Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: a pooled analysis

作者：Kao Jia Horng^*; Jensen Donald M; Manns Michael P; Jacobson Ira; Kumada Hiromitsu; Toyota Joji; Heo Jeong; Yoffe Boris; Sievert William; Bessone Fernando; Peng Cheng Yuan; Roberts Stuart K; Lee Youn Jae; Bhore Rafia; Mendez Patricia; Hughes Eric; Noviello Stephanie

来源：Liver International, 2016, 36(7): 954-962.

DOI：10.1111/liv.13049

• cirrhosis
• direct acting antiviral
• hepatitis C
• safety

Background & AimsWe compared outcomes by cirrhosis status across studies of the all-oral combination of daclatasvir (DCV) plus asunaprevir (ASV).
MethodsOutcomes from global and Japanese phase 2 and 3 clinical studies of DCV+ASV in patients with genotype (GT) 1b infection were assessed by cirrhosis status. Sustained virological response (SVR) was assessed in individual phase 3 studies; a pooled analysis was carried out for safety outcomes.
ResultsIn the Japanese phase 3 study, SVR12 was achieved by 91% of patients with cirrhosis (n = 22) and 84% of patients without cirrhosis (n = 200); in the global phase 3 study, SVR12 was achieved by 84% of patients with cirrhosis (n = 206) and by 85% of patients without cirrhosis (n = 437). The frequency of serious adverse events, adverse events leading to treatment discontinuation and treatment-emergent grade 3/4 laboratory abnormalities was low (<10%) and similar among patients with (n = 229) or without (n = 689) compensated cirrhosis receiving DCV+ASV. Grade 3/4 reductions in platelets and neutrophils were more common among patients with cirrhosis (1.3 and 2.2%, respectively) compared with those without cirrhosis (both 0.6%). Grade 3/4 liver function test abnormalities were less common among patients with cirrhosis (1.8%) compared with those without cirrhosis (3.5-4.7%). Alanine aminotransferase elevations were not associated with hepatic decompensation.
ConclusionsThe safety and efficacy of DCV+ASV were similar in patients with or without compensated cirrhosis. This all-oral, interferon- and ribavirin-free combination is an effective and well-tolerated treatment option for patients with HCV GT1b infection and cirrhosis. Trial registrations numbers: identifiers: NCT01012895; NCT01051414; NCT01581203; NCT01497834.

• 出版日期2016-7
• 单位中国医科大学