Hepatitis C Virus Reinfection Research Articles

GRAND PLAN: Safety and Efficacy of Glecaprevir/Pibrentasvir for the Treatment of Hepatitis C Virus Infection Among People Initially Disengaged From Health Care Who Use Drugs-A Systematic Multidisciplinary Approach.

GRAND PLAN is a prospective, open-label, phase 4 study. Based at a single center and with a single arm, GRAND PLAN evaluated the safety and efficacy of an 8-week course of glecaprevir/pibrentasvir (G/P) among active drug users with hepatitis C virus (HCV) infection in a population enriched for factors that may reduce treatment uptake and success, such as disengagement from health care and unstable housing. Participants were ≥19 years old and actively using drugs and were confirmed viremic, noncirrhotic, and HCV treatment naive. All participants provided informed consent before any study procedures. They received G/P for 8 weeks within a multidisciplinary model of care, with daily, weekly, or monthly dispensing of medications to optimize adherence. We identified 117 eligible patients with a median age of 46 years (range, 22-75): 27% were female, 21.4% were Indigenous, 48.7% were unstably housed, and 95.7% were active drug users (94.9% fentanyl). One patient did not start treatment, and 4 underwent <1 week of treatment, leaving 112 completed treatments with 94.6% picking up medications weekly. HCV RNA was undetectable at the end of treatment in all 112 patients. One died of unknown causes shortly after treatment. A cure was demonstrated in 108 of 111 (97.3%) cases at the SVR12 time point (sustained virologic response at ≥12 weeks); the other 3 experienced virologic relapse. Considering the entire cohort, the intent-to-treat success rate was 92.3% (108/117). HCV reinfection was documented at SVR24 in 5 cases, 2 of which were successfully retreated. GRAND PLAN demonstrates that administration of an 8-week course of G/P to inner-city residents with HCV infection leads to a cure >95%. With a short course of treatment, G/P is an attractive option for this population in helping us achieve the World Health Organization's HCV objectives by 2030.

Hepatitis C virus reinfection incidence among gay and bisexual men with HIV in Australia from 2016 to 2020.

There is some concern that hepatitis C virus (HCV) reinfection might impact HCV micro-elimination efforts among gay and bisexual men (GBM) with HIV. However, there is a limited understanding of reinfection incidence in the context of unrestricted government-funded HCV treatment. We aimed to estimate HCV reinfection incidence among GBM with HIV in Australia from 2016 to 2020. Data were from 39 clinics participating in ACCESS, a sentinel surveillance network for blood borne viruses and sexually transmissible infections across Australia. GBM with HIV who had evidence of treatment or spontaneous clearance with at least one positive HCV RNA test, a subsequent negative HCV RNA test, and at least one additional HCV RNA test between 1st January 2016 and 31st December 2020 were eligible for inclusion. A new HCV RNA positive test and/or detectable viral load was defined as a reinfection. Generalised linear modelling was used to examine trends in reinfection. Among 12 213 GBM with HIV who had at least one HCV test, 540 were included in the reinfection incidence analysis, of whom 38 (7%) had evidence of reinfection during the observation period. Over 1124 person-years of follow-up, the overall rate of reinfection was 3.4/100PY (95% CI 2.5-4.6). HCV reinfection incidence declined on average 30% per calendar year (Incidence Rate Ratio 0.70, 95% CI 0.54-0.91). HCV reinfection incidence has declined among GBM with HIV in Australia since government-funded unrestricted DAAs were made available. Ongoing HCV RNA testing following cure and prompt treatment for anyone newly diagnosed is warranted to sustain this.

Changes in incidence of hepatitis C virus reinfection and access to direct-acting antiviral therapies in people with HIV from six countries, 2010–19: an analysis of data from a consortium of prospective cohort studies

Reinfection after successful treatment with direct-acting antivirals is hypothesised to undermine efforts to eliminate hepatitis C virus (HCV) infection among people with HIV. We aimed to assess changes in incidence of HCV reinfection among people with HIV following the introduction of direct-acting antivirals, and the proportion of all incident cases attributable to reinfection. We pooled individual-level data on HCV reinfection in people with HIV after spontaneous or treatment-induced clearance of HCV from six cohorts contributing data to the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC) in Australia, Canada, France, the Netherlands, Spain, and Switzerland between Jan 1, 2010, and Dec 31, 2019. Participants were eligible if they had evidence of an HCV infection (HCV antibody or RNA positive test) followed by spontaneous clearance or treatment-induced clearance, with at least one HCV RNA test after clearance enabling measurement of reinfection. We assessed differences in first reinfection incidence between direct-acting antiviral access periods (pre-direct-acting antiviral, limited access [access restricted to people with moderate or severe liver disease and other priority groups], and broad access [access for all patients with chronic HCV]) using Poisson regression. We estimated changes in combined HCV incidence (primary and reinfection) and the relative contribution of infection type by calendar year. Overall, 6144 people with HIV who were at risk of HCV reinfection (median age 49 years [IQR 42-54]; 4989 [81%] male; 2836 [46%] men who have sex with men; 2360 [38%] people who inject drugs) were followed up for 17 303 person-years and were included in this analysis. The incidence of first HCV reinfection was stable during the period before the introduction of direct-acting antivirals (pre-introduction period; 4·1 cases per 100 person-years, 95% CI 2·8-6·0). Compared with the pre-introduction period, the average incidence of reinfection was 4% lower during the period of limited access (incidence rate ratio [IRR] 0·96, 95% CI 0·78-1·19), and 28% lower during the period of broad access (0·72, 0·60-0·86). Between 2015 and 2019, the proportion of incident HCV infections due to reinfection increased, but combined incidence declined by 34%, from 1·02 cases per 100 person-years (95% CI 0·96-1·07) in 2015 to 0·67 cases per 100 person-years (95% CI 0·59-0·75) in 2019. HCV reinfection incidence and combined incidence declined in people with HIV following direct-acting antiviral introduction, suggesting reinfection has not affected elimination efforts among people with HIV in InCHEHC countries. The proportion of incident HCV cases due to reinfection was highest during periods of broad access to direct-acting antivirals, highlighting the importance of reducing ongoing risks and continuing testing in people at risk. Australian National Health and Medical Research Council.

Therapy as prevention toward HCV elimination in maintenance hemodialysis: a multi-center, prospective cohort study.

The World Health Organization has established interim guidance for hepatitis C virus (HCV) elimination. We aimed to prove the concept of "treatment as prevention" by conducting a prospective HCV elimination program for hemodialysis (HD) patients. A universal HCV screen was launched in 22 HD centers in 2019. HCV-viremic patients were linked to care with direct-acting antivirals (DAAs). The second screen was performed in 2021 to evaluate the effect of link-to-care in lowering the prevalence of HCV viremia and the incidence of HCV new/re-infections. Of 2336 patients enrolled in the first screening in 2019, 320 (13.7%) were seropositive for anti-HCV and 181 (7.7%) were HCV-viremic. Of 152 patients successfully linked to treat with DAA, 140 (92.1%) patients achieved a sustained virological response. Of them, 1733 patients participated in the second surveillance. Five anti-HCV-negative patients experienced anti-HCV seroconversion. Of 119 DAA-cured patients and 102 spontaneous HCV clearance patients, none had HCV reinfection. The annual incidence of HCV new infection was 0.1%. Sixty-one of the 620 (9.8%) newly enrolled patients were anti-HCV-seropositive in the second survey. The overall HCV-viremic rate decreased from 7.7% in 2019 to 0.6% (15/2353) in 2021. At the institutional level, 45.5% (10/22) eradicated HCV and 82% (18/22) of HD units had no HCV new infections or reinfections. The link-to-care project proved the concept of "treatment as prevention" by which HCV microelimination helps to prevent reinfection and new infections in the HD population.Trial registration: ClinicalTrials.gov identifier: NCT03803410 and NCT03891550.

Determining reinfection rates by hepatitis C testing interval among key populations: A systematic review and meta-analysis.

Detecting hepatitis C virus (HCV) reinfection among key populations helps prevent ongoing transmission. This systematic review aims to determine the association between different testing intervals during post-SVR follow-up on the detection of HCV reinfection among highest risk populations. We searched electronic databases between January 2014 and February 2023 for studies that tested individuals at risk for HCV reinfection at discrete testing intervals and reported HCV reinfection incidence among key populations. Pooled estimates of reinfection incidence were calculated by population and testing frequency using random-effects meta-analysis. Forty-one single-armed observational studies (9453 individuals) were included. Thirty-eight studies (8931 individuals) reported HCV reinfection incidence rate and were included in meta-analyses. The overall pooled estimate of HCV reinfection incidence rate was 4.13 per 100 per person-years (py) (95% confidence interval [CI]: 3.45-4.81). The pooled incidence estimate among people who inject drugs (PWID) was 2.84 per 100 py (95% CI: 2.19-3.50), among men who have sex with men (MSM) 7.37 per 100 py (95% CI: 5.09-9.65) and among people in custodial settings 7.23 per 100 py (95% CI: 2.13-16.59). The pooled incidence estimate for studies reporting a testing interval of ≤6 months (4.26 per 100 py; 95% CI: 2.86-5.65) was higher than studies reporting testing intervals >6 months (5.19 per 100 py; 95% CI: 3.92-6.46). HCV reinfection incidence was highest in studies of MSM and did not appear to change with retesting interval. Shorter testing intervals are likely to identify more reinfections, help prevent onward transmission where treatment is available and enable progress towards global HCV elimination, but additional comparative studies are required.

Incidence and molecular epidemiology of hepatitis C virus reinfection in prisons in Catalonia, Spain (Re-HCV study)

Hepatitis C virus (HCV) reinfection may hamper HCV elimination in prisons. We aimed to (i) determine the reinfection rate in people treated for HCV in Catalan prisons, (ii) measure reinfection in people entering prisons, and (iii) characterize the molecular epidemiology of HCV in prisons and people who inject drugs (PWID) in the community. Re-HCV was a prospective study in eight prisons (2019–2020) including two groups: (1) people cured with treatment in prison and followed-up every 6 months, and (2) people testing HCV-RNA positive at incarceration. Bio-behavioral data were collected. HCV isolates were sequenced and phylogenetically analyzed with those of PWID in the community. Reinfection follow-up after treatment was achieved in 97 individuals (103.05 person-years). Two reinfections were detected, resulting in an incidence ≤ 10/100 person-years. Among people entering prison, 2% (359/17,732) were viremic, of which 334 (93.0%) were included, and 44 (13.5%) presented with reinfection (84.7% being PWID). Frequently, HCV isolates in prisons and PWID in the community were phylogenetically related. Although HCV reinfection is low after treatment, it is common in people entering Catalan prisons. To maintain a low HCV prevalence in prisons, harm-reduction services and test-and-treat programs for PWID should be strengthened both inside and outside prisons.

Sexual and drug use risk behaviour trajectories among people treated for recent HCV infection: the REACT study.

Exploration of sexual and drug use behaviours following treatment for recent hepatitis C virus (HCV) is limited. This analysis modelled behavioural trajectories following treatment for recent HCV and assessed reinfection. Participants treated for recent HCV in an international trial (enrolled 2017-2019) were followed at 3-monthly intervals for up to 2 years to assess longitudinal behaviours. Population-averaged changes were assessed using generalized estimating equations. Distinct behavioural trajectories were identified using group-based trajectory modelling. HCV reinfection incidence was calculated using person-years (PY) of observation. During the follow-up of 212 participants (84% gay and bisexual men [GBM]; 69% HIV; 26% current injecting drug use [IDU]), behavioural trajectories for IDU and stimulant use (past month) did not change. However, population-averaged decreases in the likelihood of daily IDU (adjusted odds ratio [AOR] 0.83; 95% CI 0.72, 0.95) and opioid use (AOR 0.84; 95% CI 0.75, 0.93) were observed. Among GBM, behavioural trajectories for chemsex did not change. Population-averaged decreases in condomless anal intercourse with casual male partners (CAI-CMP) (AOR 0.95; 95% CI 0.90, 0.99) and group-sex (AOR 0.86; 95% CI 0.80, 0.93) were observed, but masked distinct trajectories. While a proportion had a decreased probability of CAI-CMP (23%) and group-sex (59%) post-treatment, a substantial proportion retained a high probability of these behaviours. High HCV reinfection incidence was observed for the sustained high probability IDU (33.0/100 PY; 95% CI 17.7, 61.3) and chemsex (23.3/100 PY; 95% CI 14.5, 37.5) trajectories. Limited sexual and drug use behavioural change was observed following treatment for recent HCV, supporting access to surveillance and (re)treatment.

Analysis of Patients' Characteristics and Treatment Profile of People Who Use Drugs (PWUDs) with and without a Co-Diagnosis of Viral Hepatitis C: A Real-World Retrospective Italian Analysis.

Hepatitis C virus (HCV) spreads from contact with blood of an infected person. HCV infections are common among people who use drugs (PWUDs), when sharing needles, syringes, or other equipment for injected drugs. The advent of pangenotypic direct-antiviral agents (DAA) in 2017 transformed the treatment landscape for HCV, but PWUDs remain a complex and hard-to-treat population with high risk of HCV reinfection. The aim of this real-world analysis was to characterize the demographic and clinical features of PWUDs in Italy, also focusing on comorbidity profile, treatment with DAAs, resource consumptions for the National Health System (NHS). During 01/2011-06/2020, administrative databases of Italian healthcare entities, covering 3,900,000 individuals, were browsed to identify PWUDs with or without HCV infection. Among HCV+ patients, a further stratification was made into treated and untreated with DAAs. The date of PWUD or HCV first diagnosis or DAA first prescription was considered as index-date. Patients were then followed-up for one year. Alcohol-dependency was also investigated. Total 3690 PWUDs were included, of whom 1141 (30.9%) PWUD-HCV+ and 2549 (69.1%) PWUD-HCV-. HCV-positive were significantly older (43.6 vs 38.5 years, p < 0.001), had a worse comorbidity profile (Charlson-index: 0.8 vs 0.4, p < 0.001), and high rates of psychiatric, respiratory, dermatological, musculoskeletal diseases and genitourinary (sexually transmitted) infections. Moreover, they received more drug prescriptions (other than DAAs, like anti-acids, antiepileptics, psycholeptics) and had undergone more frequent hospitalization, predominantly for hepatobiliary, respiratory system and mental disorders. DDA-untreated had significantly higher Charlson-index than DAA-treated (0.9 vs 0.6, p = 0.003). Alcoholism was found in 436 (11.8%) cases. This Italian real-world analysis suggests that PWUDs with HCV infection, especially those untreated with DAAs, show an elevated drug consumption due to their complex clinical profile. These findings could help to ameliorate the healthcare interventions on PWUDs with HCV infection.

Reinfection incidence and risk among people treated for recent hepatitis C virus infection.

Reinfection poses a challenge to hepatitis C virus (HCV) elimination. This analysis assessed incidence of, and factors associated with reinfection among people treated for recent HCV (duration of infection <12 months). Participants treated for recent HCV (primary infection or reinfection) in an international randomized trial were followed at 3-monthly intervals for up to 2 years to assess for reinfection. Reinfection incidence was calculated using person-time of observation. Factors associated with HCV reinfection were assessed using Cox proportional hazards regression analysis. Of 222 participants treated for recent HCV, 196 (62% primary infection, 38% reinfection) were included in the cohort at risk for reinfection, of whom 87% identified as gay or bisexual men, 71% had HIV and 20% injected drugs in the month prior to enrolment. During 198 person-years of follow-up, 28 cases of HCV reinfection were identified among 27 participants, for an incidence of 14.2 per 100 person-years [95% confidence interval (CI) 9.8-20.5]. Reinfection was associated with prior HCV reinfection [adjusted hazards ratio (aHR) 2.42; 95% CI 1.08-5.38], injection drug use posttreatment (aHR 2.53; 95% CI 1.14-5.59), condomless anal intercourse with casual male partners (aHR 3.32; 95% CI 1.14-9.65) and geographic region (United Kingdom, aHR 0.21; 95% CI 0.06-0.75). Among gay and bisexual men (GBM), reinfection was also associated with sexualized drug use involving injecting posttreatment (aHR 2.97; 95% CI 1.10-8.02). High reinfection incidence following treatment for recent HCV among people with ongoing sexual and drug use risk behaviour highlights the need for posttreatment surveillance, rapid retreatment of reinfection and targeted harm reduction strategies.

Immunological scars after cure of hepatitis C virus infection: Long-HepC?

Hepatitis C virus (HCV) infection provides a unique opportunity to study the effects of spontaneous or treatment-induced viral elimination on the human immune system. Twenty to 50% of patients with acute HCV infection spontaneously clear the virus, which is related to the quality of the individual's immune response, while the chronic infection is associated with an altered and impaired immune response. Direct-acting antiviral agents are now available that provide sustained viral elimination in more than 95% of patients with chronic HCV infection. Viral elimination leads to a decrease in disease sequelae such as cirrhosis and hepatocellular carcinoma, and extrahepatic manifestations also improve. However, some patients may still experience long-term complications, and viral elimination does not protect against HCV reinfection. This review addresses the question of whether the altered and impaired immune response caused by HCV normalizes after viral elimination and if this may affect the long-term clinical course after HCV cure.

HCV Management: Recent Updates

Background: Hepatitis C virus (HCV) has been a major public health threatboth worldwide and in Bangladesh due to itsconsiderable disease burden, morbidities, and death. An individualized, cost-effective, standard treatment regimen can help combat and eliminate HCV once and for all. Methods: This is an executive summary of the latest EASL (European Association for the Study of the Liver) recommendationsbased on existing literature, and clinical expertise from a panel of specialists chosen by the EASL Governing Board. Additionally, author’s clinical experience is undertaken for considering country level context. Results: HCV infection requires personalized treatment, based on factors such as genotype, liver fibrosis stage, and comorbidities. Direct-acting antiviral (DAA) regimens have replaced interferon, and are recommended as the first-line treatment for all patients with chronic HCV infection, irrespective of genotype. It is recommended to initiate treatment as soon as possible to prevent the progression of liver disease, and associated complications. For patients with decompensated cirrhosis, liver transplantation should be considered as a treatment option after weighing risk-benefit. Additionally, the management of special populations such as children, pregnant women, lactating mother, HCVpatients co-infected with HIV, HBV or SARS-CoV-2, patients with renal impairment, haemoglobin-opathies or bleeding disorders require special attention. Monitoring patients during and after treatment is recommended to ensure sustained virologic response (SVR), to detect any potential complication, and to check potential HCV reinfection. Conclusion: The EASL recommendations provide a comprehensive overview on personalized treatment of HCV, and monitoring for optimal patient outcomes, ushering high hopes for HCV elimination in the future. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 188

Management of dialysis patients with hepatitis C virus in the era of direct-acting antiviral therapy.

The clinical use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection has dramatically changed management of patients with HCV liver disease since 2014; this is also true for patients undergoing dialysis. Due to the high tolerability and antiviral efficacy of anti-HCV therapy, most dialysis patients with HCV infection should currently be candidates for this treatment. Many patients with HCV antibodies no longer have HCV infection, and it is difficult to identify patients with actual HCV infection based only on HCV antibody assays. Despite the high rate of successful HCV eradication, the risk of liver-related events such as hepatocellular carcinoma (HCC), the major complication of HCV infection, persists even after HCV cure, and patients at risk of HCC should undergo continuous HCC surveillance. Finally, the rarity of HCV reinfection and the survival benefit of HCV eradication in dialysis patients should be explored in further studies.

Determining antigen-specific T cell phenotypes in cases of Hepatitis C virus clearance versus chronic infection.

Abstract Globally, approximately 1.5 million new Hepatitis C virus (HCV) infections occur annually. A vaccine to prevent chronic HCV infection would limit HCV transmission and pathogenesis of HCV. To understand immunity to HCV infection in high risk populations, we prospectively followed HCV antibody negative high-risk people who inject drugs (PWIDs) in a protocol designed for monthly follow-up. We demonstrated previously that HCV reinfection in PWIDs is associated with a reduction in the magnitude and duration of viremia versus the initial infection and broadened cellular immune responses, consistent with protective immunity against chronic disease. We have characterized CD8+ HCV-specific T cells from the acute phase of HCV using high dimensional spectral flow cytometry to define the simultaneous expression of 25 intracellular metabolic and cell surface molecules. We found that HCV-specific CD8+ T cells from those who progress to chronic infection have a unique acute phase phenotype that clusters separately from those who later successfully control HCV. Acute phase CD8+ HCV-specific T cells from those who subsequently clear an initial HCV infection show increased expression of CD127 and CXCR3 and decreased expression of GLUT1, PD-1 and CD39 compared to acute phase T cells in those who later progress to chronic infection. Understanding HCV specific T cell phenotypes in successful control of HCV infection and reinfection will guide goals for vaccine induced immunity to prevent chronic HCV infection. Supported by grants from the NIH (U19 AI159822)

Investigating rates and risk factors for hepatitis C virus reinfection in people receiving antiviral treatment in England.

England has committed to the World Health Organization target to eliminate hepatitis C virus (HCV) as a public threat by the year 2030. Given successful treatments for HCV in recent years, it is unclear whether HCV reinfection will impact England's ability to achieve HCV elimination. We aimed to estimate the HCV reinfection rate among a cohort of patients receiving antiviral treatment using available surveillance data. Linkage between a treatment dataset from 2015 to 2019 and an HCV RNA testing dataset were used to identify people who experienced reinfection using three criteria. A Cox proportional hazards model was used to determine risk factors associated with HCV reinfection among a cohort who received treatment and had follow-up HCV RNA testing. The reinfection rate among those receiving HCV treatment was 7.91 per 100 person-years (PYs, 95% confidence interval (CI) 7.37-8.49) and highest among current injecting drug users (22.55 per 100 PYs, 95% CI 19.98-25.46) and people who had been in prison (20.42 per 100 PYs, 95% CI 17.21-24.24). In the adjusted model, women had a significantly reduced risk of reinfection. Being of younger age, current injecting drug users, and receipt of first treatment in prison were each significantly associated with increased risk of reinfection. Two-fifths of those with reinfection (43%, n=329/767) were linked to treatment after reinfection, and of those starting treatment, three quarters (75%, n=222/296) achieved a sustained virologic response. Guidance for testing groups at risk of reinfection and harm reduction strategies to minimize transmission should be implemented if England is to achieve HCV elimination targets.

Evaluating interventions to reduce behaviour associated with HCV reinfection in men who have sex with men: study protocol for a non-blinded, phase 2, randomised trial

BackgroundAs highly effective therapy against hepatitis C virus (HCV) infection is available with rapid uptake, there is newfound optimism for HCV elimination. Nevertheless, certain key populations have a high risk of HCV reinfection, in particular men who have sex with men (MSM) in Western European countries. Modelling data indicate that HCV elimination will not be feasible without reduction in risk behaviour, thus supporting the need for effective interventions aimed at reducing risk behaviour and preventing reinfections in MSM.MethodsThe ICECREAM study is an international, multi-centred, phase 2, 3-arm randomised trial comparing run-in and intervention periods enrolling MSM with a history of a cured or spontaneously cleared HCV infection. Individuals are followed in routine care for 6 months (i.e. run-in period) and then randomly allocated (1:1:1) to one of the following: a tailored, interactive online risk-reduction behavioural intervention, a validated home-based HCV-RNA self-sampling test service using dried blood spots, or a combination of both. After randomisation, individuals are followed every 6 months until 18 months (i.e. intervention period). Interventions are delivered in addition to standard of care. Online questionnaire measuring risk behaviour over the past 6 months is administered at every visit. The primary outcome is the proportion at risk of HCV infection during run-in versus intervention periods assessed by using the HCV-MOSAIC risk score. The risk score consists of six self-reported HCV-related risk behaviours. Secondary outcomes include incidence of HCV reinfection, changes in the individual risk behaviour items and changes in sexual well-being since changes in sexual behaviour may have an impact on sexual experience. Two hundred forty-six MSM aged 18 years or older will be invited to participate.DiscussionThe ICECREAM study is a trial aimed at establishing interventions that could effectively decrease the incidence of HCV re-infection in MSM with a previous HCV infection. By offering an online behavioural risk-reduction intervention and HCV-RNA self-sampling, both of which are aimed to influence risk behaviour, we are able to provide products to at-risk MSM that could further reduce population-level HCV incidence and ultimately help reach HCV micro-elimination.Trial registrationClinicalTrials.gov NCT04156945. Registered on November 8, 2019

Consensus recommendations on the management of hepatitis C in Australia's prisons.

Prison settings represent the highest concentration of prevalent hepatitis C cases in Australia due to the high rates of incarceration among people who inject drugs. Highly effective direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection are available to people incarcerated in Australian prisons. However, multiple challenges to health care implementation in the prison sector present barriers to people in prison reliably accessing hepatitis C testing, treatment, and prevention measures. This Consensus statement highlights important considerations for the management of hepatitis C in Australian prisons. High coverage testing, scale-up of streamlined DAA treatment pathways, improved coverage of opioid agonist therapy, and implementation and evaluation of regulated provision of prison needle and syringe programs to reduce HCV infection and reinfection are needed. The recommendations set current best practice standards in hepatitis C diagnosis, treatment and prevention in the Australian prison sector based on available evidence. Prison-based health services should strive to simplify and improve efficiency in the provision of the hepatitis C care cascade, including strategies such as universal opt-out testing, point-of-care testing, simplified assessment protocols, and earlier confirmation of cure. Optimising hepatitis C management in prisons is essential to prevent long term adverse outcomes for a marginalised population living with HCV. Scale-up of testing and treatment in prisons will make a major contribution towards Australia's efforts to eliminate hepatitis C as a public health threat by 2030.

Hepatitis C Virus Reinfection in a Real-World Cohort of Homeless-Experienced Individuals in Boston.

People experiencing homelessness are disproportionately affected by hepatitis C virus (HCV) infection compared with housed populations. Surveillance for HCV reinfection after successful treatment is a critical step in the care cascade, but limited data on reinfection are available among this highly marginalized group. This study assessed posttreatment reinfection risk in a real-world cohort of homeless-experienced individuals in Boston. Individuals receiving HCV direct-acting antiviral treatment through Boston Health Care for the Homeless Program during 2014-2020 with posttreatment follow-up assessment were included. Reinfection was identified based on recurrent HCV RNA at 12 weeks posttreatment with HCV genotype switch or any recurrent HCV RNA following sustain virologic response. A total of 535 individuals were included (81% male, median age 49 years, 70% unstably housed or homeless at treatment initiation). Seventy-four HCV reinfections were detected, including 5 second reinfections. HCV reinfection rate was 12.0/100 person-years (95% confidence interval [CI]: 9.5-15.1) overall, 18.9/100 person-years (95% CI: 13.3-26.7) among individuals with unstable housing and 14.6/100 person-years (95% CI: 10.0-21.3) among those experiencing homelessness. In adjusted analysis, experiencing homelessness (vs stable housing, adjusted hazard ratio, 2.14; 95% CI: 1.09-4.20; P = .026) and drug use within 6 months before treatment (adjusted hazard ratio, 5.23; 95% CI: 2.25-12.13; P < .001) were associated with increased reinfection risk. We found high HCV reinfection rates in a homeless-experienced population, with increased risk among those homeless at treatment. Tailored strategies to address the individual and systems factors impacting marginalized populations are required to prevent HCV reinfection and to enhance engagement in posttreatment HCV care.

Progress of Hepatitis C elimination in Viennese people living with HIV after two decades of increasing cure rates

Background & Aims Interferon(IFN)-based hepatitis C virus (HCV) therapy has been replaced by direct-acting antivirals (DAAs). We assessed temporal trends in patient characteristics, transmission risks, treatment initiation, and cure rates in eras of IFN, restricted DAA-access, and unrestricted DAA-access in Viennese HCV/HIV-coinfected patients (HIV/HCV). Methods Consecutive HIV/HCV-coinfected patients starting HCV treatment at the Vienna General Hospital between 2002 and 2020 were retrospectively enrolled. Results Of all N = 508 HIV/HCV, 78% (398/508) were male and the mean age was 41.8 ± 9.5 years. ‘People-who-inject-drugs’ (PWID) accounted for 61% (311/508), while 31% (156/508) were ‘men who have sex with men’ (MSM). In the IFN-era, restricted DAA-era and unrestricted DAA-era, N = 152, N = 129, and N = 227 HCV treatments were started and 49% (74/152), 95% (122/129), and 88% (200/227) achieved sustained virologic response, respectively. Treatment during the IFN-era was a strong predictor for virologic non-response (aOR 12.69; 6.93–23.24) and loss-to-follow-up (aOR 6.12; 2.99–12.54), while virologic non-response was less common in ‘MSM’ (aOR 0.28; 0.13–0.62). Ninety three percent (50/54) of the observed HCV reinfections occurred in the unrestricted DAA-era. A substantial increase in ‘MSM’ transmission was observed since 2010 with 66% (107/161) in the DAA-era versus 15% (49/330) prior to the DAA-era. Conclusions HCV cure rates in Viennese HIV patients increased from 49% in the IFN-era to 88–95% in the DAA-era. MSM-related risk behaviour and reinfections became the key challenges towards HCV elimination in HIV-coinfected patients.

Liver Transplantation from a Human Leukocyte Antigen-Matched Sibling Donor: Effectiveness of Direct-Acting Antiviral Therapy against Hepatitis C Virus Infection

Through living-donor liver transplantation (LDLT) from a human leukocyte antigen (HLA)-matched sibling donor, it may be possible to stop the use of immunosuppressants. It is possible that acute antibody-mediated rejection and chronic active antibody-mediated rejection through the positivity of donor-specific anti-HLA antibodies and/or T cell-mediated rejection may affect the prognosis of liver transplantation. The etiologies of liver diseases of the recipient may also affect the post-transplantation course. Herein, we report on the successful re-treatment with direct-acting antiviral (DAA) therapy against hepatitis C virus (HCV) infection in a patient who underwent a LDLT from HLA-matched sibling donor. After liver transplantation for HCV-related liver diseases, it is easy for HCV to re-infect the graft liver under a lack of immunosuppressants. DAA therapy against HCV re-infection immediately after transplantation should be commenced, and it is important to eradicate HCV for better prognosis of the recipients in LDLT for HCV-related liver diseases.

Differential immune transcriptomic profiles between vaccinated and resolved HCV reinfected subjects.

Successive episodes of hepatitis C virus (HCV) infection represent a unique natural rechallenge experiment to define correlates of long-term protective immunity and inform vaccine development. We applied a systems immunology approach to characterize longitudinal changes in the peripheral blood transcriptomic signatures in eight subjects who spontaneously resolved two successive HCV infections. Furthermore, we compared these signatures with those induced by an HCV T cell-based vaccine regimen. We identified a plasma cell transcriptomic signature during early acute HCV reinfection. This signature was absent in primary infection and following HCV vaccine boost. Spontaneous resolution of HCV reinfection was associated with rapid expansion of glycoprotein E2-specifc memory B cells in three subjects and transient increase in E2-specific neutralizing antibodies in six subjects. Concurrently, there was an increase in the breadth and magnitude of HCV-specific T cells in 7 out of 8 subjects. These results suggest a cooperative role for both antibodies and T cells in clearance of HCV reinfection and support the development of next generation HCV vaccines targeting these two arms of the immune system.