Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease in industrialized economies. With no licensed treatment currently available, together with a growing prevalence that parallels global increases in obesity and type 2 diabetes, NAFLD will dominate the landscape of hepatology for the foreseeable future. A multifaceted etiopathogenesis, paucity of reproducible preclinical models that effectively recreate human NAFLD, and lack of robust surrogate trial endpoints have presented major hurdles in drug discovery and development. Smooth collaboration between bench scientists, biotechnology, pharmaceutical industries, and clinicians will be pivotal to target identification, development of effective therapies, biomarker discovery, and ultimately to bring pipeline drugs to market. This review examines the key challenges remaining in NAFLD drug development, outlines early and late phase clinical trials of candidate treatments, and discusses the journey toward biomarker discovery which may facilitate development of novel endpoints in NAFLD clinical trials, enabling meaningful response to be determined noninvasively.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728526 | PMC |
| http://dx.doi.org/10.1016/j.jceh.2019.03.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
New Hydrogenated Phenanthrene Glycosides from the Edible Vegetable W.T.Wang with DPP-IV Inhibitory and Hepatoprotective Activity.
J Agric Food Chem
January 2025
Ph.D. Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
Based on molecular networking-guided isolation, 15 previously undescribed hydrogenated phenanthrene glycosides, including eight hexahydro-phenanthrenone glycosides, four tetrahydro-phenanthrenone glycosides, one dihydro-phenanthrenol glycoside, two dimers, and two known dihydrophenanthrene glycosides, were isolated from W.T.Wang, a popular regional edible vegetable at the northwest region of Vietnam.
View Article and Find Full Text PDFModulating intestinal neuroimmune VIPergic signaling attenuates the reduction in ILC3-derived IL-22 and hepatic steatosis in MASLD.
Hepatol Commun
November 2024
Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as NAFLD) is a major driver of cirrhosis and liver-related mortality. However, therapeutic options for MASLD, including prevention of liver steatosis, are limited. We previously described that vasoactive intestinal peptide-producing neurons (VIP-neurons) regulate the efficiency of intestinal dietary fat absorption and IL-22 production by type 3 innate lymphoid cells (ILC3) in the intestine.
View Article and Find Full Text PDFAssociation of gut microbiota and gut metabolites and adverse outcomes in biliary atresia: A longitudinal prospective study.
Hepatol Commun
November 2024
Paediatric Liver, GI and Nutrition Centre and Mowatlabs, King's College Hospital, London, UK.
Background: The Kasai portoenterostomy (KPE) aims to re-establish bile flow in biliary atresia (BA); however, BA remains the commonest indication for liver transplantation in pediatrics. Gut microbiota-host interplay is increasingly associated with outcomes in chronic liver disease. This study characterized fecal microbiota and fatty acid metabolites in BA.
View Article and Find Full Text PDFFAK inhibition delays liver repair after acetaminophen-induced acute liver injury by suppressing hepatocyte proliferation and macrophage recruitment.
Hepatol Commun
November 2024
Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
Background: Overdose of acetaminophen (APAP), a commonly used antipyretic analgesic, can lead to severe liver injury and failure. Current treatments are only effective in the early stages of APAP-induced acute liver injury (ALI). Therefore, a detailed examination of the mechanisms involved in liver repair following APAP-induced ALI could provide valuable insights for clinical interventions.
View Article and Find Full Text PDFPost-translational modifications drive the effects of HMGB1 in alcohol-associated liver disease.
Hepatol Commun
November 2024
Department of Pathology, University of Illinois Chicago, Chicago, Illinois, USA.
Background: We previously identified that high-mobility group box-1 (HMGB1) is increased and undergoes post-translational modifications (PTMs) in response to alcohol consumption. Here, we hypothesized that specific PTMs, occurring mostly in hepatocytes and myeloid cells, could contribute to the pathogenesis of alcohol-associated liver disease (AALD).
Methods: We used the Lieber-DeCarli (LD) model of early alcohol-induced liver injury, combined with engineered viral vectors and genetic approaches to regulate the expression of HMGB1, its PTMs (reduced [H], oxidized [O], acetylated [Ac], both [O + Ac]), and its receptors (RAGE, TLR4) in a cell-specific manner (hepatocytes and/or myeloid cells).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!