Efficacy and safety of peginterferon alfa-2a and ribavirin treatment of chronic hepatitis C in the Republic of Serbia

Abstract

Introduction. Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. Pegylated interferon alfa-2a or 2b (PEG IFN alfa-2a or 2b) and ribavirin (RBV) represent a standard treatment of chronic hepatitis C (CHC). Sustained virological response (SVR), defined as continued undetectable HCV RNA 24 weeks after completion of treatment, is universally considered as an indicator of treatment efficacy. Objective. The aim of this study was to determine efficacy and safety of PEG IFN alfa-2a and RBV treatment in patients with CHC in Serbia. Methods. One hundred seventy-six patients with CHC were included in this multicenter trial from 8 reference centers in Serbia. The patients were treated with standard PEG IFN alfa- 2a and RBV protocol. We performed the following virological testing: anti-HCV (ELISA), HCV RNK (quantitative PCR), HCV genotype (type-specific PCR), HBsAg, anti-HBs, anti-HBc and anti-HIV (ELISA). Histological activity and the degree of fibrosis were determined according to the Metavir scoring system. Potential predictors for achieving SVR were evaluated using multivariable logistic regression analysis. Results. Of the treated patients with CHC 65.9% were male, and 60.2% of them aged over 40 years. Of the treated patients 68.2% had infection over 5 years, 63% had HCV RNA >400.000 IU/mL, 76.1% had HCV G1/4, and 60.1% had a mild to moderate liver fibrosis. SVR was achieved in 78.9% of patients (G1/4 79.1%; G2/3 78.1%). The factors that indicated a poorer efficacy of the treatment were age >40 (p<0.05), high basal viremia (p=0.013), and the reduction of PEG IFN alfa-2a and RBV doses, with interruption of therapy (p<0.001). Of the treated patients 45.9% had adverse affects (G1/4 50.8%; G2/3 29.7%). Conclusion. Treatment of CHC with PEG IFN alfa-2a and RBV was efficient in 78.9% of patients. The safety profile of therapy was satisfactory. Longer therapy increases the possibility of the development of adverse affects. No life-threatening adverse effects were recorded in our patients.Uvod. Infekcija virusom hepatitisa C (HCV) jedan je od glavnih uzroka hronicnih bolesti jetre ljudi u celom svetu. Standardna terapija hronicnog hepatitisa C (HHC) su pegilovani interferon alfa- 2a ili 2b (PEG-IFN ?-2a ili 2b) i ribavirin (RBV). Opste je prihvaceno da se delotvornost terapije meri postizanjem stabilnog virusoloskog odgovora, koji podrazumeva da se HCV RNK, primenom testa PCR, ne belezi 24 nedelje po zavrsetku terapije. Cilj rada. Cilj ispitivanja bio je da se procene efikasnost i sigurnost primene PEG-IFN ?-2a i RBV u lecenju bolesnika sa HHC u Republici Srbiji. Metode rada. U ispitivanje je ukljuceno 176 bolesnika sa HHC iz osam referentnih centara Srbije. PEG-IFN ?-2a i RBV su primenjeni prema standardnom protokolu. Od virusoloskih ispitivanja uradjena su: antitela na HCV (test ELISA), HCV RNK (kvantitativni PCR test), genotip HCV (specificna PCR tehnika), markeri HBV i HIV infekcije (ELISA). Histoloski stepen aktivnosti i napredovanja bolesti jetre odredjen je prema sistemu METAVIR. Rezultati. Medju ispitanicima sa HHC bilo je vise bolesnika: muskog pola (65,9%), starijih od 40 godina (60,2%), sa infekcijom koja je trajala duze od pet godina (68,2%), sa HCV RNK vecim od 400.000 IU/ml (63%), u grupi sa genotipom G1/4 (76,1%) i sa fibrozom F0-2 (60,1%). Stabilan virusoloski odgovor je postignut kod 79,1% ispitanika sa G1/4 i 78,1% ispitanika sa G2/3. Faktori koji su ukazivali na slabiji uspeh terapije bili su: starost preko 40 godina (p<0,05), visoka bazalna viremija (p=0,013) i smanjenje doza PEG-IFN ?-2a i RBV, s prekidima u kontinuitetu terapije (p<0,001). Nezeljeni efekti su zapazeni kod ukupno 45,9% bolesnika (G1/4 50,8%; G2/3 29,7%). Zakljucak. Terapija HHC primenom PEG-IFN ?-2a i RBV bila je delotvorna kod 78,9% bolesnika. Sigurnosni profil terapije je bio dobar. Mogucnost da se nezeljeni efekti pojave povecava se s produzenjem lecenja. Nisu zabelezena nezeljena dejstva opasna po zivot.