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Background and Aims: In the REALM (Randomized, Observational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Patients with Chronic HBV Infection) study, 12,378 patients with chronic hepatitis B virus (HBV) infection received up to 10 years of randomized therapy with entecavir or another HBV nucleos(t)ide analogue. Monitored clinical outcome events (COEs) included malignant neoplasms, HBV disease progression events, and deaths. An external event adjudication committee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize potential adverse effects of the large cohort, interdisciplinary outcome assessments, geographic scope, and long duration. Methods: The EAC comprised an international group of hepatologists and oncologists with expertise in diagnosis of targeted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria captured in the EAC charter. Operational processes, including data collection and query procedures, were implemented to optimize efficiency of data recovery to maximize capture of adjudicated COEs, the primary study outcome measure. Results: A total of 1724 COEs were reported and 1465 of these events were adjudicated by the EAC as reported by the investigators (85.0% overall concordance). Concordance by COE type varied: deaths, 99.6%; hepatocellular carcinoma (HCC), 83.3%; non-HCC malignancies, 88.0%; non-HCC HBV disease progression, 68.2%. Reasons for lack of concordance were most commonly lack of adequate supporting data to support an adjudicated diagnosis or evidence that the event pre-dated the study. Conclusions: The REALM EAC performed a critical role in ensuring data quality and consistency; EAC performance was facilitated by well-defined diagnostic criteria, effective data capture, and efficient operational processes. Trial registration: ClinicalTrials.gov NCT00388674.

Although drug‐induced liver injury (DILI) is a rare clinical event, it carries significant morbidity and mortality, leaving it as the leading cause of acute liver failure in the United States. It is one of the most challenging diagnoses encountered by gastroenterologists. The development of various drug injury networks has played a vital role in expanding our knowledge regarding drug‐related and herbal and dietary supplement–related liver injury. In this review, we discuss what defines liver injury, epidemiology of DILI, its biochemical and pathologic patterns, and management., Although drug‐induced liver injury (DILI) is a rare clinical event, it carries significant morbidity and mortality, leaving it as the leading cause of acute liver failure in the United States. It is one of the most challenging diagnoses encountered by gastroenterologists. DILI is also the most common single adverse event that has led to withdrawal of drugs from the marketplace, drug attrition, and failure of implicated drugs to obtain Food and Drug Administration approval. The development of various drug injury networks have played a vital role in expanding our knowledge regarding drug‐related and herbal and dietary supplement–related liver injury. In this review, we discuss what defines liver injury, epidemiology of DILI, its biochemical and pathologic patterns, and management.

Herbal and dietary supplement usage has increased steadily over the past several years in the United States. Among the non-bodybuilding herbal and dietary supplements, weight loss supplements were among the most common type of HDS implicated in liver injury. While drug induced liver injury is rare, its consequences are significant and on the rise. The purpose of this review is to highlight case reports of weight loss products such as Hydroxycut and OxyElite Pro as one form of HDS that have hepatotoxic potential and to characterize its clinical effects as well as pattern of liver injury. We also propose future strategies in the identification and study of potentially hepatotoxic compounds in an effort to outline a diagnostic approach for identifying any drug induced liver injury.

Despite the improved efficacy of peginterferons, the rate of sustained virologic response is suboptimal in cirrhotic patients, relative to non-cirrhotic patients. However, the treatment of patients with compensated cirrhosis has recently been encouraged by expert panels. Interferon-based therapy may provide additional benefit by reducing the risk of hepatocellular carcinoma in cirrhotic patients as suggested in preliminary studies. Results of two ongoing prospective studies are awaited to answer the important question of the effectiveness of suppressive interferon therapy, even in the absence of sustained virologic response. Given the importance of recurrent HCV following liver transplantation, attention has been directed toward the antiviral treatment of patients with advanced liver disease. This approach needs to be pursued with caution given the potential morbidity of the therapy. Recently, a low accelerating dosage regimen has provided excellent results and is the subject of additional inquiry.