Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Aliment Pharmacol Ther. 2014 May;39(10):1059-70. doi: 10.1111/apt.12717. Epub 2014 Mar 24.
Genetic factors can play an important role for treatment response and disease progression in chronic viral hepatitis.
To review the influence of host genetic factors on the clinical course as well as on treatment response in patients with viral hepatitis.
Review of the literature.
A landmark genome-wide association study (GWAS) identified polymorphisms in the IL28B gene on chromosome 19 (19q13.13) associated with response to therapy with pegylated interferon-α (PEG-IFN) and ribavirin (RBV) and spontaneous viral clearance in acute hepatitis C. Furthermore, IL28B genotype is associated with changes of lipid metabolism and insulin resistance. A further GWAS demonstrated that ITPA genetic variants protect HCV genotype 1 patients from RBV-induced anaemia. Another polymorphism in the patatin-like phospholipase domain containing 3 (PNPLA3) is associated with hepatic steatosis. Difficult-to-treat hepatitis C patients homozygous for GG had an up to five-fold lower chance of viral clearance on PEG/RBV than non-GG patients. In chronic hepatitis B patients treated with PEG-IFN several retrospective analyses of IL28B rs12980275 and rs12979860 genotypes yielded conflicting results which can be explained by the heterogeneity between the study populations. Some variants of the HLA-DP locus (HLA-DPA1 A allele and HLA-DPB1) protect against progression of chronic hepatitis B infection.
The determination of IL28B polymorphisms may be useful to individualise treatment options when using PEG/RBV based therapies for chronic hepatitis C infection. In contrast, so far identified genetic factors play only a minor role in chronic hepatitis B infection.
遗传因素在慢性病毒性肝炎的治疗反应和疾病进展中起着重要作用。
综述宿主遗传因素对病毒性肝炎患者临床病程及治疗反应的影响。
文献复习。
一项具有里程碑意义的全基因组关联研究（GWAS）确定了染色体 19（19q13.13）上 IL28B 基因的多态性与聚乙二醇干扰素-α（PEG-IFN）和利巴韦林（RBV）治疗应答以及急性丙型肝炎的自发性病毒清除有关。此外，IL28B 基因型与脂代谢和胰岛素抵抗的变化有关。进一步的 GWAS 表明，ITPA 基因变异可保护 HCV 基因型 1 患者免受 RBV 诱导的贫血。载脂蛋白样磷脂酶结构域包含 3（PNPLA3）的另一种多态性与肝脂肪变性有关。GG 纯合子的难治性丙型肝炎患者在接受 PEG/RBV 治疗时，病毒清除的几率比非 GG 患者低五倍。在接受 PEG-IFN 治疗的慢性乙型肝炎患者中，对 IL28B rs12980275 和 rs12979860 基因型的几项回顾性分析得出了相互矛盾的结果，这可以用研究人群之间的异质性来解释。HLA-DP 基因座（HLA-DPA1 A 等位基因和 HLA-DPB1）的一些变体可预防慢性乙型肝炎感染的进展。
当使用基于 PEG/RBV 的疗法治疗慢性丙型肝炎感染时，确定 IL28B 多态性可能有助于个体化治疗方案。相比之下，目前已确定的遗传因素在慢性乙型肝炎感染中只起次要作用。
