Bio

Clinical Focus


  • Liver Transplantation
  • Gastroenterology

Academic Appointments


Honors & Awards


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

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

Teaching

2013-14 Courses


Graduate and Fellowship Programs


Publications

Journal Articles


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

    Abstract

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

    View details for DOI 10.1016/j.cgh.2012.08.011

    View details for Web of Science ID 000312265900021

    View details for PubMedID 22902757

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

    Abstract

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

    View details for DOI 10.1002/hep.24308

    View details for Web of Science ID 000291307300009

    View details for PubMedID 21425314

  • 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

  • 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

    Abstract

    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

    Abstract

    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

    Abstract

    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

    Abstract

    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

    Abstract

    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

    Abstract

    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

    Abstract

    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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