title: High baseline bilirubin and low albumin predict liver decompensation and serious adverse events in HCV-infected patients treated with sofosbuvir-containing regimens.
abstract: To conduct surveillance and determine the safety profile of new hepatitis C virus treatments in real-world clinical practice. Hepatic decompensation and other serious adverse events were investigated in an observational cohort study of 511 patients treated with regimens containing sofosbuvir, December 2013-June 2014. Among 499 previously stable patients (no history of hepatic decompensation during the previous 12 months), a nested case-control study was performed to identify predictors of decompensation/serious adverse event. Cases and controls were matched 1:5 based on treatment regimen and duration. Matched conditional logistic regression was used for analysis. Providers scored the likelihood that events were treatment-related (scale = 0-4). The cumulative incidence of decompensation/events was 6.4% for the total cohort. Among 499 previously stable patients, the incidence of decompensation/events was 4.5%; the mortality rate was 0.6%. Sixteen of the 499 experienced one or more serious complications considered to be at least potentially treatment-related, and the sustained virological response rate was 7/16 (44%). Two cases, both on sofosbuvir/simeprevir (without interferon or ribavirin), had complications consistent with autoimmune events (score 3, 'likely treatment-related'), and one experienced a flare of autoimmune hepatitis. Compared to controls, cases had higher baseline median model for end-stage liver disease scores (14 vs 8, P < 0.01). Decompensation/events was independently associated with lower baseline albumin (OR = 0.12/g/dL, P = 0.01) and higher total bilirubin (OR = 4.31/mg/dL, P = 0.01). Reduced hepatic function at baseline increased the risk of liver decompensation/events.
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Recanati Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: P V
authors.initials: PV
authors.lastname: Perumalswami
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: N
authors.initials: N
authors.lastname: Patel
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: K
authors.initials: K
authors.lastname: Bichoupan
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Ku
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Yalamanchili
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Harty
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Recanati Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: D
authors.initials: D
authors.lastname: Motamed
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Recanati Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: V
authors.initials: V
authors.lastname: Khaitova
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Recanati Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chang
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Recanati Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Grewal
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Recanati Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Recanati Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Schiano
authors.affiliation: Nuffield Department of Population Health, The George Institute for Global Health, University of Oxford, Oxford, UK.|The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Woodward
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Dieterich
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Branch
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood*; D016022:Case-Control Studies; D003661:Decision Support Techniques; D005260:Female; D048550:Hepatic Insufficiency / Q000453:epidemiology*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012709:Serum Albumin / Q000032:analysis*; D000075462:Serum Albumin, Human; D000069616:Simeprevir / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: C422455:ALB protein, human; D000998:Antiviral Agents; D012709:Serum Albumin; D000069616:Simeprevir; D001663:Bilirubin; D000069474:Sofosbuvir; D000075462:Serum Albumin, Human
keywords: hepatic decompensation; hepatitis C virus; mortality; serious adverse events; sofosbuvir