Division of Clinical and Molecular Hepatology, University Hospital of Messina, Via Consolare Valeria, 1, 98124 Messina, Italy; Department of Pediatric, Gynecologic, Microbiological and Biomedical Sciences, University Hospital of Messina, Via Consolare Valeria, 1, 98124 Messina, Italy.
Division of Clinical and Molecular Hepatology, University Hospital of Messina, Via Consolare Valeria, 1, 98124 Messina, Italy; Department of Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy.
J Hepatol. 2014 Aug;61(2):408-17. doi: 10.1016/j.jhep.2014.04.041. Epub 2014 May 5.
The emergence and takeover of hepatitis B virus (HBV) variants carrying mutation(s) in the preS/S genomic region is a fairly frequent event that may occur spontaneously or may be the consequence of immunoprophylaxis or antiviral treatments. Selection of preS/S mutants may have relevant pathobiological and clinical implications. Both experimental data and studies in humans show that several specific mutations in the preS/S gene may induce an imbalance in the synthesis of the surface proteins and their consequent retention within the endoplasmic reticulum (ER) of the hepatocytes. The accumulation of mutated surface proteins may cause ER stress with the consequent induction of oxidative DNA damage and genomic instability. Viral mutants with antigenically modified surface antigen may be potentially infectious to immune-prophylaxed patients and may account for cases of occult HBV infection. In addition, preS/S variants were reported to be associated with cases of fulminant hepatitis as well as of fibrosing cholestatic hepatitis, and they are associated with cirrhosis and hepatocellular carcinoma development.
乙型肝炎病毒（HBV）前 S/S 区基因突变株的出现和流行是一个相当常见的现象，可自发产生，也可继发于免疫预防或抗病毒治疗。前 S/S 突变株的选择可能具有相关的病理生物学和临床意义。实验数据和人体研究均表明，前 S/S 基因的某些特定突变可导致表面蛋白合成失衡，进而导致其在肝细胞内质网（ER）内滞留。突变表面蛋白的蓄积可导致 ER 应激，进而诱导氧化 DNA 损伤和基因组不稳定性。具有抗原性改变的表面抗原的病毒突变株可能对免疫预防的患者具有潜在感染性，并可导致隐匿性 HBV 感染。此外，有报道称前 S/S 变异株与暴发性肝炎以及纤维性胆汁性肝炎有关，还与肝硬化和肝细胞癌的发生有关。
