Hepatitis C Virus Notification Research Articles

Returning incidentally discovered Hepatitis C RNA-seq results to COPDGene study participants

The consequences of returning infectious pathogen test results identified incidentally in research studies have not been well-studied. Concerns include identification of an important health issue for individuals, accuracy of research test results, public health impact, potential emotional distress for participants, and need for IRB permissions. Blood RNA-sequencing analysis for non-human RNA in 3984 participants from the COPDGene study identified 228 participants with evidence suggestive for hepatitis C virus (HCV) infection. We hypothesized that incidentally discovered HCV results could be effectively returned to COPDGene participants with attention to the identified concerns. In conjunction with a COPDGene Participant Advisory Panel, we developed and obtained IRB approval for a process of returning HCV research results and an HCV Follow-Up Study questionnaire to capture information about previous HCV diagnosis and treatment information and participant reactions to return of HCV results. During phone calls following the initial HCV notification letter, 84 of 124 participants who could be contacted (67.7%) volunteered that they had been previously diagnosed with HCV infection. Thirty-one of these 124 COPDGene participants were enrolled in the HCV Follow-Up Study. Five of the 31 HCV Follow-Up Study participants did not report a previous diagnosis of HCV. For four of these participants, subsequent clinical HCV testing confirmed HCV infection. Thus, 30/31 Follow-Up Study participants had confirmed HCV diagnoses, supporting the accuracy of the HCV research test results. However, the limited number of participants in the Follow-Up Study precludes an accurate assessment of the false-positive and false-negative rates of the research RNA sequencing evidence for HCV. Most HCV Follow-Up Study participants (29/31) were supportive of returning HCV research results, and most participants found the process for returning HCV results to be informative and not upsetting. Newly diagnosed participants were more likely to be pleased to learn about a potentially curable infection (p = 0.027) and showed a trend toward being more frightened by the potential health risks of HCV (p = 0.11). We conclude that HCV results identified incidentally during transcriptomic research studies can be successfully returned to research study participants with a carefully designed process.

Stages of care for patients with chronic hepatitis C at a hospital in southern Brazil.

Hepatitis C virus (HCV) is defined as a public health problem by the World Health Organization (WHO) and since then has defined targets through the HCV elimination. The HCV cascade of care highlights the progress towards these goals and essential interventions that need to be delivered along this continuum care. To document the treatment cascade for patients with HCV infection at the Hospital Nossa Senhora da Conceição (HNSC), defining the percentage of antibody-positive patients who collected molecular biology tests (polymerase chain reaction), attended outpatient clinic assistance, underwent treatment, and achieved a virologic cure termed sustained virologic response (SVR). With the retrospective cohort design, patients diagnosed with HCV infection in the period between January 1, 2015 and December 31, 2020 were included. Data from HCV notification forms, electronic medical records, Computerized Laboratory Environment Manager System, and Medicine Administration System (evaluation of special medications) were collected in 2022 and all information up to that period was considered. The data were analyzed with IBM SPSS version 25, and Poisson regression with robust simple variance was performed for analysis of variables in relation to each step of the cascade. Variables with P < 0.20 were included in the multivariate analysis with P < 0.05 considered significant. Pearson's chi-square test was applied to compare the groups of patients who persisted in follow-up at the HNSC and who underwent follow-up at other locations. Results were lower than expected by the WHO with only 49% of candidates receiving HCV treatment and only 29% achieving SVR, despite the 98% response rate to direct acting antivirals documented by follow-up examination. The city of origin and the place of follow-up were the variables associated with SVR and all other endpoints. When comparing the cascade of patients who remained assisted by the HNSC vs external patients, we observed superior data for HNSC patients in the SVR. Patients from the countryside and metropolitan region were mostly assisted at the HNSC and the specialized and continuous care provided at the HNSC was associated with superior results, although the outcomes remain far from the goals set by the WHO. With the elaboration of the HCV cascade of care using local data, it was possible to stratify and evaluate risk factors associated with losses between each step of the cascade, to inform new strategies to guide elimination efforts in the future.

Factors associated with hepatitis C treatment uptake among females of childbearing age in New South Wales, Australia: A population‐based study

Females of childbearing age with hepatitis C virus (HCV) face increased marginalisation with intersecting, sex-specific barriers to direct acting antiviral (DAA) therapy. We assessed the factors associated with uptake of DAA therapy among females of childbearing age, including those with evidence of recent drug dependence. HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, perinatal, HIV notifications, deaths and prescription databases. Recent drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT occurring in the DAA era (2016-2018). Logistic regression was used to analyse factors associated with DAA uptake among females of childbearing age (18-44), including those with recent drug dependence. Among 57,467 people with evidence of chronic HCV in the DAA era (2016-2018), 20,161 (35%) were female, including 33% (n = 6563/20,161) of childbearing age (18-44). Among all females of childbearing age (n = 6563) and those with evidence of recent drug dependence (n = 2278/6563, 35%), DAA uptake was lower among those who had given birth in the DAA era (vs. no birth record, all females of childbearing age; aOR: 0.74, 95% CI 0.61, 0.89; those with recent drug dependence; aOR 0.69, 95% CI 0.51, 0.93) and Aboriginal and Torres Strait Islander peoples (all females of childbearing age; aOR 0.81, 95% CI 0.71, 0.93; those with recent drug dependence aOR 0.75, 95% CI 0.62, 0.90). Females of childbearing age should be considered a key population for DAA therapy. Enhancing antenatal and postnatal HCV care may be critical in the pursuit towards elimination.

Hepatitis C care cascade before and during the direct-acting antiviral eras in New South Wales, Australia: A population-based linkage study.

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.

Evaluation of the hepatitis C cascade of care among people living with HIV in New South Wales, Australia: A data linkage study.

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.

Opportunities to Enhance Linkage to Hepatitis C Care Among Hospitalized People With Recent Drug Dependence in New South Wales, Australia: A Population-based Linkage Study.

People who inject drugs are at greater risk of hepatitis C virus (HCV) infection and hospitalization, yet admissions are not utilized for HCV treatment initiation. We aimed to assess the extent to which people with HCV notification, including those with evidence of recent drug dependence, are hospitalized while eligible for direct-acting antiviral (DAA) therapy, and treatment uptake according to hospitalization in the DAA era. We conducted a longitudinal, population-based cohort study of people living with HCV in the DAA era (March 2016-December 2018) through analysis of linked databases in New South Wales, Australia. Kaplan-Meier estimates were used to report HCV treatment uptake by frequency, length, and cause-specific hospitalization. Among 57 467 people, 14 938 (26%) had evidence of recent drug dependence, 50% (n = 7506) of whom were hospitalized while DAA eligible. Incidence of selected cause-specific hospitalization was highest for mental health-related (15.84 per 100 person-years [PY]), drug-related (15.20 per 100 PY), and injection-related infectious disease (9.15 per 100 PY) hospitalizations, and lowest for alcohol use disorder (4.58 per 100 PY) and liver-related (3.13 per 100 PY). In total, 65% (n = 4898) of those who were hospitalized had been admitted ≥2 times, and 46% (n = 3437) were hospitalized ≥7 days. By the end of 2018, DAA therapy was lowest for those hospitalized ≥2 times, for ≥7 days, and those whose first admission was for injection-related infectious disease, mental health disorders, and drug-related complications. Among people who have evidence of recent drug dependence, frequent hospitalization-particularly mental health, drug, and alcohol admissions-presents an opportunity for engagement in HCV care.

Declining hepatitis C virus-related liver disease burden in the direct-acting antiviral therapy era in New South Wales, Australia

Population-level evidence for the impact of direct-acting antiviral (DAA) therapy on hepatitis C virus (HCV)-related disease burden is lacking. We aimed to evaluate trends in HCV-related decompensated cirrhosis and hepatocellular carcinoma (HCC) hospitalisation, and liver-related and all-cause mortality in the pre-DAA (2001-2014) and DAA therapy (2015-2017) eras in New South Wales, Australia. HCV notifications (1993-2016) were linked to hospital admissions (2001-2017) and mortality (1995-2017). Segmented Poisson regressions and Poisson regression were used to assess the impact of DAA era and factors associated with liver-related mortality, respectively. Among 99,910 people with an HCV notification, 3.8% had a decompensated cirrhosis diagnosis and 1.8% had an HCC diagnosis, while 3.3% and 10.5% died of liver-related and all-cause mortality, respectively. In the pre-DAA era, the number of decompensated cirrhosis and HCC diagnoses, and liver-related and all-cause mortality consistently increased (incidence rate ratios 1.04 [95% CI 1.04-1.05], 1.08 [95% CI 1.07-1.08], 1.07 [95% CI 1.06-1.07], and 1.05 [95% CI 1.04-1.05], respectively) over each 6-monthly band. In the DAA era, decompensated cirrhosis diagnosis and liver-related mortality numbers declined (incidence rate ratios 0.97 [95% CI 0.95-0.99] and 0.96 [95% CI 0.94-0.98], respectively), and HCC diagnosis and all-cause mortality numbers plateaued (incidence rate ratio 1.00 [95% CI 0.97-1.03] and 1.01 [95% CI 1.00-1.02], respectively) over each 6-monthly band. In the DAA era, alcohol-use disorder (AUD) was common in patients diagnosed with decompensated cirrhosis and HCC (65% and 46% had a history of AUD, respectively). AUD was independently associated with liver-related mortality (incidence rate ratio 3.35; 95% CI 3.14-3.58). In the DAA era, there has been a sharp decline in liver disease morbidity and mortality in New South Wales, Australia. AUD remains a major contributor to HCV-related liver disease burden, highlighting the need to address comorbidities. Rising hepatitis C-related morbidity and mortality is a major public health issue. However, development of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) means hepatitis C could be eliminated as a public health threat by 2030. This study shows a sharp decline in liver disease morbidity and mortality since the introduction of DAAs in New South Wales, Australia. Despite this, heavy alcohol use remains an important risk factor for liver disease among people with hepatitis C. To ensure that the benefits of new antiviral treatments are not compromised, management of major comorbidities, including heavy alcohol use must improve among people with hepatitis C.

Hepatitis C virus notification rates in Australia are highest in socioeconomically disadvantaged areas.

BackgroundPoor access to health services is a significant barrier to achieving the World Health Organization’s hepatitis C virus (HCV) elimination targets. We demonstrate how geospatial analysis can be performed with commonly available data to identify areas with the greatest unmet demand for HCV services.MethodsWe performed an Australia-wide cross-sectional analysis of 2015 HCV notification rates using local government areas (LGAs) as our unit of analysis. A zero-inflated negative binomial regression was used to determine associations between notification rates and socioeconomic/demographic factors, health service and geographic remoteness area (RA) classification variables. Additionally, component scores were extracted from a principal component analysis (PCA) of the healthcare service variables to provide rankings of relative service coverage and unmet demand across Australia.ResultsAmong LGAs with non-zero notifications, higher rates were associated with areas that had increased socioeconomic disadvantage, more needle and syringe services (incidence rate ratio [IRR] 1.022; 95%CI 1.001, 1.044) and more alcohol and other drug services (IRR 1.019; 1.005, 1.034). The distribution of PCA component scores indicated that per-capita healthcare service coverage was lower in areas outside of major Australian cities. Areas outside of major cities also contained 94% of LGAs in the lowest two socioeconomic quintiles, as well as 35% of HCV notifications despite only representing 29% of the population.ConclusionsAs countries aim for HCV elimination, routinely collected data can be used to identify geographical areas for priority service delivery. In Australia, the unmet demand for HCV treatment services is greatest in socioeconomically disadvantaged and non-metropolitan areas.

Mortality trends among people with hepatitis B and C: a population-based linkage study, 1993-2012

BackgroundThis study evaluated cause-specific mortality trends including liver-related mortality among people with a hepatitis B virus (HBV) and hepatitis C virus (HCV) notification in New South Wales, Australia.MethodsNotifications 1993-2012 were linked to cause-specific mortality records 1993-2013.ResultsAmong 57,929 and 92,474 people with a HBV and HCV notification, 4.8% and 10.0% died since 1997. In early 2010s, 28% and 33% of HBV and HCV deaths were liver-related, 28% and 17% were cancer-related (excluding liver cancer), and 5% and 15% were drug-related, respectively. During 2002-2012, annual HBV-related liver death numbers were relatively stable (53 to 68), while HCV-related liver death numbers increased considerably (111 to 284). Age-standardised HBV-related liver mortality rates declined from 0.2 to 0.1 per 100 person-years (PY) (P < 0.001); however, HCV-related rates remained stable (0.2 to 0.3 per 100 PY, P = 0.619). In adjusted analyses, older age was the strongest predictor of liver-related mortality [birth earlier than 1945, HBV adjusted hazard ratio (aHR) 28.1, 95% CI 21.0, 37.5 and; HCV aHR 31.9, 95% CI 26.8, 37.9], followed by history of alcohol-use disorder (HBV aHR 7.0, 95% CI 5.5, 8.8 and; HCV aHR 8.3, 95% CI 7.6, 9.1).ConclusionsDeclining HBV-related liver mortality rates and stable burden suggest an impact of improved antiviral therapy efficacy and uptake. In contrast, the impact of interferon-containing HCV treatment programs on liver-related mortality individual-level risk and population-level burden has been limited. These findings also highlight the importance of HBV/HCV public health interventions that incorporate increased antiviral therapy uptake, and action on health risk behaviors.

Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively) and mortality (1995-2013/2014/2015, respectively). Age-standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58487, 84529 and 31924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8years in 2001-2006 and 2007-2011) and NSW (0.9years in 2001-2006 and 2007-2013) and improved in Scotland (0.7years in 2001-2006 to 1.5years in 2007-2014). Across the settings, HCC burden increased, individual-level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon-based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

The contribution of alcohol use disorder to decompensated cirrhosis among people with hepatitis C: An international study

The advent of direct-acting antivirals (DAAs) has led to ambitious targets for hepatitis C virus (HCV) elimination. However, in the context of alcohol use disorder the ability of DAAs to achieve these targets may be compromised. The aim of this study was to evaluate the contribution of alcohol use disorder to HCV-related decompensated cirrhosis in three settings. HCV notifications from British Columbia, Canada; New South Wales, Australia, and Scotland (1995-2011/2012/2013, respectively) were linked to hospital admissions (2001-2012/2013/2014, respectively). Alcohol use disorder was defined as non-liver-related hospitalisation due to alcohol use. Age-standardised decompensated cirrhosis incidence rates were plotted, associated factors were assessed using Cox regression, and alcohol use disorder-associated population attributable fractions (PAFs) were computed. Among 58,487, 84,529, and 31,924 people with HCV in British Columbia, New South Wales, and Scotland, 2,689 (4.6%), 3,169 (3.7%), and 1,375 (4.3%) had a decompensated cirrhosis diagnosis, and 28%, 32%, and 50% of those with decompensated cirrhosis had an alcohol use disorder, respectively. Age-standardised decompensated cirrhosis incidence rates were considerably higher in people with alcohol use disorder in New South Wales and Scotland. Decompensated cirrhosis was independently associated with alcohol use disorder in British Columbia (aHR 1.92; 95% CI 1.76-2.10), New South Wales (aHR 3.68; 95% CI 3.38-4.00) and Scotland (aHR 3.88; 95% CI 3.42-4.40). The PAFs of decompensated cirrhosis-related to alcohol use disorder were 13%, 25%, and 40% in British Columbia, New South Wales and Scotland, respectively. Alcohol use disorder was a major contributor to HCV liver disease burden in all settings, more distinctly in Scotland. The extent to which alcohol use would compromise the individual and population-level benefits of DAA therapy needs to be closely monitored. Countries, where appropriate, must develop strategies combining promotion of DAA treatment uptake with management of alcohol use disorders, if World Health Organization 2030 HCV mortality reduction targets are going to be achieved. The burden of liver disease has been rising among people with hepatitis C globally. The recent introduction of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) has brought renewed optimism to the sector. DAA scale-up could eliminate hepatitis C as a public health threat in the coming decades. However, our findings show heavy alcohol use is a major risk factor for liver disease among people with hepatitis C. If continued, heavy alcohol use could compromise the benefits of new antiviral treatments at the individual- and population-level. To tackle hepatitis C as a public health threat, where needed, DAA therapy should be combined with management of heavy alcohol use.

Survival following hospitalization with hepatocellular carcinoma among people notified with hepatitis B or C virus in Australia (2000-2014).

We assessed trends in HCC survival in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in New South Wales, Australia. Data on HBV (n = 54,399) and HCV (n = 96,908) notifications (1993‐2012) were linked to a hospitalization database (July 2000‐June 2014), the New South Wales Cancer Registry, and the New South Wales Death Registry. A total of 725 (1.3%) first HBV‐hepatocellular carcinoma (HCC) and 1,309 (1.4%) first HCV‐HCC hospitalizations were included. Death occurred in 60.4% of HBV‐HCC and 69.6% of HCV‐HCC patients. Median survival following first HBV‐HCC hospitalization improved from 0.6 years (95% confidence interval [CI] 0.39‐1.28) in 2000‐2004 to 2.8 years (1.54‐5.54) in 2010‐2014. Median survival following first HCV‐HCC hospitalization was 0.8 years (0.45‐1.33) in 2000‐2004 and 0.9 (0.67‐1.18) in 2010‐2014. One‐year HBV‐HCC survival in 2010‐2014 compared to 2000‐2004 improved for those with (94% versus 81%) and without (42% versus 33%) potentially curative procedures (liver resection, liver transplantation, and radiofrequency ablation). Factors associated with improved survival following HBV‐HCC were later study period (hazard ratio [HR] = 0.74; 95% CI, 0.57‐0.97) and potentially curative procedures (liver resection, liver transplantation, and radiofrequency ablation) (HR = 0.23; 95% CI, 0.17‐0.29), while male gender (HR = 1.37; 95% CI, 1.03‐1.82), human immunodeficiency virus coinfection (HR = 3.06; 95% CI, 1.36‐6.88), and Charlson Comorbidity Index ≥3 (HR = 1.81; 95% CI, 1.35‐2.40) were associated with reduced survival. Factors associated with improved survival following HCC‐HCV were Asia‐Pacific country of birth (HR = 0.68; 95% CI, 0.55‐0.84) and potentially curative procedures (HR = 0.21; 95% CI, 0.17‐0.25), while age (HR = 1.01; 95% CI, 1.01‐1.02), rural place of residence (HR = 1.46; 95% CI, 1.22‐1.74), and human immunodeficiency virus coinfection (HR = 2.71; 95% CI, 1.19‐6.15) were associated with reduced survival. Conclusion: All‐cause survival following HBV‐HCC has improved considerably, suggesting an impact of more effective antiviral therapy and earlier HCC diagnosis; in contrast, all‐cause survival for HCV‐HCC is unchanged. (Hepatology Communications 2017;1:736–747)

HCV management in resource-constrained countries.

With the arrival of all-oral directly acting antiviral (DAA) therapy with high cure rates, the promise of hepatitis C virus (HCV) eradication is within closer reach. The availability of generic DAAs has improved access to countries with constrained resources. However, therapy is only one component of the HCV care continuum, which is the framework for HCV management from identifying patients to cure. The large number of undiagnosed HCV cases is the biggest concern, and strategies to address this are needed, as risk factor screening is suboptimal, detecting <20% of known cases. Improvements in HCV confirmation through either reflex HCV RNA screening or ideally a sensitive point of care test are needed. HCV notification (e.g., Australia) may improve diagnosis (proportion of HCV diagnosed is 75%) and may lead to benefits by increasing linkage to care, therapy and cure. Evaluations for cirrhosis using non-invasive markers are best done with a biological panel, but they are only moderately accurate. In resource-constrained settings, only generic HCV medications are available, and a combination of sofosbuvir, ribavirin, ledipasvir or daclatasvir provides sufficient efficacy for all genotypes, but this is likely to be replaced with pangenetypic regimens such as sofosbuvir/velpatasvir and glecaprevir/pibrentaasvir. In conclusion, HCV management in resource-constrained settings is challenging on multiple fronts because of the lack of infrastructure, facilities, trained manpower and equipment. However, it is still possible to make a significant impact towards HCV eradication through a concerted effort by individuals and national organisations with domain expertise in this area.

Chronic hepatitis C burden and care cascade in Australia in the era of interferon-based treatment.

Interferon-free direct-acting antiviral regimens for hepatitis C virus (HCV) infection have been recently available in Australia, beginning a new era in clinical and public health management of HCV infection. This study provided updated estimates of the HCV infection care cascade and burden in Australia as a reliable platform for assessing the future impact of interferon-free therapies. A modeling approach was applied to estimate the number of individuals living with chronic HCV infection and with various liver disease stages. Data from national registries of HCV notification and liver transplantation, literature review, and expert consensus informed the model parameters. HCV notification and Pharmaceutical Benefits Scheme data were used to estimate the number of HCV diagnosed individuals and treatment uptake. In 2014, an estimated 230 470 individuals (range: 180 490-243 990) were living with HCV, among whom 75% were diagnosed (n = 172 720; range: 156 720-188 770), 20% had ever received treatment (n = 45 000; range: 39 280-50 720), and 11% had been cured (n = 24 750; range: 21 520-27 990). Among individuals with HCV infection, the proportion with hepatic fibrosis stage ≥F3 doubled during the last decade, increasing from 9% (n = 18 580) in 2004 to 19% (n = 44,730) in 2014. Individuals initiating HCV treatment increased from 1100 in 1997 to 3840 in 2007, plateaued until 2010 and decreased to 2790 in 2014. The burden of HCV-related liver disease has increased markedly. Although the proportion diagnosed was high, treatment uptake remained low, with no increase over the last 7 years. Reducing the HCV burden in Australia requires scale-up of interferon-free HCV therapies.

Trends in hepatocellular carcinoma among people with HBV or HCV notification in Australia (2000–2014)

This study evaluates trends in hepatocellular carcinoma (HCC) among people with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in New South Wales (NSW), Australia between 2000 and 2014. Data on HBV and HCV notifications between January 1993 and December 2012 were linked to the NSW Admitted Patients Data Collection database between July 2000 and June 2014 and NSW Registry of Births Deaths and Marriages. The burden, crude and age-standardised incidence of HCC based on first hospitalization were calculated. In NSW between 2000-2014, there were 54,399, 93,099 and 3,809 individuals notified with HBV, HCV and HBV/HCV coinfection respectively. There were 725 (1.3%) with HCC among those with HBV notification as compared to 1,309 with HCC (1.4%) in those with HCV notification. The population-level burden of new HCC cases per year has stabilised in the HBV cohort (53 in 2001 and 44 in 2013), but increased markedly in the HCV cohort (49 in 2001 to 151 in 2013). The age-standardised incidence rates of HCC (per 1,000 person-years) declined from 2.3 (95% confidence interval (CI) 1.4, 3.1) in 2001 to 0.9 (95% CI 0.6, 1.2) in 2012 among those with HBV and remained stable between 2001 (1.4; 95% CI 0.8, 1.9) and 2012 (1.5; 95% CI 1.2, 1.7) in those with HCV. Main factors associated with HCC in those with HBV included later study period (2005-2009; 2010-2014) (hazard ratio (HR)=0.54, 95% CI 0.42, 0.70), male gender (HR=4.50, 95% CI 3.6, 5.6), Asia-Pacific country of birth (HR=3.84, 95% CI 2.58, 5.71) and alcohol dependency (HR=2.84, 95% CI 1.95, 4.13). Main factors associated with HCC in those with HCV included male gender (HR=2.56, 95% CI 2.20, 2.98), rural place of residence (HR=0.73, 95% CI 0.62, 0.86), Asia-Pacific country of birth (HR=2.37, 95% CI 1.99, 2.82) and alcohol dependency (HR=3.90, 95% CI 3.39, 4.49). Individual-level risk of HBV-related HCC has declined, suggesting an impact of more effective antiviral therapy from mid-2000s. In contrast, the interferon-containing HCV treatment era had no impact on individual-level HCV-related HCC risk and has seen escalating population-level HCC burden. Individual-level risk of HBV-related HCC has declined, suggesting an impact of more effective antiviral therapy from mid-2000s. In contrast, the interferon-containing HCV treatment era had no impact on individual-level HCV-related HCC risk and has seen escalating population-level HCC burden.

Time to decompensated cirrhosis and hepatocellular carcinoma after an HBV or HCV notification: A population-based study

Delayed hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis may increase risk of advanced liver disease complications, including decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC). The aim of this study was to characterise "late hepatitis notification" among people with an HBV/HCV notification and advanced liver disease in New South Wales, Australia. HBV/HCV notifications 1995-2012 were linked to cancer registry and hospital admissions. Late hepatitis notification was defined by a notification after, at the time, or within two years before DC/HCC diagnosis. HBV and HCV cohorts comprised 50,958 and 79,727 individuals, respectively. Among people with DC (n=3869), late HBV notification declined from 64% (88/138) during 2001-2002 to 31% (46/149) in 2011-2012 (p<0.001), and late HCV notification declined from 52% (179/341) during 2001-2002 to 22% (134/605) in 2011-2012 (p<0.001). Among people with HCC (n=1656), late HBV notification declined from 68% (59/87) during 2001-2002 to 29% (37/128) in 2011-2012 (p<0.001), and late HCV notification declined from 51% (40/79) during 2001-2002 to 17% (49/288) in 2011-2012 (p<0.001). Despite significant declines in late hepatitis notification since early 2000s, efforts to enhance hepatitis screening, particularly for HBV, are required. Late hepatitis notification as described in this study could be used as a measure of population-level HBV/HCV screening. Delayed hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis may increase the risk of advanced liver disease complications, including decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC). The aim of this study was to characterise "late hepatitis notification" among people with an HBV or HCV notification in New South Wales, Australia. Late hepatitis notifications have significantly declined since early 2000s; however, efforts to enhance hepatitis screening, particularly for HBV, are required. Late hepatitis notification as described in this study could be used as a measure of population-level HBV/HCV screening.

Hepatitis C enhanced surveillance: results from a southeastern Sydney pilot program.

Hepatitis C virus (HCV) is a potentially serious bloodborne virus, which persists in the majority of those infected. Long-term sequelae include liver cirrhosis, liver cancer and premature death. Early identification of newly acquired infection is important for protection of public health. Routine surveillance based on laboratory notification of HCV infection is not sufficient to differentiate between newly acquired and chronic infections. Enhanced surveillance systems have been trialled globally in a number of settings. This pilot program aimed to increase identification of newly acquired HCV cases in southeastern Sydney residents and to ascertain the likely mode of transmission. All HCV notifications in southeastern Sydney residents with specimen dates from 1 July to 31 December 2012 were included in a pilot program. Demographic data, Australian Indigenous identification and previous laboratory results were collected from electronic medical records, where available. Enhanced surveillance forms were sent to referring doctors to seek information about clinical symptoms and previous hepatitis C pathology. Data were collated to assess, according to Australian national case definitions, whether cases were newly acquired or not, or were unable to be determined on the available information. There were 104 notifications of HCV infection during the surveillance period. Forms were sent to 100 requesting doctors, with 72 forms returned. Six newly acquired cases were identified, a rate of 8%, compared with 1-3% classified by routine surveillance. Twenty cases (28%) were not newly acquired and the status of 46 (64%) was unable to be determined. Of the six newly acquired cases, sexual transmission was deemed to be the likely route of exposure for four cases, and injecting drug use for the remaining two. Enhanced surveillance increased the rate of identification of newly acquired infections. However, the process was labour-intensive and the status of most cases was unable to be determined. Since identification of newly acquired cases has an important public health benefit in understanding factors in disease transmission, other approaches should be examined.

Opioid substitution therapy is associated with increased detection of hepatitis C virus infection: A 15-year observational cohort study

BackgroundStrategies are needed to enhance screening of hepatitis C virus (HCV) infection among people who inject drugs to improve engagement in HCV treatment, and stem the growing burden of HCV-related morbidity and mortality. MethodsWe linked routinely collected data on enrolment in opioid substitution therapy (OST) and HCV notifications. We calculated rates of incident HCV notifications, and compared rates in and out of OST. ResultsFollowing adjustment for sex, age and calendar period, rates of incident HCV notification were significantly higher during periods of OST, compared to periods out of OST (adjusted incident rate ratio: 1.91; 95% confidence interval: 1.86, 1.97). This effect was seen across multiple treatment periods. ConclusionsHCV screening in OST settings increases detection of HCV infection among people who inject drugs.

Partner notification among HCV-positive couples who inject drugs

Background: This study examines predictors of partner notification (PN) confirmed by a test counselor among people who inject drugs (PWID) and their sexual partners in Kazakhstan.Methods: We used baseline data from an HIV couple-based intervention study, restricting the sample to couples where both partners knew they were hepatitis C virus (HCV)-positive prior to participation in the study (N = 136 individuals). Cross-tabulation and logistic regression were used to examine predictors of PN, including socio-demographic characteristics, sexual and drug risk behaviors, and access to health services.Results: Of the sample, 68 (50%) participants notified their partners of their HCV status. PN was associated with participation in a needle/syringe exchange program and sexually transmitted infection counseling or education in the past 6 months. In the adjusted model, concurrent HIV infection (OR = 2.4, p < 0.05), having more than one sexual partner (OR = 2.5, p < 0.05), and participation in a needle exchange program (OR = 4.3, p < 0.01) were positively associated with notifying one's partner.Conclusions: The findings from this study emphasize the importance of service access among PWID and point to the need for additional research on HCV counseling and notification strategies as a component of health services for injection drug users.

Lower life expectancy among people with an HCV notification: a population-based linkage study.

Among people with hepatitis C virus (HCV) infection, liver disease-related deaths have risen over the last 20 years. Life expectancy has not been estimated in this population. HCV notifications (mandatory notification of anti-HCV-positive serology since 1991) reported to the New South Wales Health Department from 1992 to 2006 were linked to cause of death data. Abridged life tables were constructed from age-specific mortality rates. Life expectancy from ages 18-70 years for non-drug-related mortality causes was estimated using competing risk methods and compared to the general population of Australia. The cohort comprised 81 644 individuals with an HCV notification, with median follow-up of 7.6 years. Median age at notification was 34 years [interquartile range (IQR) 28-42] and 63% were male. Between 1992 and 2006, 4607 deaths occurred. Median age at liver- and drug-related death among males was 51 (IQR 45-66) and 36 (IQR 31-42) years, respectively, and among females was 63 (IQR 49-74) and 36 (IQR 30-41) years, respectively. In each year of follow-up before 2000, 15-21% of deaths were liver- and 30-39% were drug-related. After 2000, liver-related deaths increased to 20-26% of deaths in each year and drug-related deaths decreased to 13-19%. Excluding drug-related causes of death, life expectancy was lowered by an average of 4.2 (SD ± 1.0) and 5.4 (SD ± 0.7) years for males and females, respectively. Among people with an HCV notification, an increasing proportion of deaths are liver-related. Following removal of drug-related mortality, life expectancy in this population remained considerably lower, compared with the general population.