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. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. Approach and Results: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7–21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7–59.9, p < 0.001) when these 2 conditions were met. Conclusions: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Background and Aims Endoscopic retrograde cholangiography (ERC) is the method of choice to treat biliary strictures in patients with primary sclerosing cholangitis (PSC). However, in a subgroup of PSC patients, biliary stenoses are complex and endoscopic biliary drainage cannot be established using ERCP. There is no generally accepted recommendation how to proceed in this situation, highlighting a severe lack of data. The aim of this study was to investigate the risks, benefits and clinical outcomes of PSC patients after percutaneous transhepatic cholangiodrainage (PTCD) in an international, multicentre study.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease with unknown pathogenesis. Activated T effector cells seem to play a crucial role. Here, we tested the hypothesis that T cell activation in AIH is inappropriately controlled. We investigated various molecules involved in the regulation of T cell activation in liver and blood of patients with AIH in comparison to healthy individuals and to other immune-mediated liver diseases.

Autoimmune Hepatitis (AIH) is a chronic inflammatory liver disease, which leads to liver failure if left untreated. The pathogenesis of AIH is unclear, however, it is believed that CD4+ T-cells play an important role in the disease pathogenesis. We here sought to characterise the cellular drivers of AIH pathogenesis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease and immune dysregulation is considered to be part of disease pathogenesis. We could recently show that in patients with PSC, IL-17 producing T cells were located around the bile ducts. In vitro stimulation of peripheral blood mononuclear cells (PBMC) with pathogens, that were previously identified to be of clinical relevance for PSC, resulted in increased Th17-responses compared to controls and healthy individuals. In this study, we analyzed whether Th17-differentiation in PSC already occurs in vivo and aimed to identify potentialmechanisms involved in the differentiation to Th17 cells.

Drug-induced liver injury (DILI) is a heterogenous entity leading to acute liver damage. Large DILI registries like in the United States have identified the most frequent agents causing DILI, among those mainly antibiotics such as amoxicillin-clavulanate and analgetics such as diclofenac. The RUCAM score has been established to assess causality for DILI. We have analysed the most frequent drugs causing DILI at our tertiary centre.

Die Autoimmune Hepatitis (AIH) ist eine seltene autoimmune Lebererkrankung, die bei persistierender Entzündungsaktivität zur Entwicklung einer Leberzirrhose führen kann. Die Leberbiopsie ist maßgeblich zur Diagnosestellung und auch im Verlauf der Erkrankung häufig erforderlich, um eine Aussage über die histologische Entzündungsaktivität zu erhalten. Neben den Gammaglobulinen ist der Immunglobulin G-Spiegel (IgG) als Parameter zur Abschätzung der AIH-Aktivität etabliert. Normwertige Transaminasen (ALT, AST) und normwertiges IgG gelten als beste Surrogatmarker für eine histologische Remission. Ziel der Studie war es zu untersuchen, ob Transaminasen und/oder IgG als Surrogatmarker der histologischen Aktivität der AIH auch bei Patienten mit bestehender Leberzirrhose verwendet werden können.

Die Autoimmune Hepatitis (AIH) galt früher als Erkrankung junger Frauen, kann aber Patienten jeden Alters und Geschlechts betreffen. Neue Daten zeigen eine steigende Prävalenz bei älteren Patienten und einen Inzidenzgipfel in der 6. Lebensdekade. Bislang veröffentlichte Studien definierten ältere Patienten ab einem Lebensalter von 60 bzw. 65 Jahren. Nach aktueller Datenlage entspricht diese Definition jedoch eher einem typischen Kollektiv. Daher besteht Unsicherheit bezüglich des Krankheitsverlaufes und Therapieansprechens der AIH bei Patienten, die älter als 70 Jahre sind.

The presence of selectively elevated IgG levels is a hallmark of AIH and has found its way into diagnostic scores. Nevertheless, about 15% of patients show normal IgG levels. The clinical significance of normal IgG values at diagnosis has so far not been explored in detail.

Summary Background In patients with primary sclerosing cholangitis follow‐up magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is performed by many centres, particularly for the early detection of biliary malignancies and strictures. Clinically meaningful MRI ‐based definitions of primary sclerosing cholangitis related complications are, however, lacking. Aim To investigate how primary sclerosing cholangitis experts interpret follow‐up MRI/MRCP with a focus on conclusions that may impact clinical decision‐making in primary sclerosing cholangitis. Methods Within the International Primary Sclerosing Cholangitis Study Group, an online survey on 16 real‐life primary sclerosing cholangitis cases including clinical and biochemical information as well as a T2‐weighted liver MRI/3D‐MRCP was conducted. The interpretation of images and subsequent recommendations were assessed using a multiple‐choice questionnaire. An inter‐rater reliability calculation (Fleiss′ kappa) was performed and factors potentially affecting the interpretation of magnetic resonance images were analysed using generalised linear mixed‐effect models. Results Forty‐four members/associates of the International Primary Sclerosing Cholangitis Study Group (median experience in the care of primary sclerosing cholangitis patients: 14 years) completed the survey. The MRI interpretation significantly varied among the participants. The lowest agreement was found with respect to the indication to perform subsequent endoscopic retrograde cholangiopancreatography (ERCP; Κ = 0.12, 95% CI 0.11‐0.14). Elevated total bilirubin was the variable with the strongest effect on the rate of suspected dominant strictures, cholangiocarcinoma or ERCP recommendations. Liver cirrhosis did not prevent participants from recommending ERCP. Overall, the survey participants′ recommendations contrasted the real‐life management and outcome. Conclusions In primary sclerosing cholangitis, the interpretation of follow‐up MRI/3D‐MRCP significantly varies even among experts and seems to be primarily affected by bilirubin levels. Generally accepted MRI‐based definitions of primary sclerosing cholangitis‐related complications are urgently needed.

The prevalence of autoimmune liver diseases (AILD) is unknown in Germany. We therefore aimed to determine the population-based prevalence of AILD and to assess “real-life” treatment regimes.

The role of unconventional T cells like natural killer T (NKT) cells, gamma-delta (gd) T cells und mucosal associated invariant T (MAIT) was analyzed in human autoimmune liver diseases (AILD). So far, NKT cells have been mainly characterized in mouse models and are subdivided into pathogenic type I NKT cells and more protective type II NKT cells with immunoregulatory potential.

Sicherheit und Effektivität von endoskopischen Interventionen bei Patienten mit primär sklerosierender Cholangitis (PSC) und Leberzirrhose sind nicht ausreichend durch Studien untersucht.