Esther J. Aspinall

Treatment of Hepatitis C Virus Infection Among People Who Are Actively Injecting Drugs: A Systematic Review and Meta-analysis

BACKGROUND Although guidelines recommend that people who inject drugs (PWID) should not be excluded from hepatitis C (HCV) treatment, some services remain reluctant to treat PWID. The aim of this review was to investigate sustained virologic response (SVR), adherence, discontinuation, and HCV reinfection among PWID. METHODS A search of Medline, Embase, and Cochrane databases (between 2002 and January 2012) was conducted for primary articles/conference abstracts examining HCV treatment outcomes in PWID. Meta-analysis was used to obtain pooled estimates of SVR, adherence, discontinuation, and HCV reinfection. RESULTS Ten primary articles and 1 conference abstract met the inclusion criteria. Across 6 studies (comprising 314 drug users, of whom 141 [45%] were PWID), pooled SVR was 56% (95% confidence interval [CI], 50%-61%) for all genotypes, 37% (95% CI, 26%-48%) for genotypes 1/4, and 67% (95% CI, 56%-78%) for genotypes 2/3. Pooled 80/80/80 adherence was 82% (95% CI, 74%-89%) across 2 studies, and pooled treatment discontinuation was 22% (95% CI, 16%-27%) across 4 studies. Across 5 studies (comprising 131 drug users) examining reinfection, pooled risk was 2.4 (95% CI, .9-6.1) per 100 person-years. CONCLUSIONS HCV treatment outcomes are acceptable in PWID, supporting treatment guidelines. The pooled estimate of HCV reinfection risk was low, but there was considerable uncertainty around this estimate. Further studies on the risk of reinfection are needed to assess the long-term effectiveness of HCV treatment in PWID.

Are needle and syringe programmes associated with a reduction in HIV transmission among people who inject drugs: a systematic review and meta-analysis

BACKGROUND Needle and syringe programmes (NSP) aim to reduce the risk of HIV by providing people who inject drugs (PWID) with sterile injecting equipment. A recent review of reviews (ROR) concluded that there was only tentative evidence to support the effectiveness of NSP in reducing HIV. We carried out a systematic review and meta-analysis to assess the association between NSP and HIV transmission. METHODS Relevant primary articles presenting data on the risk of HIV transmission associated with NSP were identified in two stages: (i) from reviews identified in two published RORs (covering the period 1980-2008); and (ii) a literature search of CINAHL, Cochrane Library, EMBASE, MEDLINE and PsychINFO for primary articles published since the most recent high quality review (covering the period 2008-12). Study results were synthesized using random-effects meta-analysis. RESULTS There were 12 studies comprising at least 12 000 person-years of follow-up. Exposure to NSP was associated with a reduction in HIV transmission: pooled effect size 0·66 [95% confidence interval (CI) 0·43, 1·01] across all studies, and 0·42 (95% CI 0·22, 0·81) across six higher quality studies (according to the Newcastle-Ottawa tool). CONCLUSIONS There is evidence to support the effectiveness of NSP in reducing the transmission of HIV among PWID, although it is likely that other harm reduction interventions have also contributed to the observed reduction in HIV risk. NSP should be considered as just one component of a programme of interventions to reduce both injecting risk and other types of HIV risk behaviour.

Hepatitis B prevention, diagnosis, treatment and care: a review

Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality worldwide. Chronic hepatitis B (CHB) infection is associated with an increased risk of cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). The likelihood of developing CHB is related to the age at which infection is acquired; the risk being lowest in adults and >90% in neonates whose mothers are hepatitis B e antigen positive. Treatment of CHB infection aims to clear HBV DNA and prevent the development of complications. There are currently seven drugs available for the treatment of CHB: five nucleos(t)ide analogues and two interferon-based therapies. Long-term treatment is often required, and the decision to treat is based on clinical assessment including the phase of CHB infection and the presence and extent of liver damage. A safe and effective HBV vaccine has been available since the early 1980s. Vaccination plays a central role in HBV prevention strategies worldwide, and a decline in the incidence and prevalence of HBV infection following the introduction of universal HBV vaccination programmes has been observed in many countries including the USA and parts of South East Asia and Europe. Post-exposure prophylaxis (PEP) with HBV vaccine +/- hepatitis B immunoglobulin is highly effective in preventing mother to child transmission and in preventing transmission following sharps injuries, sexual contact and other exposures to infected blood and body fluids. Transmission of HBV in the health care setting has become an increasingly rare event in developed nations. However, it remains a significant risk in developing countries reflecting the higher prevalence of CHB, limited access to HBV vaccination and PEP and a lack of adherence to standard infection control precautions.

Does informing people who inject drugs of their hepatitis C status influence their injecting behaviour? Analysis of the Networks II study.

BACKGROUND People who inject drugs (PWID) are at risk of hepatitis C virus (HCV). It is plausible that PWID who receive a diagnosis of HCV will reduce their injecting risk out of concern for their injecting partners, although evidence for this is currently limited. The aim of this study was to investigate whether informing PWID of their HCV diagnosis was associated with a change in injecting behaviour. METHODS Prospective, longitudinal study of PWID recruited from street drug markets across Melbourne, Australia. Interviews and HCV testing were conducted at 3-monthly intervals. The association between receiving a diagnosis of HCV and (i) injecting frequency and (ii) injecting equipment borrowing, was examined using generalized estimating equations (GEE) analysis. RESULTS Thirty-five individuals received a diagnosis of HCV during the study period. Receiving a diagnosis of HCV was associated with a decrease of 0.35 injections per month (p=0.046) but there was no change in injecting equipment borrowing (p=0.750). CONCLUSIONS A small reduction in injecting frequency was observed in PWID who received a diagnosis of HCV. This finding should be investigated further in larger studies examining a wider range of injecting risk behaviours.

Current and emerging antiviral treatments for hepatitis C infection

Newly licensed direct acting antivirals for hepatitis C virus HCV are able to cure up to 75% of patients chronically infected with genotype‐1 infection, which is the predominant HCV strain in Europe and North America. Emerging antiviral therapies promise further increases in virological response, as well as improved tolerability, reduced duration of therapy, and will potentially eliminate the need for interferon use. This review highlights the main therapeutic agents used in current standard of care, including telaprevir and boceprevir. It goes on to evaluate the mechanisms of emerging drugs, their stage of development and response rates seen in research to date. Finally, it projects into the not too distant future to consider treatment strategies involving combinations of agents and interferon‐free therapies, and in which patients they might prove most successful.

Hepatitis C reinfection following treatment induced viral clearance among people who have injected drugs.

BACKGROUND Although people who inject drugs (PWID) are an important group to receive Hepatitis C Virus (HCV) antiviral therapy, initiation onto treatment remains low. Concerns over reinfection may make clinicians reluctant to treat this group. We examined the risk of HCV reinfection among a cohort of PWID (encompassing all those reporting a history of injecting drug use) from Scotland who achieved a sustained virological response (SVR). METHODS Clinical and laboratory data were used to monitor RNA testing among PWID who attained SVR following therapy between 2000 and 2009. Data were linked to morbidity and mortality records. Follow-up began one year after completion of therapy, ending on 31st December, 2012. Frequency of RNA testing during follow-up was calculated and the incidence of HCV reinfection estimated. Cox proportional hazards regression was used to examine factors associated with HCV reinfection. RESULTS Among 448 PWID with a SVR, 277 (61.8%) were tested during follow-up, median 4.5 years; 191 (69%) received one RNA test and 86 (31%) received at least two RNA tests. There were seven reinfections over 410 person years generating a reinfection rate of 1.7/100py (95% CI 0.7-3.5). For PWID who have been hospitalised for an opiate or injection related cause post SVR (11%), the risk of HCV reinfection was greater [AHR=12.9, 95% CI 2.2-76.0, p=0.002] and the reinfection rate was 5.7/100py (95% CI 1.8-13.3). CONCLUSION PWID who have been tested, following SVR, for HCV in Scotland appear to be at a low risk of reinfection. Follow-up and monitoring of this population are warranted as treatment is offered more widely.

Modelling the impact of incarceration and prison‐based hepatitis C virus (HCV) treatment on HCV transmission among people who inject drugs in Scotland

Abstract Background and Aims People who inject drugs (PWID) experience high incarceration rates, and previous incarceration is associated with elevated hepatitis C virus (HCV) transmission risk. In Scotland, national survey data indicate lower HCV incidence in prison than the community (4.3 versus 7.3 per 100 person‐years), but a 2.3‐fold elevated transmission risk among recently released (< 6 months) PWID. We evaluated the contribution of incarceration to HCV transmission among PWID and the impact of prison‐related prevention interventions, including scaling‐up direct‐acting antivirals (DAAs) in prison. Design Dynamic mathematical modelling of incarceration and HCV transmission, using approximate Bayesian computation for model calibration. Setting Scotland, UK. Participants A simulated population of PWID. Measurements Population‐attributable fraction (PAF) of incarceration to HCV transmission among PWID. Decrease in HCV incidence and chronic prevalence due to current levels of prison opiate substitution therapy (OST; 57% coverage) and HCV treatment, as well as scaling‐up DAAs in prison and/or preventing the elevated risk associated with prison release. Findings Incarceration contributes 27.7% [PAF; 95% credible interval (CrI) –3.1 to 51.1%] of HCV transmission among PWID in Scotland. During the next 15 years, current HCV treatment rates (10.4/6.8 per 1000 incarcerated/community PWID annually), with existing prison OST, could reduce incidence and chronic prevalence among all PWID by a relative 10.7% (95% CrI = 8.4–13.3%) and 9.7% (95% CrI = 7.7–12.1%), respectively. Conversely, without prison OST, HCV incidence and chronic prevalence would decrease by 3.1% (95% CrI = –28.5 to 18.0%) and 4.7% (95% CrI = –11.3 to 14.5%). Additionally, preventing the heightened risk among recently released PWID could reduce incidence and chronic prevalence by 45.0% (95% CrI = 19.7–57.5%) and 33.3% (95% CrI = 15.6–43.6%) or scaling‐up prison HCV treatments to 80% of chronic PWID prison entrants with sufficient sentences (>16 weeks) could reduce incidence and prevalence by 45.6% (95% CrI = 38.0–51.3%) and 45.5% (95% CrI = 39.3–51.0%), respectively. Conclusions Incarceration and the elevated transmission risk following prison release can contribute significantly to hepatitis C virus transmission among people who inject drugs. Scaling‐up hepatitis C virus treatment in prison can provide important prevention benefits.

Trends in mortality after diagnosis of hepatitis C virus infection: An international comparison and implications for monitoring the population impact of treatment

BACKGROUND & AIMS People living with hepatitis C virus (HCV) are at increased risk of all-cause and liver-related mortality, although successful treatment has been shown to reduce this risk. The aim of this study was to provide baseline data on trends in cause-specific mortality and to establish an international surveillance system for evaluating the population level impact of HCV treatments. METHODS Population level HCV diagnosis databases from Scotland (1997-2010), Australia (New South Wales [NSW]) (1997-2006), and Canada (British Columbia [BC]) (1997-2003) were linked to corresponding death registries using record linkage. For each region, age-adjusted cause-specific mortality rates were calculated, and trends in annual age-adjusted liver-related mortality were plotted. RESULTS Of 105,138 individuals diagnosed with HCV (21,810 in Scotland, 58,484 in NSW, and 24,844 in BC), there were 7275 deaths (2572 in Scotland, 2655 in NSW, and 2048 in BC). Liver-related deaths accounted for 26% of deaths in Scotland, 21% in NSW, and 22% in BC. Temporal trends in age-adjusted liver related mortality were stable in Scotland (males p=0.4; females p=0.2) and NSW (males p=0.9; females p=0.9), while there was an increase in BC (males p=0.002; females p=0.04). CONCLUSIONS The risk of liver-related mortality after a diagnosis of HCV has remained stable or increased over time across three regions with well-established diagnosis databases, highlighting that HCV treatment programmes to-date have had minimal impact on population level HCV-related liver disease. With more effective therapies on the horizon, and greater uptake of treatment anticipated, the potential of future therapeutic strategies to reduce HCV-related mortality is considerable.

Hepatitis E virus infection in Europe: surveillance and descriptive epidemiology of confirmed cases, 2005 to 2015

Hepatitis E virus (HEV) is an under-recognised cause of acute hepatitis in high-income countries. The purpose of this study was to provide an overview of testing, diagnosis, surveillance activities, and data on confirmed cases in the European Union/European Economic Area (EU/EEA). A semi-structured survey was developed and sent to 31 EU/EEA countries in February 2016, 30 responded. Twenty of these countries reported that they have specific surveillance systems for HEV infection. Applied specific case definition for HEV infection varied widely across countries. The number of reported cases has increased from 514 cases per year in 2005 to 5,617 in 2015, with most infections being locally acquired. This increase could not be explained by additional countries implementing surveillance for HEV infections over time. Hospitalisations increased from less than 100 in 2005 to more than 1,100 in 2015 and 28 fatal cases were reported over the study period. EU/EEA countries are at different stages in their surveillance, testing schemes and policy response to the emergence of HEV infection in humans. The available data demonstrated a Europe-wide increase in cases. Standardised case definitions and testing policies would allow a better understanding of the epidemiology of HEV as an emerging cause of liver-related morbidity.

Global policy and access to new hepatitis C therapies for people who inject drugs

People who inject drugs (PWID) are disproportionately affected by hepatitis C virus (HCV). This review outlines policy recommendations made in the 2014 World Health Organisation (WHO) Guidelines on Screening, Care and Treatment of HCV and their relevance to PWID. It also canvasses issues that will affect translation of these global guidelines into practice. The first global HCV guidelines released by WHO have recently advocated targeted HCV testing for PWID, assessment of liver disease and support for alcohol reduction during care. They also strongly advocate treatment using currently licensed direct-acting antiviral agents for all individuals, in particular PWID as a key affected population. New HCV treatment regimens have the potential to cure more than 90% of treated individuals. Scaling-up treatment among PWID has the potential to improve individual and population health by reducing HCV transmission, improving quality of life and supporting behaviour modifications that lead to less risk-taking over time. PWID face several barriers to accessing HCV care and treatment that need to be overcome. Testing services need re-orientation toward PWID, individuals need to be informed of their results and provided with direct linkage to ongoing care. Health services need to provide care in the community using simpler, cheaper and more accessible modes of delivery. Healthcare costs and pharmaceutical costs need to be minimised so PWID, who are highly marginalised, can access HCV treatment. Sustained scale-up of treatment for PWID could simultaneously improve individual health and achieve the goal of eliminating HCV transmission among this high-risk and vulnerable group.