Efficacy of Ledipasvir and Sofosbuvir Treatment of HCV Infection in Patients Coinfected With HBV
Efficacy of Ledipasvir and Sofosbuvir Treatment of HCV Infection in Patients Coinfected With HBV
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DOI：
10.1053/j.gastro.2017.11.011
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发表时间：
2018-03-01
期刊：
影响因子：
29.4
通讯作者：
Chen, Pei-Jer
中科院分区：
文献类型：
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作者：
Liu, Chun-Jen;Chuang, Wan-Long;Chen, Pei-Jer
背景与目的：有报道称，在用直接作用抗病毒药物治疗丙型肝炎病毒（HCV）感染期间，乙型肝炎病毒（HBV）感染重新激活。我们对 HBV 感染患者使用雷迪帕韦和索磷布韦治疗 HCV 感染的风险和结果进行了一项前瞻性研究。方法：我们在台湾对 111 名 HCV 感染患者（61% HCV 基因型 1，39% HCV 基因 2 感染；62% 女性，16% 代偿性肝硬化）和 HBV 感染患者进行了一项 3b 期、多中心、开放标签研究。除 1 人外，其余所有人乙型肝炎表面抗原 (HBsAg) 呈阳性； 1 名筛查时 HBsAg 阳性的患者在基线时被发现为 HBsAg 阴性。总体而言，33% 的参与者之前接受过 HCV 治疗，5% 之前接受过 HBV 治疗；研究开始时没有患者接受乙肝治疗。所有患者均接受 90 mg HCV NS5A 抑制剂雷迪帕韦 (ledipasvir) 与 400 mg NS5B 核苷酸类似物抑制剂索磷布韦 (sofosbuvir) 的固定剂量组合，每日一次，持续 12 周。主要终点是治疗结束后 12 周的持续病毒学应答。结果：所有 111 名患者 (100%) 均实现了持续的病毒学应答。在 37 名基线 HBV DNA 低于 20 IU/mL 的患者中，有 31 名 (84%) 到治疗后第 12 周至少有 1 次可量化的 HBV DNA。在 74 名基线 HBV DNA 水平为 20 IU/mL 或更高的患者中，39 名 (53%) 到治疗后第 12 周 HBV DNA 增加超过 1 log10 IU/mL。总体而言，5 名患者 HBV DNA 水平增加治疗后第 12 周，丙氨酸氨基转移酶水平 > 正常上限的 2 倍。其中 3 名患者开始 HBV 治疗。此外，1 名患者自第 8 周起 HBV 再激活，并在治疗后第 48 周伴随丙氨酸氨基转移酶升高>正常上限的 2 倍，在治疗后第 53 周开始治疗。该患者出现与 HBV 再激活相关的临床体征和症状。最常见的不良事件是头痛、上呼吸道感染和疲劳。结论：在一项前瞻性研究中，雷迪帕韦和索磷布韦联合治疗 12 周，在合并 HBV 感染的 HCV 感染患者中产生了 100% 的持续病毒学应答。大多数患者的 HBV DNA 水平升高，但与体征或症状无关。
BACKGROUND & AIMS: There have been reports of reactivation of hepatitis B virus (HBV) infection during treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents. We performed a prospective study of risks and outcomes of HCV infection treatment with ledipasvir and sofosbuvir in patients with HBV infection. METHODS: We performed a phase 3b, multicenter, open-label study in Taiwan of 111 patients with HCV infection (61% HCV genotype 1, 39% HCV genotype 2 infection; 62% women, 16% with compensated cirrhosis) along with HBV infection. All but 1 were positive for the hepatitis B surface antigen (HBsAg); 1 patient who was HBsAg-positive at screening was found to be HBsAg-negative at baseline. Overall, 33% of participants had received prior treatment for HCV and 5% had previously been treated for HBV; no patient was on HBV therapy at the start of the study. All patients received a fixed-dose combination of 90 mg of the HCV NS5A inhibitor ledipasvir with 400 mg of the NS5B nucleotide analogue inhibitor sofosbuvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of therapy. RESULTS: All 111 patients (100%) achieved a sustained virologic response. Of the 37 patients with baseline HBV DNA below 20 IU/ mL, 31 (84%) had at least 1 episode of quantifiable HBV DNA through posttreatment week 12. Of the 74 patients with baseline HBV DNA levels of 20 IU/ mL or more, 39 (53%) had increases of HBV DNA greater than 1 log10 IU/ mL through posttreatment week 12. Overall, 5 patients had increased levels of HBV DNA concomitant with a level of alanine aminotransferase > 2 times the upper limit of normal through posttreatment week 12. Of these, 3 patients started HBV treatment. In addition, 1 patient with HBV reactivation since week 8 and concomitant alanine aminotransferase elevation > 2 times upper limit of normal at posttreatment week 48 started treatment at posttreatment week 53. This patient had clinical signs and symptoms associated with HBV reactivation. The most common adverse events were headache, upper respiratory infection, and fatigue. CONCLUSIONS: In a prospective study, the combination of ledipasvir and sofosbuvir for 12 weeks produced a sustained virologic response in 100% of patients with HCV infection who were coinfected with HBV. Most patients had an increase in level of HBV DNA not associated with signs or symptoms.