Elevated Risk of Biliary and Pancreas Cancer in Chronic Hepatitis C Patients

By Liz Highleyman

It is well known that over years or decades, chronic hepatitis C virus (HCV) infection can lead to advanced liver disease including hepatocellular carcinoma (HCC), a type of liver cancer at originates in hepatocytes (liver cells). But other types of cancer of the liver, pancreas, and biliary system (gall bladder and associated structures) have been less extensively studied in this population.

As reported in the January 2009 issue of Hepatology, Hashem El-Serag of Baylor College of Medicine and colleagues looked at the prevalence of "hepatopancreaticobiliary" cancers in a retrospective cohort study of more than 718,000 patients who received care at U.S. Veterans Affairs (VA) health facilities.

Previous case-control studies indicated a possible association between HCV infection and intrahepatic cholangiocarcinoma (ICC), or cancer of the bile ducts within the liver, the researchers noted as background. Little is known, however, about its relationship to extrahepatic cholangiocarcinoma (ECC; cancer of the bile ducts outside the liver) or pancreatic cancer.

In this analysis, 146,394 hepatitis C patients who had at least 2 clinic visits between 1996 and 2004 were matched with up to 4 HCV-uninfected control subjects of the same age and sex. Participants were followed for an average of 2.3 years. Risks of HCC, ICC, ECC, and pancreatic cancer were assessed using proportional hazards regression.

Results

During the 1.37 million person-years of follow-up beginning 6 months after the baseline visit, the researchers identified:

37 cases of ICC;
75 cases of ECC;
617 cases of pancreatic cancer;
1679 cases of HCC.

As expected, the risk of HCC associated with HCV was very high (hazard ratio [HR] 15.09, or about a 15-fold risk).

The risk of ICC was elevated to a lesser extent in patients with chronic HCV infection (HR 2.55, or 2.55-fold).

Adjusting for potentially confounding factors including liver cirrhosis, diabetes, inflammatory bowel disease, hepatitis B virus (HBV) infection, heavy alcohol use, and alcoholic liver disease did not reduce the excess risk of ICC below 2-fold.

The risk of pancreatic cancer was slightly elevated in hepatitis C patients (HR 1.23, or 23% higher), but this was attenuated after adjusting for alcohol use, pancreatitis, and other variables.

The risk of ECC was not significantly increased in the HCV-infected group (HR 1.50).

In conclusion, the study authors wrote, "Findings indicated that HCV infection conferred a more than 2-fold elevated risk of ICC."

"Absence of an association with ECC was consistent in adjusted and unadjusted models," they continued. "A significant association with pancreatic cancer was erased by alcohol use and other variables."

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

Department of Medicine, Baylor College of Medicine, Houston, TX; Houston Center for Quality of Care and Utilization Studies, Health Services Research and Development Service, Department of Veterans Affairs Medical Center, Houston, TX; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.

1/27/09

Reference
HB El-Serag, EA Engels, O Landgren, and others. Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans. Hepatology 49(1): 116-123. January 2009. (Abstract).