Hepatitis B Virus Associated With Pancreatic Cancer

Roxanne Nelson

October 03, 2008

October 3, 2008 — Past exposure to the hepatitis B virus (HBV) might be associated with the development of pancreatic cancer, researchers report. In addition, there is a potential for HBV to be reactivated when patients undergo chemotherapy treatment.

This is the first study to investigate the association between viral hepatitis and pancreatic cancer, the researchers note in the October 1 issue of the Journal of Clinical Oncology. They found that the prevalence of past exposure to HBV was significantly higher in patients with pancreatic cancer than in healthy controls (7.6% vs 3.2%). However, exposure to hepatitis C (HCV) was not significantly different in the 2 groups.

Senior author James Abbruzzese, MD, professor and chair of the department of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center and associate medical director of the Gastrointestinal Center, in Houston, speculated that the reason for this might be due to the innate differences between HBV and HCV.

"HBV tends to be a systemic virus that circulates throughout the body," he told Medscape Oncology in an interview. "HCV is much more hepatotrophic, and we can speculate that it may be 1 of the reasons that it doesn't appear to increase the risk of pancreatic cancer. It also tends to be a lower-grade infection and manifests over a long period of time, so the natural history of these 2 viruses is quite different."

Both HBV and HCV are significantly associated with end-stage chronic liver diseases, including hepatocellular carcinoma and cholangiocarcinoma, but hepatitis is also a systemic disease with extrahepatic manifestations. The association between the hepatitis virus and extrahepatic cancers has only been studied in non-Hodgkin's lymphoma to date; other studies have investigated the reactivation of HBV infection in cancer patients undergoing cytotoxic or immunosuppressive therapy.

The pancreas could be another potential target for the hepatitis virus because of its proximity to the liver, and because the 2 organs share common blood vessels and ducts, the authors write. Studies have found elevated levels of pancreatic enzyme in a substantial percentage of patients with acute or chronic HBV or HCV infection, which supports the possibility that viral hepatitis can lead to pancreatic damage.

Past Exposure to Hepatitis B Was Significant

Dr. Abbruzzese and colleagues recruited 476 patients with pathologically confirmed adenocarcinoma of the pancreas and 879 matched controls. Blood samples from both groups were tested for the presence of HCV antibodies, HBV surface antigen (HBsAg), antibodies against HBV core antigen (anti-HBc), and antibodies against HBsAg (anti-HBs).

They found that the prevalence of past exposure to HBV, which was indicated by the presence of anti-HBc, was significantly higher among patients with pancreatic cancer than among controls (7.6% vs 3.2%). Past exposure to HBV with evidence of HBV recovery or immunity was also significantly associated with an increased risk for pancreatic cancer (adjusted odds ratio [AOR], 2.3), but past exposure without evidence of HBV recovery was associated with an even greater risk (AOR, 4.0).

After adjustment for risk factors, a history of diabetes mellitus, cigarette smoking, and a positive family history of cancer were significantly associated with the development of pancreatic cancer. The presence of diabetes also significantly increased the risk for pancreatic cancer in patients with past exposure to HBV.

The researchers did not find a significant association between HCV and pancreatic cancer. The prevalence of HCV antibodies was 1.5% among pancreatic cancer patients and 1% among the control group.

Reactivation of Occult Infection During Chemotherapy

An important point raised by this study is that the observed high prevalence of anti-HBc-positive status might be an indication of an occult HBV infection, which might lead to the reactivation of HBV during chemotherapy. HBV reactivation is associated with hepatic failure among cancer patients who undergo chemotherapy, although the underlying mechanism of viral reactivation remains unclear. One hypothesis is that chemotherapy enhances the replication of HBV.

"In patients who have any history of high-risk behaviors or who work in settings where they may be exposed to the virus, it would be reasonable to check for HBV status before beginning chemotherapy," said Dr. Abbruzzese. "It is so easy and inexpensive to test the blood and, if needed, a patient can be put on antiviral medications that will lessen or even eliminate the virus."

Dr. Abbruzzese explained that he hoped that other groups would begin reviewing their case–control studies to see if HBV is an issue. "We would like to see validation of our study," he said. If the association between HBV infection and pancreatic cancer can be confirmed by other studies, these findings would offer additional insight into the cause of pancreatic cancer. They might even identify a readily modifiable risk factor for pancreatic cancer.

However, at this point, Dr. Abbruzzese said it would be a stretch to recommend screening patients with a history of HBV for pancreatic cancer. "Right now, the risk appears fairly low, and what we're trying to do is combine diabetes and other risk factors, along with molecular factors, into a risk profile that we can use to identify high-risk patients."

The study was supported by grants from the National Institutes of Health and a research grant from the Lockton Research Funds. The researchers have disclosed no relevant financial relationships.

J Clin Oncol. 2008:26:4557-4562. Abstract


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