BACKGROUND AND AIMS We investigated the relative etiological role of prior hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) in the development of non-B non-C, non-alcohol or specific cause-related hepatocellular carcinoma (NBNC-NA-NS HCC) in an HBV-endemic area of Korea.

METHODS A total of 329 patients with NBNC-NA-NS HCC were enrolled in this study. Prior HBV infection was defined as the presence of isolated IgG hepatitis B core antibody (anti-HBc), and NAFLD was diagnosed by the findings from the imaging in the absence of a history of excessive alcohol consumption.

RESULTS Prior HBV infection was the most common cause of underlying liver disease (76.6%). Only 8.2% of the patients had NAFLD as the only risk factor and the same proportion of patients had evidence of both prior HBV infection and NAFLD. Patients without definitive causes accounted for 7.0% of the cases. During the past 10 years, the relative proportion of isolated IgG anti-HBc-positive HCC decreased significantly from 86.6% in 2001-2005 to 67.4% in 2006-2010 (p < 0.0001) and that of NAFLD-related HCC increased from 3.8% to 12.2% in the same period, respectively (p = 0.008). The mean age of NAFLD-related HCC patients (67.3 years) was significantly older than that of HCC patients related to prior HBV infection (61.2 years, p < 0.001).

CONCLUSIONS NAFLD-related HCC increased significantly while HCC related to prior HBV infection decreased during the past 10 years in an HBV-endemic area of Korea; however, the relative etiological role of prior HBV infection was still greater than that of NAFLD in the development of NBNC-NA-NS HCC.