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Background: The World Health Organization (WHO) has set a goal to eliminate hepatitis C virus (HCV) infection by 2030, including a 90% reduction of HCV incidence. With the introduction of a needle syringe program (NSP) in Stockholm, Sweden, and unrestricted availability of direct acting antiviral (DAA) treatment, we investigate the change of prevalence and incidence of HCV infection among people who inject drugs (PWID) over time., Methods: All persons attending the Stockholm NSP 2013-2021 (n=4,138) were included. The prevalence of viremic HCV infection was investigated yearly. For incidence analysis, PWID at risk with at least one follow-up test were included. Participants were divided into naive defined as anti-HCV negative (n=791), and exposed, defined as anti-HCV positive with a negative HCV RNA (n=1,030). Risk factors for HCV infection were analyzed using parametric exponential proportional hazards regression models., Results: The prevalence of viremic HCV infection decreased from 62% to 30% year 2013-2021 while the prevalence of cured after treatment increased from 0 to 22%, corresponding to 42% cured after treatment out of eligible in 2021. The overall incidence rate in naive was 16.9 (95% CI 15.0-19.0) and in exposed 12.8 (95% CI 11.6-14.2) per 100 person years (PY) and was not significantly reduced years 2013-2015 to 2020-2021 in either group. Risk factors for incident HCV infection in multivariable analysis were sharing needles/syringes, younger age, custody/prison past year, and homelessness, whereas opioid agonist treatment was protective., Conclusion: The prevalence of HCV was halved in PWID as unrestricted DAA treatment became available and NSP was established in Stockholm. However, overall incidence was not reduced. To meet the WHO incidence goal, targeting PWID with high injection risk behaviors for testing and treatment is essential, along with engagement in harm reduction services., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Martin Kåberg has received honoraria for lectures/consultancy from AbbVie, Gilead, MSD and has received research grants from Gilead. Olav Dalgard received research grants from MSD and Gilead and fees for lectures from Abbvie, Gilead and MSD. Soo Aleman has received honoraria for lectures and educational events from Gilead, AbbVie, MSD and Biogen, and reports grants from Gilead and AbbVie, (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Norway aims to eliminate hepatitis C virus (HCV) infection within the end of 2023. Before the introduction of direct-acting antivirals, the prevalence of chronic HCV infection among people who inject drugs (PWID) in Oslo was 40-45 %. The primary aim of the study was to assess changes in HCV prevalence among PWID in Oslo from 2018 to 2021. The secondary aim was to assess change in prevalence in selected subgroups., Methods: Point prevalence studies were conducted in 2018 and 2021 among PWID attending low-threshold health services in downtown Oslo. Assessments included blood samples analysed for anti-HCV and HCV RNA, and a questionnaire about drug use. Information about previous HCV treatment was only collected in the 2021 cohort. We calculated HCV RNA prevalence estimates for 2018 and 2021 and used logistic regression analysis to identify factors associated with detectable HCV RNA and previous HCV treatment., Results: A total of 281 and 261 participants were included in 2018 and 2021, respectively. The median age was 40.6 and 44.0 years, 73.7 % and 72.8 % were men, and 74.5 % and 78.6 % reported recent (past four weeks) injecting drug use, respectively. HCV RNA prevalence decreased significantly from 26.3 % (95 % CI 21.3-31.9) in 2018 (74 of 281) to 14.2 % (95 % CI 10.2-19.0) in 2021 (37 of 261). The odds of detectable HCV RNA were significantly lower in 2021 compared to 2018 (aOR 0.41; 95 % CI 0.26-0.67). In the 2021 cohort, detectable HCV RNA was associated with recent amphetamine injecting (aOR 7.21; 95 % CI 1.41-36.95), and mixed heroin/amphetamine injecting (aOR 7.97; 95 % CI 1.55-41.07). The odds of previous treatment were lower among women (aOR 0.52; 95 % CI 0.27-1.00)., Conclusion: A substantial decrease in HCV RNA prevalence among PWID in Oslo between 2018 and 2021 was observed. To reach elimination, adaptive services must be further developed., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: OD has received lecture fees from AbbVie and research grants from AbbVie and MSD. KU has received lecture fees from AbbVie, MSD and Gilead and research grant from Gilead. ØB has received lecture fees from AbbVie, MSD and Gilead. TF has received lecture fees from AbbVie. HM has received lecture fees from Abbie, Gilead and MSD. EO, HS and LECW have no conflicts of interest to declare. No pharmaceutical grants were received in the development of this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declarations of Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. K.M., A.F., L.W., and K.B.K. have no conflicts of interest. K.U. has received lecture grants from Gilead and MSD. J.H. is an industry-sector Ph.D-student funded by AbbVie and the Norwegian Research Council. No funding was received from AbbVie related to this study. O.D. has received lecture, research support and consultancy fees from MSD and Abbvie. H.M. has received lecture and consultancy fees from Gilead, MSD and Abbvie. No pharmaceutical grants were received in the development of this study., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: People who inject drugs (PWID) are at a high risk of hepatitis C virus (HCV) infection. HCV cure is associated with improved patient-reported outcomes (PROs), but there are little data among PWID. This study aimed to assess the change in PROs during and after HCV direct-acting antiviral (DAA) treatment., Methods: This analysis used data from 2 clinical trials of DAA treatment in PWID. PROs assessed included health-related quality of life, social functioning, psychological distress, housing, and employment. Generalized estimating equations and group-based trajectory modeling were used to assess changes in PROs over time., Results: No significant changes in the 3-level version of EQ-5D scores, EQ visual analogue scale scores, social functioning, psychological distress, and housing were observed over the 108-week study period. There was a significant increase in the proportion of participants employed (18% [95% confidence interval (CI) 12%-23%] at baseline to 28% [95% CI 19%-36%] at the end of the study). Participants were more likely to be employed at 24 weeks and 108 weeks after commencing treatment. Having stable housing increased the odds of being employed (odds ratio 1.70; 95% CI 1.00-2.90). The group-based trajectory modeling demonstrated that most outcomes remained stable during and after DAA treatment., Conclusions: Although no significant improvement was identified in health-related quality of life after HCV DAA treatment, there was a modest but significant increase in employment during study follow-up. The study findings support the need for multifaceted models of HCV care for PWID addressing a range of issues beyond HCV treatment to improve quality of life., (Copyright © 2023. Published by Elsevier Inc.)

Background: The aims were to evaluate HCV treatment effectiveness, estimate reinfection rates, and demonstrate the feasibility of reinfection surveillance and retreatment among marginalized people who inject drugs (PWID)., Methods: Prospective observational study including consecutive HCV RNA positive individuals attending a low-threshold clinic in Oslo, Norway, between 2013 and 2020. Participants were offered individually tailored HCV treatment and post-treatment HCV RNA surveillance at three months intervals., Results: Of 488 HCV RNA positive individuals, 363 initiated treatment (median age 48.7 years, 72.5% male, 17.2% liver cirrhosis, 54.3% unstable housing). All participants had a history of injecting drug use, 71.1% received opioid agonist treatment, and 70.1% reported recent (past 3 months) injecting. In intention-to-treat analysis, excluding those with HCV RNA results pending, virologic response was achieved in 306 of 340 (90.0%) participants. In modified intention-to-treat analysis, also excluding those with loss to follow-up during treatment, virologic response was achieved in 306 of 323 (94.7%). Virologic response was not associated with recent injecting drug use or socio-demographic factors. Reinfection surveillance was accomplished in 297 individuals (308.2 PY of follow-up; median 0.50 years). Eight cases of reinfection were detected for an incidence of 2.60/100 PY (95% CI 1.12-5.11) overall, and 3.74/100 PY (95% CI 1.62-7.37) among those with injecting drug use during follow-up (n = 205). Reinfection was associated with younger age (IRR 0.37; 95% CI 0.18-0.74), and all cases occurred in participants aged below 49 years with ongoing injecting drug use who reported mixed heroin/amphetamine injecting. Successful retreatment was provided in all cases and no second reinfections were observed., Conclusion: The findings consolidate previous evidence supporting the effectiveness of HCV treatment among PWID, provide novel data on reinfection rates and associated factors, and demonstrate the feasibility of reinfection surveillance and retreatment in a real-world setting., Competing Interests: Declarations of Interest Håvard Midgard, Kjersti Ulstein, Øystein Backe and Olav Dalgard report personal lecture and advisory fees from Abbvie, Gilead and MSD. The other authors report no potential conflicts of interest. The HCV clinic has previously used a mobile FibroScan(Ⓡ) donated from Abbvie., (Copyright © 2021. Published by Elsevier B.V.)

Background & Aims: HCV reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and those receiving opioid agonist therapy (OAT)., Methods: We searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies., Results: Thirty-six studies were included (6,311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% CI 4.1-8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI 4.3-9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI 2.5-5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95% CI 3.1-9.5) and direct-acting antiviral (3.9/100 person-years; 95% CI 2.5-5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI 0.8-2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI 4.0-8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI 3.4-12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio [aRR] per year increase in mean/median follow-up 0.77; 95% CI 0.69-0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR 3.50; 95% CI 1.62-7.53), and those with recent drug use not receiving OAT (aRR 3.96; 95% CI 1.82-8.59) had higher reinfection rates., Conclusion: HCV reinfection risk following treatment was higher among people with recent drug use and lower among those receiving OAT. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment., Lay Summary: Our findings demonstrate that although reinfection by hepatitis C virus occurs following successful treatment in people with recent drug use, the rate of hepatitis C reinfection is lower than the rates of primary infection reported in the literature for this population - reinfection should not be used as a reason to withhold therapy from people with ongoing injecting drug use. The rate of hepatitis C reinfection was lowest among people receiving opioid agonist therapy with no recent drug use. These data illustrate that harm reduction services are required to reduce the reinfection risk, while regular post-treatment hepatitis C assessment is required for early detection and retreatment., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Direct-acting antiviral therapy for hepatitis C virus (HCV) infection is safe and effective, but there are little data among people who have recently injected drugs. This study evaluated the efficacy, and safety of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin for chronic HCV genotype (G) 1 among people with recent injecting drug use and/or receiving OST., Methods: D3FEAT is an international open-label study that recruited treatment-naïve participants with recent injecting drug use (previous 6 months) and/or receiving OST with chronic HCV G1 infection between June 2016 and February 2017 in seven countries. Participants received paritaprevir/ritonavir, ombitasvir, dasabuvir with (G1a) or without ribavirin (G1b) administered twice daily in a one-week electronic blister pack (records timing of each dose) for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (SVR12)., Results: Among 87 participants (median age 48 years), 23% were female, 8% had cirrhosis, and 90% had G1a. Overall, 71% were receiving OST, 61% injected in the previous six months, 45% injected in the previous month, and 15% injected > daily. Treatment completion was 97% (84 of 87). There were no virological breakthroughs, but three discontinuations (loss to follow-up, n = 1; non-adherence, n = 1; incarceration, n = 1). SVR was 91% (79 of 87, 95% CI, 83%-96%). Five participants who completed treatment did not have SVR (loss to follow-up, n = 1; death, n = 1; virologic relapse, n = 3). Drug use prior to and during treatment did not impact SVR12. Treatment-related adverse events were observed in 46 (53%) patients (six grade 3, no grade 4). Five (6%) patients had at least one serious adverse event (two possibly/probably related to therapy; nausea and myoclonus). Two cases of reinfection were observed., Conclusion: Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for 12 weeks is effective among people with HCV genotype 1 with recent injecting drug use and/or receiving OST., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: This study investigated treatment adherence among people with recent injecting drug use in a study of sofosbuvir/velpatasvir therapy for HCV infection., Methods: SIMPLIFY is an international open-label, single-arm multicentre study that recruited participants with recent injecting drug use (previous six months) and chronic HCV genotype (G) 1-6 infection between March and October 2016 in seven countries (19 sites). Participants received sofosbuvir/velpatasvir once-daily for 12 weeks administered in a one-week electronic blister pack (records the time and date of each dose) for 12 weeks. We evaluated non-adherence (<90% adherent) as measured by electronic blister-pack assessed using logistic regression and generalised estimating equations (continuous) with detailed analyses of dosing dynamics., Results: Among 103 participants, 97% (n = 100) completed treatment. Median adherence to therapy was 94%. Overall, 32% (n = 33) were considered non-adherent (<90% adherence). Adherence significantly decreased over the course of therapy. Recent stimulant injecting (cocaine and/or amphetamines) at treatment initiation and during treatment was independently associated with non-adherence. Inconsistent dose timing (standard deviation of daily dose timing of ≥240 min) was also independently associated with non-adherence to therapy. Factors associated with inconsistent dose timing included lower levels of education and recent stimulant injecting. SVR was similar among adherent and non-adherent populations (94% vs. 94%, P = 0.944)., Conclusion: This study demonstrated high adherence to once-daily sofosbuvir/velpatasvir therapy among a population of people with recent injecting drug use. Recent stimulant injecting prior to and during DAA therapy and inconsistent dose-timing during treatment was associated with non-adherence. However, there was no impact of non-adherence on response to therapy, suggesting that adherence is not a significant barrier to successful DAA therapy in people with recent injecting drug use., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background & Aims: Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years., Methods: We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID., Results: At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12-24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18-79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5-17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20-80%., Conclusions: The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe., Lay Summary: Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment)., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: There are few data on treatment for hepatitis C virus (HCV) infection among people with ongoing injecting drug use. This study evaluated the efficacy of response-guided therapy for chronic HCV genotypes 2/3 infection among people with ongoing injecting drug use or receiving opioid substitution therapy (OST). A secondary aim was to identify predictors of HCV treatment response., Methods: ACTIVATE was a multicentre clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Participants were recruited from drug treatment clinics, private practices, hospital clinics and community clinics in Australia, Canada, and five countries in Europe. The primary study outcome was sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment)., Results: Among 93 people with ongoing injecting drug use or receiving OST treated for HCV genotype 2/3, 59% had recently (past month) injected drugs, 77% were receiving OST and 56% injected drugs during therapy. Overall SVR was 66% (61/93). SVR was 84% in those with undetectable HCV RNA at week 4 (12 weeks) compared to 38% in those without (24 weeks). In adjusted analysis, cirrhosis vs. no/mild fibrosis [adjusted OR (aOR) 0.33, 95% CI 0.13, 0.86] predicted reduced SVR, while response at week 4 was associated with increased SVR [aOR 8.11, 95% CI 2.73, 24.10]. Recent injecting drug use at baseline or during therapy was not associated with SVR., Conclusion: This study demonstrates that people with recent injecting drug use or OST with chronic HCV can achieve responses to interferon-based therapy similar to other populations, despite injecting drugs prior to or during therapy. Cirrhosis was predictive of reduced response to HCV therapy, while response at week 4 (despite shortened therapy) was predictive of improved response., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The risk of hepatitis C virus (HCV) reinfection due to continued injecting risk behaviours might remain a barrier to HCV treatment among people who inject drugs. We aimed to evaluate changes in risk behaviours during and following HCV treatment among people with ongoing injecting drug use or receiving opioid substitution treatment (OST)., Methods: ACTIVATE was an international multicentre clinical trial conducted between 2012 and 2014. Participants with HCV genotypes 2/3 infection were treated with peg-interferon/ribavirin for 12 or 24 weeks and completed a self-administered behavioural questionnaire at each study visit. The impact of time in treatment and follow-up on longitudinally measured recent (past month) behavioural outcomes was evaluated using generalized estimating equations., Results: Among 93 enrolled participants (83% male, median age 41 years), 55 (59%) had injected in the past month. Any injecting drug use decreased during HCV treatment and follow-up (OR 0.89 per incremental study visit; 95% CI 0.83-0.95). No significant changes were found in ≥daily injecting (OR 0.98; 95% CI 0.89-1.07), use of non-sterile needles (OR 0.94; 95% CI 0.79-1.12), sharing of injecting paraphernalia (OR 0.87; 95% CI 0.70-1.07) or non-injecting drug use (OR 1.01; 95% CI 0.92-1.10). Hazardous alcohol use decreased throughout (OR 0.56; 95% CI 0.40-0.77) and OST increased between enrolment and end of treatment (OR 1.48; 95% CI 1.07-2.04)., Conclusions: Recent injecting drug use and hazardous alcohol use decreased, while OST increased during and following HCV treatment among participants with ongoing injecting drug use. These findings support further expansion of HCV care among PWID., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection, including an estimated 7.5 million people who have recently injected drugs (PWID). There is an additional large, but unquantified, burden among those PWID who have ceased injecting. The incidence of HCV infection among current PWID also remains high in many settings. Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase, despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates >95%. As a result of this important clinical breakthrough, there is potential to reverse the rising burden of advanced liver disease with increased treatment and strive for HCV elimination among PWID. Unfortunately, there are many gaps in knowledge that represent barriers to effective prevention and management of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table consisted of a one-day workshop held on 6 September, 2016, in Oslo, Norway, prior to the International Symposium on Hepatitis in Substance Users (INHSU 2016). International experts in drug and alcohol, infectious diseases, and hepatology were brought together to discuss the available scientific evidence, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper highlights the outcomes of the roundtable discussion focused on future research priorities for enhancing HCV prevention, testing, linkage to care and DAA treatment for PWID as we strive for global elimination of HCV infection., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Injecting risk behaviours among people who inject drugs (PWID) and high-risk sexual practices among men who have sex with men (MSM) are important routes of hepatitis C virus (HCV) transmission. Current direct-acting antiviral treatment offers unique opportunities for reductions in HCV-related liver disease burden and epidemic control in high-risk groups, but these prospects could be counteracted by HCV reinfection due to on-going risk behaviours after successful treatment. Based on existing data from small and heterogeneous studies of interferon-based treatment, the incidence of reinfection after sustained virological response range from 2-6/100 person years among PWID to 10-15/100 person years among human immunodeficiency virus-infected MSM. These differences mainly reflect heterogeneity in study populations with regards to risk behaviours, but also reflect variations in study designs and applied virological methods. Increasing levels of reinfection are to be expected as we enter the interferon-free treatment era. Individual- and population-level efforts to address and prevent reinfection should therefore be undertaken when providing HCV care for people with on-going risk behaviour. Constructive strategies include acknowledgement, education and counselling, harm reduction optimization, scaled-up treatment including treatment of injecting networks, post-treatment screening, and rapid retreatment of reinfections., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: On-going risk behaviour can lead to hepatitis C virus (HCV) reinfection following successful treatment. We aimed to assess the incidence of persistent HCV reinfection in a population of people who inject drugs (PWID) who had achieved sustained virological response (SVR) seven years earlier., Methods: In 2004-2006 we conducted a multicentre treatment trial comprising HCV genotype 2 or 3 patients in Sweden, Norway and Denmark (NORTH-C). Six months of abstinence from injecting drug use (IDU) was required before treatment. All Norwegian patients who had obtained SVR (n=161) were eligible for participation in this long-term follow-up study assessing virological and behavioural characteristics., Results: Follow-up data were available in 138 of 161 (86%) individuals. Persistent reinfection was identified in 10 of 94 (11%) individuals with a history of IDU prior to treatment (incidence rate 1.7/100 person-years (PY); 95% CI 0.8-3.1) and in 10 of 37 (27%) individuals who had relapsed to IDU after treatment (incidence rate 4.9/100 PY; 95% CI 2.3-8.9). Although relapse to IDU perfectly predicted reinfection, no baseline factor was associated with reinfection. Relapse to IDU was associated with age <30 years (vs. ⩾40 years) at treatment (adjusted odds ratio [aOR] 7.03; 95% CI 1.78-27.8) and low education level (aOR 3.64; 95% CI 1.44-9.18)., Conclusions: Over time, persistent HCV reinfection was common among individuals who had relapsed to IDU after treatment. Reinfection should be systematically addressed and prevented when providing HCV care for PWID., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Telaprevir plus pegylated interferon/ribavirin (TPV+PegIFN/RBV) remains a therapeutic option for chronic hepatitis C virus (HCV) genotype (GT) 1 infection in many regions. We conducted two open-label, phase IIIb trials comparing safety and efficacy of all-oral ombitasvir/paritaprevir/ritonavir and dasabuvir±ribavirin (OBV/PTV/r+DSV±RBV) and TPV+PegIFN/RBV., Methods: Treatment-naïve (MALACHITE-I) or PegIFN/RBV-experienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r+DSV+weight-based RBV, OBV/PTV/r+DSV (treatment-naïve, GT1b-infected patients only), or 12weeks of TPV+PegIFN+weight-based RBV and 12-36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12weeks post-treatment (SVR12). Patient-reported outcome questionnaires evaluated mental and physical health during the studies., Results: Three hundred eleven treatment-naïve and 148 treatment-experienced patients were randomized and dosed. Among treatment-naïve patients, SVR12 rates were 97% (67/69) and 82% (28/34), respectively, in OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV-treated GT1a-infected patients; SVR12 rates were 99% (83/84), 98% (81/83), and 78% (32/41) in OBV/PTV/r+DSV+RBV, OBV/PTV/r+DSV, and TPV+PegIFN/RBV-treated GT1b-infected patients. Among treatment-experienced patients, SVR12 rates were 99% (100/101) and 66% (31/47) with OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV. Mental and physical health were generally better with OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV. Rates of discontinuation due to adverse events (0-1% and 8-11%, respectively, p<0.05) and rates of hemoglobin decline to <10g/dl (0-4% and 34-47%, respectively, p<0.05) were lower for OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV., Conclusions: Among non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97-99% with 12week, multi-targeted OBV/PTV/r+DSV±RBV regimens and 66-82% with 24-48 total weeks of TPV+PegIFN/RBV. OBV/PTV/r+DSV±RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

In high income countries, the majority of new and existing hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). In many low and middle income countries large HCV epidemics have also emerged among PWID populations. The burden of HCV-related liver disease among PWID is increasing, but treatment uptake remains extremely low. There are a number of barriers to care which should be considered and systematically addressed, but should not exclude PWID from HCV treatment. The rapid development of interferon-free direct-acting antiviral (DAA) therapy for HCV infection has brought considerable optimism to the HCV sector, with the realistic hope that therapeutic intervention will soon provide near optimal efficacy with well-tolerated, short duration, all oral regimens. Further, it has been clearly demonstrated that HCV treatment is safe and effective across a broad range of multidisciplinary healthcare settings. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment and treatment in this group are urgently needed. These recommendations demonstrate that treatment among PWID is feasible and provide a framework for HCV assessment and care. Further research is needed to evaluate strategies to enhance testing, linkage to care, treatment, adherence, viral cure, and prevent HCV reinfection among PWID, particularly as new interferon-free DAA treatments for HCV infection become available., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background & Aims: There is a paucity of unbiased data on the natural history of hepatitis C virus (HCV) infection in injecting drug users (IDUs). The purpose of this study was to assess the risk of developing advanced fibrosis associated with chronic hepatitis C (CHC) infection among injecting drug users (IDUs) who underwent an autopsy., Methods: A longitudinal cohort design was applied, in which the stage of liver fibrosis in anti-HCV positive IDUs with or without chronic HCV infection was assessed in liver tissue from autopsies performed up to 35 years after HCV exposure. The cohort originated from 864 IDUs consecutively admitted for drug abuse treatment 1970-1984. Stored sera, mostly drawn at the time of admission for drug treatment, were available in 635 subjects. 220 out of 523 anti-HCV positive subjects had died before 2009. Liver tissue from autopsies was available from 102/220 subjects, of which 61 were HCV RNA positive. Liver sections were classified according to METAVIR scores for fibrosis. Two pathologists, both blinded for serologic results, scored sections of liver tissue., Results: Among HCV RNA positive subjects 16.4% (10/61) had septal fibrosis (F3) or cirrhosis (F4) compared to 2.4% (1/41) among anti HCV positive/HCV RNA negative subjects (p=0.026). Of 18 HCV RNA positive subjects autopsied <15 years after HCV exposure none had F3 or F4. Among subjects autopsied >25 years after exposure 35% (6/17) had F3-F4., Conclusions: Among IDUs chronically infected by HCV, 1/3 developed septal fibrosis or cirrhosis 25 years or more after exposure., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: The course of chronic hepatitis C virus (HCV) in injecting drug users (IDUs) has not been well described. The aim of this study was to compare long-term all-cause and liver-related mortality among anti-HCV positive IDUs with and without persisting HCV infection., Methods: A retrospective-prospective controlled cohort design was applied. All IDUs admitted to resident drug treatment (1970-1984) and with available stored sera were screened for anti-HCV antibody. Anti-HCV positive individuals were further tested for the presence of HCV RNA. All-cause and liver-related mortality was compared between HCV RNA positive (n=328) and HCV RNA negative individuals (n=195). The observation was accomplished through register linkage to national registers. Mean observation time was 33 years., Results: All-cause mortality rate was 1.85 (95% CI 1.62-2.11) per 100 person-years, male 2.11 (95% CI 1.84-2.46), female 1.39 (95% CI 1.07-1.79). Mortality rates were not influenced by persisting HCV infection. Main causes of death were intoxications (45.0%), suicide (9.1%), and accidents (8.2%). Liver disease was the cause of death in 7.5% of deaths among HCV RNA positive subjects. Five of 13 deaths among male IDUs with persisting HCV infection occurring after the age of 50 years were caused by liver disease., Conclusions: The all-cause mortality in IDUs is high and with no difference between HCV RNA positive and HCV RNA negative individuals, the first three decades after HCV transmission. However, among IDUs with chronic HCV infection who have survived until 50years of age, HCV infection emerges as the main cause of death., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: We have shown that 12-14 weeks treatment is effective in HCV-2 or -3 patients with undetectable HCV-RNA after 4 weeks of therapy (rapid virologic response)., Patients: To identify predictors of sustained virologic response, rapid virologic response and relapse following short treatment, we pooled data from the original Italian and Norwegian studies. Four hundreds and three patients were treated with PegIFN alpha-2b (1.0, n=281 or 1.5 microg/kg, n=122) and ribavirin (800-1200 mg) for 12-14 or 24 weeks, depending on negative or positive HCV-RNA at week 4., Results: Sustained virologic response differed between cases with and without rapid virologic response (85% versus 62%, P<0.0001), mild and severe fibrosis (83% versus 67%, P=0.004), and HCV-2 and -3 (81% versus 73%, P=0.05). In a regression model, RVR (odds ratio 3.49, confidence interval 1.73-5.36) and mild fibrosis (odds ratio 2.91, confidence interval 1.57-5.38) independently predicted sustained virologic response. Rapid virologic response was obtained in 274 (68%) patients, 163/242 (67%) HCV-2, and 111/161 (69%) HCV-3. Patients with RVR had more frequently mild fibrosis (70% versus 54%, P=0.03), and high PegIFN dose (78% versus 64%, P=0.005). In a regression model, mild fibrosis independently predicted rapid virologic response (odds ratio 1.87, confidence interval 1.10-3.16). In rapid virologic response patients, sustained virologic response was achieved in 85% of both HCV-2 and -3. Virologic relapse was observed in 10.6% rapid virologic response patients and was more frequent among those with low ALT (14% versus 2%, P=0.04)., Conclusion: In HCV-2 or -3, the HCV-RNA status after 4 weeks of therapy may guide treatment duration. HCV-2 and HCV-3 patients with severe fibrosis are less likely to experience both rapid virologic response and sustained virologic response, and more frequently relapse after a 12 or 14 weeks duration of antiviral therapy.