Review
NAFLD: A multisystem disease

https://doi.org/10.1016/j.jhep.2014.12.012Get rights and content
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Summary

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that is predicted to become also the most frequent indication for liver transplantation by 2030. Over the last decade, it has been shown that the clinical burden of NAFLD is not only confined to liver-related morbidity and mortality, but there is now growing evidence that NAFLD is a multisystem disease, affecting extra-hepatic organs and regulatory pathways. For example, NAFLD increases risk of type 2 diabetes mellitus (T2DM), cardiovascular (CVD) and cardiac diseases, and chronic kidney disease (CKD). Although the primary liver pathology in NAFLD affects hepatic structure and function to cause morbidity and mortality from cirrhosis, liver failure and hepatocellular carcinoma, the majority of deaths among NAFLD patients are attributable to CVD. This narrative review focuses on the rapidly expanding body of clinical evidence that supports the concept of NAFLD as a multisystem disease. The review discusses the factors involved in the progression of liver disease in NAFLD and the factors linking NAFLD with other extra-hepatic chronic diseases, such as T2DM, CVD, cardiac diseases and CKD. The review will not discuss NAFLD treatments as these are discussed elsewhere in this issue of the Journal. For this review, PubMed was searched for articles using the keywords “non-alcoholic fatty liver disease” or “fatty liver” combined with “diabetes”, “cardiovascular (or cardiac) disease”, “cardiovascular mortality” or “chronic kidney disease” between 1990 and 2014. Articles published in languages other than English were excluded.

Abbreviations

AF
atrial fibrillation
ATGL
Adipose triglyceride lipase
AST/ALT
aspartate aminotransferase to alanine aminotransferase ratio
APRI
aspartate to platelet ratio index
CRP
C-reactive protein
CVD
cardiovascular disease
CGI-58
Comparative Gene Identification-58
CKD
chronic kidney disease
DAG
di-acyl glycerol
Di-P PA
di-palmitoyl phosphatidic acid
ELF
Enhanced Liver Fibrosis panel
FGF-21
fibroblast growth factor-21
FIB4
Fibrosis-4 Score
GFR
glomerular filtration rate
HCC
hepatocellular carcinoma
HF
heart failure
HR
hazard ratio
IRS-1
insulin receptor substrate-1
IL-6
interleukin 6
LCFAs
long chain fatty acids
LPA
lysophosphatidic acid
LV
left ventricular
MetS
metabolic syndrome
MRI
magnetic resonance imaging
MRS
magnetic resonance spectroscopy
NAFLD
non-alcoholic fatty liver disease
NHANES
National Health and Examination Survey
NASH
non-alcoholic steatohepatitis
NF-κB
nuclear factor-kappa B
OR
odds ratio
PTEN
phosphatase and tensin homolog
PA
phosphatidic acid
PAI-1
plasminogen activator inhibitor-1
PKCε
protein kinase Cε
T2DM
type 2 diabetes mellitus
TAG
triacylglycerol
TLR-4
toll-like receptor-4
TNF-α
tumour necrosis factor-α
VLDL
very-low-density lipoprotein

Keywords

Non-alcoholic fatty liver disease
Hepatocellular carcinoma
Type 2 diabetes
Insulin resistance
Cardiovascular disease
Cardiac disease
Cardiac arrhythmias
Chronic kidney disease

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