Nonalcoholic fatty liver disease: A comprehensive review of a growing epidemic

Table 1 Genes and proteins Implicated in non-alcoholic fatty liver disease

Gene	Protein	Function
APOc3	Apolipoprotein C3	Surface component of VLDL and inhibits LPL[227]
ATGL	Adipose triglyceride lipase	Catalyzes the initial step in triglyceride hydrolysis[228]
CGI-58	Comparative Gene Identification-58	Activator of triglyceride hydroxylases (including ATGL)[228]
GCKR	Glucokinase regulatory Protein	Downregulation of glucokinase[229]
LXR	Liver X Receptor	Transcription factor for numerous target genes involved in glucose and lipid metabolism[230]
PNPLA3	Palatin-like phospholipase-containing protein 3	Unknown, possible triglyceride hydroxylase[16]
PPARα	Peroxisome proliferator-activated receptor α	Nuclear receptor that promotes the catabolism of fatty acids[231]
PPARγ	Peroxisome Proliferator-Activated Receptor γ	Nuclear receptor that promotes storage and processing of fatty acids[232]
PPP1R3B	Glycogen Binding Subunit of Protein Phosphatase 1	Subunit in Protein Phosphatase which activates glycogen synthase[233]
SBERP1c	Sterol regulatory element-binding protein	Transcription factor for genes involved in de novo lipogenesis[234]

ATGL: Adipocyte TG lipase; LPL: Lipoprotein lipase; VLDL: Very-low-density lipoproteins.

Table 2 Summary of included variables in scoring methods for non-alcoholic fatty liver disease

	NAFLD Fibrosis Score	Fibrotest	FIB-4	ELF	BARD	NICE	NASH test
Age	×	×	×	×			×
BMI	×				×
AST	×		×		×		×
ALT	×		×		×	x	×
Platelet Count	×		×
Albumin	×
α2-MG		×					×
Total bilirubin		×					×
Apo A1		×					×
GGT		×					×
PIIINP				×
HA				×
TIMP				×
DM					×
MS						×
CK-18						×
Sex							×
Height							×
Weight							×
HG							×
TGL							×
CL							×

α2-MG: α2 macroglobulin; ALT: Alanine aminotransferase; ApoA1: Apolipoprotein A1; AST: Aspartate aminotransferase; BMI: Body mass index; CK-18: Cytokeratin-18; CL: Cholesterol levels; DM: Diabetes mellitus; ELF: European Liver Fibrosis Test; GGT: Gamma-glutamyl transpeptidase; HA: Hyaluronic acid; HG: Haptoglobin; MS: Metabolic syndrome; PIIINP: Aminoterminal propeptide of type III collagen; TGL: Triglyceride levels; TIMP: Tissue inhibitor of metalloproteinases; NASH: Nonalcoholic steatohepatitis.

Table 3 Statistical analysis of various scoring methods for non-alcoholic fatty liver disease

	NAFLD fibrosis score	Fibrotest	FIB-4	ELF	BARD	NICE	NASH test
AUROC	0.84	0.75-0.86	0.86	0.87	0.81	0.88	0.79
Sens (%)	82	77	85	89		84	33
Spec (%)	98	98	65	96		86	94
PPV (%)	90	90	36	80	43	44	66
NPV (%)	93	73	95	98	96	98	81

NAFLD: Nonalcoholic fatty liver disease; AUROC: Area under the receiver operating characteristic curve; ELF: European Liver Fibrosis Test; PPV: Positive predictive value; NPV: Negative predictive value; Sens: Sensitivity; Spec: Specificity; NASH: Nonalcoholic steatohepatitis.