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Globally, 130–170 million people have HCV infection; however, distribution patterns are highly variable. This Review outlines the latest information on the epidemiology and natural history of HCV infection. The disease burden and mortality of HCV-related diseases, and the potential effect of HCV treatment on disease burden, are also outlined. Worldwide, an estimated 130–170 million people have HCV infection. HCV prevalence is highest in Egypt at >10% of the general population and China has the most people with HCV (29.8 million). Differences in past HCV incidence and current HCV prevalence, together with the generally protracted nature of HCV disease progression, has led to considerable diversity in the burden of advanced liver disease in different countries. Countries with a high incidence of HCV or peak incidence in the recent past will have further escalations in HCV-related cirrhosis and hepatocellular carcinoma (HCC) over the next two decades. Acute HCV infection is difficult to detect because of the generally asymptomatic nature of the disease and the marginalization of at-risk populations. Around 25% of patients with acute HCV infection undergo spontaneous clearance, with increased rates among those with favourable IL28B genotypes, acute symptoms and in women. The remaining 75% of patients progress to chronic HCV infection and are subsequently at risk of progression to hepatic fibrosis, cirrhosis and HCC. Chronic hepatitis C generally progresses slowly in the initial two decades, but can be accelerated during this time as a result of advancing age and co-factors such as heavy alcohol intake and HIV co-infection. Key Points Although many countries in Asia have a low-to-intermediate prevalence of HCV, around half of the global population of patients infected with HCV reside in this region Many countries have 'ageing cohorts' of people with HCV owing to peak HCV incidences in the recent past (2000 in Australia, 1980s in the USA) or distant past (1920–1940s in Japan) Changes in levels of HCV RNA during acute HCV infection might guide early therapeutic intervention, with levels in patients with viral clearance or persistence diverging after 3–4 months of infection The disease progression of chronic HCV infection often accelerates after 20 years of infection, with lifestyle factors key drivers of hepatic fibrosis Direct-acting antiviral therapies should provide a paradigm shift in treatment over the next few years However, unless rates of diagnosis of HCV and access to treatment improve dramatically, direct-acting antivirals will have a limited effect on global disease burden

Key Points HCV prevalence and incidence among people who inject drugs (PWID) remains high Direct-acting antiviral agents (DAA) for HCV with cure in >95% provide a tool for addressing HCV-related liver-disease burden among PWID Adherence and response to DAA therapy among people receiving opioid substitution therapy (OST), including those with ongoing drug use, are comparable to other HCV-infected populations, although more data are required among current PWID who are not on OST HCV reinfection can occur, so strategies to maximize prevention of reinfection (including OST and needle and syringe programmes) and access to DAA retreatment are crucial Improved health services for PWID are needed to enhance HCV prevention, testing, access to care and treatment Continued global leadership and advocacy is required to ensure that HCV prevention, care and treatment for PWID are accessible to all Direct-acting antiviral agents (DAAs) are highly effective treatments for HCV, but are not always accessible to people who inject drugs (PWID). Here, Grebely and colleagues outline the epidemiology of HCV in PWID, discuss current data on DAA outcomes in this population and highlight steps required to broaden access to HCV therapy with the eventual goal of HCV elimination. Globally, 12 million people are estimated to have injected drugs in the past year, 50% of whom have chronic HCV infection, with people who have previously injected drugs presenting an additional large reservoir of infection. The availability of simple and tolerable interferon-free direct-acting antiviral agents (DAAs) for HCV infection, which have a cure rate of >95% represents one of the most exciting advances in clinical medicine in the past few decades. Adherence and response to DAA therapy among people who inject drugs (PWID) receiving opioid substitution therapy (OST) in clinical trials are comparable to populations without a history of injecting drugs. Further data are required among current PWID not receiving OST. Given the potential prevention benefits of treatment, DAAs have enhanced cost-effectiveness among PWID. As HCV therapy is expanded to populations of PWID with high-risk behaviours for re-exposure, acknowledgement that HCV reinfection will occur is crucial, and appropriate strategies must be in place to maximize prevention of reinfection and offer retreatment for reinfection. This Review will also discuss essential components for broadening access to HCV care for PWID as we strive for the global elimination of HCV infection.

The management of acute HCV infection has not been standardized following the availability of direct-acting antiviral agents (DAAs) for chronic HCV infection, and substantial uncertainty exists regarding the optimal treatment regimen and duration. Despite the lack of direct evidence, the 2016 American Association for the Study of Liver Diseases (AASLD)–Infectious Diseases Society of America (IDSA) guidelines supported “the same regimens for acute HCV as recommended for chronic HCV infection … owing to high efficacy and safety”, whereas the 2016 European Association for the Study of the Liver (EASL) guidelines recommended sofosbuvir–ledipasvir, sofosbuvir–velpatasvir or sofosbuvir plus daclatasvir for 8 weeks in acute HCV infection, with a longer duration of 12 weeks recommended for those infected with HIV and/or baseline HCV RNA levels >1,000,000 IU/ml. This Review outlines the epidemiology, natural history and diagnosis of acute HCV infection and provides contemporary information on DAAs for acute and recent HCV infection. The Review also discusses the 2016 AASLD–IDSA and EASL recommendations for acute HCV infection management in light of available evidence and highlights key differences in study populations and design that influence interpretation. We focus on populations at high risk of HCV transmission and acquisition, including people who inject drugs and HIV-positive men who have sex with men, and highlight the potential effects of diagnosis and treatment of acute HCV infection in contributing to HCV elimination.

Background In 2018–2019, Canada introduced a Prison Needle Exchange Program (PNEP) across nine federal facilities to mitigate the harms associated with drug injection among incarcerated people. However, program uptake has been limited. We explored the barriers and facilitators to improving PNEP services among key stakeholders in prison. Methods Stakeholders in nine federal prisons with active PNEP participated in focus groups using nominal group technique to achieve rapid consensus. Responses were generated, rank-ordered, and prioritized by each stakeholder group (correctional officers, healthcare workers, and people in prison). We identified the highest-ranking responses to questions about barriers and solutions to PNEP uptake and described them using the five levels of the Socioecological Model: individual, interpersonal, organizational, system, and structural/policy. Results Between September 2023 and February 2024, 34 focus groups were conducted with 215 participants ( n  = 51 correctional officers (24%); n  = 67 healthcare workers (31%); n  = 97 people in prison (45%)). Key barriers identified were lack of confidentiality and privacy across all levels and fear of repercussions from drug use and fear of being targeted at the individual-interpersonal levels. Preferred solutions included comprehensive education across all levels, and establishment of supervised/safe injection sites and external program management, potentially involving peers, at the structural level. Conclusions Several multi-level modifiable barriers to improving PNEP uptake in Canadian federal prisons were shared among key stakeholders. Structural changes to PNEP delivery, including supervised/safe injecting sites and peer-led programs, were proposed as solution-driven enablers to increasing PNEP uptake among incarcerated people who inject drugs. These data will inform Canadian efforts to expand PNEP provision.

Australia was one of the first countries to introduce government-funded unrestricted access to direct-acting antiviral (DAA) therapy, with 88,790 treated since March 2016. However, treatment uptake is declining which could potentially undermine Australia’s progress towards the WHO HCV elimination targets. Using mathematical modelling, we updated estimates for those living with chronic HCV in Australia, new cases of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and liver-related mortality among the HCV-cured and viraemic populations from 2015 to 2030. We considered various DAA treatment scenarios incorporating annual treatment numbers to 2020, and subsequent uptake per year of 6,790 (pessimistic), 8,100 (intermediate), and 11,310 (optimistic). We incorporated the effects of excess alcohol consumption and reduction in progression to DC and HCC among cirrhosis-cured versus viraemic individuals. At the end of 2020, we estimated 117,810 Australians were living with chronic HCV. New cases per year of DC, HCC, and liver-related mortality among the HCV viraemic population decreased rapidly from 2015 (almost eliminated by 2030). In contrast, the growing population size of those cured with advanced liver disease meant DC, HCC, and liver-related mortality declined slowly. The estimated reduction in liver-related mortality from 2015 to 2030 in the combined HCV viraemic and cured population is 25% in the intermediate scenario. With declining HCV treatment uptake and ongoing individual-level risk of advanced liver disease complications, including among cirrhosis-cured individuals, Australia is unlikely to achieve all WHO HCV elimination targets by 2030.

Limited surveillance data have hindered understanding of SARS-CoV-2 transmission within prisons. We integrated routine surveillance data with viral sequencing to investigate transmission dynamics and associated factors during a Delta variant outbreak in a maximum-security prison in Sydney, New South Wales, Australia. Infection incidence and associated factors were determined by using person-time and Cox regression. We generated transmission chains by integrating epidemiologic and viral sequencing data. Of 1,562 patients, SARS-CoV-2 infection was diagnosed in 169 (11%), predominantly acquired in prison and asymptomatic. Prisonwide testing identified substantial unrecognized transmission, and 4 subvariants indicated multiple viral introductions. Infection was associated with housing location, having a cellmate (regardless of infection status), and vaccination status. Our findings underscore the inadequacy of symptom-based testing and the efficacy of entry-quarantine, strategic housing, extensive testing, and vaccination in reducing transmission. This integrated approach to surveillance and genomic sequencing offers a valuable model for enhancing infectious disease surveillance in correctional settings.

This study aimed to identify the factors associated with timely (within four weeks) HCV RNA testing and timely (within six months) DAA initiation following HCV notification in the DAA era. We conducted a cohort study of people with an HCV notification in NSW, Australia. Notifications of positive HCV serology were linked to administrative datasets. Weights were applied to account for spontaneous clearance. Logistic regression analyses were performed. Among 5582 people with an HCV notification during 2016–2017, 3867 (69%) were tested for HCV RNA, including 2770 (50%) who received timely testing. Among an estimated 3925 people with chronic HCV infection, 2372 (60%) initiated DAA therapy, including 1370 (35%) who received timely treatment. Factors associated with timely HCV RNA testing included age (≥30 years), female sex, non-Aboriginal ethnicity, country of birth being Australia, and no history of drug dependence. Factors associated with timely treatment were age (≥30 years), male sex, non-Aboriginal ethnicity, country of birth being Australia, no history of drug dependence, and HCV/HIV co-infection. In the DAA era, 50% of people with an HCV notification did not receive timely HCV RNA testing. Most people with an HCV infection received therapy; however, DAA initiation was delayed among many.

Background Hepatitis B is a chronic viral infection, a leading cause of primary liver cancer and identified as a major public health priority by the World Health Organization. Despite a high proportion of people in Australia who have been diagnosed with hepatitis B, significant gaps remain in health care access and in accurate knowledge about hepatitis B. Most people with hepatitis B in Australia were born in China, where the infection has an intergenerational impact with significant social implications resulting from the infection. Understanding how people of Chinese ethnicity with hepatitis B understand and respond to hepatitis B is imperative for reducing morbidity, mortality, and the personal and social impact of the infection. Methods Qualitative semi-structured interviews with people with hepatitis B of Chinese ethnicity recruited through a specialist service identified the advice people with hepatitis B thought was important enough to inform the experience of people newly diagnosed with hepatitis B. A thematic analysis of the data privileged the lived experience of participants and their personal, rather than clinical, explanations of the virus. Results Hepatitis B infection had psychological and physical consequences that were informed by cultural norms, and to which people had responded to with significant behavioural change. Despite this cohort being engaged with specialist clinical services with access to the most recent, comprehensive, and expert information, much of the advice people with hepatitis B identified as important for living with hepatitis B was not based on biomedical understandings. Key suggestions from people with hepatitis B were to form sustainable clinical relationships, develop emotional resilience, make dietary changes, regulate energy, and issues related to disclosure. Conclusions The study highlights conflicts between biomedical and public health explanations and the lived experience of hepatitis B among people of Chinese ethnicity in Australia. Beliefs about hepatitis B are embedded within cultural understandings of health that can conflict with bio-medical explanations of the infection. Acknowledging these perspectives provides for insightful communication between health services and their clients, and the development of nuanced models of care informed by the experience of people with hepatitis B.

This study evaluated HCV treatment initiation among people who inject drugs (PWID) following an intervention of campaign days involving peer connection, point-of-care HCV RNA testing, and linkage to nursing support. ETHOS Engage is an observational cohort study of PWID attending 25 drug treatment clinics and needle and syringe programs in Australia (May 2018–September 2019). Point-of-care results were provided to the nurse, facilitating confirmatory testing and treatment. The study aimed to evaluate treatment uptake and factors associated with treatment at 24 months post-enrolment. There were 317 people with current HCV infection and eligible for treatment (median age 43, 65% male, 15% homeless, 69% receiving opioid agonist treatment, 70% injected in last month). Overall, 15% (47/317), 27% (85/317), 38% (120/317), and 49% (155/317) of people with current HCV infection had initiated treatment at 3-, 6-, 12-, and 24-months following testing, respectively. Homelessness (adjusted hazard ratio (aHR): 0.40; 95% confidence interval: 0.23, 0.71) and incarceration in the past 12 months (vs. never, aHR:0.46; 0.28, 0.76) were associated with decreased treatment initiation in the 24 months post-enrolment. This testing campaign intervention facilitated HCV treatment uptake among PWID. Further interventions are needed to achieve HCV elimination among people experiencing homelessness or incarceration.

IntroductionLow-cost generic direct-acting antiviral (DAA) regimens for treatment of hepatitis C virus (HCV) are available in several low-income/middle-income countries, important for treatment scale-up. This study evaluated the cost-effectiveness of genotype-dependent and pan-genotypic DAA regimens in Iran as an example of a resource-limited setting.MethodsA Markov model was developed to simulate HCV natural history. A decision tree was developed for HCV treatment, assuming four scenarios, including scenario 1: genotyping, sofosbuvir/ledipasvir (SOF/LDV) for genotype 1, and sofosbuvir/daclatasvir (SOF/DCV) for genotype 3; scenario 2: genotyping, SOF/LDV for genotype 1, and sofosbuvir/velpatasvir (SOF/VEL) for genotype 3; scenario 3: no genotyping and SOF/DCV for all; and scenario 4: no genotyping and SOF/VEL for all. A 1-year cycle length was used to calculate the cumulative cost and effectiveness over a lifetime time horizon. We calculated quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) using a health system perspective. Costs were converted to US dollars using purchasing power parity exchange rate ($PPP). All costs and outcomes were discounted at an annual rate of 3%.ResultsAmong people with no cirrhosis, scenario 3 had the minimum cost, compared with which scenario 4 was cost-effective with an ICER of 4583 $PPP per QALY (willingness-to-pay threshold: 9,311 $PPP per QALY). Among both people with compensated or decompensated cirrhosis, scenario 4 was cost saving. In sensitivity analysis, scenario 4 would be also cost-saving among people with no cirrhosis provided a 39% reduction in the cost of 12 weeks SOF/VEL.ConclusionInitiating all patients on pan-genotypic generic DAA regimens with no pretreatment genotyping was cost-effective compared with scenarios requiring pretreatment HCV genotype tests. Among generic pan-genotypic DAA regimens, SOF/VEL was cost-effective, for people with no cirrhosis and cost-saving for those with cirrhosis.