慢性HBV感染仍是全球重大公共卫生问题。慢性乙型肝炎(慢乙肝)临床治愈(亦称功能性治愈)即完成有限疗程治疗后,血清HBsAg和HBV DNA持续检测不到、HBeAg阴转、伴或不伴HBsAg血清学转换,肝脏炎症缓解和组织病理学改善,终末期肝病发生率显著降低,是目前国内外最新慢乙肝防治指南推荐的理想治疗目标。临床实践证明,以直接抗病毒药物(DAA)[如核苷(酸)类似物(NA)]或免疫调节剂[如聚乙二醇化干扰素(PEG-IFN)α]序贯或联合治疗的优化方案针对部分优势人群显示出良好的疗效,开展了系列成功实现HBsAg阴转的多中心随机对照临床研究。《慢性乙型肝炎临床治愈(功能性治愈)专家共识》阐述了联合治疗方案的最新循证医学依据,并总结了慢乙肝临床治愈路线图,以指导临床医师治疗决策的制订。

乙型肝炎,慢性 /  乙型肝炎表面抗原 /  功能性治愈 /  临床治愈 / Abstract:

Chronic hepatitis B virus (HBV) infection remains a major world public health problem. Current guidelines for the prevention and treatment of chronic hepatitis B (CHB) have suggested clinical cure (also known as functional cure) as the ideal therapeutic goal, which is associated with decreased risk of cirrhosis and hepatocellular carcinoma. Clinical cure is defined as sustained, undetectable serum HBsAg, HBeAg and HBV DNA with or without seroconversion to anti-HBs, but with the persistence of residual cccDNA, accompanied by resolution of liver injury after the completion of a finite course of treatment. Accumulating data from a series of randomized controlled trials as well as clinical practice have confirmed certain clinical benefit of optimal sequential/combination strategies of direct acting antiviral drugs (DAA) [such as nucleoside analogues (NA) ]or immunomodulators [such as pegylated interferon alpha (PEG-IFN) ]for appropriately selected CHB patients. This consensus provides an updated and comprehensive analysis of the data supporting the use of combination therapies and summarizes the roadmap towards clinical cure of CHB to guide decision-making in clinical practice.

Key words: hepatitis B, chronic /  hepatitis B surface antigens /  functional cure /  clinical cure /  consensus  [49] TANGKIJVANICH P, CHITTMITTRAPRAP S, POOVORAWAN K, et al. A randomized clinical trial of peginterferon alpha-2b with or without entecavir in patients with HBe Ag-negative chronic hepatitis B:Role of host and viral factors associated with treatment response[J]. J Viral Hepat, 2016, 23 (6) :427-438. [65] LI GJ, YU YQ, CHEN SL, et al. Sequential combination therapy with pegylated interferon leads to loss of hepatitis B surface antigen and hepatitis B e antigen (HBe Ag) seroconversion in HBe Ag-positive chronic hepatitis B patients receiving longterm entecavir treatment[J]. Antimicrob Agents Chemother, 2015, 59 (7) :4121-4128. [67] BOURLIRE M, RABIEGA P, GANNE-CARRIE N, et al.Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos (t) ide analogue therapy versus nucleos (t) ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA:A randomised, controlled, open-label trial[J]. Lancet Gastroenterol Hepatol, 2017, 2 (3) :177-188.