Safety and efficacy of simeprevir plus sofosbuvir with or without ribavirin in patients with decompensated genotype 1 hepatitis C cirrhosis

Abstract

Combination antiviral therapy involving sofosbuvir (SOF) and simeprevir (SIM) is a treatment option in patients with genotype 1 chronic hepatitis C; however, the safety of this regimen in patients with decompensated cirrhosis is not established. Data from a combined treatment cohort of 2 large hepatology referral centers were evaluated to assess for safety and efficacy of SIM plus SOF with or without ribavirin (RBV) in patients with Child B or C cirrhosis. All (n 5 42) patients included in the analysis had Child B (n 5 35) or C (n 5 7) cirrhosis and received 400 mg daily of SOF plus 150 mg daily of SIM, with (n 5 7) or without (n 5 35) RBV, for 12 weeks. Of the 42 patients in this cohort, 31 (74%) were male, 22 (52%) had failed prior treatments, and 28 (67%) were genotype 1a. Prior decompensating events included encephalopathy (57%), fluid overload (88%), or variceal hemorrhage (24%). Median Model for End-Stage Liver Disease score was 12 (range, 6-25). Treatment was well tolerated overall with more than one-half (57%) reporting no adverse events. In those reporting adverse events, the most common were fatigue (n 5 6), insomnia (n 5 4), headache (n 5 5), nausea (n 5 4), and grade 1 rash (n 5 1). One patient developed chemical pancreatitis that did not require treatment discontinuation. Three of 7 patients who received RBV developed anemia, with 2 requiring blood transfusions and 1 requiring a dose reduction. No episodes of decompensation requiring hospitalization or deaths occurred on treatment. Of 42 patients, 38 (90%) patients had negative viral load at end of treatment (EOT), and 31 of 42 patients (74%) achieved sustained virological response 12 weeks after EOT; 10 of 10 patients (100%) with HCV genotype 1b achieved sustained virological response for 12 weeks (SVR12). In conclusion, SOF plus SIM was very well tolerated in patients with advanced Child B/C decompensated cirrhosis. Overall, 74% of patients achieved SVR12; 100% of patients with genotype 1b decompensated cirrhosis achieved SVR12. Liver Transpl 22:281-286, 2016. V C 2015 AASLD.

Direct-acting agents for hepatitis C virus before and after liver transplantation

“…Sofosbuvir and simeprevir was well-tolerated, resulting in a sustained viral response for 12 weeks (SVR12) of 74% and 100% in patients with genotype 1a and 1b, respectively (8). In a multicenter study (9) with the same regimen in decompensated and compensated patients reported an SVR12 of 74% and 91%, respectively.…”

Management of Chronic Hepatitis C Virus Infection: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases-2017 Update

“…Buna karşılık siklosporinle birlikte kullanımı SMV'nin plazma konsantrasyonunda anlamlı artışla ("hepatic uptake transporter" inhibisyonu nedeniyle) sonuçlanmaktadır ve bu nedenle bu ilaçların birlikte kullanımı önerilmemektedir (39,67,92,93). DEA ilaçlarla antiretroviral (Tablo 5), narkotik (Tablo 6), kardiyovasküler (Tablo 7), lipid metabolizmasını etkileyen (Tablo 8), santral sinir sistemine etkili (Tablo 9) ve immünosüpresif (Tablo 10) ilaçlar arasındaki etkileşimler ilgili tablolarda özet-lenmiştir.…”

Management of Hepatitis C Infection with Direct Action Antiviral Drugs (DAA)

“…Simeprevir undergoes oxidative metabolism from the CYP3A system (high interaction with drugs that suffer this metabolism) and subsequent excretion into the bile may cause jaundice and the elevation of ALT. In coinfection, HIV-HCV (only genotype 1) simeprevir should be used with antiretroviral drugs with which it does not have clinically significant interactions: abacavir, emtricitabine, enfuvirtide, lamivudine, maraviroc, raltegravir (and probably dolutegravir), rilpivirine, and tenofovir [44].…”