Protective role of ITPA rs1127354-CA polymorphism against anemia in HCV patients using sofosbuvir ribavirin therapy: age and gender match case-control study

Sameen Amjed, Hafiz Ghulam Murtaza Saleem, Sajjad Ullah, Shahzad Latif, Shabana Irfan, Junaid Jafar, Ahmed Bilal Waqar


Background: Hepatitis C virus is affecting around 80 million people. Sofosbuvir ribavirin-based therapy is associated with certain side effects, especially anemia. Inosine triphosphatase (ITPA) genetic polymorphisms cause functional impairment in ITPase enzyme, leading protection against anemia and improving sustained viral response. This study aims to explore the impact of ITPA variants on hemoglobin decline, ribavirin dose reduction, and sustained viral response (SVR) achievement.

Methods: This is prospective gender and age matched case-control study of HCV genotype-3a infected individuals taking sofosbuvir-ribavirin treatment. Patient CBC, viral RNA, liver function test, and ribavirin dose reduction were recorded monthly. ITPApolymorphisms-rs1127354 were determined and confirmed by restriction fragment length polymorphism and sanger sequencing. Effects of polymorphism on hemoglobin level, ribavirin dose and treatment outcome were analyzed.

Results: ITPA rs1127354-CC genotype patients experience significant reduction in level of Hb leading to ribavirin dose reduction. Low mean Hb levels were observed in these individuals at first and last month of treatment. No statistical difference was observed in adverse effects on basis of ITPA genotype except fever. Age, BMI, and ITPA genotype rs1127354-CC were independently associated (p< 0.05) with a decrease in Hb level ≥ 2g/dl below the baseline and ribavirin dose reduction. All patients with rs1127354 CA-genotype achieve SVR.

Conclusion: Pretreatment determination of ITPA polymorphism can further optimize HCV treatment with new direct-acting antivirals. ITPA rs1127354-CA has a protective role against ribavirin-associated anemia development and individualized management of ribavirin dose and along with the achievement of better SVR rates.

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