Yuan Chunyan, Peng Jing, Xia Renxiang, He Jian, Qiu Tianji, Yao Yunqing
Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Microbiol. 2022 Mar 10;13:865124. doi: 10.3389/fmicb.2022.865124. eCollection 2022.
Up to now, it has not been clear whether occult hepatitis B virus (HBV) infection (OBI) can be treated with antiviral therapy whether OBI can develop drug resistance gene mutation or not. We report a middle-aged female patient with OBI who showed HBV reactivation (HBVr) during more than 3 years of intermittent entecavir (ETV) antiviral therapy: seropositive HBV surface antigen (HBsAg), increased e antigen (HBeAg), and repeatedly elevated serum HBV DNA. Genotype analysis showed that the patient was infected with HBV type B. Genetic sequencing of HBV showed the mutants of S143T, D144G, and G145R in the S gene region, and the mutant of site 1896 in the pre-Core region coexisted with the wild type (G1896A/G). No mutation was found in other HBV gene segments. Drug resistance gene analysis found RtL229W mutant, resistant to lamivudine but sensitive to ETV and other nucleoside analogs. This case of OBI provides us with the following clinical experiences: Firstly, it is necessary to detect HBV genotype, mutation, and drug-resistant genes at the initial diagnosis, which can be helpful for reasonable treatment. Secondly, identifying the risk factors and mechanisms associated with HBVr could help quantify the risk of HBVr and manage the clinical consequences. Thirdly, the OBI patients with hepatitis B e antigen-positive, HBV DNA > 1 × 10 IU/ml should be recommended regular and continuous antiviral therapy as soon as possible to prevent the occurrence of hepatocirrhosis and hepatocellular carcinoma (HCC).
到目前为止，隐匿性乙型肝炎病毒（HBV）感染（OBI）是否可用抗病毒治疗，以及OBI是否会发生耐药基因突变尚不清楚。我们报告一例中年女性OBI患者，在3年多的恩替卡韦（ETV）间歇抗病毒治疗期间出现HBV再激活（HBVr）：HBV表面抗原（HBsAg）血清学阳性、e抗原（HBeAg）增加，且血清HBV DNA反复升高。基因分型分析显示该患者感染B型HBV。HBV基因测序显示S基因区有S143T、D144G和G145R突变，前C区1896位点突变与野生型（G1896A/G）共存。其他HBV基因片段未发现突变。耐药基因分析发现RtL229W突变，对拉米夫定耐药，但对ETV和其他核苷类似物敏感。该OBI病例为我们提供了以下临床经验：首先，初诊时检测HBV基因型、突变及耐药基因很有必要有助于合理治疗。其次，识别与HBVr相关的危险因素和机制有助于量化HBVr风险并处理临床后果。第三，对于乙肝e抗原阳性、HBV DNA＞1×10 IU/ml的OBI患者，应尽早建议进行规律且持续的抗病毒治疗，以预防肝硬化和肝细胞癌（HCC）的发生。
