ITPase activity modulates the severity of anaemia in HCV-related cirrhosis treated with ribavirin-containing interferon-free regimens.
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.
Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy.
Nicola
N
Coppola
Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy.
Stefania
S
De Pascalis
Infectious Diseases Unit, AO Caserta, Caserta, Italy.
Vincenzo
V
Messina
Infectious Diseases Unit, AO Caserta, Caserta, Italy.|HIV Unit, Second University of Naples, Naples, Italy.
Giovanni
G
Di Caprio
HIV Unit, Second University of Naples, Naples, Italy.
Salvatore
S
Martini
IX Interventional Ultrasound Unit for Infectious Diseases, AORN dei Colli, P.O. Cotugno, Naples, Italy.
Giorgio
G
de Stefano
Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy.
Mario
M
Starace
Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy.
Gianfranca
G
Stornaiuolo
Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy.
Maria
M
Stanzione
IX Interventional Ultrasound Unit for Infectious Diseases, AORN dei Colli, P.O. Cotugno, Naples, Italy.
Tiziana
T
Ascione
Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy.
Carmine
C
Minichini
Infectious Diseases Unit, AORN dei Colli, P.O. Cotugno, Naples, Italy.
Vincenzo
V
Sangiovanni
Internal Medicine Unit, Department of Medical Science, Second University of Naples, Naples, Italy.
Rosa
R
Zampino
Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy.
Federica
F
Calò
Internal Medicine Unit, Department of Medical Science, Second University of Naples, Naples, Italy.
Luca
L
Rinaldi
Internal Medicine Unit, University of Salerno, Salerno, Italy.
Marcello
M
Persico
Gastroenterology Unit, Second University of Naples, Naples, Italy.
Alessandro
A
Federico
Infectious Diseases Unit, University Federico II, Naples, Italy.
Antonio Riccardo
AR
Buonomo
Infectious Diseases Unit, University Federico II, Naples, Italy.
Guglielmo
G
Borgia
Infectious Diseases Unit, Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy.
Giovanni Battista
GB
Gaeta
Infectious Diseases Unit, AO Caserta, Caserta, Italy.
Pietro
P
Filippini
Infectious Diseases Unit, University Federico II, Naples, Italy.
Ivan
I
Gentile
D000368:Aged; D000483:Alleles; D000740:Anemia / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D004198:Disease Susceptibility; D004359:Drug Therapy, Combination; D004789:Enzyme Activation; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D012720:Severity of Illness Index; D000097630:Inosine Triphosphatase
D000998:Antiviral Agents; D011755:Pyrophosphatases; D012254:Ribavirin; D000097630:Inosine Triphosphatase