Liver infiltrating T cells regulate bile acid metabolism in experimental cholangitis

In primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), T cells are likely involved in targeting biliary epithelial cells [1]. Chronic bile duct inflammation leads to cholestasis, biliary fibrosis and potential malignant transformation in the case of PSC [2]. Adaptive immune responses are considered to contribute to early as well as late stages of disease [3]. Numerous genetic risk loci for PBC and PSC were identified that encode for genes involved in adaptive immune responses [4 –6] and portal infiltrates that were predominantly composed of CD4+ and CD8+ T cells have been described in the livers of PBC and PSC patients [7–9].
Source: Journal of Hepatology - Category: Gastroenterology Authors: Source Type: research

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walder Luedde The IκBKinase (IKK) complex represents a central signaling nexus in the TNF-dependent activation of the pro-inflammatory NF-κB pathway. However, recent studies suggested that the distinct IKK subunits (IKK, IKK, and NEMO) might withhold additional NF-κB-independent functions in inflammation and cancer. Here, we generated mice lacking all three IKK subunits in liver parenchymal cells (LPC) (IKK//NEMOLPC-KO) and compared their phenotype with mice lacking both catalytic subunits (IKK/LPC-KO), allowing to functionally dissect putative I-κB-Kinase-independent function...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Semin Liver Dis DOI: 10.1055/s-0039-1688501The authors conducted a systematic review and meta-analysis to assess the effect of antibiotic therapy in primary sclerosing cholangitis (PSC). Effect of antibiotic therapy on Mayo PSC Risk Score (MRS), serum alkaline phosphatase (ALP), total serum bilirubin (TSB), and adverse events (AEs) rates were calculated and expressed as standardized difference of means or proportions. Five studies including 124 PSC patients who received antibiotics were included. Overall, antibiotic treatment was associated with a statistically significant reduction in ALP, MRS, and TSB by 33.2, 36.1, and ...
Source: Seminars in Liver Disease - Category: Gastroenterology Authors: Tags: Review Article Source Type: research
ConclusionNeonatal cholestasis poses diagnostic challenges in practice. Recent advances in the pathophysiology and in molecular genetics together with clinical features, histopathologic findings and careful reasoning remains paramount to put together the pieces of the jigsaw.
Source: Italian Journal of Pediatrics - Category: Pediatrics Source Type: research
Publication date: May–June 2019Source: Journal of Clinical and Experimental Hepatology, Volume 9, Issue 3Author(s): Joseph J. Valamparampil, Kshetra Rinaldhy, Mettu Srinivas Reddy, Naresh Shanmugam, Mohamed Rela
Source: Journal of Clinical and Experimental Hepatology - Category: Gastroenterology Source Type: research
ConclusionsThe metabolisms of urinary Bas were altered in the AHP group compared with the ICP group and the control group. Urinary BA profiling analysis can serve as an effective tool for the diagnosis of AHP and the differential diagnosis of AHP and ICP.
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research
Niemann-Pick disease type C (NP-C) is an inherited neurodegenerative disease (1 per 100 000 newborns) caused by NPC proteins impairment that leads to unesterified cholesterol accumulation in late endosomal/lys...
Source: BMC Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Research article Source Type: research
FOSTER CITY, Calif., July 9, 2019 /PRNewswire/ -- Mirum Pharmaceuticals today announced the dosing of the first patient in the Phase 3 MARCH-PFIC clinical trial of its lead drug candidate, maralixibat, in pediatric patients with...
Source: - Clinical Trials - Category: Pharmaceuticals Source Type: clinical trials
CONCLUSION: Among others, efforts have continued to focus on BSEP, as it is the primary route for hepatic biliary clearance. In addition to inhibition, drug-induced BSEP repression or the combination of these two has emerged as important alternative mechanisms leading to DIC. Furthermore, there has been an evolution in the approaches to studying DIC including 3D cell cultures and computational modeling. PMID: 31288715 [PubMed - as supplied by publisher]
Source: Current Drug Metabolism - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Metab Source Type: research
CONCLUSION: Children with IFALD are at risk for vitamin K deficiency during cholestasis reversal. Close monitoring and quantified supplementation of vitamin K may be warranted during this period. However, this should not be guided by INR alone, as it is a poor indicator of vitamin K status. PMID: 31282035 [PubMed - as supplied by publisher]
Source: JPEN Journal Of Parenteral And Enteral Nutrition - Category: Nutrition Authors: Tags: JPEN J Parenter Enteral Nutr Source Type: research
In this study, the mitotoxic potentials of BA mixtures were assessed in isolated mitochondria and a better-suited hepatic model, HepaRG cells. BAs induced structural alterations and a loss of mitochondrial membrane potential (MMP) in isolated mitochondria however, this toxicity did not translate to HepaRG cells. There were no changes in oxygen consumption rate, MMP or ATP levels in glucose and galactose media, indicating that there was no direct mitochondrial toxicity mediated via electron transport chain dysfunction in HepaRG cells. Assessment of key biliary transporters revealed that there was a time-dependent reduction ...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research
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