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To assess the impact on diagnosis targets, cost, and cost-effectiveness of universal hepatitis B screening in Australia.Markov model simulation of disease and care cascade progression for people with chronic hepatitis B in Australia.Three scenarios were compared: 1. no change to current hepatitis B virus (HBV) testing practice; 2. universal screening strategy, with the aim of achieving the WHO diagnosis target by 2030 (90% of people with chronic hepatitis B diagnosed), based on opportunistic (general practitioner-initiated) screening for HBsAg; 3. universal screening strategy, and also ensuring that 50% of people with chronic hepatitis B are receiving appropriate clinical management by 2030.Projected care cascade for people with chronic hepatitis B, cumulative number of HBV-related deaths, intervention costs, and health utility (quality-adjusted life-years [QALYs] gained during 2020-2030). An incremental cost-effectiveness ratio (ICER) threshold (v scenario 1) of $50 000 per QALY gained was applied.Compared with scenario 1, 80 HBV-related deaths (interquartile range [IQR], 41-127 deaths) were averted during 2020-2030 in scenario 2, 315 HBV-related deaths (IQR, 211-454 deaths) in scenario 3. Scenario 2 cost $84 million (IQR, $41-106 million) more than scenario 1 during 2020-2030 (+8%), yielding an ICER of $104 921 (IQR, $49 587-107 952) per QALY gained. Scenario 3 cost $263 million (IQR, $214-316 million) more than scenario 1 during 2020-2030 (+24%), yielding an ICER of $47 341 (IQR, $32 643-58 200) per QALY gained. Scenario 3 remained cost-effective if the test positivity rate was higher than 0.35% or the additional costs per person tested did not exceed $4.02.Universal screening for hepatitis B will be cost-effective only if the cost of testing is kept low and people receive appropriate clinical management.

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.

Hepatitis B is a chronic condition, primarily associated with hepatitis B viral infection in early life. The failure of prevention and appropriate management can lead to subsequent liver cirrhosis and cancer. Hepatitis B most commonly affects people born in Asia and Sub-Saharan Africa and their global diasporas. The physical, psychological, and social impacts of hepatitis B are strongly influenced by sex and gender. Inequities in access to timely, sensitive diagnosis and effective management arise from interactions between structural inequalities related to race, ethnicity, Indigenous/settler status, class, and geography. The biomedical response to hepatitis B has led to advances in prevention, diagnosis, and treatment, but many affected communities have explanatory health belief models that differ from that of biomedicine. We argue that an intersectional approach, led by affected people and communities, can integrate biomedicine with the lived experience and social context that give purpose to and shape all personal, communal, clinical, and public health responses to hepatitis B. This approach has the potential to enable a consciously equitable, effective response to the biopsychosocial complexities of hepatitis B, improve the health and wellbeing of people living with hepatitis B, and reduce hepatitis B-associated mortality.

Few studies investigate sexual health among Chinese international students in Australia. We recruited domestic (n = 623) and Chinese international (n = 500) students for separate online surveys on sexual behaviours and knowledge. Samples were compared using Chi square, Fisher’s exact and equality of medians tests. Domestic students were more likely than international students to have ever touched a partner’s genitals (81% vs. 53%, p

Background In Australia, only 22% of people with chronic hepatitis B (CHB) are clinically managed; and a national effort is engaging primary care workforce in providing CHB-related care. This study explored CHB-related knowledge, attitudes, barriers and support needs of general practitioners (GPs). Methods A survey was sent to a random sample of 1,000 Australian GPs in April- October 2018; 134 of 978 eligible GPs completed the questionnaire (14%). Results Respondents had high knowledge of at-risk populations (> 79%) and hepatitis B serology (82%), and most saw hepatitis B testing and monitoring as part of their work (95% and 86%, respectively). However, the survey revealed low knowledge, awareness and intention with respect to hepatitis B treatment: 23% correctly understood treatment initiation; 40% were aware that treatment for CHB could be dispensed in the community; 23% agreed that prescribing was part of their work. Lack of time was considered the greatest barrier (38%) and clear guidelines was the most important facilitator to providing care (72%). Conclusion Interventions are needed to generate interest and skills to provide CHB-related care by GPs.

Background Myanmar has set national hepatitis C (HCV) targets to achieve 50% of people diagnosed and 50% treated by 2030. The WHO has additional targets of reducing incidence by 80% and mortality by 65% by 2030. We aimed to estimate the impact, cost, cost-effectiveness and net economic benefit of achieving these targets. Methods Mathematical models of HCV transmission, disease progression and the care cascade were calibrated to 15 administrative regions of Myanmar. Cost data were collected from a community testing and treatment program in Yangon. Three scenarios were projected for 2020–2030: (1) baseline (current levels of testing/treatment); and testing/treatment scaled up sufficiently to reach (2) the national strategy targets; and (3) the WHO targets. Findings Without treatment scale-up, 333,000 new HCV infections and 97,000 HCV-related deaths were estimated to occur in Myanmar 2020–2030, with HCV costing a total $100 million in direct costs (testing, treatment, disease management) and $10.4 billion in lost productivity. In the model, treating 55,000 people each year was sufficient to reach the national strategy targets and prevented a cumulative 40,000 new infections (12%) and 25,000 HCV-related deaths (25%) 2020–2030. This was estimated to cost a total $189 million in direct costs ($243 per DALY averted compared to no treatment scale-up), but only $9.8 billion in lost productivity, making it cost-saving from a societal perspective by 2024 with an estimated net economic benefit of $553 million by 2030. Reaching the WHO targets required further treatment scale-up and additional direct costs but resulted in greater longer-term benefits. Interpretation Current levels of HCV testing and treatment in Myanmar are insufficient to reach the national strategy targets. Scaling up HCV testing and treatment in Myanmar to reach the national strategy targets is estimated to generate significant health and economic benefits. Funding Gilead Sciences.

Background In Australia, Chinese migrants are among the populations most affected by hepatitis B virus (HBV) infection but often experience late diagnosis or access to clinical care. This study aims to explore approaches to increase HBV testing in Australia’s Chinese community and inform evaluation planning, specifically to i) assess the feasibility and acceptability of HBV educational programs, and ii) compare HBV testing uptake in people receiving a tailored education resource focussing on liver cancer prevention compared with a standard HBV education package. Methods This is a pre-post mixed-methods pilot and feasibility study. People of Chinese ethnicity and unsure of their HBV infection or immunity status were recruited from ten community sites in Melbourne, Australia in 2019–2020. Participants were randomised to receive an education package (comprised of a leaflet and in-person one-on-one educational session) with a focus on either 1) standard HBV-related information, or 2) liver cancer prevention. Participants completed a baseline questionnaire prior to receiving the intervention and were followed up at 6 months’ time for a questionnaire and an opt-in semi-structured interview. Primary study outcomes included feasibility of study procedures, measured by recruitment, participation, and retention rates; acceptability of the education program assessed by acceptability scores; and HBV testing uptake rate in each arm. Secondary outcomes include HBV-related knowledge change, assessed by pre-post comparison; and factors affecting participants’ testing behaviour analysed using qualitative data. Results Fifty-four participants received an education package; baseline and follow-up data from 33 (61%) were available. The study procedures of recruitment and retention were feasible; the acceptability of the education program was moderate with improved HBV-related knowledge observed. Four participants self-reported being tested: one (1/15, 7%) in the standard HBV information group and three (3/18, 17%) in the liver cancer prevention information group. Factors identified as affecting testing included perceived relevance and seriousness of HBV, healthcare access and costs of testing, and perceptions of the role of primary care providers in HBV-related care. Conclusion A tailored education program targeting ethnic Chinese in Australia was feasible with moderate acceptability. A larger study is required to determine if a liver cancer prevention message would improve HBV testing uptake in Chinese community than standard HBV education message. Supports from healthcare providers, community-based testing programs, and public health education programs are likely needed to motivate diagnostic testing among Chinese people at risk of HBV infection.

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.

Despite the heavy disease burden posed by hepatitis B, around 90% of people living with hepatitis B are not diagnosed globally. Many of the affected populations still have limited or no access to essential blood tests for hepatitis B. Compared to conventional blood tests which heavily rely on centralised laboratory facilities, point-of-care testing for hepatitis B has the potential to broaden testing access in low-resource settings and to engage hard-to-reach populations. Few hepatitis B point-of-care tests have been ratified for clinical use by international and regional regulatory bodies, and countries have been slow to adopt point-of-care testing into hepatitis B programs. This review presents currently available point-of-care tests for hepatitis B and their roles in the care cascade, reviewing evidence for testing performance, utility, acceptability, costs and cost-effectiveness when integrated into hepatitis B diagnosis and monitoring programs. We further discuss challenges and future directions in aspects of technology, implementation, and regulation when adopting point-of-care testing in hepatitis B programs.

METHOD: Data from qualitative semi-structured interviews with 19 participants from primary care settings were thematically analysed. RESULTS: Critical elements in providing clinical care in primary care settings were identified at an organisational and provider level. A supportive organisational culture included leadership, a multidisciplinary team approach, community engagement and cultural competency, while provider-related issues included authorisation to prescribe, access to linguistic and cultural mediators and effective relationships with relevant specialist services. DISCUSSION: The research identified practice leadership, organisational culture and a patient focus supported hepatitis B clinical management transitioning from specialist to primary care services.

Summary Background Hepatitis B causes more than 800 000 deaths globally each year. Perinatal infections are a major driver of this burden but can be prevented by vaccination within 24 h of birth. Currently, only 44% of newborn babies in low-income and middle-income countries (LMICs) receive a timely birth dose. We investigated the effects and cost-effectiveness of implementing ambient storage of hepatitis B vaccines under a controlled temperature chain (CTC) protocol and the use of compact prefilled auto-disable (CPAD) devices for community births. Methods In this mathematical modelling study of perinatal hepatitis B transmission and disease progression, we estimated the coverage impact and cost-effectiveness of implementing CTC and CPAD interventions in the six Global Burden of Disease (GBD) regions containing LMICs. Combinations of four different scenarios of birth dose delivery strategies (cold chain, CTC) and interventions (needle and syringe, CPAD) were modelled across facility or community birth locations. We also estimated the minimum cost and most cost-effective strategy to achieve the WHO 90% hepatitis B birth dose coverage target in GBD regions and in 46 LMICs with a reported coverage of less than 90%. Findings Current delivery protocols achieved a maximum coverage of 65% (IQR 64–65) across GBD regions. Reaching 90% hepatitis B birth dose coverage across all GBD regions was estimated to cost a minimum of US$687·5 million per annum ($494·0 million more than the estimated current expenditure), of which $516·5 million (75%) was required for CTC and CPAD interventions. Reaching 90% coverage in this way was estimated to be cost saving in five of the six regions (and in 40 of 46 LMICs individually assessed) due to the disease costs averted, with the cost per disability-adjusted life-years averted being less than $83·27 otherwise. Interpretation Hepatitis B birth dose coverage of 90% is unlikely to be reached under current protocols. CTC and CPAD vaccine strategies present cost-effective solutions to overcome coverage barriers. Funding The Burnet Institute.

Background Primary liver cancer is a lethal malignancy with a high mortality worldwide. Currently, sorafenib is the most effective molecular-targeted drug against hepatocellular carcinoma (HCC). However, the sorafenib resistance rate is high. The molecular mechanism of this resistance has not been fully elucidated. High mobility group box 1 (HMGB1) is a multifaceted protein that plays a key role in the proliferation, apoptosis, metastasis and angiogenesis of HCC cells. In addition, HMGB1 has been suggested to contribute to chemotherapy resistance in tumours, including lung cancer, osteosarcoma, neuroblastoma, leukaemia, and colorectal cancer. This study investigated the association between HMGB1 and sorafenib resistance in HCC. Methods HepG2 cells with HMGB1 knockdown or overexpression were generated. The efficacy of sorafenib in these cells was tested using flow cytometry and a cell counting assay. The subcellular localization of HMGB1 in HepG2 cells following sorafenib treatment was measured by western blotting and confocal microscopy. A murine subcutaneous HCC model was generated to examine the association between HMGB1 and the sensitivity of sorafenib treatment. Results The HMGB1 knockdown cells exhibited a significantly higher apoptotic level and lower cell viability than the normal HMGB1 expressing cells following the sorafenib treatment. In addition, the cell viability observed in the HMGB1 overexpressing cells was higher than that observed in the control cells following the sorafenib intervention. Sorafenib had a better tumour inhibition effect in the HMGB1 knockdown group in vivo. The amount of mitochondrial HMGB1 decreased, while the amount of cytosolic HMGB1 increased following the exposure to sorafenib. Altogether, HMGB1 translocated from the mitochondria to the cytoplasm outside the mitochondria following the exposure of HepG2 cells to sorafenib. Conclusions A novel potential role of HMGB1 in the regulation of sorafenib therapy resistance in HCC was observed. The knockdown of HMGB1 restores sensitivity to sorafenib and enhances HepG2 cell death, while HMGB1 overexpression blunts these effects. The translocation of HMGB1 from the mitochondria to the cytosol following sorafenib treatment provides new insight into sorafenib resistance in HCC. Electronic supplementary material The online version of this article (10.1186/s12885-017-3868-2) contains supplementary material, which is available to authorized users.

Objective Intermediate phenotypes of microcirculation (retinal microvascular caliber) are associated with cardiovascular (CV) risk factors and independently predict CV events. However, the effect of microcirculation variation on the vascular system is unclear. We conducted a systematic review and meta-analysis of observational studies to quantify associations of retinal microvascular caliber (arteriolar, venular caliber, arteriole-to-venule ratio) and preclinical CV measures (large arterial function and structure). Methods We identified studies in MEDLINE, EMBASE, and PubMed (1946 to March 2018) studying (a) general population samples and (b) patients with cardiometabolic disease. Study-specific correlation estimates were combined into meta-analysis where possible. Results Of 1294 studies identified, 26 met inclusion criteria (general population 16, patients 10), of which five studies were included in meta-analysis. Most studied middle-aged adults cross-sectionally, with one childhood study. Large arterial function and structure were predominantly assessed by pulse wave velocity and carotid intima-media thickness, respectively. Only arteriolar caliber was consistently associated with arterial function and structure, with stronger associations observed in cardiometabolic patients. Narrower (worse) arteriolar caliber was associated with faster (poorer) pulse wave velocity (correlation coefficient (r) -0.17, 95% CI -0.25 to -0.10) and greater (poorer) intima-media thickness (r -0.05, 95%CI -0.09 to -0.02) across all adult participants. Conclusions Retinal arteriolar, but not venular caliber, was modestly associated with large arterial function and weakly associated with large arterial structure, with stronger evidence in patients with cardiometabolic disease. This suggests that preclinical changes in large arteries and the microcirculation have some shared but mainly unique pathways to associate with cardiovascular disease.

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.