Antiviral therapy · 2017
ITPase activity modulates the severity of anaemia in HCV-related cirrhosis treated with ribavirin-containing interferon-free regimens.
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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
Аннотация
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.
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.
Предметные рубрики MeSH
AgedAllelesAnemiaAntiviral AgentsDisease SusceptibilityDrug Therapy, CombinationEnzyme ActivationFemaleGene FrequencyGenotypeHepatitis C, ChronicHumansLiver CirrhosisMaleMiddle AgedOdds RatioPolymorphism, Single NucleotidePyrophosphatasesRibavirinRisk FactorsSeverity of Illness IndexInosine Triphosphatase