Gabriel Garcia, MD

All Publications

• A Nationwide Study of Inpatient Admissions, Mortality, and Costs for Patients with Cirrhosis from 2005 to 2015 in the USA. Digestive diseases and sciences Zou, B., Yeo, Y. H., Jeong, D., Park, H., Sheen, E., Lee, D. H., Henry, L., Garcia, G., Ingelsson, E., Cheung, R., Nguyen, M. H. 2019

  Abstract

  BACKGROUND AND AIMS: Liver cirrhosis is a substantial health burden in the USA, but population-based data regarding the trend and medical expenditure are limited and outdated. We investigated the trends of inpatient admissions, costs, and inpatient mortality from 2005 to 2015 among cirrhotic patients.METHODS: A retrospective analysis was conducted using the National Inpatient Sample database. We adjusted the costs to 2015 US dollars using a 3% inflation rate. National estimates of admissions were determined using discharge weights.RESULTS: We identified 1,627,348 admissions in cirrhotic patients between 2005 and 2015. From 2005 to 2015, the number of weighted admissions in cirrhotic patients almost doubled (from 505,032 to 961,650) and the total annual hospitalization cost in this population increased three times (from 5.8 to 16.3 billion US dollars). Notably, admission rates varied by liver disease etiology, decreasing from 2005 to 2015 among patients with hepatitis C virus (HCV)-related cirrhosis while increasing (almost tripled) among patients with nonalcoholic fatty liver disease (NAFLD)-related cirrhosis. The annual inpatient mortality rate per 1000 admissions overall decreased from 63.8 to 58.2 between 2005 and 2015 except for NAFLD (27.2 to 35.8) (P<0.001).CONCLUSIONS: Rates and costs of admissions in cirrhotic patients have increased substantially between 2005 and 2015 in the USA, but varied by liver disease etiology, with decreasing rate for HCV-associated cirrhosis and for HBV-associated cirrhosis but increasing for NAFLD-associated cirrhosis. Inpatient mortality also increased by one-third for NAFLD, while it decreased for other diseases. Cost also varied by etiology and lower for HCV-associated cirrhosis.

  View details for DOI 10.1007/s10620-019-05869-z

  View details for PubMedID 31598919

• PD-1 Blockade in a Liver Transplant Recipient With Microsatellite Unstable Metastatic Colorectal Cancer and Hepatic Impairment. Journal of the National Comprehensive Cancer Network : JNCCN Chen, J. A., Esteghamat, N., Kim, E. J., Garcia, G., Gong, J., Fakih, M. G., Bold, R. J., Cho, M. T. 2019; 17 (9): 1026–30

  Abstract

  Immune checkpoint inhibitors represent a newly established standard of care in patients with refractory metastatic colorectal cancer with mismatch repair deficiency and microsatellite instability. However, the use of immunotherapy is unclear in recipients of liver transplants with or without concurrent liver function abnormalities. Clinical trials investigating immunotherapy have mostly excluded liver transplant recipients and patients with abnormal liver function. This report presents the first case, to our knowledge, of a liver transplant patient with mismatch repair-deficient colon adenocarcinoma with liver metastases and concurrent abnormal liver function who safely responded to immunotherapy. We also review the literature on checkpoint inhibitor use in patients with other metastatic solid tumors after liver transplant and those with baseline liver function abnormalities. An increasing body of evidence supports the safety of checkpoint inhibition in patients with cancer and solid organ transplants, but further prospective studies are warranted. Use of immunotherapy in liver transplant recipients who have metastatic colorectal cancer with microsatellite instability is feasible but should be performed in a multidisciplinary team setting.

  View details for DOI 10.6004/jnccn.2019.7328

  View details for PubMedID 31487676

• National Estimates of Overall and Liver-Related Inpatient Care Cost in Cirrhotic Patients with Diverse Etiologies and Ethnicities in the United States (US) Zou, B., Yeo, Y., Jeong, D., Cheung, R., Sheen, E., Park, H., Lee, D., Garcia, G., Nguyen, M. H. WILEY. 2018: 110A

  View details for Web of Science ID 000446020500176

• Higher mortality and hospital charges in patients with cirrhosis and acute respiratory illness: a population-based study SCIENTIFIC REPORTS Zou, B., Yeo, Y., Jeong, D., Sheen, E., Park, H., Nguyen, P., Hsu, Y., Garcia, G., Nguyen, M. H. 2018; 8

  View details for DOI 10.1038/s41598-018-28317-w

  View details for Web of Science ID 000436955000024

• Temporal trends in disease presentation and survival of patients with hepatocellular carcinoma: A real-world experience from 1998 to 2015. Cancer Kim, N. G., Nguyen, P. P., Dang, H., Kumari, R., Garcia, G., Esquivel, C. O., Nguyen, M. H. 2018

  Abstract

  Hepatocellular carcinoma (HCC) is one of the few cancers whose incidence continues to increase. The goal of the current study was to investigate the presentation and survival trends of patients with HCC presenting to a university hospital between 1998 and 2015.Study data were ascertained by individual chart review with survival data also supplemented by National Death Index query up to December 31, 2015. Patients were divided into three 6-year groups by diagnosis date (1998-2003, 2004-2009, and 2010-2015).A total of 2106 consecutive patients with HCC were included. The majority of patients had either hepatitis C (56.7%) or hepatitis B (22.1%), but cases of nonalcoholic steatohepatitis HCC increased by 68% over the most recent time period. Screening/surveillance identified 61% of HCC cases, but only 31% of these patients underwent curative treatment, which did not increase significantly over time. The overall median survival was 29.8 months (2.48 years) and without improvement over time. On multivariable analysis, Asian or Hispanic ethnicity, meeting Milan criteria, and receiving any of the standard HCC treatments were found to be significantly associated with improved survival, but diagnosis time period and liver disease etiology were not.Over the last 18 years, the percentage of cases of nonalcoholic steatohepatitis HCC has increased but not overall survival. It is interesting to note that only 31% of patients with HCC identified via screening/surveillance received any curative treatment. Further research is needed to better understand the barriers to curative care for patients with HCC and the causes of the lack of improvement in survival in the more recent patient cohort. Cancer 2018. © 2018 American Cancer Society.

  View details for PubMedID 29624631

• Higher mortality and hospital charges in patients with cirrhosis and acute respiratory illness: a population-based study. Scientific reports Zou, B., Yeo, Y. H., Jeong, D., Sheen, E., Park, H., Nguyen, P., Hsu, Y. C., Garcia, G., Nguyen, M. H. 2018; 8 (1): 9969

  Abstract

  Both cirrhosis and acute respiratory illness (ARI) carry substantial disease and financial burden. To compare hospitalized patients with cirrhosis with ARI to cirrhotic patients without ARI, a retrospective cohort study was conducted using the California Office of Statewide Health Planning and Development database. To balance the groups, propensity score matching (PSM) was used. We identified a total of 46,192 cirrhotic patients during the three study periods (14,049, 15,699, and 16,444 patients, respectively). Among patients hospitalized with cirrhosis, the ARI prevalence was higher in older age groups (p < 0.001), the Asian population (p = 0.002), non-Hispanic population (p = 0.001), and among Medicare patients (p < 0.001). Compared to controls, patients with ARI had 53.8% higher adjusted hospital charge ($122,555 vs. $79,685 per patient per admission, p < 0.001) and 35.0% higher adjusted in-hospital mortality (p < 0.001). Older patients, patients with alcoholic liver disease or liver cancer were at particularly higher risk (adjusted hazard ratio = 2.94 (95% CI: 2.26-3.83), 1.22 (95% CI: 1.02-1.45), and 2.17 (95% CI: 1.76-2.68) respectively, p = 0.028 to <0.001). Mortality rates and hospital charges in hospitalized cirrhotic patients with ARI were higher than in cirrhotic controls without ARI. Preventive efforts such as influenza and pneumococcal vaccination, especially in older patients and those with liver cancer, or alcoholic liver disease, would be of value.

  View details for PubMedID 29967363

• Real-world experience with interferon-free, direct acting antiviral therapies in Asian Americans with chronic hepatitis C and advanced liver disease. Medicine Chang, C. Y., Nguyen, P., Le, A., Zhao, C., Ahmed, A., Daugherty, T., Garcia, G., Lutchman, G., Kumari, R., Nguyen, M. H. 2017; 96 (6)

  Abstract

  Real-life data on interferon (IFN)-free direct acting antiviral (DAA) therapies for chronic hepatitis C (CHC) is limited for Asian Americans.To evaluate sustained virologic response (SVR) and adverse events (AE) in Asian Americans treated with sofosbuvir (SOF)-based, IFN-free DAA therapies.This is a retrospective study of 110 consecutive Asian Americans with HCV genotypes 1 to 3 or 6 treated with IFN-free SOF-based regimens for 8 to 24 weeks between February 2014 and March 2016 at a university center in Northern California.Mean age was 63 ± 12 years, mean BMI was 25 ± 6 (kg/m), and about half (52%) were male. Most patients were infected with HCV genotype 1 (HCV-1, 64%), followed by HCV-2 (14%), HCV-6 (13%), and HCV-3 (8%). Half had cirrhosis, and the majority of these (67%) had decompensation. Overall SVR12 was 93% (102/110), and highest among patients without cirrhosis, liver transplant, or HCC (100%, 37/37). SVR12 was lower among patients with HCC (82%, 14/17), decompensated cirrhosis (84%, 31/37), or liver transplant (89%, 17/19), regardless of treatment and genotype. Most common AEs were anemia (25%), fatigue (20%), and headache (12%). Anemia was highest in patients receiving SOF/RBV (67%). There was 1 treatment-unrelated serious adverse effect (SAE). There were 7 dose reductions due to anemia or fatigue from RBV and 2 treatment discontinuations due to fatigue or loss of insurance authorization.This real-life cohort of Asian American CHC patients treated with IFN-free SOF-based therapies showed high overall treatment response and good tolerability, despite very high rates of advanced disease and prior treatment failure.

  View details for DOI 10.1097/MD.0000000000006128

  View details for PubMedID 28178174

• The Effect of Gastric Acid Suppression on Ledipasivir-Sofosbuvir Effectiveness in Chronic Hepatitis C Infection Swanner, A., Kumari, R., Garcia, G., Daugherty, T., Nguyen, M. H., Ahmed, A., Kim, W., Lutchman, G. A. WILEY. 2016: 947A

  View details for Web of Science ID 000385493804275

• Sex differences in disease presentation, treatment and clinical outcomes of patients with hepatocellular carcinoma: a single-centre cohort study. BMJ open gastroenterology Ladenheim, M. R., Kim, N. G., Nguyen, P., Le, A., Stefanick, M. L., Garcia, G., Nguyen, M. H. 2016; 3 (1)

  Abstract

  Although sex differences in hepatocellular carcinoma (HCC) risk are well known, it is unclear whether sex differences also exist in clinical presentation and survival outcomes once HCC develops.We performed a retrospective cohort study of 1886 HCC patients seen in a US medical centre in 1998-2015. Data were obtained by chart review with survival data also by National Death Index search.The cohort consisted of 1449 male and 437 female patients. At diagnosis, men were significantly younger than women (59.9±10.7 vs 64.0±11.6, p<0.0001). Men had significantly higher rates of tobacco (57.7% vs 31.0%, p<0.001) and alcohol use (63.2% vs 35.1%, p<0.001). Women were more likely to be diagnosed by routine screening versus symptomatically or incidentally (65.5% vs 58.2%, p=0.03) and less likely to present with tumours >5 cm (30.2% vs 39.8%, p=0.001). Surgical and non-surgical treatment utilisation was similar for both sexes. Men and women had no significant difference in median survival from the time of diagnosis (median 30.7 (range=24.5-41.3) vs 33.1 (range=27.4-37.3) months, p=0.84). On multivariate analysis, significant predictors for improved survival included younger age, surgical or non-surgical treatment (vs supportive care), diagnosis by screening, tumour within Milan criteria and lower Model for End-Stage Liver Disease score, but not female sex (adjusted HR=1.01, CI 0.82 to 1.24, p=0.94).Although men have much higher risk for HCC development, there were no significant sex differences in disease presentation or survival except for older age and lower tumour burden at diagnosis in women. Female sex was not an independent predictor for survival.

  View details for DOI 10.1136/bmjgast-2016-000107

  View details for PubMedID 27493763

  View details for PubMedCentralID PMC4964155

• Lesbian, Gay, Bisexual, and Transgender Patient Care: Medical Students' Preparedness and Comfort. Teaching and learning in medicine White, W., Brenman, S., Paradis, E., Goldsmith, E. S., Lunn, M. R., Obedin-Maliver, J., Stewart, L., Tran, E., Wells, M., Chamberlain, L. J., Fetterman, D. M., Garcia, G. 2015; 27 (3): 254-263

  Abstract

  Phenomenon: Lesbian, gay, bisexual, and transgender (LGBT) individuals face significant barriers in accessing appropriate and comprehensive medical care. Medical students' level of preparedness and comfort caring for LGBT patients is unknown.An online questionnaire (2009-2010) was distributed to students (n = 9,522) at 176 allopathic and osteopathic medical schools in Canada and the United States, followed by focus groups (2010) with students (n = 35) at five medical schools. The objective of this study was to characterize LGBT-related medical curricula, to determine medical students' assessments of their institutions' LGBT-related curricular content, and to evaluate their comfort and preparedness in caring for LGBT patients.Of 9,522 survey respondents, 4,262 from 170 schools were included in the final analysis. Most medical students (2,866/4,262; 67.3%) evaluated their LGBT-related curriculum as "fair" or worse. Students most often felt prepared addressing human immunodeficiency virus (HIV; 3,254/4,147; 78.5%) and non-HIV sexually transmitted infections (2,851/4,136; 68.9%). They felt least prepared discussing sex reassignment surgery (1,061/4,070; 26.1%) and gender transitioning (1,141/4,068; 28.0%). Medical education helped 62.6% (2,669/4,262) of students feel "more prepared" and 46.3% (1,972/4,262) of students feel "more comfortable" to care for LGBT patients. Four focus group sessions with 29 students were transcribed and analyzed. Qualitative analysis suggested students have significant concerns in addressing certain aspects of LGBT health, specifically with transgender patients. Insights: Medical students thought LGBT-specific curricula could be improved, consistent with the findings from a survey of deans of medical education. They felt comfortable, but not fully prepared, to care for LGBT patients. Increasing curricular coverage of LGBT-related topics is indicated with emphasis on exposing students to LGBT patients in clinical settings.

  View details for DOI 10.1080/10401334.2015.1044656

  View details for PubMedID 26158327

• Sexual and Gender Minority Identity Disclosure During Undergraduate Medical Education: "In the Closet" in Medical School ACADEMIC MEDICINE Mansh, M., White, W., Gee-Tong, L., Lunn, M. R., Obedin-Maliver, J., Stewart, L., Goldsmith, E., Brenman, S., Tran, E., Wells, M., Fetterman, D., Garcia, G. 2015; 90 (5): 634-644

  Abstract

  To assess identity disclosure among sexual and gender minority (SGM) students pursuing undergraduate medical training in the United States and Canada.From 2009 to 2010, a survey was made available to all medical students enrolled in the 176 MD- and DO-granting medical schools in the United States and Canada. Respondents were asked about their sexual and gender identity, whether they were "out" (i.e., had publicly disclosed their identity), and, if they were not, their reasons for concealing their identity. The authors used a mixed-methods approach and analyzed quantitative and qualitative survey data.Of 5,812 completed responses (of 101,473 eligible respondents; response rate 5.7%), 920 (15.8%) students from 152 (of 176; 86.4%) institutions identified as SGMs. Of the 912 sexual minorities, 269 (29.5%) concealed their sexual identity in medical school. Factors associated with sexual identity concealment included sexual minority identity other than lesbian or gay, male gender, East Asian race, and medical school enrollment in the South or Central regions of North America. The most common reasons for concealing one's sexual identity were "nobody's business" (165/269; 61.3%), fear of discrimination in medical school (117/269; 43.5%), and social or cultural norms (110/269; 40.9%). Of the 35 gender minorities, 21 (60.0%) concealed their gender identity, citing fear of discrimination in medical school (9/21; 42.9%) and lack of support (9/21; 42.9%).SGM students continue to conceal their identity during undergraduate medical training. Medical institutions should adopt targeted policies and programs to better support these individuals.

  View details for DOI 10.1097/ACM.0000000000000657

  View details for Web of Science ID 000353879700027

  View details for PubMedID 25692563

• From Patients to Providers: Changing the Culture in Medicine Toward Sexual and Gender Minorities ACADEMIC MEDICINE Mansh, M., Garcia, G., Lunn, M. R. 2015; 90 (5): 574-580

  Abstract

  Equality for sexual and gender minorities (SGMs)-including members of the lesbian, gay, bisexual, and transgender communities-has become an integral part of the national conversation in the United States. Although SGM civil rights have expanded in recent years, these populations continue to experience unique health and health care disparities, including poor access to health care, stigmatization, and discrimination. SGM trainees and physicians also face challenges, including derogatory comments, humiliation, harassment, fear of being ostracized, and residency/job placement discrimination. These inequities are not mutually exclusive to either patients or providers; instead, they are intertwined parts of a persistent, negative culture in medicine toward SGM individuals.In this Perspective, the authors argue that SGM physicians must lead this charge for equality by fostering diversity and inclusion in medicine. They posit that academic medicine can accomplish this goal by (1) modernizing research on the physician workforce, (2) implementing new policies and programs to promote safe and supportive training and practice environments, and (3) developing recruitment practices to ensure a diverse, competent physician workforce that includes SGM individuals.These efforts will have an immediate impact by identifying and empowering new leaders to address SGM health care reform, creating diverse training environments that promote cultural competency, and aligning medicine with other professional fields (e.g., business, law) that already are working toward these goals. By tackling the inequities that SGM providers face, academic medicine can normalize sexual and gender identity disclosure and promote a welcoming, supportive environment for everyone in medicine, including patients.

  View details for DOI 10.1097/ACM.0000000000000656

  View details for Web of Science ID 000353879700015

  View details for PubMedID 25650825

• 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., Nguyen, K., da Silveira, E., Daugherty, T., Ahmed, A., Garcia, G., Lutchman, G. A., Nguyen, M. H. 2014; 12 (8): 1363-1370

  Abstract

  Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment-naive patients. However, most of these studies used either direct polymerase chain reaction 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 by using a line probe assay.In a prospective, cross-sectional study, we enrolled 198 treatment-naive patients with chronic hepatitis B (52.5% male; mean age, 41 years) from February 2009 to May 2011 from 3 gastroenterology and liver clinics in Northern California. Exclusion criteria included infection with hepatitis C or D viruses or human immunodeficiency virus. 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 by 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-naive patients with chronic hepatitis B, we detected mutations in HBV DNA polymerase in only 1%. Because of the low prevalence of these mutations and the uncertain clinical significance of such quasispecies, routine HBV DNA polymerase mutation analysis cannot be recommended before initiation of antiviral therapy for treatment-naive 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

• 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., Nguyen, K., da Silveira, E., Daugherty, T., Ahmed, A., Garcia, G., Lutchman, G. A., Nguyen, M. H. 2014; 12 (8): 1363-1370

  View details for DOI 10.1016/j.cgh.2013.11.036

  View details for PubMedID 24342744

• 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

• 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 2 years 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. 21 months, 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

• 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

• 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-naïve 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 < 7.5 log10  IU/mL (hazard ratio [HR] = 2.59 [1.04-6.44]), P = 0.041) and alanine transaminase (ALT) > 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

• 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 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

• 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 α-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

  View details for PubMedCentralID PMC3511850

• 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

• 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 ≥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

• 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

• HEPATITIS B VIRUS (HBV) REVERSE TRANSCRIPTASE MUTATION IS RARE IN TREATMENT-NAIVE PATIENTS WITH CHRONIC HEPATITIS B (CHB): A PROSPECTIVE MULTICENTER STUDY USING INNO-LIPA HBV DR3 ASSAY 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Nguyen, M. H., Trinh, H. N., Garcia, R. T., Nguyen, H. A., Levitt, B. S., Cooper, A. D., Keeffe, E. B., Khanh Nguyen, K., Daugherty, T., Lutchman, G. A., Ayoub, W. S., Ahmed, A., Garcia, G., Da Silveira, E. B. WILEY-BLACKWELL. 2011: 1080A–1080A

  View details for Web of Science ID 000295578003737

• LOW INCIDENCE OF HEPATITIS B E ANTIGEN (HBEAG) SEROCONVERSION WITH ORAL MONOTHERAPY IN CHRONIC HEPATITIS B (CHB) TREATMENT-NAiVE PATIENTS AT YEAR 1 IN CLINICAL PRACTICE 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Lin, B., Ha, N. B., Liu, A., Trinh, H. N., Nguyen, H. A., Nguyen, K., Garcia, R. T., Keeffe, E. B., Garcia, G., Ahmed, A., Nguyen, M. H. WILEY-BLACKWELL. 2011: 1045A–1046A

  View details for Web of Science ID 000295578003664

• Lesbian, Gay, Bisexual, and Transgender-Related Content in Undergraduate Medical Education JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Obedin-Maliver, J., Goldsmith, E. S., Stewart, L., White, W., Tran, E., Brenman, S., Wells, M., Fetterman, D. M., Garcia, G., Lunn, M. R. 2011; 306 (9): 971-977

  Abstract

  Lesbian, gay, bisexual, and transgender (LGBT) individuals experience health and health care disparities and have specific health care needs. Medical education organizations have called for LGBT-sensitive training, but how and to what extent schools educate students to deliver comprehensive LGBT patient care is unknown.To characterize LGBT-related medical curricula and associated curricular development practices and to determine deans' assessments of their institutions' LGBT-related curricular content.Deans of medical education (or equivalent) at 176 allopathic or osteopathic medical schools in Canada and the United States were surveyed to complete a 13-question, Web-based questionnaire between May 2009 and March 2010.Reported hours of LGBT-related curricular content.Of 176 schools, 150 (85.2%) responded, and 132 (75.0%) fully completed the questionnaire. The median reported time dedicated to teaching LGBT-related content in the entire curriculum was 5 hours (interquartile range [IQR], 3-8 hours). Of the 132 respondents, 9 (6.8%; 95% CI, 2.5%-11.1%) reported 0 hours taught during preclinical years and 44 (33.3%; 95% CI, 25.3%-41.4%) reported 0 hours during clinical years. Median US allopathic clinical hours were significantly different from US osteopathic clinical hours (2 hours [IQR, 0-4 hours] vs 0 hours [IQR, 0-2 hours]; P = .008). Although 128 of the schools (97.0%; 95% CI, 94.0%-99.9%) taught students to ask patients if they "have sex with men, women, or both" when obtaining a sexual history, the reported teaching frequency of 16 LGBT-specific topic areas in the required curriculum was lower: at least 8 topics at 83 schools (62.9%; 95% CI, 54.6%-71.1%) and all topics at 11 schools (8.3%; 95% CI, 3.6%-13.0%). The institutions' LGBT content was rated as "fair" at 58 schools (43.9%; 95% CI, 35.5%-52.4%). Suggested successful strategies to increase content included curricular material focusing on LGBT-related health and health disparities at 77 schools (58.3%, 95% CI, 49.9%-66.7%) and faculty willing and able to teach LGBT-related curricular content at 67 schools (50.8%, 95% CI, 42.2%-59.3%).The median reported time dedicated to LGBT-related topics in 2009-2010 was small across US and Canadian medical schools, but the quantity, content covered, and perceived quality of instruction varied substantially.

  View details for Web of Science ID 000294542600015

  View details for PubMedID 21900137

• Criminal Background Checks Upon Acceptance to Medical School: The Wrong Policy at the Wrong Time ACADEMIC MEDICINE Halperin, E. C., Garcia, G. 2011; 86 (7): 808-808

  View details for DOI 10.1097/ACM.0b013e31821e4176

  View details for Web of Science ID 000292283200011

  View details for PubMedID 21715995

• 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 PubMedID 19904247

• ASIAN ETHNICITY IS A SIGNIFICANT PREDICTOR OF SUSTAINED VIROLOGIC RESPONSE (SVR) TO COMBINATION THERAPY WITH PEGINTERFERON (PEG IFN) AND RIBAVIRIN (RBV) IN CHRONIC HEPATITIS C (CHC) 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases Vutien, P., Nguyen, N. H., Gorcia, R. T., Trinh, H. N., Nguyen, L. H., Keefe, E. B., Garcia, G., Nguyen, K. K., Nguyen, H. A., Levitt, B. S., Nguyen, M. H. WILEY-BLACKWELL. 2008: 876A–876A

  View details for Web of Science ID 000259757401652

• 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

• Liver transplantation at Stanford University Medical Center. Clinical transplants Millan, M. T., Keeffe, E. B., Berquist, W. E., Castillo, R. O., Cox, K. L., Garcia, G., Imperial, J. C., Monge, H., So, S. K., Esquivel, C. O. 1998: 287-296

  Abstract

  Because of the unique demographics of our patient population, we have had the opportunity to dedicate further studies of the management of hepatitis B and hepatitis C. We have experienced a very low HBV recurrence rate with the use of HBIG in patients transplanted for hepatitis B. Investigations, including the use of new antiviral agents, and the development of approaches to minimize or abrogate disease recurrence such as lower levels of immunosuppression are ongoing. Using a standardized approach to the proper evaluation and selection of patients for liver transplantation with alcoholic liver disease or other liver diseases with coexistent alcohol abuse, we report favorable long-term results in these patients. We have reviewed our results and our approach to the management of EBV and posttransplant lymphoproliferative disorder. There is a firm commitment in our laboratories and outpatient clinics to the investigation of disease prevention, reliable detection and screening methods, and treatment modalities for EBV-related disease. We have addressed specific technical considerations to pediatric liver transplant and have discussed unique aspects of postoperative management in these patients. One-third of the transplants performed at Stanford are in children, 42% of whom are less than one year old. Results with our pediatric transplant recipients compare favorably with those of our adult recipients with patient and graft survival rates approaching 90% at one year and exceeding 80% at 46 months for both groups. As a response to the limited organ supply, we have extended our criteria for suitable donors. Most notably, we have utilized older donors and grafts with significant microsteatosis and have observed good results with these grafts as long as ischemia time is minimized. We have also successfully used reduced size grafts for our pediatric patients with good results and are continuing to expand the use of living-related partial grafts and split allografts.

  View details for PubMedID 10503106

• Volume-mediated pulmonary responses in liver transplant candidates CLINICAL TRANSPLANTATION Kuo, P. C., Schroeder, R. A., Vagelos, R. H., Valantine, H., Garcia, G., Alfrey, E. J., Haddow, G., Dafoe, D. C. 1996; 10 (6): 521-527

  Abstract

  Pulmonary hypertension, defined as mean pulmonary artery pressure (mPAP) greater than or equal to 25 mmHg, is a recognized complication of hepatic dysfunction with portal hypertension and is considered a relative contraindication to liver transplantation. To characterize pulmonary hemodynamic responses in OLT candidates without pre-existing primary pulmonary hypertension, 22 consecutive patients referred for OLT at the Stanford University Hospital underwent prospective right heart catheterization with pressure determinations at baseline and following infusion of 11 crystalloid over 10 min. In addition, EKG, chest X-ray and transthoracic echocardiograms were performed as a part of the routine evaluation. Eleven non-cirrhotic patients served as controls. At baseline, 1/22 (4.5%) OLT patients had pulmonary hypertension while 9/22 (41%) developed pulmonary hypertension following volume infusion (p < 0.0001). In contrast, 0/11 controls manifested elevated pulmonary pressures at baseline or following volume challenge. OLT candidates were found to have significant increases in mean pulmonary pressure and capillary wedge pressure (PCWP) compared to controls, suggesting intravascular volume overload or left ventricular dysfunction as potential causes. OLT candidates who manifested volume-dependent pulmonary hypertension (a) had a 2-fold higher baseline PCWP, (b) currently smoked, and (c) had previously undergone portosystemic shunts. Aggregate analysis of EKG, echo and CXR for determination of volume-mediated pulmonary hypertension revealed a sensitivity of 25%, specificity of 75% and a positive predictive value of 40%. Preoperative identification of patients with a predisposition to manifesting elevated pulmonary pressures in the context of rapid volume infusion offers the potential for improved risk stratification and optimized clinical management.

  View details for Web of Science ID A1996WC09400009

  View details for PubMedID 8996773

• Late complications of infection with Opisthorchis viverrini WESTERN JOURNAL OF MEDICINE Chiu, A., Neff, M., Garcia, G. 1996; 164 (2): 174-176

  View details for Web of Science ID A1996TX54100016

  View details for PubMedID 8775739

• ORTHOTOPIC LIVER-TRANSPLANTATION WITH SELECTIVE USE OF VENOVENOUS BYPASS 47th Annual Meeting of the Southwestern Surgical Conference Kuo, P. C., Alfrey, E. J., Garcia, G., Haddow, G., Dafoe, D. C. CAHNERS PUBL CO. 1995: 671–75

  Abstract

  To determine the utility of selective use of venovenous bypass (VVB), an algorithm based upon hemodynamic criteria was instituted at Stanford University Medical Center: the bypass was used if the systolic blood pressure decreased below 100 mm Hg with a trial of caval and portal clamping.Eleven consecutive patients underwent orthotopic liver transplantation (OLT) with use of VVB on a selective basis; using the hemodynamic exclusion criteria, none required VVB. A group of 20 patients undergoing OLT with VVB served as historical controls.Overall patient and graft survival were identical in both groups (75%). Avoidance of VVB decreased operative and warm ischemia time and decreased peak transaminase and total bilirubin values, but increased rates of intraoperative blood loss. However, the absolute numbers of blood products administered were not different between groups.Selective use of VVB for OLT does not incur increased morbidity or mortality. Potential advantages include cost savings with decreased operative and anesthetic time.

  View details for Web of Science ID A1995TH94200031

  View details for PubMedID 7492024

• MAGNETIC-RESONANCE IMAGING-DERIVED PARAMETER OF PORTAL FLOW PREDICTS VOLUME-MEDIATED PULMONARY-HYPERTENSION IN LIVER-TRANSPLANTATION CANDIDATES 52nd Annual Meeting of the Central-Surgical-Association Kuo, P. C., Alfrey, E. J., Li, K., Vagelos, R., Valantine, H., Garcia, G., Dafoe, D. C. MOSBY-ELSEVIER. 1995: 685–92

  Abstract

  Pulmonary hypertension is a source of perioperative mortality after orthotopic liver transplantation (OLT). The purpose of this study is to (1) characterize the pulmonary hemodynamic response in OLT candidates, and (2) determine whether portal flow index (PFI), a magnetic resonance imaging (MRI)-derived parameter, is a useful predictor of the pulmonary hemodynamic response.Twenty-five consecutive OLT candidates underwent right heart catheterization with pressure measurements at baseline and after infusion of 1 L of crystalloid. MRI, chest roentgenography, electrocardiography, and echocardiography were also performed as routine screening techniques. Sixteen patients in intensive care unit with normal liver function served as controls.After volume infusion, pulmonary hypertension (mean pulmonary artery pressure greater than 25 mm Hg) developed in 9 of 25 OLT candidates with elevations in both pulmonary capillary wedge and mean pulmonary pressures. In contrast, 0 of 16 controls experienced pulmonary hypertension (p < 0.01). Although routine modalities did not predict this hemodynamic response, PFI had a 94% specificity and 78% sensitivity.OLT candidates exhibit volume-induced pulmonary hypertension with responses suggestive of left ventricular dysfunction. The significance of this observation is unknown, but the MRI-derived parameter, PFI, may serve as a screening technique to limit catheterization to a select group of OLT candidates.

  View details for Web of Science ID A1995RY29700016

  View details for PubMedID 7570323

• MAGNETIC-RESONANCE-IMAGING AND HEPATIC HEMODYNAMICS - CORRELATION WITH METABOLIC FUNCTION IN LIVER-TRANSPLANTATION CANDIDATES SURGERY Kuo, P. C., Li, K., Alfrey, E. J., Jeffrey, R. B., Garcia, G., Dafoe, D. C. 1995; 117 (4): 373-379

  Abstract

  Preoperative assessment of orthotopic liver transplantation candidates requires definition of both the anatomy and metabolic function of the native liver. Current evaluation techniques combine computed tomographic scanning, duplex ultrasonography with blood chemistry analysis, and physical stigmata of end-stage liver disease. Recently, magnetic resonance imaging (MRI) has emerged as an alternative method for delineation of hepatic and portal venous anatomy. In addition, MRI accurately measures hepatic volume and portal venous blood flow.To examine the role of MRI-derived indexes of hepatic hemodynamics in the preoperative assessment of liver function, 39 consecutive liver transplantation candidates were studied in a prospective manner. Liver function (aspartate aminotransferase), alanine aminotransferase, alkaline phosphatase, total bilirubin, and albumin levels), hematologic indexes (complete blood cell count, prothrombin time), and Child's classification were determined at the time of evaluation. Axial breath-held multiplanar spoiled-gradient echo MRI measured hepatic volume, whereas a cine phase-contrast sequence perpendicular to the portal vein measured flow.Hepatic index, defined as hepatic mass corrected for body surface area, was found to correlate with prothrombin time (p < 0.04) and platelet count (p < 0.03) by multivariate regression analysis. Portal flow index (PFI), defined as portal flow corrected for hepatic mass), was associated with aspartate aminotransferase (p < 0.02), alanine aminotransferase (p < 0.04), and albumin (p < 0.03) by multivariate regression analysis. In addition, PFI was closely correlated with the patients' functional status as determined by Child's classification system. Increasing values of PFI were associated with declining hepatic functional reserve. Child's class A patients had a mean PFI that was two times less than that of Child's class B patients (0.26 +/- 0.04 versus 0.04 +/- 0.06 ml/min/gm; p < 0.02) and five times less than that of Child's class C patients (0.26 +/- 0.04 versus 1.05 +/- 0.14 ml/min/gm; p < 0.001). Similarly, the mean PFI associated with Child's class B was two times less than that of Child's class C (0.46 +/- 0.06 versus 1.05 +/- 0.14 ml/min/gm; p < 0.01). These data show that MRI-derived indexes of portal hemodynamics and hepatic mass (1) correlate well with biochemical indexes of hepatic dysfunction and (2) serve as anatomic and hemodynamic correlates to Child's functional classification.We conclude that MRI may serve to noninvasively delineate preoperative hepatic vascular anatomy and metabolic dysfunction in candidates undergoing examination for liver transplantation.

  View details for Web of Science ID A1995QQ96800003

  View details for PubMedID 7716717

• EFFECT OF SULINDAC ON SPORADIC COLONIC POLYPS GASTROENTEROLOGY LADENHEIM, J., Garcia, G., Titzer, D., HERZENBERG, H., Lavori, P., Edson, R., Omary, M. B. 1995; 108 (4): 1083-1087

  Abstract

  We sought to determine in a double-blinded, placebo-controlled study if the nonsteroidal anti-inflammatory drug sulindac causes regression of sporadic colonic polyps. The impetus for this study is the profound regressive effect of sulindac on polyps in familial adenomatous polyposis.Asymptomatic patients undergoing routine screening flexible sigmoidoscopy were enrolled if they had polyps of < or = 1 cm in size. Of 162 patients screened, 22 patients were randomly enrolled to take 150 mg of sulindac twice daily, and 22 patients took a placebo. Treatment duration was 4 months and was followed by colonoscopy with removal of all polyps.Four patients were dropped from the study (sulindac group) due to urosepsis (1 patient), heartburn (2 patients), and anemia (1 patient). Compliance (determined by monthly pill counting), mean age, and the effect of sulindac vs. placebo on polyp regression or size were not statistically different in the two treatment groups. Analysis of our data indicated that there is only a 0.8% chance that the probability of polyp regression with sulindac is as large as 50%.Four months of treatment with sulindac does not result in a clinically significant regression of sporadic colonic polyps, although a small effect may not have been detected by the size of our study. Our data suggest that the biological response of sporadic and familial polyposis polyps to sulindac is different.

  View details for Web of Science ID A1995QP79200017

  View details for PubMedID 7698575

• Hepatitis C virus infection in the immunocompromised patient. Seminars in gastrointestinal disease Garcia, G., Terrault, N., Wright, T. L. 1995; 6 (1): 35-45

  Abstract

  With this review we have attempted to highlight key issues in the diagnosis and management of HCV infection in immunocompromised patients. Much of the information is preliminary and will require careful assessment with prospective collection of data in large numbers of patients. With the advent of new assays, our ability to diagnose infection is accurate. We are still lacking sufficient data regarding the natural history of infection to aid substantially in the management of these patients. Finally, we desparately need new therapeutic approaches to this disease. Hopefully, with greater understanding of the replication of this virus and the mechanism of liver pathogenicity, novel approaches to treatment will be developed.

  View details for PubMedID 7894966

• FATTY LIVER DUE TO HETEROZYGOUS HYPOBETALIPOPROTEINEMIA AMERICAN JOURNAL OF GASTROENTEROLOGY Wishingrad, M., Paaso, B., Garcia, G. 1994; 89 (7): 1106-1107

  View details for Web of Science ID A1994NV56300029

  View details for PubMedID 8017374

• LIMITATIONS OF LIVER SURFACE US IN THE DIAGNOSIS OF CIRRHOSIS RADIOLOGY LADENHEIM, J. A., LUBA, D. G., Yao, F., Gregory, P. B., Jeffrey, R. B., Garcia, G. 1992; 185 (1): 21-23

  Abstract

  Ultrasound (US) of the liver surface with a high-frequency, small-parts, short-focused probe has been proposed as a method of diagnosing cirrhosis. US of the liver was performed in 50 consecutive patients undergoing diagnostic liver biopsy to assess the clinical usefulness of this noninvasive procedure in diagnosing hepatic cirrhosis. Eight patients had histologically proved cirrhosis, and 42 had no histologic evidence of cirrhosis. Seven of the eight patients with cirrhosis had a normal liver surface at US, and five of the 42 patients without cirrhosis had an abnormal liver surface. US of the liver surface with this probe was not reliable in this heterogeneous patient population.

  View details for Web of Science ID A1992JN60800005

  View details for PubMedID 1523310

• THE SULFONE SYNDROME IN A PATIENT RECEIVING DAPSONE PROPHYLAXIS FOR PNEUMOCYSTIS-CARINII PNEUMONIA WESTERN JOURNAL OF MEDICINE MOHLEBOETANI, J., AKULA, S. K., Holodniy, M., KATZENSTEIN, D., Garcia, G. 1992; 156 (3): 303-306

  View details for Web of Science ID A1992HJ56900020

  View details for PubMedID 1595261

• FAILURE TO DETECT HEPATITIS-C VIRUS GENOME IN HUMAN SECRETIONS WITH THE POLYMERASE CHAIN-REACTION HEPATOLOGY Hsu, H. H., Wright, T. L., LUBA, D., Martin, M., Feinstone, S. M., Garcia, G., Greenberg, H. B. 1991; 14 (5): 763-767

  Abstract

  Although hepatitis C infection has been clearly demonstrated to be transmitted through blood products or blood contamination, most cases of sporadic hepatitis C infection are unassociated with parenteral risk factors, and it is unclear how infection might be acquired by nonparenteral means. One potential mode of nonparenteral transmission is through body secretions. We used a highly sensitive and specific polymerase chain reaction assay to determine whether hepatitis C viral genomic RNA could be detected in secretions obtained from nineteen individuals with chronic hepatitis C virus infection. Although hepatitis C genomic RNA was found in all 19 sera, hepatitis C virus RNA was not detected in any samples of saliva, semen, urine, stool or vaginal secretions from these patients. Viral titers in serum ranged from 10(2) to 10(7) polymerase chain reaction units/ml. The sensitivity of our polymerase chain reaction assay indicates that, if hepatitis C virus were in secretions, it would be present in amounts less than 1 to 4 polymerase chain reaction units/ml. This contrasts with hepatitis B virus infection, in which serum titers frequently are in excess of 10(9) copies of hepatitis B genomes/ml. Body secretions have been found to contain up to 10(6) copies of hepatitis B genomes/ml. Our findings support seroepidemiological studies indicating that nonparenteral transmission of hepatitis C through secretions is uncommon and probably much less efficient than hepatitis B virus infection.

  View details for Web of Science ID A1991GN09800003

  View details for PubMedID 1657752

• ACUTE DELTA HEPATITIS DURING TREATMENT WITH ADENOSINE ARABINOSIDE MONOPHOSPHATE WITH RESOLUTION OF THE HBSAG CARRIER STATE WESTERN JOURNAL OF MEDICINE Garcia, G., Smedile, A., BERGMANN, K. F., Gerin, J. L., Gregory, P. B., Merigan, T. C., Robinson, W. S. 1990; 153 (1): 80-82

  View details for Web of Science ID A1990DQ62200023

  View details for PubMedID 1697132

• ADENINE-ARABINOSIDE MONOPHOSPHATE (VIDARABINE PHOSPHATE) IN COMBINATION WITH HUMAN-LEUKOCYTE INTERFERON IN THE TREATMENT OF CHRONIC HEPATITIS-B - A RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED TRIAL ANNALS OF INTERNAL MEDICINE Garcia, G., Smith, C. I., WEISSBERG, J. I., Eisenberg, M., Bissett, J., Nair, P. V., MASTRE, B., ROSNO, S., ROSKAMP, D., Waterman, K., Pollard, R. B., Tong, M. J., Brown, B. W., Robinson, W. S., Gregory, P. B., Merigan, T. C. 1987; 107 (3): 278-285

  Abstract

  Study Objective: To determine the efficacy of adenine arabinoside monophosphate (Ara-AMP vidarabine phosphate) with or without human leukocyte interferon in chronic hepatitis B. Study Design: Randomized, double-blinded, placebo-controlled trial with 6-month treatment and an 18-month follow-up. Setting: Referral-based liver-disease clinics at three university medical centers. Patients: Twenty-five patients with chronic active hepatitis or cirrhosis and 39 with chronic persistent hepatitis. Interventions: Thirteen patients received intramuscular Ara-AMP, 2.5 mg/kg body weight, twice daily, alternated monthly for 6 months with subcutaneous human leukocyte interferon, 5 million units, twice daily. Painful paresthesia of the legs necessitated dosage reduction and early discontinuation of enrollment. Twenty-four patients received intramuscular Ara-AMP, 2.5 mg/kg, twice daily, alternated monthly for 6 months with a matching placebo given subcutaneously twice daily. Twenty-seven patients received placebo by intramuscular and subcutaneous injections twice daily for 6 months. Measurements and Main Results: Of the 64 patients, 95% had symptomatic and virologic data available and 64% had biopsies at 12 months; at 24 months, 77% had data available and 56% had repeat biopsies. The highest dropout rate was seen in the group receiving Ara-AMP. The group receiving the placebo was less symptomatic (Karnofsky score of 96% compared with 91% in the group receiving Ara-AMP/placebo and 92% in the group receiving Ara-AMP/human leukocyte interferon, p = 0.02) at 12 but not at 24 months. Loss of DNA polymerase, the hepatitis B e antigen, and the serum hepatitis B virus DNA was similar in all three groups. Histologically, erosion of the limiting plate and lobular activity favored Ara-AMP at 12 but not at 24 months and these differences did not result in differences in the histologic diagnosis. Conclusion: These results do not support the use of Ara-AMP and human leukocyte interferon in chronic persistent or chronic active hepatitis B.

  View details for Web of Science ID A1987J946200002

  View details for PubMedID 2441633

• PRELIMINARY OBSERVATION OF HEPATITIS B-ASSOCIATED MEMBRANOUS GLOMERULONEPHRITIS TREATED WITH LEUKOCYTE INTERFERON HEPATOLOGY Garcia, G., Scullard, G., Smith, C., Weissberg, J., Alexander, S., Robinson, W. S., Gregory, P., Merigan, T. C. 1985; 5 (2): 317-320

  View details for Web of Science ID A1985AFD8700027

  View details for PubMedID 3979964

• SURVIVAL IN CHRONIC HEPATITIS-B - AN ANALYSIS OF 379 PATIENTS ANNALS OF INTERNAL MEDICINE WEISSBERG, J. I., ANDRES, L. L., Smith, C. I., Weick, S., Nichols, J. E., Garcia, G., Robinson, W. S., Merigan, T. C., Gregory, P. B. 1984; 101 (5): 613-616

  Abstract

  Survival data from 379 patients with chronic hepatitis B were analyzed to determine life expectancy for the patient from the time of first contact. One hundred twenty-one patients had chronic persistent hepatitis, 128 had chronic active hepatitis, and 130 had chronic active hepatitis with cirrhosis. The frequency of symptoms (p less than 0.001), stigmata of chronic liver disease (p less than 0.001), and liver function test abnormalities (p less than 0.001) increased as the histologic features worsened, whereas the percentage of patients with circulating hepatitis B DNA polymerase declined (p less than 0.001). Women were uncommon in our series and had less severe disease than men (p less than 0.02). Fifty-one patients had died by the time of this analysis. The estimated 5-year survival rates were 97% for patients with chronic persistent hepatitis, 86% for those with chronic active hepatitis, and 55% for those with chronic active hepatitis with cirrhosis. The usual cause of death was liver failure and its sequelae. A multivariate analysis found age of 40 years or more, total bilirubin level of 1.5 mg/dL or more, ascites, and spider nevi to be factors that identified patients at a higher risk of death. The prognosis for patients with chronic hepatitis B is similar to that for patients with chronic hepatitis of other causes.

  View details for Web of Science ID A1984TR73200006

  View details for PubMedID 6486592