Chapter
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Hepatitis C virus (HCV) infection is a serious public health problem, with globally 71 million people estimated to be chronically infected and at risk of long-term sequelae, including liver cirrhosis and hepatocellular carcinoma [1–3]. Acute infection is typically asymptomatic, and owing to HCV’s ability to evade the immune system, 70–80% of infections become chronic [4–6]. In those chronically infected, it may be decades after initial infection before significant sequelae develop. If left untreated, chronic liver disease will progress to cirrhosis in 5–20%, and 1–5% will die from decompensated cirrhosis or hepatocellular carcinoma [7]. HCV infection contributes to around 27% of liver cirrhosis cases and 25% of primary liver cancers, and resulted in an estimated 400,000 deaths worldwide from these complications in 2015 [1, 8]. Co-infections with HIV are an increasing problem in countries with HIV epidemics in people who inject drugs, and among men who have sex with men, and underlying viral hepatitis is becoming a major cause of death among people with HIV [1, 9].

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

ResearchGate has not been able to resolve any citations for this publication.
Article
Full-text available
Hepatitis C virus (HCV) was discovered more than two decades ago, but progress towards a vaccine has been slow. HCV infection will spontaneously clear in about 25% of people. Studies of spontaneous HCV clearance in chimpanzees and human beings have identified host and viral factors that could be important in the control of HCV infection and the design of HCV vaccines. Although data from studies of chimpanzees suggest that protection against reinfection is possible after spontaneous clearance, HCV is a human disease. Results from studies of reinfection risk after spontaneous clearance in injecting drug users are conflicting, but some people seem to have protection against HCV persistence. To guide future vaccine development, we assess data from studies of HCV reinfection after spontaneous clearance, discuss flaws in the methods of previous human studies, and suggest essential components for future investigations of control of HCV infection.
Article
Full-text available
Background: Increasing the proportion diagnosed with and on treatment for chronic hepatitis C (CHC) is key to the elimination of hepatitis C in Europe. This study contributes to secondary prevention planning in the European Union/European Economic Area (EU/EEA) by estimating the number of CHC (anti-HCV positive and viraemic) cases among migrants living in the EU/EEA and born in endemic countries, defining the most affected migrant populations, and assessing whether country of birth prevalence is a reliable proxy for migrant prevalence. Methods: Migrant country of birth and population size extracted from statistical databases and anti-HCV prevalence in countries of birth and in EU/EEA countries derived from a systematic literature search were used to estimate caseload among and most affected migrants. Reliability of country of birth prevalence as a proxy for migrant prevalence was assessed via a systematic literature search. Results: Approximately 11% of the EU/EEA adult population is foreign-born, 79% of whom were born in endemic (anti-HCV prevalence ≥1%) countries. Anti-HCV/CHC prevalence in migrants from endemic countries residing in the EU/EEA is estimated at 2.3%/1.6%, corresponding to ~580,000 CHC infections or 14% of the CHC disease burden in the EU/EEA. The highest number of cases is found among migrants from Romania and Russia (50-60,000 cases each) and migrants from Italy, Morocco, Pakistan, Poland and Ukraine (25-35,000 cases each). Ten studies reporting prevalence in migrants in Europe were identified; in seven of these estimates, prevalence was comparable with the country of birth prevalence and in three estimates it was lower. Discussion: Migrants are disproportionately affected by CHC, account for a considerable number of CHC infections in EU/EEA countries, and are an important population for targeted case finding and treatment. Limited data suggest that country of birth prevalence can be used as a proxy for the prevalence in migrants.
Article
Full-text available
Background Direct acting antivirals (DAA) cure 95% of patients infected with hepatitis C (HCV). Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch HIV-positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAA became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Methods Two prospective acute HCV treatment studies enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the year preceding and following unrestricted DAA availability. We compared the HCV incidence in both years. Results The acute HCV incidence decreased from 93 infections during 8290 person years of follow up in 2014 (11.2/1000 PYFU, 95% CI 9.1-13.7) to 49 during 8961 PYFU in 2016 (5.5/1000, 95% CI 4.1–7.2). The incidence rate ratio of 2016 compared with 2014 was 0.49 (95% C.I. 0.35-0.69). Simultaneously, a significant increase in the percentage positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the Netherlands and contradicts a decrease in risk behavior as an alternative explanation. Conclusions Unrestricted DAA availability in the Netherlands was followed by a 51% decrease in acute HCV infections among HIV-positive MSM.
Article
Full-text available
Background Six distinct genetic variants (genotypes 1 − 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions than in others but, globally, genotype 3 (GT3) is the second most common. Patients infected with HCV GT1, 2, 4, 5 or 6 recover to a greater extent, as measured by sustained virological response (SVR), following treatment with regimens based on direct-acting antivirals (DAAs) than after treatment with older regimens based on pegylated interferon (Peg-IFN). GT3, however, is regarded as being more difficult to treat as it is a relatively aggressive genotype, associated with greater liver damage and cancer risk; some subgroups of patients with GT3 infection are less responsive to current licensed DAA treatments. Newer DAAs have become available or are in development. Methods According to PRISMA guidance, we conducted a systematic review (and descriptive statistical analysis) of data in the public domain from relevant clinical trial or observational (real-world) study publications within a 5-year period (February 2011 to May 2016) identified by PubMed, Medline In-Process, and Embase searches. This was supplemented with a search of five non-indexed literature sources, comprising annual conferences of the AASLD, APASL, CROI, EASL, and WHO, restricted to a 1-year period (April 2015 to May 2016). Results Of the all-oral regimens, the efficacy (SVR12 ≥ 90%) of sofosbuvir plus daclatasvir- and velpatasvir-based regimens in clinical trials supports and reinforces their recommendation by guidelines. Other promising regimens comprise grazoprevir + elbasvir + sofosbuvir, and ombitasvir + paritaprevir/ribavirin + sofosbuvir. Newer regimens incorporating pibrentasvir + glecaprevir or grazoprevir + ruzasvir + MK-3682 (uprifosbuvir), offer all-oral, ribavirin-free SVR12 rates consistently greater than 95%. Observational studies report slightly lower overall SVR rates but reflect corresponding clinical trial data in terms of treatments most likely to achieve good responses. Conclusions On the basis of SVR12, we established that for treating GT3 infections (i) regimens incorporating newer DAAs are more effective than those comprising older DAAs, and (ii) ribavirin may be of less benefit in newer DAA regimens than in older DAA regimens. The analysis provides evidence that DAA regimens can replace Peg-IFN-based regimens for GT3 infection. Electronic supplementary material The online version of this article (10.1186/s12879-017-2820-z) contains supplementary material, which is available to authorized users.
Article
Full-text available
Background: Sharing of equipment used for injecting drug use (IDU) is a substantial cause of disease burden and a contributor to blood-borne virus transmission. We did a global multistage systematic review to identify the prevalence of IDU among people aged 15-64 years; sociodemographic characteristics of and risk factors for people who inject drugs (PWID); and the prevalence of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among PWID. Methods: Consistent with the GATHER and PRISMA guidelines and without language restrictions, we systematically searched peer-reviewed databases (MEDLINE, Embase, and PsycINFO; articles published since 2008, latest searches in June, 2017), searched the grey literature (websites and databases, searches between April and August, 2016), and disseminated data requests to international experts and agencies (requests sent in October, 2016). We searched for data on IDU prevalence, characteristics of PWID, including gender, age, and sociodemographic and risk characteristics, and the prevalence of HIV, HCV, and HBV among PWID. Eligible data on prevalence of IDU, HIV antibody, HBsAg, and HCV antibody among PWID were selected and, where multiple estimates were available, pooled for each country via random effects meta-analysis. So too were eligible data on percentage of PWID who were female; younger than 25 years; recently homeless; ever arrested; ever incarcerated; who had recently engaged in sex work, sexual risk, or injecting risk; and whose main drugs injected were opioids or stimulants. We generated regional and global estimates in line with previous global reviews. Findings: We reviewed 55 671 papers and reports, and extracted data from 1147 eligible records. Evidence of IDU was recorded in 179 of 206 countries or territories, which cover 99% of the population aged 15-64 years, an increase of 31 countries (mostly in sub-Saharan Africa and the Pacific Islands) since a review in 2008. IDU prevalence estimates were identified in 83 countries. We estimate that there are 15·6 million (95% uncertainty interval [UI] 10·2-23·7 million) PWID aged 15-64 years globally, with 3·2 million (1·6-5·1 million) women and 12·5 million (7·5-18·4 million) men. Gender composition varied by location: women were estimated to comprise 30·0% (95% UI 28·5-31·5) of PWID in North America and 33·4% (31·0-35·6) in Australasia, compared with 3·1% (2·1-4·1) in south Asia. Globally, we estimate that 17·8% (10·8-24·8) of PWID are living with HIV, 52·3% (42·4-62·1) are HCV-antibody positive, and 9·0% (5·1-13·2) are HBV surface antigen positive; there is substantial geographic variation in these levels. Globally, we estimate 82·9% (76·6-88·9) of PWID mainly inject opioids and 33·0% (24·3-42·0) mainly inject stimulants. We estimate that 27·9% (20·9-36·8) of PWID globally are younger than 25 years, 21·7% (15·8-27·9) had recently (within the past year) experienced homelessness or unstable housing, and 57·9% (50·5-65·2) had a history of incarceration. Interpretation: We identified evidence of IDU in more countries than in 2008, with the new countries largely consisting of low-income and middle-income countries in Africa. Across all countries, a substantial number of PWID are living with HIV and HCV and are exposed to multiple adverse risk environments that increase health harms. Funding: Australian National Drug and Alcohol Research Centre, Australian National Health and Medical Research Council, Open Society Foundation, World Health Organization, the Global Fund, and UNAIDS.
Article
Full-text available
Background: People who inject drugs (PWID) are a key population affected by the global HIV and hepatitis C virus (HCV) epidemics. HIV and HCV prevention interventions for PWID include needle and syringe programmes (NSP), opioid substitution therapy (OST), HIV counselling and testing, HIV antiretroviral therapy (ART), and condom distribution programmes. We aimed to produce country-level, regional, and global estimates of coverage of NSP, OST, HIV testing, ART, and condom programmes for PWID. Methods: We completed searches of peer-reviewed (MEDLINE, Embase, and PsycINFO), internet, and grey literature databases, and disseminated data requests via social media and targeted emails to international experts. Programme and survey data on each of the named interventions were collected. Programme data were used to derive country-level estimates of the coverage of interventions in accordance with indicators defined by WHO, UNAIDS, and the UN Office on Drugs and Crime. Regional and global estimates of NSP, OST, and HIV testing coverage were also calculated. The protocol was registered on PROSPERO, number CRD42017056558. Findings: In 2017, of 179 countries with evidence of injecting drug use, some level of NSP services were available in 93 countries, and there were 86 countries with evidence of OST implementation. Data to estimate NSP coverage were available for 57 countries, and for 60 countries to estimate OST coverage. Coverage varied widely between countries, but was most often low according to WHO indicators (<100 needle-syringes distributed per PWID per year; <20 OST recipients per PWID per year). Data on HIV testing were sparser than for NSP and OST, and very few data were available to estimate ART access among PWID living with HIV. Globally, we estimate that there are 33 (uncertainty interval [UI] 21-50) needle-syringes distributed via NSP per PWID annually, and 16 (10-24) OST recipients per 100 PWID. Less than 1% of PWID live in countries with high coverage of both NSP and OST (>200 needle-syringes distributed per PWID and >40 OST recipients per 100 PWID). Interpretation: Coverage of HIV and HCV prevention interventions for PWID remains poor and is likely to be insufficient to effectively prevent HIV and HCV transmission. Scaling up of interventions for PWID remains a crucial priority for halting the HIV and HCV epidemics. Funding: Open Society Foundations, The Global Fund, WHO, UNAIDS, United Nations Office on Drugs and Crime, Australian National Drug and Alcohol Research Centre, University of New South Wales Sydney.
Article
Full-text available
Background: Controlling HCV transmission among people who inject drugs (PWID) has focused on preventing sharing syringes and drug preparation paraphernalia, but it is unclear if HCV incidence linked to sharing paraphernalia reflects contamination of the paraphernalia or syringe-mediated contamination when drugs are shared. Methods: In experiments designed to replicate real-world injection practices when drugs are shared, the residual contents of HCV contaminated syringes with detachable or fixed needled were passed through the 'cookers' and filters used by PWID in preparing drugs for injection and then introduced into a second syringe. All items were tested for the presence of infectious HCV using a chimeric HCV with a luciferase gene. Results: HCV could not be recovered from 'cookers' regardless of input syringe type or 'cooker' design. Recovery was higher when comparing detachable needles to fixed needles for residue in input syringes (73.8% vs 0%), filters (15.4% vs. 1.4%), and receptive syringes (93.8% vs. 45.7%). Conclusions: Our results, consistent with the hypothesis that sharing paraphernalia does not directly result in HCV transmission but is a surrogate for transmissions resulting from sharing drugs, have important implications for HCV prevention efforts and programs that provide education and safe injection supplies for PWID populations.
Article
Full-text available
Individuals with a history of injecting drugs have a high prevalence of chronic hepatitis C (HCV) infection. Many have a history of opioid use disorder (OUD). Despite novel treatments with improved efficacy and tolerability, treatment is limited in the group. A faculty of experts shared insights from clinical practice to develop an HCV care-readiness model. Evidence and expert knowledge was collected. Ten experts developed a model of three factors (with measures): 'healthcare engagement', 'guidance' and 'place'. Overall, 40-90% of individuals with OUD engage with drug treatment services. Ten of 12 HCV guidelines provided specific advice for the OUD population. Ten of 12 OUD care guidelines provided useful HCV care advice. In 11 of 12 cases, location of HCV/drug treatment care was in different places. This readiness assessment shows that there are important limitations to successful HCV care in OUD. Specific actions should be taken: maintain/increase access to OUD treatment services/opioid agonist therapy, updating HCV guidance, locate care in the same place and allow wider prescribing of anti HCV medicines.
Article
Full-text available
Purpose of review: Highly effective, well-tolerated interferon-free direct-acting antivirals (DAA) have revolutionised hepatitis C virus (HCV) therapeutics, with the opportunity for broad treatment scale-up among marginalised or "high-risk" populations, including people who inject drugs (PWID) and people with HIV/HCV coinfection. Recent findings: Concern that HCV reinfection may compromise HCV treatment outcomes is sometimes cited as a reason for not offering treatment to current and former PWID. However, the incidence of reinfection following interferon-based treatment for chronic HCV is low among PWID. Reinfection rates in HIV-positive men-who-have-sex-with-men (MSM) are varied, with high incidence reported in some cohorts. Mathematical modelling suggests that substantial reductions in HCV incidence and prevalence could be achieved with targeted DAA therapy among those at the highest risk of ongoing transmission. This review will summarise the recent literature on DAA efficacy in PWID and people with HIV/HCV coinfection, discuss the individual- and population-level impact of DAA treatment scale-up and reinfection, and highlight ongoing and future research questions in expanding HCV care and treatment to those populations at high risk of ongoing HCV transmission.
Technical Report
Full-text available
This report provides an update on infectious diseases related to drug use in Europe for the period up to June 2016. It covers the most recent data both on infectious diseases among people who inject drugs in Europe, collected with the EMCDDA Drug-related infectious diseases (DRID) indicator, and on the responses in the area. It includes highlights and new findings discussed during the DRID indicator’s annual expert meeting, held in Lisbon on 6–8 June 2016. Full text: http://www.emcdda.europa.eu/system/files/publications/3393/TD0416796ENN.pdf
Article
Full-text available
Background Highly effective hepatitis C virus (HCV) therapies have spurred a rapid scale up of treatment to populations at greater risk of reinfection after sustained virologic response (SVR). Reinfection may be higher in HIV-HCV co-infection but prior studies have considered small selected populations. We assessed risk factors for reinfection after SVR in a broadly representative cohort of Canadian co-infected patients in clinical care. Methods All patients achieving SVR after HCV treatment were followed with HCV RNA measurements every six months in an ongoing prospective cohort study. We used Bayesian Cox regression to estimate reinfection rates according to patient reported injection drug use (IDU) and sexual activity among men-having-sex-with-men (MSM). Results Of 497 patients treated for HCV, 257 achieved SVR and had at least one subsequent RNA measurement. During 589 person-years of follow-up (PYFU) after SVR, 18 (7%) became HCV RNA positive. The adjusted reinfection rate (per 1000 PYFU) in the first year after SVR was highest in those reporting high frequency IDU (58, 95% credible interval [CrI], 18–134), followed by MSM reporting high risk sexual activity (26, 95% CrI, 6–66) and low frequency IDU (22, 95% CrI, 4–68). The rate in low risk MSM (16, 95% CrI, 4–38) was similar to that in reference patients (10, 95% CrI, 4–20). Reinfection rates did not diminish with time. Conclusions HCV reinfection rates varied considerably according to risk. Measures are needed to reduce risk behaviours and increase monitoring in high risk IDU and MSM if HCV elimination targets are to be realised.
Article
Full-text available
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1) transmissions among people who inject drugs (PWID) continue to pose a challenging global health problem. Here, we aimed to analyse a universally applicable inactivation procedure, namely microwave irradiation, as a safe and effective method to reduce the risk of viral transmission. The exposure of HCV from different genotypes to microwave irradiation resulted in a significant reduction of viral infectivity. Furthermore, microwave irradiation reduced viral infectivity of HIV-1 and of HCV/HIV-1 suspensions indicating that this inactivation may be effective at preventing co-infections. To translate microwave irradiation as prevention method to used drug preparation equipment, we could further show that HCV as well as HIV-1 infectivity could be abrogated in syringes and filters. This study demonstrates the power of microwave irradiation for the reduction of viral transmission and establishment of this safety strategy could help reduce the transmission of blood-borne viruses.
Article
Full-text available
Hepatitis C virus (HCV) infection is a major public health burden in Europe, causing an increasing level of liver-related morbidity and mortality, characterized by several regional variations in the genotypes distribution. A comprehensive review of the literature from 2000 to 2015 was used to gather country-specific data on prevalence and genotype distribution of HCV infection in 33 European countries (about 80 % of the European population), grouped in three geographical areas (Western, Eastern and Central Europe), as defined by the Global Burden of Diseases project (GBD). The estimated prevalence of HCV in Europe is 1.7 % showing a decrease than previously reported (− 0.6 %) and accounting over 13 million of estimated cases. The lowest prevalence (0.9 %) is reported from Western Europe (except for some rural areas of Southern Italy and Greece) and the highest (3.1 %) from Central Europe, especially Romania and Russia. The average HCV viraemic rate is 72.4 %, with a population of almost 10 million of HCV RNA positive patients. Genotype distribution does not show high variability among the three macro-areas studied, ranging between 70.0 % (Central Europe), 68.1 % (Eastern Europe) and 55.1 % (Western Europe) for genotype 1, 29.0 % (Western Europe), 26.6 % (Eastern Europe) and 21.0 % (Central Europe) for genotype 3. Genotype 2 seems, instead, to have a major prevalence in the Western Europe (8.9 %), if compared to Eastern (4.3 %) or Central (3.2 %), whereas genotype 4 is present especially in Central and Western area (4.9 % and 5.8 %, respectively). Despite the eradication of transmission by blood products, HCV infection continues to be one of the leading blood-borne infections in Europe. The aim of this review is, therefore, to provide an update on the epidemiology of HCV infection across Europe, and to foster the discussion about eventual potential strategies to eradicate it.
Chapter
Full-text available
http://www.emcdda.europa.eu/publications/insights/hepatitis-c-among-drug-users-in-europe
Article
Full-text available
New direct-acting antivirals have the potential to transform the hepatitis C (HCV) treatment landscape, with rates of sustained viral response in excess of 90%. As these new agents are expensive, an important question is whether to focus on minimizing the consequences of severe liver disease, or reducing transmission via 'treatment as prevention'. A back-calculation model was used to estimate the impact of treatment of mild, moderate and compensated cirrhosis on incident cases of HCV-related end-stage liver disease/hepatocellular carcinoma (ESLD/HCC). In addition, a dynamic model was used to determine the impact on incidence and prevalence of chronic infection in people who inject drugs (PWID), the main risk group in England. Treating 3500 cirrhotics per year was predicted to reduce ESLD/HCC incidence from 1100 (95% CrI 970-1240) cases per year in 2015 to 630 (95% CrI 530-770) in 2020, around half that currently expected, although treating moderate-stage disease will also be needed to sustain this reduction. Treating mild-stage PWID was required to make a substantial impact on transmission: with 2500 treated per year, chronic prevalence/annual incidence in PWID was reduced from 34%/4.8% in 2015 to 11%/1.4% in 2030. There was little overlap between the two goals: treating mild stage had virtually no impact on ESLD/HCC within 15 years, but the long timescale of liver disease means relatively few PWID reach cirrhosis before cessation of injecting. Strategies focussing on treating advanced disease have the potential for dramatic reductions in severe morbidity, but virtually no preventative impact.
Article
Full-text available
Background: We report on the hepatitis C virus(HCV) epidemic among HIV-positive men who have sex with men(MSM) in the UK and model its trajectory with or without scaled-up HCV direct-acting antivirals(DAAs). Methods: A dynamic HCV transmission model among HIV-diagnosed MSM in the UK was calibrated to HCV prevalence(Ab+ or RNA+), incidence, and treatment from 2004-2011 among HIV-diagnosed MSM in the UK collaborative HIV cohort(UK CHIC). The epidemic was projected with: current or scaled-up HCV treatment, with or without a 20% behavioral risk reduction. Results: HCV prevalence among HIV-positive MSM in UK CHIC increased from 7.3% in 2004 to 9.9% in 2011, whereas primary incidence was flat(1.02-1.38 per 100 person-years). Over the next decade, modelling suggests 94% of infections are attributable to high-risk individuals, comprising 7% of the population. Without treatment, HCV chronic prevalence could have been 38% higher in 2015(11.9% vs 8.6%). With current treatment and SVR rates(status quo), chronic prevalence is likely to increase to 11% by 2025, but stabilize with DAA introduction in 2015. With DAAs scale-up to 80% within one year of diagnosis (regardless of disease stage), 20%/yr thereafter, chronic prevalence could reduce by 71% (to 3.2%) compared to status quo in 2025. With additional behavioural interventions, chronic prevalence could reduce further to <2.5% by 2025. Conclusions: Epidemiological data and modelling suggest a continuing HCV epidemic among HIV-diagnosed MSM in the UK driven by high-risk individuals, despite high treatment rates. Substantial reductions in HCV transmission could be achieved through scale-up of DAAs and moderately effective behavioural interventions.
Article
Full-text available
Background: Prisoners have a high prevalence of Hepatitis C virus (HCV), but case-finding may not have been cost-effective because treatment often exceeded average prison stay combined with a lack of continuity-of-care. We assess the cost-effectiveness of increased HCV case-finding and treatment in UK prisons using short-course therapies. Methods: A dynamic HCV transmission model assesses the cost-effectiveness of doubling HCV case-finding (achieved through introducing opt-out HCV testing in UK pilot prisons) and increasing treatment in UK prisons, compared to status-quo voluntary risk-based testing (6% prison entrants/year), using currently recommended therapies(8-24 weeks) or IFN-free DAAs(8-12 weeks, 95% SVR, £3300/wk). Costs(GBP£) and health utilities(quality-adjusted life-years,QALYs) were used to calculate mean incremental cost-effectiveness ratios(ICERs). We assume 56% referral and 2.5%/25% of referred people who inject drugs(PWID)/exPWID treated within 2 months of diagnosis in prison. PWID and ex/nonPWID are in prison an average 4/8 months, respectively. Results: Doubling prison testing rates with existing treatments produces a mean ICER of £19,850/QALY gained compared to current testing/treatment, and is 45% likely to be cost-effective under a £20,000 willingness-to-pay(WTP) threshold. Switching to 8-12 week IFN-free DAAs in prisons could increase cost-effectiveness(ICER £15,090/QALY gained). Excluding prevention benefit decreases cost-effectiveness. If >10% referred PWID are treated in prison (2.5% base-case), either treatment could be highly cost-effective(ICER<£13,000). HCV case-finding and IFN-free DAAs could be highly cost-effective if DAA cost is 10% lower or 8 weeks duration. Conclusions Increased HCV testing in UK prisons (such as through opt-out testing) is borderline cost-effective compared to status-quo voluntary risk-based testing under a £20,000 WTP with current treatments, but likely to be cost-effective if short-course IFN-free DAAs are used, and could be highly cost-effective if PWID treatment rates were increased. This article is protected by copyright. All rights reserved.
Article
Full-text available
Background: Treatment for hepatitis C virus (HCV) can lead to sustained virological response (SVR) in over 90% of people. Subsequent recurrence of HCV, either from late relapse or reinfection, reverses the beneficial effects of SVR. Methods: A search identified studies analysing HCV recurrence post-SVR. The recurrence rate for each study was calculated using events/person years of follow-up (PYFU). Results were pooled using a random-effects model and used to calculate 5-year recurrence risk. Three patient groups were analysed: (1) Mono-HCV infected "low-risk" patients; (2) Mono-HCV infected "high-risk" patients (injecting drug users or prisoners); (3) human immunodeficiency virus (HIV)/HCV coinfected patients. Recurrence was defined as confirmed HCV RNA detectability post-SVR. Results: In the 43 studies of HCV mono-infected "low-risk" patients (n = 7969) the pooled recurrence rate was 1.85/1000 PYFU (95% confidence interval [CI], .71-3.35; I(2) = 73%) leading to a summary 5-year recurrence risk of 0.95% (95% CI, .35%-1.69%). For the 14 studies of HCV monoinfected "high-risk" patients (n = 771) the pooled recurrence rate was 22.32/1000 PYFU (95% CI, 13.07-33.46; I(2) = 27%) leading to a summary 5-year risk of 10.67% (95% CI, 6.38%-15.66%). For the 4 studies of HIV/HCV coinfected patients the pooled recurrence rate was 32.02/1000 PYFU (95% CI, .00-123.49; I(2) = 96%) leading to a summary 5-year risk of 15.02% (95% CI, .00%-48.26%). The higher pooled estimates of recurrence in the high-risk and coinfected cohorts were driven by an increase in reinfection rather than late relapse. Conclusions: SVR appears durable in the majority of patients at 5 years post-treatment. The large difference in 5 year event rate by risk group is driven mainly by an increased reinfection risk.
Article
Full-text available
Background & aims: Hepatitis C virus (HCV) infection is a significant global health issue that leads to 350,000 preventable deaths annually due to associated cirrhosis and hepatocellular carcinoma (HCC). Immigrants and refugees (migrants) originating from intermediate/high HCV endemic countries are likely at increased risk for HCV infection due to HCV exposure in their countries of origin. The aim of this study was to estimate the HCV seroprevalence of the migrant population living in low HCV prevalence countries. Methods: Four electronic databases were searched from database inception until June 17, 2014 for studies reporting the prevalence of HCV antibodies among migrants. Seroprevalence estimates were pooled with a random-effect model and were stratified by age group, region of origin and migration status and a meta-regression was modeled to explore heterogeneity. Results: Data from 50 studies representing 38,635 migrants from all world regions were included. The overall anti-HCV prevalence (representing previous and current infections) was 1.9% (95% CI, 1.4-2.7%, I2 96.1). Older age and region of origin, particularly Sub-Saharan Africa, Asia, and Eastern Europe were the strongest predictors of HCV seroprevalence. The estimated HCV seroprevalence of migrants from these regions was >2% and is higher than that reported for most host populations. Conclusion: Adult migrants originating from Asia, Sub-Saharan Africa and Eastern Europe are at increased risk for HCV and may benefit from targeted HCV screening.
Article
Full-text available
Objectives: We evaluated time trends in sharing needles and other injection equipment from 1994 to 2013 among injection drug users in the Seattle, Washington, area. Methods: We combined data from 4 sources: the Risk Activity Variables, Epidemiology, and Network (RAVEN) study, recruited from institutional settings; the Kiwi study, recruited from jails; National HIV Behavioral Surveillance system (NHBS) surveys, which used respondent-driven sampling; and surveys at needle-exchange sites. Results: Levels of needle sharing were higher in the earlier studies: RAVEN, 1994 to 1997 (43%) and Kiwi, 1998 to 2002 (61%). In the NHBS surveys, the initial level of 44% in 2005 declined to 31% in the period 2009 to 2012. Across needle-exchange surveys (2009-2013) the level was 21%. There was a parallel reduction in sharing other injection equipment. These trends persisted after control for sociodemographic and risk-associated variables. There was a contemporaneous increase in the number of needles distributed by local needle exchanges and a decline in the number of reported HIV cases among injection drug users. Conclusions: The apparent long-term reduction in sharing injection equipment suggests substantial success in public health efforts to reduce the sharing of injection equipment. (Am J Public Health. Published online ahead of print December 21, 2015: e1-e7. doi:10.2105/AJPH.2015.302959).
Article
Full-text available
The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.
Article
Full-text available
Background: Hepatitis C virus (HCV) infection is a leading cause of morbidity and mortality in patients with HIV-1. The C-EDGE CO-INFECTION study assessed the efficacy, safety, and tolerability of grazoprevir (MK-5172) plus elbasvir (MK-8742) in patients with HCV and HIV co-infection. Methods: In this uncontrolled, non-randomised, phase 3, open-label, single-arm study, treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection and HIV co-infection, with or without cirrhosis, were enrolled from 37 centres in nine countries across Europe, the USA, and Australia. Patients were either naive to treatment with any antiretroviral therapy (ART) or stable on ART for at least 8 weeks. All patients received grazoprevir 100 mg plus elbasvir 50 mg in a fixed-dose combination tablet once daily for 12 weeks. The primary endpoint was sustained virological response (HCV RNA <15 IU/mL) 12 weeks after the end of therapy (SVR12). The primary population for efficacy analyses was all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT02105662. Findings: Between June 11, 2014, and Aug 29, 2014, 218 patients were enrolled and received grazoprevir plus elbasvir for 12 weeks, all of whom completed follow-up at week 12. SVR12 was achieved by 210 (96%) of 218 patients (95% CI 92·9-98·4). One patient did not achieve SVR12 because of a non-virological reason, and seven patients without cirrhosis relapsed (two subsequently confirmed as reinfections). All 35 patients with cirrhosis achieved SVR12. The most common adverse events were fatigue (29; 13%), headache (27; 12%), and nausea (20; 9%). No patient discontinued treatment because of an adverse event. Two patients receiving ART had transient HIV viraemia. Interpretation: This HCV treatment regimen seems to be effective and well tolerated for patients co-infected with HIV with or without cirrhosis. These data are consistent with previous trials of this regimen in the monoinfected population. This regimen continues to be studied in phase 3 trials. Funding: Merck Sharp & Dohme Corp.
Technical Report
Full-text available
This report provides an update on infectious diseases related to injecting drug use in Europe for the period up to June 2015. The report covers both the EMCDDA Drug-related infectious diseases indicator, which collects data on the situation, and the responses in the area. It includes highlights and new findings discussed during the indicator's annual expert meeting, held in Lisbon on 15 and 16 June 2015. This two-day event offered a platform for discussion among experts from the 28 EU Member States, Norway and Turkey. Topics receiving particular attention include: an update of the HIV situation and concerns in some countries; bacterial infections, including botulism outbreaks in Scotland and Norway; and changing patterns of injection in Europe and their implications for public health. Challenges in scaling up HCV treatments and good national examples in this area are also discussed.
Article
Full-text available
The epidemiology of the incidence of sexually transmitted hepatitis C virus (HCV) infection in HIV-positive MSM is only partially understood. In the presence of HIV, HCV infection is more likely to become chronic and liver fibrosis progression is accelerated. A systematic review and meta-analysis was used to synthesize data characterizing sexually transmitted HCV in HIV-positive MSM. Electronic and other searches of medical literature (including unpublished reports) were conducted. Eligible studies reported on HCV seroconversion or on reinfection postsuccessful HCV treatment in HIV-positive MSM who were not injecting drugs. Pooled incidence rates were calculated using random-effects meta-analysis, and meta-regression was used to assess study-level moderators. Attributable risk measures were calculated from statistically significant associations between exposures and HCV seroconversion. More than 13 000 HIV-positive MSM in 17 studies were followed for more than 91 000 person-years between 1984 and 2012; the pooled seroconversion rate was 0.53/100 person-years. Calendar time was a significant moderator of HCV seroconversion, increasing from an estimated rate of 0.42/100 person-years in 1991 to 1.09/100 person-years in 2010, and 1.34/100 person-years in 2012. Reinfection postsuccessful HCV treatment (n = 2 studies) was 20 times higher than initial seroconversion rates. Among the seroconverters, a large proportion of infections were attributable to high-risk behaviours including mucosally traumatic sex and sex while high on methamphetamine. The high reinfection rates and the attributable risk analysis suggest the existence of a subset of HIV-positive MSM with recurring sexual exposure to HCV. Approaches to HCV control in this population will need to consider the changing epidemiology of HCV infection in MSM.
Article
Full-text available
liver disease stage, HIV co-infection, prescriber type, and drug or alcohol use. Of the 42 states with known Medicaid reimbursement criteria for sofosbuvir, 74% limit sofosbuvir access to persons with advanced fibrosis (Meta-Analysis of Histologic Data in Viral Hepatitis [METAVIR] fibrosis stage F3) or cirrhosis (F4). One quarter of states require persons co-infected with HCV and HIV to be receiving antiretroviral therapy or to have suppressed HIV RNA levels. Two thirds of states have restrictions based on prescriber type, and 88% include drug or alcohol use in their sofosbuvir eligibility criteria, with 50% requiring a period of abstinence and 64% requiring urine drug screening. Heterogeneity is present in Medicaid reimbursement criteria for sofosbuvir with respect to liver disease staging, HIV co-infection, prescriber type, and drug or alcohol use across the United States. Restrictions do not seem to conform with recommendations from professional organizations, such as the Infectious Diseases Society of America and the American Association for the Study of Liver Diseases. Current restrictions seem to violate federal Medicaid law, which requires states to cover drugs consistent with their U.S. Food and Drug Administration labels.
Article
Full-text available
Background. The hepatitis C virus (HCV) epidemic is evolving rapidly in patients infected with human immunodeficiency virus (HIV). We aimed to describe changes in treatment uptake and outcomes of incident HCV infections before and after 2006, the time-point at which major changes in HCV epidemic became apparent. Methods. We included all adults with an incident HCV infection before June 2012 in the Swiss HIV Cohort Study, a prospective nationwide representative cohort of individuals infected with HIV. We assessed the following outcomes by time period: the proportion of patients starting an HCV therapy, the proportion of treated patients achieving a sustained virological response (SVR), and the proportion of patients with persistent HCV infection during follow-up. Results. Of 193 patients with an HCV seroconversion, 106 were diagnosed before and 87 after January 2006. The proportion of men who have sex with men increased from 24% before to 85% after 2006 (P < .001). Hepatitis C virus treatment uptake increased from 33% before 2006 to 77% after 2006 (P < .001). Treatment was started during early infection in 22% of patients before and 91% after 2006 (P < .001). An SVR was achieved in 78% and 29% (P = .01) of patients treated during early and chronic HCV infection. The probability of having a detectable viral load 5 years after diagnosis was 0.67 (95% confidence interval [CI], 0.58–0.77) in the group diagnosed before 2006 and 0.24 (95% CI, 0.16–0.35) in the other group (P < .001). Conclusions. In recent years, increased uptake and earlier initiation of HCV therapy among patients with incident infections significantly reduced the proportion of patients with replicating HCV.
Article
Objective To identify the routes of transmission during an outbreak of infection with hepatitis C virus (HCV) genotype 2a/2c in a hemodialysis unit. Design A matched case-control study was conducted to identify risk factors for HCV seroconversion. Direct observation and staff interviews were conducted to assess infection control practices. Molecular methods were used in a comparison of HCV infecting isolates from the case-patients and from patients infected with the 2a/2c genotype before admission to the unit. Setting A hemodialysis unit treating an average of 90 patients. Patients A case-patient was defined as a patient receiving hemodialysis with a seroconversion for HCV genotype 2a/2c between January 1994 and July 1997 who had received dialysis in the unit during the 3 months before the onset of disease. For each case-patient, 3 control-patients were randomly selected among all susceptible patients treated in the unit during the presumed contamination period of the case-patient. Results HCV seroconversion was associated with the number of hemodialysis sessions undergone on a machine shared with (odds ratio [OR] per additional session, 1.3; 95% confidence interval [CI 95 ], 0.9 to 1.8) or in the same room as (OR per additional session, 1.1; CI 95 , 1.0 to 1.2) a patient who was anti-HCV (genotype 2a/2c) positive. We observed several breaches in infection control procedures. Wetting of transducer protectors in the external pressure tubing sets with patient blood reflux was observed, leading to a potential contamination by blood of the pressure-sensing port of the machine, which is not accessible to routine disinfection. The molecular analysis of HCV infecting isolates identified among the case-patients revealed two groups of identical isolates similar to those of two patients infected before admission to the unit. Conclusions The results suggest patient-to-patient transmission of HCV by breaches in infection control practices and possible contamination of the machine. No additional cases have occurred since the reinforcement of infection control procedures and the use of a second transducer protector.
Article
Objective: High hepatitis C virus (HCV) treatment uptake combined with effective direct-acting antiviral-based regimens resulted in a dramatic decline of HCV infection in French people living with HIV (PLWH). We assessed the yearly incidence of new HCV infection in PLWH enrolled in the large French Dat'AIDS cohort from 2012 to 2016 with a specific focus on MSM. Methods: The incidence of new HCV infection was determined yearly in HCV-negative PLWH with serological follow-up during 2012-2016. The incidence of HCV reinfection was determined in patients who were cured of a previous infection. Results: Among 40 714 PLWH, HCV status was available in 38 217 (94%). A total of 5557 PLWH (15%) were HCV infected at first time-point, 82% of whom were cured of HCV by the end of 2016. Among 21 519 HCV-negative PLWH with serological follow-up (63 449 patient-years), 219 first HCV infections occurred (MSM: 188, others: 31). Similarly, among 3406 patients who were cured of a previous infection (10 602 patient-years), 73 reinfections occurred (MSM: 51, others: 22). From 2012 to 2016, the incidence of a first infection in MSM rose from 0.5 to 0.92% patient-years, whereas the incidence or reinfection remained stable (2.52-2.90% patient-years). Conclusion: Despite a high HCV treatment uptake and cure rate, the incidence of new HCV infection (first infection or reinfection) regularly increased in French HIV-positive MSM between 2012 and 2016. The incidence of reinfection fluctuated but remained constantly higher than the incidence of first infection, suggesting that a subgroup of MSM pursued high-risk practices following cure of a first infection.
Article
Background and aims: There is limited real-world information on the effectiveness of antiviral treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAA) in people on opioid substitution therapy (OST). This study compared sustained virological response (SVR) rates and proportion of lost to follow-up (LTFU) between OST and non-OST patients in the German Hepatitis C-Registry (DHC-R). Design: National multi-centre prospective real-world registry (German Hepatitis C-Registry, DHC-R). Non-OST patients comprised patients with former/current drug use (non-OST/DU) and patients never consuming drugs (non-OST/NDU). Setting: A total of 254 medical centres in Germany, including 123 centres providing OST. Participants: A total of 7747 chronic HCV patients started DAA therapy (739 OST and 7008 non-OST; 1500 non-OST/DU; 5508 non-OST/NDU) patients. Five hundred and twenty-eight OST and 5582 non-OST patients had completed antiviral therapy and at least one follow-up documentation [intention-to-treat (ITT) population]. Measurements: Study outcomes were SVR, proportion of LTFU and safety of treatment. Findings: SVR (ITT) was documented in 85% (450 of 528) OST patients versus 86% (969 of 1126) in non-OST/DU (P = 0.651) and 92% (4113 of 4456) non-OST/NDU (P < 0.001) patients. Independent predictors for SVR (P < 0.01 in multivariate analysis) included HCV genotype non-3 [adjusted odds ratio (aOR) = 1.11; 95% confidence interval (CI) = 1.07-1.15], female sex (aOR = 1.59; CI = 1.30-1.94), platelet counts >90 × 109/l (aOR = 1.51, CI = 1.14-2.01), cirrhosis (aOR = 0.77; CI = 0.62-0.96) and patient group (OST/DI (aOR = 0.58; CI = 0.42-0.78); non-OST/DU (OR: 0.63; CI = 0.50-0.78). In per-protocol analysis (PP), SVR rates were ≥ 94% in all patient groups. In OST the proportion of LTFU was higher (10.2%) than in non-OST/DU (8.5%) and non-OST/NDU (3.2%, P < 0.001) patients. Independent factors for LTFU (P < 0.01) were HCV genotype non-3 (aOR = 0.92; CI = 0.88-0.96), female sex (aOR: 0.7; CI = 0.53-0.92), pre-treatment (aOR = 0.64; CI = 0.50-0.82), OST/DI (aOR = 3.35; CI = 2.35-4.78) and non-OST/DU (aOR = 2.38; CI = 1.80-3.14). Conclusions: In Germany, direct-acting antiviral treatment of former or current drug users with or without opioid substitution therapy can achieve equally high sustained virological response rates as in patients with no history of drug use.
Article
The availability of effective, simple, well tolerated oral direct acting antiviral (DAA) hepatitis C regimens have raised optimism for HCV elimination at the population level. HCV reinfection in key populations such as people who inject drugs (PWID) and HIV-infected men who have sex with men (MSM) however threatens the achievement of this goal both from a patient, provider and population perspective. The goal of this review is to synthesize our current understanding of estimated rates and factors associated with HCV reinfection. This review also proposes interventions to aid understanding of and reduce hepatitis C reinfection among PWID and HIV-infected MSM in the oral direct acting antiviral era.
Article
Objectives: To compare US trends in rates of injection drug use (IDU), specifically opioid injection, with national trends in the incidence of acute HCV infection to assess whether these events correlated over time. Methods: We calculated the annual incidence rate and demographic and risk characteristics of reported cases of acute HCV infection using surveillance data from 2004 to 2014 and the annual percentage of admissions to substance use disorder treatment facilities reporting IDU for the same time period by type of drug injected and demographic characteristics. We then tested for trends. Results: The annual incidence rate of acute HCV infection increased more than 2-fold (from 0.3 to 0.7 cases/100 000) from 2004 to 2014, with significant increases among select demographic subgroups. Admissions for substance use disorder attributed to injection of heroin and prescription opioid analgesics increased significantly, with an almost 4-fold increase in prescription opioid analgesic injection. Significant increases in opioid injection mirrored those for reported cases of acute HCV infection among demographic subgroups. Conclusions: These findings strongly suggest that the national increase in acute HCV infection is related to the country's opioid epidemic and associated increases in IDU. (Am J Public Health. Published online ahead of print December 21, 2017: e1-e7. doi:10.2105/AJPH.2017.304132).
Article
Objectives and design: Hepatitis C virus (HCV) has been recognised as an emerging sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). However, HIV-negative MSM at high risk for HIV might also be at increased risk for HCV. We studied the HCV prevalence in HIV-negative MSM who start pre-exposure prophylaxis (PrEP) in Amsterdam. Phylogenetic analysis was used to compare HCV strains obtained from HIV-negative and HIV-positive MSM. Methods: At enrolment in the Amsterdam PrEP (AMPrEP) demonstration project, HIV-negative MSM were tested for the presence of HCV antibodies and HCV RNA. If positive for HCV RNA, an HCV NS5B gene fragment (709 bp) was sequenced and compared with HCV isolates from HIV-positive MSM (n = 223) and risk groups other than MSM (n = 153), using phylogenetic analysis. Results: Of 375 HIV-negative MSM enrolled in AMPrEP, 18 (4.8%, 95%CI 2.9%-7.5%) of participants were anti-HCV and/or HCV RNA positive at enrolment; 15/18 (83%) had detectable HCV RNA. HCV genotyping showed genotype 1a (73%), 4d (20%) and 2b (7%). All HCV-positive MSM starting PrEP were part of MSM-specific HCV clusters containing MSM with and without HIV. Conclusion: HCV prevalence among HIV-negative MSM who started PrEP was higher than previously reported. All HIV-negative HCV-positive MSM were infected with HCV strains already circulating among HIV-positive MSM. The increasing overlap between sexual networks of HIV-positive and HIV-negative MSM might result in an expanding HCV-epidemic irrespective of HIV-status. Hence, routine HCV testing should be offered to MSM at high risk for HIV, especially for those enrolling in PrEP programs.
Article
Background: Rapid improvements in hepatitis C virus (HCV) therapy have led to the approval of multiple oral direct-acting antiviral (DAA) regimens by the U.S. Food and Drug Administration (FDA) for treatment of chronic HCV infection. Purpose: To summarize published literature on the efficacy and safety of oral DAAs for treatment of persons with chronic HCV infection. Data sources: MEDLINE and EMBASE from inception through 1 November 2016. Study selection: 42 English-language studies from controlled and single-group registered clinical trials of adults with HCV infection that evaluated at least 8 weeks of an FDA-approved interferon-free HCV regimen that included at least 2 DAAs. Data extraction: Two investigators abstracted data on study design, patient characteristics, and virologic and safety outcomes sequentially and assessed quality independently. Data synthesis: Six DAA regimens showed high sustained virologic response (SVR) rates (>95%) in patients with HCV genotype 1 infection without cirrhosis, including those with HIV co-infection. Effective treatments for HCV genotype 3 infection are limited (2 DAA regimens). Patients with hepatic decompensation, particularly those with Child-Turcotte-Pugh class C disease, had lower SVR rates (78% to 87%) than other populations. The addition of ribavirin was associated with increased SVR rates for certain DAA regimens and patient groups. Overall rates of serious adverse events and treatment discontinuation were low (<10% in the general population); regimens that included ribavirin had more mild or moderate adverse events than those without. Limitations: Twenty-three studies had moderate risk of bias (10 were open-label single-group trials, 11 had limited information on concealment of the allocation scheme, and 5 had selective outcome reporting). All but 1 of the studies were industry-funded. Heterogeneity of interventions precluded pooling. Conclusion: Multiple oral DAA regimens show high rates of safety, tolerability, and efficacy for treatment of HCV genotype 1 infection, particularly among persons without cirrhosis. Primary funding source: Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42014009711).
Article
Chronic HCV infection is a global health problem that affects >184 million people worldwide. HCV is associated with several hepatic and extrahepatic disorders, including several malignancies. The burden of HCV-related disorders is influenced by the number of new and existing cases, number of existing cases and the natural history of the infection. The natural history of HCV is affected by several demographic, virological, clinical and lifestyle factors. Major variations exist in the burden of HCV among different populations and geographical regions, as well as over time. With the advent of new and efficacious antiviral treatments, it is important to learn the determinants of HCV burden to design appropriate strategies for detection, prognostication and treatment. Furthermore, with the expected growth of patients cured of HCV, it is essential to learn about the possible change in natural history and burden of disease in these patients. In this Review, we will discuss the global epidemiology and burden of HCV and its complications, as well as the natural history and clinical course of chronic and cured HCV infection.
Article
Background & aims: Moderate cure rates of acute hepatitis C virus (HCV) infections with pegylated interferon and ribavirin have been described in the last decade in men who have sex with men (MSM), who are also coinfected with the human immunodeficiency virus (HIV). However, a subsequent high incidence of HCV reinfections has been reported regionally in men who both clear the infection spontaneously or who respond to treatment. Methods: Retrospective analysis of reinfections in HIV infected MSM in eight centers from Austria, France, Germany, and the UK within the NEAT network between May 2002 and June 2014. Results: Of 606 individuals who cleared HCV spontaneously or were successfully treated, 149 (24.6%) presented with a subsequent HCV reinfection. Thirty out of 70 (43%) who cleared again or were successfully treated, presented with a second reinfection, 5 with a third, and one with a fourth reinfection. The reinfection incidence was 7.3/100 person-years (95% CI 6.2-8.6). We found a trend for lower incidence among individuals who had spontaneously cleared their incident infection than among individuals who were treated (Hazard ratio 0.62, 95% CI 0.38-1.02, p=0.06). Spontaneous clearance of reinfection was associated with ALT levels >1000IU/ml and spontaneous clearance of a prior infection. Conclusions: HCV reinfection is an issue of major concern in HIV-positive MSM. Prevention strategies are needed for high risk groups to reduce morbidity and treatment costs. HIV-positive MSM with a prior HCV infection should be tested every 3 to 6months for reinfection. Those who had achieved a reinfection should be tested every 3months. Lay summary: We evaluated the occurrence of HCV reinfection in HIV-positive men who have sex with men. We found an alarming incidence of 7.3/100 person-years. Prevention measures need to address this specific subgroup of patients at high risk for HCV.
Article
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.
Article
Background: Advances in therapy for hepatitis B virus (HBV) and hepatitis C virus (HCV) have ushered in a new era in chronic hepatitis treatment. To maximise the effectiveness of these medicines, individuals must be engaged and retained in care. We analysed operational interventions to enhance chronic viral hepatitis testing, linkage to care, treatment uptake, adherence, and viral suppression or cure. Methods: We did a systematic review of operational interventions, and did meta-analyses for sufficiently comparable data. We searched PubMed, Embase, WHO library, International Clinical Trials Registry Platform, PsycINFO, and CINAHL for randomised controlled trials and controlled non-randomised studies that examined operational interventions along the chronic viral hepatitis care continuum, published in English up to Dec 31, 2014. We included non-pharmaceutical intervention studies with primary or secondary outcomes of testing, linkage to care, treatment uptake, treatment adherence, treatment completion, treatment outcome, or viral endpoints. We excluded dissertations and studies of children only. Data were extracted by two independent reviewers, with disagreements resolved by a third reviewer. Studies were assessed for bias. Data from similar interventions were pooled and quality of evidence was assessed using GRADE. This study was registered in PROSPERO (42014015094). Findings: We identified 7583 unduplicated studies, and included 56 studies that reported outcomes along the care continuum (41 for HCV and 18 for HBV). All studies except one were from high-income countries. Lay health worker HBV test promotion interventions increased HBV testing rates (relative risk [RR] 2·68, 95% CI 1·82-3·93). Clinician reminders to prompt HCV testing during clinical visits increased HCV testing rates (3·70, 1·81-7·57). Nurse-led educational interventions improved HCV treatment completion (1·14, 1·05-1·23) and cure (odds ratio [OR] 1·93, 95% CI 1·44-2·59). Coordinated mental health, substance misuse, and hepatitis treatment services increased HCV treatment uptake (OR 3·03, 1·24-7·37), adherence (RR 1·22, 1·05-1·41), and cure (RR 1·21, 1·07-1·38) compared with usual care. Interpretation: Several simple, inexpensive operational interventions can substantially improve engagement and retention along the chronic viral hepatitis care continuum. Further operational research to inform scale-up of hepatitis services is needed in low-income and middle-income countries. Funding: World Health Organization and US Fulbright Program.
Article
Background: With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. Methods: We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). Findings: Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86–0·94) to 1·45 million (1·38–1·54); YLLs from 31·0 million (29·6–32·6) to 41·6 million (39·1–44·7); YLDs from 0·65 million (0·45–0·89) to 0·87 million (0·61–1·18); and DALYs from 31·7 million (30·2–33·3) to 42·5 million (39·9–45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. Interpretation: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health.
Article
Background At global level, there are 37 million people infected with HIV and 115 million people with antibodies to hepatitis C virus (HCV). Little is known about the extent of HIV–HCV co-infection. We sought to characterise the epidemiology and burden of HCV co-infection in people living with HIV. Methods In this systematic review and meta-analysis we searched MEDLINE, Embase, CINAHL+, POPLINE, Africa-wide Information, Global Health, Web of Science, and the Cochrane Library and WHO databases for studies measuring prevalence of HCV and HIV, published between Jan 1, 2002, and Jan 28, 2015. We included studies in HIV population samples of more than 50 individuals and recruited patients based on HIV infection status or other behavioural characteristics. We excluded editorials or reviews containing no primary data, samples of HCV or HIV–HCV co-infected individuals, or samples relying on self-reported infection status. We also excluded samples drawn from populations with other comorbidities or undergoing interventions that put them at increased risk of co-infection. Populations were categorised according to HIV exposure, with the regional burden of co-infection being derived by applying co-infection prevalence estimates to published numbers of HIV-infected individuals. We did a meta-analysis to estimate the odds of HCV in HIV-infected individuals compared with their HIV-negative counterparts. Findings From 31 767 citations identified, 783 studies met the inclusion criteria, resulting in 902 estimates of the prevalence of HIV–HCV co-infection. In HIV-infected individuals, HIV–HCV co-infection was 2·4% (IQR 0·8–5·8) within general population samples, 4·0% (1·2–8·4) within pregnant or heterosexually exposed samples, 6·4% (3·2–10·0) in men who have sex with men (MSM), and 82·4% (55·2–88·5) in people who inject drugs (PWID). Odds of HCV infection were six times higher in people living with HIV (5·8, 95% CI 4·5–7·4) than their HIV-negative counterparts. Worldwide, there are approximately 2 278 400 HIV–HCV co-infections (IQR 1 271 300—4 417 000) of which 1 362 700 (847 700–1 381 800) are in PWID, equalling an overall co-infection prevalence in HIV-infected individuals of 6·2% (3·4–11·9). Interpretation We noted a consistently higher HCV prevalence in HIV-infected individuals than HIV-negative individuals across all risk groups and regions, but especially in PWID. This study highlights the importance of routine HCV testing in all HIV-infected individuals, but especially in PWID. There is also a need to improve country-level surveillance of HCV prevalence across different population groups in all regions.
Article
Background: We determine the optimal HCV treatment prioritization strategy for interferon-free HCV direct-acting antivirals(IFN-free DAAs) by disease stage and risk status incorporating treatment of people who inject drugs(PWID). Methods: A dynamic HCV transmission and progression model compares the cost-effectiveness of treating patients early versus delaying until cirrhosis for patients with mild or moderate fibrosis where PWID chronic HCV prevalence is 20, 40 or 60%. Treatment is 12 weeks, £3300/wk, 95% sustained viral response, varied by genotype/stage in alternative scenarios. We estimate long-term health costs(in £UK=€1.3=$1.5) and outcomes as quality adjusted life-years gained(QALYs) using a £20,000 willingness-to-pay per QALY threshold. We rank strategies with Net Monetary Benefit(NMB); negative NMB implies delay treatment. Results: The most cost-effective group to treat were PWID with moderate fibrosis(mean NMB per early treatment £60,640/£23,968 at 20%/40% chronic prevalence, respectively), followed by PWID with mild fibrosis(NMB £59,258 and £19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis(NMB £9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed(NMB -£3,650). In populations with 60% chronic HCV among PWID it is only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections are averted. One extra HCV-related death is averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied SVR/duration by genotype/fibrosis stage. Conclusions: Treating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high.
Article
The burden of hepatitis C virus (HCV) is high among people who inject drugs (PWID) and prisoners, and increasing among HIV-infected MSM, who are key populations for HCV transmission in high-income countries and may also play a role in many in low- and middle-income countries. There is an increasing interest in the use of HCV antiviral treatment for prevention in these populations. Numerous theoretical modelling studies have explored the potential impact of HCV treatment for prevention among PWID in a range of global settings, generally finding that modest and achievable levels of HCV treatment, especially with interferon-free direct-acting antiviral therapy (IFN-free DAAs), could substantially reduce HCV chronic prevalence among PWID within the next 10-20 years. In addition, modelling studies have shown HCV testing and treatment in prison (including prevention benefits) could be cost-effective if continuity of care is ensured, or HCV treatments are shortened with DAAs. Modelling work among HIV-infected MSM has shown that further HCV treatment scale-up is likely required despite high treatment rates in this population. However, no empirical studies have explored whether HCV treatment can reduce HCV prevalence and prevent onwards transmission among those at risk of transmission. HCV treatment for key populations such as PWID, prisoners and MSM could become an important HCV prevention intervention, especially in the IFN-free DAA era. However, there is an urgent need to test these hypotheses through empirical studies.
Article
Acute hepatitis C virus (AHCV) infections are frequently seen worldwide in certain risk groups with an annual incidence rate varying between 0.08% and 66%. Although this incidence is substantial, a delayed diagnosis during chronic infection is most often made in the absence of clinical symptoms in the acute phase of the infection. Current used methods to diagnose AHCV are IgG antibody seroconversion and repeated HCV RNA measurements though no definite diagnostic test is currently available. Progress in the field of adaptive and innate immune responses has aided to both advancements in the field of HCV vaccine development and a more basic understanding of viral persistence. The rapid changes in the treatment of chronic HCV will affect therapeutic regimens in AHCV in the coming years leading to shorter treatment courses and pegylated interferon-free modalities. This review gives an overview of the current knowledge and uncertainties together with some future perspectives on acute HCV epidemiology, virology, immunology and treatment. Copyright © 2015. Published by Elsevier Ltd.