Walid Ayoub

Review article: current antiviral therapy of chronic hepatitis B

Background  The long‐term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of cirrhosis and hepatocellular carcinoma.

Transarterial Chemoinfusion for Hepatocellular Carcinoma as Downstaging Therapy and a Bridge toward Liver Transplantation

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

Biliary Complications Following Liver Transplantation

The aphorism that reconstruction of the biliary anastomosis is the “Achilles heel” of liver transplantation remains valid as biliary complications following liver transplantation remain a major source of morbidity with an incidence of 5–32%. Biliary complications include biliary strictures, biliary leaks, and stones. Biliary strictures can be divided into anastomotic and non-anastomotic. The management of biliary complications previously relied on surgical intervention. However, advances in endoscopic and radiological interventions have resulted in less-invasive options. The management of biliary complications post-liver transplantation requires a multidisciplinary approach and continues to evolve. Biliary complications also reflect the continued expansion of the donor pool with extended, live, and non-heart beating donors.

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.

Incidence of hepatocellular carcinoma among US patients with cirrhosis of viral or nonviral etiologies.

BACKGROUND & AIMS 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. METHODS 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). RESULTS 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. CONCLUSIONS 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.

Prospective study of risk factors for hepatitis C virus acquisition by Caucasian, Hispanic, and Asian American patients

Summary.  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.

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.

Both HCV and HBV are Major Causes of Liver Cancer in Southeast Asians

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.

First Look: One Year Since Inception of Regional Share 35 Policy

BACKGROUND More than 10,000 patients are awaiting liver transplantation, and more than 1300 die waiting yearly. The Share 35 policy was implanted 1 year ago with expectations to decrease waitlist mortality. The purpose of our study was to look at waitlist outcomes and organ usage. METHODS We compared data from the United Network of Organ Sharing before and after the initiation of Share 35, looking at waitlist mortality, organs shared with Model for End-Stage Liver Disease (MELD) score ≥ 35, organ discards, travel distance, cold ischemia time, MELD score at transplantation, donor characteristics, and waitlist times. The χ(2) test was used to compare the data from two time periods. RESULTS Comparing the 1-year periods, we found no change in waitlist mortality rate; transplants in MELD score ≥ 35 increased from 19% to 27% and decreased in MELD score 15 to 34 from 74% to 67%; high-risk donors increased from 13% to 17%; and a 40% decrease in time on the waitlist before removal because of death from 58 to 35 days. CONCLUSIONS One year since Share 35, there has been no change in waitlist mortality rate. Unfortunately, it will take several years to know the impact of Share 35 on changes in patient life-years saved.

Magnetic resonance imaging and transient elastography in the management of Nonalcoholic Fatty Liver Disease (NAFLD)

ABSTRACT Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and cirrhosis worldwide and the second most common cause of liver transplantation in major medical centers. Because liver steatosis and fibrosis severity are related to disease morbidity and mortality, the extent of disease, and disease progression, they need to be assessed and monitored. In addition, innovation with new drug developments requires disease staging and monitoring in both phase 2 and 3 clinical trials. Currently, disease assessment in both clinical practice and research is mostly performed by liver biopsy, an invasive, procedure with risks. Noninvasive, highly accurate tests are needed that could be used in clinical trials as surrogate endpoints and in clinical practice for monitoring patients. Area Covered: We discuss noninvasive tests, transient elastography (TE) with controlled attenuation parameter (CAP), magnetic resonance imaging (MRI), and MR elastography (MRE), summarize the available evidence of their usefulness for assessing steatosis and fibrosis. Therefore they could be used as clinical trials outcomes and in disease monitoring in clinical practice. Expert Commentary: TE with CAP, MRI and MRE are highly accurate noninvasive diagnostic tools for quantifying hepatic steatosis and fibrosis. Therefore they could be used as clinical trials outcomes and in disease monitoring in clinical practice.