Hepatitis C virus (HCV) six times likely to develop non-Hodgkin's lymphoma (NHL)

Risk of Non-Hodgkin Lymphoma and Lymphoproliferative Precursor Diseases in US Veterans With Hepatitis C Virus

Thomas P. Giordano, MD, MPH; Louise Henderson, MSPH, PhD; Ola Landgren, MD, PhD; Elizabeth Y. Chiao, MD, MPH; Jennifer R. Kramer, PhD, MPH; Hashem El-Serag, MD, MPH; Eric A. Engels, MD, MPH

JAMA. 2007;297(18):2010-2017.

Context Hepatitis C virus (HCV) infection causes livercancer and cirrhosis and may also increase the risk of othertumors, particularly hematopoietic malignancies and thyroidcancer. Previous studies have been too small to adequately assessthese risks.

Objective To test the hypothesis that HCV infection isassociated with increased risk for hematological malignancies,related lymphoproliferative disorders, and thyroid cancer.

Design, Setting, and Patients A retrospective cohort studyof users of US Veterans Affairs health care facilities from 1997-2004, which included 146 394 patients infected with HCV who had at least 2 visits with a diagnostic code for HCVinfection, and 572 293 patients uninfected with HCV. Toassemble the HCV-uninfected cohort, we randomly selected upto 4 patients per patient infected with HCV from all veteranswho matched on age, sex, and baseline visit date and type (inpatientor outpatient). Individuals with human immunodeficiency viruswere excluded.

Main Outcome Measures Risks of hematopoietic malignancies,related lymphoproliferative precursor diseases, and thyroid cancer, adjusting for selection factors, race, era of military service, and use of medical services.

Results The mean (SD) age of the patients was 52 (8) years,and 97% were men. Risks for non-Hodgkin lymphoma (n = 1359),Waldenström macroglobulinemia (n = 165), and cryoglobulinemia (n = 551) were increased with HCVinfection (adjusted hazard ratio [HR], 1.28; 95% confidenceinterval [CI], 1.12-1.45; adjusted HR, 2.76; 95% CI, 2.01-3.79;and adjusted HR, 3.98; 95% CI, 3.36-4.72; respectively). Wefound no significantly increased risk for other hematologicalmalignancies. Although thyroiditis risk was slightly increased,risk for thyroid cancer (n = 320) was not (adjustedHR, 0.72; 95% CI, 0.52-0.99). Adjusted P values for non-Hodgkinlymphoma, Waldenström macroglobulinemia, cryoglobulinemia,and thyroiditis were all <.0038, the Bonferroni thresholdfor statistical significance considering multiple comparisons.

Conclusions Hepatitis C virus infection confers a 20% to 30% increased risk of non-Hodgkin lymphoma overall, and a 3-fold higher risk of Waldenström macroglobulinemia, alow-grade lymphoma. Risks were also increased for cryoglobulinemia.These results support an etiological role for HCV in causinglymphoproliferation and causing non-Hodgkin lymphoma.

Author Affiliations: Department of Medicine, Baylor College of Medicine, and the Houston Center for Quality of Care and Utilization Studies, Health Services Research and Development Service, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Tex (Drs Giordano, Henderson, Chiao, Kramer, and El-Serag); and the National Cancer Institute, National Institutes of Health, Rockville, Md (Drs Landgren and Engels).

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Lymphoma
Brian Pace, Cassio Lynm, and Richard M. Glass
JAMA. 2007;297(18):2044.
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Study Shows Increased Risk of Non-Hodgkin's Lymphoma and Other Nonhepatic Malignancies in Swedish Patients with HCV Infection

The incidence of malignant non-Hodgkin’s lymphoma (NHL) appears to be increasing in recent years worldwide. In Sweden the large-scale spread of hepatitis C virus (HCV) infection began in the late 1960s and 1970s. As a result, there could be an emergence of increasingly larger numbers of patients with HCV-related complications.

The report of a cluster of four NHL cases among young hepatitis C patients in a HCV cohort of 554 individuals has raised the issue of a potential association between NHL and HCV in Sweden.

The aim of the current study was to evaluate the association between hepatitis C virus (HCV) infection and non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), thyroid cancer (TC), chronic lymphatic leukemia (CLL), acute lymphatic leukemia (ALL), and Hodgkin's lymphoma (HL).

A Swedish cohort of 27,150 HCV-infected persons notified during 1990-2000 was included in the study. The database was linked to other national registers to calculate the observation time, expressed as person-years, and to identify all incident malignancies in the cohort.

The patients were stratified according to assumed time of previous HCV infection.

During 1990-2000 there were 50 NHL, 15 MM, 14 ALL, 8 TC, 6 CLL, and 4 HL diagnoses in the cohort. Altogether, 20 NHL, 7 MM, 5 TC, 4 CLL, 1 ALL, and 1 HL patient fulfilled the criteria to be included in the statistical analysis. The observation time was 122,272 person-years.

The risk of NHL and MM was significantly increased in the stratum with more than 15 years of infection. The association was not significant in TC or CLL.

In conclusion, the authors write, “We report the incidence of several malignancies in a nationwide cohort of HCV-infected persons. Although the delayed diagnosis of HCV probably has resulted in an underestimation of the risk, this study showed a significantly increased risk of Non Hodgkin’s lymphoma and multiple myeloma.”

Reference
A-S Duberg and others. Non-Hodgkin's lymphoma and other nonhepatic malignancies in Swedish patients with hepatitis C virus infection. Hepatology 41(3): 652-659. March 2005.

Hepatitis C virus linked to non-hodgkin's lymphoma
Category: Cancer/Oncology News
Article Date: 18 Oct 2004

Patients infected with the hepatitis C virus (HCV) are six times as likely to develop non-Hodgkin's lymphoma (NHL) than individuals that are virus free, according to research presented today at the Third Annual Frontiers in Cancer Prevention Research meeting.

HCV infected patients have a seventeen fold higher risk for developing diffuse large B-Cell lymphoma, researchers from British Columbia documented. Diffuse large B-cell lymphoma is the most common variety of NHL, comprising approximately 30 percent of all NHL patients.

Compared to Europe and Japan, incidence of hepatitis C viral infection is fairly low in North America, and previous studies from Canada and the United States have not shown an association between the virus and development of NHL, said Ms Agnes Lai, lead author for the research. The British Columbia study examined HCV status in 550 NHL cases and 205 population controls. The study had the strength of numbers of patients to ascertain an association between HCV and NHL, confirming the viral-cancer link suspected in studies from other areas of the world where the virus is more prevalent.

"People who have been exposed to the virus comprise a high risk group for developing non-Hodgkin's lymphoma, particularly diffuse b-cell lymphoma," said John Spinelli, a cancer researcher from the British Columbia Cancer Agency, Vancouver, BC, and principal investigator of the research study.

The spread of hepatitis C in the United States has dropped significantly since the 1980s. Currently, the number of new cases per year is around 25,000. Approximately 3.8 million Americans have been infected with the virus. The most common means of infection in the past was blood transfusion, and in recent years is among drug users who share needles.

Approximately 53,000 patients were diagnosed with NHL in the United States in 2003. There were 23,000 deaths from the disease that year.

Spinelli and Lai conducted their research with colleagues Randy Gascoyne, Joseph Connors, Pat Lee, Rozmin Janoo-Galani, and Richard Gallagher, BC Cancer Agency; Anton Andonov, Health Canada National Microbiology Laboratories, Winnipeg, Manitoba, and Darrel Cook, British Columbia Centre for Disease Control.

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