Peer support in small towns: A decentralized mobile Hepatitis C virus clinic for people who inject drugs

Background & aims: New models of HCV care are needed to reach people who inject drugs (PWID). The primary aim was to evaluate HCV treatment uptake among HCV RNA positive individuals identified by point-of-care (POC) testing and liver disease assessment in a peer-driven decentralized mobile clinic. Methods: This prospective study included consecutive patients assessed in a mobile clinic visiting 32 small towns in Southern Norway from November 2019 to November 2020. The clinic was staffed by a bus driver and a social educator offering POC HCV RNA testing (GeneXpert®), liver disease staging (FibroScan® 402) and peer support. Viremic individuals were offered prompt pan-genotypic treatment prescribed by local hospital-employed specialists following a brief telephone assessment. Results: Among 296 tested individuals, 102 (34%) were HCV RNA positive (median age 51 years, 77% male, 24% advanced liver fibrosis/cirrhosis). All participants had a history of injecting drug use, 71% reported past 3 months injecting, and 37% received opioid agonist treatment. Treatment uptake within 6 months following enrolment was achieved in 88%. Treatment uptake was negatively associated with recent injecting (aHR 0.60; 95% CI 0.36-0.98), harmful alcohol consumption (aHR 0.44; 95% CI 0.20-0.99), and advanced liver fibrosis/cirrhosis (aHR 0.44; 95% CI 0.25-0.80). HCV RNA prevalence increased with age (OR 1.81 per 10-year increase; 95% 1.41-2.32), ranging from 3% among those <30 years to 55% among those ≥60 years. Conclusions: A peer-driven mobile HCV clinic is an effective and feasible model of care that should be considered for broader implementation to reach PWID outside the urban centres. Keywords: hepatitis C virus; peer support; people who inject drugs; point of care; treatment. © 2022 The Authors. Liver International published by John Wiley & Sons Ltd.publishedVersio

Hepatitis C treatment uptake among people who inject drugs in Oslo, Norway: A registry-based study

Background Improving HCV treatment uptake among people who inject drugs (PWID) is crucial to achieving the WHO elimination targets. The aims were to evaluate HCV treatment uptake and HCV RNA prevalence in a large cohort of PWID in Norway. Methods Registry-based observational study where all users of the City of Oslo's low-threshold social and health services for PWID between 2010–2016 ( n = 5330) were linked to HCV notifications (1990–2019) and dispensions of HCV treatment, opioid agonist treatment (OAT) and benzodiazepines (2004–2019). Cases were weighted to account for spontaneous HCV clearance. Treatment rates were calculated using person-time of observation, and factors associated with treatment uptake were analysed using logistic regression. HCV RNA prevalence was estimated among individuals alive by the end of 2019. Results Among 2436 participants with chronic HCV infection (mean age 46.8 years, 30.7% female, 73.3% OAT), 1118 (45.9%) had received HCV treatment between 2010–2019 (88.7% DAA-based). Treatment rates increased from 1.4/100 PY (95% CI 1.1–1.8) in the pre-DAA period (2010–2013) to 3.5/100 PY (95% CI 3.0–4.0) in the early DAA period (2014–2016; fibrosis restrictions) and 18.4/100 PY (95% CI 17.2–19.7) in the late DAA period (2017–2019; no restrictions). Treatment rates for 2018 and 2019 exceeded a previously modelled elimination threshold of 50/1000 PWID. Treatment uptake was less likely among women (aOR 0.74; 95% CI 0.62–0.89) and those aged 40–49 years (aOR 0.74; 95% CI 0.56–0.97), and more likely among participants with current OAT (aOR 1.21; 95% CI 1.01–1.45). The estimated HCV RNA prevalence by the end of 2019 was 23.6% (95% CI 22.3–24.9). Conclusion Although HCV treatment uptake among PWID increased, strategies to improve treatment among women and individuals not engaged in OAT should be addressed.This research received funding from the following sources. KM receives research grants from the South-Eastern Norway Regional Health Authority , grant number: 2020011 . The funding sponsor has not been involved in study design, collection of data, analysis/interpretation of data, in the writing of the article, or in the decision to submit the article for publication.publishedVersio

Integrated treatment of hepatitis C virus infection among people who inject drugs:A multicenter randomized controlled trial (INTRO-HCV)

BackgroundThe standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID.Methods and findingsINTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment.ConclusionsIntegrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV.Trial registrationClinicalTrials.gov.no NCT03155906

The Consensus Hepatitis C Cascade of Care:standardized reporting to monitor progress toward elimination

Cascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate, in simple terms, the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of individuals with HCV to diagnosis, treatment, and cure. The value of reporting would be enhanced if a standardized approach were used for generating CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway, and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and for ensuring accurate monitoring of progress toward WHO's 2030 hepatitis C elimination targets.</p

Adherence to response-guided pegylated interferon and ribavirin for people who inject drugs with hepatitis C virus genotype 2/3 infection: the ACTIVATE study

Background: The aims of this analysis were to investigate treatment completion and adherence among people with ongoing injecting drug use or receiving opioid substitution therapy (OST) in a study of response-guided therapy for chronic HCV genotypes 2/3 infection. Methods: ACTIVATE was a multicenter clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b (PEG-IFN) and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Outcomes included treatment completion, PEG-IFN adherence, ribavirin adherence, and sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment). Results: Among 93 people treated, 59% had recently injected drugs (past month), 77% were receiving OST and 56% injected drugs during therapy. Overall, 76% completed treatment. Mean on-treatment adherence to PEG-IFN and ribavirin were 98.2% and 94.6%. Overall, 6% of participants missed > 1 dose of PEG-IFN and 31% took <95% of their prescribed ribavirin., Higher treatment completion was observed among those receiving 12 vs. 24 weeks of treatment (97% vs. 46%, P < 0.001) while the proportion of participants with 95% on-treatment ribavirin adherence was similar between groups (67% vs. 72%, P = 0.664). Receiving 12 weeks of therapy was independently associated with treatment completion. No factors were associated with 95% RBV adherence. Neither recent injecting drug use at baseline nor during therapy was associated with treatment completion or adherence to ribavirin. In adjusted analysis, treatment completion was associated with SVR (aOR 23.9, 95% CI 2.9-193.8). Conclusions: This study demonstrated a high adherence to directly observed PEG-IFN and self-administered ribavirin among people with ongoing injecting drug use or receiving OST. These data also suggest that shortening therapy from 24 to 12 weeks can lead to improved treatment completion. Treatment completion was associated with improved response to therapy

Leverfibrose hos hepatitt C-pasienter med pakistansk versus skandinavisk opprinnelse

Abstract Background and aims: Chronic hepatitis C infection represents an increasing health problem globally, not least in the developing countries. The natural history of the disease is controversial and is poorly studied in Pakistanis. The aim of this study was to determine the significance of native country for the stage of liver fibrosis in a population of HCV patients of Pakistani or Scandinavian origin living in Oslo. Patients and methods: A total of 133 HCV patients, 78 of Scandinavian and 55 of Pakistani origin, met the inclusion criteria based on detectable serum HCV-RNA and an available liver biopsy. Demographical, clinical, virological, biochemical and histological data for the two groups were examined retrospectively. Results: Among the patients of Pakistani origin, more patients had bridging fibrosis/cirrhosis on liver biopsy than among the Scandinavian patients (49% vs. 19%; p<.0003). There were also more patients with liver steatosis (64% vs. 32%; p=.001) and ALT and AST levels above the reference range (95% vs. 83%; p=.044 and 87% vs. 66%; p=.005) in the Pakistani group. Logistic regression analysis identified age and Pakistani origin as the only independent predictors of bridging fibrosis/cirrhosis. Conclusions: HCV patients of Pakistani origin had more advanced liver disease than those of Scandinavian origin. This can be explained by longer duration of the infection and more comorbidity like liver steatosis, diabetes mellitus and HBV co-infection in the Pakistani group. We encourage Norwegian physicians to take this into consideration when encountering this patient group

Management of hepatitis C virus infection among people who inject drugs: Treatment uptake, reinfection and risk behaviours

The burden of hepatitis C virus (HCV) related liver disease among people who inject drugs (PWID) is increasing. Current highly efficient, simple, and tolerable directacting antiviral (DAA) HCV treatment provides new opportunities to reduce disease burden and transmission among PWID. The World Health Organization therefore targets HCV elimination within 2030. The aim of this thesis was to describe key aspects of HCV infection among PWID related to treatment uptake, reinfection incidence and risk behaviours. Through a series of observational studies, the thesis provides contextual and baseline evidence to inform strategies for HCV elimination in Norway. Study I was a registry linkage study showing that treatment uptake among HCVinfected people receiving opioid substitution treatment (OST) was low (14% over 10 years) prior to the availability of DAA therapies in Norway. Treatment uptake was associated with long-term stability in OST and absence of heavy benzodiazepine use. Study II was a clinical follow-up of a cohort successfully treated for HCV infection in a Scandinavian trial 7 years earlier. The incidence of reinfection was 1.7/100 personyears among all PWID and 4.9/100 person-years among those who had injected drugs after treatment. Relapse to drug use was associated with young age and low education level. Study III was an international multi-centre study evaluating changes in risk behaviours during and following HCV treatment. It demonstrated reductions in reported injecting drug use and hazardous alcohol consumption, but no changes in sharing of injecting equipment. Study IV was a review article covering HCV epidemiology and reinfection incidence in high-risk groups for transmission. The findings emphasize the need for increased treatment uptake among PWID combined with strategies to reduce the risk of reinfection among individuals with ongoing risk behaviours. This will require coordinated efforts across different levels of the health-care system

Hepatitis C Treatment Uptake among Patients Who Have Received Opioid Substitution Treatment: A Population-Based Study

Background and Aims There is limited data on hepatitis C (HCV) treatment uptake among people who inject drugs including individuals receiving opioid substitution treatment (OST). We aimed to calculate cumulative HCV treatment uptake, estimate annual treatment rates, and identify factors associated with HCV treatment among individuals who have received OST in Norway. Methods This observational study was based on linked data from The Norwegian Prescription Database and The Norwegian Surveillance System for Communicable Diseases between 2004 and 2013. Both registries have national coverage. From a total of 9919 individuals who had been dispensed OST (methadone, buprenorphine or buprenorphine-naloxone), we included 3755 individuals who had been notified with HCV infection. In this population, dispensions of HCV treatment (pegylated interferon and ribavirin), benzodiazepines, selective serotonin reuptake inhibitors and antipsychotics were studied. Results Among 3755 OST patients notified with HCV infection, 539 (14%) had received HCV treatment during the study period. Annual HCV treatment rates during OST ranged between 1.3% (95% confidence interval [CI] 0.7-2.2) in 2005 and 2.6% (95% CI 1.9-3.5) in 2008 with no significant changes over time. HCV treatment uptake was not associated with age or gender, but associated with duration of active OST (adjusted odds ratio [aOR] 1.11 per year; 95% CI 1.07-1.15), high (> 80%) OST continuity (aOR 1.62; 95% CI 1.17-2.25), and heavy benzodiazepine use (aOR 0.65; 95% CI 0.49-0.87). Conclusions Cumulative HCV treatment uptake among OST patients notified with HCV infection in Norway between 2004 and 2013 was 14%. Annual treatment rates during OST remained unchanged below 3% per year. High continuity of OST over time and absence of heavy benzodiazepine use predicted HCV treatment uptake. Increased awareness for HCV among OST patients is needed as tolerable and efficient directly acting antiviral treatment is being introduced