Flower Barnaby, McCabe Leanne, Le Ngoc Chau, Le Manh Hung, Le Thanh Phuong, Dang Trong Thuan, Vo Thi Thu, Vu Thi Kim Hang, Nguyen Tat Thanh, Phan Thi Hong Dao, Nguyen Thi Chau An, Dinh Thi Tan, Tran Thi Tuyet Nga, Tarning Joel, Kingsley Cherry, Kestelyn Evelyne, Pett Sarah L, Thwaites Guy, Nguyen Van Vinh Chau, Smith David, Barnes Eleanor, Ansari M Azim, Turner Hugo, Rahman Motiur, Walker Ann Sarah, Day Jeremy, Cooke Graham S
Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam.
Department of Infectious Disease, Imperial College London, United Kingdom.
Open Forum Infect Dis. 2021 Jun 9;8(7):ofab267. doi: 10.1093/ofid/ofab267. eCollection 2021 Jul.
Genotype 6 is the most genetically diverse lineage of hepatitis C virus, and it predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the least expensive treatment combination globally. In regional guidelines, longer treatment durations of SOF/DCV (24 weeks) are recommended for cirrhotic individuals, compared with other pangenotypic regimens (12 weeks), based on sparse data. Early on-treatment virological response may offer means of reducing length and cost of therapy in patients with liver fibrosis.
In this prospective trial in Vietnam, genotype 6-infected adults with advanced liver fibrosis or compensated cirrhosis were treated with SOF/DCV. Day 14 viral load was used to guide duration of therapy: participants with viral load <500 IU/mL at day 14 were treated with 12 weeks of SOF/DCV and those ≥500 IU/mL received 24 weeks. Primary endpoint was sustained virological response (SVR).
Of 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a and 34% had 6e. The remainder had 6h, 6k, 6l, or 6o. One hundred percent had viral load <500 IU/mL by day 14, meaning that all received 12 weeks of SOF/DCV. One hundred percent achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions at baseline.
Prescribing 12 weeks of SOF/DCV results in excellent cure rates in this population. These data support the removal of costly genotyping in countries where genotype 3 prevalence is <5%, in keeping with World Health Organization guidelines. NS5A resistance-associated mutations in isolation do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.
基因6型是丙型肝炎病毒基因多样性最高的谱系，在越南占主导地位。它可用索磷布韦联合达卡他韦（SOF/DCV）治疗，这是全球最便宜的治疗方案组合。在区域指南中，基于稀少的数据，与其他泛基因型治疗方案（12周）相比，对于肝硬化患者，推荐SOF/DCV更长的治疗疗程（24周）。治疗早期的病毒学反应可能为降低肝纤维化患者的治疗时长和费用提供方法。
在越南的这项前瞻性试验中，对感染基因6型且有晚期肝纤维化或代偿期肝硬化的成年人采用SOF/DCV治疗。第14天的病毒载量用于指导治疗疗程：第14天病毒载量<500 IU/mL的参与者接受12周的SOF/DCV治疗，病毒载量≥500 IU/mL的参与者接受24周治疗。主要终点是持续病毒学应答（SVR）。
在开始治疗的41例晚期纤维化或代偿期肝硬化患者中，51%为基因6a型，34%为基因6e型。其余为基因6h、6k、6l或6o型。到第14天，100%的患者病毒载量<500 IU/mL，这意味着所有患者均接受12周的SOF/DCV治疗。尽管基线时假定的NS5A抑制剂耐药相关替代突变频率较高，但100%的患者实现了12周持续病毒学应答。
给予12周的SOF/DCV治疗可使该人群获得极高的治愈率。这些数据支持在基因3型患病率<5%的国家取消昂贵的基因分型检测，这与世界卫生组织的指南一致。单独的NS5A耐药相关突变不影响SOF/DCV治疗的疗效。有必要对反应指导治疗进行更广泛的评估。
