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Meeting the World Health Organisation 2030 target of treating 80% of people with hepatitis C virus (HCV) in Australia requires accessible testing and treatment services for at-risk populations. Previous clinical trials, including those in Australia, have demonstrated the efficacy of outreach programmes to community pharmacies offering opioid agonist therapy (OAT). This analysis evaluates the potential cost-effectiveness of introducing an outreach programme in community pharmacies. Using a decision analytic model, we estimated the impact of adding a temporary hepatitis C outreach and treatment programme in community pharmacies to the standard treatment pathway available through general practice. We compared the expected number of tests, diagnoses, cures and costs occurring through the addition of this outreach and treatment programme to those expected through general practice alone over a 12-month time horizon. We examined costs from the perspective of the health system and conducted one-way and probabilistic sensitivity analyses to assess uncertainty in model parameters and test key assumptions. In the model adding the outreach programme pathway increased the number of tests from 4178 to 8737, the number of diagnoses from 615 to 1285 and the number of cures from 223 to 777 among people on OAT over a 12-month period. Each additional cure achieved through the addition of the outreach programme was estimated to incur $48,964 (AUD 2023) to the health system, with > 85% of these costs attributable to medication and dispensing expenses. The average cost per cure was estimated to be $49,152 through routine care and $49,018 in the outreach programme. Although outreach models of care incur large upfront costs, they can capture otherwise unreached populations and result in comparable or favourable cost per cure, due to higher levels of engagement and lower rates of loss to follow-up., (© 2024 The Author(s). Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Recent guidance from the World Health Organization strongly recommended hepatitis C virus (HCV) self-testing. We implemented the Vend-C pilot study to explore the effectiveness and feasibility of distributing rapid HCV antibody self-test kits to people who inject drugs via needle/syringe dispensing machines (SDMs). Over a 51-day study period between August and September 2022, we distributed HCV antibody self-test kits via two SDMs. During the study period, 63 self-test kits were dispensed, averaging 1.2 self-test kits per day. Our access methods for evaluation questionnaires failed to attract participants (n = 4). We implemented the Vend-C pilot study in direct response to recent WHO recommendations. While self-test kits were effectively distributed from the two SDMs, our evaluation methodology failed. Consequently, we cannot determine the success of linkage to care. Even so, with HCV treatment numbers dropping in Australia, innovative engagement solutions are needed, and considering the number of self-test kits provided in our pilot, the model could have an important future place in HCV elimination efforts., (© 2023 John Wiley & Sons Ltd.)

Whilst the testing and treatment of people who inject drugs (PWID) in Australia is a priority for local hepatitis C (HCV) elimination efforts, perceived stigma related to injecting drug use (IDU) has been identified as a major barrier for PWID engaging in health services. We used data from the EC Experience cohort study to explore associations between IDU-related perceived stigma and the number of different health services accessed by PWID in Melbourne, Australia. Data from the baseline questionnaire were used. Primary outcome was self-reported experience of stigma due to IDU (never, rarely, sometimes, often, always) in the previous 12 months. An ordinal logistic regression model assessed the association between stigma experienced and the number of different health services used (1-2, 3-4, 5-6, 7-10 different services) adjusted for recent IDU and key socio-demographics. Between September 2018 and February 2020, 281 participants were recruited from four health services. Sixty-nine per cent were male, median age was 42, 83% reported past-month IDU, 34% had never tested/tested >12 months, 8% tested negative <12 months, 43% were HCV-positive but not treated and 16% had been treated. Those accessing 5-6 services had 2.2 times greater odds of experiencing stigma (95% CI 0.86-6.65) compared with those using <5 services and those reporting 7-10 services had 2.43 times greater odds of experiencing stigma (95% CI 0.85-6.92) compared with those accessing <7 services. In conclusion, experiences of stigma may not necessarily be a barrier for PWID to access health services, but high rates of health service use may further expose, exacerbate or exaggerate stigma amongst PWID. Further examination of how stigma may be in/directly impact on hepatitis C treatment uptake is important and place-based interventions aimed at reducing stigma experienced by PWID may be needed., (© 2021 John Wiley & Sons Ltd.)

Financial incentives may reduce opportunity costs associated with people who become lost to follow-up in hepatitis C treatment programs. We estimated the impact that different financial incentive amounts would need to have on retention in care to maintain the same unit cost per (1) RNA-positive person completing testing (defined as awareness of RNA status) and (2) RNA diagnosed person initiating treatment. Costing data were obtained from a 2019 community-based testing campaign focused on engaging people who inject drugs. For different financial incentive amounts, we modelled the corresponding improvements in retention in care that would be needed to maintain the same overall (1) unit cost per testing completion and (2) unit cost per treatment initiation. In the testing campaign, the unit cost per RNA-positive person completing testing was A$3215 and the unit cost per RNA diagnosed person initiating treatment was A$1055. Modelling found that an incentive of A$500 per RNA-positive person completing testing would result in more people completing testing for the same unit cost if the percentage of attendees receiving their test results increased from 63% to 74%. An incentive of A$200 per RNA diagnosed person initiating treatment would result in more people initiating treatment for the same unit cost if the percentage initiating treatment increased from 67% to 83%. Monetary incentives for completing testing and initiating treatment may be an effective way to increase retention in care without increasing the overall unit cost of completing testing/initiating treatment., (© 2021 John Wiley & Sons Ltd.)

Background and Aim: The recent downward revision of the estimated number of people living with chronic hepatitis C in Australia means that the annual number of new hepatitis C infections should also be revised. We aimed to estimate the annual number of new hepatitis C infections among people who inject drugs (PWID) in Australia in 2015, prior to the introduction of direct-acting antiviral (DAA) treatment for hepatitis C, as an updated baseline measure for assessing the impact of DAAs on hepatitis C incidence over the next 10 years., Methods: A systematic review identified articles estimating hepatitis C incidence rates among PWID between 2002 and 2015. Reported incidence rates were adjusted to account for unrepresentative needle and syringe program (NSP) coverage among study participants compared with PWID overall. The total number of PWID in Australia and the hepatitis C RNA prevalence among PWID were taken from published estimates. The annual number of new infections was estimated by multiplying the pooled NSP coverage-adjusted incidence rate by the number of susceptible PWID in 2015., Results: Five studies were included, with unadjusted incidence rates ranging from 7.6 to 12.8 per 100 person-years. The overall pooled incidence rate (after adjusting for NSP coverage) was 9.9 per 100 person-years (95% confidence interval: 8.3-11.8). This led to an estimate of 4126 (range 2499-6405) new hepatitis C infections in 2015., Conclusions: Our updated estimate provides an important baseline for evaluating the impact of hepatitis C elimination efforts and can be used to validate outcomes of future modeling studies., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The impact of hepatitis C cure with direct-acting antivirals (DAAs) on patient-reported outcomes (PROs) in community settings remains unclear. We aimed to assess changes in PROs over time and whether treatment was associated with sustained improved PROs in a cohort of people who inject drugs. This study is a sub-analysis of the Treatment and Prevention Study, a nurse-led trial where people who inject drugs and their injecting partners were recruited in a community setting, in Melbourne, Australia. Three participant groups were characterized: treatment, untreated and non-viremic (hepatitis C RNA negative at screening). PROs included assessment of health-related quality of life using the Short Form-8 (SF-8) Survey and life satisfaction using Personal Wellbeing Index (PWI). PROs were measured at baseline and every 12 weeks until week 84. Generalized estimating equations were used to measure whether treatment was associated with longitudinal PRO change. A total of 215 participants were included in this analysis. PWI scores were significantly higher at week 12 for both treatment group (p = 0.0309) and non-viremic group (p = 0.0437) compared to baseline. However, treatment was not associated with longitudinal change in PRO scores. In conclusion, we found DAA treatment did not significantly improve PRO scores compared to those not receiving treatment and without hepatitis C. The measures used in this study may not be sensitive enough to capture the hepatitis C specific improvements in quality of life that treatment affords or factors other than treatment may be influencing quality of life scores in this cohort., (© 2021 John Wiley & Sons Ltd.)

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., (© 2021 John Wiley & Sons Ltd.)

An increasing number of countries are committing to meet the World Health Organization (WHO) targets to eliminate hepatitis C virus (HCV) as a public health threat by 2030. These include service coverage targets (90% diagnosed and 80% of diagnosed patients treated) and impact targets (80% and 65% reductions in incidence and mortality, respectively, compared to 2015 levels). Currently, a dozen countries are on track to reach 2030 WHO HCV targets. However, while striving for the WHO targets is important, it should be recognized that progress on impact targets is derived from mathematical models projecting decreases in incidence and mortality on a global scale. Despite HCV treatment access in many counties for a number of years, limited empirical data are available to evaluate progress towards elimination. In some countries, substantial incidence and mortality reductions based on reaching the WHO service coverage targets may be unachievable. For example, in countries with ageing hepatitis C-infected populations, even if they have a quality hepatitis C response, high hepatitis C-related morbidity at baseline may not be reversible even with increased HCV treatment uptake and diagnosis. Finally, WHO targets are not necessarily easily or reliably measurable. Measuring relative impact targets requires high-quality data at baseline (ie 2015) and longitudinal data to assess temporal trends. In this commentary, we propose alternative additional measures to track progress on reducing the HCV burden, offer examples where the WHO targets may not be informative or achievable, and potential practical solutions., (© 2020 John Wiley & Sons Ltd.)

Interactions between the host immune system and the viral variants determine persistence of hepatitis C virus (HCV) infection after the acute phase of infection. This study describes the genetic variability of within-host HCV viral variants in acute infection and correlates it with host- and virus-related traits and infection outcome. Next generation sequence data (Illumina, MiSeq platform) of viral genomes from 116 incident acute infections (within 180 days of infection) were analysed to determine all the single nucleotide polymorphism (SNP) frequencies above a threshold of 0.1%. The variability of the SNPs for the full open reading frame of the genome as well as for each protein coding region were compared using mean standardized Shannon entropy (SE) values calculated separately for synonymous and nonsynonymous mutations. The envelope glycoproteins regions (E1 and E2) had the highest SE values (indicating greater variability) followed by the NS5B region. Nonsynonymous mutations rather than synonymous mutations were the main contributors to genomic variability in acute infection. The mean difference of Shannon entropy was also compared between subjects after categorizing the samples according to host and virus-related traits. Host IFNL3 allele CC polymorphism at rs12979860 (vs others) and viral genotype 1a (vs 3a) were associated with higher genomic variability across the viral open reading frame. Time since infection, host gender or continent of origin was not associated with the viral genomic variability. Viral genomic variability did not predict spontaneous clearance., (© 2018 John Wiley & Sons Ltd.)

Hepatitis C virus contributes to substantial and growing mortality and morbidity. Fortunately, the advent of highly effective interferon-free direct-acting antiviral (DAA) medications and new diagnostic tests has the potential to dramatically alter the epidemiologic trajectory of hepatitis C, particularly for "hard-to-reach" populations. Treatment advances and cure will also likely alter the individual experience of living with hepatitis C. However, it is not yet known in what capacity. This paper provides an overview of the population-level impact of DAA treatment, highlighting the need to further our understanding of the impact of treatment on behaviour, health and wellbeing through lived experience and more sensitive patient-reported outcome measures., (© 2018 John Wiley & Sons Ltd.)

Modelling suggests that more frequent screening of people who inject drugs (PWID) and an improved care cascade are required to achieve the WHO hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030. We determined the testing frequencies (2-yearly, annually, 6-monthly and 3-monthly) and retention in care required among PWID to achieve the HCV incidence reduction target through treatment as prevention in low (25%), medium (50%) and high (75%) chronic HCV prevalence settings. Mathematical modelling of HCV transmission among PWID, capturing testing, treatment and other features of the care cascade were employed. In low-prevalence settings, 2-yearly antibody testing of PWID was estimated to reach the elimination target by 2027-2030 depending on retention in care, with annual testing reducing the time by up to 3 years. In medium-prevalence settings, if close to 90% testing coverage were achieved, then annual antibody testing of PWID would be sufficient. If testing coverage were lower (80%), 6-monthly antibody testing with at least 70% retention in care or annual HCV RNA/cAg testing would be required. In high-prevalence settings, even 3-monthly HCV RNA/cAg testing of PWID was unable to achieve the incidence reduction target. Thus, for geographical areas or subpopulations with high prevalence, WHO incidence targets are unlikely to be met without 3-monthly RNA/cAg testing accompanied by other prevention measures. Novel testing strategies, such as rapid point-of-care antibody testing or replacing antibody testing with RNA/cAg tests as a screening tool, can provide additional population-level impacts to compensate for imperfect follow-up or testing coverage., (© 2018 John Wiley & Sons Ltd.)

To increase access to treatment, the Australian government enabled general practitioners (GPs) to prescribe direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV)-in consultation with a specialist if inexperienced in HCV management. This study describes the establishment and outcomes of a remote consultation pathway supporting GPs to treat HCV. Key stakeholders from primary and tertiary healthcare services in the Barwon South Western region developed and implemented an HCV remote consultation pathway. Pharmaceutical Benefits Schedule prescription data were used to evaluate GP DAA prescription 12 months pre-and post- pathway implementation. A retrospective review of patients referred for remote consultation for 12 months post- pathway inception was undertaken to determine the care cascade. HCV treatment initiation by GPs increased after implementation of the remote consultation pathway. In the 12-month study period, 74 GPs referred 169 people for remote consultation; 114 (67%) were approved for GP DAA treatment; 48 (28%) were referred for specialist assessment. In total, 119 (71%) patients commenced DAA; 69 were eligible for SVR12 assessment. Post-treatment HCV RNA data were available for 52 (75%) people; 37 achieved SVR12; 15 achieved SVR ranging from week 5 to 11 post-treatment. No treatment failure was detected. Collaborative development and implementation of a remote consultation pathway has engaged regional GPs in managing HCV. Follow-up post-treatment could be improved; however, no treatment failure has been documented. To eliminate HCV as a public health threat, it is vital that specialists support GPs to prescribe DAA., (© 2018 John Wiley & Sons Ltd.)

A nationwide programme for the treatment of all patients infected with hepatitis C virus (HCV) was launched in Iceland in January 2016. By providing universal access to direct-acting antiviral agents to the entire patient population, the two key aims of the project were to (i) offer a cure to patients and thus reduce the long-term sequelae of chronic hepatitis C, and (ii) to reduce domestic incidence of HCV in the population by 80% prior to the WHO goal of HCV elimination by the year 2030. An important part of the programme is that vast majority of cases will be treated within 36 months from the launch of the project, during 2016-2018. Emphasis is placed on early case finding and treatment of patients at high risk for transmitting HCV, that is people who inject drugs (PWID), as well as patients with advanced liver disease. In addition to treatment scale-up, the project also entails intensification of harm reduction efforts, improved access to diagnostic tests, as well as educational campaigns to curtail spread, facilitate early detection and improve linkage to care. With these efforts, Iceland is anticipated to achieve the WHO hepatitis C elimination goals well before 2030. This article describes the background and organization of this project. Clinical trial number: NCT02647879., (© 2018 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Inadequate response to injecting drug use (IDU) is a significant problem the world over. Low levels of funding, political inaction, poor levels of health service coverage, high prevalence and incidence of IDU-related blood-borne viruses (BBVs) and ongoing stigmatization/marginalization affect people who inject drugs (PWID) regardless of the income status of the country they reside in. These barriers and system failings are, however, exacerbated in low and middle-income countries (LMICs), meaning that the potential consequences of inaction are more pressing. In this narrative review, we describe the levels of IDU and IDU-specific BBV prevalence in LMICs; levels of harm reduction implementation; the consequences of late or insufficient response, the shortcomings of data collection and dissemination; and the barriers to effective LMIC harm reduction implementation. We also exemplify cases where IDU-related harms and BBV epidemics have been successfully curtailed in LMICs, showing that effective response, despite the barriers, is possible. In conclusion, we suggest four key priorities on the basis of the review: confirming the presence or absence of IDU in LMICs, improving the collection and dissemination of national IDU-specific data, increasing the level of harm reduction programme implementation in LMICs, and increasing both national and international advocacy for PWID and attendant public health interventions., (© 2017 John Wiley & Sons Ltd.)

Combining phylogenetic and network methodologies has the potential to better inform targeted interventions to prevent and treat infectious diseases. This study reconstructed a molecular transmission network for people with recent hepatitis C virus (HCV) infection and modelled the impact of targeting directly acting antiviral (DAA) treatment for HCV in the network. Participants were selected from three Australian studies of recent HCV from 2004 to 2014. HCV sequence data (Core-E2) from participants at the time of recent HCV detection were analysed to infer a network by connecting pairs of sequences whose divergence was ≤.03 substitutions/site. Logistic regression was used to identify factors associated with connectivity. Impact of targeting HCV DAAs at both HIV co-infected and random nodes was simulated (1 million replicates). Among 236 participants, 21% (n=49) were connected in the network. HCV/HIV co-infected participants (47%) were more likely to be connected compared to HCV mono-infected participants (16%) (OR 4.56; 95% CI; 2.13-9.74). Simulations targeting DAA HCV treatment to HCV/HIV co-infected individuals prevented 2.5 times more onward infections than providing DAAs to randomly selected individuals. Results demonstrate that genetic distance-based network analyses can be used to identify characteristics associated with HCV transmission, informing targeted prevention and treatment strategies., (© 2016 John Wiley & Sons Ltd.)

One challenge to HCV elimination through therapeutic intervention is reinfection. The aim of this analysis was to calculate the incidence of HCV reinfection among both HIV-positive and HIV-negative individuals treated for recent HCV infection (estimated infection duration <18 months). Individuals with recent HCV infection who achieved an end-of-treatment response in four open-label studies between 2004 and 2015 in Australia and New Zealand were assessed for HCV reinfection, confirmed by sequencing of the Core-E2 and/or NS5B regions. Reinfection incidence was calculated using person-time of observation. Exact Poisson regression analysis was used to assess factors associated with HCV reinfection. The cohort at risk for reinfection (n=120; 83% male; median age 36 years) was composed of HIV-positive men-who-have-sex-with-men (53%) and people who inject drugs (current 49%, ever 69%). Total follow-up time at risk was 135 person-years (median 1.08 years, range 0.17, 2.53). Ten cases of HCV reinfection were identified, for an incidence of 7.4 per 100 py (95% CI 4.0, 13.8). Reinfection incidence was significantly higher among participants who reported injection drug use at end of or post-treatment, irrespective of HIV status (15.5 per 100 py, 95% CI 7.8, 31.1). In adjusted analysis, factors associated with reinfection were older age (aIRR 5.3, 95% CI 1.15, 51.5, P=.042) and injection drug use at end of or post-treatment (aIRR 7.9, 95% CI 1.6, 77.2, P=.008). High reinfection incidence following treatment for recent HCV infection in individuals with ongoing risk behaviour emphasizes the need for post-treatment surveillance, harm reduction strategies and education in at-risk populations., (© 2016 John Wiley & Sons Ltd.)

Cross-continental phylogenetic analysis is important to understand subtle molecular differences of currently circulating hepatitis C virus (HCV) subtypes. Existence of such differences can be crucial in pursuing a universal hepatitis C vaccine. We characterized molecular epidemiology of early HCV infections identified across nine cohorts [North America (n=4), Australia (n=4) and Europe (n=1)] in the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC 3 ). One hundred and ninety-two full-length HCV genomes were amplified from plasma of incident infections and subjected to next generation sequencing to establish the largest cross-continental, full-length acute HCV genomic data set available to date. Genomes from the most common subtypes (1a: n=94, 2b: n=15 and 3a: n=68) were used in phylogenetic analysis. Using full genome trees, 78 sequences (44%) were found to lie within 29 phylogenetic clusters/pairs defined on the basis of molecular similarity of consensus sequences. Of these, 26 each had exclusively Australian or North American sequences indicating a strong geographical bias for molecular similarity. On further analysis of behavioural and demographic associations, binary logistic regression analysis showed that older age and non-Caucasian ethnicity were significantly associated with clustering. HCV probably evolves in micro-epidemics within geographically isolated communities., (© 2016 John Wiley & Sons Ltd.)

Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naïve patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up., (© 2016 John Wiley & Sons Ltd.)

Background: Hepatitis C (HCV), hepatitis B (HBV), alcohol-related liver disease (ALD), and non-alcohol-related fatty liver disease (NAFLD) are leading indications for adult liver transplantation in Australia and New Zealand. However, these diseases are potentially preventable through effective primary and/or secondary prevention strategies. This study evaluates the relative contribution of potentially preventable liver diseases to liver transplant numbers in Australia and New Zealand over time., Methods: Prospectively recorded clinical, demographic, and outcome data were collected from the Australian and New Zealand Liver Transplant Registry for all primary adult liver transplants performed in Australia and New Zealand from 1 January 1985 until 31 December 2012. Potentially preventable liver disease was defined as HBV, HCV, NAFLD, ALD, and HCC. The etiology of liver disease leading to liver transplantation and the proportion of preventable liver disease-related liver transplantation was compared between Era 1 (1985-1993), Era 2 (1994-2003), and Era 3 (2004-2012)., Results: Overall, 1252 of 3266 adult primary liver transplants (38.3%) were performed for potentially preventable liver disease. There was a significant increase in the proportion of liver transplants because of preventable liver disease from 21.2% (93 of 439) in Era 1, to 49.8% (623 of 1252) in Era 2 and 63.5% (1000 of 1575) in Era 3 (P < 0.0001). Over time, there was a significant increase in HCV (P < 0.0001), ALD (P = 0.002), and NAFLD (P < 0.0001) as a primary indication for adult liver transplant, whereas HBV has significantly decreased from Era 1 to Era 3 as an indication for transplant (P < 0.0001). The number of transplants performed for HCC also increased across Eras (P < 0.0001), with 84% due to underlying potentially preventable liver disease., Conclusion: Since 2004, the majority of primary adult liver transplants within Australia and New Zealand have been because of potentially preventable liver diseases and the prevalence of these diseases has increased over time. This finding represents an opportunity for clinicians to make a significant impact on the overall burden of advanced liver disease in Australia and New Zealand by improving primary and secondary prevention measures., (© 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co-infected. SVR among those with HCV mono-infection was 64% by intention to treat; SVR was 68% among HCV/HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85-0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13-4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03-4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31-6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision-making., (© 2015 John Wiley & Sons Ltd.)

Improved understanding of natural history of hepatitis C virus (HCV) RNA levels in chronic infection provides enhanced insights into immunopathogenesis of HCV and has implications for the clinical management of chronic HCV infection. This study assessed factors associated with HCV RNA levels during early chronic infection in a population with well-defined early chronic HCV infection. Data were from an international collaboration of nine prospective cohorts studying acute HCV infection (InC(3) study). Individuals with persistent HCV and detectable HCV RNA during early chronic infection (one year [±4 months] postinfection) were included. Distribution of HCV RNA levels during early chronic infection was compared by selected host and virological factors. A total of 308 individuals were included. Median HCV RNA levels were significantly higher among males (vs females; 5.15 vs 4.74 log IU/mL; P < 0.01) and among individuals with HIV co-infection (vs no HIV; 5.89 vs 4.86; P = 0.02). In adjusted logistic regression, male sex (vs female, adjusted odds ratio [AOR]: 1.93; 95%CI: 1.01, 3.69), interferon lambda 4 (IFNL4) rs12979860 CC genotype (vs TT/CT; AOR: 2.48; 95%CI: 1.42, 4.35), HIV co-infection (vs no HIV; AOR: 3.27; 95%CI: 1.35, 7.93) and HCV genotype G2 (vs G3; AOR: 5.40; 95%CI: 1.63, 17.84) were independently associated with high HCV RNA levels (>5.6 log IU/mL = 400 000 IU/mL). In conclusion, this study demonstrated that IFNL4 rs12979860 CC genotype, male sex, HIV co-infection and HCV genotype G2 are associated with high HCV RNA levels in early chronic infection. These factors exert their role as early as one year following infection., (© 2015 John Wiley & Sons Ltd.)

There are over 500-750 000 deaths per year because of hepatitis B virus (HBV)-related cirrhosis and liver cancer worldwide and the World Health Organization Western Pacific Region has some of the highest endemic levels of HBV in the world, particularly within China, South East Asia and Pacific Island Countries and Territories (PICT). The PICT have unique ethnic diversity and a very high prevalence of smoking and metabolic syndrome, both important risk factors for liver fibrosis and liver cancer. However, in contrast to many Asian countries, there is little published data on HBV prevalence and related liver disease burden in PICT. In this review, the available published literature and World Health Organization data for HBV prevalence and related liver disease and liver cancer burden in PICT is outlined, and unmet needs for improving HBV prevention and control in the region are highlighted., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background and Aim: T-cell responses against hepatitis C are believed to be critical in achieving both natural and treatment-induced clearance. However, rapid clearance of antigen with early treatment of primary infection may result in reduced or poorly sustained cellular immunity. This study longitudinally examined Th1 and Th2 hepatitis C virus (HCV)-specific cytokine production and T-cell effector function from subjects enrolled in the Australian Trial in Acute Hepatitis C comparing three groups: treatment-induced clearance (sustained virological response [SVR]), treatment non-response, and untreated spontaneous clearance., Methods: HCV-specific T-cell responses were characterized by HCV peptide ELISpot, in vitro cytokine production, and T-cell flow cytometry assays., Results: Treated subjects with a sustained virological response (SVR) displayed a better maintenance of HCV-specific Th1 responses compared to treatment non-responders (higher interferon [IFN]-γ and interleukin (IL)-2 magnitude at week 24, broader IFN-γ responses at weeks 24 and 48, P < 0.05) and significantly increased IFN-γ responses between screening and week 48 (magnitude P = 0.026, breadth P = 0.009). Treatment-induced viral clearance was also associated with a trend toward decreased IL-10 responses (screening to week 48, P = 0.070), higher expression of CD45RO (P = 0.042) and CD38 (P = 0.088) on CD4+ T cells, and higher IFN-γR expression (CD56+ IFN-γR+ P = 0.033) compared to treatment non-responders. Untreated subjects with viral clearance also displayed high magnitude and broad HCV-specific IFN-γ and IL-2 responses early in infection; however, IFN-γ responses were not as well maintained compared to treated subjects with a SVR (week 48 magnitude, breadth P = 0.064)., Conclusion: Treatment-induced viral clearance of recent HCV infection is associated with maintenance of HCV-specific Th1 responses., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Accurate incidence estimates are essential for quantifying hepatitis C virus (HCV) epidemic dynamics and monitoring the effectiveness of public health programmes, as well as for predicting future burden of disease and planning patient care. In Egypt, the country with the largest HCV epidemic worldwide, two modelling studies have estimated age-specific incidence rates that, applied to the age pyramid, would correspond to more than 500 000 Egyptians getting infected annually. This is in contrast to figures of the Egyptian Ministry of Health and Population that estimates new infections to be approximately 100 000 per year. We performed new analyses of nationwide data to examine the modelling assumptions that led to these estimates. Thus, we found that the key assumption of these models of a stationary epidemic is invalid. We propose an alternate approach to estimating incidence based on analysing cohort data; we find that the number of annual new infections is <150 000., (© 2012 Blackwell Publishing Ltd.)

Background and Aim: Pegylated interferon (PEG-IFN) treatment for hepatitis C virus (HCV) infection has neuropsychiatric side effects. Data on the effect of HCV treatment on mental health among injecting drug users (IDUs) are limited. We assessed mental health during treatment of recently acquired HCV, within a predominantly IDU population., Methods: Participants with HCV received PEG-IFN-α-2a (180 µg/week) for 24 weeks; HCV/HIV received PEG-IFN with ribavirin. Depression was assessed using the Mini-International Neuropsychiatric Interview (MINI). Logistic regression was used to identify factors associated with depression at enrolment and during treatment. Also, the effect of depression prior to and during treatment on sustained virological response (SVR) was assessed., Results: Of 163 participants, 111 received treatment (HCV, n = 74; HCV/HIV, n = 37), with 76% ever reporting IDU. At enrolment, 16% had depression (n = 25). In adjusted analysis, depression at enrolment occurred less often in participants full-/part-time employed (adjusted odds ratio [AOR] 0.23; 95% confidence interval [CI]: 0.06, 0.82, P = 0.023) and more often in recent IDUs (AOR 3.04; 95% CI: 1.19, 7.72, P = 0.019). During treatment, 35% (n = 31) developed new-onset depression. In adjusted analysis, poorer social functioning (higher score) was associated with new-onset depression (score ≤ 9 vs score ≥ 17; OR 5.69; 95% CI: 1.61, 20.14, P = 0.007). SVR was similar among participants with and without depression at enrolment (60% vs 61%, P = 0.951) and in those with and without new-onset depression (74% vs 63%, P = 0.293)., Conclusions: Although depression at enrolment and during treatment was common among participants with recent HCV, neither influenced SVR. Participants with poor social functioning may be most at risk of developing depression during HCV therapy., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

The critical events in clearance or persistence of hepatitis C virus (HCV) infection are unknown but likely to be determined early in acute infection. Type 1 and type 2 cytokine production was assessed by HCV peptide ELISpot and multiplex in vitro cytokine production assays in longitudinally collected samples from 20 untreated participants enrolled in the Australian Trial in Acute Hepatitis C (ATAHC); a prospective cohort of acute HCV infection (77% injecting drug users, IDU). Significantly higher interleukin-10 (IL-10) production (P = 0.048), in the relative absence of interferon-gamma (IFN-γ) and IL-2 production, was present early in HCV infection in those who progressed to chronic infection. In contrast, viral clearance was associated with a greater magnitude and broader specificity of IFN-γ (magnitude P < 0.001, breadth P = 0.004) and IL-2 responses, in the relative absence of IL-10. Early IL-10 production was correlated with higher HCV RNA level at baseline (P = 0.046) and week 12 (P = 0.018), while IFN-γ and IL-2 production was inversely correlated with HCV RNA level at baseline (IFN-γ P = 0.020, IL-2 P = 0.050) and week 48 (IFN-γ P = 0.045, IL-2 P = 0.026). Intracellular staining (ICS) indicated the HCV-specific IFN-γ response was primarily from CD8(+) T cells and NK cells, whereas IL-10 production was predominantly from monocytes, with a subset of IL-10 producing CD8(+) T cells present only in those who progressed to chronic infection. IL-10, an immunoregulatory cytokine, appears to play a key role in progression to chronic HCV infection., (© 2010 Blackwell Publishing Ltd.)

Background and Aim: Regular monitoring of hepatitis C (HCV)-related surveillance data is essential to inform and evaluate strategies to reduce the expanding HCV burden. The aim of this study was to examine trends in the epidemiology and treatment of HCV in Australia., Methods: We reviewed data about HCV notifications, treatment of HCV infection through the Highly Specialised Drugs (s100) Program, and liver transplants (Australia and New Zealand Liver Transplant Registry) for the period 1997-2006., Results: HCV case notification rates declined by almost 50% between 1999 and 2006, with the greatest reductions between 2001 and 2002 and amongst young adults. For newly acquired HCV cases, 89% were Australian-born and 90% reported injecting drug use as a risk factor for infection. Overall, 30% of liver transplant recipients had HCV-related cirrhosis, but the number and proportion of HCV diagnoses increased between 1997 and 2006. HCV treatment also increased over the review period. However, only 1.4% of the 202,400 people estimated to be living with chronic HCV at the end of 2006 received treatment that year., Conclusion: The decline in HCV notifications is consistent with a decline in HCV incidence in Australia. However, the burden of advanced HCV disease continues to expand. To reduce this burden, treatment uptake needs to increase. Consistent and sensitive surveillance mechanisms are required to detect newly acquired cases together with an expansion of surveillance for chronic HCV infections.

Background and Aim: Hepatitis C treatment uptake in Australia is low. We describe the rate of acute hepatitis C treatment in the Australian state of Victoria by linking the centralized passive notifications system for hepatitis C with the Australian Trial in Acute Hepatitis C (ATAHC), a nationwide clinical trial aimed at providing people with newly acquired hepatitis C with 24 weeks' pegylated interferon monotherapy., Methods: Mandatory notifications of clinical or laboratory evidence of hepatitis C were further investigated for evidence of newly acquired infection. Followed-up individuals were then screened for eligibility for the ATAHC study (which included documented hepatitis C antibody positivity within the previous 6 months) and offered acute hepatitis C treatment if this was the case. We examined the first 18 months of the recruitment., Results: A total of 4591 hepatitis C cases were notified with 414 (9%) of these flagged as being potentially newly acquired. Through follow-up of doctors and patients, 160 of these were confirmed as newly acquired; 87 of these 160 (54%) were potentially eligible for ATAHC and were referred to ATAHC researchers. Fourteen (16%) were successfully enrolled in ATAHC. Eight individuals commenced acute hepatitis C treatment during this period., Conclusion: The use of hepatitis C surveillance system has been successful in identifying cases of newly acquired hepatitis C which are often difficult to identify in a clinical setting. In addition, marginalized patients who may otherwise never have been referred to a clinic are able to access hepatitis C treatment and specialist services. Despite this, only eight out of 87 eligible individuals (9%) began acute hepatitis C treatment.

Background and Aims: The objective of this study was to describe the prevalence of pathogenic microorganisms in asymptomatic individuals in a community study in Melbourne, Australia., Methods: The study population was a subset of 2803 individuals participating in the Water Quality Study; a community based randomized trial. Faecal specimens (1091) were collected over a 3-month period from asymptomatic individuals. Specimens were tested for a range of bacteria including Salmonella, Shigella and Campylobacter species. Rotavirus and adenovirus were detected using a Rota-Adeno latex kit, and protozoa were detected using a permanent stain (modified iron-haemotoxylin)., Results: Twenty-eight known pathogens were identified from the 1091 faecal specimens, a total carriage rate of 2.6%. Giardia species were present in 18 specimens (1.6%), Salmonella in four (0.4%), Campylobacter in one (0.1%), Cryptosporidium in four (0.4%) and adenovirus in one (0.1%). Blastocystis hominis was found in 65 specimens. The median age of those without a pathogen was 12.5 years compared with 6.6 years for those with a pathogen (P=0.02)., Conclusions: Except for Giardia, pathogens were rarely found in asymptomatic individuals in the community. The prevalence of pathogens was higher in children than adults.