The cascade of care for hepatitis C in Victoria, Australia: a data linkage cohort study.

BACKGROUND: Highly effective hepatitis C therapies are available in Australia. However, people living with hepatitis C face various barriers to accessing care and treatment. AIMS: To identify gaps in the cascade of care for hepatitis C and generate estimates of the number living with untreated infection according to population group, using a representative longitudinal study population. METHODS: We linked hepatitis C notification data from Victoria to national pathology, prescribing and death registry data. We assessed receipt of key clinical services in a large cohort who tested positive for hepatitis C from 1 January 2000 to 31 December 2016, with follow-up to 30 June 2018. We estimated the number still living with hepatitis C, adjusting for spontaneous clearance and mortality. RESULTS: The cohort comprised 45 391 people positive for hepatitis C. Of these, 13 346 (29%) received treatment and an estimated 28% (95% confidence interval (CI): 26-30%) were still living with chronic infection at 30 June 2018, with the remainder still living following spontaneous clearance (30%, 95% CI: 29-32%) or having died (12%, 95% CI: 12-12%). Half (50%) of those still living with hepatitis C were born from 1965 to 1980, and 74% first tested positive before 2011. CONCLUSIONS: Despite an enabling policy environment and subsidised therapy, many people in this cohort were not treated. Increased measures may be needed to engage people in care, including those who acquired hepatitis C more than 10 years ago.

Missed opportunities for diagnosis of hepatitis B and C in individuals diagnosed with decompensated cirrhosis or hepatocellular carcinoma.

BACKGROUND AND AIM: This study aimed to assess utilization of health-care services in people with decompensated cirrhosis (DC) or hepatocellular carcinoma (HCC) and a "late diagnosis" of hepatitis B or hepatitis C. METHODS: Hepatitis B and C cases during 1997-2016 in Victoria, Australia, were linked with hospitalizations, deaths, liver cancer diagnoses, and medical services. A late diagnosis was defined as hepatitis B or hepatitis C notification occurring after, at the same time, or within 2 years preceding an HCC/DC diagnosis. Services provided during the 10-year period before HCC/DC diagnosis were assessed, including general practitioner (GP) or specialist visits, emergency department presentations, hospital admissions, and blood tests. RESULTS: Of the 25 766 notified cases of hepatitis B, 751 (2.9%) were diagnosed with HCC/DC, and hepatitis B was diagnosed late in 385 (51.3%). Of 44 317 cases of hepatitis C, 2576 (5.8%) were diagnosed with HCC/DC, and hepatitis C was diagnosed late in 857 (33.3%). Although late diagnosis dropped over time, missed opportunities for timely diagnosis were observed. Most people diagnosed late had visited a GP (97.4% for hepatitis B, 98.9% for hepatitis C) or had a blood test (90.9% for hepatitis B, 88.6% for hepatitis C) during the 10 years before HCC/DC diagnosis. The median number of GP visits was 24 and 32, and blood tests 7 and 8, for hepatitis B and C, respectively. CONCLUSIONS: Late diagnosis of viral hepatitis remains a concern, with the majority having frequent health-care service provision in the preceding period, indicating missed opportunities for diagnosis.

Australian consensus recommendations for the management of hepatitis B.

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.

Incidence of Invasive Pneumococcal Disease Higher Among People Notified With Markers of Hepatitis C Virus Infection: Population-based Surveillance in Victoria, Australia, 2001-2017.

BACKGROUND: Worse outcomes from invasive pneumococcal disease (IPD) have been reported among those coinfected with hepatitis C. We aimed to establish if IPD notification rates are higher among people notified with markers of hepatitis C virus infection than the general population. METHODS: IPD cases notified in Victoria, Australia, from July 2001-December 2017 were linked with hepatitis C cases (diagnosed by serology or PCR testing) notified from January 1991-December 2017. IPD incidence was calculated using population data and the estimated number of Victorians with hepatitis C. RESULTS: From July 2001-December 2017, 6407 IPD cases were notified. Hepatitis C infection was notified in 342 (5.3%) of IPD cases overall, and 24.4% among IPD cases aged 45-49 years. Among IPD cases also notified with hepatitis C, 55.3% were infected with 13-valent pneumococcal conjugate vaccine serotypes and 82.8% with 23-valent pneumococcal polysaccharide vaccine serotypes. Compared with IPD cases without hepatitis C, IPD cases also notified with hepatitis C were younger (mean age, 45.7 vs 49.4 years; P = .011) and more often male (65.5% vs 55.5%, P < .001). Annual IPD notification incidence was 6.8/100 000 among people without hepatitis C and 39.4/100 000 among people with hepatitis C (IRR, 5.8; 95% CI, 5.2-6.4; P < .001). CONCLUSIONS: IPD notification incidence was 5 times higher among people notified with markers of hepatitis C than the general population. Pneumococcal vaccination should be offered to people with markers of hepatitis C virus infection. To facilitate appropriate treatment, young and middle-aged adults with IPD should be tested for hepatitis C.

Modeling Progress Toward Elimination of Hepatitis B in Australia.

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) is a significant global health concern, and the most prevalent blood-borne virus in Australia. World Health Organization (WHO) member states have committed to global elimination, with targets to diagnose 90% of people living with CHB, treat 80% of those eligible, and reduce attributable deaths by 65% by the year 2030. Australia has committed to national targets of 80% diagnosed, 20% on treatment, and a 30% reduction in deaths by 2022. APPROACH AND RESULTS: We constructed and implemented a mathematical model to estimate the burden of CHB incorporating vaccination, phases of infection, cirrhosis progression, and mortality attributed to decompensated cirrhosis and hepatocellular carcinoma and examined the population-level impact of antiviral therapy. Diversity was integrated according to migration patterns, CHB prevalence by country of birth, Indigenous status, and age. Modelled outcomes were subjected to multivariate uncertainty analysis. Of the estimated 221,420 people living with CHB in Australia in 2017, 68% were diagnosed and 8.7% were receiving treatment (less than one-third of those estimated to be eligible). Based on current trends, the proportion of people living with CHB who have been diagnosed will reach 71% by 2022 and 81% by 2030, and treatment uptake will rise to 11.2% by 2022 and 12.9% by 2030, resulting in a 5.7% reduction in CHB-attributable deaths from 2015 to 2030. CHB treatment has prevented approximately 2,300 deaths in Australia between 2000 and 2017. CONCLUSIONS: Australia is not on track to meet local and global targets regarding CHB. Comprehensive and regularly updated modelling approaches accounting for diversity within the population are a useful tool to measure progress and impact of interventions, and quantify further improvements required to meet elimination goals.

Trends in chronic hepatitis B prevalence in Australian women by country of birth, 2000 to 2016.

Routine antenatal screening for chronic hepatitis B (HBV) in countries with high migrant populations provides an opportunity to monitor trends in HBV prevalence and can inform estimates locally and in countries with limited seroprevalence data. We linked perinatal birth register records with HBV notifications in the largest Australian state, over the period 2000-2016. Among women aged 15-44 years, we estimated age-standardized chronic HBV prevalence overall and by country of birth and also estimated trends in age-standardized HBV prevalence over time using regression modelling. Among 903 831 women, 8001 linked to a chronic HBV infection record (overall age-standardized prevalence 0.76%, 95% CI: 0.74-0.78). Prevalence varied by country of birth with the highest estimates among women born in Sierra Leone (11.13%, 95% CI: 8.29-13.96), Taiwan (8.08%, 95% CI: 6.74%-9.43%), Cambodia (7.47%, 95% CI: 6.50%-8.45%) and Vietnam (7.36%, 95% CI: 6.97%-7.75%); more moderate estimates among women from North Korea (2.76%, 95% CI: 1.99-3.53) and Samoa (2.64%, 95% CI: 1.99%-3.29%); prevalence was 0.18% (95% CI: 0.17-0.19) in Australian-born women. Over 17 years, there were significant reductions in HBV prevalence among all women (from 0.88% in 2000 to 0.57% in 2016; P < .0001). Among women from high prevalence countries, the greatest absolute reductions were observed among those from Taiwan (10.1%, P < .001) followed by Tonga (5.4%, P < .001), whereas no reductions were observed for women born in Vietnam (P = .08), South Korea (P = .41) and Sudan (P = .06). In conclusion, routine antenatal HBV testing can be used to inform HBV prevalence estimates and vaccine programme impact in countries with limited surveillance and high migration to Australia.

Adherence in chronic hepatitis B: associations between medication possession ratio and adverse viral outcomes.

BACKGROUND: Antiviral therapy for chronic hepatitis B (CHB) is effective and can substantially reduce the risk of progressive liver disease and hepatocellular carcinoma but is often administered for an indefinite duration. Adherence has been shown in clinical trials to maximize the benefit of therapy and prevent the development of resistance, however the optimal threshold for predicting clinical outcomes has not been identified. The aim of this study was to analyse adherence using the medication possession ration (MPR) and its relation to virological outcomes in a large multi-centre hospital outpatient population, and guide development of an evidence-based threshold for optimal adherence. METHODS: Pharmacy and pathology records of patients dispensed CHB antiviral therapy from 4 major hospitals in Melbourne between 2010 and 2013 were extracted and analysed to determine their MPR and identify instances of unfavourable viral outcomes. Viral outcomes were classified categorically, with unfavourable outcomes including HBV DNA remaining detectable after 2 years treatment or experiencing viral breakthrough. The association between MPR and unfavourable outcomes was assessed according to various thresholds using ROC analysis and time-to-event regression. RESULTS: Six hundred forty-two individuals were included in the analysis. Median age was 46.6 years, 68% were male, 77% were born in Asia, and the median time on treatment was 27.5 months. The majority had favourable viral outcomes (91.06%), with most having undetectable HBV DNA at the end of the study period. The most common unfavourable outcome was a rise of < 1 log in HBV DNA (6.54% of the total), while 2.49% of participants experienced viral breakthrough. Adherence was linearly associated with favourable outcomes, with increasing risk of virological breakthrough as MPR fell. Decreasing the value of MPR, at which a cut-point was taken, was associated with a progressively larger reduction in the rate of unfavourable event; from a 60% reduction under a cut-point of 1.00 to a 79% reduction when the MPR cut-point was set at 0.8. CONCLUSION: Lower adherence as measured using the MPR was strongly associated with unfavourable therapeutic outcomes, including virological failure. Optimising adherence is therefore important for preventing viral rebound and potential complications such as antiviral resistance. The evidence of dose-response highlights the need for nuanced interventions.

Where has all the influenza gone? The impact of COVID-19 on the circulation of influenza and other respiratory viruses, Australia, March to September 2020.

The coronavirus disease pandemic was declared in March 2020, as the southern hemisphere's winter approached. Australia expected co-circulation of severe acute respiratory syndrome coronavirus 2, influenza and other seasonal respiratory viruses. However, influenza notifications were 7,029 (March-September) compared with an average 149,832 for the same period in 2015-2019 [corrected], despite substantial testing. Restrictions on movement within and into Australia may have temporarily eliminated influenza. Other respiratory pathogens also showed remarkably changed activity in 2020.

Bridging the access gap: Medicare ineligibility in people living with chronic hepatitis B.

People living in Australia on temporary student or work visas are excluded from Medicare access and can face barriers to adequate healthcare, even if they are privately insured. This analysis aimed to quantify this issue in relation to people living with chronic hepatitis B, the majority of whom in Australia were born overseas. The data suggest that an estimated 25 000 people living with chronic hepatitis B in Australia are ineligible for Medicare, 10% of the total number affected, with considerable potential impact in access to effective healthcare and prevention of adverse outcomes.

Chronic hepatitis B prevalence in Australian Aboriginal and Torres Strait Islander people before and after implementing a universal vaccination program: a systematic review and meta-analysis.

Background A higher prevalence of chronic hepatitis B (CHB) has been reported in Aboriginal and Torres Strait Islander (Aboriginal) compared with non-Aboriginal Australians. An Australian infant and adolescent hepatitis B virus (HBV) vaccination program was implemented in 2000. Meta-analysis methods will be used to examine if the pooled prevalence of CHB decreased after 2000 among Aboriginal Australians. METHODS: Embase, Medline and Web of Science were searched from 1 January 1981 to 29 March 2018 and all issues of the Northern Territory and New South Wales Public Health Bulletins. Studies needed to report the number of individuals who were tested and tested positive for hepatitis B surface antigen (HBsAg). RESULTS: There were 36 studies; 16 before and 20 after 2000; reporting 84 prevalence estimates. Population groups included: adults (14 studies), pregnant women (13 studies), prisoners (five studies) children or teenagers (10 studies) and infants (two studies). The pooled prevalence of HBsAg decreased overall (from 10.8% before 2000 vs 3.5% after 2000), in women (4.2% vs 2.2%), in males (17.5% vs 3.5%), in regional (7.8% vs 3.9%) and remote (14.4% vs 5.7%) areas, in New South Wales (12.3% vs 3.0%), in the Northern Territory (6.1% vs 5.1%), in adults (15.3% vs 4.3%) and in pregnant women (3.6% vs 2.6%). CONCLUSION: The prevalence of HBsAg decreased among Aboriginal people after 2000.

Hepatocellular carcinoma over three decades in Victoria, Australia: epidemiology, diagnosis and trends, 1984-2013.

BACKGROUND: Liver cancer continues to be a health priority in Australia, with the majority attributable to preventable causes, and certain populations at higher risk. AIMS: Epidemiological assessment of incidence, trends and distribution to inform prevention, and reassessment of data in light of recent changes to registry case definitions. METHODS: Reported cases of hepatocellular carcinoma (HCC) in Victoria, Australia, 1984-2013, were obtained from the Victorian Cancer Registry. Demographic characteristics were examined, incidence and survival assessed using Poisson and Cox regression, and geographic distribution mapped. Incidence was compared before and after inclusion of non-histologically confirmed cases in Registry data to assess impacts on incidence trends. RESULTS: Diagnoses of HCC rose substantially between 1984 and 2013, increasing sixfold from 0.9 to 5.9 per 100 000. The rate of increase per year accelerated from 5.3% between 1984 and 2003 to 9.5% between 2004 and 2013. Cases were disproportionately male (80%), median age at diagnosis was 66 years and 53% were born overseas. Even during 2004-2013, 5-year survival was only 16%, although higher among younger people, metropolitan residents and people born overseas. Incidence showed strong geographic clustering. The proportion of cases diagnosed clinically increased from 1% during 1984-2004 to 43% in 2009-2013. The revised case definition added 993 cases (27.3% of total). CONCLUSION: Cases of HCC are becoming increasingly common, and revised incidence estimates highlight the impact of case definitions in the context of changing diagnostic approaches. The ongoing burden, disproportionate population distribution and low survival emphasise the importance of prevention and early detection as a public health imperative.

Epidemiology and phylogenetic analysis of hepatitis D virus infection in Australia.

BACKGROUND: The incidence and trends of the hepatitis D virus (HDV) in Australia have not been recently assessed, and the circulating genotypes have never been determined. AIM: To characterise the current virology and epidemiology of HDV. METHODS: Notifiable disease surveillance and laboratory testing data were analysed to assess demographics, risk factors and trends. HDV serology and RNA testing were performed on requested samples from 2010 to 2016. Sequencing of a 500-nucleotide amplicon of the delta antigen and phylogenetic analysis of the strains from 2009 to 2016 were also conducted. RESULTS: Ninety HDV notifications were reported to the Victorian Department of Health and Human Services between 2010 and 2016. The majority (64.4%) of those diagnosed were born overseas, most commonly in Sudan, Pakistan and Vietnam. Over the same period, 190 patients tested positive for anti-HDV serology and 166 for HDV RNA. Sequencing of isolates from 169 individuals between 2009 and 2016 found that 80.5% strains were genotype 1, 16% genotype 5 and 3.5% genotype 2. Phylogenetic analysis confirmed the relatedness of strains from birth country, demonstrated the presence of the 'Pacific Island' genotype 1 strain in Queensland and supported possible transmission in correctional facilities and within families. CONCLUSIONS: This study demonstrates the ongoing need for routine HDV screening and engagement in clinical care for people living with HBV in Australia. Epidemiological findings highlight the diversity in those affected and provide insights into local and global geographic distribution and transmission patterns.

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013.

BACKGROUND: With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS: We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS: Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION: Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING: Bill & Melinda Gates Foundation.

The challenge of liver cancer surveillance in general practice: Do recall and reminder systems hold the answer?

BACKGROUND: Hepatocellular carcinoma (HCC) surveillance reduces mortality in at-risk people living with chronic hepatitis B (CHB), but is difficult to achieve in practice. The objective of this study was to measure participation and adherence to liver cancer HCC surveillance in eligible patients in a community health centre, following support from the Integrated Hepatitis B Service (IHBS). METHODS: A retrospective analysis of the medical records of patients with CHB who met the indications for HCC surveillance over a 4.5-year period of IHBS involvement was conducted. Data collected included the date of ultrasound examinations and HBV DNA viral load tests. RESULTS: Sixty-seven patients underwent HCC surveillance, representing 213 person years. The participation rate was 75%. Adherence to surveillance was considered good in 18 (27%) patients, suboptimal in 29 (43%) patients and poor in 20 (30%) patients. A greater proportion of patients were receiving HCC surveillance at the final audit (56%) than at baseline (10%; P DISCUSSION: It is difficult to achieve optimal adherence to HCC surveillance, even with additional support.