Epidemiology, Treatment Patterns and Survival in Canadian Patients With Chronic Hepatitis B-Related Hepatocellular Carcinoma.

Chronic hepatitis B (CHB) is the leading cause of hepatocellular carcinoma (HCC) globally. We described and evaluated the outcomes of patients with CHB-HCC in Canada. In this retrospective cross-sectional cohort study, data were analysed from CHB mono-infected subjects seen between 1 January 2012 and 31 December 2022, and entered the Canadian Hepatitis B Network Registry.

Exploring autoantibodies as predictors of severe fibrosis or cirrhosis in metabolic dysfunction associated with steatotic liver disease.

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) and metabolic dysfunction associated steatohepatitis (MASH) are rapidly growing public health concerns. Identifying predictive markers for advanced liver disease in MASLD patients is crucial for early intervention. This study investigates the association between autoantibody positivity and risk for severe fibrosis or cirrhosis across various subgroups.

Comparison of different definitions of metabolic syndrome and their associations with non-alcoholic fatty liver disease: a retrospective study.

Background: Metabolic syndrome (MetS) is considered an important risk factor for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to measure the prevalence of MetS based on six different MetS definitions and compare the performance of various definitions for identifying diabetes, hypertension, and dyslipidemia among NAFLD patients.

Methods: The definitions compared were those developed by the World Health Organization (WHO), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), International Diabetes Federation (IDF), American Association of Clinical Endocrinologists (AACE), American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI), and Interim Joint Statement "harmonized" criteria.

Insulin secretion in liver transplant recipients following conversion to a prolonged release tacrolimus formulation.

Background: Post liver transplant diabetes mellitus (PLTDM) occurs in 10-40% of liver transplant recipients and is associated with increased morbidity and mortality. An important cause of PLTDM is tacrolimus induced, concentration-dependent, inhibition of insulin secretion.

Objective: To determine if a newly licenced formulation of tacrolimus (Envarsus-PA), which achieves peak tacrolimus concentrations 20-30% lower than other tacrolimus formulations has less of an inhibitory effect on insulin secretion.

Binge drinking does not appear to have an adverse effect on non-alcoholic fatty liver disease: Findings from a study of four First Nations communities.

Binge drinking and non-alcoholic fatty liver disease (NAFLD) are common health problems throughout the world. However, the impact of binge drinking on NAFLD has yet to be described. The objective of this study was to document the extent of liver disease in community-based NAFLD patients who self-reported monthly binge drinking and compare the findings to NAFLD patients from the same communities who denied binge drinking (controls).

Clinical Outcomes and Quantitative HBV Surface Antigen Levels in Diverse Chronic Hepatitis B Patients in Canada: A Retrospective Real-World Study of CHB in Canada (REVEAL-CANADA).

Background: Hepatitis B surface antigen (HBsAg) loss is associated with improved clinical outcomes for individuals with chronic hepatitis B (CHB); however, the effects of varying HBsAg levels on clinical outcomes in diverse cohorts are understudied.

Methods: In this cross-sectional, multicentre, retrospective study, the data on adult subjects enrolled in the Canadian HBV Network with CHB seen from 1 January 2012 to 30 January 2021 with the treatment and virologic data within 1 year of HBsAg testing were analyzed. Patients were tested for HBsAg using qualitative (for HBsAg-negative samples) and/or commercial quantitative assays.

Unconjugated hyperbilirubinemia may exacerbate certain underlying chronic liver diseases.

Negative correlations have been described between elevated serum unconjugated bilirubin levels and the prevalence/severity of various chronic inflammatory conditions. Whether a similar association exists for patients with unconjugated hyperbilirubinemia (UCB) and underlying chronic liver diseases (CLD) has yet to be reported. The aim of this study was to document hepatic necro-inflammatory disease activity and fibrosis in CLD patients with and without UCB and otherwise normal liver function tests (albumin and INR).

Post-transplant diabetes mellitus in Canadian liver and renal transplant recipients.

Post-transplant diabetes mellitus (PTDM) occurs in 10%-40% of liver and renal transplant recipients. Whether the risk factors for PTDM in liver and renal transplant recipients are similar and whether Indigenous Canadians, who have a high underlying prevalence of diabetes mellitus (DM), are at increased risk of developing PTDM have yet to be determined. To describe and compare those variables associated with PTDM in adult Canadian liver and renal transplant recipients.

Nationwide retrospective study of hepatitis B virological response and liver stiffness improvement in 465 patients on nucleos(t)ide analogue.

Background: Hepatitis B virus (HBV) nucleos(t)ide analog (NA) therapy reduces liver disease but requires prolonged therapy to achieve hepatitis B surface antigen (HBsAg) loss. There is limited North American real-world data using non-invasive tools for fibrosis assessment and few have compared 1 generation NA or lamivudine (LAM) to tenofovir disoproxil fumarate (TDF).

Aim: To assess impact of NA on virological response and fibrosis regression using liver stiffness measurement (LSM) (, FibroScan).

Liver enzymes and fibrosis markers in patients with non-alcoholic fatty liver disease and concomitant chronic viral hepatitis.

The impact of non-alcoholic fatty liver disease (NAFLD) on patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections has yet to be determined. In this retrospective, cross-sectional analysis, untreated chronic HBV, hepatitis B e-antigen (HBeAg)-positive patients with NAFLD had similar liver biochemistry and FIB-4 values as age-, gender-, and viral-load-matched HBeAg-positive patients without NAFLD. Among HBeAg-negative patients with NAFLD, although liver biochemistry findings were similar, mean FIB-4 values were significantly lower (0.

Hepatic adenomatosis in a young woman with non-familial maturity-onset diabetes of the young type 3.

Hepatic adenomatosis (HA) is a rare condition in which multiple adenomas exist in an otherwise healthy liver. The most common subtype (H-HA) is associated with bi-allelic, somatic hepatic nuclear factor 1-alpha (HNF1A) mutations. Maturity-onset diabetes of the young type 3 (MODY3) is most often seen in young individuals with heterozygous, germline mutations in HNF1A.

The Effects of Pathogen-Associated Molecular Patterns on Peripheral Blood Monocytes in Patients with Non-alcoholic Fatty Liver Disease.

Background: Innate immune responses to gut-derived pathogen-associated molecular patterns (PAMPs) have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether NAFLD patients have increased sensitivity to PAMP exposure has yet to be reported.

Methods: Peripheral blood mononuclear cell (PBMC)/monocytes were exposed to lipopolysaccharide (LPS), Pam3CSK4, or BSA conjugated palmitate .

Comparison of growth features and cancer stem cell prevalence in intrahepatic and extrahepatic cholangiocarcinoma cell lines.

Aim Of The Study: Intra- and extrahepatic cholangiocarcinoma (I-CCA and E-CCA respectively) exhibit different growth features that contribute to different clinical outcomes. Cancer stem cells (CSCs) influence tumor growth and thereby may be responsible for these differences. The aim of this study was to document and compare the growth features of human I-CCA and E-CCA cell lines and determine whether any differences observed could be explained by differences in the prevalence and/or stem cell surface marker (SCSM) expression profiles of CSCs within the tumor cell lines.

Molecular epidemiology and clinical characteristics of hepatitis D virus infection in Canada.

Background & Aims: HDV affects 4.5-13% of chronic hepatitis B (CHB) patients globally, yet the prevalence of HDV infection in Canada is unknown. To investigate the prevalence, genotype, demographics, and clinical characteristics of HDV in Canada, we conducted a retrospective analysis of (1) HDV antibody and RNA positivity among referred specimens, and (2) a cross-sectional subset study of 135 HDV seropositive +/-RNA (HDV+) patients compared with 5,132 HBV mono-infected patients in the Canadian HBV Network.

Severe Hepatic Steatosis Is Associated With Low-Level Viremia and Advanced Fibrosis in Patients With Chronic Hepatitis B in North America.

Background And Aims: The obesity epidemic has increased the risk of nonalcoholic fatty liver disease (NAFLD) in both the general and chronic hepatitis B (CHB) populations. Our study aims to determine the prevalence of NAFLD in patients with CHB based on controlled attenuation parameter (CAP) and the epidemiological, clinical, and virological factors associated with severe hepatic steatosis.

Methods: The Canadian Hepatitis B Network cohort was utilized to provide a cross-sectional description of demographics, comorbidities, antiviral treatment, and hepatits B virus (HBV) tests.

Fibroblast Growth Factor 19 Induced Changes in Non-malignant Cholangiocytes.

Background And Aims: Fibroblast growth factor (FGF)19 has been implicated in the pathogenesis of murine hepatocellular carcinoma. Whether it plays a role in the development or course of human cholangiocarcinoma remains to be determined. The aim of this study was to determine whether prolonged exposure to FGF19 results in the transformation of non-malignant human cholangiocytes into cells with malignant features.

Pharmacokinetics of a once-daily tacrolimus formulation in first nations and caucasian liver transplant recipients.

Patient ethnicity may influence the pharmacokinetics (PK) of tacrolimus. Because the Canadian First Nations (FN) constitute a large and increasing segment of the liver transplant population, we undertook to determine whether PK differences exist for a once-daily, extended release formulation of tacrolimus (Advagraf) in FN compared to Caucasian (CAUC) liver transplant recipients. Following achievement of a steady state with Advagraf, blood samples were drawn at 0, 1, 2, 4, 6, 8 and 24 hours for whole blood tacrolimus levels by commercial immunoassay and CYP3A4 and CYP3A5 allele analyses were performed by polymerase chain reactions.

The effects of binge drinking on healthy and diseased livers.

The estimated global prevalence of alcohol abuse is 5%-15%, with 15%-20% of these individuals being considered binge drinkers. Despite the high prevalence, the effects of binge drinking on healthy and diseased livers remain unclear. This review focuses on the effects of binge drinking in adults with otherwise healthy livers and those with a variety of common underlying chronic liver diseases.

Low serum alkaline phosphatase levels in patients with chronic liver diseases: Possible contributions to disease pathogenesis.

Objectives: A low serum alkaline phosphatase (ALP) level is an uncommon finding in patients with chronic liver disease (CLD). The prevalence of this finding and whether low ALP expression influences CLD remain to be determined. The objectives of this study were: (1) to document the prevalence of low serum ALP levels in adult CLD patients and (2) compare features of CLD in patients with low versus normal or elevated serum ALP levels.

Efficacy and Safety of Cenicriviroc in Patients With Primary Sclerosing Cholangitis: PERSEUS Study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease with no approved treatments. C-C chemokine receptor types 2 and 5 (CCR2/CCR5) play an important role in inflammation and fibrosis and are potential therapeutic targets for PSC. We evaluated the efficacy and safety of cenicriviroc (CVC), a dual antagonist of CCR2 and CCR5, for the treatment of PSC.

Distinct Hepatitis B and HIV co-infected populations in Canada.

Due to shared modes of exposure, HIV-HBV co-infection is common worldwide. Increased knowledge of the demographic and clinical characteristics of the co-infected population will allow us to optimize our approach to management of both infections in clinical practice. The Canadian Hepatitis B Network Cohort was utilized to conduct a cross-sectional evaluation of the demographic, biochemical, fibrotic and treatment characteristics of HIV-HBV patients and a comparator HBV group.

Chronic Liver Disease and Metabolic Comorbidities in Healthy Young Males Followed for 65 Years: The Manitoba Follow-up Study.

Background & Aims: The prevalence of chronic liver disease (CLD) is largely derived from cross-sectional epidemiologic surveys. The goal of this long-term, prospective study was to document the lifetime risk of developing chronic liver disease and determine the impact of common metabolic conditions associated with metabolic syndrome (MetS) on the development and outcomes of CLD.

Methods: 3,983 air force men were enrolled in the Manitoba Follow-up Study in 1948.

Alterations in chemokine receptor CCR5 activity influence tumor cell biology in human cholangiocarcinoma cell lines.

Introduction And Objectives: Intrahepatic (I-CCA) and extrahepatic (E-CCA) cholangiocarcinoma (CCA) have different growth patterns and risks for tumor metastasis. Inhibition and/or activation of the chemokine receptor CCR subclasses have been reported to alter tumor cell biology in non-CCA cancers. In this study we documented CCR expression profiles in representative human I-CCA and E-CCA cell lines and the in vitro effects of CCR antagonists and agonists on tumor cell biology.

Enhanced gemcitabine cytotoxicity with knockdown of multidrug resistance protein genes in human cholangiocarcinoma cell lines.

Background And Aim: Cholangiocarcinoma (CCA) is an often fatal primary cancer of the liver that tends to be resistant to chemotherapy. Multidrug resistance proteins (MRPs) contribute to the chemoresistance of these tumors. The objectives of the study were to document MRP expression profiles in two representative human intrahepatic and extrahepatic CCA cells lines (HuCCT1 and KMBC, respectively) and gemcitabine-induced cytotoxicity prior to and following MRP knockdown.