Role of Tissue Biopsy in Drug Development for Nonalcoholic Fatty Liver Disease and Other Metabolic Disorders

2019 ◽  
pp. 245-274
Author(s):  
Andrew J. Krentz ◽  
Pierre Bedossa
Keyword(s):  
Liver Disease ◽  
Drug Development ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Nonalcoholic Fatty Liver ◽  
Tissue Biopsy

scholarly journals Nonalcoholic fatty liver disease and the gut microbiome: Are bacteria responsible for fatty liver?

2019 ◽  
Vol 244 (6) ◽  
pp. 408-418 ◽  
Author(s):  
Tien S Dong ◽  
Jonathan P Jacobs
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Metabolic Disorders ◽  
Microbial Composition ◽  
Future Directions ◽  
Nonalcoholic Fatty Liver

Over the last several years, a growing body of literature has linked the gut microbiome to human health and diseases such as obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). This paper will review the current literature investigating the influence of diets associated with metabolic disorders on the microbiome and how those changes promote susceptibility to metabolic disorders. It will then focus in-depth on the role of the gut microbiome in NAFLD. The review will highlight associations of microbial composition and function with progression of NAFLD in patients and discuss potential mechanisms that link the gut microbiome to NAFLD. Finally, it will address limitations of existing studies along with future directions for microbiome research in NAFLD, including potential microbe-related treatments. Impact statement This invited minireview for the upcoming thematic issue on the microbiome addresses the role of the microbiome in nonalcoholic fatty liver disease (NAFLD). The incidence of NAFLD has increased greatly in recent years in parallel with the rise in obesity and is now believed to have a population prevalence of 20–40%. It is anticipated to soon become the primary cause of liver-related morbidity and mortality, and unfortunately, there are few treatment options. Therefore, there is a critical need for improved understanding of NAFLD pathophysiology to provide new avenues for therapeutic intervention. In this paper, we have reviewed evidence from human and animal model studies that have associated microbiome composition and microbial metabolites with development and progression of NAFLD. We have also discussed proposed mechanisms by which the microbiome could contribute to NAFLD pathogenesis and addressed future directions for this field.

scholarly journals Role of Docosahexaenoic Acid Treatment in Improving Liver Histology in Pediatric Nonalcoholic Fatty Liver Disease

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e88005 ◽  
Author(s):  
Valerio Nobili ◽  
Guido Carpino ◽  
Anna Alisi ◽  
Rita De Vito ◽  
Antonio Franchitto ◽  
...  
Keyword(s):  
Liver Disease ◽  
Docosahexaenoic Acid ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Acid Treatment ◽  
Liver Histology ◽  
Nonalcoholic Fatty Liver

scholarly journals Role of folate in nonalcoholic fatty liver disease

2017 ◽  
Vol 95 (10) ◽  
pp. 1141-1148 ◽  
Author(s):  
Victoria Sid ◽  
Yaw L. Siow ◽  
Karmin O
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Serum Folate ◽  
Nonalcoholic Fatty Liver ◽  
Obesity And Diabetes

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.

scholarly journals Efficacy of Ursodeoxycholic Acid in Nonalcoholic Fatty Liver Disease: An Updated Meta-Analysis of Randomized Controlled Trials

2019 ◽  
Author(s):  
Wenyue Zhang ◽  
Yao Tang ◽  
Juan Huang ◽  
Hong Ren ◽  
Yixuan Yang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Ursodeoxycholic Acid ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Total Bilirubin ◽  
Meta Analysis ◽  
Nonalcoholic Fatty Liver ◽  
Randomized Controlled

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a kind of chronic liver disease among general population. Recent years, more and more new experiments have made the role of ursodeoxycholic acid (UDCA) become clearer. In this meta-analysis, we analyzed the efficacy of ursodeoxycholic acid (UDCA) for the treatment of nonalcoholic fatty liver disease (NAFLD). Methods We searched the Web of Science, Pubmed, Embase and Cochrane library databases for relavent studies published before March 1, 2019. We examined 134 randomized controlled trials (RCTs) that investigated the effectiveness of UDCA in NAFLD against placebo or other treatments. Next, we conducted meta-analysis by Stata(version 12.0) to examine the change among several indices: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), Alkaline phosphatase (AP), total bilirubin and albumin. Results Following the application of different inclusion and exclusion criteria, 9 articles with 1106 participants were finally selected. The forest plot displayed that UDCA treatment can significantly decrease the ALT levels among the NAFLD patients (SMD=0.17,95%CI [0.03 to 0.3], P=0.07). However, UDCA treatment did not significantly affect the AST, GGT, AP, total bilirubin and albumin levels. Further, the subgroup analyses suggested the significant role of UDCA treatment in different geographical regions, age group and treatment duration (P=0.003 in people from Europe, P=0.001 in people older than 50 years and P=0.008 in longer duration(>6 months)). Conclusion In this study, several indices we analyzed among 9 articles. UDCA treatment was found beneficial in lowering the ALT levels in NAFLD patients. The remaining indices like AST, GGT, AP showed non-significant changes in this analysis. This could be attributed for the insufficient number of trials because all parameters were not analyzed in each individual RCT. Therefore, future meta-analysis will be required to fully confirm and validate the efficacy of UDCA in NAFL.

scholarly journals Role of insulin resistance in the pathogenesis of nonalcoholic fatty liver disease

2010 ◽  
Vol 18 (30) ◽  
pp. 3175
Author(s):  
Bing-Fang Wang ◽  
Pei-Ying Tian ◽  
Kun Feng ◽  
Fu-Rong Wu ◽  
Yong-Gao Lu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

scholarly journals Role of Bile Acids in Dysbiosis and Treatment of Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Caihua Wang ◽  
Chunpeng Zhu ◽  
Liming Shao ◽  
Jun Ye ◽  
Yimin Shen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Bile Acid Receptors

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.

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