellular carcinoma in hepatitis C virus cirrhosis HEPATOLOGY Nguyen, M. H., Garcia, R. T., Simpson, P. W., Wright, T. L., Keeffe, E. B. 2002; 36 (2): 410-417

    Abstract

    alpha-Fetoprotein (AFP) is frequently used as a diagnostic marker for hepatocellular carcinoma (HCC). Most available data concerning AFP come from studies of patients with chronic hepatitis B or other chronic liver diseases of mixed etiologies. Limited data concerning the diagnostic value of AFP for hepatitis C virus (HCV)-related HCC have to date come only from Asian and European studies, and results are conflicting. There may be significant differences in AFP levels depending on racial backgrounds and etiologies of primary liver disease. We conducted a multicenter, retrospective, case-control study of 163 HCC patients with HCV infection and 149 control patients with HCV-related cirrhosis. The positive likelihood ratios for AFP at 0 to 20, 21 to 50, 51 to 100, and 101 to 200 ng/mL were 0.46, 1.31, 1.15, and 6.90, respectively. No controls had AFP greater than 200 ng/mL. The sensitivity of AFP for the diagnosis of HCC in African Americans with HCV infection was lower than that of patients of all other ethnic groups combined (57.1% vs. 81.6% for AFP > 10 ng/mL, P =.02, and 42.9% vs. 66.0% for AFP > 20 ng/mL, P =.05). The area under the receiver operating characteristics curve was 0.81 for non-African Americans but only 0.56 for African Americans. In conclusion, AFP greater than 200 ng/mL can be used to confirm HCC in patients with HCV-related cirrhosis and a hepatic mass. However, AFP is insensitive for the diagnosis of HCC in African Americans.

    View details for DOI 10.1053/jhep.2002.34744

    View details for Web of Science ID 000177085100018

    View details for PubMedID 12143050

  • Does isoniazid cause more serious hepatotoxicity in hepatitis B virus carriers? AMERICAN JOURNAL OF GASTROENTEROLOGY Nguyen, M. H., Garcia, G. 2002; 97 (5): 1092-1093

    View details for Web of Science ID 000175460900004

    View details for PubMedID 12014711

  • Therapeutic advances in the management of hepatitis B and hepatitis C CURRENT OPINION IN INFECTIOUS DISEASES Nguyen, M. H., Wright, T. L. 2001; 14 (5): 593-601

    Abstract

    Until recently, interferon monotherapy has been the only available therapeutic option for patients with chronic hepatitis B and hepatitis C. Lamivudine has emerged as another effective first-line therapy for chronic hepatitis B as well as a beneficial treatment option for patients with decompensated hepatitis B cirrhosis. Viral resistance with long-term lamivudine therapy remains a major concern but new data continue to show benefits despite the development of YMDD mutations. Combination therapy with ribavirin and pegylated interferon-alpha has revolutionized the treatment of chronic hepatitis C. The rate of sustained virological response can now be expected to be as high as nearly 50% for genotype 1 and 80% for non-1 genotypes of hepatitis C.

    View details for Web of Science ID 000171324300014

    View details for PubMedID 11964881

  • DIFFERENTIAL MIGRATION OF ASTROCYTES GRAFTED INTO THE DEVELOPING RAT-BRAIN GLIA Hatton, J. D., Nguyen, M. H., U, H. S. 1993; 9 (2): 113-119

    Abstract

    Fetal and neonatal astrocytes migrate in specific patterns when transplanted into the adult rat host brain. However, it is unclear whether these astrocytes demonstrate the same degree of mobility during early brain development. In the present study, neonatal cortical, hippocampal, and hypothalamic astrocytes were collected from the brains of 1- to 3-day-old rats and placed in tissue culture. After 14 to 21 days, cultures enriched in astrocytes were harvested and labelled with either the fluorescent dye Fast Blue or fluorescein-labelled latex beads. They were then transplanted into the right frontal cerebrum of neonatal rats at 2, 5, 8, and 11 days postpartum. Seven days after transplantation, animals were sacrificed and their brains were fixed by immersion in aldehydes, sectioned on a cryostat, and examined with fluorescence microscopy. Transplanted astrocytes migrated along the corpus callosum, internal capsule, glial limitans, ventricular linings, and hippocampal structure. Labelled cells were also found in the contralateral hemisphere in day 2 brains. Migration in a radial fashion from the injection site toward the periphery was a particularly obvious pattern, and was most pronounced in these younger hosts. In days 5 and 8 rat brains, astrocyte migration became more restricted to the hemisphere of implantation. In 11-day-old host brains, hemispheric restriction and other region-specific influences became manifest and specifically modulated migration. Radial migration was absent in the 11-day-old host group except for cells of cortical origin. The observed results demonstrate that neonatal cortical, hippocampal, and hypothalamic astrocytes transplanted into the neonatal cerebrum migrate in patterns that are more extensive than in the adult brain.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1993LZ51400003

    View details for PubMedID 8244533

Conference Proceedings


  • Unsedated ultrathin EGD is well accepted by most patients: A randomized trial of unsedated ultrathin EGD (UT-EGD) vs. sedated conventional EGD (C-EGD) Garcia, R. T., Cello, J. P., Rogers, S. J., Rodas, A., Nguyen, M. H., Trinh, H., Stollman, N. H., McQuaid, K. R. NATURE PUBLISHING GROUP. 2002: S306-S306

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