Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea.
Clin Gastroenterol Hepatol. 2019 Jun;17(7):1348-1355.e2. doi: 10.1016/j.cgh.2018.10.037. Epub 2018 Oct 26.
BACKGROUND & AIMS: There are no globally agreed upon treatment guidelines for patients with chronic hepatitis B virus (HBV) with multidrug resistance (MDR). We conducted a multicenter, prospective, real-world cohort study of effects of tenofovir disoproxyl fumarate (TDF) monotherapy and TDF-based combination therapy, as rescue therapy, in patients with multidrug-resistant chronic HBV infections.
We recruited patients with chronic HBV infection with resistance to antivirals from 8 tertiary hospitals in Korea. Patients (n=423) received rescue therapy with TDF monotherapy (n=174) or TDF-based combination therapy (n=249). The median follow-up period was 180 weeks. A virologic response was defined as a serum HBV DNA level of <20 IU/mL.
Cumulative rates of virologic response did not differ significantly between the groups that received TDF monotherapy vs combination therapy at 48 weeks (71.7% vs 68.9%), 96 weeks (85.1% vs 84.2%), 144 weeks (92.1% vs 92.7%), 192 weeks (93.4% vs 95.7%), or 240 weeks (97.7% vs 97.2%). Serum levels of HBV DNA below 4.0 log IU/mL (odds ratio, 2.478; 95% CI 1.959-3.135; P < .001) and the absence of mutations associated with resistance to adefovir (odds ratio, 1.570; 95% CI 1.279-1.926; P < .001) were associated with virologic response in patients with MDR. There was no significant difference of virologic response among patients of different ages, sex, patients with vs without cirrhosis, positivity for hepatitis B e antigen, or renal function (all P > .05).
In a multicenter, real-world cohort study, long-term use of TDF monotherapy showed non-inferior antiviral efficacy compared with that of TDF-based combination therapy in patients with MDR.
目前尚无针对多重耐药（MDR）慢性乙型肝炎病毒（HBV）患者的全球共识治疗指南。我们进行了一项多中心、前瞻性、真实世界的队列研究，评估了替诺福韦酯（TDF）单药治疗和 TDF 联合治疗作为挽救治疗在多重耐药慢性 HBV 感染患者中的效果。
我们从韩国 8 家三级医院招募了对抗病毒药物耐药的慢性 HBV 感染患者。患者（n=423）接受 TDF 单药治疗（n=174）或 TDF 联合治疗（n=249）的挽救治疗。中位随访时间为 180 周。病毒学应答定义为血清 HBV DNA 水平<20 IU/mL。
TDF 单药治疗组与联合治疗组在第 48 周（71.7% vs 68.9%）、96 周（85.1% vs 84.2%）、144 周（92.1% vs 92.7%）、192 周（93.4% vs 95.7%）和 240 周（97.7% vs 97.2%）时的病毒学应答累积率无显著差异。血清 HBV DNA 水平低于 4.0 log IU/mL（比值比，2.478；95%置信区间，1.959-3.135；P<.001）和不存在阿德福韦耐药相关突变（比值比，1.570；95%置信区间，1.279-1.926；P<.001）与 MDR 患者的病毒学应答相关。不同年龄、性别、有无肝硬化、乙型肝炎 e 抗原阳性、肾功能的患者之间的病毒学应答无显著差异（均 P>.05）。
在一项多中心、真实世界的队列研究中，TDF 单药长期使用在抗病毒疗效方面不劣于 TDF 联合治疗，适用于 MDR 患者。
