Short summary

In Denmark the majority of chronic hepatitis C infections are found in patients infected by intravenous drug use which is also the main driver of incident infections. Testing people for blood borne infections by finger prick (dried blood spots) and provide decentralized treatment have been shown to improve test and treatment uptake. By implementing these interventions at drug treatment center, hepatitis C may potentially be eliminated in the drug use population. The study will produce estimates of the effect of outreach testing and on site treatment towards elimination of hepatitis C in people with drug use at a population level.

Rationale

Chronic infection with hepatitis C (HCV) is worldwide one of the leading causes of liver disease and death. WHO has launched a goal to eliminate hepatitis C by 2030. Denmark has signed the WHO hepatitis strategy, but no national plan has been launched to achieve hepatitis C elimination. The WHO framework for elimination defines 80% reduction in incidence and 65% reduction in mortality as targets for elimination of hepatitis C. To achieve this it is deemed necessary that 90% of infections are diagnosed and 80% of eligible treated. The current estimate in Denmark is that only half of all patients with HCV have been diagnosed and only one quarter attends clinical care based on 2007 data. Among Danish HCV patients 85% have been infected by drug use, and intravenous drug use is the main driver of incident infections. Therefore is has been recommended for decades to test drug users for HCV and refer infected for treatment evaluation. According to national guidelines HCV testing is recommended on a yearly base of clients attending drug treatment centers (DTC). However, due to logistic problems and a difficult treatment in the past, this has had a very low coverage, and in most centers less than 10% of infected drug users have achieved cure. This was all changes with the new drugs "the DAA revolution" implemented in 2014 and now HCV is an "easy to treat", curable disease. A major obstacle of hepatitis C screening in Denmark has been a restriction for treatment of patients with HCV to only those with significant fibrosis (liver stiffness > 10kPa). However, following the rest of the western world, the Medical Council of Denmark approved treatment for all HCV patients in November 2018. In the Region of Southern Denmark (RSD) twenty-two years ago our group at Odense University Hospital started outreach care and research in prisons and DTC in the county of Funen, a part of RSD with a population of half a million. We have shown that 90% of every and 95% of current opioid substitution therapy (OST) recipients have been tested and currently 35% have hepatitis C. The high testing rate in Funen is the result of a longstanding corporation with the DTC in Funen delivering on-site care and treatment for HCV. This model of care is called the "BEST" (Bedre HCV behandling af stofbrugere/better HCV treatment of drug users) model. With the new possibility of "test and treat" we think this model can be expanded to include all DTC in RSD. A major problem to identify HCV patients in outreach settings is the lack of on-site skilled phlebotomists and pour venous access in many drug users. We have therefore validated a dry blood spot test (DBS) for HCV, hepatitis B( HBV) and human immunodeficiency virus (HIV) in one sample. Testing by DBS has the advantage of providing both HCV-RNA and anti-HCV thus making it ideal for surveillance of both exposure and current (re)infection. Sampling is simple and can be performed without professional training and we have implemented DBS at prisons in Funen, and showed it to be feasible with and 80% participation rate in this population. The introduction of treatment of all patients with HCV regardless of the fibrosis stage makes it possible to eliminate HCV. Treating as many clients at the same time as possible in one setting (a DTC) is likely to reduce re-infection rates that have been reported between 5-20% depending on setting. Study aim: Establishing sustainable hepatitis C surveillance and simple algorithms for referral and treatment in the drug treatment setting is the key to ensure elimination of Hepatitis C and is the main aim of this study. We believe it is possible to fulfill WHO targets and obtain HCV elimination in Denmark before 2030. Due to the new treatment guidelines with treatment to everybody and the easier tools to test it is now more feasible to test and treat people who inject drugs (PWID). Access to health care services can be challenging for this population. The purpose of the study is to establish routine testing at all DTC in RSD and find the HCV infected clients and make sure that they are offered treatment according to the natrional Guidelines. The study is a part of a multi-level intervention with the purpose of eliminating hepatitis C in RSD. Our hypothesis is that the prevalence and incidence of HCV in RSD will decrease. Retesting at the DTC after treatment will monitor the reinfection.

Description of the cohort

People who use drugs (PWUD) above 25 years connected to a drug treatment center in the Region of Southern Denmark.

Data and biological material

Data Sources from the following registers: The national database of drug users in treatment (SIB) Laboratory Register (DANVIR) Infcare Civil Registration system (CRS) The National Patients Register (LPR) The Danish Pathology Register (LRP) The Danish Cancer Registry (CAR) National Registry of Alcohol Treatment (NAB) The Danish National Prescription Registry (LSR)

Collaborating researchers and departments

Department of Infectious Diseases, Odense University Hospital

• MD, PhD-student Sandra Dröse
• Chief Physician, PhD Anne Øvrehus