Hepatic decompensation/serious adverse events in post-liver transplantation recipients on sofosbuvir for recurrent hepatitis C virus

World J Gastroenterol. 2016 Mar 7;22(9):2844-54. doi: 10.3748/wjg.v22.i9.2844.

Abstract

Aim: To determine the safety profile of new hepatitis C virus (HCV) treatments in liver transplant (LT) recipients with recurrent HCV infection.

Methods: Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events (SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIV-infected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite outcome.

Results: Median age of the 42 patients was 60 years [Interquartile Range (IQR): 56-65 years], 33% (14/42) were female, 21% (9/42) were Hispanic, and 9% (4/42) were Black. The median time from transplant to treatment initiation was 5.4 years (IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62% (8/13) patients, while 54% (7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31% (95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin (OR = 0.61 per g/dL, 95%CI: 0.40-0.88, P < 0.01), estimated glomerular filtration rate (OR = 0.95 per mL/min per 1.73 m(2), 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin (OR = 2.43 per mg/dL, 95%CI: 1.17-8.65, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for cases.

Conclusion: Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.

Keywords: Anemia; Hepatic decompensation; Hepatitis C virus; Liver transplant; Ribavirin; Serious adverse event; Sofosbuvir.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Anemia / chemically induced
  • Antiviral Agents / adverse effects*
  • Drug Therapy, Combination
  • End Stage Liver Disease / diagnosis
  • End Stage Liver Disease / surgery*
  • End Stage Liver Disease / virology
  • Female
  • Hepacivirus / drug effects*
  • Hepacivirus / pathogenicity
  • Hepatitis C / diagnosis
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology
  • Humans
  • Kaplan-Meier Estimate
  • Liver Failure / chemically induced*
  • Liver Failure / diagnosis
  • Liver Transplantation / adverse effects*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Recurrence
  • Ribavirin / adverse effects
  • Risk Factors
  • Sofosbuvir / adverse effects*
  • Time Factors
  • Treatment Outcome
  • Virus Activation / drug effects

Substances

  • Antiviral Agents
  • Ribavirin
  • Sofosbuvir