Liver-restricted Type I IFN Signature Precedes Liver Damage in Chronic Hepatitis B Patients Stopping Antiviral Therapy.

Immune-mediated liver damage is the driver of disease progression in patients with chronic hepatitis B virus (HBV) infection. Liver damage is an Ag-independent process caused by bystander activation of CD8 T cells and NK cells. How bystander lymphocyte activation is initiated in chronic hepatitis B patients remains unclear.

Addition of PEG-interferon to long-term nucleos(t)ide analogue therapy enhances HBsAg decline and clearance in HBeAg-negative chronic hepatitis B: Multicentre Randomized Trial (PAS Study).

We studied whether 48 weeks of PEG-IFN alfa-2a add-on increases HBsAg-decline and clearance in HBeAg-negative patients on long-term nucleo(s)tide analogue (NA) therapy. In this investigator-initiated, randomized, controlled trial conducted in Europe and Canada, HBeAg-negative patients treated with NA > 12 months, with HBVDNA < 200 IU/mL, were enrolled. Patients were randomized 2:1 to 48 weeks of PEG-IFN alfa-2a add-on (180 μg per week) or continued NA-monotherapy with subsequent follow-up to Week 72.

Biliary disease progression in childhood onset autoimmune liver disease: A 30-year follow-up into adulthood.

Background & Aims: Long-term follow-up studies of paediatric onset autoimmune liver disease (AILD) are invaluable in helping better understand the clinical course of disease. In day-to-day practice clinicians struggle with disease definitions whilst patients and parents lack clear prognostic information.

Methods: The clinical progression of 159 patients with childhood onset AILD between June 1990 and December 2013 was reviewed, capturing data up to adulthood (ending May 2021).

Single-cell, single-nucleus, and spatial transcriptomics characterization of the immunological landscape in the healthy and PSC human liver.

Background & Aims: Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease for which there is an unmet need to understand the cellular composition of the affected liver and how it underlies disease pathogenesis. We aimed to generate a comprehensive atlas of the PSC liver using multi-omic modalities and protein-based functional validation.

Methods: We employed single-cell and single-nucleus RNA sequencing (47,156 cells and 23,000 nuclei) and spatial transcriptomics (one sample by 10x Visium and five samples with Nanostring GeoMx DSP) to profile the cellular ecosystem in 10 PSC livers.

Characterising the effectiveness of social determinants of health-focused hepatitis B interventions: a systematic review.

Social determinants of health are important in designing effective interventions for hepatitis B virus (HBV) infection. This systematic review characterises equity-oriented, social determinants of health-focused HBV interventions, and describes their effectiveness in terms of the prevention, care, or treatment of HBV in high-income countries. We searched electronic databases for central concepts of 'HBV', 'equity', 'social determinants of health', 'intervention', and 'Organization for Economic Co-operation and Development (OECD) countries'.

We have reached single-visit testing, diagnosis, and treatment for hepatitis C infection, now what?

Introduction: Progress toward hepatitis C virus (HCV) elimination is impeded by low testing and treatment due to the current diagnostic pathway requiring multiple visits leading to loss to follow-up. Point-of-care testing technologies capable of detecting current HCV infection in one hour are a 'game-changer.' These tests enable diagnosis and treatment in a single visit, overcoming the barrier of multiple visits that frequently leads to loss to follow-up.

IL-2 produced by HBV-specific T cells as a biomarker of viral control and predictor of response to PD-1 therapy across clinical phases of chronic hepatitis B.

Background: There are no immunological biomarkers that predict control of chronic hepatitis B (CHB). The lack of immune biomarkers raises concerns for therapies targeting PD-1/PD-L1 because they have the potential for immune-related adverse events. Defining specific immune functions associated with control of HBV replication could identify patients likely to respond to anti-PD-1/PD-L1 therapies and achieve a durable functional cure.

Primary Biliary Cholangitis: Pathophysiology.

Primary biliary cholangitis (PBC) is the most common of the autoimmune liver diseases, in which there is chronic small bile duct inflammation. The pathophysiology of PBC is multifactorial, involving immune dysregulation and damage to biliary epithelial cells, with influences from genetic factors, epigenetics, the gut-liver axis, and environmental exposures.

Hepatocellular carcinoma risk in sub-Saharan African and Afro-Surinamese individuals with chronic hepatitis B living in Europe.

Background & Aims: Sub-Saharan African (SSA) ethnicity has been associated with a higher risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis B in cross-sectional studies. However, the incidence of HCC and performance of HCC risk scores in this population are unknown.

Methods: We conducted an international multicenter retrospective cohort study of all consecutive HBV-monoinfected individuals of SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain.

Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis.

Background: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications.

Outcomes of early vs late treatment initiation in solid organ transplantation from hepatitis C virus nucleic acid test-positive donors to hepatitis C virus-uninfected recipients: Results from the HCV-TARGET study.

Curative hepatitis C virus (HCV) therapy has increased transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients (D+/R-). We evaluated outcomes of early and late HCV treatment among D+/R- nonliver organ transplants. Patients received HCV regimens per local standard (n = 10 sites).

What Is Needed to Move Toward Single-Step Diagnosis of Current HCV Infection?

Despite remarkable therapeutic advances, hepatitis C virus (HCV) infection continues to be a major global problem. While the development of highly effective direct-acting antivirals has ensured that almost all those who are treated achieve viral cure, progress toward HCV elimination globally has stalled due to challenges upstream of treatment in the cascade of care, namely diagnosis and linkage to care. The major challenge continues to be the relative complexity of HCV diagnosis with the current requirement for a confirmatory HCV RNA test after an initial antibody-positive result.

Symptoms of Liver Disease During Tenofovir Therapy With or Without Peginterferon: Results from the Hepatitis B Research Network Immune Active Trial.

Aims: Evaluate patient-reported liver symptoms during treatment for chronic hepatitis B viral (HBV) infection and associations between changes in symptoms and levels of alanine aminotransferase (ALT) and viral markers.

Methods: Data from 200 participants in the Hepatitis B Research Network Immune Active Trial who completed symptom assessments were analyzed. Patients were treated with tenofovir, with or without peginterferon (TDF + PegIFN vs.

Epidemiology and trends of alcohol use disorder and alcohol-associated liver disease.

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Call to Improve the Quality of Prediction Tools for Intrahepatic Cholangiocarcinoma Resection: A Critical Appraisal, Systematic Review, and External Validation Study.

Objective: To conduct a systematic review, critical appraisal, and external validation of survival prediction tools for patients undergoing intrahepatic cholangiocarcinoma (iCCA) resection.

Summary Background Data: Despite the development of several survival prediction tools in recent years for patients undergoing iCCA resections, there is a lack of critical appraisal and external validation of these models.

Methods: We conducted a systematic review and critical appraisal of survival and recurrence prediction models for patients undergoing curative-intent iCCA resections.

The impact of the early COVID-19 pandemic on healthcare system resource use and costs in two provinces in Canada: An interrupted time series analysis.

Introduction: The aim of our study was to assess the initial impact of COVID-19 on total publicly-funded direct healthcare costs and health services use in two Canadian provinces, Ontario and British Columbia (BC).

Methods: This retrospective repeated cross-sectional study used population-based administrative datasets, linked within each province, from January 1, 2018 to December 27, 2020. Interrupted time series analysis was used to estimate changes in the level and trends of weekly resource use and costs, with March 16-22, 2020 as the first pandemic week.