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Reply to antiviral therapy and hepatocellular carcinogenesis

We appreciate the interest of Testino et al in our recent review. We agree that the risk of hepatocellular carcinoma (HCC) remains elevated for patients who achieve a sustained virological response (SVR), particularly for those who already have cirrhosis. This is a particular group of patients who likely warrant continued regular screening for HCC. Indeed, a subgroup analysis of trials enrolling only hepatitis C virus (HCV) patients with advanced fibrosis and cirrhosis found a 3-fold–increased risk of HCC in patients who achieved SVR in comparison with trials enrolling patients at all stages of fibrosis. As we discuss in our review, a critical area of research will be identifying for continued screening and treatment those patients who attain SVR and continue to be at the highest risk for HCC. We also agree that type 2 diabetes mellitus and alcohol consumption are additional risk factors for HCC, particularly for those patients with preexisting cirrhosis. Emerging data suggest that in addition to serving as independent risk factors for the development of HCC, nonalcoholic steatohepatitis (a known result of type 2 diabetes mellitus) and alcoholic steatohepatitis act to increase the risk for HCC in HCV patients who have attained SVR. These findings support the developing model of multidisciplinary care for HCV patients, which will include hepatologists and other specialists who are able to assist in managing comorbid factors, including alcohol use, obesity, and diabetes, to maximize their prognosis.