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Robaeys G.,Ziekenhuis Oost Limburg | Robaeys G.,Hasselt University | Grebely J.,University of New South Wales | Mauss S.,Center for and Hepatogastroenterology | And 19 more authors.
Clinical Infectious Diseases | Year: 2013

In the developed world, the majority of new and existing hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). The burden of HCV-related liver disease in this group is increasing, but treatment uptake among PWID remains low. Among PWID, there are a number of barriers to care that should be considered and systematically addressed, but these barriers should not exclude PWID from HCV treatment. Furthermore, it has been clearly demonstrated that HCV treatment is safe and effective across a broad range of multidisciplinary healthcare settings. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment and treatment in this group are urgently needed. These recommendations demonstrate that treatment among PWID is feasible and provides a framework for HCV assessment, management, and treatment. Further research is needed to evaluate strategies to enhance assessment, adherence, and SVR among PWID, particularly as new treatments for HCV infection become available. © 2013 The Author 2013.

Lamoury F.M.J.,University of New South Wales | Jacka B.,University of New South Wales | Bartlett S.,University of New South Wales | Bull R.A.,University of New South Wales | And 9 more authors.
PLoS ONE | Year: 2015

Sequencing is important for understanding the molecular epidemiology and viral evolution of hepatitis C virus (HCV) infection. To date, there is little standardisation among sequencing protocols, in-part due to the high genetic diversity that is observed within HCV. This study aimed to develop a novel, practical sequencing protocol that covered both conserved and variable regions of the viral genome and assess the influence of each subregion, sequence concatenation and unrelated reference sequences on phylogenetic clustering analysis. The Core to the hypervariable region 1 (HVR1) of envelope-2 (E2) and non-structural- 5B (NS5B) regions of the HCV genome were amplified and sequenced from participants from the Australian Trial in Acute Hepatitis C (ATAHC), a prospective study of the natural history and treatment of recent HCV infection. Phylogenetic trees were constructed using a general time-reversible substitution model and sensitivity analyses were completed for every subregion. Pairwise distance, genetic distance and bootstrap support were computed to assess the impact of HCV region on clustering results as measured by the identification and percentage of participants falling within all clusters, cluster size, average patristic distance, and bootstrap value. The Robinson-Foulds metrics was also used to compare phylogenetic trees among the different HCV regions. Our results demonstrated that the genomic region of HCV analysed influenced phylogenetic tree topology and clustering results. The HCV Core region alone was not suitable for clustering analysis; NS5B concatenation, the inclusion of reference sequences and removal of HVR1 all influenced clustering outcome. The Core-E2 region, which represented the highest genetic diversity and longest sequence length in this study, provides an ideal method for clustering analysis to address a range of molecular epidemiological questions. Copyright: © 2015 Lamoury et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Grebely J.,University of New South Wales | Feld J.J.,University of Toronto | Applegate T.,University of New South Wales | Matthews G.V.,University of New South Wales | And 13 more authors.
Hepatology | Year: 2013

Systemic levels of interferon-gamma-inducible protein-10 (IP-10) are predictive of treatment-induced clearance in chronic hepatitis C virus (HCV). In the present study, factors associated with plasma IP-10 levels at the time of acute HCV detection and the association between IP-10 levels and spontaneous clearance were assessed in three cohorts of acute HCV infection. Among 299 individuals, 245 (181 male, 47 human immunodeficiency virus-positive [HIV+]) were HCV RNA+ at acute HCV detection. In adjusted analysis, factors independently associated with IP-10 levels ≥150 pg/mL (median level) included HCV RNA levels >6 log IU/mL, HIV coinfection and non-Aboriginal ethnicity. Among 245 HCV RNA+ at acute HCV detection, 214 were untreated (n = 137) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n = 77). Spontaneous clearance occurred in 14% (29 of 214). Individuals without spontaneous clearance had significantly higher mean plasma IP-10 levels at the time of acute HCV detection than those with clearance (248 ± 32 versus 142 ± 22 pg/mL, P = 0.008). The proportion of individuals with spontaneous clearance was 0% (0 of 22, P = 0.048) and 16% (27 of 165) and in those with and without plasma IP-10 levels ≥380 pg/mL. In adjusted analyses, favorable IL28B genotype was associated with spontaneous clearance, while higher HCV RNA level was independently associated with lower odds of spontaneous clearance. Conclusion: High IP-10 levels at acute HCV detection were associated with failure to spontaneously clear HCV. Patients with acute HCV and high baseline IP-10 levels, particularly >380 pg/mL, should be considered for early therapeutic intervention, and those with low levels should defer therapy for potential spontaneous clearance. © 2013 American Association for the Study of Liver Diseases.

Thein H.-H.,University of New South Wales | Thein H.-H.,University of Toronto | Thein H.-H.,Ontario Cancer Institute | Walter S.R.,University of New South Wales | And 6 more authors.
Hepatology Research | Year: 2012

Aim: Little is known about the patterns of care and the impact of hepatocellular carcinoma (HCC) treatment on health outcomes at a population level. We conducted a population-based cohort study to examine HCC survival trends among people diagnosed with hepatitis B (HBV) or hepatitis C virus (HCV) infection, to determine predictors of receiving potentially curative therapy for HCC, and to examine the impact of HCC treatment on survival in New South Wales, Australia. Methods: The Kaplan-Meier method was used to estimate survival, logistic regression to determine predictors of potentially curative therapy and Cox proportional hazards models to determine the impact of HCC treatment on survival. Years of potential life lost (YPLL) were calculated. Results: During the period 1993-2007, 1081 cases of HCC were diagnosed. Median survival increased from 10.4months during 1993-1997 to 18.4months during 1998-2002, with no further improvement thereafter. Younger age at diagnosis (<65years), being Asian-born and having multiple comorbid conditions increased the odds of receiving curative therapy. The effect of HCC treatment on the risk of mortality was similar between the HBV- and HCV-related HCC groups. Tumor-specific therapies had adjusted hazard ratios ranging 0.06-0.25 and palliative/supportive therapy alone had adjusted hazard ratios ranging 0.76-1.08. The average YPLL per person was 23.3. Conclusion: The burden of viral hepatitis-related HCC is substantial. Despite treatment advances in recent years, there has been no significant improvement in HCC survival. Efforts to improve HCC screening and early diagnosis are required to deliver curative treatment which clearly has a survival advantage. © 2012 The Japan Society of Hepatology.

Thein H.-H.,University of New South Wales | Thein H.-H.,University of Toronto | Walter S.R.,University of New South Wales | Gidding H.F.,University of New South Wales | And 5 more authors.
Journal of Viral Hepatitis | Year: 2011

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major risk factors for hepatocellular carcinoma (HCC). We examined trends in the incidence of HCC among a population-based cohort of people infected with HBV or HCV. HBV and HCV cases notified to the New South Wales Health Department between 1992 and 2007 were linked to the Central Cancer Registry, Registry of Births, Deaths and Marriages, and National HIV/AIDS Registries. Crude HCC incidence rates were estimated using person-time methodology. Age-standardized incidence rates were calculated using the 2001 Australian population. Trends in incidence were examined using join point regression models. Between 1992 and 2007, 1201 people had a linked HCC record: 556 of those with HBV; 592 with HCV; 45 with HBV/HCV co-infection; and 8 with HIV co-infection. The overall age-standardized HCC incidence rates declined non-significantly from 148.0 (95% confidence intervals (CI) 63.7, 287.4) per 100 000 population in 1995 to 101.2 (95% CI 67.3, 144.6) in 2007 among the HBV monoinfected group and significantly from 151.8 (95% CI 62.4, 299.8) per 100 000 population to 75.3 (95% CI 50.8, 105.5) among the HCV monoinfected group. However, incidence rates in the HCV monoinfected group progressively increased from the period 1992-1997 to 2004-2007 when adjusted for age, sex, and birth cohort, and the total number of cases per annum continued to increase. Despite declines in the age-adjusted incidence rates of HCC over time, the absolute number of cases increased likely due to the ageing cohort and an increasing prevalence of both hepatitis B and C in Australia. © 2011 Blackwell Publishing Ltd.

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