Abstract
Background/Aims: We intended to evaluate the association between specific human leukocyte antigen (HLA)-DRB1 gene polymorphism and antiviral response to lamivudine (LAM) therapy in chronic hepatitis B (CHB) patients. Methods: Six-digit HLA-DRB1 genotypes were determined using sequence-based typing in 334 CHB patients initially treated with LAM for at least 12 months. Antiviral response was evaluated every 3–6 months during LAM therapy. Results: Median age of the subjects was 43 years (range, 16–72). Median duration of LAM therapy was 69 months (range, 13–140). Median baseline serum hepatitis B virus (HBV DNA) level was 7.0 log10 copies/ml (range, 5.5–9.1). At 12 months of LAM therapy, serum HBV DNA was undetectable by solution hybridization method in 308 (88%) patients. Among 25 HLA-DRB1 alleles identified, HLA-DRB1*090102, *080302, and *070101 were the most frequent alleles (>10%). HLA-DRB1*010101 was identified in 5.4% (18/334). The frequency of the HLA-DRB1*010101 allele was significantly lower in patients with virological response at 12 months of LAM therapy than in patients without it (4.2 vs. 19.2%, p = 0.025). The other HLA-DRB1 alleles were not associated with virological response. HBeAg loss/seroconversion and alanine aminotransferase normalization were not associated with HLA-DRB1 alleles. Conclusion: The HLA-DRB1*010101 allele is closely associated with poor virological response to initial LAM therapy in CHB patients.
Journal Section:
Paper
References
1.
Dienstag JL: Hepatitis B virus infection. N Engl J Med 2008;359:1486–1500.
[PubMed]
2.
Lok AS, McMahon BJ: Chronic hepatitis B: update 2009. Hepatology 2009;50:661–662.
[PubMed]
3.
Merican I, Guan R, Amarapuka D, et al: Chronic hepatitis B virus infection in Asian countries. J Gastroenterol Hepatol 2000;15:1356–1361.
[PubMed]
4.
Pungpapong S, Kim WR, Poterucha JJ: Natural history of hepatitis B virus infection: an update for clinicians. Mayo Clin Proc 2007;82:967–975.
[PubMed]
5.
Thursz MR: Host genetic factors influencing the outcome of hepatitis. J Viral Hepat 1997;4:215–220.
[PubMed]
6.
Chisari FV, Ferrari C: Hepatitis B virus immunopathogenesis. Annu Rev Immunol 1995;13:29–60.
[PubMed]
7.
Singh R, Kaul R, Kaul A, et al: A comparative review of HLA associations with hepatitis B and C viral infections across global populations. World J Gastroenterol 2007;13:1770–1787.
[PubMed]
8.
Thursz MR, Kwiatkowski D, Allsopp CE, et al: Association between an MHC class II allele and clearance of hepatitis B virus in the Gambia. N Engl J Med 1995;332:1065–1069.
[PubMed]
9.
Hohler T, Gerken G, Notghi A, et al: HLA-DRB1*1301 and *1302 protect against chronic hepatitis B. J Hepatol 1997;26:503–507.
[PubMed]
10.
Cho SW, Cheong JY, Ju YS, et al: Human leukocyte antigen class II association with spontaneous recovery from hepatitis B virus infection in Koreans: analysis at the haplotype level. J Korean Med Sci 2008;23:838–844.
[PubMed]
11.
Jiang YG, Wang YM: Study on the polymorphism of human leukocyte antigen-DRB1, -DQA1 and -DQB1 alleles in patients with hepatitis B (in Chinese). Zhonghua Liu Xing Bing Xue Za Zhi 2004;25:337–340.
[PubMed]
12.
Chu RH, Ma LX, Wang G, et al: Influence of HLA-DRB1 alleles and HBV genotypes on interferon-alpha therapy for chronic hepatitis B. World J Gastroenterol 2005;11:4753–4757.
[PubMed]
13.
Han YN, Yang JL, Zheng SG, et al: Relationship of human leukocyte antigen class II genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients. World J Gastroenterol 2005;11:5721–5724.
[PubMed]
14.
Lee YS, Suh DJ, Lim YS, et al: Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy. Hepatology 2006;43:1385–1391.
[PubMed]
15.
Sayer D, Whidborne R, Brestovac B, et al: HLA-DRB1 DNA sequencing based typing: an approach suitable for high throughput typing including unrelated bone marrow registry donors. Tissue Antigens 2001;57:46–54.
[PubMed]
16.
Hoppe B, Salama A: Sequencing-based typing of HLA. Methods Mol Med 2007;134:71–80.
[PubMed]
17.
Di Lelio A, Cestari C, Lomazzi A, et al: Cirrhosis: diagnosis with sonographic study of the liver surface. Radiology 1989;172:389–392.
[PubMed]
18.
Baumert TF, Thimme R, von Weizsacker F: Pathogenesis of hepatitis B virus infection. World J Gastroenterol 2007;13:82–90.
[PubMed]
19.
Tsubota AK, Arase Y, Ren FR, et al: Genotype may correlate with liver carcinogenesis and tumor characteristics in cirrhotic patients infected with hepatitis B virus subtype ADW. J Med Virol 2001;65:257–265.
[PubMed]
20.
Liaw YF, Leung N, Kao JH, et al: Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int 2008;2:263–283.
[PubMed]
21.
EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 2009;50:227–242.
[PubMed]
22.
Chan HL, Tse CH, Mo F, et al: High viral load and hepatitis B virus subgenotype CE are associated with increased risk of hepatocellular carcinoma. J Clin Oncol 2008;26:177–182.
[PubMed]
23.
Delmonico FL, Jenkins RL, Freeman R, et al: The high-risk liver allograft recipient. Should allocation policy consider outcome? Arch Surg 1992;127:579–584.
[PubMed]
24.
Chen CJ, Yang HI, Su J, et al: Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295:65–73.
[PubMed]
25.
Lacap PA, Huntington JD, Luo M, et al: Associations of human leukocyte antigen DRB with resistance or susceptibility to HIV-1 infection in the Pumwani Sex Worker Cohort. AIDS 2008;22:1029–1038.
[PubMed]
26.
Newton-Nash DK, Eckels DD: Effects of localized HLA class II beta chain polymorphism on binding of antigenic peptide and stimulation of T cells. Hum Immunol 1992;33:213–223.
[PubMed]
27.
Lok AS, McMahon BJ: Chronic hepatitis B. Hepatology 2007;45:507–539.
[PubMed]
28.
European Association for the Study of the Liver: EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 2009;50:227–242.
[PubMed]
29.
Bunce M, Fanning GC, Welsh KI: Comprehensive, serologically equivalent DNA typing for HLA-B by PCR using sequence-specific primers (PCR-SSP). Tissue Antigens 1995;45:81–90.
[PubMed]
30.
Bunce M, O’Neill CM, Barnardo MC, et al: Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP). Tissue Antigens 1995;46:355–367.
[PubMed]
31.
Almarri A, Batchelor JR: HLA and hepatitis B infection. Lancet 1994;344:1194–1195.
[PubMed]
32.
Diepolder HM, Jung MC, Albert E, et al: HLA and hepatitis B infection. Lancet 1994;344:1772–1773.
[PubMed]
33.
Cano P, Klitz W, Mack SJ, et al: Common and well-documented HLA alleles: report of the Ad-Hoc Committee of the American Society for Histocompatibility and Immunogenetics. Hum Immunol 2007;68:392–417.
[PubMed]
© 2011 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2011
You do not currently have access to this content.
