Limited utility of ITPA deficiency to predict early anemia in HCV patients with advanced fibrosis receiving Telaprevir.
BACKGROUND
Severe anemia is a common side effect of Pegylated Interferon + Ribavirin (PR) and Telaprevir (TVR) in hepatitis C virus (HCV) genotype 1 patients with advanced fibrosis or cirrhosis (F3-F4). Inosine triphosphatase (ITPA) genetic variants are associated with RBV- induced anemia and dose reduction.


OBJECTIVE
To test the association of ITPA polymorphisms rs1127354 and rs7270101 with hemoglobin (Hb) decline, need for RBV dose reduction (RBV DR), erythropoietin (EPO) support and blood transfusions during the first 12 weeks of TVR triple therapy.


METHODS
69 consecutive HCV-1 patients (mean age 57 years) with F3-F4 who received PR and TVR were genotyped for ITPA polymorphisms rs1127354 and rs7270101. Estimated ITPA deficiency was graded on severity (0-3, no deficiency/mild/moderate/severe).


RESULTS
ITPA deficiency was absent in 48 patients (70%), mild in 12 (17%) and moderate in 9 patients (13%). Mean week 4 Hb decline was higher in non ITPA deficient patients (3,85 g/dL) than in mildly or moderately ITPA deficient patients (3,07 g/dL and 1,67 g/dL, p<0.0001). Grade 3-4 anemia developed in 81% non ITPA deficient patients versus 67% mild deficient and 55% moderate deficient patients (p = ns). Grade of ITPA deficiency was not associated with RbvDR (no deficiency: 60%, mild: 58%, moderate: 67%; p = ns), EPO use (no deficiency: 65%, mild: 58%, moderate:56%; p = ns) or need for blood transfusion (no deficiency: 27%, mild: 17%, moderate: 33%; p = ns).


CONCLUSIONS
In patients with F3-F4 chronic hepatitis C receiving TVR based therapy, ITPA genotype does not impact on the management of early anemia.
A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Alessio
A
Aghemo
A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Eleonora
E
Grassi
Hepatology Unit, Ospedale San Giuseppe, IRCCS Multimedica, Università degli Studi di Milano, Milan, Italy.
Maria Grazia
MG
Rumi
A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Roberta
R
D'Ambrosio
A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Enrico
E
Galmozzi
A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Elisabetta
E
Degasperi
Department of Informatics, Systemistic and Comunication (DISCo), Universita' degli Studi di Milano - Bicocca, Milan, Italy.
Davide
D
Castaldi
A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Roberta
R
Soffredini
A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Massimo
M
Colombo
D000328:Adult; D000368:Aged; D000740:Anemia / Q000175:diagnosis* / Q000209:etiology; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D042241:Early Diagnosis; D005260:Female; D005355:Fibrosis; D014644:Genetic Variation; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage; D000097630:Inosine Triphosphatase
D000998:Antiviral Agents; D009842:Oligopeptides; D011755:Pyrophosphatases; D012254:Ribavirin; C486464:telaprevir; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase