Veterans Affairs San Diego Healthcare System, San Diego, California.
San Francisco Veterans Affairs Healthcare System, San Francisco, California.
Clin Gastroenterol Hepatol. 2017 Feb;15(2):282-288. doi: 10.1016/j.cgh.2016.05.024. Epub 2016 May 27.
BACKGROUND & AIMS: We conducted a phase 4, open-label study with limited exclusion criteria to evaluate the safety and efficacy of sofosbuvir and ribavirin in veterans with hepatitis C virus genotype 2 infection, and compensated cirrhosis. This population is often excluded from clinical studies.
We performed a prospective study of treatment-naive (n = 47) and treatment-experienced (n = 19) patients with chronic hepatitis C virus genotype 2 infection and compensated cirrhosis at 15 Department of Veterans Affairs sites. All subjects were given sofosbuvir (400 mg, once daily) plus ribavirin (1000-1200 mg/day) in divided doses for 12 weeks. Patients with major psychiatric diseases or alcohol or substance use disorders were not excluded. The primary endpoint was sustained virologic response 12 weeks after therapy.
Fifty-two patients achieved a sustained virologic response 12 weeks after therapy (79%; 95% confidence interval, 67%-88%); 16 of these patients were treatment experienced (84%; 95% confidence interval, 60%-97%) and 36 were treatment naive (77%; 95% confidence interval, 62%-88%). All patients had at least 1 comorbidity. Thirty-five percent had depression, 24% had posttraumatic stress disorder, and 30% had anxiety disorder. In addition, 29% had current substance use. Of the 7 patients (11%) who discontinued the study treatment prematurely, 3 did so because of adverse events. The most common adverse events were fatigue, anemia, nausea, and headache. Serious adverse events occurred in 8 patients. Only 2 of the serious adverse events (anemia and nausea) were considered to be related to study treatment.
In a phase 4 study, 12 weeks treatment with sofosbuvir and ribavirin led to a sustained virologic response 12 weeks after therapy in almost 80% of veterans with hepatitis C virus genotype 2 infection, compensated cirrhosis, and multiple comorbidities, regardless of their treatment history. ClinicalTrials.gov, Number: NCT02128542.
我们开展了一项纳入标准有限的 4 期、开放性标签研究，旨在评估索磷布韦和利巴韦林治疗慢性丙型肝炎病毒基因型 2 感染合并代偿性肝硬化退伍军人的安全性和有效性。这一人群通常被排除在临床试验之外。
我们在 15 个退伍军人事务部地点对 47 例初治（n=47）和 19 例经治（n=19）慢性丙型肝炎病毒基因型 2 感染合并代偿性肝硬化患者进行了前瞻性研究。所有患者均接受索磷布韦（400mg，每日 1 次）联合利巴韦林（1000-1200mg/日，分剂量给药）治疗 12 周。未排除患有重大精神疾病或酒精或药物使用障碍的患者。主要终点是治疗 12 周后的持续病毒学应答。
52 例患者治疗 12 周后获得持续病毒学应答（79%；95%置信区间，67%-88%）；其中 16 例患者为经治（84%；95%置信区间，60%-97%），36 例为初治（77%；95%置信区间，62%-88%）。所有患者均存在至少 1 种合并症。35%的患者患有抑郁症，24%的患者患有创伤后应激障碍，30%的患者患有焦虑症。此外，29%的患者存在当前的物质使用情况。在提前停止研究治疗的 7 例患者（11%）中，有 3 例因不良事件停药。最常见的不良事件是疲劳、贫血、恶心和头痛。8 例患者发生严重不良事件。仅 2 例严重不良事件（贫血和恶心）被认为与研究治疗有关。
在这项 4 期研究中，在患有慢性丙型肝炎病毒基因型 2 感染、代偿性肝硬化和多种合并症的退伍军人中，无论其治疗史如何，接受 12 周的索磷布韦和利巴韦林治疗后，12 周时的持续病毒学应答率接近 80%。ClinicalTrials.gov，编号：NCT02128542。
