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DOUBLE THERAPY WITH PEGYLATED INTERFERON AND RIBAVIRIN FOR CHRONIC HEPATITIS C. A PHARMACOGENETIC GUIDE FOR PREDICTING ADVERSE EVENTS

ADINA MARIA KAMAL ^1#, PAUL MITRUȚ ^1#, ANCA OANA DOCEA ^2#, SIMONA ȘERBAN ȘOȘOI ^3#, CONSTANTIN KAMAL KAMAL ^4#*, RADU MITRUȚ ^5#, DRAGOȘ MĂRGĂRITESCU ^6#, DANIELA CĂLINA ^7#, CRISTIAN BANCIU ^8#, OANA SORINA TICA ^9#, ANDREI ADRIAN TICA ^9#, DRAGOȘ O. ALEXANDRU ^10#

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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.