Chen Xin-Xin, Xiang Kuan-Hui, Zhang Hai-Ping, Kong Xiang-Sha, Huang Chun-Yang, Liu Yan-Min, Lou Jin-Li, Gao Zu-Hua, Yan Hui-Ping
Center for Clinical Laboratory and Department of Immunological Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China.
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
J Microbiol Immunol Infect. 2020 Dec;53(6):946-954. doi: 10.1016/j.jmii.2019.04.009. Epub 2019 May 18.
BACKGROUND/PURPOSE: Occult HBV infection (OBI) could have serious clinical consequences in patients receiving immunosuppressive therapy. We aimed to investigate the prevalence of OBI in Chinese patients with autoimmune hepatitis (AIH) and to analyze its clinical and virological features.
103 AIH cases were enrolled. Hepatitis B virus (HBV) serological markers were screened by chemiluminescence. HBV-DNA were detected by nest-PCR and real-time PCR. HBV genotyping and mutation analysis were performed by Sanger sequencing.
Twenty-four out of 103 (23.30%) AIH patients had OBI as evidenced by positive HBV-DNA and negative hepatitis B surface antigen (HBsAg). HBV genotype C is the predominant genotype (57.89%), which had more amino acid (AA) substitutions in S region than that of B-genotype group (P = 0.001). The distribution of AA substitution in the 'α' determinant region between genotype C and B were significantly different (P = 0.042). In addition to those already reported OBI-associated AA substitutions (e.g., sG145R and sV184A), some new OBI-associated AA substitutions (e.g., sV106A, sC137* and sL176P) were found in AIH patients in our study. Three out of 24 (12.50%) OBI patients were diagnosed as decompensated cirrhosis, one patient with S deletion mutation and two patients with HBV extensive AA substitutions.
There was a higher proportion of AIH patients with OBI than the general population in China, which can be either seropositive or seronegative-OBI in AIH patients is associated with some specific AA substitutions. The presence of deletion mutations and the extent of AA substitutions in the HBV S region may have predictive clinical implications.
背景/目的:隐匿性乙型肝炎病毒(HBV)感染(OBI)在接受免疫抑制治疗的患者中可能会产生严重的临床后果。我们旨在调查中国自身免疫性肝炎(AIH)患者中OBI的患病率,并分析其临床和病毒学特征。
纳入103例AIH病例。采用化学发光法筛查乙型肝炎病毒(HBV)血清学标志物。采用巢式PCR和实时荧光定量PCR检测HBV-DNA。采用Sanger测序法进行HBV基因分型和突变分析。
103例AIH患者中有24例(23.30%)存在OBI,表现为HBV-DNA阳性且乙型肝炎表面抗原(HBsAg)阴性。HBV基因C型是主要基因型(57.89%),其S区氨基酸(AA)替代比B基因型组更多(P = 0.001)。基因C型和B型在“α”决定簇区域的AA替代分布有显著差异(P = 0.042)。除了已报道的与OBI相关的AA替代(如sG145R和sV184A)外,我们的研究在AIH患者中还发现了一些新的与OBI相关的AA替代(如sV106A、sC137*和sL176P)。24例OBI患者中有3例(12.50%)被诊断为失代偿期肝硬化,1例患者存在S区缺失突变,2例患者存在HBV广泛AA替代。
中国AIH患者中OBI的比例高于普通人群,AIH患者中OBI可以是血清学阳性或血清学阴性,与一些特定的AA替代有关。HBV S区缺失突变的存在和AA替代的程度可能具有临床预测意义。