We appreciate the interest of Dr. Raimondo and colleagues in our article.1 Of the 91 patients with hepatocellular carcinoma (HCC) who were tested for hepatitis B core antibody (anti-HBc) in serum, 39 of 53 (74%) patients negative for anti-HBc and 32 of 38 (84%) patients positive for anti-HBc met criteria for definite HCC. Among the 28 patients with HCC who were tested for hepatitis B virus (HBV) DNA in the liver, 18 of 25 (72%) HBV DNA–negative and two of three (67%) HBV DNA–positive patients met criteria for definite HCC. We would like to point out that the diagnostic criteria for presumed HCC in the HALT-C Trial protocol—a new mass on ultrasound in conjunction with two other imaging studies showing a lesion with arterial enhancement, with or without washout or evidence of progression on follow-up—are very stringent and most, if not all, patients with presumed HCC would have met the current guidelines for diagnosis of HCC. Of the 25 patients with HCC who had undetectable HBV DNA in the liver, 10 were randomized to maintenance peginterferon and 14 to no treatment, whereas one developed HCC during the lead-in phase and was not randomized. All three patients with HCC who had detectable HBV DNA in the liver were in the control group. We acknowledge the limitations of the data based on testing of HBV DNA in the liver; however, serological data showed clearly that despite evidence of a high prevalence of prior HBV infection, there was absolutely no association with HCC. We note that failure to find an association of prior or occult HBV infection and HCC among patients with HCV-related cirrhosis is not confined to the United States. Even in Italy, one large study found no association between anti-HBc in serum and HCC or liver-related deaths.2


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  • 1
    Lok AS, Everhart JE, Di BisceglieAM, Kim HY, Hussain M, Morgan TR; the HALT-C Trial Group. Occult and previous hepatitis B virus infection are not associated with hepatocellular carcinoma in US patients with chronic hepatitis C. HEPATOLOGY 2011; doi: 10.1002/hep.24257.
  • 2
    Stroffolini R, Almasio P, Persico M, Bollani S, Benvegnù L, Di Costanzo G, et al. Lack of correlation between serum anti-HBcore detectability and hepatocellular carcinoma in patients with HCV-related cirrhosis. Am J Gastroenterol 2008; 103: 1966-1972.

Anna S. Lok M.D.*, James E. Everhart M.D.†, * Division of Gastroenterology, University of Michigan Medical Center Ann Arbor, MI, † National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.