Patients' experience of accessing hepatitis C treatment through the Myanmar national hepatitis C treatment program: a qualitative evaluation.

BACKGROUND: Globally, 56.8 million people are living with hepatitis C and over three-quarters of those reside in low and middle-income countries (LMICs). Barriers and enablers to hepatitis C care among people who inject drugs in high-income countries are well documented. However, there is scant literature describing the patient experience in LMICs. Understanding the barriers and enablers to care from the patient perspective is important to inform service refinements to improve accessibility and acceptability of hepatitis C care. METHODS: We conducted a qualitative evaluation of the patient experience of accessing the national hepatitis C program at eight hospital sites in Myanmar. Semi-structured interviews were conducted with four to five participants per site. Interview data were analysed thematically, with deductive codes from Levesque et al.'s (2013) Framework on patient-centred access to healthcare. RESULTS: Across the eight sites, 38 participants who had completed treatment were interviewed. Barriers to accessing care were mostly related to attending for care and included travel time and costs, multiple appointments, and wait times. Some participants described how they did not receive adequate information on hepatitis C, particularly its transmission routes, and on the level of cirrhosis of their liver and what they were required to do after treatment (i.e. reduce alcohol consumption, liver cirrhosis monitoring). Many participants commented that they had few or no opportunities to ask questions. Provision of treatment at no cost was essential to accessibility, and gratitude for free treatment led to high acceptability of care, even when accessing care was inconvenient. CONCLUSIONS: These findings highlight the importance of streamlining and decentralising health services, adequate human resourcing and training, and affordable treatment in maximising the accessibility and acceptability of hepatitis C care in LMICs. Findings from this work will inform future service delivery refinements for national program and other decentralised programs to improve accessibility and acceptability of hepatitis C care in Myanmar.

Hepatitis C incidence among patients attending primary care health services that specialise in the care of people who inject drugs, Victoria, Australia, 2009 to 2020.

BACKGROUND: Monitoring trends in hepatitis C virus (HCV) incidence is critical for evaluating strategies aimed at eliminating HCV as a public health threat. We estimate HCV incidence and assess trends in incidence over time among primary care patients. METHODS: Data were routinely extracted, linked electronic medical records from 12 primary care health services. Patients included were aged ≥16 years, tested HCV antibody negative on their first test recorded and had at least one subsequent HCV antibody or RNA test (January 2009-December 2020). HCV incident infections were defined as a positive HCV antibody or RNA test. A generalised linear model assessed the association between HCV incidence and calendar year. RESULTS: In total, 6711 patients contributed 17,098 HCV test records, 210 incident HCV infections and 19,566 person-years; incidence was 1.1 per 100 person-years (95% confidence interval (CI): 0.9 to 1.2). Among 559 (8.2%) patients ever prescribed opioid-related pharmacotherapy (ORP) during the observation period, 135 infections occurred during 2,082 person-years (incidence rate of 6.5 per 100 person-years (95% CI: 5.4 to 7.7)). HCV incidence declined 2009-2020 overall (incidence rate ratio per calendar year 0.8 (95% CI: 0.8 to 0.9) and among patients ever prescribed ORT (incidence rate ratio per calendar year 0.9, 95% CI: 0.75 to 1.0). CONCLUSION: HCV incidence declined among patients at primary care health services including among patients ever prescribed ORP and during the period following increased access to DAA therapy.

Current issues in the prevalence, diagnosis and management of hepatocellular carcinoma in Australia.

Hepatocellular carcinoma (HCC) is the commonest primary liver cancer encountered in the community and a leading cause of cancer morbidity and mortality. In Australia, there are several current important issues that need to be addressed in HCC management. There is a dramatically rising incidence of HCC in Australia with comparatively poorer outcomes in remote regions and in socioeconomic disadvantaged groups. Aboriginal people have a greater incidence of HCC on a background of increased liver disease prevalence and face several barriers to delivery of better healthcare outcomes compared to other Australians. The previously adopted use of imaging alone to diagnose HCC is now being challenged with biopsy likely to become increasingly necessary with the increased uptake of personalised medicine management. Managing HCC is complex involving many disciplines with the multidisciplinary team approach being the current accepted standard of care for patients. New immunotherapy combinations promise to offer patients with advanced HCC promising novel management options. However, the Australian inequities in prevalence, diagnosis and service provision, especially in Aboriginal people, need to be redressed concurrently with the adoption of new HCC management options.

A global investment framework for the elimination of hepatitis B.

BACKGROUND & AIMS: More than 292 million people are living with hepatitis B worldwide and are at risk of death from cirrhosis and liver cancer. The World Health Organization (WHO) has set global targets for the elimination of viral hepatitis as a public health threat by 2030. However, current levels of global investment in viral hepatitis elimination programmes are insufficient to achieve these goals. METHODS: To catalyse political commitment and to encourage domestic and international financing, we used published modelling data and key stakeholder interviews to develop an investment framework to demonstrate the return on investment for viral hepatitis elimination. RESULTS: The framework utilises a public health approach to identify evidence-based national activities that reduce viral hepatitis-related morbidity and mortality, as well as international activities and critical enablers that allow countries to achieve maximum impact on health outcomes from their investments - in the context of the WHO's 2030 viral elimination targets. CONCLUSION: Focusing on hepatitis B, this health policy paper employs the investment framework to estimate the substantial economic benefits of investing in the elimination of hepatitis B and demonstrates how such investments could be cost saving by 2030. LAY SUMMARY: Hepatitis B infection is a major cause of death from liver disease and liver cancer globally. To reduce deaths from hepatitis B infection, we need more people to be tested and treated for hepatitis B. In this paper, we outline a framework of activities to reduce hepatitis B-related deaths and discuss ways in which governments could pay for them.

Estimates of the global reduction in liver disease-related mortality with increased coffee consumption: an analysis of the Global Burden of Disease Dataset.

BACKGROUND: Epidemiological data suggest that coffee has a dose-dependent protective effect on liver-related mortality. AIM: To estimate the potential impact of increased per capita coffee consumption on global liver-related mortality. METHODS: Using the Global Burden of Disease 2016 dataset (adults > 15 years), we modelled the impact of increased per capita coffee consumption on liver-related mortality in 2016 for 194 countries using published risk ratios for >2 cups coffee/ day (RR 0.54, 95% CI 0.42-0.69) and ≥4 cups/ day (RR 0.29, 95% CI 0.17-0.50), adjusted for confounders and tested model assumptions using sensitivity analyses. RESULTS: Worldwide, there were an estimated 1,240,201 (95% CI 118 4300-1 354 410) adult liver-related deaths in 2016. Median global liver mortality rate in 2016 was 15 deaths/ 100 000 population/ year (all ages, both genders; IQR 11-21 deaths per 100 000). If all countries with per capita coffee intake ≤2 cups/ day increased to >2 cups/ day, the predicted total number of liver-related deaths would have been 630 947 in 2016 (95% CI 629 693-631 861) with 452 861 (95% CI 451 948-454 116) deaths averted (PPR 7.8 liver-related deaths/ 100 000/ year). If per capita consumption was ≥ 4 cups/ day, the predicted number of liver-related deaths in 2016 would have been 360 523 (95% CI 359 825-361 992) with 723 287 (95% CI 721 817-723 984) deaths averted (PPR 12.1 liver-related deaths/100 000/year). CONCLUSION: Increasing per capita coffee consumption to > 2 cups per day on a population level has the potential to avert hundreds of thousands of liver-related deaths annually if the impact of coffee on liver-related mortality is confirmed in clinical trials.

A model of the economic benefits of global hepatitis C elimination: an investment case.

Major gains in reducing the burden of hepatitis C are now possible because of the discovery of a cure. The prevention of premature deaths and increased workforce participation among people who are cured are likely to provide substantial indirect economic benefits. We developed an investment case for hepatitis C for the six WHO world regions, which, to our knowledge, is the first to consider both indirect and direct economic benefits in this context. Scaling up of testing and treatment to reach the 2030 WHO hepatitis C elimination targets was estimated to prevent 2·1 million (95% credible interval 1·3-3·2 million) hepatitis C-related deaths and 10 million (4-14 million) new hepatitis C virus infections globally between 2018 and 2030. This elimination strategy was estimated to cost US$41·5 billion (33·1-48·7 billion) in testing, treatment, and health care between 2018 and 2030 ($23·4 billion more than the status quo scenario of no testing or treatment scale up), with a global average of $885 (654-1189) per disability-adjusted life-year averted at 2030. Compared with the status quo scenario, the elimination scenario generated $46·1 billion (35·9-53·8 billion) in cumulative productivity gains by 2030. These indirect costs made elimination cost-saving by 2027, with a net economic benefit of $22·7 billion (17·1-27·9 billion) by 2030. This model shows that countries might be underestimating the true burden of hepatitis C and will benefit from investing in elimination.

Global hepatitis C elimination: an investment framework.

WHO has set global targets for the elimination of hepatitis B and hepatitis C as a public health threat by 2030. However, investment in elimination programmes remains low. To help drive political commitment and catalyse domestic and international financing, we have developed a global investment framework for the elimination of hepatitis B and hepatitis C. The global investment framework presented in this Health Policy paper outlines national and international activities that will enable reductions in hepatitis C incidence and mortality, and identifies potential sources of funding and tools to help countries build the economic case for investing in national elimination activities. The goal of this framework is to provide a way for countries, particularly those with minimal resources, to gain the substantial economic benefit and cost savings that come from investing in hepatitis C elimination.

Enhancing the hepatitis B care cascade in Australia: A cost-effectiveness model.

If Australia is to successfully eliminate hepatitis B as a public health threat, it will need to enhance the chronic hepatitis B (CHB) care cascade. This study used a Markov model to assess the impact, cost and cost-effectiveness of scaling up CHB diagnosis, linkage to care and treatment to reach national and international elimination targets for hepatitis B in Australia. Compared to continued current trends, the model calculated the difference in care cascade projection, disability-adjusted life years (DALYs), costs and the incremental cost-effectiveness ratio (ICER), of scaling up CHB diagnosis, linkage to care and treatment to reach: (a) Australia's 2022 national targets and (b) the WHO's 2030 global targets. Achieving the national and WHO targets had ICERs of A$13 435 (A$10 236-A$21 165) and A$14 482 (A$13 031-A$25 641) per DALY averted between 2016 and 2030 in Australia, respectively. However, this excluded implementation and demand generation costs. The ICER for the National Strategy and WHO Strategy remained under A$50 000 per DALY averted if Australia spent up to A$328 or A$538 million, respectively, per annum (for 2016-2030) on implementation and demand generation activities. Sensitivity analysis showed that cost-effectiveness was predominately driven by the cost of CHB treatment and influenced by disease progression rates. Hence for Australia to reach the National Hepatitis B Strategy 2022 targets and WHO Strategy 2030 targets, it requires an improvement in the CHB care cascade. We estimated it is cost-effective to spend up to A$328 million or A$538 million per year to reach the National and WHO Strategy targets, respectively.

A cost-effectiveness analysis of primary versus hospital-based specialist care for direct acting antiviral hepatitis C treatment.

BACKGROUND: Hepatitis C virus elimination may be possible by scaling up direct-acting antiviral (DAA) treatment. Due to the safety and simplicity of DAA treatment, primary care-based treatment delivery is now feasible, efficacious and may be cheaper than hospital-based specialist care. In this paper, we use Prime Study data - a randomised controlled trial comparing the uptake of DAA treatment between primary and hospital-based care settings amongst people who inject drugs (PWID) - to estimate the cost of initiating treatment for PWID diagnosed with hepatitis C in primary care compared to hospital-based care. METHODS: The total economic costs associated with delivering DAA treatment (post hepatitis C diagnosis) within the Prime study - including health provider time/training, medical tests, equipment, logistics and pharmacy costs - were collected. Appointment data were used to estimate the number/type of appointments required to initiate treatment in each case, or the stage at which loss to follow up occurred. RESULTS: Among the hepatitis C patients randomised to be treated within primary care, 43/57 (75%) commenced treatment at a mean cost of A$885 (95% CI: A$850-938) per patient initiating treatment. In hospital-based care, 18/53 hepatitis C patients (34%) commenced treatment at a mean cost of A$2078 (range: A$2052-2394) per patient initiating treatment - more than twice as high as primary care. The lower cost in the primary care arm was predominantly the result of increased retention in care compared to the hospital-based arm. CONCLUSIONS: Compared to hospital-based care, providing hepatitis C services for PWID in primary care can improve treatment uptake and approximately halve the average cost of treatment initiation. To improve treatment uptake and cure, countries should consider primary care as the main model for hepatitis C treatment scale-up.

Innovative strategies for the elimination of viral hepatitis at a national level: A country case series.

Viral hepatitis is a leading cause of morbidity and mortality worldwide, but has long been neglected by national and international policymakers. Recent modelling studies suggest that investing in the global elimination of viral hepatitis is feasible and cost-effective. In 2016, all 194 member states of the World Health Organization endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, but complex systemic and social realities hamper implementation efforts. This paper presents eight case studies from a diverse range of countries that have invested in responses to viral hepatitis and adopted innovative approaches to tackle their respective epidemics. Based on an investment framework developed to build a global investment case for the elimination of viral hepatitis by 2030, national activities and key enablers are highlighted that showcase the feasibility and impact of concerted hepatitis responses across a range of settings, with different levels of available resources and infrastructural development. These case studies demonstrate the utility of taking a multipronged, public health approach to: (a) evidence-gathering and planning; (b) implementation; and (c) integration of viral hepatitis services into the Agenda for Sustainable Development. They provide models for planning, investment and implementation strategies for other countries facing similar challenges and resource constraints.

The increasing burden of potentially preventable liver disease among adult liver transplant recipients: A comparative analysis of liver transplant indication by era in Australia and New Zealand.

BACKGROUND: Hepatitis C (HCV), hepatitis B (HBV), alcohol-related liver disease (ALD), and non-alcohol-related fatty liver disease (NAFLD) are leading indications for adult liver transplantation in Australia and New Zealand. However, these diseases are potentially preventable through effective primary and/or secondary prevention strategies. This study evaluates the relative contribution of potentially preventable liver diseases to liver transplant numbers in Australia and New Zealand over time. METHODS: Prospectively recorded clinical, demographic, and outcome data were collected from the Australian and New Zealand Liver Transplant Registry for all primary adult liver transplants performed in Australia and New Zealand from 1 January 1985 until 31 December 2012. Potentially preventable liver disease was defined as HBV, HCV, NAFLD, ALD, and HCC. The etiology of liver disease leading to liver transplantation and the proportion of preventable liver disease-related liver transplantation was compared between Era 1 (1985-1993), Era 2 (1994-2003), and Era 3 (2004-2012). RESULTS: Overall, 1252 of 3266 adult primary liver transplants (38.3%) were performed for potentially preventable liver disease. There was a significant increase in the proportion of liver transplants because of preventable liver disease from 21.2% (93 of 439) in Era 1, to 49.8% (623 of 1252) in Era 2 and 63.5% (1000 of 1575) in Era 3 (P < 0.0001). Over time, there was a significant increase in HCV (P < 0.0001), ALD (P = 0.002), and NAFLD (P < 0.0001) as a primary indication for adult liver transplant, whereas HBV has significantly decreased from Era 1 to Era 3 as an indication for transplant (P < 0.0001). The number of transplants performed for HCC also increased across Eras (P < 0.0001), with 84% due to underlying potentially preventable liver disease. CONCLUSION: Since 2004, the majority of primary adult liver transplants within Australia and New Zealand have been because of potentially preventable liver diseases and the prevalence of these diseases has increased over time. This finding represents an opportunity for clinicians to make a significant impact on the overall burden of advanced liver disease in Australia and New Zealand by improving primary and secondary prevention measures.

Overview of hepatitis B prevalence, prevention, and management in the Pacific Islands and Territories.

There are over 500-750 000 deaths per year because of hepatitis B virus (HBV)-related cirrhosis and liver cancer worldwide and the World Health Organization Western Pacific Region has some of the highest endemic levels of HBV in the world, particularly within China, South East Asia and Pacific Island Countries and Territories (PICT). The PICT have unique ethnic diversity and a very high prevalence of smoking and metabolic syndrome, both important risk factors for liver fibrosis and liver cancer. However, in contrast to many Asian countries, there is little published data on HBV prevalence and related liver disease burden in PICT. In this review, the available published literature and World Health Organization data for HBV prevalence and related liver disease and liver cancer burden in PICT is outlined, and unmet needs for improving HBV prevention and control in the region are highlighted.

Paracetamol overdose in Victoria remains a significant health-care burden.

BACKGROUND AND AIM: Paracetamol is the most frequently used analgesic in Australia and can be purchased without a prescription. We aimed to investigate the epidemiology and outcome of paracetamol overdoses occurring in Victoria, Australia. METHODS: The Victorian admitted episode dataset was examined for all patients who had a diagnosis of paracetamol poisoning (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification [ICD-10-AM]: T39.1) or paracetamol adverse effect in therapeutic use (Y45.5) from July 1, 2000 to June 30, 2007. Data extracted included all ICD-10 codes related to their admissions, gender, age range, date of admission, and cause of death (if applicable). RESULTS: Over 7 years, there was a total of 14,662 hospital admissions for paracetamol overdose with a mean of 2095 cases per year. Accidental overdoses comprised 15% (n = 2149) of cases. The overdose rate fell from 46 cases per 100,000 in 2001 to 39 cases per 100,000 in 2006 (P < 0.001). Most overdoses occurred in women (71%), and patients between 15 and 50 years old comprised 78% of all cases. Complications and mortality were relatively uncommon, with only 26 deaths directly attributable to paracetamol overdose over the 7 years. No child under 15 years old died from their overdose. CONCLUSION: Admission to Victorian hospitals with paracetamol overdose presents an enormous and in many cases preventable health-care burden. Fortunately, there has been a gradual fall in admissions, and most cases appear relatively benign. Further reductions in overdose could be achieved with increased awareness by physicians and the general public regarding the potential for accidental overdose, and increasing funding for mental health initiatives.

Assessment of cognitive function in the heterozygous reeler mouse.

RATIONALE: The heterozygous reeler mouse has been proposed as a genetic mouse model of schizophrenia based on several neuroanatomical and behavioral similarities between these mice and patients with schizophrenia. However, the effect of reelin haploinsufficiency on one of the cardinal symptoms of schizophrenia, the impairment of prefrontal-cortex-dependent cognitive function, has yet to be determined. OBJECTIVE: Here, we investigated multiple aspects of cognitive function in heterozygous reeler mice that are known to be impaired in schizophrenic patients. METHODS: Heterozygous reeler mice were assessed for (1) cognitive flexibility in an instrumental reversal learning task, (2) impulsivity in an inhibitory control task, (3) attentional function in a three-choice serial reaction time task, and (4) working memory in a delayed matching-to-position task. RESULTS: No differences were found between heterozygous reeler mice and wild-type littermate controls in any prefrontal-related cognitive measures. However, heterozygous reeler mice showed deficits in the acquisition of two operant tasks, consistent with a role for reelin in certain forms of learning. CONCLUSIONS: These findings suggest that heterozygous reeler mice may not be an appropriate model for the core prefrontal-dependent cognitive deficits observed in schizophrenia, but may model more general learning deficits that are associated with many psychiatric disorders.