title: Safety and Efficacy of Simeprevir/Sofosbuvir in Hepatitis C-Infected Patients With Compensated and Decompensated Cirrhosis.
abstract: Risks and benefits of simeprevir plus sofosbuvir (SIM+SOF) in patients with advanced cirrhosis are unknown. We assessed the safety and sustained virological responses (SVR) of SIM+SOF with and without ribavirin (RBV) in patients with Child-Pugh (CP)-B/C versus CP-A cirrhosis and compared to matched untreated controls. This study was of a multicenter cohort of adults with hepatitis C virus genotype 1 and cirrhosis treated with SIM+SOF with/without RBV for 12 weeks. Controls were matched on treatment center, age, CP class, and Model for End-Stage Liver Disease (MELD) score. Of 160 patients treated with SIM+SOF with/without RBV, 35% had CP-B/C and 64% had CP-A, with median baseline MELD 9 (interquartile range, 8-11). Sustained virological response at week 12 (SVR12) was achieved by 73% of CP-B/C versus 91% of CP-A (P < 0.01). CP-B/C versus CP-A had more early treatment discontinuations (11% vs. 1%), adverse events (AEs) requiring hospitalization (22% vs. 2%), infections requiring antibiotics (20% vs. 1%), and hepatic decompensating events (20% vs. 3%; all P < 0.01). There were 2 deaths: 1 CP-B/C (liver related) and 1 CP-A (not liver related). In multivariate analysis, CP-B/C independently predicted lack of SVR12 (odds ratio, 0.27; 95% confidence interval: 0.08-0.92). In comparing SIM+SOF-treated patients versus matched untreated controls, AEs requiring hospitalization (9% vs. 13%; P = 0.55), infections (8% vs. 6%; P = 0.47), and events of decompensation (9% vs. 10%; P = 0.78) occurred at similar frequency.
  
  
  CONCLUSIONS
  SIM+SOF with/without RBV has lower efficacy and higher rates of AEs in patients with CP-B/C cirrhosis, compared to CP-A. Frequency of adverse safety outcomes were similar to matched untreated controls, suggesting that safety events reflect the natural history of cirrhosis and are not related to treatment.
authors.affiliation: University of California San Francisco, San Francisco, CA.
authors.forename: Varun
authors.initials: V
authors.lastname: Saxena
authors.affiliation: Kaiser Permanente Southern California, San Diego, CA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nyberg
authors.affiliation: Kaiser Permanente Northern California, Oakland, CA.
authors.forename: Marypat
authors.initials: M
authors.lastname: Pauly
authors.affiliation: University of California San Francisco, San Francisco, CA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Dasgupta
authors.affiliation: Kaiser Permanente Southern California, San Diego, CA.
authors.forename: Anders
authors.initials: A
authors.lastname: Nyberg
authors.affiliation: Kaiser Permanente Colorado, Denver, CO.
authors.forename: Barbara
authors.initials: B
authors.lastname: Piasecki
authors.affiliation: Kaiser Permanente Mid-Atlantic, Rockville, MD.
authors.forename: Bradley
authors.initials: B
authors.lastname: Winston
authors.affiliation: Kaiser Permanente Mid-Atlantic, Rockville, MD.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Redd
authors.affiliation: Kaiser Permanente Northern California, Oakland, CA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ready
authors.affiliation: University of California San Francisco, San Francisco, CA.
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000008:administration & dosage; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D061214:Patient Safety; D012016:Reference Values; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D012720:Severity of Illness Index; D000069616:Simeprevir / Q000008:administration & dosage* / Q000009:adverse effects; D000069474:Sofosbuvir / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D000069616:Simeprevir; D000069474:Sofosbuvir