HEPATOLOGY Association of human leukocyte antigen polymorphism with outcomes of hepatitis B virus infection Amitis Ramezani,* Mohammad Reza Hasanjani Roshan, † Ebrahim Kalantar, ‡ Ali Eslamifar,* Mohammad Banifazl, § Jaleh Taeb,* Arezoo Aghakhani,* Latif Gachkar ¶ and Ali Akbar Velayati †† *Clinical Research Department, Pasteur Institute of Iran, Tehran, † Babol University of Medical Sciences, Babol, ‡ School of Allied Medical Sciences, Iran Medical University, § Iranian Society for Supporting Patients with Infectious Disease, ¶ Infectious Diseases Research Center, Shaheed Beheshti University of Medical Sciences, and †† Masih Daneshvari Hospital, Tehran, Iran Abstract Background and Aim: Host genetic and environmental factors are viewed as a common basis of the different outcomes of hepatitis B virus (HBV) infection. Human leukocyte antigen (HLA) plays an important role in immunological reaction to HBV infection. In this study, we aimed to determine the association between HBV infection and HLA-A, B, and DRB1 alleles in northern Iran. Methods: HLA-A, B, and DRB1 alleles in 33 patients with chronic hepatitis B (CHB) and 31 healthy carriers as the persistent group, and 30 subjects who had spontaneously recov- ered from HBV infection were analyzed by using the polymerase chain reaction (PCR)– sequence-specific primer (PCR-SSP) technique. Results: The frequency of the HLA-A*33 allele was higher in the persistent group than in the recovered group (10.16% vs 0%, P < 0.008); the frequency of the DRB1*13 allele was lower in the persistent group than in the recovered group (3.13% vs 11.67%, P < 0.03). The frequency of the B*52 allele was higher in CHB patients than healthy carriers (7.58% vs 0%, P < 0.05). The logistic regression model showed that the presence of the HLA- DRB1*13 allele was the significant factor associated with protection against the persis- tency of HBV. There were significant differences between the HBV recovered group, CHB patients, and healthy carriers regarding age, hepatitis B e antigen, and anti-hepatitis B e positivity. Conclusion: HLA-A*33 was closely related with susceptibility to persisting hepatitis B infection, and HLA-DRB1*13 was closely related with protection against persisting hepa- titis B in an Iranian population. These findings emphasized that the host HLA polymor- phism is an important factor in determining the outcome of HBV infection. Key words allele, hepatitis B, human leukocyte antigen (HLA). Accepted for publication 27 February 2008. Correspondence Dr Amitis Ramezani, Clinical Research Department, Pasteur Institute of Iran, 13164, Pasteur Ave., Tehran, Iran. Email: iiccom@iiccom.com Introduction Hepatitis B virus (HBV) infection is a major public health problem worldwide. The clinical features of HBV infection vary from clear- ance of the virus to fulminant hepatitis. The mechanism of sus- ceptibility to chronic persistent HBV infection is not well clarified, while the outcome of HBV infection mainly depends on the host immune response. Human leukocyte antigen (HLA) is an integral component of the immune response on which majority of host genetic studies have concentrated. Many different HLA alleles have been demonstrated as playing roles in HBV infection. 1 It has been reported that the HLA polymorphism correlates with the outcome of HBV infection, but this relationship is not universal on the basis of investigated populations. In Caucasians 2,3 and Koreans, 4 for example, HLA-DRB1*1301-02 has been found to be associated with acute self-limited hepatitis B. In Taiwanese people, HLA-DRB1*0406 is associated with recovery from HBV infection in the Han Chinese, as is HLA-B*4001 in indigenous Taiwanese people. 5 Han Chinese with HLA-DR12 (especially one of its alleles, DRB1*1201) or HLA-DRB1*1101/1104 have been shown to be able to resist HBV infection, and those with HLA-DR9, DQ9, HLA-DRB1*0301, HLA-DQB1*0301, 6,7 and DRB1*10 have been revealed to have a relationship with suscep- tibility to chronic HBV infection 8 . In this study, we aimed to determine the association between HBV infection and HLA-A, B, and DRB1 alleles in northern Iran. Methods Study population A total of 94 HBV infected patients (55 males, 39 females; mean age, 32.9  10.5 years [range, 14–60 years]) who admitted to a hepatitis referral center in northern Iran from October 2006 to doi:10.1111/j.1440-1746.2008.05482.x 1716 Journal of Gastroenterology and Hepatology 23 (2008) 1716–1721 © 2008 The Authors Journal compilation © 2008 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd