Chronic hepatitis C – a journey to curable disease

Virus hepatitisa C otkriven je krajem 1980-tih godina. Prvi pokušaji liječenja bili su interferonom (IFN)-α čija je upotreba, unatoč zadovoljavajućoj stopi bolesnika s održivim virusološkim odgovorom (engl. sustained virologic response, SVR), bila ograničena brojnim nuspojavama. Terapijski su rezultati poboljšani promjenom doziranja IFN-α, te pegiliranjem. Sredinom 1990-tih godina IFN-α dodan je ribavirin, čime su postignuti još bolji rezultati u liječenju bolesnika s hepatitisom C, te je ta kombinacija od 1999. predstavljala standard u liječenju. Značajan napredak postignut je upoznavanjem životnog ciklusa virusa, što je omogućilo razvoj izravnodjelujućih lijekova, od kojih su prvi pokazivali obećavajuće rezultate, premda uz brojne nuspojave. Sljedećih se godina razvijaju brojni izravnodjelujući lijekovi, te ih danas dijelimo na četiri skupine: inhibitore virusne proteaze, nukleotidne analoge, ne-nuklozidne analoge i inhibitore NS5A. Od 2014. godine počela je era bez PegIFN-α, te je sada moguće postići SVR nakon 12 ili 24 tjedana sa samo oralnim liječenjem. Prema nekim procjenama za smanjenje prevalencije HCV-a za 90% u Hrvatskoj potrebno je godišnje liječiti 450-500 bolesnika, te svakako intenzivirati javnozdravstvene kampanje s ciljem ranog otkrivanja zaraženih bolesnika. Još uvijek glavni problem predstavljaju financijska sredstva.Hepatitis C virus was discovered at the end of the 1980s. The first treatment attempts were with interferon (IFN)-α whose use, although satisfying in terms of rates of patients with sustained virologic response rate (SVR), was limited by numerous side effects. These rates were further improved by adjusting the dose and pegylation. In the mid-1990s, ribavirin was added to IFN-α, achieving even better results in the treatment of patients with hepatitis C, and the combination represented the standard of treatment since 1999. Significant progress has been made after the virus life cycle was unraveled, enabling the development of direct-acting antivirals (DAA), the first of which had promising results, albeit with numerous side effects. More than few DAA developed in the following years, and today they are divided into four groups: viral protease inhibitors, nucleotide analogues, non-nucleoside analogues and NS5A inhibitors. Since 2014, the PEGIFN-free era is finally beginning, with SVR possible with all-oral therapy after 12 or 24 weeks. According to some research, to achieve 90% reduction in HCV prevalence in Croatia, we should treat 450 to 500 patients per year, and of course intensify public health campaigns with the aim of early detection of infected patients. The main problem still remain financial resources