Hepatitis C treatment at a Swedish needle exchange program, a successful model of care - the ACTIONNE study.

BACKGROUND: To engage people who inject drugs (PWID) in HCV care, innovative models of care are urgently needed. A needle exchange program (NEP) could serve as an ideal platform for comprehensive HCV management including post treatment follow up. METHODS: 50 actively injecting patients at the Malmö Needle exchange program (MNEP) were consecutively enrolled between April 2018 and May 2019. All patients received a fixed-dose combination of once-daily glecaprevir/pibrentasvir for 8 or 12 weeks. Patients were monitored weekly during treatment and data on adherence and side effects was recorded. The primary endpoint was SVR12. Adherence to treatment was the secondary endpoint. RESULTS: 47/50 (94%) patients completed treatment. 45/50 were HCV negative at 12 weeks post treatment giving an SVR12 rate per ITT of 90% and an SVR12 rate per protocol of 96%. One patient showed reinfection 12 weeks post treatment and one patient was lost to follow up and did not produce an SVR12 result. The mean adherence per week, according to pill count, was 98%. CONCLUSION: Our study shows that the NEP can be a useful tool for engaging actively injecting PWID in HCV management and that SVR rates, comparable to those in non-PWID settings, can be achieved.

Mortality among amphetamine users with hepatitis C virus infection: A nationwide study.

AIMS: To investigate liver-related and all-cause mortality among amphetamine users with hepatitis C virus (HCV) infection and compare this with opioid users with HCV infection and the uninfected general population. METHODS: In this national register study of mortality in persons notified with HCV infection 1990-2015 and a substance-related diagnosis in Sweden, amphetamine users (n = 6,509) were compared with opioid users (n = 5,739) and a matched comparison group without HCV infection/substance use (n = 152,086). RESULTS: Amphetamine users were observed for 91,000 years and 30.1% deceased. Crude liver-related mortality was 1.8 times higher in amphetamine users than opioid users (crude mortality rate ratio 1.78, 95% CI 1.45-2.19), but there was no significant difference when adjusting for age and other defined risk factors. An alcohol-related diagnosis was associated with liver-related death and was more common among amphetamine users. Crude and adjusted liver-related mortality was 39.4 and 5.8 times higher, respectively, compared with the uninfected group. All-cause mortality was lower than in opioid users (adjusted mortality rate ratio 0.78, 95% CI 0.73-0.84), but high compared with the uninfected group. External causes of death dominated in younger ages whereas liver-related death was more common among older individuals. CONCLUSIONS: This national register study presents a higher crude risk of liver-related death among HCV-infected amphetamine users compared with opioid users or the uninfected general population. The higher risk of liver-related death compared with opioid users may be explained by lower competing death risk and higher alcohol consumption. Treatment of HCV infection and alcohol use disorders are needed to reduce the high liver-related mortality.

Hepatitis C elimination in Sweden: Progress, challenges and opportunities for growth in the time of COVID-19.

BACKGROUND & AIMS: In 2014, the burden of hepatitis C virus (HCV) in Sweden was evaluated, to establish a baseline and inform public health interventions. Considering the changing landscape of HCV treatment, prevention, and care, and in light of the COVID-19 pandemic, this analysis seeks to evaluate Sweden's progress towards the World Health Organization (WHO) elimination targets and identify remaining barriers. METHODS: The data used for modelling HCV transmission and disease burden in Sweden were obtained through literature review, unpublished sources and expert input. A dynamic Markov model was employed to forecast population sizes and incidence of HCV through 2030. Two scenarios ('2019 Base' and 'WHO Targets') were developed to evaluate Sweden's progress towards HCV elimination. RESULTS: At the beginning of 2019, there were 29 700 (95% uncertainty interval: 19 300-33 700) viremic infections in Sweden. Under the base scenario, Sweden would achieve and exceed the WHO targets for diagnosis, treatment and liver-related death. However, new infections would decrease by less than 10%, relative to 2015. Achieving all WHO targets by 2030 would require (i) expanding harm reduction programmes to reach more than 90% of people who inject drugs (PWID) and (ii) treating 90% of HCV + PWID engaged in harm reduction programmes and ≥7% of PWID not involved in harm reduction programmes, annually by 2025. CONCLUSIONS: It is of utmost importance that Sweden, and all countries, find sustainability in HCV programmes by broadening the setting and base of providers to provide stability and continuity of care during turbulent times.

High risk of non-alcoholic liver disease mortality in patients with chronic hepatitis C with illicit substance use disorder.

Aims: Hepatitis C virus (HCV) is a slowly progressive disease, often transmitted among people who inject drugs (PWID). Mortality in PWID is high, with an overrepresentation of drug-related causes. This study investigated the risk of death in patients with chronic hepatitis C virus (HCV) infection with or without illicit substance use disorder (ISUD).Methods: Patients with HCV were identified using the Swedish National Patient Registry according to the International Classification of Diseases-10 (ICD-10) code B18.2, with ≤5 matched comparators from the general population. Patients with ≥2 physician visits with ICD-10 codes F11, F12, F14, F15, F16, or F19 were considered to have ISUD. The underlying cause of death was analyzed for alcoholic liver disease, non-alcoholic liver disease, liver cancer, drug-related and external causes, non-liver cancers, or other causes. Mortality risks were assessed using the standardized mortality ratio (SMR) with 95% CIs and Cox regression analyses for cause-specific hazard ratios.Results: In total, 38,186 patients with HCV were included, with 31% meeting the ISUD definition. Non-alcoholic liver disease SMRs in patients with and without ISUD were 123.2 (95% CI, 103.7-145.2) and 69.4 (95% CI, 63.8-75.3), respectively. The significant independent factors associated with non-alcoholic liver disease mortality were older age, being unmarried, male sex, and having ISUD.Conclusions: The relative risks for non-alcoholic liver disease mortality were elevated for patients with ISUD. Having ISUD was a significant independent factor for non-alcoholic liver disease. Thus, patients with HCV with ISUD should be given HCV treatment to reduce the risk for liver disease.

Mortality and causes of death among people who inject amphetamine: A long-term follow-up cohort study from a needle exchange program in Sweden.

BACKGROUND: Abuse of amphetamines is a worldwide problem with around 34 million users, and amphetamine is commonly used by people who inject drugs (PWID). Despite this, there is relatively little research on mortality and cause of death among people who use amphetamines primarily. The present study aimed to examine mortality and causes of death among people who inject amphetamine, and compare these results to the general population. METHODS: This retrospective cohort study was based on data from The Malmö Needle Exchange Program in Sweden (MNEP) and on data from The Swedish National Cause of Death Register. Participants in the MNEP, between 1987 and 2011, with registered national identity number and amphetamine as their primary drug of injection use, were included in the study. Standardized mortality ratios (SMR) was calculated for overall mortality and categories of causes of death. RESULTS: 2019 individuals were included (mean follow-up-time 13.7 years [range 0.02-24.2 years], a total of 27,698 person-years). Of the 448 deceased, 428 had a registered cause of death. The most common causes of death were external causes (n = 162, 38%), followed by diseases of the circulatory system (n = 67, 16%). SMR were significantly elevated (8.3, 95% CI [7.5-9.1]) for the entire study population, and for every category of causes of death respectively. CONCLUSIONS: People injecting amphetamine as a primary drug were found to have significantly elevated mortality compared with the general population, with high rates of both external and somatic causes of death.

Death from liver disease in a cohort of injecting opioid users in a Swedish city in relation to registration for opioid substitution therapy.

INTRODUCTION AND AIMS: Injecting opioid users are at elevated risk of death. Although liver disease (especially hepatitis C) is common, its impact on mortality is low in active injectors. Because opioid substitution therapy (OST) reduces the risk of death from directly drug related causes, we hypothesised that the proportion of liver-related deaths would increase in subjects receiving OST. We investigated liver-related mortality in a cohort of injecting opioid users attending a needle exchange program (NEP) in a Swedish city in relation to OST exposure. DESIGN AND METHODS: Participants enrolled in the NEP between 1987 and 2011 with available national identity numbers, and registered use of opioids, were included. Linkage based on national identity numbers was performed with national registers for death, emigration and prescription of OST. Participants were categorised as non-OST recipients until the registered date of first OST prescription, and hence as OST recipients. Hazard ratios were calculated by Cox regression for overall and liver-related mortality in relation to OST, with OST as a time-dependent variable. RESULTS: Among 4494 NEP participants, 1488 opioid users were identified; 711/1488 had been prescribed OST. During a follow-up period of 15 546 person-years 368 deaths occurred. Sixteen deaths were caused by liver disease; 10 of these occurred in OST recipients. The risk of liver-related death was significantly increased in OST receiving participants (hazard ratio 3.08, 95% confidence interval [1.09, 8.68], P = 0.03). CONCLUSIONS: Liver related mortality among opioid users was significantly elevated in OST recipients, showing the long-term importance of chronic liver disease in this population. [Jerkeman A, Håkansson A, Rylance R, Wagner P, Alanko Blomé M, Björkman P. Death from liver disease in a cohort of injecting opioid users in a Swedish city in relation to registration for opioid substitution therapy. Drug Alcohol Rev 2017;36:424-431].

Treatment for chronic hepatitis C in a cohort of opiate substitution therapy recipients in three Swedish cities - completion rates and efficacy.

OBJECTIVES: Opiate substitution treatment (OST) programs could provide opportunities for management of comorbidities, such as hepatitis C virus (HCV) infection, in people who inject drugs. We aimed to prospectively evaluate the real-life feasibility of interferon/ribavirin-based HCV treatment in OST recipients, with a special focus on psychiatric status and health-related quality of life. METHODS: Patients from a cohort of OST recipients from three cities in Sweden were selected for HCV treatment on the basis of structured investigation for HCV-related liver disease. Therapy was delivered in collaboration between infectious disease and OST clinics, with monitoring for completion and adherence, treatment response, adverse events, health-related quality of life (HRQoL) (SF-36) and signs of depression (MADRS-S), or relapse into drug abuse. The primary endpoint was completion of prescribed treatment; the secondary endpoints were sustained virological response (SVR), adherence, and incidence of depression. RESULTS: Among 69 patients with an indication for antiviral therapy, 41 initiated treatment; 34/41 (83%) completed treatment and 19/41 (46%) achieved SVR. Adequate adherence was observed in 29/41 patients (71%). Two serious adverse events occurred, including one death because of liver failure. Baseline scores for self-assessed health were low, with a significant reduction during treatment. Seventy-one percent of patients (29/41) fulfilled the criteria for clinically significant depression at some time point during treatment. Baseline scores for HRQoL/MADRS-S were associated with treatment completion, SVR, and depression during treatment. CONCLUSION: Despite the low HRQoL and the high occurrence of depression, HCV treatment was feasible and showed satisfactory rates of completion in this cohort of unselected OST recipients.

Chronic hepatitis C in Swedish subjects receiving opiate substitution therapy--factors associated with advanced fibrosis.

BACKGROUND: Opiate substitution therapy (OST) reduces the risk of death from directly drug-related causes in heroin users, allowing other chronic health problems to emerge. People who inject drugs (PWID) are exposed to hepatitis C virus (HCV), with an associated risk of chronic liver disease. We investigated HCV prevalence and liver-related morbidity in a cohort of OST recipients, and analyzed factors associated with significant hepatic fibrosis. METHODS: All patients registered on 1 April 2008 in 4 clinics providing OST in the 3 largest cities in Sweden were eligible for inclusion. HCV viremic subjects were evaluated for fibrosis stage by liver biopsy, transient elastometry (TE), and/or a biochemical fibrosis index (Göteborg University Cirrhosis Index; GUCI). Factors associated with severity of fibrosis were determined by logistic regression analysis. RESULTS: Out of 524 eligible patients, 277 consented to enrolment. Two hundred and thirty-six subjects (88%) were anti-HCV-positive, and 162 of these were viremic (69%). Significant liver fibrosis (defined as Ishak stages F3-F6, TE value ≥ 8.85 kPa, or GUCI > 0.33) was found in 69 out of 103 (67%) tested viremic patients, and was associated with alcohol intake (p = 0.03), higher body mass index (BMI; p = 0.04), and the presence of anti-HBc antibodies (indicating exposure to hepatitis B virus (HBV); p = 0.02). CONCLUSIONS: Significant liver fibrosis was detected in two-thirds of HCV viremic OST recipients in this cohort, and was associated with alcohol use, high BMI, and exposure to HBV. These findings indicate that the management of HCV and associated risk factors should be emphasized in Swedish OST programs.