ITPase activity modulates the severity of anaemia in HCV-related cirrhosis treated with ribavirin-containing interferon-free regimens.

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.

• Authors: Nicola Coppola, Stefania De Pascalis, Vincenzo Messina, Giovanni Di Caprio, Salvatore Martini, Giorgio de Stefano, Mario Starace, Gianfranca Stornaiuolo, Maria Stanzione, Tiziana Ascione, Carmine Minichini, Vincenzo Sangiovanni, Rosa Zampino, Federica Calò, Luca Rinaldi, Marcello Persico, Alessandro Federico, Antonio Riccardo Buonomo, Guglielmo Borgia, Giovanni Battista Gaeta, Pietro Filippini, Ivan Gentile
• Journal: Antiviral therapy (Antivir Ther) Vol. 22 Issue 7 Pg. 551-558 ( 2017) ISSN: 2040-2058 [Electronic] England
• PMID: 28165327 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• Ribavirin
• Pyrophosphatases

Topics

• Aged
• Alleles
• Anemia (diagnosis, etiology, metabolism)
• Antiviral Agents (adverse effects, therapeutic use)
• Disease Susceptibility
• Drug Therapy, Combination
• Enzyme Activation
• Female
• Gene Frequency
• Genotype
• Hepatitis C, Chronic (complications, drug therapy)
• Humans
• Liver Cirrhosis (complications, etiology)
• Male
• Middle Aged
• Odds Ratio
• Polymorphism, Single Nucleotide
• Pyrophosphatases (genetics, metabolism)
• Ribavirin (adverse effects, therapeutic use)
• Risk Factors
• Severity of Illness Index
• Inosine Triphosphatase