Chronic hepatitis C is associated with peripheral rather than hepatic insulin resistance.

Background & Aims: Chronic hepatitis C (CHC) is associated with insulin resistance (IR), liver steatosis (genotype 3), and increased diabetes risk. The site and mechanisms of IR are unclear.

Methods: We compared cross-sectionally 29 nonobese, normoglycemic males with CHC (genotypes 1 and 3) to 15 adiposity and age-matched controls using a 2-step hyperinsulinemic-euglycemic clamp with [6,6-(2)H(2)] glucose to assess insulin sensitivity in liver and peripheral tissues and (1)H-magnetic resonance spectroscopy to evaluate liver and intramyocellular lipid.

Poor criterion validity of self-reported hepatitis B infection and vaccination status among injecting drug users: a review.

Issues: Limited resources may dictate the use of self-reported hepatitis B virus (HBV) status to determine the need for testing and/or vaccination in resource-poor settings, as well as in research and surveillance.

Approach: A synthesis of the literature on the criterion validity of self-reported HBV infection and vaccination history among injecting drug users (IDU) in order to determine the utility or otherwise of self-reports in this area.

Key Findings: The degree of agreement between self-reported and serological HBV status is consistently poor among IDU.

Factors associated with uptake of treatment for recent hepatitis C virus infection in a predominantly injecting drug user cohort: The ATAHC Study.

Despite that the majority of hepatitis C virus (HCV) infection occurs among injection drug users (IDUs), little is known about HCV treatment uptake in this group, particularly during recent infection. We evaluated uptake of treatment for recent HCV infection, including associated factors, within a population predominantly made up of IDUs. The Australian Trial in Acute Hepatitis C was a study of the natural history and treatment of recent HCV infection.

In vitro and in vivo evaluation of the inhibition potential of risperidone toward clozapine biotransformation.

Aims: To study the impact of risperidone (RISP) on clozapine (CLZ) biotransformation in vitro in microsomal fractions containing varying expression of CYP oxidases and in vivo in patients.

Methods: Human liver microsomes (n= 11) were assessed for expression of CYPs 1A2, 2D6 and 3A4, because these enzymes mediate RISP and CLZ oxidation. Inhibition of CLZ oxidation by RISP was assessed.

The epidemiology of hepatitis C in Australia: notifications, treatment uptake and liver transplantations, 1997-2006.

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.

Effective treatment of injecting drug users with recently acquired hepatitis C virus infection.

Background & Aims: Patients with acute hepatitis C virus (HCV) infection who receive treatment achieve high rates of sustained virologic response (SVR), but few studies have examined outcomes among injecting drug users (IDUs). We evaluated the efficacy of treatment of recent HCV infection in IDUs with acute and early chronic HCV.

Methods: We analyzed data from the Australian Trial in Acute Hepatitis C-a prospective study of the natural history and treatment outcomes of patients with recent HCV infection.

IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.

Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals.

Presence of the APOE epsilon4 allele modifies the relationship between type 2 diabetes and cognitive performance: the Maine-Syracuse Study.

Aims/hypothesis: The primary aim of this study was to determine whether the presence of one or more APOE epsilon4 alleles modifies the association between diabetes (defined by glucose > or =7 mmol/l or treatment) and cognitive function.

Methods: Diabetic status and APOE genotype interactions were assessed cross-sectionally for 826 community-dwelling, stroke-free, non-demented individuals (526 non-diabetic non-APOE epsilon4 carriers, 174 non-diabetic APOE epsilon4 carriers, 87 diabetic APOE epsilon4 non-carriers, 39 diabetic APOE epsilon4 carriers) ranging in age from 50 to 98 years. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the similarities subtest from the Wechsler Adult Intelligence Scale, and four composite scores derived from 17 additional neuropsychological tests.

Impact of high-dose peginterferon alfa-2A on virological response rates in patients with hepatitis C genotype 1: a randomized controlled trial.

Unlabelled: This study tested the hypothesis that high-dose peginterferon alfa-2a (PEG-IFNalpha-2a) for the first 12 weeks would increase early and sustained virological response (SVR) rates in patients with chronic hepatitis C genotype 1. Eight hundred ninety-six patients were randomized 1:1 to 360 microg (n = 448) or 180 microg (n = 448) PEG-IFNalpha-2a weekly plus ribavirin at 1000-1200 mg/day for 12 weeks, followed by 36 weeks of 180 microg PEG-IFNalpha-2a weekly plus ribavirin at 1000-1200 mg/day with 871 patients evaluable for the intention-to-treat analysis. Virological responses were assessed by TaqMan (limit of detection 15 IU/mL) at week 4, 8, 12, 24, 48 (end of therapy), and 24 weeks following therapy (SVR).

First report and detailed characterization of B. pertussis isolates not expressing Pertussis Toxin or Pertactin.

Bordetella pertussis isolates not expressing Pertussis Toxin (PT) or Pertactin (PRN) have been collected, for the first time in 2007, in France, a highly vaccinated country with acellular vaccines. Non-expression was due to deletion of the entire ptx locus, to IS481 insertion in the prn gene or deletion of a part of this gene. Genome sequencing does not indicate any regions of differences when compared to other circulating isolates.

Combination HBV therapy is linked to greater HBV DNA suppression in a cohort of lamivudine-experienced HIV/HBV coinfected individuals.

Objectives: To determine if highly active antiretroviral therapy (HAART) with combination anti-hepatitis B virus (HBV) therapy compared to HAART with HBV monotherapy leads to greater HBV DNA suppression in an HIV/HBV coinfected cohort.

Design: A cross-sectional analysis of 122 HIV/HBV coinfected patients from Australia and the United States.

Methods: Univariate analysis and ordinal logistic regression were used to determine factors associated with an HBV DNA less than 100 IU/ml.

Impaired quality of the hepatitis B virus (HBV)-specific T-cell response in human immunodeficiency virus type 1-HBV coinfection.

Hepatitis B virus (HBV)-specific T cells play a key role both in the control of HBV replication and in the pathogenesis of liver disease. Human immunodeficiency virus type 1 (HIV-1) coinfection and the presence or absence of HBV e (precore) antigen (HBeAg) significantly alter the natural history of chronic HBV infection. We examined the HBV-specific T-cell responses in treatment-naïve HBeAg-positive and HBeAg-negative HIV-1-HBV-coinfected (n = 24) and HBV-monoinfected (n = 39) Asian patients.

Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men.

Background & Aims: Since 2000, there has been a marked rise in acute hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). We conducted an international phylogenetic study to investigate the existence of an HCV transmission network among MSM.

Methods: HIV-positive MSM diagnosed with recent HCV (n = 226) in England (107), The Netherlands (58), France (12), Germany (25), and Australia (24) between 2000 and 2006 were enrolled into a molecular phylogenetic study.

Clinical trial literacy among injecting drug users in Sydney, Australia: A pilot study.

This pilot study examined knowledge, understanding and perceived acceptability of key methodological concepts in clinical trials among injecting drug users (IDUs) in Sydney, Australia. Participants were clinical trial-experienced (n = 17) and trial-naïve (n = 99) IDUs recruited from community needle and syringe programs, and through institutions involved in clinical trials with IDU participants. Cross-sectional data were collected via a study-specific interviewer-administered survey.

Antiviral therapy for hepatitis B-related liver cancer prevention is more cost-effective than cancer screening.

Background/aims: In Australia, Asian-born populations are 6-12 times more likely to develop hepatocellular cancer (HCC) than Australian-born individuals. We therefore, modelled the consequences of different management strategies for chronic hepatitis B (CHB) in Asian-born adults aged > or = 35 years.

Methods: A Markov model compared (1) enhanced surveillance for HCC alone (HCC surveillance), or (2) enhanced HCC surveillance coupled with CHB treatment (HCC prevention) to the current practice, of low CHB treatment uptake.

Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden.

Worldwide, 350 million people are chronically infected with hepatitis B virus (HBV) who are at greater risk of hepatocellular carcinoma (HCC) compared with uninfected people. The relative risks of HCC among people infected with HBV ranges from 5 to 49 in case-control studies and from 7 to 98 in cohort studies. More than 50% of HCC cases worldwide and 70-80% of HCC cases in highly HBV endemic regions are attributable to HBV.

Chronic kidney disease, creatinine and cognitive functioning.

Background: Non-dialysis-dependent chronic kidney disease (CKD) is related to cognitive impairment. Previous studies have not explored the extent of impairment across multiple cognitive domains. We examined the range of specific cognitive abilities affected by CKD and whether the associations of CKD with cognition were eliminated by statistical control for cardiovascular disease correlates of CKD.

Arterial pulse wave velocity and cognition with advancing age.

We hypothesized that carotid-femoral pulse wave velocity (PWV), a marker of arterial stiffness, interacts with age such that the magnitude of associations between PWV and cognitive performance are greater with increasing age and that this interaction is observed despite adjustments for demographic variables, mean arterial pressure, and cardiovascular risk factors. PWV was estimated using applanation tonometry in 409 dementia- and stroke-free participants of the Maine-Syracuse Longitudinal Study (24 to 92 years of age; 62.3% women).

Immunopathogenesis of hepatic flare in HIV/hepatitis B virus (HBV)-coinfected individuals after the initiation of HBV-active antiretroviral therapy.

Background: The pathogenesis of and risk factors for hepatic flare (HF) after the initiation of hepatitis B virus (HBV)-active antiretroviral therapy (ART) in HIV/HBV-coinfected individuals is not well understood.

Methods: We studied HF in ART-naive HIV/HBV-coinfected individuals in Thailand (n = 36) who were beginning HBV-active ART as part of a prospective clinical trial. HF was defined as an alanine aminotransferase (ALT) level>5 times the upper limit of normal or >200 IU/L higher than that at baseline.

Characteristics and treatment outcomes among HIV-infected individuals in the Australian Trial in Acute Hepatitis C.

Background: The Australian Trial in Acute Hepatitis C (ATAHC) is a National Institutes of Health-funded prospective cohort study of the natural history and efficacy of treatment in individuals with recently acquired hepatitis C. Enrollment is open to both human immunodeficiency virus (HIV)-infected and -uninfected individuals. The aim of this article was to evaluate characteristics and virological outcomes among HIV-infected individuals enrolled in ATAHC.

Predictors and survival in hepatitis B-related hepatocellular carcinoma in New South Wales, Australia.

Background And Aim: Incidence and mortality of hepatocellular carcinoma (HCC) has increased markedly over the last three decades in Australia. An increasing proportion of HCC cases is related to chronic viral hepatitis including hepatitis B virus (HBV) infection. However, there is very limited data on HBV-related HCC survival.

Viral dynamics of hepatitis B virus DNA in human immunodeficiency virus-1-hepatitis B virus coinfected individuals: similar effectiveness of lamivudine, tenofovir, or combination therapy.

Unlabelled: Following treatment of hepatitis B virus (HBV) infection with nucleos(t)ide reverse transcriptase inhibitors (NRTIs), there is a biphasic clearance of HBV, similar to that seen following treatment of human immunodeficiency virus-1 (HIV-1) and hepatitis C virus. Little is known about the impact of combination NRTIs and HIV-1 coinfection on HBV viral kinetic parameters following the initiation of HBV-active highly active antiretroviral therapy (HAART). HIV-1-HBV coinfected patients (n = 21) were enrolled in a viral kinetics substudy of the Tenofovir in HIV-1-HBV Coinfection study (TICO).

Modelling and calibration of the hepatitis C epidemic in Australia.

Hepatitis C virus (HCV) infection in Australia is predominantly transmitted through injecting drug use. A reduction in the heroin supply in Australia in late 2000 and early 2001 may have impacted the number of injecting drug users (IDUs) and the number of new hepatitis C infections. This paper updates estimates of HCV incidence between 1960 and 2005 and models long-term sequelae from infection.