丙肝病毒直接抗病毒药物治疗慢性丙型肝炎临床研究

Clinical Study on Direct Antiviral Therapy for Chronic Hepatitis C

摘要: 目的：探讨丙肝病毒直接抗病毒药物治疗慢性丙型肝炎的疗效及安全性。方法：选择2015年10月至2016年6月我科门诊及住院的慢性丙型肝炎及丙型肝炎后肝硬化患者24例，根据丙肝病毒基因分型及是否有肝硬化分别给予：方案1 (S + L)： sofosbuvir (索菲布韦) + ledipasvir (雷迪帕韦) (S + L)；方案2 (S + D)： sofosbuvir (索菲布韦) + daclatasvir (达卡他韦)；方案3 (S + L + R)： S + L + RBV (利巴韦林)；方案4 (S+D + R)： S + D + RBV (利巴韦林)，慢性丙型肝炎疗程12周，丙型肝炎后肝硬化疗程24周，观察治疗后1周、2周、4周、12周、24周及停药后12周、24周HCV-RNA (高灵敏检测)、肝肾功能、血凝4项、血常规的变化。结果：24例患者治疗1周时17例行HCV-RNA检查，阴转率为53%；治疗2周时23例行HCV-RNA检查，阴转率为91%；治疗4周时18例行HCV-RNA检查，阴转率为100%，治疗2周以前已经转阴者6例未行检查，所以治疗4周时阴转率为100%；6例肝硬化患者中5例治疗24周时维持100%阴转率，1例治疗12周后因经济原因自行停药，停药12周后复查HCV-RNA仍为阴性；停药12周有14例患者行HCV-RNA复查，维持100%阴转率；10例患者停药24周行HCV-RNA复查，维持100%阴转率。结论：丙肝病毒直接抗病毒药物治疗慢性丙型肝炎及丙型肝炎后肝硬化疗效肯定、不良反应少、疗程短，对肝肾功能、凝血功能及血常规无明显影响，可作为标准治疗方案用于丙型肝炎患者的治疗。治疗期间HCV-RNA检测时间点选择治疗4周、12周、24周为宜，治疗1周、2周两个时间点可以不行HCV-RNA检测，以期节约医疗费用。肝硬化患者联合利巴韦林治疗似乎可以实现HCV-RNA更早期的阴转。sofosbuvir (索菲布韦) + daclatasvir (达卡他韦)方案对1型及2型丙型肝炎均具有理想的抗病毒疗效，对部分经济较为困难者可不查HCV基因分型直接给予该方案治疗。丙型肝炎后肝硬化患者12周与24周治疗方案的远期疗效值得进一步研究。

Abstract: Objective: To explore the efficacy and safety of direct antiviral therapy for chronic hepatitis C. Methods: 24 patients with chronic hepatitis C and post-hepatitis C cirrhosis in our clinic and hos-pital from October 2015 to June 2017 were selected. Basing on HCV genotyping and presence of cirrhosis, the patients were given one of the following regimens. Regimen 1: sofosbuvir + ledipasvir (SL); Regimen 2: sofosbuvir + daclatasvir (SD); Regimen 3: sofosbuvir + ledipasvir + ribavirin (SLR); and Regiment 4: sofosbuvir + daclatasvir + ribavirin (SDR). Patients with chronic hepatitis C but without cirrhosis were treated for 12 weeks, while those with cirrhosis were treated for 24 weeks. Changes in HCV-RNA (highly sensitive detection), liver and kidney function, the 4 major blood coagulation indexes, and blood routines were monitored at 1, 2, 4, 12, and 24 weeks after the beginning of treatment and 12 and 24 weeks after drug withdrawal. Results: After 1 week of treatment, 17 patients underwent high-sensitivity HCV-RNA detection, and showed a virological response rate of 53%. After 2 weeks of treatment, 23 patients underwent highly sensitive HCV-RNA detection, and showed a virological response rate of 91%. After 4 weeks of treatment, all 50 patients underwent highly sensitive HCV-RNA detection, and the virological response rate was 100%. After 12 weeks and 24 weeks of treatment (for patients with decompensated cirrhosis), the virological response rate was also 100%. At 12 and 24 weeks after drug withdrawal, virological response rate remained 100%. Regimen 2 showed equal antiviral efficacy as Regimens 3 and 4. In addition, Regimen 2 was also used for 20 patients with ungenotyped HCV, and also showed 100% virological response after 4, 12 or 24 weeks of treatment. Conclusion: treatment of chronic hepatitis C and hepatitis C cirrhosis directly with antiviral drugs shows good efficacy and little adverse effect, and the course of treatment is also short and shows no significant effect on coagulation function and blood routines of the patients, so it can be used as a standard treatment plan for patients with hepatitis C. The sofosbuvir + daclatasvir regimen shows satisfactory efficacy for both HCV Type 1 and 2, and may be directly used for patients who can’t afford HCV genotyping.