Association between inosine triphosphatase rs1127354 polymorphisms and ribavirin-induced anaemia and outcome in hepatitis C virus-infected patients: A meta-analysis

J Clin Pharm Ther. 2020 Dec;45(6):1218-1227. doi: 10.1111/jcpt.13232. Epub 2020 Jul 31.

Abstract

What is known and objectives: The association between inosine triphosphatase (ITPA) rs1127354 polymorphisms in HCV-infected patients receiving ribavirin (RBV)-based therapy, and the risk of adverse drug reaction and outcomes is still unclear. A meta-analysis was conducted to summarize and clarify this association systematically.

Methods: A comprehensive search was performed in PubMed, Embase and Web of Sciences, and twenty-two studies were selected from the literature search. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were estimated by either fixed- or random-effects models.

Results: Four outcomes were evaluated: (a) haemoglobin decline: significant associations with haemoglobin decline were found for rs1127354 CC VS CA + AA (OR = 10.59, 95% CI = 6.39-17.54); (b) severe anaemia: significant association with severe anaemia was observed for rs1127354 CC VS CA + AA (OR = 16.24, 95% CI = 6.21-42.43); (c) sustained virological response (SVR): CC genotype carriers had a decrease SVR during treatment (OR = 0.65, 95% CI = 0.52-0.81); (d) RBV dose reduction or stopping treatment: although statistical evidence of an association was found between the polymorphism and RBV dose reduction during treatment (OR = 1.80, 95% CI = 1.03-3.13), the sensitivity analysis suggested this result was not robust.

What is new and conclusion: Patients with ITPA rs1127354 CC polymorphism are more likely to develop haemolytic anaemia, severe anaemia and decreased SVR. Testing for this genetic polymorphism may benefit patients.

Keywords: HCV therapy; ITPA; chronic hepatitis C; ribavirin; rs1127354; severe anaemia; sustained virological response.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Anemia / chemically induced*
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C / drug therapy
  • Hepatitis C / virology
  • Humans
  • Inosine Triphosphatase
  • Polymorphism, Single Nucleotide
  • Pyrophosphatases / genetics*
  • Ribavirin / administration & dosage*
  • Ribavirin / adverse effects
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Ribavirin
  • Pyrophosphatases