Maryam Alavi

Background: Viral hepatitis, alcohol‐related liver disease (ARLD) and nonalcoholic fatty liver disease (NAFLD) are the main risk factors for hepatocellular carcinoma (HCC) in many countries. In Australia, given the access to hepatitis C virus (HCV) direct‐acting antiviral (DAA) therapy since 2016, a temporal change in HCC aetiology was hypothesized. This study evaluated the temporal change in the aetiology and characteristics of HCC in New South Wales (NSW).Methods: Patients diagnosed with HCC, admitted to three public hospitals in NSW between 2008 and 2021, were included in the analyses. We assessed the annual frequency of each HCC aetiology and the distribution of HCC characteristics in participants.Results: Among 1370 patients, the most common HCC etiologies were HCV (n = 483, 35%), ARLD (n = 452, 33%), NAFLD (n = 347, 25%) and hepatitis B virus (n = 301, 22%). The proportion of HCV‐related HCC was the highest in 2011–2016 (41%) and significantly declined to 30% in 2017–2021 (odds ratio [OR], 0.53 [95% confidence interval (CI), 0.35–0.79]; P = 0.002). The proportion of HCC diagnosed at an early stage (Barcelona Clinic Liver Cancer stage O/A) increased from 41% in 2008–2009 to 56% in 2020–2021 (OR per annum, 1.05 [95% CI, 1.02–1.08]; P = 0.002), and the proportion of patients receiving potentially curative HCC management increased from 29% in 2008–2009 to 41% in 2020–2021 (OR per annum, 1.06 [95% CI, 1.03–1.10]; P < 0.001).Conclusion: The contribution of HCV to HCC burden has been decreasing in the DAA era, suggesting the role of HCV elimination in decreasing HCC risk. Increasing frequency of less advanced HCC at diagnosis over time suggests improved HCC surveillance.

Routinely collected and linked healthcare administrative datasets could be used to monitor mortality among people with hepatitis B (HBV) and C (HCV). This study aimed to evaluate the concordance in records of liver‐related mortality among people with an HBV or HCV notification, between data on hospitalization for end‐stage liver disease (ESLD) and death certificates. In New South Wales, Australia, HBV and HCV notifications (1993–2017) were linked to hospital admissions (2001–2018), all‐cause mortality (1993–2018) and cause‐specific mortality (1993–2016) datasets. Hospitalization for ESLD was defined as a first‐time hospital admission due to decompensated cirrhosis (DC) or hepatocellular carcinoma (HCC). Consistency of liver death definition of mortality following hospitalization for ESLD was compared with two death certificate‐based definitions of liver deaths coded among primary and secondary cause‐specific mortality data, including ESLD‐related (deaths due to DC and HCC) and all‐liver deaths (ESLD‐related and other liver‐related causes). Of 63,292 and 107,430 individuals with an HBV and HCV notification, there were 4478 (2.6%) post‐ESLD hospitalization deaths, 5572 (3.3%) death certificate liver disease deaths and 2910 (1.7%) death certificate ESLD deaths. Between 2001 and 2016, among HBV post‐ESLD hospitalization deaths (n = 891), 63% (562) had death certificate ESLD recorded, and 83% (741) had death certificate liver disease recorded. Between 2001 and 2016, among HCV post‐ESLD hospitalization deaths (n = 3587), 58% (2082) had death certificate ESLD recorded, and 87% (3135) had death certificate liver disease recorded. At least one‐third of death certificates with DC and HCC as cause of death had no mention of HBV, HCV or viral hepatitis. Our study identified limitations in estimating and tracking HBV and HCV liver disease mortality using death certificate‐based data only. The optimum data for this purpose is either ESLD hospitalisations with vital status information or a combination of these with cause‐specific death certificate data.

The hepatitis C virus (HCV) care cascade characterization is important for monitoring progress towards HCV elimination. This study evaluated HCV care cascade and factors associated with treatment during pre‐DAA (2011–2012 and 2013–2015) and DAA (2016–2018) eras in New South Wales (NSW), Australia. We conducted a cohort study of people with an HCV notification (1993 to 2017) through end 2018, linked to administrative datasets, including HCV treatment and non‐hospital services. Those aged <18 years, died within first 6 months of study period or notification, and who had successful HCV treatment in period before were excluded. Sex‐specific spontaneous viral clearance was incorporated to estimate treatment‐eligible population. The study population in each period were cumulative and brought forward from one period to the next. Among 115,667 people with HCV notification, 87,063 fulfilled eligibility criteria. During 2011 to 2012, 2013 to 2015, and 2016 to 2018, cumulative HCV notifications were 71,677, 77,969, and 80,017; 52,016, 56,793, and 57,467 were eligible for treatment; 29%, 48%, and 64% confirmed HCV RNA positive; and 0.6%, 5%, and 38% initiated HCV treatment, respectively. Birth cohort 1945 to 1964 (vs. ≥1965), males, non‐Aboriginal ethnicity, regional/rural area of residence, and HCV/HIV co‐infection were associated with higher treatment uptake. Incarceration and drug dependence were associated with higher treatment uptake during the DAA era. In Australia, many marginalized populations including those incarcerated and those with drug dependence have equitable treatment uptake in the DAA era. Targeted strategies are required to enhance treatment uptake for females and Aboriginal populations.

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.

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.

People living with HIV (PLHIV) are a priority population to receive hepatitis C virus (HCV) screening and treatment. We aimed to characterize the HCV care cascade among PLHIV between 2010 and 2018 and to compare HCV testing and treatment uptake pre‐ and post‐availability of direct‐acting antivirals (DAAs) in New South Wales (NSW), Australia. Records of all HCV notifications (1993–2017) were linked to HIV notifications, deaths, hospitalizations, incarcerations, opioid agonist therapy, HCV RNA testing and treatment databases. Numbers and proportions were calculated for all stages of the care cascade and factors associated with HCV testing, and DAA treatment uptake were evaluated using logistic regression. From 383 individuals with HCV notification (2009–2017), 349 (91%) were ever HCV RNA tested, 285 (74%) had an indicator of chronic HCV infection, and from those eligible for treatment, 210 (74%) received HCV treatment. HCV testing was recorded for 85% pre‐DAA era and reached a cumulative proportion of 90% post‐DAA while treatment uptake had a 10‐fold increase from 7% pre‐ to 73% post‐DAA era. Younger age (adjusted odds ratio [aOR] 0.98; 95% CI 0.96–0.99), female gender (aOR 1.87; 95% CI 1.10–3.19), and rural region residence at notification (aOR 1.56; 95% CI 1.03–2.36) were associated with not receiving HCV testing. No identified factor was associated with not receiving treatment post‐DAA era. Removing barriers to HCV testing, expanding treatment to a variety of settings and continuous education and harm reduction are essential to achieve HCV elimination among PLHIV in Australia.

The World Health Organization 2030 targets for hepatitis C virus (HCV) elimination include diagnosing 90% of people with HCV and treating 80% of people diagnosed with HCV. This systematic review assessed reported data on the HCV care cascade in various countries and populations, with a focus on direct‐acting antiviral (DAA) treatment uptake. Bibliographic databases and conference presentations were searched for studies reporting the HCV care cascade (DAA treatment uptake was a requirement) among the overall population with HCV or sub‐populations at greater risk of HCV. Population‐based studies, with participants representative of a city, province/state or country were eligible. Twenty eligible studies were included, reporting HCV care cascade in 28 populations/sub‐populations from 11 countries. DAA treatment uptake at national levels was reported from Iceland (95%), Egypt (92%), Georgia (79%), Norway (18%) and Sweden (8%), and at sub‐national levels from the Netherlands (52%), Canada (50%), the United States (29%) and Denmark (5%). Among people with HIV‐HCV co‐infection, DAA treatment uptake was 62% in Canada, 44% in the Netherlands, 21% in Switzerland and 18% in the United States. Among people who inject drugs, DAA treatment uptake was 50% in Georgia, 40% in Canada, 37% in Australia and 13% in the United States. Data among people experiencing homelessness were only available from the United States (treatment uptake: 12%–14%). We found no eligible study reporting HCV care cascade data in prisons. Relatively few countries reported HCV care cascade at the national level. DAA treatment uptake was widely varied across populations/sub‐populations, with higher rates reported in recent years.