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The growth of thefield of hepatologyover thepast 30 years has largely been driven by the burgeoning incidences and prevalences of two diseases: hepatitis C and nonalcoholic fatty liver disease (NAFLD). This issue of the Seminars in Liver Disease, guest-edited by Professor Jean-Michel Pawlotsky, is devoted principally to the recent explosion of knowledge about the biology of the hepatitis C virus (HCV) and the resulting appearance of multiple new drugs that dramatically increase the success of HCV treatment. In addition, an editor’s choice article from the Longitudinal Assessment of Bariatric Surgery (LABS) Consortium raises important questions about NAFLD. NAFLD is a common and potentially life-threatening obesity-related comorbidity. Nonalcoholic steatohepatitis (NASH), one component of the widely accepted NAFLD spectrum, may be the most common form of chronic hepatitis in the United States, and has been projected to replace hepatitis C–related liver disease as the leading indication for liver transplant.1,2 Bariatric surgery (BS) patients are among the highest risk population for NAFLD, which affects up to 98% of patients in some series, and the possible use of BS as a therapeutic approach to treat NAFLD is gaining attention.3 However, the natural history of NAFLD in BS patients and the impact of BS on NAFLD disease progression remain incompletely described. The depth of our uncertainty about key aspects of fatty liver disease is reflected in recent publications challenging the basic concepts that simple hepatic steatosis is part of the broader spectrum that includes NASH, NASH with fibrosis, and cirrhosis,4 or that the proportion of total liver transplants going to patients with fatty liver disease is significantly increasing.5 In this issue of the Seminars in Liver Disease, Kleiner and colleagues6 report histologic findings from intraoperative liver biopsies in a subset of patients in the LABS study cohort. While biopsies were not performed universally or in an unbiased manner, the burden of liver disease in this populationwas predictably high, with borderline or definitive NASH found in over a third of biopsied patients and bridging fibrosis or cirrhosis in 4.2%. Perhaps most striking was that among patients with alanine aminotransferase (ALT) < 35 IU/L, a widely accepted upper limit of normal, 24% had borderline or definitive steatohepatitis, 6.4% had a NAFLD activity score (NAS) 5, and 2% had bridging fibrosis or cirrhosis. When evenmore stringent ALT criteriawere used (normal: < 30 IU/ L for men and < 19 IU/L for women),7 19% had borderline or definitive steatohepatitis, 3.7% had NAS 5, and 1.6% had bridging fibrosis or cirrhosis, rendering even these cutoffs for ALT inadequate to exclude clinically important liver disease in these very high-risk patients. The authors then used logistic regression modeling as a crude indicator of how much liver diseasemay have gone undiagnosed in the patientswhowere not biopsied; the models suggested that almost 6% of unbiopsied patients have bridging fibrosis or cirrhosis and almost half of the patients have borderline or definitive steatohepatitis. As visual inspection of the liver by the surgeon in the operating roommay be insufficiently sensitive to detect significant hepatic pathology, much of the important liver disease in the cohort remains undiagnosed. This report reminds us of just how littleweknowabout the burden of liver disease in the BS population, and perhaps supports the growing sentiment that liver biopsy at the time of BS should be universally considered. Several lines of evidence support the fact that a clearer understanding of the liver histology in BS patients will benefit both individual patients and the medical community.

Liver Biopsy at the Time of Bariatric Surgery: A Benefit for Patients and the Medical Community