Intergenic risk variant rs56258221 skews the fate of naive CD4 T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease of unknown pathogenesis, with a high risk to develop cirrhosis and malignancies. Functional dysregulation of T cells and association with genetic polymorphisms in T cell-related genes were previously reported for PSC. Here, we genotyped a representative PSC cohort for several disease-associated risk loci and identified rs56258221 (BACH2/MIR4464) to correlate with not only the peripheral blood T cell immunophenotype but also the functional capacities of naive CD4 T (CD4 T) cells in people with PSC.

Corrigendum: PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease.

[This corrects the article DOI: 10.3389/fimmu.2023.

PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease.

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune-related adverse events (irAE) are a frequent concern in clinical practice. The safety profile of ICI for the treatment of malignancies in patients diagnosed with autoimmune and cholestatic liver disease (AILD) remains unclear.

Accuracy of controlled attenuation parameter measurement for the detection of steatosis in autoimmune liver diseases.

Background & Aims: Concurrent fatty liver disease represents an emerging challenge in the care of individuals with autoimmune liver diseases (AILD). Therefore, we aimed to validate the ultrasound-based method of controlled-attenuation parameter (CAP) as a non-invasive tool to detect hepatic steatosis in individuals with AILD.

Methods: The diagnostic performance of CAP to determine biopsy-proven hepatic steatosis (>5%) was assessed in individuals with AILD (autoimmune hepatitis [AIH], primary biliary cholangitis [PBC], primary biliary cholangitis [PSC], or variant syndromes) who underwent liver biopsy at the University Medical Center Hamburg-Eppendorf between 2015-2020 by calculating the area under the receiver operating characteristic (AUROC) curves.

is a risk haplotype for primary sclerosing cholangitis mediating activation of NKp44+ NK cells.

Objective: Primary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring liver transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind the activating NK-cell receptor NKp44, we investigated the role of HLA-DP/NKp44-interactions in PSC.

Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?

Background And Aims: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA.

Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report.

Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article summarises the major topics discussed at a joint International Conference held between the Drug-Induced Liver Injury consortium and the International Autoimmune Hepatitis Group.

Right and left liver lobe biopsies by minilaparoscopy reveal clinically significant sampling error in staging and grading of autoimmune hepatitis.

Backgrounds/aims: Liver diseases may affect the liver heterogeneously, especially in autoimmune hepatitis (AIH). Hence, the aim of this study was to assess the added benefit of double biopsy of both liver lobes during minilaparoscopy in guiding treatment decisions in patients with AIH.

Methods: We identified all patients with AIH or variant syndromes (AIH/PBC and AIH/PSC) at our center, who underwent a double biopsy of both liver lobes via minilaparoscopy between 01/2016 and 12/2020.

Research gaps and opportunities in autoimmune hepatitis-Results of the international autoimmune hepatitis group research workshop 2022.

Autoimmune hepatitis (AIH) is a rare autoimmune liver disease that is characterised by a chronic inflammatory immune reaction directed against hepatocytes. The disease results in a substantial reduction in quality of life and potentially leads to liver-related complications or death. The International Autoimmune Hepatitis Group (IAIHG) initiated a series of research workshops to uncover the scientific gaps and opportunities in AIH.

Etiology and Outcome of Adult and Pediatric Acute Liver Failure in Europe.

Acute liver failure (ALF) is rare but life-threatening. Common causes include intoxications, infections, and metabolic disorders. Indeterminate etiology is still frequent.

Histological and serological features of acute liver injury after SARS-CoV-2 vaccination.

Background & Aims: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features.

Methods: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included.

[Sarcoidosis as prime example of a granulomatous disease].

Sarcoidosis is the most frequent immunologically related granulomatous disease and can serve as a model for understanding diseases within this category. The evidence on the diagnostics and treatment is so far limited. It is therefore all the more important that two new and significant guidelines on diagnosis and treatment of sarcoidosis were published during the last 2 years.

Analysis of the humoral and cellular response after the third COVID-19 vaccination in patients with autoimmune hepatitis.

Background & Aims: To explore the humoral and T-cell response to the third COVID-19 vaccination in autoimmune hepatitis (AIH).

Methods: Anti-SARS-CoV-2 antibody titers were prospectively determined in 81 AIH patients and 53 healthy age- and sex-matched controls >7 days (median 35) after the first COVID-19 booster vaccination. The spike-specific T-cell response was assessed using an activation-induced marker assay (AIM) in a subset of patients.

Microplastics detected in cirrhotic liver tissue.

Background: The contamination of ecosystem compartments by microplastics (MPs) is an ubiquitous problem. MPs have been observed in mice tissues, and recently in human blood, stool and placenta. However, two aspects remain unclear: whether MPs accumulate in peripheral organs, specifically in the liver, and if liver cirrhosis favours this process.

Inflammatory type 2 conventional dendritic cells contribute to murine and human cholangitis.

Background & Aims: Primary sclerosing cholangitis (PSC) is a progressive cholangiopathy characterised by fibrotic stricturing and inflammation of bile ducts, which seems to be driven by a maladaptive immune response to bile duct injury. The histological finding of dendritic cell expansion in portal fields of patients with PSC prompted us to investigate the role of dendritic cells in orchestrating the immune response to bile duct injury.

Methods: Dendritic cell numbers and subtypes were determined in different mouse models of cholangitis by flow cytometry based on lineage-imprinted markers.

[Hepatic granuloma-A diagnostic challenge].

Hepatic granulomas can have various causes and their detection requires a systematic diagnostic evaluation. First, identification of risk factors for granulomatous diseases and the exclusion of extrahepatic organ manifestation are necessary. Laboratory investigations and serological screening for the most common underlying diseases of liver granulomas in Germany, such as primary biliary cholangitis (PBC), sarcoidosis and infectious causes (primarily tuberculosis and hepatitis C infections), are recommended.

SARS-CoV-2 vaccination response in patients with autoimmune hepatitis and autoimmune cholestatic liver disease.

Background/aims: In this observational study, we explored the humoral and cellular immune response to SARS-CoV-2 vaccination in patients with autoimmune hepatitis (AIH) and patients with cholestatic autoimmune liver disease (primary sclerosing cholangitis [PSC] and primary biliary cholangitis [PBC]).

Methods: Anti-SARS-CoV-2 antibody titers were determined using the DiaSorin LIAISON and Roche immunoassays in 103 AIH, 64 PSC, and 61 PBC patients and 95 healthy controls >14 days after the second COVID-19 vaccination. The spike-specific T-cell response was assessed using an activation-induced marker assay (AIM) in a subset of individuals.

Consensus recommendations for histological criteria of autoimmune hepatitis from the International AIH Pathology Group: Results of a workshop on AIH histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology: Results of a workshop on AIH histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology.

Background & Aims: Diagnostic histological criteria for autoimmune hepatitis (AIH) have not been clearly established. Previously published criteria focused mainly on chronic AIH, in which inflammatory changes mainly occur in portal/periportal regions and may not be applicable to acute presentation of AIH, in which inflammatory changes are typically predominantly lobular in location. International consensus criteria for the diagnosis and assessment of disease severity in both acute and chronic AIH are thus urgently needed.