Biliary Atresia: Clinical and Research Challenges for the Twenty‐First Century DOI Open Access
Jorge A. Bezerra, Rebecca G. Wells, Cara L. Mack

et al.

Hepatology, Journal Year: 2018, Volume and Issue: 68(3), P. 1163 - 1173

Published: March 31, 2018

Biliary atresia (BA) is a fibroinflammatory disease of the intrahepatic and extrahepatic biliary tree. Surgical hepatic portoenterostomy (HPE) may restore bile drainage, but progression results in complications portal hypertension advanced cirrhosis most children. Recognizing that further progress field unlikely without better understanding underlying cause(s) pathogenesis disease, National Institutes Diabetes Digestive Kidney Diseases (NIDDK) sponsored research workshop focused on innovative promising approaches identifying future areas research. Investigators discussed recent advances using gestational ultrasound newborn BA screening with serum direct (conjugated) bilirubin support prenatal onset injury. Experimental human studies implicate toxic properties environmental toxins (e.g., biliatresone) viruses cytomegalovirus) to system. Among host factors, sequence variants genes related development ciliopathies, notable lack cholangiocyte glycocalyx submucosal collagen bundles neonatal ducts, an innate proinflammatory bias immune system contribute increased susceptibility damage obstruction following epithelial These form foundation for agenda factor(s) cause BA, potential use population screening, mechanisms prominent fibrosis young infants, determinations clinical surrogates progression, design trials target subgroups patients initial drainage HPE. (Hepatology 2018; 00:000-000).

Language: Английский

Recent Insights into the Pathogenesis of Nonalcoholic Fatty Liver Disease DOI Open Access
Juan Pablo Arab, Marco Arrese, Michael Trauner

et al.

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2018, Volume and Issue: 13(1), P. 321 - 350

Published: Jan. 24, 2018

Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic cardiometabolic mortality. The rapidly increasing prevalence of this its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches based on profound understanding pathogenesis to halt progression advanced fibrosis or cirrhosis cancer. NAFLD involves complex interaction among environmental factors (i.e., Western diet), obesity, changes in microbiota, predisposing genetic variants resulting disturbed lipid homeostasis excessive accumulation triglycerides other species hepatocytes. Insulin resistance central mechanism that leads lipotoxicity, endoplasmic reticulum stress, autophagy, and, ultimately, hepatocyte injury death triggers inflammation, stellate cell activation, progressive fibrogenesis, thus driving progression. In the present review, we summarize currently available data NAFLD, emphasizing most recent advances. A better NAFLD/NASH crucial design new efficient interventions.

Language: Английский

Citations

482
The role of the microbiome in NAFLD and NASH DOI Creative Commons
Aleksandra A. Kolodziejczyk,

Danping Zheng,

Oren Shibolet

et al.

EMBO Molecular Medicine, Journal Year: 2018, Volume and Issue: 11(2)

Published: Dec. 27, 2018

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of cardiometabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. It rapidly becoming most prevalent worldwide. A sizable minority NAFLD patients develop nonalcoholic steatohepatitis (NASH), characterized by inflammatory changes that can lead to progressive damage, cirrhosis, hepatocellular carcinoma. Recent studies have shown in addition genetic predisposition diet, gut microbiota affects carbohydrate lipid metabolism as well influences balance between pro-inflammatory anti-inflammatory effectors liver, thereby impacting its progression NASH In this review, we will explore impact microbiota-derived compounds on development NASH, unexplored factors related potential microbiome contributions common disease.

Language: Английский

Citations

445
Bile Acid Metabolism in Liver Pathobiology DOI
John Y.L. Chiang, Jessica M. Ferrell

Gene Expression, Journal Year: 2018, Volume and Issue: 18(2), P. 71 - 87

Published: Jan. 12, 2018

Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver other tissues cells from toxicity. metabolism tightly regulated by synthesis in the biotransformation intestine. are endogenous ligands that activate a complex network of nuclear receptor farnesoid X membrane G protein-coupled receptor-1 regulate hepatic lipid glucose metabolic homeostasis energy metabolism. The gut-to-liver axis plays critical role regulation enterohepatic circulation acids, pool size, composition. control gut bacteria overgrowth, metabolize host Alteration high-fat diets, sleep disruption, alcohol, drugs reshapes microbiome causes dysbiosis, obesity, disorders. Gender differences metabolism, FXR signaling, microbiota have been linked higher prevalence fatty disease hepatocellular carcinoma males. contributes cholestatic diseases, inflammatory diseases digestive system, diabetes. acid-activated receptors potential therapeutic targets developing treat

Language: Английский

Citations

420
Determinants of fibrosis progression and regression in NASH DOI

Detlef Schuppan,

Rambabu Surabattula, Xiaoyu Wang

et al.

Journal of Hepatology, Journal Year: 2017, Volume and Issue: 68(2), P. 238 - 250

Published: Nov. 14, 2017

Language: Английский

Citations

419
A metabolic pathway for bile acid dehydroxylation by the gut microbiome DOI

Masanori Funabashi,

Tyler L. Grove, Min Wang

et al.

Nature, Journal Year: 2020, Volume and Issue: 582(7813), P. 566 - 570

Published: June 17, 2020

Language: Английский

Citations

385
NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial DOI
Stephen A. Harrison, Mary E. Rinella, Manal F. Abdelmalek

et al.

The Lancet, Journal Year: 2018, Volume and Issue: 391(10126), P. 1174 - 1185

Published: March 1, 2018

Language: Английский

Citations

381
Nonalcoholic Fatty Liver Disease: Basic Pathogenetic Mechanisms in the Progression From NAFLD to NASH DOI Open Access

I. Pierantonelli,

Gianluca Svegliati‐Baroni

Transplantation, Journal Year: 2018, Volume and Issue: 103(1), P. e1 - e13

Published: Oct. 9, 2018

Nonalcoholic fatty liver disease (NAFLD) represents a growing cause of chronic injury, especially in western countries, where it is becoming the most frequent indication for transplantation. encompasses spectrum diseases that from simple steatosis (pure NAFLD) can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. The pathogenesis NAFLD mechanisms behind its progression NASH have been extensively studied. However, although processes determine fat accumulation are mostly clear, associated with not fully characterized. In predisposed patients, lipid promote lipotoxicity mitochondrial dysfunction, thus triggering hepatocyte death, inflammation fibrosis. specific role different lipids has identified free acids as well cholesterol toxic species. To make picture more complex, involves pathological connections between several organs, including adipose tissue gut, liver. "inflamed" plays key release lipids, whereas alterations gut-liver axis mediated by dysbiosis, alteration intestinal barrier, finally bacterial translocation, which trigger proinflammatory profibrogenetic pathways, leading development.

Language: Английский

Citations

377
Role of Bile Acids in Metabolic Control DOI
Antonio Molinaro, Annika Wahlström, Hanns‐Ulrich Marschall

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2017, Volume and Issue: 29(1), P. 31 - 41

Published: Nov. 29, 2017

Language: Английский

Citations

376
Interactions between Bacteria and Bile Salts in the Gastrointestinal and Hepatobiliary Tracts DOI Creative Commons

Verónica Urdaneta,

Josep Casadesús

Frontiers in Medicine, Journal Year: 2017, Volume and Issue: 4

Published: Oct. 3, 2017

Bile salts and bacteria have intricate relationships. The composition of the intestinal pool bile is shaped by bacterial metabolism. In turn, play a role in homeostasis controlling size microbiota. As consequence, alteration microbiome-bile salt can hepatic gastrointestinal pathological conditions. Intestinal use as environmental signals certain cases nutrients electron acceptors. However, are antibacterial compounds that disrupt membranes, denature proteins, chelate iron calcium, cause oxidative damage to DNA, control expression eukaryotic genes involved host defense immunity. Bacterial species adapted mammalian gut able endure activities multiple physiological adjustments include remodeling cell envelope activation efflux systems stress responses. Resistance permits bile-resistant pathogens colonize hepatobiliary tract, an outstanding example chronic infection gall bladder

Language: Английский

Citations

371
Targeting the gut-liver axis in liver disease DOI Creative Commons

Reiner Wiest,

Agustı́n Albillos, Michael Trauner

et al.

Journal of Hepatology, Journal Year: 2017, Volume and Issue: 67(5), P. 1084 - 1103

Published: May 16, 2017

Summary

The gut-liver axis is widely implicated in the pathogenesis of liver diseases, where it increasingly focus clinical research. Recent studies trialling an array therapeutic and preventative strategies have yielded promising results. Considering these strategies, armamentarium for targeting will continue to expand. Further trials, translated from our current knowledge axis, promise exciting future treatment.

Language: Английский

Citations

364