Hepatitis C Elimination in the Region of Southern Denmark

Research output: ThesisPh.D. thesis

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Abstract

Background
Hepatitis C is a viral blood-borne infection with an estimated prevalence of 0.22 % in Denmark. Above 85 % of hepatitis C patients are infected through injection drug use. For decades, treatment options have been limited to patients with advanced disease. It was a paradigm shift when direct-acting antivirals (DAAs) were released for treatment for all hepatitis C patients in Denmark in November 2018. Besides being short and easy to administer it has nearly no side effects and a success rate of over 95%. In 2016 WHO announced to work towards the elimination of Hepatitis C by 2030 with the target of reducing the number of new infections with 90% and treating 80% of infected. To achieve this goal a regional elimination plan has been created to become a hepatitis C-free Region of Southern Denmark by 2025. To reach the goal of elimination in a low prevalent country like Denmark it is crucial to focus on risk groups and to treat the hepatitis C infected who have been diagnosed, but dropped out of the treatment system for whatever reason. This thesis is part of the C-Free-South strategy and includes four studies. One describes the thoughts behind the elimination strategy for the Region of Southern Denmark and the three others are interventions in different populations focusing on the elimination of hepatitis C in the Region of Southern Denmark.

Aims & methods
Study 1: “A multi-level intervention to eliminate hepatitis C from the Region of Southern Denmark: the CFree-South project” aimed to describe how the micro-elimination strategy for the Region of SouthernDenmark had been designed. The strategy was based on the latest estimate of hepatitis C infected inDenmark with a calculation of diagnosed patients not in care and an expected amount of undiagnosedpatients in Denmark at a regional level. The interventions in the program focused on how to reach thedifferent groups and how to establish surveillance of the interventions. 

Study 2: “Retrieval of patients with hepatitis C who were lost to follow-up in Southern Denmark” (Call-back)The study aimed to evaluate the efficacy of recalling hepatitis C infected who had been lost to follow-up.Patients who had been discharged with a positive HCV RNA from the two outpatient clinics in the Regionbefore treatment options were available in November 2018 were “called-back”. Patients were contactedand offered treatment. The first contact attempt was either phone or letter, while the second contactattempt was a letter sent two months after the first contact if they had not responded. In case of noresponse, we informed their general practitioner to refer the patients if interested. The study wasconducted from 2019-2022.

Study 3: “Hepatitis C screening and linkage to care with a mobile unit in Southern Denmark” (Line C)We aimed to access the HCV prevalence among people with different risk profiles by visiting facilitiesaddressing marginalized populations with a mobile clinic. Furthermore, we wanted to assess treatmentuptake among HCV RNA positive. Test facilities were divided into three groups. The first group of facilitieswere predominantly for people with current or former injection drug use, group two were facilitiestargeting people with overuse of alcohol and/or psychiatric diseases and the third group waspredominantly the general population tested at ports and markets. The mobile clinic offered point of care(HCV Ab/HCV RNA) as well as dried blood spot tests for hepatitis C and study participants were handed aquestionnaire about risk behavior. People with active HCV infection were linked to care for HCV treatment.The mobile unit had been testing throughout the Region of Southern Denmark since September 2020. Dataincluded in the study are from 2020-2022.

Study 4: “High Hepatitis C treatment uptake in substance use treatment centers after an intervention withimplementation of dried blood spot testing and decentralized treatment”. (Test & Treat)The primary aim of the study was to estimate the treatment uptake after introducing dried blood spots andestablishing outreach hepatitis clinics in all substance use treatment centers in the Regions of SouthernDenmark. A secondary aim was to estimate the proportion of those registered in the “Registry of DrugAbusers Undergoing Treatment” who were treated during the intervention period in the outreach hepatitisclinics compared to the standard of care. Additionally, the two geographical parts of the Region werecompared to find predictors for initiating treatment. Historically there had been an intensified effort foroutreach hepatitis test and treatment on Funen (the eastern part of the region) with already twoestablished outreach clinics in the two largest substance use treatment centers on the Island compared toJutland (the Western part of the region) were no outreach clinics had been established. The study was ahealthcare system intervention with a register-based cohort study. In March 2019, the intervention wasinitiated sequentially in all substance use treatment centers with the introduction of DBS, except in twocenters with established outreach hepatitis C clinics. After a test period, each center had a treatment phasewhere hepatitis C treatment assessment, as well as treatment, was established onsite. The “Registry ofDrug Abusers Undergoing Treatment” was used to form a retrospective cohort comprising individualcitizens enrolled in the substance use treatment centers at the date of intervention start for each center.This cohort was linked with the outreach hepatitis C cohort (those HCV-infected identified through theintervention) enabling us to characterize the population based on the use of opioid agonist therapy (OAT),history of injecting drug use, age in years at OAT initiation, and duration of enrolment in a substance usetreatment center. In addition, data were linked to the National Registry of Alcohol Treatment to identify ifindividuals had been ever received treatment for alcohol abuse. The intervention took place from 2019-2021 with data inclusion until August 2022.

Results
In paper one, we described the individual interventions we had planned based on the data and knowledgeat that time. Three important interventions had been carried out and were part of this PhD thesis. HepatitisC patients who were diagnosed, but no longer in care (Study 2) were found by going through our hepatitis Cdatabase consisting of data from 2002 onwards. We found 69 eligible persons discharged with positive HCVRNA. Of those 54 (78%) responded and 15 (22%) did not respond despite two contact attempts. Forty-five(65%) had initiated treatment, 1 (1%) rejected treatment and eight (12%) were interested but neverattended several appointments. Of the treated individuals 20 (44%) responded after the first contactattempt either by phone or letter while 18 (40%) responded after the second attempt and seven (16%)patients responded after a letter was sent to their general practitioner. 

In Study 3 we searched for undiagnosed hepatitis C infected with the mobile clinic. We tested 802 personsthroughout the region in shelters, cafés and facilities for marginalized people from September 2020 untilNovember 2022. In the whole study population, we found an HCV Ab prevalence of 13% and an HCV RNAprevalence of 3%. The HCV Ab/HCV RNA prevalence in group 1 was 20%/5%, while the HCV Ab prevalencewas 2% in group 2. We found no one with positive HCV RNA in group 2 and 3 and in addition, none in group3 had positive HCV Ab. This resulted in a change in the test strategy by focusing on facilities primarilytargeting people with former or current injecting drug use. Treatment uptake among infected was 95%(20/21).

The test and treatment intervention (Study 4) found a treatment uptake of 81.4% (n=303) in the outreachhepatitis C clinics, with a higher treatment uptake in Jutland 86.4% (n=146) compared with Funen 77.3%(n=157). On Funen, a significantly higher proportion of persons had ever received OAT 54.1% (n=708) and60% (n=785) reported injection drug use ever in comparison to Jutland where 37.9% (n=580) reported OATand 50% (n=766) had a history of injecting drug use. Among all HCV treatments (n=489) of all peopleenrolled in a substance use treatment center during the intervention period, the majority (62%) receivedtheir treatment through the outreach hepatitis C clinics compared with standard of care (38%). The oddsfor treatment uptake were significantly lower when living on Funen. 

Conclusion
Study 1 is the recipe for the micro elimination program in the Region of Southern Denmark. Looking backon the estimated numbers, we would have expected a higher number of infected hepatitis C patients withthe mobile clinic. In combination with results from other interventions in the C-Free-South project, thisindicates that the original estimates of HCV-infected might be too high. However, the interventions,demonstrated that repeated and persistent contact attempts increase the number of successful hepatitistreatment initiations in the lost to follow-up patient group. Searching for the group of undiagnosed had avery low yield. By focusing on former and active injection drug users we increased the number of diagnosedcases significantly. Despite the small numbers, the study was important in developing a focused teststrategy and the high treatment uptake shows the high impact on linkage to care. The introduction of driedblood spots and the establishment of outreach clinics had a numerical great impact by treating 82% of allHCV- infected addressed in this PhD. In addition, the study contributes to a sustainable easier access to testand treatment facilities in the Region of Southern Denmark. 
Original languageEnglish
Awarding Institution
  • University of Southern Denmark
Supervisors/Advisors
  • Christensen, Peer Brehm, Principal supervisor
  • Øvrehus, Anne Lindebo Holm, Co-supervisor
  • Holm, Dorte Kinggaard, Co-supervisor
  • Dillon, John, Co-supervisor, External person
Date of defence8. Mar 2024
Publisher
DOIs
Publication statusPublished - 7. Feb 2024

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