Hepatitis C Linked to Increased Risk of Intrahepatic Cholangiocarcinoma

NEW YORK (Reuters Health) Jan 15 - The risk of intrahepatic cholangiocarcinoma is significantly elevated in patients infected with hepatitis C virus (HCV), according to a large case-control study of US veterans.

The risk of pancreatic cancer also appears to be slightly elevated in patients with HCV, although this risk was attenuated after adjusting for alcohol use and other variables, the research team reports in the January issue of Hepatology.

Previous studies investigating the link between HCV infection and cancers of the hepatopancreaticobiliary tumors other than hepatocellular carcinoma tended to be small or subject to bias, note Dr. Hashem B. El-Serag, at the Houston VA Medical Center, and colleagues there and at the National Cancer Institute in Rockville, Maryland.

To clarify these issues, Dr. El-Serag's team obtained data for 146,394 HCV-infected subjects and 572,293 HCV-uninfected subjects for the period between 1988 and 2004. The mean patient age was 52 years old, the mean follow-up was 2.3 years, and most of the patients were men (96.7%).

When comparing HCV-infected with HCV-uninfected subjects, the hazard ratios for hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and pancreatic cancer were 15.09, 2.55, and 1.23, respectively. The risk of extrahepatic cholangiocarcinoma was not significantly elevated, which according to the authors, supports the theory that intracellular and extracellular cholangiocarcinoma are distinct malignancies.

Analyses adjusting for other variables, such as alcohol use, pancreatitis, and cholelithiasis, confirmed the strong association between HCV and hepatocellular carcinoma and intrahepatic cholangiocarcinoma, the report indicates. However, the association between HCV and pancreatic cancer was no longer statistically significant.

"HCV is a strong risk factor for hepatocellular carcinoma and hepatocytes and cholangiocytes have the same progenitor cell," the authors note. "It could be postulated the HCV could induce carcinogenesis in both cell types by the same mechanism."

Finally, Dr. El-Serag and colleagues maintain, the mixed findings of this study regarding the association between HCV and pancreatic cancer "merit additional investigation."

"From a clinical perspective," they conclude, "early intervention strategies, including screening HCV-positive individuals earlier or more rigorously, may improve the outcomes for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma."

Hepatology 2009;49:116-123.