Dataset Information

Non-alcoholic fatty liver disease in 2016.

ABSTRACT:

Introduction

Non-alcoholic fatty liver disease is the commonest cause of liver disease worldwide, and is rapidly becoming the leading indication for liver transplantation.

Sources of data

Original articles, reviews and meta-analyses, guidelines.

Areas of agreement

NAFLD strongly correlates with obesity and insulin resistance; currently, the best management strategy is weight loss and treatment of the metabolic syndrome.

Areas of controversy

Recent data suggest that the presence of fibrosis and not non-alcoholic steatohepatitis (NASH) is the predictor of clinical outcome.

Growing points

Many phase 2 and 3 trials are underway. Drugs hoped to be effective are obeticholic acid, elafibranor, glucagon-like peptide-1 analogues and CCR2/5 inhibitors.

Areas timely for developing research

Improved understanding of the pathophysiology of NAFLD should help us identify which patients progress to significant liver disease and to develop therapies to target this population.

SUBMITTER: Townsend SA

PROVIDER: S-EPMC5862239 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Publications

Non-alcoholic fatty liver disease in 2016.

Townsend S A SA Newsome Philip N PN

British medical bulletin 20160819 1

<h4>Introduction</h4>Non-alcoholic fatty liver disease is the commonest cause of liver disease worldwide, and is rapidly becoming the leading indication for liver transplantation.<h4>Sources of data</h4>Original articles, reviews and meta-analyses, guidelines.<h4>Areas of agreement</h4>NAFLD strongly correlates with obesity and insulin resistance; currently, the best management strategy is weight loss and treatment of the metabolic syndrome.<h4>Areas of controversy</h4>Recent data suggest that t ...[more]

PMID: 27543499

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Project description:Background & Aims: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting non-invasive diagnosis and treatment before clinical sequelae emerge. We investigated whether DNA methylation profiles can distinguish patients with mild disease from those with advanced NAFLD, and how these patterns are functionally related to hepatic gene expression. Methods: We collected frozen liver biopsies and clinical data from patients with biopsy-proven NAFLD (56 in the discovery cohort and 34 in the replication cohort). Samples were divided into groups based on histologic severity of fibrosis: F0?1 (mild) and F3?4 (advanced). DNA methylation profiles were determined and coupled with gene expression data from the same biopsies; differential methylation was validated in subsets of the discovery and replication cohorts. We then analyzed interactions between the methylome and transcriptome. Results: Clinical features did not differ between patients known to have mild or advanced fibrosis based on biopsy analysis. There were 69,247 differentially methylated CpG sites (76% hypomethylated, 24% hypermethylated) in patients with advanced vs mild NAFLD (P<.05). Methylation at FGFR2, MAT1A, and CASP1 was validated by bisulfite pyrosequencing and the findings were reproduced in the replication cohort. Methylation correlated with gene transcript levels for 7% of differentially methylated CpG sites, indicating that differential methylation contributes to differences in expression. In samples with advanced NAFLD, many tissue repair genes were hypomethylated and overexpressed, whereas genes in certain metabolic pathways, including 1-carbon metabolism, were hypermethylated and under-expressed. Conclusions: Functionally relevant differences in methylation can distinguish patients with advanced vs mild NAFLD. Altered methylation of genes that regulate processes such as steatohepatitis, fibrosis, and carcinogenesis indicate the role of DNA methylation in progression of NAFLD. Three technical replicates were included for quality control along with 35 mild NAFLD (33 unique samples) and 24 advanced NAFLD (23 unique sample). One sample per technical duplication was randomly included for a total of 56 NAFLD samples used for study.

Dataset Information

Non-alcoholic fatty liver disease in 2016.

Introduction

Sources of data

Areas of agreement

Areas of controversy

Growing points

Areas timely for developing research

Publications

Non-alcoholic fatty liver disease in 2016.

Similar Datasets

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