Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: A population-based study

Background & Aims: A significant increase in the incidence of hepatocellular carcinoma (HCC) has been reported in the United States. The risk factors underlying this increase remain unclear. Methods: By using Surveillance, Epidemiology, and End-Results program (SEER)-Medicare-linked data, we conducted a population-based study to examine temporal changes in risk factors for patients 65 years and older diagnosed with HCC between 1993 and 1999. Only patients with continuous Medicare enrollment for 2 years before and up to 2 years after HCC diagnosis were examined. Univariate and multiple logistic regression analyses were used to evaluate changes in risk factors over time (January 1993-June 1996 and July 1996-December 1999). Results: The age-adjusted incidence of HCC among persons 65 years of age and older significantly increased from 14.2 per 100,000 in 1993 to 18.1 per 100,000 in 1999. We identified 2584 patients with continuous Medicare enrollment 2 years before and up to 2 years after HCC diagnosis. The proportion of hepatitis C virus (HCV)-related HCC increased from 11% during January of 1993 to June of 1996 to 21% during July of 1996 to December of 1999, whereas hepatitis B virus (HBV)-related HCC increased from 6% to 11% (P < .0001). In multiple logistic regression analyses that adjusted for age, sex, race, and geographic region, the risk for HCV-related HCC and HBV-related HCC increased by 226% and 67%, respectively. Idiopathic HCC decreased from 43% to 39%. This decrease did not fully account for the significant increases observed for HCV and HBV. No significant changes over time were observed for alcohol-induced liver disease, nonspecific cirrhosis, or nonspecific hepatitis. Conclusions: There has been a significant recent increase in HCV- and HBV-related HCC. Increasing rates of HCV-related HCC can explain a substantial proportion of the reported increase in HCC incidence during recent years.