Diagnosis and treatment of hepatitis C

Abstract

Virusološka dijagnostika HCV infekcije temelji se na primjeni standardiziranih seroloških i molekularnih testova. U molekularnoj dijagnostici HCV infekcije koriste se vrlo osjetljivi testovi za kvantifikaciju HCV RNK i genotipizaciju HCV-a. Genotip HCV-a važan je čimbenik pred-terapijske obrade bolesnika koji određuje trajanje liječenja, dozu ribavirina a omogućuje i procjenu vjerojatnosti uspjeha liječenja. Međutim, detekcija i/ili kvantifikacija HCV RNK u serumu preporučuje se za dokazivanje aktivne virusne replikacije u sklopu pred-terapijske obrade bolesnika kao i za praćenje virusološkog odgovora tijekom liječenja. Rezultati praćenja distribucije genotipova HCV-a u Referentnom centru za virusni hepatitis Ministarstva zdravstva R. Hrvatske pokazuju da je oko 60 % bolesnika s kroničnim hepatitisom C zaraženo genotipom 1 HCV-a, 36 % genotipom 3a, a svega 4 % bolesnika genotipovima 2 i 4. Zlatni standard liječenja kroničnog hepatitisa C (KHC) posljednjih sedam godina je kombinacija pegiliranog interferona alfa (PEG IFN) i ribavirina. Međutim, standardna terapija ne dovodi do izliječenja u 50 % bolesnika s genotipom 1, te oko 30 % bolesnika s genotipom 3a. Stoga se suvremeno liječenje bolesnika s kroničnim hepatitisom C temelji se na individualnom pristupu koji uključuje prilagodbu algoritma liječenja genotipu virusa, viremiji, stadiju fibroze te praćenju virusne kinetike. Modifikacija algoritma liječenja u bolesnika s genotipom 1 i sporim virusološkim odgovorom uključuje produljenje liječenja na 72 tjedna dok se liječenje bolesnika zaraženih genotipom 3a koji imaju nisku viremiju, a postignu brzi virusološki odgovor, liječenje može skratiti na 16 tjedana. Bolesnike s visokim stadijem fibroze (obilna vezivna septa) nije uputno liječiti prema visini viremije, jer u toj skupini bolesnika niska viremija ne predstavlja prediktor trajnog virusološkog odgovora. Bolesnike s akutnim hepatitisom C treba liječiti monoterapijom pegiliranim interferonom alfa u trajanju od 24 tjedna.Virological diagnostics of HCV infection is based on standardized serological and molecular assays. Molecular diagnostics of HCV infection includes assays for HCV RNK detection and/or quantification as well as genotyping assays. HCV genotype is an important parameter in the pre-treatment diagnostic workup that determines treatment duration, ribavirin dosage and represents an excellent predictor of treatment success. Detection and/or quantification of HCV RNK in the serum provides direct evidence of active viral replication in patients with chronic hepatitis C and enables determination of virological response during treatment. According to the Croatian Reference Center for Viral Hepatitis, 60 % of patients with chronic hepatitis C in Croatia are infected with genotype 1, 36 % of patients with genotype 3a and only 4 % of patients with genotypes 2 and 4. Standard treatment regimen for chronic hepatitis C over the past seven years is a combination of pegylated interferon alpha (PEG IFN) and ribavirin (guanosine analogue). However, standard treatment regimen based on the combination of PEG IFN and ribavirin for 48 weeks fails to achieve sustained viral response in 50 % of patients with genotype 1. Furthermore, 25 % of patients infected with genotype 3a will fail to respond to a standard 24 week regiment. Up-to date treatment of chronic hepatitis C should be individualized (treatment guided) according to the genotype, liver fibrosis, early viral kinetics and viremia. Modification of treatment algorithm in patients with genotype 1 who are late responders to treatment should include prolonged treatment (72 weeks). In patients infected with genotypes 2 and 3 and low viremia who are rapid responders, therapy can be shortened to 16 weeks. Patients with higher fibrosis rates (fibrotic septa) should not be treated according to viremia because in those patients viremia does not correlate with the ability to achieve sustained viral response. Meta-analysis of recent clinical trials on the treatment of acute hepatitis C showed that monotherapy with PEG IFN for 24 weeks is the suggested treatment regimen for this group of patients