#4237 EFFICACY AND TOLERABILITY OF DIRECT-ACTING ANTIVIRALS IN HEMODIALYSIS PATIENTS WITH CHRONIC HEPATITIS C
Authors: Tomanoski Vasilije , Gjorgjievska Gordana , Krecova Vasiliki , Nakovska Margarita , Andonoski Aleksandar , Zvezdakovska Jasminka , Kachakova Angela , -Atanasovska Sintia Kepeska , Micajkova Marija , Veliu Ramazan , Ferati Bejane , Tomanoska Ana , Zabzun Zana , Borisova Irena , Kjamili Gojard , Kjamili Merima , Izairi Shpresa , Jagupi Shpresim , Veseli Leonora , Trifunovska Nada , Matevska Adriana , Ristevska Tatjana , Lozanoski Davor , Dimova Katerina , Stojanova Elena 
Published: June 2023

Abstract

Background and Aims
Hepatitis C virus (HCV) infection is common in hemodialysis (HD) patients and is associated with increased morbidity and mortality. In recent years major progress in the treatment of HCV infection has been made with the entry into use of direct-acting antivirals (DAA), which target viral proteins, leading to increases in sustained virological response (SVR) and a marked decrease in side effects. The aim of the study was to evaluate the efficacy and frequency of side-effects of DAA therapy in HD patients with HCV infection.

Method
The multicentric prospective cohort study included 42 HD patients with HCV infection over the last two years. DAAs therapy was administered according to HCV genotype and drug interactions considering guidelines for a period of 12 weeks (for HCV genotype 1: Elbasvir/Grazoprevir or Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir, and for HCV genotype 4: Elbasvir/Grazoprevir or Ombitasvir/Paritaprevir/Ritonavir). The following clinical parameters at weeks 0, 4, 8, 12, and 24 (12 weeks after the completion of treatment with DAA) were analyzed: presence of side effects, PCR HCV titer (ref. range: &lt;12 IU/ml negative), hemoglobin (Hgb-g/L), epoetin dose (IU/kg/week), alanine aminotransferase level (ALT-U/L), and gamma-glutamyl transferase level (GGT-U/L). Before treatment with DAA liver fibrosis score (F0-F4) was defined by Fibroscan and the patients with liver stiffness over 12,5 kPa (Fibrosis score F4) were considered cirrhotic, but only patients with compensated cirrhosis (Child-Pugh score class A) were treated. For statistical analysis chi-square test and combined analysis of variance for repeated measures were performed by IBM SPSS softver. PCR HCV titer was analyzed with logarithmic transformation of data.

Results
Over the observed period 42 HD patients with HCV infection (25M and 17F) with the average age 56,78±11,6 years and average HD vintage 159±75 months were included in the study. Twenty-six patients (61,9%) were with HCV genotype 1 and 16 patients (38,1%) with HCV genotype 4. Ten patients (23,8%) were with compensated cirrhosis (F4 fibrosis score by Fibroscan). Three patients (7,1%) had mild gastrointestinal side effects and only one patient (2,4%) discontinuated the therapy during the first week due to intolerancy to DAA. All 41 patients (100%) who completed 12 weeks DAA therapy were PCR HCV negative at 4 weeks of treatment and achieved rapid virological response (RVR) and 12 weeks after the completion of treatment and achieved sustained virological response (SVR12) that was statistically significant (p&lt;0.001). In regard to PCR HCV titer before DAA therapy there was no statistically significant difference among HD patients according to cirrhotic status and HCV genotype. There was no statistically significant change of hemoglobin level and epoetin dose in HD patients during the DAA therapy. The ALT and GGT levels statistically significantly decreased at weeks 12 and 24 compared to week 0 in all treated patients with DAA (ALTweek0 = 35,2±21,7; ALTweek12 = 21,8±16,2; ALTweek24 = 23,5±13,1; p&lt;0.001 and GGTweek0 = 53,3±67; GGTweek12 = 18,6±6,8; GGTweek24 = 19,4±11,5; p = 0.042 respectively). The therapy with DAA was equally effective in patients with compensated cirrhosis and in patients without cirrhosis and there was statistically significant decrease of ALT and GGT levels in both groups of patients (p = 0.002 and p&lt;0.05 respectively). In regard to HCV genotype DAA were equally effective in patients with HCV genotype 1 and in patients with HCV genotype 4 and ALT and GGT levels significantly decreased in both groups of patients (p&lt;0.001 and p&lt;0.05 respectively).

Conclusion
The therapy with DAA in HD patients with HCV infection was extremely effective and SVR12 was achieved in 100% of treated patients. The administered DAA were equally effective in patients with compensated cirrhosis and in patients without cirrhosis, and in patients with HCV genotype 1 and HCV genotype 4. The therapy with DAA was well tolerated, 7,1% of patients had mild side effects and 2,4% of patients discontinuated the therapy due to intolerance.