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The metabolic syndrome contributes to cardiovascular morbidity and mortality. 1-4 Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 reported a metabolic syndrome prevalence of 34%. 5 Understanding updated prevalence trends may be important given the potential effect of the metabolic syndrome and its associated health complications on the aging US population. We investigated trends in the prevalence of the metabolic syndrome through 2012.

Nonalcoholic steatohepatitis (NASH) is currently the third leading indication for liver transplantation (LT) in the U.S. and is predicted to become the leading indication for LT in the near future. The trends in NASH‐related hepatocellular carcinoma (HCC) among LT recipients in the U.S. remain undefined. We performed a retrospective cohort study to evaluate trends in the etiology of HCC among adult LT recipients in the U.S. from 2002 to 2012, using national data from the United Network for Organ Sharing registry. From 2002‐2012, there were 61,868 adults who underwent LT in the U.S., including 10,061 patients with HCC. The total number and proportion of HCC LT recipients demonstrated a significant increase following the implementation of the Model for Endstage Liver Disease (MELD) scoring system in 2002 (3.3%, n = 143 in 2000 versus 12.2%, n = 714 in 2005 versus 23.3%, n = 1336 in 2012). The proportion of hepatitis C virus (HCV)‐related HCC increased steadily from 2002 to 2012, and HCV remained the leading etiology of HCC throughout the MELD era (43.4% in 2002 versus 46.3% in 2007 versus 49.9% in 2012). NASH‐related HCC also increased significantly, and NASH is the second leading etiology of HCC‐related LT (8.3% in 2002 versus 10.3% in 2007 versus 13.5% in 2012). From 2002 to 2012, the number of patients undergoing LT for HCC secondary to NASH increased by nearly 4‐fold, and the number of LT patients with HCC secondary to HCV increased by 2‐fold. Conclusion: NASH is the second leading etiology of HCC leading to LT in the U.S. More important, NASH is currently the most rapidly growing indication for LT in patients with HCC in the U.S. (Hepatology 2014;59:2188–2195)

Nonalcoholic steatohepatitis is the most rapidly growing cause of HCC among US patients listed for liver transplantation.

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e19. Learning Objective: Upon completion of this CME activity, successful learners will be able to (1) explain the risk factors for and outcomes of acute-on-chronic liver failure (ACLF), (2) determine when supportive care for these patients may be futile, and (3) recognize factors associated with reduced patient survival after liver transplantation.

1TR002541); serving on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa; and participating on clinical end point committees for studies sponsored by Novartis and the National Institutes of Health. Dr van Meijgaard is an employee of GoodRx. Dr Mehra reported receiving travel support and consulting fees, paid to Brigham and Women's Hospital, from Abbott; fees for serving on a steering committee from Medtronic and Janssen (Johnson & Johnson); fees for serving on a data and safety monitoring board from Mesoblast; consulting fees from Portola, Bayer, and Triple Gene; and fees for serving as a scientific board member from NuPulseCV, Leviticus, and FineHeart. Dr Mehra also reported receiving personal fees from Baim Institute for Clinical Research and Roivant. Dr Joseph reported receiving grants from Novartis, Amgen, Otsuka, and Kowa and is a consultant for Novartis. No other disclosures were reported. Additional Contributions:We acknowledge Diane Li, BA, and Amanda Nguyen, PhD, employees of GoodRx, who assisted with curation and analysis of the data. They did not receive additional financial compensation for these contributions.Disclaimer: These analyses are based on a representative sample of US pharmacy claims and not based on GoodRx transactions.

Idiosyncratic drug-induced liver injury (DILI) is common in gastroenterology and hepatology practices, and it can have multiple presentations, ranging from asymptomatic elevations in liver biochemistries to hepatocellular or cholestatic jaundice, liver failure, or chronic hepatitis. Antimicrobials, herbal and dietary supplements, and anticancer therapeutics (e.g., tyrosine kinase inhibitors or immune-checkpoint inhibitors) are the most common classes of agents to cause DILI in the Western world. DILI is a diagnosis of exclusion, and thus, careful assessment for other etiologies of liver disease should be undertaken before establishing a diagnosis of DILI. Model for end-stage liver disease score and comorbidity burden are important determinants of mortality in patients presenting with suspected DILI. DILI carries a mortality rate up to 10% when hepatocellular jaundice is present. Patients with DILI who develop progressive jaundice with or without coagulopathy should be referred to a tertiary care center for specialized care, including consideration for potential liver transplantation. The role of systemic corticosteroids is controversial, but they may be administered when a liver injury event cannot be distinguished between autoimmune hepatitis or DILI or when a DILI event presents with prominent autoimmune hepatitis features.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal serum aminotransferase levels in both developed and developing countries. Patients with nonalcoholic steatohepatitis (NASH), a subset of NAFLD, are at risk for progressive liver disease and in need of effective treatment options. A practical approach may be pursued by identifying patients with NAFLD with the highest likelihood for histologic evidence of NASH. Despite decades of clinical trials, no single treatment can be recommended to all patients with NASH. Importantly, there is no evidence that pioglitazone or vitamin E improves fibrosis. Bariatric surgeries may improve hepatic histology in morbidly obese patients with NASH, although randomized clinical trials are lacking. Currently, NASH is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. The primary and secondary prevention of NAFLD may require aggressive strategies for managing obesity, diabetes, and metabolic syndrome.