Hepatitis C Virus In People Who Inject Drugs Research Articles

Barriers and enablers to testing for hepatitis C virus infection in people who inject drugs – a scoping review of the qualitative evidence

BackgroundInjection drug use is the primary mode of transmission of hepatitis C virus (HCV) infection in the developed world and guidelines recommend screening individuals with current or history of injection drug use for HCV; however, the majority of those living with HCV in Canada are not aware of their positive status. This low level of HCV status awareness suggests that screening is not effective with current testing strategies. The aim of this review is to determine what barriers and enablers people who inject drugs (PWID) experience surrounding testing for HCV to help inform the development of an engaging testing strategy.MethodsComprehensive literature searches were conducted using Medline, Embase and CINAHL in February 2021. Included studies investigated the barriers and enablers to testing for HCV in PWID and the experiences of PWID in testing for HCV. Studies were included if they were qualitative or mixed-methods design, involved people with current injection drug use or those with a history of injecting drugs, and were written in the English language. Studies were compared and common themes were coded and analyzed.ResultsThe literature search resulted in 1554 citations and ultimately nine studies were included. Common barriers included self-perception of low risk for HCV, fear of diagnosis, stigma associated with IV drug use and HCV, antipathy in relation to mainstream health care services, limited knowledge about HCV, lack of rapport with provider, lack of motivation or competing priority of drug use, and limited awareness of new treatment options. Common enablers to testing included increasing awareness of HCV testing and treatment and providing positive narratives around HCV care, positive rapport with provider, accessible testing options and individualized care.ConclusionWhile there has been some qualitative research on barriers and enablers to testing for HCV in PWID more research is needed to focus on this research question as a primary objective in order to provide more understanding from the participant’s perspective.

917. Accessible HCV Care for People Who Inject Drugs: Randomized Clinical Trial Comparing Low-Threshold Treatment at a Syringe Service Program Versus Facilitated Referral

BackgroundTo achieve hepatitis C virus (HCV) elimination, treatment programs need to be developed to engage, treat, and cure people who inject drugs (PWID).MethodsWe present final data from the Accessible Care Trial for curing HCV in PWID. The randomized clinical trial compared on-site, low-threshold HCV treatment with care-coordination at a NYC syringe service program (Accessible Care) with facilitated referral to local providers through a patient navigation program (Usual Care). Eligible participants were HCV RNA+ and had injected drugs in the past 90 days. Participants were randomized 1:1 to the Accessible Care or Usual Care arm. The primary endpoint was achievement of sustained virologic response (SVR12) within 12 months of enrollment. Secondary endpoints examined rates HCV care cascade step completion from referral to clinician, attending clinical visit, baseline lab testing, treatment initiation, and cure.ResultsAmong the 572 participants screened, 167 met eligibility criteria and were enrolled, with two excluded post-randomization (N=165). Demographics were similar with a median age of 41 years; 22% women; 59% Hispanic and 5% non-Hispanic black. At baseline, 84% of participants had injected drugs in the past 30 days with those averaging 22 injections/month, 70% were receiving either methadone or buprenorphine, 57% were recently homeless, 7% were HIV+, and 11% were HCV treatment experienced. In the intention-to-treat analysis, 55/82 (67.1%) of the Accessible Care arm and 19/83 (22.9%) of the Usual Care arm achieved SVR12 (p< 0.001). The SVR12 rates of those starting therapy were 55/64 (85.9%) and 19/22 (86.3%) in the two arms (p=0.96). Loss to follow-up (12.2% and 16.9%, p=0.51) was similar in the two arms. Significantly more participants in the Accessible Care arm achieved all steps in the care cascade with the greatest attrition in the Usual Care arm seen in referral to clinician and attending clinical visit. ConclusionAmong HCV RNA+ PWID significantly higher rates of cure were achieved using the Accessible Care model focused on low-threshold, destigmatized, flexible HCV care compared to facilitated referral. To achieve HCV elimination, expansion of treatment programs specifically geared toward engaging PWID is paramount. Disclosures Benjamin Eckhardt, MD, MS, Gilead Sciences (Grant/Research Support) Shashi Kapadia, MD, Gilead Sciences Inc (Grant/Research Support) Kristen Marks, MD, Gilead Sciences (Grant/Research Support)

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

The 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. INTRO-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. Integrated 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. ClinicalTrials.gov.no NCT03155906.

Systematic Review and Meta-Analysis of Global Prevalence of HBsAg and HIV and HCV Antibodies among People Who Inject Drugs and Female Sex Workers.

The main objective of this study was to evaluate the prevalence of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), hepatitis C virus (HCV) and hepatitis B virus (HBV) and their co-infections among people who inject drugs (PWID) and female sex workers (FSWs). Data sources were searched from January 2008 to October 2018 in different databases. Data were analyzed in Stata 16 software using the Metaprop command. The results showed that the prevalence of HIV, HCV and HBV among PWID was 15%, 60% and 6%, respectively. The prevalence of HIV, HCV and HBV among FSWs was 5%, 1% and 3%, respectively. The prevalence of HIV/HCV, HIV/HBV, HCV/HBV and HIV/HCV/HBV co-infections among PWID was 13%, 2%, 3% and 2%, respectively. The prevalence of HIV/HCV and HIV/HBV co-infections among FSWs was 3% and 1%, respectively. The results show that the prevalence of HCV and HIV infections in PWID and the prevalence of HIV in FSWs is higher than their prevalence in the general population. Interventions for the prevention of HIV and HCV in PWID appear to be poor, and may not be sufficient to effectively prevent HIV and HCV transmission.

The status of hepatitis C virus infection among people who inject drugs in the Middle East and North Africa.

Background and aimsPeople who inject drugs (PWID) are a key population at high risk of hepatitis C virus (HCV) infection. The aim of this study was to delineate the epidemiology of HCV in PWID in the Middle East and North Africa (MENA).MethodsSyntheses of data were conducted on the standardized and systematically assembled databases of the MENA HCV Epidemiology Synthesis Project, 1989–2018. Random‐effects meta‐analyses and meta‐regressions were performed. Meta‐regression variables included country, study site, year of data collection and year of publication [to assess trends in HCV antibody prevalence over time], sample size and sampling methodology. Numbers of chronically infected PWID across MENA were estimated. The Shannon Diversity Index was calculated to assess genotype diversity.ResultsBased on 118 HCV antibody prevalence measures, the pooled mean prevalence in PWID for all MENA was 49.3% [95% confidence interval (CI) = 44.4–54.1%]. The country‐specific pooled mean ranged from 21.7% (95% CI = 4.9–38.6%) in Tunisia to 94.2% (95% CI = 90.8–96.7%) in Libya. An estimated 221 704 PWID were chronically infected, with the largest numbers found in Iran at 68 526 and in Pakistan at 46 554. There was no statistically significant evidence for a decline in HCV antibody prevalence over time. Genotype diversity was moderate (Shannon Diversity Index of 1.01 out of 1.95; 52.1%). The pooled mean percentage for each HCV genotype was highest in genotype 3 (42.7%) and in genotype 1 (35.9%).ConclusionHalf of people who inject drugs in the Middle East and North Africa appear to have ever been infected with hepatitis C virus, but there are large variations in antibody prevalence among countries. In addition to > 200 000 chronically infected current people who inject drugs, there is an unknown number of people who no longer inject drugs who may have acquired hepatitis C virus during past injecting drug use. Harm reduction services must be expanded, and innovative strategies need to be employed to ensure accessibility to hepatitis C virus testing and treatment.

Integrated treatment of hepatitis C virus infection among people who inject drugs: study protocol for a randomised controlled trial (INTRO-HCV)

BackgroundA large proportion of people who inject drugs (PWID) living with hepatitis C virus (HCV) infection have not been treated. It is unknown whether inclusion of HCV diagnostics and treatment into integrated substance use disorder treatment and care clinics will improve uptake and outcome of HCV treatment in PWID. The aim is to assess the efficacy of integrating HCV treatment to PWID and this paper will present the protocol for an ongoing trial.MethodsINTRO-HCV is a multicentre, randomised controlled clinical trial that will compare the efficacy of integrated treatment of HCV in PWID with the current standard treatment. Integrated treatment includes testing for HCV, assessing liver fibrosis with transient elastography, counselling, treatment delivery, follow-up and evaluation provided by integrated substance use disorder treatment and care clinics. Most of these clinics for PWID provide opioid agonist therapy while some clinics provide low-threshold care without opioid agonist therapy. Standard care involves referral to further diagnostics, treatment and treatment follow-up given in a hospital outpatient clinic with equivalent medications. The differences between the delivery platforms in the two trial arms involve use of a drop-in approach rather than specific appointment times, no need for additional travelling, less blood samples taken during treatment, and treatment given from already known clinicians. The trial will recruit approximately 200 HCV infected individuals in Bergen and Stavanger, Norway. The primary outcomes are time to treatment initiation and sustained virologic response, defined as undetectable HCV RNA 12 weeks after end of treatment. Secondary outcomes are cost-effectiveness, treatment adherence, changes in quality of life, fatigue and psychological well-being, changes in drug use, infection related risk behaviour, and risk of reinfection. The target group is PWID with HCV diagnosed receiving treatment and care within clinics for PWID.DiscussionThis study will inform on the effects of an integrated treatment program for HCV in clinics for PWID compared to standard care aiming to increase access to treatment and improving treatment adherence. If the integrated treatment model is found to be safe and efficacious, it can be considered for further scale-up.Trial registrationClinicalTrials.gov.no. NCT03155906.

How does Trieste treat HCV in PWID? An effective coordination between addiction treatment service (SerD), the infective disease department and the liver clinic

According to Italian data, people who inject drugs (PWID) have high prevalence of Hepatitis C Virus (HCV) infection (30-60%). PWID have inadequate access to directly acting antivirals (DAA) due to (1) their mistrust towards the healthcare system and (2) the lack of coordination between medical specialists who play a pivotal role in the diagnosis and treatment of HCV infection. We aim to describe the HCV -treatment cascade of care in Trieste on PWID.

Cost-effectiveness of Direct Antiviral Agents for Hepatitis C Virus Infection and a Combined Intervention of Syringe Access and Medication-assisted Therapy for Opioid Use Disorders in an Injection Drug Use Population.

There are too many plausible permutations and scale-up scenarios of combination hepatitis C virus (HCV) interventions for exhaustive testing in experimental trials. Therefore, we used a computer simulation to project the health and economic impacts of alternative combination intervention scenarios for people who inject drugs (PWID), focusing on direct antiviral agents (DAA) and medication-assisted treatment combined with syringe access programs (MAT+). We performed an allocative efficiency study, using a mathematical model to simulate the progression of HCV in PWID and its related consequences. We combined 2 previously validated simulations to estimate the cost-effectiveness of intervention strategies that included a range of coverage levels. Analyses were performed from a health-sector and societal perspective, with a 15-year time horizon and a discount rate of 3%. From a health-sector perspective (excluding criminal justice system-related costs), 4 potential strategies fell on the cost-efficiency frontier. At 20% coverage, DAAs had an incremental cost-effectiveness ratio (ICER) of $27 251/quality-adjusted life-year (QALY). Combinations of DAA at 20% with MAT+ at 20%, 40%, and 80% coverage had ICERs of $165 985/QALY, $325 860/QALY, and $399 189/QALY, respectively. When analyzed from a societal perspective (including criminal justice system-related costs), DAA at 20% with MAT+ at 80% was the most effective intervention and was cost saving. While DAA at 20% with MAT+ at 80% was more expensive (eg, less cost saving) than MAT+ at 80% alone without DAA, it offered a favorable value compared to MAT+ at 80% alone ($23 932/QALY). When considering health-sector costs alone, DAA alone was the most cost-effective intervention. However, with criminal justice system-related costs, DAA and MAT+ implemented together became the most cost-effective intervention.

Intensive Models of Hepatitis C Care for People Who Inject Drugs Receiving Opioid Agonist Therapy: A Randomized Controlled Trial.

Many people who inject drugs (PWID) are denied treatment for hepatitis C virus (HCV) infection, even if they are receiving opioid agonist therapy (OAT). Research suggests that HCV in PWID may be treated effectively, but optimal models of care for promoting adherence and sustained virologic response (SVR) have not been evaluated in the direct-acting antiviral (DAA) era. To determine whether directly observed therapy (DOT) and group treatment (GT) are more effective than self-administered individual treatment (SIT) in promoting adherence and achieving SVR among PWID receiving OAT. Three-group, randomized controlled trial conducted from October 2013 to April 2017. (ClinicalTrials.gov: NCT01857245). Three OAT programs in Bronx, New York. Persons aged 18 years and older with genotype 1 HCV infection who were willing to receive HCV therapy on site in the OAT program. Of 190 persons screened, 158 were randomly assigned to a study group and 150 initiated treatment: DOT (n= 51), GT (n= 48), and SIT (n= 51). 2 intensive interventions (DOT and GT) and 1 control condition (SIT). Primary: adherence, measured by using electronic blister packs. Secondary: HCV treatment completion and SVR 12 weeks after treatment completion. Mean age was 51 years; 65% of participants had positive results on urine drug testing during the 6 months before treatment, and 75% reported ever injecting drugs. Overall adherence, estimated from mixed-effects models using the daily timeframe, was 78% (95% CI, 75% to 81%) and was greater among participants randomly assigned to DOT (86% [CI, 80% to 92%]) than those assigned to SIT (75% [CI, 70% to 81%]; difference, 11% [CI, 5% to 18%]; Bonferroni-corrected P= 0.001). No significant difference in adherence was observed between participants randomly assigned to GT (80% [CI, 74% to 86%]) and those assigned to SIT (difference, 4.7% [CI, -2% to 11%]; Bonferroni-corrected P= 0.29). The HCV treatment completion rate was 97%, with no differences among groups (P= 0.53). Overall SVR was 94% (CI, 89% to 97%); the SVR rate was 98% in the DOT group, 94% in the GT group, and 90% in the SIT group (P= 0.152). These findings may not be generalizable to PWID not enrolled in OAT programs. All models of onsite HCV care delivered to PWID in OAT programs resulted in high SVR, despite ongoing drug use. Directly observed therapy was associated with greater adherence than SIT. National Institute on Drug Abuse and Gilead Sciences.

Prevalence of hepatitis C virus in young people who inject drugs in four Colombian cities: A cross-sectional study using Respondent Driven Sampling

BackgroundColombia has a growing population of young people who inject drugs (PWID). Despite the previously reported association of injection drug use with hepatitis c virus (HCV) in other countries, studies on HCV prevalence in PWID in Colombia are lacking. The objective of this study is to determine the prevalence, demographics, and correlations of risky injection behaviours in HCV seropositive PWID in four Colombian cities (Armenia, Bogotá, Cúcuta and Pereira). MethodsThis was a cross-sectional study carried out between January and June of 2014 that included 918 PWID from four Colombian cities, recruited by Respondent Driven Sampling. A survey was administered to each participant, and blood samples were collected. Binary logistic regression and multivariate analyses for each city were conducted. ResultsAverage participant age was 26 years (SD 6.5). Of all participants, 27.3% of PWID were HCV seropositive, of which 52% were 25 years old or younger. In Pereira, increased risk of HCV infection was found for PWID that: had a history of injection drug use of 5 years or more (AOR: 3.0, CI: 1.7–7.8); were between 25 and 28 years of age (AOR: 5.2, CI: 1.0–26.3); had higher injection frequency (AOR: 2.5, CI: 1.4–4.2), and daily use of gifted, sold, or rented needles or syringes (AOR: 4.5, CI: 1.0–7.1). Additionally, in Cucuta, being HIV seropositive appeared to be greatly associated with risk of HCV seropositivity (AOR: 16.9, CI: 3.5–81.5). ConclusionAlthough prevalence of HCV in PWID in Colombia is lower than that reported for other countries, the described demographic characteristics and diverse risky injection behaviors on each city, in the context of a young PWID population with a short injection drug use history, should be taken into account in order to guide efforts towards preventing and reducing risk of HCV infection in PWID in Colombia.

The hepatitis C cascade of care in people who inject drugs in Dar es Salaam, Tanzania.

SummaryThe World Health Organisation has recently called for hepatitis C virus (HCV) elimination and has identified people who inject drugs (PWID) as a key population to scale‐up screening and linkage to care. This study reports the cascade of care for HCV in PWID attending the largest opioid substitution treatment (OST) clinic in Dar‐es‐Salaam, Tanzania. Between February 2011 and March 2016, HCV serology for all PWID registered at the Muhimbili National Hospital OST clinic, Dar‐es‐Salaam were obtained from records. In 2015, consecutive HCV‐seropositive PWID were invited to undergo a clinical evaluation including epidemiological questionnaire, liver stiffness measurement (Fibroscan) and virological analysis (HCV RNA viral load and genotyping). During the study period, 1350 persons registered at the OST clinic: all had a HCV serology including 409 (30%) positive results. Among the HCV‐seropositive individuals, 207 (51%) were active attenders and 153 (37%) were enrolled for clinical assessment: 141 (92%) were male, median age: 38 years (IQR 34‐41), and 65 (44%) were co‐infected with HIV; 116 patients (76%) had detectable HCV RNA, with genotypes 1a (68%) and 4a (32%); 21 (17%) had clinically significant fibrosis (≥F2) and 6 (5%) had cirrhosis (F4). None were offered HCV treatment. Chronic hepatitis C among PWID enrolled in the OST centre in Dar‐es‐Salaam is frequent, but its continuum of care is insufficient; integration of HCV diagnosis and treatment should form a part of OST intervention in PWID in Tanzania.

Prevalence of hepatitis C and pre-testing awareness of hepatitis C status in 1500 consecutive PWID participants at the Stockholm needle exchange program

Background: People who inject drugs (PWID) are the driving force of the hepatitis C virus (HCV) epidemic. Still, treatment is scarcely offered and the awareness of HCV status in PWID is poor. Prevention includes clean needles, syringes and other paraphernalia. HCV awareness was investigated in 1500 PWID in a needle exchange program (NEP) in Stockholm, Sweden, together with HCV prevalence, and time to HCV infection after start of injection drug use.Methods: 1500 PWID in the Stockholm NEP were consecutively enrolled. At baseline, awareness of the individual pre-test HCV status was measured followed with tests for anti-HCV and HCV RNA if anti-HCV was positive.Results: Mean age of participants was 39 years and the mean time of injection drug use 18 (0–51) years. The overall anti-HCV prevalence was 82% whereof 76% were HCV RNA positive. Within 4 years after start of injection drug use 50% of the participants were anti-HCV positive. Self-awareness of HCV status was low. Hence, 32% who believed that they never have encountered HCV were anti-HCV positive, and 24% were HCV RNA positive. For those who reported not being aware of their HCV status 62% were anti-HCV positive, and 47% were HCV RNA positive.Conclusion: The very high prevalence of chronic HCV in PWID in Stockholm indicates that both measures for prevention with increased awareness of HCV, and a higher antiviral treatment utilisation in combination need to be implemented in order to reduce the HCV prevalence and combat the HCV epidemic.

Incidence of hepatitis C among people who inject drugs in Ireland

BackgroundComprehensive information on the incidence and duration of hepatitis C virus (HCV) infection for people who inject drugs (PWID) in Ireland is not available. We created an incidence curve of injecting drug use in Ireland and subsequently estimated incidence of hepatitis C virus (HCV) infection.MethodsAnonymised data from the National Drug Treatment Reporting System (NDTRS) were used to identify all people who inject drugs (PWIDs) and who entered drug treatment for the first time between 1991 and 2014. A curve, estimating the incidence of injecting, was created to plot PWIDs by year of commencing injecting. The curve was adjusted for missing data on PWIDs in treatment and for PWIDs who were never treated. An adjustment was made to account for injectors who had never shared injecting equipment. The incidence of HCV infection and chronic infection in PWIDs was estimated by applying published rates.ResultsBetween 1991 and 2014, 14,320 injectors were registered on NDTRS. The majority were young (median age 25 years), male (74%), lived in Dublin (73%) and injected an opiate (e.g. heroin) (94%). The estimated total number of injectors up to the end of 2014 was 16,382. An estimated 12,423 (95% CI 10,799-13,161) were infected with HCV, and 9,317 (95% CI 8,022-9,996) became chronically infected. The estimated annual number of new HCV infections among PWIDs increased steeply from the late 1970s and peaked in 1998. By 2014, almost 30% of injectors were estimated to have been infected for over 20 years.ConclusionsThis is the first comprehensive national estimate of the incidence of HCV in PWIDs in Ireland and will inform planning and developing appropriate health care services.

The Berlin Hepatitis C Manifesto: access to prevention, testing, treatment and care for people who use drugs.

The treatment of hepatitis C has entered a new era since the advent of curative pharmaceuticals. As policy, government and civil society assemble in response, there are still gaps to be addressed. The Manifesto on Hepatitis C and Drug Use, launched in Berlin during the Correlation Hepatitis C Initiative conference in October 2014, was formulated and endorsed by many key organizations in the hepatitis field. The Manifesto takes strides to pinpoint shortcomings in hepatitis action oriented towards the population most affected by the hepatitis C virus (HCV): active drug users.Despite a considerable amount of evidence that active drug users are disproportionately affected by HCV, barriers to care remain. Engagement with representatives of communities of people who inject drugs (PWID) is imperative in order to effectively create guidelines which reflect reality. Unfortunately, widespread systemic stigmatization and lack of trust between affected communities, decision-makers and healthcare professionals have reproduced this divide. The Berlin Manifesto has identified a disconnect between evidence and action which must be answered.In this roundtable discussion, experts from diverse parts of the hepatitis community have contributed their perspectives and experience on access to prevention, testing, and treatment for HCV in PWID. The authors discuss relevant topics such as realities of access to HCV treatment in the United Kingdom, interventions of a regional network of active drug users in Europe and lack of PWID involvement in government policy in Catalonia. Collectively they challenge the neglect of HCV in PWID by many decision-makers and health care professionals and promote a scale-up of integrated prevention and treatment strategies focusing on this population. The authors’ conclusions aim to clarify the discourse on hepatitis in order to prevent disease, save lives and work towards eventual hepatitis elimination.

Antiviral Treatment to Prevent Transmission of Hepatitis C in People Who Inject Drugs

The hepatitis C virus (HCV) is common among people who inject drugs (PWID) and causes significant morbidity and mortality. Opiate replacement therapy and needle exchange programs have effectively prevented the transmission of the Human immunodeficiency virus (HIV) but have been less effective for HCV. Other HCV prevention strategies are needed. Antiviral therapy with all oral direct acting antivirals is currently available and appears to be highly effective even in PWID and offers a possible strategy to further prevention efforts. This paper will review current evidence for treatment as prevention for HCV in PWID.

Urgent action to fight hepatitis C in people who inject drugs in Europe.

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and liver cancer, is curable in most people. Injecting drug use currently accounts for 80 % of new HCV infections with a known transmission route in the European Union (EU). HCV has generally received little attention from the public or policymakers in the EU, with major gaps in national-level strategies, action plans, guidelines and the evidence base. Specifically, people who inject drugs (PWID) are often excluded from treatment owing to various patient, healthcare provider and health system factors.All policymakers responsible for health services in EU countries should ensure that prevention, treatment, care and support interventions addressing HCV in PWID are developed and implemented. According to current best practice, PWID should have access to comprehensive, evidence-based multiprofessional harm reduction (especially opioid substitution therapy and clean needles and syringes) and support/care services based in the community and modified with community involvement to accommodate this hard-to-reach population. Other recommended components of care include vaccination against hepatitis B and other infections; peer support interventions; HIV testing, prevention and treatment; drug and alcohol services; psychological care as needed; and social support services. HCV testing should be performed regularly in PWID to identify infected persons and engage them in care. HCV-infected PWID should be considered for antiviral treatment (based on an individualised assessment and delivered within multidisciplinary care/support programmes) both to cure infected individuals and prevent onward transmission. Modelling data suggest that the HCV disease burden can only be cut substantially if antiviral treatment is scaled up together with prevention programmes. Measures should be taken to reduce stigma and discrimination against PWID at the provider and institutional levels.In conclusion, strategic action at the policy level is urgently needed to increase access to HCV prevention, testing and treatment among PWID, the group at highest risk of HCV infection. Such action has the potential to substantially reduce the number of infected persons, along with the disease burden and related care costs.

Clinicians' Views of Hepatitis C Virus Treatment Candidacy With Direct-Acting Antiviral Regimens for People Who Inject Drugs

ABSTRACTBackground: Direct-acting antivirals (DAAs) are curative in most persons with chronic hepatitis C virus (HCV) infection. However, high cost and concerns about adherence and reinfection may present continued barriers to treatment, particularly for people who inject drugs (PWID). Objective: To understand changes in assessments of treatment candidacy, given advances in treatment. Methods: Clinicians attending the Liver Meeting® in 2014 who reported prescribing HCV treatment in the past three years were invited to complete a survey regarding HCV treatment decisions. Participants assessed their likelihood to treat HCV in PWID in association with time of abstinence from injection drug use and what impacts their decision to provide treatment using interferon and DAAs. Results: 108 clinicians completed the survey; 10% were willing to treat an active PWID (last injection within 30 days) using interferon-containing regimens, and 15% with all-oral regimens. For each increasing time interval of injection abstinence, there was an increase in the odds of a clinician reporting willingness to treat with DAAs (Odds Ratio (OR) 2.57, 95% CI 2.18, 3.03) and with interferon-based treatment (OR 2.22 (95% CI 1.90, 2.61), Reinfection and medication cost were cited as most important concerns when determining candidacy. Conclusions: A cure is now the norm in HCV treatment, and there is an increasing need to address the barriers to treating PWID, the population with the highest burden of infection. Understanding treatment candidacy assessments is essential to improving uptake. This study provides insight into how clinicians view treatment candidacy in this era of DAAs and can help identify supportive treatment environments and concurrent programs.

A national multidisciplinary healthcare network for treatment of hepatitis C in people who inject drugs in Slovenia.

A national multidisciplinary healthcare network for treatment of hepatitis C in people who inject drugs in Slovenia.

KIR2DL3+NKG2A− natural killer cells are associated with protection from productive hepatitis C virus infection in people who inject drugs

Despite continuous high-risk behavior, a subgroup among people who inject drugs (PWID) remains seronegative for hepatitis C virus (HCV) suggesting that a state of "natural resistance" to HCV Infection may exist. Homozygosity for KIR2DL3 and its ligand HLA-C1 group alleles has been associated with control of HCV infection, however, the mechanism mediating this protective effect remained unclear. Peripheral NK cells from PWID (n=104) were phenotypically and functionally characterized by multicolor flow cytometry. Expression levels of the NK cell receptor ligands were analysed in liver biopsies and primary human hepatocytes. HCV seronegative PWID (n=34) had increased levels of KIR2DL3(+)NKG2A(-) NK cells compared to healthy controls (n=10; p<0.001) and PWID with chronic (n=38; p<0.001) or resolved infection (n=37; p<0.001). There was an inverse correlation between the frequency of KIR2DL3(+) and NKG2A(+) NK cells (r=-0.53; p<0.0001). Importantly, expression of HLA-E, the ligand for NKG2A, was significantly upregulated in liver biopsies of HCV infected patients (n=51) compared to HBV infected patients (n=22; p<0.01) and correlated with HCV viral load (r=0.32; p<0.0029). In functional analyses KIR2DL3(-)NKG2A(+) NK cells but not KIR2DL3(+)NKG2A(-) NK cells were significantly inhibited by HLA-E ligation. Accordingly, interferon gamma secretion of NK cells from PWID with chronic infection but not from HCV seronegative PWID was significantly suppressed in the presence of HLA-E. KIR2DL3(+)NKG2A(-) NK cells are not sensitive to HLA-E-mediated inhibition and may thereby control early HCV infection prior to seroconversion and result in an apparent state of "natural resistance" to HCV in PWID.

Eradication of hepatitis C infection: The importance of targeting people who inject drugs

Hepatitis C virus (HCV) affects ~170 million people worldwide and causes significant morbidity and mortality.1 In high-income countries, people who inject drugs (PWID) are at greatest risk of HCV infection.2 Until recently HCV eradication seemed unlikely, but recent advances in HCV treatment and improved understanding of the effectiveness of harm-reduction intervention effectiveness give reason for optimism. Current HCV treatments can cure ~75% of patients and new drugs will further improve effectiveness (over 90% cure) and improve tolerability.3 If HCV treatment can be delivered effectively to those at highest risk of onward transmission, significant reductions in future HCV cases are possible. The feasibility of disease eradication must be assessed on both scientific criteria (e.g., epidemiological susceptibility, effective and practical intervention available, and demonstrated feasibility of elimination) and political criteria (e.g., burden of disease, cost of intervention).4 With effective, curative treatment now available, HCV meets these criteria.