Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries

Table 1 Peripheral biomarkers used for the assessment of necro-inflammation and fibrotic injury in non-alcoholic fatty liver disease

Pathogenic mechanism	Biomarker		NASH	Advanced fibrosis	Ref.
Hepatocyte apoptosis	Apoptotic markers	CK-18 ↑	X		El Bassat et al[11]
		sFas ↑	X
Oxidative stress	Lipid peroxidation products	Ox-LDL ↑	X		Kawanaka et al[12]
		TBARS ↑	X		Machado et al[13]
		MDA ↑	X
		HNE ↑	X
	Indicators of altered redox potential	GSH ↑	X
		SOD ↓	X
		TRX ↑	X
Chronic inflammation	Acute phase reactants	CRP	X		Jarrar et al[14]
		Ferritin	X		Braunersreuther et al[15]
		PTX3	X
	Adipocytokines	Leptin	X
		Adiponectin		X
		TNF-α	X
		IL-1β	X
		IL-6		X
		TGF-α/β1	X
Increased hepatocellular turnover	Extracellular matrix components	HA		X	Baranova et al[16]
		Laminin		X
		Type IV collagen 7S		X
		PIIINP		X
		MMP-2/9		X
		TIMP-1		X

CK-18: Cytokeratin-18; sFAS: Soluble Fas; Ox-LDL: Oxidized low-density lipoprotein cholesterol; TBARS: Thiobarbituric acid reactive substances; MDA: Malondialdehyde; HNE: Hydroxynonenal; GSH: Reduced glutathione; SOD: Superoxide dismutase; TRX: Thioredoxin; CRP: C-reactive protein; PTX3: Pentraxin 3; TNF-α: Tumor necrosis factor α; IL: Interleukin; TGF: Transforming growth factor; HA: Hyaluronic acid; NASH: Non-alcoholic steatohepatitis; MMP: Matrix metalloproteinase; PIIINP; Procollagen 3 n-terminal propeptide; TIMP: Tissue inhibitor of metalloproteinase.

Table 2 Composite diagnostic models for non-alcoholic steatohepatitis

Biomarker panel	Components	Formula	AUC	Ref.
HAIR score	Hypertension	Weighted sum (0-4)	0.9	Dixon et al[52]
	Elevated ALT (> 40 IU/L)
	Insulin Resistance (index > 5)
Gholam's model	DM II	Algorithm	0.9	Gholam et al[53]
	AST level
NASH clinical scoring system for morbid obesity	Hypertension	Weighted sum (0-7)	Not reported	Campos et al[54]
	DM II
	Elevated AST (> 27 IU/L)
	Elevated ALT (> 27 IU/L)
	OSA
	non-black race
Ulitsky's score	DM II	Weighted sum (0-5)	Not reported	Ulitsky et al[55]
	Elevated ALT (> 40 IU/L)
	Elevated triglycerides (> 150 mg/dL)
	OSA
NASH predictive index	Female sex	Algorithm	0.78	Zein et al[56]
	Body mass index
	HOMA-IR
	AST levels
	ALT levels

AUC: Area under curve; ALT: Alanine aminotransferase; DM II: Diabetes mellitus type II; AST: Aspartate aminotransferase; OSA: Obstructive sleep apnoea; HOMA-IR: Homeostatic Measurement Assessment of Insulin Resistance; NASH: Non-alcoholic steatohepatitis.

Table 3 Composite predictive models for advanced hepatic fibrosis in chronic liver disease

Biomarker panel	Components	Formula	Validated in adult NAFLD	Ref.
APRI index	AST, platelet count	Ratio	√	Kruger et al[96]
BAAT score	Age, BMI, ALT, triglycerides	Weighted sum	√	Ratziu et al[97]
BARD score	BMI, AST, ALT, DM II	Weighted sum	√	Harrison et al[98]
Cirrhosis discrimination score	AST, ALT, platelet count, INR	Weighted sum	×	Udell et al[99]
FIB-4 index	Age, AST, ALT, platelet count	Algorithm	√	Shah et al[100]
Fibrosis probability index	Age, AST, previous alcohol use, HOMA-IR, cholesterol	Algorithm	×	Sud et al[101]
Forns index	Age, platelet count, GGT, cholesterol	Algorithm	√	Forns et al[102]
Gholam's score	ALT, HbA1C	Weighted score	√	Gholam et al[53]
Hui model	BMI, bilirubin, albumin, platelet count	Algorithm	×	Hui et al[103]
King score	Age, AST, platelet count, INR	Algorithm	×	Cross et al[104]
Lok index	AST, ALT, platelet count, INR	Algorithm	×	Lok et al[105]
NAFLD fibrosis score	Age, BMI, platelet count, albumin, AAR, IFG/DM II	Algorithm	√	Angulo et al[106]

NAFLD: Non-alcoholic fatty liver disease; APRI: Aspartate aminotransferase to platelet ratio index; AST: Aspartate aminotransferase; BMI: Body mass index; ALT: Alanine aminotransferase; DM II: Diabetes mellitus type II; HOMA-IR: Homeostatic Measurement Assessment of Insulin Resistance; IFG: Impaired fasting glucose; GGT: Gamma glutamyl-transferase; INR: International normalized ratio; AAR: AST/ALT ratio.