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

INTRODUCTION: 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. MAIN RECOMMENDATIONS: 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. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: 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.

Eliminating hepatitis C in Australia: a novel model of hepatitis C testing and treatment for people who inject drugs at a medically supervised injecting facility.

OBJECTIVE: To evaluate the feasibility of testing and treating people who inject drugs at a supervised injecting facility for hepatitis C virus (HCV) infection. DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: People who inject drugs who attended the Melbourne supervised injecting facility, 30 June 2018 - 30 June 2020. MAIN OUTCOME MEASURES: Proportion of people tested for hepatitis C; proportions of people positive for anti-HCV antibody and HCV RNA, and of eligible people prescribed direct-acting antiviral (DAA) treatment; sustained virological response twelve weeks or more after treatment completion. RESULTS: Of 4649 people who attended the supervised injecting facility during 2018-20, 321 were tested for hepatitis C (7%); 279 were anti-HCV antibody-positive (87%), of whom 143 (51%) were also HCV RNA-positive. Sixty-four of 321 had previously been treated for hepatitis C (20%), 21 had clinically identified cirrhosis (7%), eight had hepatitis B infections (2%), and four had human immunodeficiency virus infections (1%). In multivariate analyses, people tested for hepatitis C were more likely than untested clients to report psychiatric illness (adjusted odds ratio [aOR], 9.65; 95% confidence interval [CI], 7.26-12.8), not have a fixed address (aOR, 1.59; 95% CI, 1.18-2.14), and to report significant alcohol use (aOR, 1.57; 95% CI, 1.06-2.32). The median number of injecting facility visits was larger for those tested for hepatitis C (101; interquartile range [IQR], 31-236) than for those not tested (20; IQR, 3-90). DAA treatment was prescribed for 126 of 143 HCV RNA-positive clients (88%); 41 of 54 with complete follow-up data were cured (76%). CONCLUSIONS: People who attend supervised injecting facilities can be tested and treated for hepatitis C on site. Models that provide streamlined, convenient hepatitis C care promote engagement with treatment in a group in which the prevalence of hepatitis C is high.

Efficacy and Safety of Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus (HCV) NS5A-Inhibitor Experienced Patients With Difficult to Cure Characteristics.

BACKGROUND: In clinical trials, hepatitis C virus (HCV) salvage treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort. METHODS: We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE). FINDINGS: Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n = 46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A, and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n = 82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n = 18/18, GT1b n = 2/4), 89% in GT3 (n = 59/66) and 100% in GT6 (n = 3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were 4 serious AEs including 1 death and 3 hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. CONCLUSIONS: This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most; however, serious AEs can occur in those with advanced liver disease.

Outcomes of treatment for hepatitis C in prisoners using a nurse-led, statewide model of care.

BACKGROUND & AIMS: Treatment programs for people who inject drugs (PWID), including prisoners, are important for achieving hepatitis C elimination targets. There are multiple barriers to treatment of hepatitis C in prisons, including access to specialist physicians, testing and antiviral therapy, short prison sentences, and frequent inter-prison transfer. We aimed to assess the effectiveness of a nurse-led model of care for the treatment of prisoners with hepatitis C. METHODS: A statewide program for assessment and management of hepatitis C was developed in Victoria, Australia to improve access to care for prisoners. This nurse-led model of care is supported by telemedicine to provide decentralized care within all prisons in the state. We prospectively evaluated the feasibility and efficacy of this nurse-led model of care for hepatitis C within the 14 adult prisons over a 13-month period. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) using per protocol analysis. RESULTS: There were 416 prisoners included in the analysis. The median age was 41 years, 90% were male, 50% had genotype 3 and 44% genotype 1 hepatitis C and 21% had cirrhosis. Injecting drug use was reported by 68% in the month prior to prison entry, 54% were receiving opioid substitution therapy, and 86% reported never previously engaging with specialist HCV care. Treatment duration was 8 weeks in 24%, 12 weeks in 59%, and 24 weeks in 17% of treatment courses. The SVR12 rate was 96% (301/313) per protocol. Inter-prison transfer occurred during 26% of treatment courses but was not associated with lower SVR12 rates. No treatment-related serious adverse events occurred. CONCLUSION: Hepatitis C treatment using a decentralized, nurse-led model of care is highly effective and can reach large numbers of prisoners. Large scale prison treatment programs should be considered to support hepatitis C elimination efforts. LAY SUMMARY: There is a high burden of hepatitis C infection among prisoners worldwide. Prisoners who continue to inject drugs are also at risk of developing new infections. For this reason, the prison setting provides an opportunity to treat those people at greatest risk of infection and to stop transmission to others. We developed a new method of providing hepatitis C treatment to prisoners, in which nurses rather than doctors assessed prisoners locally at each prison site. Treatment was safe and most prisoners were cured. Such programs will contribute greatly to achieving the World Health Organization's hepatitis C elimination goals.

Retreatment with elbasvir, grazoprevir, sofosbuvir ± ribavirin is effective for GT3 and GT1/4/6 HCV infection after relapse.

INTRODUCTION: Despite highly effective direct-acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection, some patients experience virological relapse. Salvage regimens should include multiple agents to suppress emergence of resistance-associated substitutions (RAS) and minimise treatment failure. The combination of sofosbuvir (SOF) and elbasvir/grazoprevir (ELB/GZR) ±ribavirin (RBV) is an effective retreatment strategy for HCV genotype (GT)1 and 4 infection. We hypothesised that SOF and ELB/GZR (±RBV) would also be an effective salvage regimen for DAA-experienced GT3 patients. METHODS: We evaluated the efficacy and safety of SOF/ELB/GZR ± RBV in DAA-experienced participants with chronic HCV infection who had prior relapse. Participants were treated at four hospitals between December 2016 and March 2018 for either 12- or 16-weeks. The primary endpoint was sustained virological response at week 12 post-treatment (SVR12) using intention-to-treat analysis. RESULTS: There were 40 participants included in the analysis. The mean age was 53 years, 53% had GT3, 33% had GT1 infection and 63% had cirrhosis. Fifty-eight percent were treated for 12 weeks, 42% were treated for 16 weeks and 90% received RBV. The SVR12 rate was 98% overall, 100% in non-GT3 participants and 95% in GT3 participants. One GT3 cirrhotic participant relapsed. ELB/GZR was stopped at week 6 in one GT3 cirrhotic participant who switched to SOF/velpatasvir/RBV for a further 12 weeks and achieved SVR12. RBV dose reduction was required in two participants. Treatment was otherwise well tolerated. DISCUSSION: The combination of SOF/ELB/GZR ± RBV is effective and safe for difficult-to-cure patients who relapse after first-line DAA, including those with cirrhosis and GT3 infection.

Terlipressin: Current and emerging indications in chronic liver disease.

Terlipressin is an analogue of vasopressin that has potent vasoactive properties and has been available for use in most countries for nearly two decades. It has both established roles and emerging indications in the management of complications of decompensated chronic liver disease. We explore historic and emerging literature regarding the use of terlipressin for a range of indications including hepatorenal syndrome, portal hypertensive bleeding, and disruptions in sodium homeostasis. Novel methods of infusion-based terlipressin administration including the beneficial effect in reduction of adverse events are explored, in addition to new indications for the use of terlipressin in decompensated cirrhosis in an outpatient setting.

Point-of-care HCV RNA testing improves hepatitis C testing rates and allows rapid treatment initiation among people who inject drugs attending a medically supervised injecting facility.

BACKGROUND: To achieve hepatitis C virus (HCV) elimination targets, simplified care engaging people who inject drugs is required. We evaluated whether fingerstick HCV RNA point-of-care testing (PoCT) increased the proportion of clients attending a supervised injecting facility who were tested for hepatitis C. METHODS: Prospective single-arm study with recruitment between 9 November 2020 and 28 January 2021 and follow-up to 31 July 2021. Clients attending the supervised injecting facility were offered HCV RNA testing using the Xpert® HCV Viral Load Fingerstick (Cepheid, Sunnyvale, CA) PoCT. Participants with a positive HCV RNA test were prescribed direct acting antiviral (DAA) therapy. The primary endpoint was the proportion of clients who engaged in HCV RNA PoCT, compared to a historical comparator group when venepuncture-based hepatitis C testing was standard of care. RESULTS: Among 1618 clients who attended the supervised injecting facility during the study period, 228 (14%) engaged in PoCT. This was significantly higher than that observed in the historical comparator group (61/1,775, 3%; p < 0.001). Sixty-five (28%) participants were HCV RNA positive, with 40/65 (62%) receiving their result on the same day as testing. Sixty-one (94%) HCV RNA positive participants were commenced on DAA therapy; 14/61 (23%) started treatment on the same day as diagnosis. There was no difference in the proportion of HCV RNA positive participants commenced on treatment with DAA therapy when compared to the historical comparator group (61/65, 94% vs 22/26, 85%; p = 0.153). However, the median time to treatment initiation was significantly shorter in the PoCT cohort (2 days (IQR 1-20) vs 41 days (IQR 22-76), p < 0.001). Among participants who commenced treatment and had complete follow-up data available, 27/36 (75%) achieved hepatitis C cure. CONCLUSIONS: HCV RNA PoCT led to a significantly higher proportion of clients attending a supervised injecting facility engaging in hepatitis C testing, whilst also reducing the time to treatment initiation.

The Importance of Prisons in Achieving Hepatitis C Elimination: Insights from the Australian Experience.

Following the availability of highly effective direct-acting antivirals (DAAs) to treat hepatitis C infection, the uptake of treatment by people living with hepatitis C rose dramatically in high- and middle-income countries but has since declined. To achieve the World Health Organization's (WHO) 2030 target to eliminate hepatitis C as a public health threat among people who inject drugs, an increase in testing and treatment is required, together with improved coverage of harm reduction interventions. The population that remains to be treated in high- and middle-income countries with high hepatitis C prevalence are among the most socially disadvantaged, including people who inject drugs and are involved in the criminal justice system, a group with disproportionate hepatitis C prevalence, compared with people in the wider community. Imprisonment provides an unrivalled opportunity for screening and treating large numbers of people for hepatitis C, who may not access mainstream health services in the community. Despite some implementation challenges, evidence of the efficacy, acceptability, and cost-effectiveness of in-prison hepatitis treatment programs is increasing worldwide, and evaluations of these programs have demonstrated the capacity for treating people in high numbers. In this Perspective we argue that the scale-up of hepatitis C prevention, testing, and treatment programs in prisons, along with the investigation of new and adapted approaches, is critical to achieving WHO elimination goals in many regions; the Australian experience is highlighted as a case example. We conclude by discussing opportunities to improve access to prevention, testing, and treatment for people in prison and other justice-involved populations, including harnessing the changed practices brought about by the COVID-19 pandemic.

Care Navigation Increases Initiation of Hepatitis C Treatment After Release From Prison in a Prospective Randomized Controlled Trial: The C-LINK Study.

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.

A costing analysis of a state-wide, nurse-led hepatitis C treatment model in prison.

BACKGROUND: Hepatitis C is highly prevalent among prisoners. The simplicity of direct-acting antiviral (DAA) treatment for hepatitis C makes it possible to use novel models of care to increase treatment uptake within prisons. We estimate the average non-drug cost of initiating a prisoner on treatment using real world data from the State-wide Hepatitis Program (SHP) in Victoria, Australia - a coordinated nurse-led model of care. METHODS: Data were considered from prisoners presenting to the SHP (following antibody-positive diagnosis) during the evaluation period, November 2015 to December 2016. All costs associated with the SHP were estimated, including staffing salaries, medical tests, pharmacy costs and overhead costs. DAA costs were excluded as in Australia an unlimited number are available, covered by a federal government risk-sharing agreement with pharmaceutical companies. The average non-drug cost of treatment initiation through the SHP was compared to equivalent costs from primary and hospital-based models of care in the community. RESULTS: The total non-drug cost accumulated by prisoners in the SHP was AUD$749,470 (uncertainty range: AUD$728,905-794,111). 659/803 were PCR positive, 424/659 had sentences long enough to be eligible for treatment, and 416/424 were initiated on treatment, resulting in an average non-drug cost of AUD$1,802 (95% CI: AUD$1799-1841) per prisoner initiated. A protocol change allowing prisoners with short sentences to start treatment reduced the average non-drug cost to AUD$1263 (95% CI: AUD$1263-1287) per prisoner initiating treatment - 11% and 56% cheaper than estimated equivalent costs in primary (AUD$1654) and hospital-based (AUD$2847) models of care in the community, respectively. CONCLUSION: Delivering hepatitis C treatment in prison using a nurse-led model of care is cheaper than delivering treatment in the community. These findings provide an economic rationale for implementing coordinated prison-based hepatitis C treatment programs.

Short-term intraperitoneal catheters: An ambulatory care intervention for refractory ascites secondary to cirrhosis during COVID-19.

BACKGROUND AND AIM: Patients with refractory ascites have frequent hospital admissions, which pose exposure risks in the context of the COVID-19 pandemic. The aim of this study was to investigate the safety and efficacy of a novel 12-week, multidisciplinary ambulatory care program allowing frequent low-volume ascitic drainage through a tunneled, intraperitoneal catheter (IPC). METHODS: Adult patients with cirrhosis complicated by refractory ascites were recruited through a liver clinic in a tertiary health service in Melbourne, Australia from April to December 2020. All patients were enrolled in a 12-week multidisciplinary program including medical, nursing, dietetics, and pharmacy support. A Rocket Medical IPC was inserted on day 1 with 1-2 L of ascitic fluid drained over 1-3 sessions per week either at the patients' homes or at the hospital day ward. Patients' demographics, death, complications, and self-reported outcomes were recorded. RESULTS: Twelve patients were enrolled with a median of 65-day (interquartile range [IQR]: 16.5-93) IPC duration between April and December 2020 across two periods of COVID-related lockdown in Melbourne, Australia. There were no IPC-related deaths. Early removal was necessitated in three patients due to leakage, nonadherence, and bacteremia. On day 30, the median self-reported health score increased from 50 (IQR: 50-70) to 78 (IQR: 50-85), attributable to a reduction in symptom burden. CONCLUSION: A multidisciplinary IPC program including the use of short-term IPC was safe and associated with a self-reported improvement in perceptions of health. In the context of the COVID-19 pandemic, the program aimed to reduce patient and clinician exposure, which is maintaining engagement and management of decompensated cirrhosis.

Non-invasive fibrosis algorithms are clinically useful for excluding cirrhosis in prisoners living with hepatitis C.

BACKGROUND AND AIMS: Prison-based HCV treatment rates remain low due to multiple barriers, including accessing transient elastography for cirrhosis determination. The AST-to-platelet ratio index (APRI) and FIB-4 scores have excellent negative predictive value (NPV) in hospital cohorts to exclude cirrhosis. We investigated their performance in a large cohort of prisoners with HCV infection. METHODS: This was a retrospective cohort study of participants assessed by a prison-based hepatitis program. The sensitivity, specificity, NPV and positive predictive value (PPV) of APRI and FIB-4 for cirrhosis were then analysed, with transient elastography as the reference standard. The utility of age thresholds as a trigger for transient elastography was also explored. RESULTS: Data from 1007 prisoners were included. The median age was 41, 89% were male, and 12% had cirrhosis. An APRI cut-off of 1.0 and FIB-4 cut-off of 1.45 had NPVs for cirrhosis of 96.1% and 96.6%, respectively, and if used to triage prisoners for transient elastography, could reduce the need for this investigation by 71%. The PPVs of APRI and FIB-4 for cirrhosis at these cut-offs were low. Age ≤35 years alone had a NPV for cirrhosis of 96.5%. In those >35 years, the APRI cut-off of 1.0 alone had a high NPV >95%. CONCLUSION: APRI and FIB-4 scores can reliably exclude cirrhosis in prisoners and reduce requirement for transient elastography. This finding will simplify the cascade of care for prisoners living with hepatitis C.

Exploring the feasibility of targeted chronic hepatitis B screening in the emergency department: A pilot study.

OBJECTIVE: To explore the feasibility of an ED chronic hepatitis B (CHB) screening programme. METHODS: Adult patients born in intermediate-high CHB prevalent regions completed a pre-screening questionnaire and were offered CHB testing. ED staff were surveyed to gauge potential barriers to the programme. RESULTS: Eighty patients demonstrated limited knowledge of hepatitis B virus transmission and perceived many barriers to screening. Among 65 tested for CHB, no new cases were detected but 36 (55.4%, 95% CI 42.6-67.5) were susceptible to infection. Staff supported the programme but reported potential barriers. CONCLUSION: Targeted ED CHB screening is feasible but effectiveness and cost-effectiveness need further exploration.