BACKGROUND:Prisons provide a key strategic opportunity to upscale hepatitis C testing and treatment in a high-prevalence setting and are crucial for elimination efforts. METHODS:A decentralized, statewide, nurse-led model of care offering hepatitis C treatment for people in prison was implemented in Victoria, Australia, in 2015. The program provides hepatitis C care at all 14 adult prisons in the jurisdiction. We prospectively evaluated treatment uptake between 1 November 2015 and 31 December 2021. Data on all people in prison who were treated were recorded in a clinical database. Primary outcomes were the number of people in prison who completed hepatitis C treatment with direct-acting antiviral (DAA) therapy and the proportion who achieved sustained virologic response (SVR12). RESULTS:A total of 3133 DAA treatment courses were prescribed to 2768 people in prison. The proportion of total Victoria DAA prescriptions the program was responsible for increased from 6% in 2016 to a peak of 23% in 2020. The median age was 39 years, 91% were male, and 9% had cirrhosis. Few (20%) had previously engaged in hepatitis C care in the community only 6% were treatment experienced. Complete follow-up data were available for 1757 of 2768 (63%) treated, with 1627 of 1757 (93%) achieving SVR12. CONCLUSIONS:A decentralized, nurse-led, statewide model of care was highly effective in treating large numbers of people in prison with hepatitis C and achieved high rates of SVR12. Nurse-led prison programs are playing a crucial role in eliminating hepatitis C as a public health threat in Australia.

Background & Aims:Short duration treatment may aid HCV elimination among key populations. This study evaluated the efficacy of glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection. Methods:In this single-arm multicentre international trial, adults with recent HCV (duration of infection <12 months) received glecaprevir-pibrentasvir 300 mg-120 mg daily for 4 weeks. Primary infection was defined as a first positive anti-HCV antibody and/or HCV RNA measurement within 6 months of enrolment and either acute clinical hepatitis within 12 months (symptomatic illness or alanine aminotransferase >10x the upper limit of normal) or antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within 6 months and prior clearance (spontaneous or treatment). The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) and per-protocol (PP) populations. Results:Twenty-three participants (96% men, 70% HIV, 57% ever injected drugs) received treatment, of whom 74% had genotype 1a infection and 35% recent reinfection. At baseline, median duration of infection was 17 weeks (IQR 11-29) and HCV RNA was 5.8 log10IU/ml (IQR 5.2-6.9). SVR12 was achieved by 78% (18/23; 95% CI 56-93%) and 82% (18/22; 95% CI 60-95%) of the ITT and PP populations, respectively, and in 100% (12/12; 95% CI 74-100%) of participants with baseline HCV RNA ≤6 log10. There were four cases of virological failure (relapse); three received retreatment with 12 weeks sofosbuvir-velpatasvir or grazoprevir-elbasvir (SVR, n = 2; loss to follow-up, n = 1). No serious adverse events were reported. Conclusion:While most achieved SVR, the efficacy of a 4-week regimen of glecaprevir-pibrentasvir was lower than observed with longer treatment durations (≥6 weeks) among people with recent HCV. Trial Registration:Clinicaltrials.gov Identifier: NCT02634008. Impact and implications:Short duration treatment may aid HCV elimination among key populations. This investigator-initiated single-arm multicentre international pilot trial demonstrated that efficacy of glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection was sub-optimal (SVR12 78% ITT, 82% PP). Baseline HCV RNA appeared to impact response, with higher efficacy among participants with lower baseline HCV RNA (≤6 log10; SVR12 100% ITT, 12/12). While most achieved SVR, the efficacy of 4 weeks of glecaprevir-pibrentasvir was below that seen with longer treatment durations (≥6 weeks).

BACKGROUND:Hepatitis C virus (HCV) reinfection after successful treatment may reduce the benefits of cure among people who inject drugs. OBJECTIVE:To evaluate the rate of HCV reinfection for 3 years after successful treatment among people receiving opioid agonist therapy (OAT). DESIGN:A 3-year, long-term, extension study of persons enrolled in the CO-STAR (Hepatitis C Patients on Opioid Substitution Therapy Antiviral Response) study (ClinicalTrials.gov: NCT02105688). SETTING:55 clinical trial sites in 13 countries. PATIENTS:Aged 18 years and older with chronic HCV infection with genotypes 1, 4, or 6 receiving stable OAT. INTERVENTION:No treatments were administered. MEASUREMENTS:Serum samples were assessed for HCV reinfection. Urine drug screening was performed. RESULTS:Among 296 participants who received treatment, 286 were evaluable for reinfection and 199 were enrolled in the long-term extension study. The rate of HCV reinfection was 1.7 [95% CI, 0.8 to 3.0] per 100 person-years; 604 person-years of follow-up). A higher rate of reinfection was seen among people with recent injecting drug use (1.9 [95% CI, 0.5 to 4.8] per 100 person-years; 212 person-years). Ongoing drug use and injecting drug use were reported by 59% and 21% of participants, respectively, at the 6-month follow-up visit and remained stable during 3 years of follow-up. LIMITATIONS:Participants were required to be 80% adherent to OAT at baseline and may represent a population with higher stability and lower risk for HCV reinfection. Rate of reinfection may be underestimated because all participants did not continue in the long-term extension study; whether participants who discontinued were at higher risk for reinfection is unknown. CONCLUSION:Reinfection with HCV was low but was highest in the first 24 weeks after treatment completion and among people with ongoing injecting drug use and needle-syringe sharing. PRIMARY FUNDING SOURCE:Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

BACKGROUND:In people with chronic hepatitis C virus (HCV) infection, viral eradication is associated with improved health-related quality of life (HRQOL). OBJECTIVE:To assess changes in HRQOL among participants receiving opioid agonist therapy undergoing treatment for HCV infection. METHODS:COSTAR (NCT02251990) was a randomized, double-blind, placebo-controlled study. Adults with HCV infection on opioid agonist therapy received elbasvir (50 mg)/grazoprevir (100 mg) or placebo for 12 weeks. HRQOL was evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey version 2 (SF-36v2) Acute Form. Participants remained blinded until 4 weeks after end of treatment. RESULTS:Overall, 201 participants received elbasvir/grazoprevir and 100 participants received placebo. Treatment difference mean change from baseline scores (elbasvir/grazoprevir minus placebo) indicated an improvement in HRQOL at 4 weeks after end of treatment in participants receiving elbasvir/grazoprevir versus those receiving placebo, driven by declining HRQOL in those receiving placebo and improved HRQOL in certain domains among participants receiving elbasvir/grazoprevir. Notable differences in SF-36v2 scores were evident in the general health (mean treatment difference [MTD], 6.00; 95% CI, 1.37-10.63), vitality (MTD, 6.81; 95% CI, 1.88-11.75), and mental health (MTD, 5.17; 95% CI, 0.52-9.82) domains and in the mental component summary score (mean, 2.83; 95% CI, 0.29-5.37). No notable between-treatment differences were evident at treatment weeks 4 or 12. CONCLUSION:HRQOL in patients receiving medication for opioid dependence was improved following treatment for HCV infection with elbasvir/grazoprevir, suggesting that eradication of HCV infection with direct-acting antivirals is associated with improved HRQOL. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov, NCT02251990.

INTRODUCTION:The prevalence of hepatitis B virus (HBV) infection in Australia is nearly 1%. In certain well defined groups the prevalence is far greater, yet an estimated 27% of people living with HBV infection remain undiagnosed. Appropriate screening improves detection, increases opportunity for treatment, and ultimately reduces the significant morbidity and mortality associated with the development of liver fibrosis and hepatocellular carcinoma (HCC).MAIN RECOMMENDATIONS:This statement highlights important aspects of HBV infection management in Australia. There have been recent changes in nomenclature and understanding of natural history, as well as a newly defined upper limit of normal for liver tests that determine phase classification and threshold for antiviral treatment. As the main burden of hepatitis B in Australia is within migrant and Indigenous communities, early identification and management of people living with hepatitis B is essential to prevent adverse outcomes including liver cancer and cirrhosis.CHANGE IN MANAGEMENT AS A RESULT OF THIS GUIDELINE:These recommendations aim to raise awareness of the current management of hepatitis B in Australia. Critically, the timely identification of individuals living with hepatitis B, and where appropriate, commencement of antiviral therapy, can prevent the development of cirrhosis, HCC and mother-to-child transmission as well as hepatitis B reactivation in immunocompromised individuals. Recognising patient and viral factors that predispose to the development of cirrhosis and HCC will enable clinicians to risk-stratify and appropriately implement surveillance strategies to prevent these complications of hepatitis B.

Virological failure occurs in a small proportion of people treated for hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapies. This study assessed retreatment for virological failure in a large real-world cohort. REACH-C is an Australian observational study (n=10843) evaluating treatment outcomes of sequential DAA initiations across 33 health services between March 2016 to June 2019. Virological failure retreatment data were collected until October 2020. Of 408 people with virological failure (81% male; median age 53; 38% cirrhosis; 56% genotype 3), 213 (54%) were retreated once; 15 were retreated twice. A range of genotype specific and pangenotypic DAAs were used to retreat virological failure in primary (n=56) and tertiary (n=157) settings. Following sofosbuvir/velpatasvir/voxilaprevir availability in 2019, the proportion retreated in primary care increased from 21% to 40% and median time to retreatment initiation declined from 294 to 152 days. Per-protocol (PP) sustained virological response (SVR12) was similar for people retreated in primary and tertiary settings (80% vs 81%; p=1.000). In regression analysis, sofosbuvir/velpatasvir/voxilaprevir (vs. other regimens) significantly decreased likelihood of second virological failure (PP SVR12 88% vs. 77%; adjusted odds ratio [AOR] 0.29; 95%CI 0.11-0.81); cirrhosis increased likelihood (PP SVR12 69% vs. 91%; AOR 4.26; 95%CI 1.64-11.09). Indigenous Australians had lower likelihood of retreatment initiation (AOR 0.36; 95%CI 0.15-0.81). Treatment setting and prescriber type were not associated with retreatment initiation or outcome. Virological failure can be effectively retreated in primary care. Expanded access to simplified retreatment regimens through decentralised models may increase retreatment uptake and reduce HCV-related mortality.

Abstract Background Prison-based hepatitis C treatment is safe and effective; however, many individuals are released untreated due to time or resource constraints. On community re-entry, individuals face a number of immediate competing priorities, and in this context, linkage to hepatitis C care is low. Interventions targeted at improving healthcare continuity after prison release have yielded positive outcomes for other health diagnoses; however, data regarding hepatitis C transitional care are limited. Methods We conducted a prospective randomized controlled trial comparing a hepatitis C care navigator intervention with standard of care for individuals released from prison with untreated hepatitis C infection. The primary outcome was prescription of hepatitis C direct-acting antivirals (DAA) within 6 months of release. Results Forty-six participants were randomized. The median age was 36 years and 59% were male. Ninety percent (n = 36 of 40) had injected drugs within 6 months before incarceration. Twenty-two were randomized to care navigation and 24 were randomized to standard of care. Individuals randomized to the intervention were more likely to commence hepatitis C DAAs within 6 months of release (73%, n = 16 of 22 vs 33% n = 8 of 24, P < .01), and the median time between re-entry and DAA prescription was significantly shorter (21 days [interquartile range {IQR}, 11–42] vs 82 days [IQR, 44–99], P = .049). Conclusions Care navigation increased hepatitis C treatment uptake among untreated individuals released from prison. Public policy should support similar models of care to promote treatment in this high-risk population. Such an approach will help achieve hepatitis C elimination as a public health threat.

Conclusion: Dry blood sampling can identify promising biomarker candidates that could improve HCC time-to-and stage-at-diagnosis.While our findings will be confirmed in a prospective study, focusing on age and risk factor stratification, we aim to translate our findings into an easy-to-use, low-cost population screening tool for HCC.

Australia was one of the first countries with unrestricted access to government subsidized direct‐acting antiviral (DAA) therapy for adults with chronic hepatitis C virus. This study assessed real‐world DAA treatment outcomes across a diverse range of Australian clinical services and evaluated factors associated with successful treatment and loss to follow‐up. Real‐world Effectiveness of Antiviral therapy in Chronic Hepatitis C (REACH‐C) consisted a national observational cohort of 96 clinical services including specialist clinics and less traditional settings such as general practice. Data were obtained on consecutive individuals who commenced DAAs from March 2016 to June 2019. Effectiveness was assessed by sustained virological response ≥12 weeks following treatment (SVR) using intention‐to‐treat (ITT) and per‐protocol (PP) analyses. Within REACH‐C, 10,843 individuals initiated DAAs (male 69%; ≥50 years 52%; cirrhosis 22%). SVR data were available in 85% (9,174 of 10,843). SVR was 81% (8,750 of 10,843) by ITT and 95% (8,750 of 9,174) by PP. High SVR (≥92%) was observed across all service types and participant characteristics. Male gender (adjusted odds ratio [aOR] 0.56, 95% confidence interval [CI] 0.43‐0.72), cirrhosis (aOR 0.52, 95% CI 0.41‐0.64), recent injecting drug use (IDU; aOR 0.64, 95% CI 0.46‐0.91) and previous DAA treatment (aOR 0.50, 95% CI 0.28‐0.90) decreased the likelihood of achieving SVR. Multiple factors modified the likelihood of loss to follow‐up including IDU ± opioid agonist therapy (OAT; IDU only: aOR 1.75, 95% CI 1.44‐2.11; IDU + OAT: aOR 1.39, 95% CI 1.11‐1.74; OAT only, aOR 1.36; 95% CI 1.13‐1.68) and age (aOR 0.97, 95% CI 0.97‐0.98). Conclusion: Treatment response was high in a diverse population and through a broad range of services following universal access to DAA therapy. Loss to follow‐up presents a real‐world challenge. Younger people who inject drugs were more likely to disengage from care, requiring innovative strategies to retain them in follow‐up.

Background Portal hypertension (PH) remains an important sequela of cirrhosis, contributing to morbidity and mortality. Non-invasive algorithms identifying patients at risk of clinically significant portal hypertension (CSPH) and high-risk gastro-oesophageal varices (varices needing treatment, VNT) are critical. We previously described an algorithm whereby liver stiffness measurement (LSM) ≤25 kPa plus platelets ≥100 excluded VNT in Child-Pugh A cirrhosis. 5 years following the inception of our initial study, this study aimed to assess the prognostic value of LSM ≤25 kPa plus platelets ≥100 in predicting long-term hepatic decompensation and death. Methods This is a retrospective multicentre study of patients from two tertiary centres. Medical records were reviewed for all subsequent gastroscopies, LSM, six-monthly laboratory tests and abdominal ultrasounds, symptoms/signs consistent with hepatic decompensation (ascites, variceal bleeding, hepatic encephalopathy), and mortality from the initial study date. Patients with an LSM >25 kPa plus platelets <100 were considered high risk for VNT, while patients with LSM ≤25 kPa and/or platelets ≥100 were considered low risk. Results 180 patients were included. Median age was 55 yrs (IQR 49-63), 70% male, with no significant difference between groups. Median follow-up was 7.7 yrs (4.5-9.0). At study inception, 30/180 (17%) were high risk. The majority (114/180, 63%) had cirrhosis secondary to HCV, similar according to risk group (p=0.752). Decompensation was significantly more common in high-risk patients (11/30 (37%) vs 26/150 (17%) respectively, p=0.016; (IDDF2021-ABS-0056 Figure 1. Decompensation according to high-risk and low-risk category)). 2/150 (1%) low-risk patients were re-classified as high-risk. 19/150 (13%) of low-risk patients had VNT compared to 7/30 (23%) in the high-risk group (p=0.043). There was a trend towards higher mortality in high-risk vs low-risk patients (12/30 (40%) vs 36/150 (24%), respectively, p=0.067; (IDDF2021-ABS-0056 Figure 2. Death according to high-risk and low-risk category)). Conclusions Our previously defined algorithm of LSM and platelets has prognostic value in predicting for subsequent decompensation and death. LSM+PLT can assist in stratifying future risk of liver-related events in Child-Pugh A cirrhotics.

An estimated 18% of people living with chronic hepatitis B (CHB) in Australia were born in China. While guideline‐based care, including regular clinical monitoring and timely treatment, prevent CHB‐related cirrhosis, cancer and deaths, over three‐quarters of people with CHB do not receive guideline‐based care in Australia. This qualitative study aimed to identify enablers to engagement in CHB clinical management among ethnic Chinese people attending specialist care. Participants self‐identified as of Chinese ethnicity and who attended specialist care for CHB clinical management were interviewed in Melbourne in 2019 (n = 30). Semi‐structured interviews covered experiences of diagnosis and engagement in clinical management services, and advice for people living with CHB. Interviews were recorded with consent; data were transcribed verbatim and thematically analysed. Receiving clear information about the availability of treatment and/or the necessity of long‐term clinical management were the main enablers for participants to engage in CHB clinical management. Additional enablers identified to maintain regular clinical monitoring included understanding CHB increases risks of cirrhosis and liver cancer, using viral load indicators to visualize disease status in patient‐doctor communication; expectations from family, peer group and medical professionals; use of a patient recall system; availability of interpreters or multilingual doctors; and largely subsidized healthcare services. In conclusion, to support people attending clinical management for CHB, a holistic response from community, healthcare providers and the public health sector is required. There are needs for public health programmes directed to communicate (i) CHB‐related complications; (ii) availability of effective and cheap treatment; and that (iii) long‐term engagement with clinical management and its benefits.

BACKGROUND:Hepatitis C virus (HCV) treatment through primary care and community-based services will be a critical component of HCV elimination. We evaluated a nurse-coordinated programme providing care across eight sites and analysed progression through the HCV care cascade. METHODS:People-accessing services from six primary care clinics, a homeless crisis accommodation provider and a mental health service were directly referred to nurses or engaged by nurses during regular clinic visits. Nurses supported HCV testing, treatment and follow-up. The prescription was provided by affiliated clinicians. Logistic regression was used to examine factors associated with treatment commencement and sustained virological response (SVR) testing. RESULTS:Of 640 people referred to and/or engaged by the nurses from January 2017 to July 2019, 518 had an HCV RNA test of whom 381 (74%) were HCV RNA positive. Treatment was commenced by 281 (74%) people of whom 161 had an SVR test, 157 (97.5%) were cured. Opioid agonist therapy was associated with treatment commencement (aOR 2.68, 95% CI 1.48-4.88). People who were homeless/unstably housed were less likely to commence treatment (aOR 0.45, 95% CI 0.23-0.87). Treatment prescription from a specialist (aOR 2.39, 95% CI 1.20-4.74) and recent injection drug use (<6 months) (aOR 2.15, 95% CI 1.07-4.31) was associated with SVR testing. CONCLUSION:A nurse-coordinated model of care led to high levels of HCV treatment uptake and cure amongst people attending primary care and community services. More tailored models of care may be beneficial for people who are homeless or have unstable housing. These results support primary care and community-based hepatitis C treatment.

BackgroundDirect acting antiviral (DAA) therapy is highly effective for hepatitis C virus (HCV) infection, but reinfection following treatment may compromise benefits of cure. This study assessed the real-world effectiveness of treatment for reinfection.MethodsReal-world effectiveness of antiviral therapy in chronic hepatitis C (REACH-C) is an observational study evaluating treatment outcomes following sequential DAA initiations across 33 health services in Australia between March 2016-June 2019. Reinfection was defined by post-treatment genotype switch or HCV viraemia after sustained virologic response (SVR12).ResultsOf the 10,843 individuals initiating DAA therapy post-treatment viraemia was reported in 526 of whom 99 were reinfections. Treatment for reinfection occurred in 88 individuals. In those with available treatment outcomes, SVR12 was similar to initial treatment in the overall REACH-C cohort (95% vs 95%; p = 0.745) and comparable across primary, tertiary, and prison settings. Classifying unknown treatment outcomes as failures, SVR12 for treatment of reinfection was lower than initial treatment in REACH-C (67% vs 81%; p = 0.002), due to higher lost to follow-up.ConclusionsTreatment of reinfection is highly effective and can be delivered in non-specialist settings. Access to treatment for reinfection in high-risk populations is crucial to HCV elimination.