Key Points Hepatitis C virus is a virus that causes hepatitis.  Hepatitis is inflammation of the liver (Question 1) Researchers found that hepatitis C virus infection raised the risk of developing non-Hodgkin’s lymphoma by 20 to 30 percent. (Question 8) Hepatitis C virus infection raised the risk of developing Waldenström's macroglobulinemia by 300 percent. (Question 8) Although hepatitis C virus infection increases the risk of developing lymphoma, the actual risk of developing any of the cancers studied is still small. (Question 14)

1. What is the Hepatitis C Virus?
Hepatitis C virus is a virus that causes hepatitis (inflammation of the liver). Hepatitis C virus is carried and passed to others through exposure to blood (needles, open wounds, etc.) or sexual contact. A blood test is performed to diagnose hepatitis C infection. Hepatitis C virus infection often causes no symptoms, but only about 30% of people recover spontaneously. Besides hepatitis, the hepatitis C virus is known to cause cirrhosis and liver cancer, and is also associated with lymphomas. It is estimated that there are 4.1 million people in the United States living with hepatitis C virus infection--or approximately 1.6 percent of the U.S. population. A study of U.S. military veterans who use the Veterans Administration (VA) medical system showed that the prevalence of hepatitis C virus infection in that population is closer to 5 percent.

2. What is hepatitis?
Hepatitis is a disease of the liver that causes inflammation. Symptoms include an enlarged liver, fever, nausea, vomiting, abdominal pain, and dark urine.

3. What is cirrhosis?
Cirrhosis is a disease that develops when liver cells are damaged and replaced with scar tissue. Cirrhosis may be caused by alcohol abuse, certain drugs and other chemicals, and certain chronic virus infections (especially hepatitis C and B viruses). About 5 percent of people with cirrhosis develop liver cancer.

4. What is lymphoma?
Lymphoma is a cancer that begins in cells of the immune system. There are two basic categories of lymphoma. One kind is Hodgkin's lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin's lymphoma, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin's lymphoma can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin's and non-Hodgkin's lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.

5. What is Waldenström's macroglobulinemia?
Waldenström's macroglobulinemia is a rare, slow-growing type of non-Hodgkin's lymphoma marked by abnormally high levels of certain antibodies in the blood and an enlarged liver, spleen, or lymph nodes. It is also called lymphoplasmacytic lymphoma.

6. Who were the patients in the Hepatitis C and Lymphoma study?
Researchers selected more than 700,000 patient records; 146,394 represented patients who were diagnosed with the hepatitis C virus, while 572,293 represented patients who were not. The two groups were similar in terms of age, gender and date of treatment in the Veterans Affairs (VA) healthcare system. Data from inpatient and outpatient visits from 1996 to 2004 were collected from VA hospitals across the country. The average age was 52 years, most of the patients were men (97 percent), and the majority of patients were Caucasian. Patients in the hepatitis C virus infected group were more likely to have served during the Vietnam era (1964-1975).

7. What was the main finding of this study?
Researchers found that hepatitis C virus infection raised the risk of developing non-Hodgkin's lymphoma by 20 to 30 percent, and raised the risk of developing Waldenström's macroglobulinemia by 300 percent. Risk for cryoglobulinemia, a condition marked by abnormal levels of certain antibodies in the blood,, was also elevated.

8. Was the connection between hepatitis C virus and lymphoma already known?
Previously there was evidence that hepatitis C virus infection could lead to cancers in places other than the liver, and a possible connection between hepatitis C virus infection and non-Hodgkin's lymphoma had been observed, but prior studies have been too small to provide enough information.

9. Were there any findings that were unexpected?
The increased risk of Waldenström's macroglobulinemia (Question 8) had not been seen in previous studies. Because this condition is rare, a possible connection to hepatitis C virus was not considered in previous studies.

10. How long is someone with hepatitis C virus infection at higher risk?
Cirrhosis, liver cancer, and other disease complications start to develop 10 to 20 years after the onset of chronic hepatitis C virus. The same is probably true for lymphoma. The researchers found that the risk of lymphomas in hepatitis C virus infected patients continues for a long period. Throughout more than five years of follow-up, the risk remained elevated.

11. Did the researchers look at other types of cancer?
The researchers also looked at thyroid cancer in relation to hepatitis C virus infection. They found no evidence that hepatitis C virus infection increases the risk of thyroid cancer.

12. Why would veterans have a higher prevalence of hepatitis C virus infection?
The higher prevalence of hepatitis C virus infection may be related to demographic and socioeconomic factors that are associated with infection. Hepatitis C virus infection is very closely tied to receiving blood transfusions prior to 1990 (before there was a blood test to detect infection and prevent transmission) and to use of injected drugs at any time.

13. What are the implications of this research?
It is possible that screening of hepatitis C virus infected individuals could identify early-stage lymphomas. Further epidemiological and biological studies are needed to further explore the relationship between hepatitis C virus infection and non-Hodgkin's lymphoma.

It is important to note that although hepatitis C virus infection increases the risk, the actual risk of developing any of the cancers studied is still small.

14. What are the limitations of this study?
This study was limited to military veterans who used the VA system, and the findings may not be applicable to the overall U.S. population.

15. Who funded this study?
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 Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas.

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/EngelsEric.html

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

Reference: Giordano TP, Henderson 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, 297 (18).

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