DOUBLE THERAPY WITH PEGYLATED INTERFERON AND
RIBAVIRIN FOR CHRONIC HEPATITIS C. A PHARMACOGENETIC
GUIDE FOR PREDICTING ADVERSE EVENTS
ADINA MARIA KAMAL1#, PAUL MITRUȚ1#, ANCA OANA DOCEA2#, SIMONA ȘERBAN ȘOȘOI3#, CONSTANTIN KAMAL KAMAL4#*, RADU MITRUȚ5#, DRAGOȘ MĂRGĂRITESCU6#, DANIELA CĂLINA7#, CRISTIAN BANCIU8#, OANA SORINA TICA9#, ANDREI ADRIAN TICA9#, DRAGOȘ O. ALEXANDRU10#
1Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Romania
2Department of Toxicology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Romania
3Department of Medical Genetics, University of Medicine and Pharmacy of Craiova, Romania
4Department of Family Medicine, University of Medicine and Pharmacy of Craiova, Romania
5University of Medicine and Pharmacy of Craiova, Romania
6Department of Surgery, University of Medicine and Pharmacy of Craiova, Romania
7Department of Clinical Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Romania
8Department of Internal Medicine, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timișoara,
Romania
9Department of Pharmacology, University of Medicine and Pharmacy of Craiova, Romania
10Department of Medical Informatics, University of Medicine and Pharmacy of Craiova, Romania
*corresponding author: kamalconstantin@gmail.com
#All authors had equal contribution to the current paper.
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Abstract:
Over 180 million people are infected with hepatitis C virus worldwide. Until 2016, the standard of care for patients with
chronic hepatitis C was double therapy with PegInterferon and Ribavirin over a course of 48 weeks. Unfortunately, the
treatment induces a wide variety of side effects. The aim of this study was to determine whether genetic variants can protect
against or predict any of the adverse events. We included 267 patients, diagnosed with chronic HCV infection. Two genotypes
were investigated: ITPA rs1127354 and C20orf194 rs6051702. Homozygous variants of the minor ITPA gene allele proved
to be protective for anaemia during therapy, whereas the “AA” allele of the c20orf194 gene is an important predictor for
anaemia (χ2 p < 0.01). The ITPA rs1127354 major C allele was found to be a positive predictor for a haemoglobin (Hb) drop
of over 2.5 g/dL at week 4 of treatment (χ2 p < 0.01). The minor AA allele of the c20orf194 gene proved to be an important
protective factor for developing leucopoenia (χ2 p = 0.03), neutropenia and thrombocytopenia (χ2 p < 0.01). We also
discovered that the c20orf194 rs6051702 gene variants correlated to some extent to achieving sustained virological response,
with 115 (43.07%) patients with SVR and AA allele compared to 30 (11.24%) with AC allele and 4 (1.5%) with CC allele
(χ2 p < 0.01). These findings demonstrate that pharmacogenetic tools could play a very important role in individually
designing every treatment.

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