Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study

Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naive and prior null-responder HCV genotype (GT) 1-infected patients receiving simeprevir+sofosbuvir±ribavirin for 12 or 24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open-label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naive and treatment-experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily+sofosbuvir 400 mg once daily for 12 or 8 weeks. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 weeks versus a composite historical control SVR rate. Enrolled were 310 patients, who were randomized and received treatment (n = 155 in each arm). SVR12 with simeprevir+sofosbuvir for 12 weeks (97% [150/155; 95% confidence interval 94%-100%]) was superior to the historical control (87%). SVR12 with simeprevir+sofosbuvir for 8 weeks (83% [128/155; 95% confidence interval 76-89%]) was not superior to the historical control (83%). The most frequent adverse events were nausea, headache, and fatigue (12-week arm: 15% [23/155], 14% [22/155], and 12% [19/155]; 8-week arm: 9% [14/155], 17% [26/155], and 15% [23/155], respectively). No patients discontinued treatment due to an adverse event. One (1%, 12-week arm) and three (2%, 8-week arm) patients experienced a serious adverse event (all unrelated to study treatment). CONCLUSION: Simeprevir+sofosbuvir for 12 weeks is highly effective in the treatment of HCV GT1-infected patients without cirrhosis, including those with Q80K. (Hepatology 2016;64:370-380)

Adefovir dipivoxil for wait-listed and post-liver transplantation patients with lamivudine-resistant hepatitis B : final long-term results

Wait-listed (n = 226) or post-liver transplantation (n = 241) chronic hepatitis B (CHB) patients with lamivudine-resistant hepatitis B virus (HBV) were treated with adefovir dipivoxil for a median of 39 and 99 weeks, respectively. Among wait-listed patients, serum HBV DNA levels became undetectable (<1,000 copies/mL) in 59% and 65% at weeks 48 and 96, respectively. After 48 weeks, alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 77%, 76%, 60%, and 84% of wait-listed patients, respectively. Among posttransplantation patients, serum HBV DNA levels became undetectable in 40% and 65% at weeks 48 and 96, respectively. After 48 weeks, ALT, albumin, bilirubin, and prothrombin time normalized in 51%, 81%, 76%, and 56% of posttransplantation patients, respectively. Among wait-listed patients who underwent on-study liver transplantation, protection from graft reinfection over a median of 35 weeks was similar among patients who did (n = 34) or did not (n = 23) receive hepatitis B immunoglobulin (HBIg). Hepatitis B surface antigen was detected on the first measurement only in 6% and 9% of patients who did or did not receive HBIg, respectively. Serum HBV DNA was detected on consecutive visits in 6% and 0% of patients who did or did not receive HBIg, respectively. Treatment-related adverse events led to discontinuation of adefovir dipivoxil in 4% of patients. Cumulative probabilities of resistance were 0%, 2%, and 2% at weeks 48, 96, and 144, respectively. In conclusion, adefovir dipivoxil is effective and safe in wait-listed or posttransplantation CHB patients with lamivudine-resistant HBV and prevents graft reinfection with or without HBIg