Short summary

Re-infections after successful treatment for hepatitis C among in people who use drugs poses a significant risk for the elimination of hepatitis C and for the individual person. This study included people treated for HCV at a center providing opioid substation therapy in Odense Denmark. Study initiated in 2019 with follow-up until 2023. The participants were screened every 6 month with a venous and a dried blood spot for HIV, HCV and HBV and was provided re-treatment if infected. The study also

Rationale

Persons who inject drugs (PWID) are a key population in WHO's strategy to eliminate new hepatitis C virus(HCV) infections and achieve the 2030 goal of a 80 % reduction in new infections. Several studies have shown that reinfection does occur after treatment with direct acting antivirals(DAA) in this population at various rates(1-10 pr. 100 person years) depending of risk behavior(1-5) The reinfection risk is besides injecting drug use dependent on the baseline prevalence of hepatitis C in the population of PWID and access to opiate substitution therapy (OST) and needle and syringe programs(NSP)(6, 7). PWID are a very diverse group ranging from very occasional or ceased users that are frequently on OST, to persons with frequent injecting drug use whether on OST or not(8). Previous studies on treatment of PWID in the interferon era have shown decreasing drug and alcohol use post cure - but there is limited data from the era of direct acting antivirals (9). The CO-STAR study showed a re-infection risk 10/100 person years in the first 6 month - and other studies have shown that this risk might increase in subsequent years (10). Currently the majority of patients being treated for HCV does not have ongoing risk behavior. However with the removal of treatment restrictions and in settings where outreach clinics and alliances with OST centers are established meaning that treatment for hepatitis C is reaching the OST and injecting drug use population the PWID fraction of those treated is about 40% (In the Odense cohort 70 of 180 alive patients treated since 2014 were treated in outreach or were on OST (Dr. Øvrehus personal communication)) Monitoring re-infection and collecting information on PWID being treated for hepatitis C is therefore important for several reasons. Primarily, re-infection will influence the prevalence of hepatitis C and if the full impact of treatment as prevention is to be evaluated, data on reinfection are crucial. In high risk groups re-infection might occur prior to 12 weeks post treatment implying treatment failure instead of reinfection. Re-infection also implies gaps in prevention measures such as OST and NSP and might identify potentials for harm reduction. In current standard of care persons cured for hepatitis C are either followed every 6 months if they have cirrhosis or are discharged from care a year after end of treatment if non-cirrhotic. Persons on OST are offered yearly surveillance testing in the municipality(as everyone connected to a drug use center) but there is a need for collecting this data and collect more detailed information from multiple sites to provide a reliable estimation of re-infection rates. Additionally there is very little knowledge on the benefits of treatment in PWID with regards to patient reported outcome measures (PROM) including health related quality of life (HRQOL) and patient experienced outcome measures (PREM) as well as drug use patterns post cure. Most outcome measures are from clinical trials excluding PWIDs thus long term outcomes are not well described in this population. If a public health intervention aiming at reducing new infections is to be successful in the PWID population we need more information on the individual level. Currently Dried Blood Spots (DBS) are being advocated as a simple solution for testing for cure, but there are no published studies that have validated this option in determining treatment outcomes and there are very few published validation studies in general (11-13). A point of care test that safely can determine and distinguish hepatitis C cure or viral recurrence will be of great value in the cascade of care for PWID. As the DBS test on the same blood spot can identify HIV and Hepatitis B infection, integrated monitoring of coinfection is also feasible. The aim of this study is to 1) evaluate the risk of reinfection in persons treated for Hepatitis C on OST or with recent injecting drug use and 2) to evaluate the long term outcome on HRQOL and 3) to validate DBS as a point of care test for cure or viral recurrence.

Description of the cohort

The cohort was including people who had either been treated for Hepatitis C before or was tested positive for HCV-RNA at the including site. Participants was included at a center providing opioid substation therapy in Odense Denmark.

Data and biological material

Blood samples (ALAT, ASAT, INR, Albumin, thrombocytes, NAT tests for HIV-RNA, HCV-RNA, HBV-DNA, quantative analysis of HCV-RNA). Fibro-scans. Short form 36 version 2 contains 8 domains measuring functional health and well-being: general health, vitality, role emotional, role physical, social well-being, mental health, and physical functioning. Patient Reported Outcome/Experience Measure for Hepatitis DAA Treatment Among People Who Inject Drugs(HCV PROM/PREM). Baseline characteristiscs of the participants (age, sex, ethnicity, employment status, education level, housing status, incarceration, medical history alcohol history and OST received) Drug use history: Drugs injected, injection frequency and sharing of needle/syringe, cookers, cotton/filter or water.

Collaborating researchers and departments

Department of Clinical Immunology, Odense University Hospital

• Dorte Kinggaard Holm Cand Scient, ph.d.

Section of Molecular Diagnostics at Aalborg University Hospital

• Head of Department Henrik Krarup

Department of Immunology and Microbiology, Copenhagen University Hospital (Hvidovre)

• Professor Jens Bukh