01 Set ITPase activity modulates the severity of anemia in patients with HCV-related cirrhosis treated with ribavirin-containing IFN-free regimens

Stefania De Pascalis

AIM: to investigate the association between the inosine triphosphatase (ITPA) activity and the degree of anemia occurring during DAA/RBV-based therapy in patients with cirrhosis.
METHODS: In a multicentric, prospective study 227 patients with HCV-related cirrhosis treated with DAA and RBV were enrolled. All patients were screened for both the rs1127354 and rs7270101 ITPA single nucleotide polymorphisms using a direct sequencing.
RESULT. One-hundred fifty (66.1%) patients had a normal (100%) ITPase activity, 48 (21.1%) had moderate (60%) activity and 29 (12.8%) minimal (<30%) activity. The ITPase activity significantly influenced the reduction of hemoglobin concentration: at day 15 the hemoglobin concentration was -1.248 (SD: +0.978) in the 150 patients with a ITPase activity of 100% and -0.616 (+0.862) in the 77 patients with a ITPase activity less than 100% (p<0.000), such as at day 30 (-1.941+1.218 vs. -1.11+1.218; p<0.000).
The 63 patients with a severe (at least 2.5g/dl) decline of hemoglobin patients compared to those without had more frequently an ITPase activity of 100% (34.2% vs. 15.8%, p=0.004), were older (mean age+SD: 66.7+8.2 vs. 61.4+9.7 years, p=0.004) and were treated with a higher ribavirin dose (13.7+2.1 vs.12.8+2.5 mg/kg/die, p=0.008). At multivariate logistic regression analysis the ITPase activity of 100% (OR: 3.17; 95% CI: 1.50-6.69), age (OR: 1.027; IC 95%: 1.006-1.107) and dose of ribavirin (OR: 1.22; IC 95%: 1.06-1.40) were independent predictors of severe decline of hemoglobin (p<0.0001).
CONCLUSION. This study suggests that the polymorphisms in the ITPA gene influences the severity of anemia during the first month of a DAA-based treatment in HCV-related cirrhosis.