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Hepatitis B Virus Infection Linked to Non-Hodgkin Lymphoma in South Korean Study


People with chronic hepatitis B virus (HBV) infection were almost twice as likely as uninfected individuals to develop non-Hodgkin lymphoma and certain other types of blood cell cancers, according to a large South Korean analysis described in the August 4, 2010 advance online edition of Lancet Oncology. Occurrence of lymphoma was uncommon overall, however, indicating that prevention and treatment of hepatitis B is unlikely to greatly affect lymphoma rates.

Eric Engels from the U.S. National Cancer Institute and colleagues from South Korea performed a study to assess whether chronic hepatitis B increased the risk of subsequent development of NHL among patients in South Korea. HBV prevalence has historically been high in Korea -- as it is throughout Asia -- though lower today due to successful vaccination campaigns.

The researchers looked at participants in the Korean Cancer Prevention Study, a cohort of South Korean workers and their dependants enrolled during 1992-1995. They excluded individuals who died before January 1, 1993, those who had cancer at or before the initial study visit, those with a history of heavy alcohol use, people with HIV or hepatitis C virus (HCV) coinfection, and those missing information about height, weight, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels.

Out of 1,284,586 eligible participants, a total of 603,585 had available baseline data on hepatitis B surface antigen (HBsAg) status and were included in the analysis. People who tested positive for HBsAg at baseline were considered to have chronic HBV infection.

Follow-up continued for up to 14 years, through December 31, 2006. The study authors used national databases of inpatient and outpatient diagnoses and death records to determine occurrence of blood-related malignancies. They assessed the incidence (new cases) of NHL overall and of NHL subtypes, malignant immunoproliferation, Hodgkin's lymphoma, multiple myeloma, and various types of leukemia.


  • Out of the 603,585 eligible participants, 53,045 (8.8%) tested HBsAg positive at baseline.
  • Subsequently, 133 HBsAg positive participants and 905 HBsAg negative individuals developed NHL, for incidence rates of 19.4 vs 12.3 per 100,000 person-years, respectively.
  • HBsAg positive participants had an increased risk of NHL overall compared with HBsAg negative people after adjusting for sex, age, and year of study enrollment (adjusted hazard ratio [HR] 1.74, or nearly twice the risk).
  • Looking at NHL subtypes, HBsAg positivity was associated with increased risk of diffuse large B-cell lymphoma (325 cases, incidence rates 6.9 vs 3.8 per 100,000 person-years; adjusted HR 2.01), as well as malignancies of unknown subtype.
  • HBsAg positive participants also had an increased risk of malignant immunoproliferation (14 cases, incidence rates 0.4 vs 0.2 per 100,000 person-years; adjusted HR 3.79).
  • Risk for these malignancies was consistently higher among HBsAg positive participants throughout 14 years of follow-up.
  • Being HBsAg positive was not, however, associated with follicular or T-cell NHL, Hodgkin's lymphoma, multiple myeloma, or various leukemias.

Based on these findings, the study authors concluded, "During extended follow-up, HBsAg positive individuals had an increased risk of NHL, suggesting that chronic HBV infection promotes lymphomagenesis."

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD; Institute of Human Genomic Study, College of Medicine, Korea University, Seoul, South Korea; Department of Epidemiology, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea



EA Engels, ER Cho, and SH Jee. Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study. Lancet Oncology (Abstract). August 4, 2010 (Epub ahead of print).