The need to improve fertility awareness.

Women and men globally are delaying the birth of their first child. In the UK, the average age of first conception in women is 29 years. Women experience age-related fertility decline so it is important that men and women are well-informed about this, and other aspects of fertility.

Toronto HCC risk index: A validated scoring system to predict 10-year risk of HCC in patients with cirrhosis.

Background & Aims: Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. We aimed to assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk.

Preemptive adefovir versus lamivudine for prevention of hepatitis B reactivation in chronic hepatitis B patients undergoing chemotherapy.

Background: This proof-of-concept study compared lamivudine (LAM) with a newer antiviral agent, adefovir dipivoxil (ADF), in preventing hepatitis B virus (HBV) reactivation in chronic HBV patients undergoing chemotherapy.

Methods: Hepatitis B surface antigen (HBsAg) positive patients intended to undergo chemotherapy were randomized to receive either LAM 100 mg daily or ADF 10 mg daily. Anti-viral therapy was started 1 week prior to chemotherapy and until 6 months after completing chemotherapy.

Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate.

Background & Aims: In a study of 266 chronic hepatitis B e antigen (HBeAg)-positive patients, 23 experienced hepatitis B surface antigen (HBsAg) loss with up to 5 years of tenofovir disoproxil fumarate (TDF) treatment. HBsAg kinetics in patients with and without HBsAg loss and predictors of HBsAg loss were evaluated.

Methods: HBsAg levels were quantified every 12 weeks.

Impact of a formal mentoring program on academic promotion of Department of Medicine faculty: a comparative study.

Purpose: To evaluate the impact of a formal mentoring program on time to academic promotion and differences in gender-based outcomes.

Methods: Comparisons of time to promotion (i) before and after implementation of a formal mentoring program and (ii) between mentored and non-mentored faculty matched for covariates. Using paired-samples t-testing and mixed repeated measures ANCOVA, we explored the effect of mentor assignment and influence of gender on time to promotion.

Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis B surface antigen levels.

Unlabelled: On-treatment levels of hepatitis B surface antigen (HBsAg) may predict response to peginterferon (PEG-IFN) therapy in chronic hepatitis B (CHB), but previously proposed prediction rules have shown limited external validity. We analyzed 803 HBeAg-positive patients treated with PEG-IFN in three global studies with available HBsAg measurements. A stopping-rule based on absence of a decline from baseline was compared to a prediction-rule that uses HBsAg levels of <1,500 IU/mL and >20,000 IU/mL to identify patients with high and low probabilities of response.

Disease burden of chronic hepatitis B among immigrants in Canada.

Background: The prevalence of chronic hepatitis B (CHB) infection among immigrants to North America ranges from 2% to 15%, 40% of whom develop advanced liver disease. Screening for hepatitis B surface antigen is not recommended for immigrants.

Objective: To estimate the disease burden of CHB among immigrants in Canada using Markov cohort models comparing a cohort of immigrants with CHB versus a control cohort of immigrants without CHB.

A 24-week dietary and physical activity lifestyle intervention reduces hepatic insulin resistance in the obese with chronic hepatitis C.

Background/aims: Obesity- and virus-mediated insulin resistance (IR) are associated with adverse hepatic and metabolic outcomes in chronic hepatitis C (CHC). This study evaluates the tolerability and effects of a dietary and physical activity (PA) intervention in obese patients with insulin-resistant CHC.

Methods: Obese patients (body mass index, BMI ≥30 kg/m(2) ) with CHC were recruited prospectively.

Hepatitis B e antigen levels and response to peginterferon: influence of precore and basal core promoter mutants.

Hepatitis B e antigen (HBeAg) levels may predict response to peginterferon (PEG-IFN) but are also influenced by presence of precore (PC) and core promoter (BCP) mutants. HBeAg was measured in 214 patients treated with PEG-IFN±lamivudine for 52weeks. Patients were classified at baseline as wildtype (WT) or non-WT (detectable PC/BCP mutants).

Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis.

Context: Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death.

Objective: To assess the association between sustained virological response (SVR) and all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis.

Design, Setting, And Patients: An international, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe and Canada of 530 patients with chronic HCV infection who started an interferon-based treatment regimen between 1990 and 2003, following histological proof of advanced hepatic fibrosis or cirrhosis (Ishak score 4-6).

Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study.

Background: Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years' treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection.

Methods: After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240.

The impact of hepatitis B knowledge and stigma on screening in Canadian Chinese persons.

Background: Chronic hepatitis B (CHB) infection is endemic in East Asia, and those who emigrate to North America have higher rates of CHB infection when compared with the general population. To date, Chinese persons residing in Canada have not been mandated to be screened for CHB infection.

Objective: To understand factors that influence hepatitis B screening behaviour among the Chinese community in Toronto, Ontario, and to determine whether stigma acts as a barrier to screening.

The impact of infection on population health: results of the Ontario burden of infectious diseases study.

Background: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting.

Methodology/principal Findings: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005-2007 data.

Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants.

To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci.

Health state utilities and quality of life in patients with hepatitis B.

Background: The effect of chronic hepatitis B (CHB) infection on health-related quality of life (HRQoL) and health state utilities has not been well characterized.

Objective: To measure utility scores and HRQoL across disease states associated with CHB infection.

Methods: Patients attending four tertiary care clinics for CHB were approached between July 2007 and March 2009.

Safety of peginterferon alfa-2a plus ribavirin in a large multinational cohort of chronic hepatitis C patients.

Background & Aims: Peginterferon plus ribavirin has been the standard of care for chronic hepatitis C for a decade and an essential component of combination regimens for this disease. This large multinational open-label study aimed to better define the incidence of serious adverse events (SAEs) and non-serious adverse events of special interest in patients receiving peginterferon alfa-2a/ribavirin.

Methods: Patients were assigned at the investigator's discretion to 24- or 48-week treatment with peginterferon alfa-2a 180 μg/week and ribavirin 800 mg/day or 1000/1200 mg/day.

Presence of precore and core promoter mutants limits the probability of response to peginterferon in hepatitis B e antigen-positive chronic hepatitis B.

Unlabelled: Peginterferon (PEG-IFN) treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) results in HBeAg loss in 30% of patients, but clearance of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) from serum is less often achieved. We investigated whether the presence of precore (PC) and basal core promoter (BCP) mutants before PEG-IFN treatment affects serological and virological response. A total of 214 HBeAg-positive CHB patients treated with PEG-IFN ± lamivudine for 52 weeks in a global randomized trial were classified at baseline as wildtype (WT) or non-WT (detectable mutants at PC/BCP) by line-probe assay.

Hepatic cell-type specific gene expression better predicts HCV treatment outcome than IL28B genotype.

Background & Aims: Cell-type specific expression patterns of hepatic interferon-stimulated genes (ISGs) and single nucleotide polymorphisms (SNPs) near the IL28B gene are associated with response to interferon-based therapy in patients with chronic hepatitis C virus (HCV) infection. It is not known how the IL28B genotype influences the ISG expression pattern and which is a better predictor of treatment response.

Methods: Patients at the Toronto Western Hospital Liver Centre with known outcome to interferon-based treatment for HCV infection were evaluated.

Durable hepatitis B surface antigen decline in hepatitis B e antigen-positive chronic hepatitis B patients treated with pegylated interferon-α2b: relation to response and HBV genotype.

Background: On-treatment decline of serum hepatitis B surface antigen (HBsAg) may reflect the immunomodulatory effect of pegylated interferon (PEG-IFN) for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). We compared HBsAg decline across HBV genotypes between combined responders (HBeAg loss and HBV DNA<10,000 copies/ml at week 78), HBeAg responders (HBeAg loss with HBV DNA>10,000 copies/ml) and non-responders.

Methods: HBsAg was measured at baseline, on-treatment and 6 months post-treatment in 221 HBeAg-positive CHB patients treated with PEG-IFN with or without lamivudine for 52 weeks, and in a representative subgroup of 142 patients at long-term follow-up (LTFU; mean 3.

Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: a pilot study.

Background: Primary biliary cirrhosis and primary sclerosing cholangitis are two cholestatic diseases characterised by hepatic accumulation of bile acids.

Aims: This study compares serum bile acid levels in patients with primary biliary cirrhosis and primary sclerosing cholangitis and from age and sex-matched non cholestatic donors.

Methods: Seventeen bile acids were quantified using liquid chromatography coupled to tandem mass spectrometry.

Biliary atresia and survival into adulthood without transplantation: a collaborative multicentre clinic review.

Background: Biliary atresia is a progressive biliary injury which occurs only in infants.

Aims: To review the experience of patients surviving into adulthood without the need for liver transplantation in childhood.

Methods: A multicentre review of patients with biliary atresia treated surgically who survived into adulthood without the need for transplantation.

Retreatment with telaprevir combination therapy in hepatitis C patients with well-characterized prior treatment response.

Unlabelled: Retreatment with peginterferon alpha and ribavirin (PR) offers a limited chance of sustained virologic response (SVR) in patients who did not achieve SVR with prior PR treatment. This study evaluated the safety and efficacy of telaprevir-based treatment in combination with PR in well-characterized patients who did not achieve SVR in the control arms of three Phase II clinical trials. Patients eligible to enroll in this open-label nonrandomized study either met on-treatment criteria for nonresponse or relapsed after 48 weeks of treatment in the control arm of the three Phase II PROVE studies.

Does hepatic vein transit time performed with contrast-enhanced ultrasound predict the severity of hepatic fibrosis?

Previously published data suggest a hepatic vein transit time (HVTT) threshold of more than 24 s can distinguish mild to moderate from advanced fibrosis. In this study, we attempted to validate HVTT as a noninvasive index of hepatic fibrosis. Patients were scanned using real-time, pulse-inversion mode following bolus injections of the contrast agent Definity.