ORIGINAL ARTICLE Association Between Polymorphism of Tumor Necrosis Factor-a Promoter and Response to Lamivudine Treatment in Patients with Chronic Hepatitis B Yong Kwang Park Æ Jung Min Lee Æ Do Young Kim Æ Hye Young Chang Æ Ja Kyung Kim Æ Chun Kyon Lee Æ Jun Yong Park Æ Sang Hoon Ahn Æ Kwan Sik Lee Æ Kwang Hyub Han Received: 15 March 2009 / Accepted: 9 September 2009 / Published online: 15 October 2009 Ó Springer Science+Business Media, LLC 2009 Abstract Background TNF-a promoter polymorphism is known to play an important role in the immunopathogenesis of infection of hepatitis B virus. Aims We investigated whether polymorphisms of TNF-a promoter at position -308 or -238 had associations with the response to lamivudine treatment. Methods A total of 89 healthy subjects (control group) and 225 patients with chronic hepatitis B treated with lamivudine were included in this study. Polymorphisms of TNF-a promoter at position -308 and -238 were analyzed by polymerase chain reaction. Recruited patients were classified according to the outcome of lamivudine treat- ment into the responder (103 patients) or non-responder (122 patients) group. Results The numbers of A allelic polymorphism of TNF-a promoter at position -238 were four (2.2%) in the control, five (2.4%) in the responder and 19 (7.8%) in the non- responder group. The A allele was noted significantly more frequently in the responder than non-responder group (P = 0.012). At position -308, a significant difference was observed between the control group (14; 7.9%) and total chronic hepatitis B patients (15; 3.3%) (P = 0.015). Conclusions Our study demonstrated that the non- response to lamivudine treatment in patients with chronic hepatitis B might be related to the A allelic polymorphism of TNF-a promoter at position -238. Keywords Hepatitis B virus Á Lamivudine Á Tumor necrosis factor-alpha Á Single nucleotide polymorphism Introduction Hepatitis B virus (HBV) is a noncytopathic, enveloped double-stranded DNA virus that causes acute and chronic liver diseases. HBV infection in adults is usually acute and completely recovers. However, 5–10% of acutely infected adults become persistently infected and develop chronic hepatitis, which is dependent upon the interaction between HBV and host’s immune response [1]. Since viral hepatitis is a liver disease caused by the destruction of HBV-infected hepatocytes, clearance of HBV without killing infected cells requires noncytolytic intracellular viral inactivation by cytotoxic T lymphocytes (CTLs)-derived cytokines which is induced by virus- activated antigen presenting cells (APCs). HBV-specific CTLs abolish intracellular HBV gene expression and replication by inflammatory cytokines such as tumor necrosis factor a (TNF-a) or interferon c (INF-c) in HBV transgenic mice [2]. In chronic HBV infection, it was Y. K. Park Á K. H. Han Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea J. M. Lee Á D. Y. Kim Á H. Y. Chang Á J. K. Kim Á J. Y. Park Á S. H. Ahn Á K. S. Lee Á K. H. Han (&) Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Korea e-mail: gihankhys@yuhs.ac D. Y. Kim Á J. K. Kim Á J. Y. Park Á S. H. Ahn Á K. S. Lee Á K. H. Han Liver Cirrhosis Clinical Research Center, Seoul, Korea C. K. Lee National Health Insurance Corporation Ilsan Hospital, Goyang, Korea 123 Dig Dis Sci (2010) 55:2043–2048 DOI 10.1007/s10620-009-0983-1