In December 2013, the FDA approved both simeprevir (SMV) and sofosbuvir (SOF) as oral treatments for chronic hepatitis C virus (HCV), providing clinicians with off-label access to an all oral-regimen for HCV genotype 1. Subgroup data from the phase 2 COSMOS study [Lawitz E et al. Lancet. 2014] showed that the combination of SMV + SOF with or without ribavirin (RBV) produced a 93% cure rate among people with Child-Pugh class A cirrhosis. However, the efficacy and safety of this drug combination with or without RBV among patients with worsening cirrhosis (Child-Pugh class B/C) remained unknown.

Varun Saxena, MD, University of California San Francisco School of Medicine, San Francisco, California, USA, presented data assessing the safety and efficacy of a 12-week combination of SMV + SOF with or without RBV in patients with cirrhosis Child-Pugh class B/C. These patients were compared with matched treated and untreated controls. The treated controls had been treated with telaprevir or boceprevir plus interferon and RBV, which was the standard of care at the time that they were treated.

Fifty-five adults with HCV genotype 1 (cases) received the drug combination; RBV was included at the discretion of the physician. Each of the 55 cases was matched with up to 3 treated and untreated controls based on age, treatment center, model for end-stage liver disease (MELD), and Child-Pugh class. At baseline, cases had a median age of 61 years. About half of patients were women; 35% had diabetes; 58% had HCV genotype 1a; 62% had previous HCV treatment; and 89% had cirrhosis Child-Pugh class B.

At baseline, patients had a median MELD score of 12; 64% had ascites; 49% had any hepatic encephalopathy; 35% had varices; and 35% had been exposed to RBV, highlighting their high morbidity. The study’s 2 primary outcomes were the percentage of patients who achieved a sustained virologic response at week 12 (SVR12) and a number of safety outcomes:

• early treatment discontinuation,

• adverse events (AEs) requiring hospitalization,

• infections requiring antibiotics,

• hepatic decompensating events, and

• death.

A total of 73% of the cases achieved SVR12. Of the 27% who did not, 3 patients had detectable HCV RNA at the end of treatment, and 12 patients relapsed after the end of treatment. Multivariate analysis revealed that the absence of hepatic encephalopathy and platelets ≥ 100 000/mm³ significantly predicted those patients likely to achieve SVR12 (OR, 3.37; 95% CI, 1.00 to 11.8; P = .05; OR, 4.29; 95% CI, 1.14 to 16.1; P = .02, respectively). Regarding safety, 11% of the cases discontinued treatment, and 11% discontinued treatment (of which 9% discontinued because of AEs); 22% were hospitalized due to AEs; 20% required antibiotics for infections; and 20% experienced hepatic decompensation. One patient died as the result of worsening liver and kidney function.

Table 1 compares the rates of HCV cure, early discontinuation, AEs, infections, and decompensation between the cases and the treated controls.

Current guidelines from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America do not recommend the use of SMV and SOF in patients with Child-Pugh B/C cirrhosis because of safety concerns [www.hcvguidelines.org. Accessed May 29, 2015]. However, Dr Saxena conjectured that these difficult patients (mostly those with Child-Pugh B cirrhosis) can be successfully treated and that data from this study may help inform future treatment recommendations.