Long H. Nguyen

Systematic review: Asian patients with chronic hepatitis C infection.

Chronic hepatitis C (CHC) infection is a risk factor for both the development of end‐stage liver disease and hepatocellular carcinoma (HCC). Globally, approximately 170 million people are chronically infected with the hepatitis C virus (HCV), and the majority of these individuals come from the western Pacific and Southeast Asia regions (94.6 million persons combined). CHC is an understudied and underappreciated health problem in many Asian countries and in the US, where Asians represent one of the fastest growing groups of new Americans.

Randomized controlled trial of pegylated interferon‐alfa 2a and ribavirin in treatment‐naive chronic hepatitis C genotype 6

Hepatitis C virus (HCV) genotype is an important criteria in determining duration of therapy and predictor of sustained virologic response (SVR) to pegylated interferon (PEG IFN) and ribavirin (RBV) therapy. Optimal duration of therapy for patients with HCV genotype 6 is not known. We conducted a multicenter, open‐label randomized controlled trial of patients with HCV genotype 6 at five gastroenterology clinics in the western U.S. Patients were stratified by viral load and histologic stage and assigned to receive PEG IFN‐α2a 180 μg subcutaneously weekly and weight‐based oral RBV 800 to 1,200 mg daily for 24 or 48 weeks. Primary outcome measurement was SVR rate by intention‐to‐treat analysis. From February 2005 to October 2007 a total of 60 patients (age 51 ± 10 years, 47% male, log HCVRNA 6.3 ± 1.1 IU/mL) were enrolled: 27 patients to 24 weeks and 33 patients to 48 weeks of therapy. In the 24‐week and 48‐week groups, 96% and 97% achieved early virologic response (P = 0.90); 89% versus 94% achieved end of therapy virologic response (P = 0.48). SVR was achieved in 70% versus 79% of patients assigned to 24 weeks versus 48 weeks (P = 0.45). Rapid virologic response (RVR) was a significant predictor of SVR in the 48‐week group and trending towards significance in the 24‐week group: 82% and 83% of those with RVR achieved SVR versus 33% and 29% for the 24‐week and 48‐week groups, respectively (P = 0.07 and P = 0.02). Conclusion: There was no significant difference in SVR rates in patients with HCV genotype 6 treated with PEG IFN‐α2a and RBV for 24 versus 48 weeks. (HEPATOLOGY 2010;52:1573‐1580)

Systematic review with meta-analysis: the proportion of chronic hepatitis B patients with normal alanine transaminase ≤40 IU/L and significant hepatic fibrosis

Chronic hepatitis B (CHB) may lead to cirrhosis, hepatocellular carcinoma and premature death. Elevated alanine transaminase (ALT) levels ≥ the upper limit of normal (ULN) are a major determinant for initiating anti‐viral therapy; however, ALT levels alone may not be predictive of hepatic fibrosis.

Ethnic disparities and liver transplantation rates in hepatocellular carcinoma patients in the recent era: Results from the surveillance, epidemiology, and end results registry

Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality. After the implementation of the Model for End‐Stage Liver Disease system, rates of liver transplantation (LT) for HCC patients increased. However, it is not clear whether this trend has continued into recent times. Using the Surveillance, Epidemiology, and End Results registry (1998‐2010), we retrospectively analyzed trends for LT among HCC patients in 3 time periods: 1998‐2003, 2004‐2008, and 2009‐2010. A total of 60,772 HCC patients were identified. In the more recent time periods, the proportion of localized‐stage HCC increased (45.0% in 1998‐2003, 50.4% in 2004‐2008, and 51.7% in 2009‐2010; P < 0.001). Although the proportion of HCC patients within the Milan criteria also increased with time (22.8% in 1998‐2003, 31.8% in 2004‐2008, and 37.1% in 2009‐2010; P < 0.001), the proportion of those patients undergoing LT increased from 1998‐2003 to 2004‐2008 but decreased from 2004‐2008 to 2009‐2010. However, the actual frequencies of LT were similar in 2004‐2008 (208.2 per year) and 2009‐2010 (201.5 per year). A multivariate logistic regression, including sex, age, ethnicity, Milan criteria, tumor stage, tumor size and number, and time periods, demonstrated a lower likelihood of LT in 2009‐2010 versus 1998‐2003 [odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.57‐0.71]. Blacks (OR = 0.48, 95% CI = 0.41‐0.56), Asians (OR = 0.65, 95% CI = 0.57‐0.73), and Hispanics (OR = 0.76, 95% CI = 0.68‐0.85) were all less likely to undergo LT in comparison with non‐Hispanic whites. Despite the increasing proportion of patients with HCC diagnosed at an earlier stage, LT rates declined in the most recent era. In addition, ethnic minorities were significantly less likely to undergo LT. The growing imbalance between the number of transplant‐eligible HCC patients and the shortage of donor livers emphasizes the need to improve donor availability and curative alternatives to LT. Liver Transpl 20:528–535, 2014.

Ethnic differences in viral dominance patterns in patients with hepatitis B virus and hepatitis C virus dual infection

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). Conclusion: 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. (HEPATOLOGY 2011;)

Low Proportion of Barrett's Esophagus in Asian Americans

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

Prevalence of hepatitis B virus DNA polymerase mutations in treatment-naïve patients with chronic hepatitis B.

Background  One of the most important factors in treatment failure using nucleos(t)ide analogues in chronic hepatitis B is anti‐viral resistance. Primary drug resistance refers to amino acid changes in the hepatitis B virus polymerase/reverse transcriptase (rt) that result in reduced susceptibility to anti‐viral agents. Pre‐existing drug resistance mutations may occur in untreated patients and may affect their treatment outcomes.

Histologic Changes in Liver Tissue From Patients With Chronic Hepatitis B and Minimal Increases in Levels of Alanine Aminotransferase: A Meta-analysis and Systematic Review

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

Systematic review with meta-analysis: rifaximin for the prophylaxis of spontaneous bacterial peritonitis

The primary and secondary prevention of spontaneous bacterial peritonitis (SBP) is recommended in high‐risk patients with cirrhosis. Several studies evaluating the efficacy of rifaximin for SBP prophylaxis have yielded conflicting results. Rifaximin has the potential advantage of preventing bacterial overgrowth and translocation without the systemic side effects of broad‐spectrum antibiotics.

Stability of the human faecal microbiome in a cohort of adult men

Characterizing the stability of the gut microbiome is important to exploit it as a therapeutic target and diagnostic biomarker. We metagenomically and metatranscriptomically sequenced the faecal microbiomes of 308 participants in the Health Professionals Follow-Up Study. Participants provided four stool samples—one pair collected 24–72 h apart and a second pair ~6 months later. Within-person taxonomic and functional variation was consistently lower than between-person variation over time. In contrast, metatranscriptomic profiles were comparably variable within and between subjects due to higher within-subject longitudinal variation. Metagenomic instability accounted for ~74% of corresponding metatranscriptomic instability. The rest was probably attributable to sources such as regulation. Among the pathways that were differentially regulated, most were consistently over- or under-transcribed at each time point. Together, these results suggest that a single measurement of the faecal microbiome can provide long-term information regarding organismal composition and functional potential, but repeated or short-term measures may be necessary for dynamic features identified by metatranscriptomics.Metagenomic and metatranscriptomic analyses of stool samples from 308 individuals over time indicate that longitudinal sampling is important for detecting dynamic functional features of the gut microbiome.