Non invasive tools for the diagnosis of liver cirrhosis

Table 1 Histology activity index for staging liver fibrosis according to various scores

	No fibrosis	Fibrous portal expansion	Portal/periportal fibrosis	Portal fibrosis with rare septa	Abundant bridging fibrosis	Marked bridging with occasional nodules	Cirrhosis
Knodell et al[16]	F0	F1	F1	F3	F3	F4	F4
Scheuer et al[17]	F0	F1	F2	F2	F3	F3	F4
IASL[18]	F0	F1	F2	F2	F3	F3	F4
Ishak et al[19]	F0	F1	F2	F3	F4	F5	F6
METAVIR[20]	F0	F1	F1	F2	F3	F4	F4

IASL: International Association for the Study of the Liver.

Table 2 Principal scoring systems taking into account the parameters used in calculating the scores, etiology of liver disease and sensitivity and specificity values of the tests

Test	Parameters	Etiology	Sensitivity	Specificity
Age-platelet index (AP)[55]	Age, platelet count	HCV	52%	93%
APRI[56]	AST/platelet count	HCV	57%	93%
ASPRI[57]	Age, spleen diameter, platelet count	HBV	75%	90%
AST/ALT ratio[58]	Aspartate aminotransferase, alanine aminotransferase	HBV	51%	71%
BARD score[59]	BMI, AST/ALT ratio, diabetes	NAFLD	62%	66%
Bonacini-index (Cirrhosis discriminant score - CDS)[60]	ALT/AST ratio, INR, platelet count	HCV	46%	98%
ELF and simplified ELF index[61]	Age, Hyaluronic acid, N-terminal propeptide of type II collagen, and TIMP-1 levels	Mixed	90%	69%
FIB-4[62]	Platelet count, AST, ALT, age	HIV/HCV	65%	97%
Fibro-α score[63]	Platelet count, AST, ALT, α-fetoprotein level	HCV	90%	57%
Fibroindex[64]	Platelet count, AST, γ-globulin	HCV	35%	97%
Fibrometer test[65]	Platelet count, prothrombin index, AST, α2-macro-globulin, hyaluronan,urea, age	VirusAlcohol	80%91%	84%92%
Fibrometer NAFLD[66]	Glucose, AST, ALT, ferritin, platelet count, body weight, age	NAFLD	79%	96%
Fibronectin discriminant score[67]	Platelet count, AST, Albumin and fibronectin levels	HCV	87%	75%
FibroQ[68]	Age, platelet count, AST, ALT, Prothrombin index	HBV/HCV	79%	71%
Fibrosis-cirrhosis index[69]	Platelet count, Alkaline phosphatase, bilirubin, albumin levels	HCV	86%	80%
Fibrosis index[70]	Platelet count, Albumin level	HCV	67%	97%
Fibrosis probability index(Sud index)[71]	Age, AST, Total cholesterol level, insulin resistance and alcohol intake	HCV	73%	74%
Fibrosis Routine Test[72]	Age, platelet count, AST, α-fetoprotein and albumin levels	HCV	83%	73%
FibroSpect II[73]	hyaluronan, TIMP-1,α2-macroglobulin	HCV	76%	73%
Fibrotest[74]	Haptoglobin, α2-macroglobulin, apolipoprotein A1, γGT, bilirubin, gender	HCV	75%	85%
Forns-index[75]	Age, platelet count, γGT, cholesterol	HCV	30%	95%
Globulin-albumin ratio[76]	Globulin and albumin levels	HCV	43%	98%
GUCI[77]	Platelet count, AST, Prothrombin index	HCV	80%	78%
HALT-C model[78]	Platelet count, TIMP-1 and hyaluronic acid levels	HCV	71%	80%
Hepascore[79]	Bilirubin, γGT, hyaluronan, α2-macroglobulin, age, gender	HCV	84%	71%
King’s score[80]	Age, platelet count, AST, INR	HCV	86%	80%
Lok index[81]	Platelet count, AST, ALT, INR	HCV	68%	72%
MP3 score[82]	MMP-1 and PIIIP levels	HCV	60%	92%
NAFLD fibrosis score[83]	Age, hyperglycemia, BMI, platelet count, albumin, AST/ALT ratio (dual cut-offs)	NAFLD	77%	96%
Pohl index[84]	Platelet count, AST, ALT	HCV	41%	99%
Sabadell NIHCED index[85]	Age, platelet count, AST, ALT, Prothrombin time, right hepatic lobe atrophy, splenomegaly, and caudate lobe hypertrophy	HCV	80%	96%
Significant fibrosis index[86]	Haptoglobin, α2-macroglobulin, TIMP-1, MMP-2, and GGT levels	HBV/HCV	71%	80%
VITRO score[87]	vWF-Ag, platelet count	HCV	83%	79%
Zeng index[88]	Age, α2-Macroglobulin, GGT, and hyaluronic acid levels	HBV	40%	90%

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; BMI: Body mass index; ELF: Enhanced liver fibrosis; NAFLD: Non-alcoholic fatty liver disease; TIMP: Tissue inhibitors of metalloproteinases; MMP-1: Matrix metalloproteinase-1; GGT: γ-glutamyl transferase.

Table 3 Diagnostic reliability acoustic radiation force impulse for liver fibrosis and optimal cut-offs

Ref.	Patients analyzed by ARFI (n)	Etiology	F≥2				F≥3				F = 4
			Cut-off m/s	Se%	Sp%	AUROC	Cut-off m/s	Se%	Sp%	AUROC	Cut-off m/s	Se%	Sp%	AUROC
Fierbinteanu-Braticevici et al[159]	74	HCV	1.22	100	71	0.91	1.54	97	100	0.99	1.94	100	98	0.99
Friedrich-Rust et al[160]	81	HCV/HBV	1.37	69	92	0.82	1.45	84	86	0.91	1.75	82	91	0.91
Lupsor et al[161]	102	HCV	1.34	68	93	0.86	1.61	79	95	0.91	2.00	80	95	0.94
Yoneda et al[162]	54	NASH					1.77	100	91	0.97	1.91	100	96	0.98
Piscaglia et al[156]	70	Mixed	1.63	59	100	0.79	1.67	75	97	0.91	1.87	81	91	0.91
Rizzo et al[163]	139	HCV	1.31	81	70	0.86	1.71	91	86	0.94	2.11	83	86	0.89
Sporea et al[164]	199	Mixed	1.27	89	68	0.89	1.56	80	89	0.88	1.71	93	87	0.93
Sporea et al[154]	93	Mixed	1.41	71	78	0.77	1.69	73	88	0.79	1.81	100	88	0.92
Sporea et al[165]	911	HCV	1.33	69	80	0.80	1.43	75	81	0.82	1.55	84	76	0.84

Se: Sensitivity; Sp: Specificity; AUROC: Area Under Receiver Operating Characteristic; F: METAVIR fibrosis stage; ARFI: Acoustic radiation force impulse; HCV: Hepatitis C virus; HBV: Hepatitis B virus; NASH: Nonalcoholic steatohepatitis.

Table 4 Results of two meta-analyses on the reliability of acoustic radiation force impulse and optimal cut-offs

Ref.	Studies (n)	Etiology	F≥2				F≥3				F = 4
			Cut-off m/s	Se%	Sp%	ROC curve	Cut-off m/s	Se%	Sp%	ROC curve	Cut-off m/s	Se%	Sp%	ROCcurve
Friedrich-Rust et al[166]	8	Mixed	1.34	79	85	0.872	1.55	86	86	0.912	1.80	92	86	0.932
Nierhoff et al[167]	36	Mixed	1.35	-	-	0.841	1.61	-	-	0.891	1.87	-	-	0.911

¹SROC: Area under the Summary Receiver Operating Characteristic;

²AUROC: Area Under Receiver Operating Characteristic. F: METAVIR fibrosis stage.

Table 5 Diagnostic reliability between acoustic radiation force impulse and transient elastography and optimal cut-offs

Ref.	Etiology	Transient elastography						ARFI
		F≥2		F≥3		F = 4		F≥2		F≥3		F = 4
		AUROC	Cu-off kPa	AUROC	Cut-off kPa	AUROC	Cut-off kPa	AUROC	Cut-off m/s	AUROC	Cut-offm/s	AUROC	Cut-offm/s
Friedrich-Rust et al[160]	HCV	0.84		0.91		0.910		0.82	1.37	0.91	1.45	0.91	1.75
Lupsor et al[161]	HCV	0.96	8.1	0.96	0.6	0.97	13.1	0.86	1.34	0.90	1.61	0.94	2.00
Yoneda et al[162]	NASH	-	-	0.99	9.9	0.998	16.0			0.97	1.77	0.97	1.99
Rizzo et al[163]	HCV	0.78	6.5	0.80	8.8	0.8	11.0	0.86	1.3	0.94	1.70	0.89	2.00
Sporea et al[164]	Mixed	0.91				0.99		0.77	1.41	0.79	1.69	0.92	1.81
Sporea et al[165]	HCV	0.82	6.7	0.87	9.6	0.93	11.9	0.81	1.36	0.86	1.47	0.885	1.69
Bota et al[168]	Mixed	0.871	-	-	-	0.931	-	0.851	1.31	-	-	0.931	1.80

¹SROC: Area under the Summary Receiver Operating Characteristic, Meta-analysis. Se: Sensitivity; Sp: Specificity; AUROC: Area Under Receiver Operating Characteristic; F: METAVIR fibrosis score; ARFI: Acoustic radiation force impulse; HCV: Hepatitis C virus; NASH: Nonalcoholic steatohepatitis.