ITPase Activity Modulates the Severity of Anaemia in HCV-Related Cirrhosis Treated with Ribavirin-Containing Interferon-Free Regimens. Issue 7 (October 2017)

• Record Type: Journal Article
• Authors: Coppola, Nicola; De Pascalis, Stefania; Messina, Vincenzo; Di Caprio, Giovanni; Martini, Salvatore; De Stefano, Giorgio; Starace, Mario; Stornaiuolo, Gianfranca; Stanzione, Maria; Ascione, Tiziana; Minichini, Carmine; Sangiovanni, Vincenzo; Zampino, Rosa; Calò, Federica; Rinaldi, Luca; Persico, Marcello; Federico, Alessandro; Buonomo, Antonio Riccardo; Borgia, Guglielmo; Gaeta, Giovanni Battista; Filippini, Pietro; Gentile, Ivan
• Is Part Of: Antiviral therapy. Volume 22:Issue 7(2017)
• Page Start: 551
• Page End: 558
• Publication Date: 2017-10
• Subjects: Antiviral agents -- Periodicals; Antiviral Agents -- therapeutic use; Virus Diseases -- therapy; Viruses -- drug effects; Antiviral agents; Periodical; Electronic journals; Periodicals; 616.9106
• DOI: 10.3851/IMP3134
• Languages: English
• ISSNs: 1359-6535

Abstract

Background: To investigate the association between inosine triphosphatase (ITPase) activity and the degree of anaemia occurring during direct-acting antiviral (DAA)/ribavirin (RBV)-based therapy in patients with cirrhosis. Methods: In a multicentre, prospective study 227 patients with HCV-related cirrhosis treated with DAA and RBV were enrolled. All patients were screened for the rs1127354 and rs7270101 ITPA single nucleotide polymorphisms using direct sequencing. Results: 150 (66.1%) patients had normal (100%) ITPase activity, 48 (21.1%) had moderate (60%) activity and 29 (12.8%) minimal (≤30%) activity. The ITPase activity significantly influenced the haemoglobin concentration: at day 15 it was -1.248 (sd ±0.978) in the 150 patients with an ITPase activity of 100% and -0.616 (±0.862) in the 77 patients with an ITPase activity less than 100% ( P <0.000), and at day 30 it was -1.941 ±1.218 versus -1.11 ±1.218 ( P <0.000). The 63 patients with a severe (at least 3/dl) haemoglobin decline, compared to those without, more frequently had an ITPase activity of 100% (82.1% versus 62.8%; P =0.021), were older (mean age ±sd : 66.7 ±8.2 versus 61.4 ±9.7 years; P =0.004) and were treated with a higher ribavirin dose (13.7 ±2.1 versus 12.8 ±2.5 mg/ kg/day; P =0.008). At multivariate logistic regression analysis, the ITPase activity of 100% (OR: 2.83; 95% CI: 1.12, 7.10), male gender (OR: 3.22; 95% CI: 1.35, 7.66), body mass index (OR: 1.17; 95% CI: 1.03, 1.34) and dose of ribavirin (OR: 1.22; 95% CI: 1.06, 1.47) were independent predictors of a severe decline in haemoglobin ( P <0.0001). Conclusions: This study suggests that the polymorphisms in the ITPA gene influence the severity of anaemia during the first month of a DAA/RBV-based treatment in HCV-related cirrhosis.