HLA-DRB1*010101 allele is closely associated with poor virological response to lamivudine therapy in patients with chronic hepatitis B.

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 log(10) 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.