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

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.

Inosine triphosphate pyrophosphatase: A guardian of the cellular nucleotide pool and potential mediator of RNA function

“…In addition, these polymorphisms were linked to a sustained virological response in HCV patients (Rembeck et al, 2014). Metanalyses further support these associations (Ma et al, 2020; Pineda‐Tenor et al, 2015).…”

Impact of ITPA gene polymorphism for predicting anemia and treatment outcome in HCV infected patients taking Sofosbuvir Ribavirin therapy

“…Literature learned from a few studies discussed the effect of rs7170101 polymorphism. They also found statistical evidence of an association between ribavirin dose reduction and ITPA polymorphism [ 4 ]. A real-life study was conducted on HCV genotype 2 patients, and it was observed that regardless of previous antiviral treatment history sofosbuvir-based treatment schedules were associated with good tolerability and SVR achievement rates, without a significant impact, on treatment ribavirin dose reductions [ 37 ].…”

“…Ribavirin-induced hemolytic anemia is the cause of ribavirin dose reduction and therapy discontinuation in 10–20% of patients which is also reported to impact antiviral therapy outcomes. The continuous advancement in the discovery of antiviral agents targeting various stages of HCV life cycle is leading towards effective interferon free direct acting antiviral (DAA) therapy [ 4 – 6 ]. The arrival of DAA along with ribavirin against HCV infection resulted over 90–95% SVR rates along with lesser side effects [ 4 , 7 ].…”

“…The continuous advancement in the discovery of antiviral agents targeting various stages of HCV life cycle is leading towards effective interferon free direct acting antiviral (DAA) therapy [ 4 – 6 ]. The arrival of DAA along with ribavirin against HCV infection resulted over 90–95% SVR rates along with lesser side effects [ 4 , 7 ].…”