High baseline bilirubin and low albumin predict liver decompensation and serious adverse events in HCV-infected patients treated with sofosbuvir-containing regimens

J Viral Hepat. 2016 Sep;23(9):667-76. doi: 10.1111/jvh.12530. Epub 2016 Mar 17.

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.

Keywords: hepatic decompensation; hepatitis C virus; mortality; serious adverse events; sofosbuvir.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antiviral Agents / therapeutic use*
  • Bilirubin / blood*
  • Case-Control Studies
  • Decision Support Techniques
  • Female
  • Hepatic Insufficiency / epidemiology*
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / pathology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prognosis
  • Serum Albumin / analysis*
  • Serum Albumin, Human
  • Simeprevir / therapeutic use
  • Sofosbuvir / therapeutic use*
  • Survival Analysis

Substances

  • ALB protein, human
  • Antiviral Agents
  • Serum Albumin
  • Simeprevir
  • Bilirubin
  • Sofosbuvir
  • Serum Albumin, Human