Mikro-eliminacija hepatitisa C v skupinah z visokim tveganjem za okužbo z virusom hepatitisa C

Černoša Perdih, Jasna (avtor), Matičič, Mojca (mentor), V. Lazarus, Jeffrey (komentor)

Uvod: Kronična okužba z virusom hepatitisa C (HCV) predstavlja pomemben javnozdravstveni problem. S pričetkom uporabe novih, varnih in na virus neposredno delujočih protivirusnih zdravil (angl. direct-acting antivirals, okr. DAA) je hepatitis C postal prva kronična virusna bolezen, ki je ozdravljiva. Zato je Svetovna zdravstvena organizacija (SZO) leta 2016 sprejela strategijo eliminacije hepatitisa C kot javnozdravstveno grožnjo do leta 2030. Za lažjo dosego tega cilja pa se je pričel uporabljati bolj praktičen, hitrejši in stroškovno ugodnejši medicinski pristop, t. i. mikro-eliminacija, kjer se v skupinah z velikim tveganjem za okužbo s HCV, z namenom njene eliminacije, sistematično uvaja ter izboljšuje preventivne, diagnostične in terapevtske ukrepe. Namen: Ocena razširjenosti okužbe s HCV in opredelitev njenih epidemioloških, kliničnih in viroloških značilnosti pri bolnikih iz skupin z velikim tveganjem za okužbo v Sloveniji ter oblikovanje najbolj primernih modelov preprečevanja, odkrivanja in zdravljenja okužbe s HCV v teh skupinah. Metode: Retrospektivna analiza pridobljenih podatkov v kohortah bolnikov s končno ledvično odpovedjo na nadomestnem zdravljenju s hemodializo, oseb s presajenimi čvrstimi organi in krvotvornimi matičnimi celicami, oseb s sočasno okužbo s HIV ter oseb na prestajanju kazni zapora (OPKZ) ter retrospektivno-prospektivna opazovalna raziskava med osebami, ki si injicirajo droge (OID) in so vključene v nizkopražni program (NP) ter so del novega modela obravnave (MoC). V kohorti HIV sookuženih sta bila izvedena multivariatna logistična regresijska analiza za opredelitev dejavnikov tveganja za okužbo s HCV ter izračun stopnje ponovno pozitivnih HCV RNA testov, slednji je bil izveden tudi v kohorti OID v NP in kohorti OPKZ. Rezultati: Mikro-eliminacija je bila dosežena med bolniki s končno ledvično odpovedjo na nadomestnem zdravljenju s hemodializo, osebami s presajenimi organi in krvotvornimi matičnimi celicami ter pri sookuženih s HIV. V skupini OPKZ mikro-eliminacija ni bila dosežena. V skupini OID, vključenih v NP, je naš MoC izboljšal potek obravnave, vendar je bila stopnja ponovnih pozitivnih HCV RNA testov 12,2/100 oseb-let, tveganje za reinfekcijo pa se je s časom povečevalo in preseglo 0,5 po štirih letih. Reinfekcije so se pojavile tudi v skupinah OPKZ (7,0/100 oseb-let) ter pri HIV sookuženih (3,0/100 oseb-let), kjer se je tveganje za reinfekcijo s časom nižalo. Model logistične regresije je pri HIV-pozitivnih osebah pokazal, da so mlajša starost, stik z virusom hepatitisa B, predhodna diagnoza klamidije, gonoreje ali sifilisa ter uporaba injicirajočih drog dejavniki tveganja za novo okužbo s HCV. Primerjava med skupinami je sicer pokazala podobne deleže pozdravljenih bolnikov (100 % bolnikov na zdravljenju s hemodializo, oseb s presajeno ledvico, oseb s presajenimi krvotvornimi matičnimi celicami, 97,8 % sookuženih s HIV, 91,8 % OPKZ ter 84,9 % OID v NP) z izjemo oseb s presajenimi jetri, kjer je bilo uspešno pozdravljenih 76,2 % bolnikov. V primerjavi deležev izgubljenih bolnikov med obravnavo HCV okužbe pa so izstopali OPKZ (37 %) ter OID v NP (19 %), medtem ko je bil delež izgubljenih bolnikov v preostalih skupinah nižji (9 % med osebami s presajenimi jetri, 7 % med HIV sookuženimi, ter 0 % med osebami s presajeno ledvico in bolniki na hemodializi). Zaključek: Slovenija je dosegla mikroeliminacijo HCV med bolniki s končno ledvično odpovedjo na nadomestnem zdravljenju s hemodializo, osebami s presajenimi črvstimi organi in krvotvornimi matičnimi celicami ter osebami s HIV sookužbo, medtem ko mikroeliminacija v skupinah OID v NP in OPKZ še poteka. Čeprav je MoC izboljšal potek obravnave med OID v NP, so potrebni dodatni ukrepi, zlasti obravnava ter presejanje na okužbo s HCV v skupnosti, medtem ko so pri OPKZ najprej potrebni sistemski ukrepi na državni ravni, zlasti uvedba rutinskega presejanja na HCV. Predvsem v skupinah HIV sookuženih, OPKZ ter OID v NP bo za ohranjanje HCV mikro-eliminacije potrebno redno testiranje na ponovno okužbo s HCV ter v primeru potrditve le-te čimprejšnje zdravljenje.

• Jezik: Slovenski jezik
• Ključne besede: mikro-eliminacija, hepatitis C, reinfekcije, osebe, ki si injecirajo droge, model obravnave
• Vrsta gradiva: Doktorsko delo/naloga
• Organizacija: MF - Medicinska fakulteta
• Leto izida: 2026
• PID: 20.500.12556/RUL-184079
• Datum objave v RUL: 26.06.2026

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Micro-elimination of hepatitis C in populations at high risk for hepatitis C virus infection

Izvleček

Background: Hepatitis C virus (HCV) infection remains a major cause of cirrhosis and hepatocellular carcinoma globally. The introduction of direct-acting antivirals (DAAs) has made HCV elimination feasible; however nationwide HCV elimination remains complex. Consequently, the concept of micro-elimination emerged, breaking down national goals into targets specific for different populations at high-risk for HCV infection. Aims: To analyse and characterise populations at high-risk for HCV infection in Slovenia, to develop most appropriate models-of-care (MoC) for HCV management in these groups and compare characteristics and progress of HCV micro-elimination among high-risk populations in Slovenia with groups of the kind reported internationally. Methods: A retrospective analysis of demographic, epidemiological, clinical and virological characteristics of HCV seropositive haemodialysis recipients (HDR), solid organ transplant (SOT) and haematopoietic stem-cell transplant (HSCT) recipients, HIV co-infected individuals and incarcerated persons was carried out during observational period from 2006 to 2022. Furthermore, a retrospective-prospective observational study was conducted between 2017 and 2022 among people who inject drugs (PWID) enrolled in low-threshold program (LTP) of the civil society organisation Svit Koper and who took part of the newly tailored model-of-care (MoC). Additionally, in HIV co-infected individuals multivariate logistic regression was performed to develop a model of risk factors for HCV infection. The rate of positive HCV RNA re-tests was calculated for cohorts of HIV co-infected, PWID in LTP and incarcerated persons. For those co-infected with HIV and PWID in LTP reinfection rate, probability of reinfection and hazard of reinfection were estimated while accounting for the uncertainty of the exact time of reinfection. The various stages of the cascade-of-care were compared between cohorts. Results: Micro-elimination was achieved in all cohorts under continuous medical supervision: HDR, SOT recipients, HSCT recipients and those co-infected with HIV. Micro-elimination among incarcerated persons was not achieved. While in PWID in LTP our MoC improved cascade-of-care, the rate of HCV RNA–positive re-test was 12.2/100 person-years with risk of reinfection increasing with time and exceeding 0.5 in 4 years. Reinfections were also noted in the cohort of incarcerated persons (rate of HCV RNA–positive re-test of 7.0/100 person-years) and among those co-infected with HIV (rate of HCV RNA–positive re-test of 3.0/100 person-years), where the risk of reinfection with time decreased. Multivariate logistic regression model in our HIV cohort showed younger age, contact with HBV, prior diagnosis of either chlamydial infection, gonorrhoea or syphilis and injecting drug use as factors for new HCV infection in HIV-positive individuals. Sustained virological response rates 12 weeks after the end of treatment (SVR12) were high across all cohorts (100% in HDR, SOT recipients and HSCR recipient; 97.8% in HIV co-infected; 91.8% in incarcerated persons; and 84.9% in PWID enrolled in LTP), with the exception of liver transplant recipients (LTR) (76.2%). The highest proportion of patients who were lost to follow-up (LFU) during HCV care was observed among incarcerated persons (37%) and PWID in LTP (19%), while the rates were lower in other cohorts (9% among LTR, 7% among HIV co-infected and 0% among renal transplant recipients and HDR). Conclusions: Slovenia has achieved HCV micro-elimination among HDR, SOT recipients, HSCT recipients and co-infected with HIV, while micro-elimination among PWID in LTP and incarcerated persons is still in progress. While our MoC improved cascade-of-care among PWID in LTP, barriers to HCV care need to be addressed, likely through using a mobile unit. On the other hand, in incarcerated persons more system-level measures are required, beginning with the implementation of routine HCV screening. Sustaining HCV micro-elimination will require continuous re-testing for reinfection and prompt re-treatment, especially among HIV co-infected individuals, PWID, and incarcerated persons.

• Ključne besede: micro-elimination, hepatitis C, reinfections, model-of-care, people, who inject drugs