Deep learning helps discriminate between autoimmune hepatitis and primary biliary cholangitis.

Background & Aims: Biliary abnormalities in autoimmune hepatitis (AIH) and interface hepatitis in primary biliary cholangitis (PBC) occur frequently, and misinterpretation may lead to therapeutic mistakes with a negative impact on patients. This study investigates the use of a deep learning (DL)-based pipeline for the diagnosis of AIH and PBC to aid differential diagnosis.

Methods: We conducted a multicenter study across six European referral centers, and built a library of digitized liver biopsy slides dating from 1997 to 2023.

Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression.

The maintenance of stable allograft status in the absence of immunosuppression (IS), known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multicenter, biomarker-strategy design, IS withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver tissue collected before initiating IS weaning.

Overweight Impacts Histological Disease Activity of De Novo Metabolic Dysfunction-Associated Steatotic Liver Disease After Liver Transplantation.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading indication for liver transplantation (LT), but also occurs after LT. The prevalence of de novo MASLD (dnMASLD) after LT, based on both surveillance (svLbx) and indication biopsies (indLbx), is unknown. Furthermore, the impact of the distinct cardiometabolic risk factors on histological disease activity has not been assessed.

Identification and functional validation of miR-190b-5p and miR-296-3p as novel therapeutic attenuators of liver fibrosis.

Background & Aims: Liver fibrosis and its end-stage form cirrhosis contribute to millions of deaths annually. The lack of robust antifibrotic molecules is in part attributed to the absence of any functional screens to identify molecular regulators using patient-derived primary human hepatic myofibroblasts, which are key drivers of fibrosis.

Methods: Here, to identify robust regulators of fibrosis, we performed functional microRNA screenings in primary human hepatic myofibroblasts followed by in vivo validation in three independent mouse models of fibrosis (toxin, cholestasis and MASH).

Prospective comparison of liver stiffness measurement methods in surveillance biopsies after liver transplantation.

Background: Liver stiffness measurements (LSMs) have proven useful for non-invasive detection of fibrosis. Previous studies of LSMs after transplantation were performed in cohorts dominated by hepatitis C reinfections and indication biopsies for the evaluation of graft dysfunction. However, the diagnostic fidelity of LSMs for fibrosis is biased by inflammation e.

Clinical Features, Diagnostics, Etiology, and Outcomes of Hospitalized Solid Organ Recipients With Community-Acquired Pneumonia: A Retrospective Cohort Analysis.

Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Limited evidence is available on the most effective diagnostic approaches, management strategies, and long-term outcomes for CAP in patients who have undergone solid organ transplantation.

Research Question: What is the acute and long-term morbidity and mortality after CAP in organ transplant recipients?

Study Design And Methods: We retrospectively analyzed hospitalizations for CAP in solid organ recipients at the largest German transplant center.

Prognostic scores for ursodeoxycholic acid-treated patients predict graft loss and mortality in recurrent primary biliary cholangitis after liver transplantation.

Background & Aims: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC.

Profiling of Commonly Used Post-transplant Immunosuppressants Reveals Distinct Impact on Antiviral T-cell Immunity Towards CMV.

Infectious complications, including widespread human cytomegalovirus (CMV) disease, frequently occur after hematopoietic stem cell and solid organ transplantation due to immunosuppressive treatment causing impairment of T-cell immunity. Therefore, in-depth analysis of the impact of immunosuppressants on antiviral T cells is needed. We analyzed the impact of mTOR inhibitors sirolimus (SIR/S) and everolimus (EVR/E), calcineurin inhibitor tacrolimus (TAC/T), purine synthesis inhibitor mycophenolic acid (MPA/M), glucocorticoid prednisolone (PRE/P) and common double (T+S/E/M/P) and triple (T+S/E/M+P) combinations on antiviral T-cell functionality.

Blockade of neutrophil extracellular trap components ameliorates cholestatic liver disease in Mdr2 (Abcb4) knockout mice.

Primary sclerosing cholangitis (PSC) is an (auto)immune-mediated cholestatic liver disease with a yet unclear etiology. Increasing evidence points to an involvement of neutrophils in chronic liver inflammation and cirrhosis but also liver repair. Here, we investigate the role of the neutrophil extracellular trap (NET) component myeloperoxidase (MPO) and the therapeutic potential of DNase I and of neutrophil elastase (NE) inhibitor GW311616A on disease outcome in the multidrug resistance 2 knockout (Mdr2) mouse, a PSC animal model.

[Treatment of autoimmune hepatitis-First-line, second-line and third-line treatment].

Autoimmune hepatitis (AIH) is a rare autoimmune inflammation of the liver mostly with a chronic course, which can also be acutely manifested up to acute liver failure. It affects women 3-4 times more frequently than men and can be diagnosed in all age groups. In one third of the patients a liver cirrhosis is present at the time of diagnosis.

Association of torque teno virus viremia with liver fibrosis in the first year after liver transplantation.

Introduction: Torque teno virus (TTV) replication is controlled by immune status, mirroring a degree of immunosuppression after solid organ transplantation. TTV viraemia (TTVv) was associated with acute cellular rejection and infection within the first year after liver transplantation (LT). Long-term data on TTV after LT and correlation with graft injury from protocol biopsies are limited.

Evaluation of immunoserological detection of anti-liver kidney microsomal, anti-soluble liver antigen and anti-mitochondrial antibodies.

Autoantibodies are the diagnostic hallmark of autoimmune liver diseases. Indirect immunofluorescence (IFT) is the reference method for the detection of anti-mitochondrial antibodies (AMA) and anti-liver kidney microsomal type-1 (anti-LKM1) antibodies, and inhibition ELISA (iELISA) for anti-soluble liver antigen (anti-SLA) antibodies. Given the complexity of these techniques, commercial ELISAs have emerged as a practical alternative, but without head-to-head validations.

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.

Combination of everolimus and low-dose tacrolimus controls histological liver allograft injury as sufficiently as high-dose tacrolimus.

Introduction: The combination of everolimus (EVR) and low-dose tacrolimus (lowTAC) prevents T cell-mediated rejection of liver grafts as sufficiently as high-dose tacrolimus (highTAC) and mycophenolate, but is associated with a preserved kidney function within the first years after orthotopic liver transplantation (OLT). However, none of the available studies assessed the histological pattern of graft injury or fibrosis in surveillance biopsies (svLbx).

Methods: All svLbx taken under at least one month of stable immunosuppression with either EVR (aim 3-8 ng/ml) combined with lowTAC (aim 3-5 ng/ml) or highTAC (aim 5-8 ng/ml) combined with mycophenolate (500-1500 mg/day) within the first three to four years after OLT at our center were included.

Quantification of extracellular matrix remodeling for the non-invasive identification of graft fibrosis after liver transplantation.

Detecting patients with early post-transplant fibrosis after liver transplantation (LT) is very important. Non-invasive tests are needed to avoid liver biopsies. We aimed to detect fibrosis in liver transplant recipients (LTR) using extracellular matrix (ECM) remodeling biomarkers.

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.

Salvage therapies of autoimmune hepatitis limit proinflammatory immune cells while sparing regulatory T cells.

Background: Autoimmune hepatitis (AIH) can be clinically controlled by first-line immunosuppressive therapy in the majority of patients. However, a selective decrease in intrahepatic regulatory T cells (Treg) was observed with immunosuppressive therapy, which was even more pronounced in patients with incomplete responses than in patients who achieved biochemical remission. The effects of salvage therapies on the number of intrahepatic T and B cells, including Treg, are unclear.