NATAP: HCV Increased Lymphoma Risk

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Hepatitis C may boost risk for non-Hodgkin's lymphoma

By Liz Szabo, USA TODAY

People infected with the hepatitis C virus may be at increased risk for a cancer called non-Hodgkin's lymphoma, according to a study in today's Journal of the American Medical Association.

Doctors have long known that the virus causes chronic hepatitis, a liver inflammation, as well as cirrhosis and liver cancer. The new analysis is one of the largest, however, to find a relationship between hepatitis C and lymphoma, according to Niederhuber, director of the National Cancer Institute, which helped finance the study.

Doctors reviewed the records of patients in the Department of Veterans Affairs medical system, including 146,000 with hepatitis C and 572,000 who were uninfected. Nationwide, about 4.1 million Americans are infected with hepatitis C, which is commonly spread through intravenous drug use.

After more than five years of follow-up, patients with hepatitis C were 20% to 30% more likely to develop non-Hodgkin's lymphoma, which develops in immune cells called lymphocytes, the findings show. The study also is financed by the E. DeBakey Veterans Affairs Medical Center in Houston.

Scientists also found that hepatitis C infection tripled the risk of a very rare lymphoma, called Waldenstrom's macroglobulinemia, which affects 1,500 people a year, according to the study.

Patients' overall risk of cancer remains low, says Engels of the NCI, an author of the study. If doctors followed 500 patients infected with hepatitis C for 10 years, for example, they would expect the virus to cause only one additional case of non-Hodgkin's lymphoma, raising the number of affected patients from five to six.

Doctors can reduce the risk of cancer and other diseases by treating hepatitis C with antiviral medications, Engels says.

Patients in the study came only from VA hospitals, and most were white men. Those infected with hepatitis C were more likely to have served during the Vietnam era. It's possible, authors say, that the relationship between hepatitis C and cancer could be slightly different for other kinds of patients, such those with private health insurance or no military background.

Yet the study could help scientists better understand the connection between infection and cancer, says Marshall Lichtman, executive vice president for research and medical progress for the Leukemia & Lymphoma Society. Several infectious agents - the Epstein-Barr virus, HIV and a bacteria called Helicobacter pylori - are all associated with lymphoma.

Engels says these organisms could cause cancer this way: Immune cells flock to the infection site, then make lots of copies of themselves to outnumber the viruses or bacteria that they want to kill. Most of the copies are normal, but a few have genetic mistakes, or mutations, that lead to cancer.

Worldwide, about one in five cancers are caused by infection, Engels says. Doctors can prevent some of these cancers with vaccines, such as the hepatitis B vaccine, which can reduce the risk of liver cancer, or the new vaccine against human papillomavirus, which protects against most cervical cancers.

Press Release from the National Cancer Institute

Risk of Lymphoma Increases with Hepatitis C Virus Infection

People infected with the hepatitis C virus (HCV) are at an increased risk of developing certain lymphomas (cancers of the lymphatic system), according to a study published in the May 8, 2007, issue of the Journal of the American Medical Association. Researchers from the National Cancer Institute (NCI), part of the National Institutes of Health, and Baylor College of Medicine, found that HCV infection increased the risk of developing non-Hodgkin's lymphoma by 20 percent to 30 percent. The risk of developing Waldenström's macroglobulinemia (a rare type of non-Hodgkin's lymphoma) went up by 300 percent and the risk for cryoglobulinemia, a condition marked by abnormal levels of certain antibodies in the blood, was also elevated for those with HCV infections.

The researchers looked at patient records collected from Veterans Affairs (VA) hospitals across the United States between 1996 and 2004. Researchers selected more than 700,000 records; 146,394 represented patients who were diagnosed with the hepatitis C virus, while 572,293 represented patients who were not. Based on that review, researchers determined, first, that the patients infected with HCV had a higher risk of developing lymphoma and, second, that HCV infection preceded development of the lymphoma. The risk of lymphomas in HCV-infected patients was charted across more than five years of follow-up.

"This is one of the largest studies ever conducted to look at the relationship between hepatitis C virus infection and cancers of the lymphatic system," said NCI Director E. Niederhuber, M.D. "Since so much is still unknown about the causes of lymphoma, establishing which factors contribute to the disease is the first step in finding ways to reduce its incidence and lessen mortality."

HCV causes hepatitis, which is an inflammation of the liver. The HCV virus is carried through the blood and is passed from person to person through the exchange of bodily fluids -- via shared needles, open wounds, and sexual contact, among other means. HCV is also known to cause cirrhosis and liver cancer.

"Although the risk of developing lymphomas is small, our research suggests that screening of HCV-infected individuals could identify conditions which may lead to cancer. It might then be possible to prevent progression to lymphoma," said investigator A. Engels, M.D., from the Viral Epidemiology Branch of NCI's Division of Cancer Epidemiology and Genetics. "More research is needed to further clarify the relationship between HCV infection and lymphoma."

In the United States, there are more than 4.1 million people living with hepatitis C virus infection -- about 1.6 percent of the population. In 2007, it is estimated that 71,380 Americans will be diagnosed with some type of lymphoma, which will take 19,730 lives.

The researchers note that this study was limited to military veterans who used the VA system, so the results may not be applicable to the overall U.S. population. The study population was mostly men (97 percent), the majority of patients were white, and the average age was 52 years. Patients in the HCV-infected group were more likely to have served during the Vietnam era (1964-1975) than were uninfected patients in the comparison group.

Previous studies1,2 found that the prevalence of HCV infection is much higher among U.S. veterans who use the VA medical system (5 percent) than in the general population, where only 1.6 percent carry the virus. Several factors have likely contributed to this higher prevalence, including demographics, socioeconomic status, and particularly a history of injection drug use or blood transfusions received before 1990, when screening for hepatitis C virus was started.

This study was funded in part by the Intramural Research Program of the National Cancer Institute, part of the National Institutes of Health, and the E. DeBakey Veterans Affairs Medical Center in Houston, Texas.

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1 RE, Hebert JR, Wynder EL. Cancer risk in male veterans utilizing the Veterans Administration medical system. Cancer. Sept. 1, 1989; 64(5):1160-1168.

2 Namboodiri KK, RE. Hematopoietic and lymphoproliferative cancer among male veterans using the Veterans Administration Medical System. Cancer. Sept. 1, 1991; 68(5):1123-1130.

For a Q & A on this finding, please go to http://www.cancer.gov/newscenter/pressreleases/HepCLymphomaQandA.

For more information about cancer, visit http://www.cancer.gov, or call NCI's Cancer Information Service at 1-800-4 CANCER.

For more information on Dr. Engels' research, go to

http://dceg.cancer.gov/people/Engels.html

For more information on NCI's Viral Epidemiology Branch, go to http://dceg.cancer.gov/viral.html

Reference: Giordano TP, L, Landgren O, Chiao EY, Kramer JR, El-Serag, H, Engels EA. Risk of Non-Hodkin Lymphoma and Lymphoproliferative Precursor Diseases among 146,394 Hepatitis C Virus Infected U.S. Veterans, Journal of the American Medical Association, May 8, 2007, 297 (18).

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