Gous Natasha, Bhimma Rajendra, Kew Michael, Kramvis Anna
Hepatitis Virus Diversity Research Programme (formerly MRC/CANSA/University Molecular Hepatology Research Unit), Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Antivir Ther. 2010;15(1):61-9. doi: 10.3851/IMP1487.
A causal relationship exists between HBV infection and membranous nephropathy. The association is especially close in Black children in sub-Saharan Africa. Interferon-alpha2b is commonly used to treat this condition, but is effective in only 30-40% of patients. The reason for the poor response is unknown. The objective of this study was to determine if mutations in the surface gene of HBV isolated from Black children with HBV-associated membranous nephropathy before, during and after interferon treatment, have any effect on treatment response and vice versa.
HBV DNA was extracted from a responder, a reverter and a non-responder before and after initiation of 16 weeks of interferon-alpha2b treatment. The preS1/preS2/S region was amplified, cloned and sequenced.
The preS2 region was the most variable in the reverter and the non-responder, and the S region was the most variable in the non-responder. Phylogenetic analysis showed that the viral population dynamics between the responder and the reverter/non-responder strains differed as a result of mutations in the surface gene.
The presence of mutations in the S region of HBV could be used as predictive markers to differentiate interferon-alpha2b responders from non-responders provided that detailed analysis of further genomes confirms our findings.
乙型肝炎病毒（HBV）感染与膜性肾病之间存在因果关系。这种关联在撒哈拉以南非洲的黑人儿童中尤为密切。α-干扰素2b常用于治疗这种疾病，但仅对30%-40%的患者有效。反应不佳的原因尚不清楚。本研究的目的是确定从患有HBV相关膜性肾病的黑人儿童中分离出的HBV表面基因在干扰素治疗前、治疗期间和治疗后的突变是否对治疗反应有任何影响，反之亦然。
在开始16周的α-干扰素2b治疗之前和之后，从一名治疗有反应者、一名病情逆转者和一名治疗无反应者中提取HBV DNA。对前S1/前S2/S区域进行扩增、克隆和测序。
前S2区域在病情逆转者和治疗无反应者中变化最大，S区域在治疗无反应者中变化最大。系统发育分析表明，由于表面基因的突变，治疗有反应者与病情逆转者/治疗无反应者菌株之间的病毒群体动态有所不同。
如果进一步基因组的详细分析证实我们的发现，HBV S区域突变的存在可作为预测标志物，以区分α-干扰素2b治疗有反应者和无反应者。
