Clinical Focus

  • Liver Transplantation
  • Gastroenterology

Academic Appointments

Honors & Awards

  • Honors in Biochemistry, University of the West Indies (1996)
  • Honors in Pharmacology, University of the West Indies (1996)
  • Honors in Obstetrics and Gynecology, University of the West Indies (1996)
  • Chin Yee Prize for Surgery, University of the West Indies (1996)
  • NIH Intramural Fellows Travel Award, National Institutes of Health (2003)
  • AASLD Advanced Hepatology Fellowship,, American Association for the Study of Liver Diseases (2007-2008)

Professional Education

  • Fellowship:UCSF Medical Center (2008) CA
  • Residency:SUNY at Brooklyn School Of Medicine (2002) NY
  • Board Certification: Transplant Hepatology, American Board of Internal Medicine (2008)
  • Board Certification: Gastroenterology, American Board of Internal Medicine (2007)
  • Board Certification, American Board of Internal Medicine, Transplant Hepatology (2008)
  • Fellowship:UCSF Medical Center (2007) CA
  • Fellowship:National Institutes of Health (2005) MD
  • Medical Education:University of the West Indies (1996) West Indies
  • Fellow, UCSF Medical Center, Transplant Hepatology (2008)
  • Research Fellow, National Institutes of Health, Hepatology Research (2005)
  • MHSc, Duke University, Clinical Research (2005)
  • Chief Resident, SUNY Downstate Medical Center, Internal Medicine (2002)
  • Resident, SUNY Downstate Medical Center, Internal Medicine (2001)
  • MBBS, University of the West Indies, Medicine (1996)

Research & Scholarship

Current Research and Scholarly Interests

My primary research intesret is in metabolic liver disease primarily non-alcoholic steatohepatitis. I also have an interset in transplant outcomes for patients with chronic hepatitis C.

Clinical Trials

  • Once-Daily Oral E5501 Tablets Used in Subjects With Chronic Liver Diseases and Thrombocytopenia Prior to Elective Surgical or Diagnostic Procedures Recruiting

    The purpose of this study is to evaluate the efficacy of once-daily Oral E5501 in subjects with chronic liver diseases and thrombocytopenia prior to elective surgical or diagnostic procedures, to evaluate the safety of short-term administration of E5501 and to evaluate the pharmacokinetics (PK) of E5501.

    View full details


Graduate and Fellowship Programs


All Publications

  • A glass half full: Implications of screening for hepatitis C virus in the era of highly effective antiviral therapy. Hepatology Lutchman, G., Kim, W. R. 2015; 61 (5): 1455-1458

    View details for DOI 10.1002/hep.27718

    View details for PubMedID 25614010

  • Recurrent Hepatocellular Carcinoma and Poorer Overall Survival in Patients Undergoing Left-sided Compared With Right-sided Partial Hepatectomy JOURNAL OF CLINICAL GASTROENTEROLOGY Valenzuela, A., Ha, N. B., Gallo, A., Bonham, C., Ahmed, A., Melcher, M., Kim, L. H., Esquivel, C., Concepcion, W., Ayoub, W. S., Lutchman, G. A., Daugherty, T., Nguyen, M. H. 2015; 49 (2): 158-164


    We aimed to determine the incidence and predictors of recurrent hepatocellular carcinoma (HCC) after partial hepatectomy.Liver transplantation is the preferred treatment for selected patients with HCC, but access to donor organs is limited. Partial hepatectomy is another accepted treatment option; however, postoperative recurrence is frequently observed.This is a retrospective cohort study of 107 consecutive patients who underwent partial hepatectomy for HCC between January 1993 and February 2011 at a US University Medical Center. Study endpoints were recurrent HCC, death, loss to follow-up, or last visit without HCC.The study cohort was 78% male with a median age of 61 years and 59% Asians. A total of 50 patients developed recurrent HCC (46.7%) after a median follow-up of 12 (1 to 69) months postresection. Recurrent HCC was significantly higher in patients with left-sided resection (41% at year 1, 54% at year 2, 62% at year 3, 81% at year 4, and 90% at year 5) compared with right-sided resection (18% at year 1, 34% at year 2, 36% at year 3, 44% at year 4, and 72% at year 5). In multivariate Cox proportional hazards model also inclusive of anatomic resection and TNM stage 3/4, left-sided resection was significantly associated with increased HCC recurrence (hazard ratio, 2.13; P=0.02; 95% confidence interval, 1.08-4.2) compared with right-sided resection.HCC recurrence rate is higher among those undergoing left-sided resection: 54% at year 2 and 81% at year 4. Liver transplantation should be considered in patients who are at high risk for recurrence.

    View details for Web of Science ID 000347720300014

    View details for PubMedID 24804988

  • Safety and efficacy of entecavir in adefovir-experienced patients JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Nguyen, N. H., Trinh, H. N., Nguyen, T. T., Do, S. T., Tran, P., Nguyen, H. A., Nguyen, K. K., Garcia, R. T., Lutchman, G. A., Nguyen, M. H. 2015; 30 (1): 43-50


    Suboptimal viral suppression with adefovir (ADV) poses a challenge in managing chronic hepatitis B (CHB). Few studies have evaluated the efficacy of entecavir (ETV) in ADV-experienced patients. Our aim is to assess treatment effectiveness of ETV in ADV-experienced patients.ADV-experienced patients switched to ETV were enrolled from six U.S. clinics. Patients completed a median of 24 months of ETV after switch. Patients were categorized into partial responders (detectable HBV DNA at switch) or complete responders (undetectable HBV DNA at switch) to ADV. Primary and secondary outcome measurements were complete viral suppression (CVS, HBV DNA <60 IU/mL) and biochemical response (BR, ALT < 40 U/L), respectively.A total of 120 patients were included in the analysis (80 ADV partial responders; 40 ADV complete responders). In partial responders, CVS rate was 84% after 24 months of ETV. BR rate was 58% at switch to ETV and increased to 90% after 24 months. All complete responders continued to experience CVS after switch. On multivariate analysis inclusive of age, male gender, ALT level at switch, and history of lamivudine (LAM) exposure, we identified positive HBeAg status before ADV and higher HBV DNA level at time of switch as significant independent negative predictors of CVS. In eight patients with ADV-resistance, seven achieved CVS after 24 months of ETV and all achieved BR.In ADV-experienced patients, high rates of CVS and BR can be achieved/sustained after switching to ETV, including those with ADV resistance or with prior exposure to LAM.

    View details for DOI 10.1111/jgh.12728

    View details for Web of Science ID 000346783900010

  • Meta-analysis: influence of host and viral factors in patients with chronic hepatitis C genotype 4 treated with pegylated interferon and ribavirin EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY Yee, B. E., Nguyen, N. H., Zhang, B., Vutien, P., Wong, C. R., Lutchman, G. A., Nguyen, M. H. 2014; 26 (11): 1189-1201
  • Meta-analysis: influence of host and viral factors in patients with chronic hepatitis C genotype 4 treated with pegylated interferon and ribavirin. European journal of gastroenterology & hepatology Yee, B. E., Nguyen, N. H., Zhang, B., Vutien, P., Wong, C. R., Lutchman, G. A., Nguyen, M. H. 2014; 26 (11): 1189-1201


    The burden of hepatitis C virus genotype 4 (HCV-4) is high in Africa and East Mediterranean countries. Previous reports estimate sustained virologic response (SVR) rates in HCV-4 to be ∼20-70%. However, many of these studies are limited by different study designs and small sample sizes. Our aim was to evaluate treatment outcome and host/viral factors on SVR in HCV-4 patients treated with pegylated interferon and ribavirin (PEG IFN+RBV) in a systematic and quantitative manner. A comprehensive literature search in MEDLINE and EMBASE for 'genotype 4' was conducted in November 2013. Abstracts from American Association for the Study of Liver Diseases, Asian Pacific Study of the Liver, Digestive Disease Week, and European Association for the Study of the Liver in 2012/2013 were reviewed. Inclusion criteria were original studies with at least 25 treatment-naive HCV-4 patients treated with PEG IFN+RBV. Exclusion criteria were coinfection with HIV, hepatitis B virus, or other genotypes. Effect sizes were calculated using random-effects models. Heterogeneity was determined by Cochrane Q-test (P<0.05) and I statistic (>50%). We included 51 studies (11 102 HCV-4 patients) in the primary analysis. Pooled SVR was 53% [95% confidence interval (CI): 50-55%] (Q-statistic=269.20, P<0.05; I=81.43). On subgroup analyses, SVR was significantly associated with lower viral load, odds ratio (OR) 3.05 (CI: 1.80-5.17, P<0.001); mild fibrosis, OR 3.17 (CI: 2.19-4.59, P<0.001); and favorable IL28B polymorphisms, rs12979860 CC versus CT/TT, OR 4.70 (CI: 2.87-7.69, P<0.001), and rs8099917 TT versus GT/GG, OR 5.21 (CI: 2.31-11.73, P<0.001). HCV-4 patients treated with PEG IFN+RBV may expect SVR rates of ∼50%. Lower viral load, mild fibrosis, and favorable IL28B (rs12979860 CC and rs8099917 TT) are positively associated with SVR.

    View details for DOI 10.1097/MEG.0000000000000147

    View details for PubMedID 25171028

  • Mutations in HBV DNA Polymerase Associated With Nucleos(t)ide Resistance Are Rare in Treatment-naive Patients CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vutien, P., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Levitt, B. S., Khanh Nguyen, K., da Silveira, E., Daugherty, T., Ahmed, A., Garcia, G., Lutchman, G. A., Nguyen, M. H. 2014; 12 (8): 1363-1370


    Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment naïve 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-naïve 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-naïve 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-naïve 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 Web of Science ID 000341119700026

  • 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


    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 Web of Science ID 000330585500029

  • 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


    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 Web of Science ID 000326888100003

  • 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


    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

  • 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


    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 ?200 mg/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

  • 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


    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

  • Screening for Hepatocellular Carcinoma After HBsAg Clearance Age Before Cirrhosis? JOURNAL OF CLINICAL GASTROENTEROLOGY Lutchman, G. A., Nguyen, M. A. 2011; 45 (1): 4-5

    View details for DOI 10.1097/MCG.0b013e3181faf0d1

    View details for Web of Science ID 000285290700002

    View details for PubMedID 21063212

  • Endoscopic Management of a Spontaneous Gallbladder Perforation and Bile Leak DIGESTIVE DISEASES AND SCIENCES Munroe, C., Padilla-Thornton, A. E., Triadafilopoulos, G., Van Dam, J., Lutchman, G. 2010; 55 (10): 2767-2769

    View details for DOI 10.1007/s10620-010-1319-x

    View details for Web of Science ID 000282093700028

    View details for PubMedID 20632104

  • Ribavirin Improves Early Responses to Peginterferon Through Improved Interferon Signaling GASTROENTEROLOGY Feld, J. J., Lutchman, G. A., Heller, T., Hara, K., Pfeiffer, J. K., Leff, R. D., Meek, C., Rivera, M., Ko, M., Koh, C., Rotman, Y., Ghany, M. G., Haynes-Williams, V., Neumann, A. U., Liang, T. J., Hoofnagle, J. H. 2010; 139 (1): 154-U239


    The therapeutic mechanisms of ribavirin for hepatitis C are unclear. Microarray analyses have shown that ribavirin increases induction of interferon-stimulated genes. We evaluated viral kinetics, serum cytokine expression, and viral mutagenesis during early stages of peginterferon therapy with and without ribavirin.Fifty patients with chronic hepatitis C virus (HCV) infection genotype 1 were randomly assigned to groups that were given peginterferon alpha-2a, with or without ribavirin, for 4 weeks; all patients then received an additional 44 weeks of combination therapy. First- and second-phase viral kinetics were evaluated. Serum levels of interferon-gamma-inducible protein-10 (IP10), monokine induced by interferon-gamma, and monocyte chemoattractant protein 1 were quantified as measures of the interferon-stimulated genes response. NS5A and NS5B were partially sequenced, and mutation rates were calculated.The first-phase decrease in HCV RNA was similar between groups. Patients who received ribavirin had a more rapid second-phase decrease, compared with patients who did not receive ribavirin-particularly those with an adequate first-phase decrease (0.61 vs 0.35 log10 IU/mL/week; P = .018). At 12 hours, fold induction of serum IP10 was higher in patients given the combination therapy than those given peginterferon only (7.6- vs 3.8-fold; P = .01); however, the difference was greatest in patients with an adequate first-phase decrease in HCV RNA. IP10-induction correlated with first- and second-phase kinetics and with ribavirin serum concentrations on day 3. HCV mutation rates were similar between groups.Ribavirin improves the kinetics of the early response to therapy in patients with an adequate initial response to peginterferon. Induction of interferon-stimulated cytokines correlates with viral kinetics following ribavirin therapy, suggesting that ribavirin promotes interferon signaling.

    View details for DOI 10.1053/j.gastro.2010.03.037

    View details for Web of Science ID 000279321000026

    View details for PubMedID 20303352

  • Reactivation of Hepatitis B With Reappearance of Hepatitis B Surface Antigen After Chemotherapy and Immunosuppression CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Palmore, T. N., Shah, N. L., Loomba, R., Borg, B. B., Lopatin, U., Feld, J. J., Khokhar, F., Lutchman, G., Kleiner, D. E., Young, N. S., Childs, R., Barrett, A. J., Liang, T. J., Hoofnagle, J. H., Heller, T. 2009; 7 (10): 1130-1137


    HBV infection may reactivate in the setting of immunosuppression, although the frequency and consequences of HBV reactivation are not well known. We report 6 patients who experienced loss of serologic markers of hepatitis B immunity and reappearance of HBsAg in the serum as a result of a variety of acquired immune deficiencies.Between 2000 and 2005, six patients with reactivation of hepatitis B were seen in consultation by the Liver Diseases Branch at the Clinical Center, National Institutes of Health. The course and outcome of these 6 patients were reviewed.All 6 patients developed reappearance of HBsAg and evidence of active liver disease after stem cell transplantation (n = 4), immunosuppressive therapy (n = 1), or change in human immunodeficiency virus antiretroviral regimen (n = 1), despite having antibody to HBsAg (anti-HBs) or antibody to hepatitis B core antigen (anti-HBc) without HBsAg before. All 6 patients developed chronic hepatitis B, 2 patients transmitted hepatitis B to their spouses, and 1 patient developed cirrhosis. The diagnosis of hepatitis B reactivation was frequently missed or delayed and often required interruption of the therapy for the underlying condition. None of the patients received antiviral prophylaxis against HBV reactivation.Serologic evidence of recovery from hepatitis B infection does not preclude its reactivation after immunosuppression. Screening for serologic evidence of hepatitis B and prophylaxis of those with positive results by using nucleoside analogue antiviral therapy should be provided to individuals in whom immunosuppressive therapy is planned.

    View details for DOI 10.1016/j.cgh.2009.06.027

    View details for Web of Science ID 000271041800022

    View details for PubMedID 19577007

  • Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis ALIMENTARY PHARMACOLOGY & THERAPEUTICS Loomba, R., Lutchman, G., Kleiner, D. E., Ricks, M., Feld, J. J., Borg, B. B., Modi, A., Nagabhyru, P., Sumner, A. E., Liang, T. J., Hoofnagle, J. H. 2009; 29 (2): 172-182


    Non-alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing agents such as metformin may be beneficial for NASH.To assess the effects of metformin on insulin sensitivity, body composition, serum alanine aminotransferase (ALT) levels and liver histology in patients with NASH.Patients underwent liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint was a three-point improvement in the histological NASH activity index.Of 28 patients enrolled, 26 (13 females; average age 44 years) completed 48 weeks of treatment and underwent repeat metabolic studies, imaging and liver biopsy. Thirty per cent achieved a histological response. Most patients lost weight, the average being 6 kg. There was a marked association between weight loss and improvements in NASH activity index and ALT levels (both, P < 0.01). Insulin sensitivity also improved, but the degree of change did not correlate with histological improvement.Metformin leads to improvements in liver histology and ALT levels in 30% of patients with NASH, probably by its effects in causing weight loss.

    View details for DOI 10.1111/j.1365-2036.2008.03869.x

    View details for Web of Science ID 000261781900003

    View details for PubMedID 18945255

  • The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis HEPATOLOGY Lutchman, G., Modi, A., Kleiner, D. E., Promrat, K., Heller, T., Ghany, M., Borg, B., Loomba, R., Liang, T. J., Premkumar, A., Hoofnagle, J. H. 2007; 46 (2): 424-429


    A pilot study of a 48-week course of pioglitazone demonstrated significant improvements in the biochemical and histological features of nonalcoholic steatohepatitis (NASH). The aim of the study was to assess the effects of stopping pioglitazone. Twenty-one patients with NASH were treated with pioglitazone (30 mg/day) for 48 weeks and underwent baseline and end-of-treatment evaluation including liver biopsy. Thirteen patients were followed for at least 48 weeks after stopping therapy and 9 underwent repeat liver biopsy. Statistical comparisons were made to evaluate whether discontinuation of pioglitazone resulted in a reversal of improvements seen on therapy. Stopping pioglitazone was associated with subsequent elevation in serum alanine aminotransferase levels (from 34 +/- 13 to 70 +/- 39 IU/l), decrease in adiponectin (from 9.7 +/- 9.1 to 5.1 +/- 4.5 microg/ml), worsening insulin sensitivity (HOMA Index: from 2.9 +/- 1.8 to 5.5 +/- 5.4), and increase in total hepatic fat (from 30% +/- 32% to 71% +/- 33%) despite no change in average body weight compared to the end of treatment. Repeat liver biopsy in 9 patients revealed significant worsening of parenchymal inflammation (from 1.2 +/- 0.7 to 2.9 +/- 1.1) and steatosis (from 0.9 +/- 0.6 to 2.1 +/- 1.3) but no change in fibrosis (from 1.1 +/- 1.2 to 1.2 +/- 1.3). NASH was again present on liver biopsy in 7 patients.These findings suggest that long-term therapy with pioglitazone may be necessary to maintain improvements in disease activity in patients with NASH, although weight gain during treatment may ultimately limit its beneficial effects.

    View details for DOI 10.1002/hep.21661

    View details for Web of Science ID 000248501600019

    View details for PubMedID 17559148

  • Mutation rate of the hepatitis C virus NS5B in patients undergoing treatment with ribavirin monotherapy GASTROENTEROLOGY Lutchman, G., Danehower, S., Song, B., Liang, T. J., Hoofnagle, J. H., Thomson, M., Ghany, M. G. 2007; 132 (5): 1757-1766


    Error catastrophe from an increase in mutation rate may be a possible mechanism of action of ribavirin in chronic hepatitis C (CHC). We sought to evaluate the mutagenic potential of ribavirin in vivo and to determine if conserved regions of hepatitis C virus (HCV) NS5B are mutated during ribavirin therapy.Thirty-one patients with CHC genotype 1 who participated in a randomized, placebo-controlled trial of ribavirin for 48 weeks were studied. After 48 weeks, patients on placebo were crossed-over to open-label ribavirin for 48 weeks. Viral RNA was extracted from paired, stored sera at day 0 and week 24 during the randomized phase and weeks 48, 52, and 72 during the cross-over phase. The entire NS5B region was sequenced and the mutation rates were calculated.An increase in mutation rate was observed after 4 weeks (4.4 x 10(-2) vs 2.1 x 10(-3) per site/y, P = .02) but not after 24 weeks (4.0 x 10(-3) vs. 5.5 x 10(-3) per site/y, P = .1) in patients who crossed over to ribavirin. Similarly, during the randomized phase no increase in the number of mutations or the mutation rate was observed at week 24 between the ribavirin- and placebo-treated patients 6.6 vs 4.3 x 10(-3) per site/y, respectively (P = .4). No mutations were observed in conserved regions of NS5B.Ribavirin therapy is associated with an early, transient increase in the mutation rate of HCV. Lethal mutagenesis and error catastrophe is unlikely to be the sole mechanism of action of ribavirin during therapy for CHC.

    View details for DOI 10.1053/j.gastro.2007.03.035

    View details for Web of Science ID 000246456400020

    View details for PubMedID 17484873

  • Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic steatohepatitis: Relationship to histological improvement CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Lutchman, G., Promrat, K., Kleiner, D. E., Heller, T., Ghany, M. G., Yanovski, J. A., Liang, T. J., Hoofnagle, J. H. 2006; 4 (8): 1048-1052


    Thiazolidinedione (TZD) therapy improves liver histology in nonalcoholic steatohepatitis (NASH) through a mechanism possibly related to its insulin-sensitizing or anti-inflammatory activity. This study was conducted to assess changes in serum levels of selected adipokines and proinflammatory cytokines and to relate these changes to the improved liver histology resulting from pioglitazone therapy for NASH.Serum samples from 18 patients with NASH obtained at day 0 and week 48 of therapy during an open-label study of pioglitazone were tested for adiponectin, leptin, interleukin (IL)-1a, IL-6, and tumor necrosis factor (TNF)-alpha levels. Paired liver biopsy specimens were scored (0-4) for steatosis, parenchymal inflammation, cell injury, and fibrosis.Adiponectin levels increased from 3.7 to 10.3 mug/mL at week 48 (P < .01); the levels of the other cytokines were unchanged: TNF-alpha, 9.1 vs 8.8 pg/mL; IL-1a, 3.9 vs 3.4 pg/mL; IL-6, 19.4 vs 13.4 pg/mL; and leptin, 24.8 vs 29.6 ng/mL (P > .05 for all). Pioglitazone therapy was associated with improvements in steatosis (2.5 vs 1.0), parenchymal inflammation (3.3 vs 2.1), cell injury (2.2 vs 0.9), and fibrosis (2.0 vs 1.4). The change in adiponectin level was associated with the improvement in steatosis (P = .03) as well as in a summary NASH activity index score (P = .01). Changes in IL-1, IL-6, TNF-alpha, and leptin levels did not correlate with improvements in the histological features.Improvements in liver histology during TZD therapy may be modulated by an adiponectin-mediated effect on insulin sensitivity and hepatic fatty acid metabolism rather than by changes in proinflammatory cytokines.

    View details for DOI 10.1016/j.cgh.2006.05.005

    View details for Web of Science ID 000239718600018

    View details for PubMedID 16814613

  • Steatosis and progression of fibrosis in untreated patients with chronic hepatitis C infection HEPATOLOGY Perumalswami, P., Kleiner, D. E., Lutchman, G., Heller, T., Borg, B., Park, Y., Liang, T. J., Hoofnagle, J. H., Ghany, M. G. 2006; 43 (4): 780-787


    Hepatic steatosis is common in patients with chronic hepatitis C (CHC) and is reported to be a risk factor for progression of fibrosis. The aims of this study were to evaluate the interactions between hepatic steatosis and fibrosis in a well-defined cohort of patients with CHC. The computerized pathology database at the National Institutes of Health Clinical Center was searched for patients with CHC who had undergone liver biopsy between 1980 and 2003. Biopsies were scored for necroinflammation using a modified histology activity index, fibrosis using the Ishak system, and steatosis as either none (<5% of cells), mild (5%-25%), or moderate-to-severe (>25%). Four hundred ninety-four patients were identified. The mean age was 44 +/- 9.8 years; 60% were male, 80% Caucasian, and 65% were infected with genotype 1. Steatosis was mild in 31% and moderate to severe in 9% of patients. In univariate analysis, steatosis was associated with increased age, body weight, body mass index (BMI), alanine aminotransferase (ALT) levels, histological necroinflammatory activity, and fibrosis. However, in multivariate analysis, steatosis was associated only with increased age, BMI, and ALT levels and not with fibrosis. One hundred thirty-six patients had 2 liver biopsies separated by 0.5 to 17 years. Worsening of fibrosis occurred in 40% of patients and correlated independently with increasing age, periportal necroinflammation, and ALT elevations but not with steatosis. In conclusion, in this cohort of patients with CHC, steatosis was associated with older age, higher BMI, and higher serum ALT levels but not with the presence of or subsequent progression of fibrosis.

    View details for DOI 10.1002/hep.21078

    View details for Web of Science ID 000236433900018

    View details for PubMedID 16557550

  • Pilot study of interferon gamma for chronic hepatitis C JOURNAL OF HEPATOLOGY Soza, A., Heller, T., Ghany, M., Lutchman, G., Liang, T. J., Germain, J., Hsu, H. H., Park, Y., Hoofnagle, J. H. 2005; 43 (1): 67-71


    Currently, there are no effective therapies available for patients with chronic hepatitis C who have failed to respond to optimal interferon alfa-based regimens. The aims of this pilot study were to assess the antiviral activity and safety of interferon gamma in chronic hepatitis C.Patients with chronic hepatitis C, genotype 1, who had not responded to or who had relapsed after therapy with interferon alfa and ribavirin were enrolled in a trial of interferon gamma 1b given in doses of 100, 200 or 400 microg subcutaneously three times weekly for 4 weeks. Frequent blood samples were obtained for HCV RNA levels.Fourteen patients were enrolled. Geometric mean HCV RNA levels remained unchanged. Serum aminotransferase levels also did not change, while there were significant decreases in neutrophil counts (-41% from baseline) and hematocrit (-5%). Low grade fever and malaise were common with the first injection of interferon gamma, but no serious side effects were encountered.Although relatively well tolerated, interferon gamma in doses of 100-400 microg thrice weekly had no effect on HCV RNA levels in patients with chronic hepatitis C who had failed to achieve a sustained response to interferon alfa-based therapies.

    View details for DOI 10.1016/j.jhep.2005.02.023

    View details for Web of Science ID 000230282300014

    View details for PubMedID 15913831

  • Pushing the treatment envelope for chronic hepatitis C - Is more necessarily better? HEPATOLOGY Lutchman, G., Ghany, M. 2005; 41 (2): 234-236

    View details for DOI 10.1002/hep.20605

    View details for Web of Science ID 000226637900003

    View details for PubMedID 15657958

  • A pilot study of ploglitazone treatment for nonalcoholic steatohepatitis HEPATOLOGY Promrat, K., Lutchman, G., Uwaifo, G. I., Freedman, R. J., Soza, A., Heller, T., Doo, E., Ghany, M., Premkumar, A., Park, Y., Liang, T. J., Yanovski, J. A., Kleiner, D. E., Hoofnagle, J. H. 2004; 39 (1): 188-196


    Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease for which there is no known effective therapy. A proportion of patients with NASH progress to advanced fibrosis and cirrhosis. NASH is considered one of the clinical features of the metabolic syndrome in which insulin resistance plays a central role. This prospective study evaluates the role of insulin-sensitizing agent in treatment of NASH. Eighteen nondiabetic patients with biopsy-proven NASH were treated with pioglitazone (30 mg daily) for 48 weeks. Tests of insulin sensitivity and body composition as well as liver biopsies were performed before and at the end of treatment. By 48 weeks, serum alanine aminotransferase values fell to normal in 72% of patients. Hepatic fat content and size as determined by magnetic resonance imaging decreased, and glucose and free fatty acid sensitivity to insulin were uniformly improved. Histological features of steatosis, cellular injury, parenchymal inflammation, Mallory bodies, and fibrosis were significantly improved from baseline (all P < 0.05). Using strict criteria, histological improvement occurred in two-thirds of patients. Pioglitazone was well tolerated; the main side effects were weight gain (averaging 4%) and an increase in total body adiposity. In conclusion, these results indicate that treatment with an insulin-sensitizing agent can lead to improvement in biochemical and histological features of NASH and support the role of insulin resistance in the pathogenesis of this disease. The long-term safety and benefits of pioglitazone require further study.

    View details for DOI 10.1002/hep.20012

    View details for Web of Science ID 000220375400023

    View details for PubMedID 14752837

  • Viral kinetics in hepatitis C HEPATOLOGY Lutchman, G., Hoofnagle, J. H. 2003; 37 (6): 1257-1259

    View details for DOI 10.1053/jhep.2003.50238

    View details for Web of Science ID 000183236700006

    View details for PubMedID 12774002

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