Non-invasive diagnosis of liver fibrosis in chronic hepatitis C

Table 1 Major advantages and limitations of liver biopsy and noninvasive fibrosis markers

	Liver biopsy	Noninvasive markers
Advantages
	Validated scoring systems	Absence of significant discomfort and risks
	Differential diagnosis and associated conditions	Allows frequent re-evaluation
	Simultaneous evaluation of necro-inflammation	Objective interpretation
		Patient acceptance
Limitations
	Invasive	Low accuracy to discriminate between intermediate stages of fibrosis
	High cost	Nonspecific for the liver (biomarkers)
	Sampling errors and intra- and inter-observer variability	Influence of several extra-hepatic factors

Table 2 Selected models including indirect markers of liver fibrosis

Score (original reference)	Variables	Performance in HCV patients1
		Significant fibrosis (≥F2)			Cirrhosis (≥F4)
		Median AUROC	Median sensitivity2	Median specificity2	Median AUROC	Median sensitivity2	Median specificity2
APRI[24]	AST and platelet count	0.77	81%	95%	0.84	77%	94%
FIB-43[41]	Age, AST, ALT and platelet count	0.74	64%	79%	0.87	90%	92%
Forns index[48]	Age, platelet count, cholesterol levels, and GGT	0.76	88%	94%	0.87	98%	91%
Fibro index[50]	Platelet count, AST, and gamma globulin	0.76	94%	97%	0.86	70%	91%

¹Based on reference number 49;

²Sensitivity values are presented for the lower cutoff and specificity for the upper cutoff (when multiple cutoffs are presented); ³Model originally proposed for HIV/HCV co-infected patients. HCV: Hepatitis C virus; AUROC: Area under the receiver operating characteristic curve; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyltransferase; HIV: Human immunodeficiency virus.

Table 3 Most studied models combining direct and indirect biomarkers for the diagnosis of liver fibrosis in chronic hepatitis C

Score (original reference)	Variables	Performance in HCV patients1
		Significant fibrosis (≥F2)			Cirrhosis (≥F4)
		Median AUROC	Median sensitivity2	Median specificity2	Median AUROC	Median sensitivity2	Median specificity2
FibroTest[53]	Age, sex, serum haptoglobin, α2-macroglobulin, apolipoprotein A1, GGT, and total bilirubin	0.79	92%	96%	0.86	85%	81%
ELF[56]	Age, TIMP-1, PIIINP and hyaluronic acid	0.81	85%	70%	0.88	-	-
Fibrometer[61]	Platelet count, prothrombin index, AST, α2-macroglobulin, hyaluronic acid, blood urea nitrogen and age	0.82	69%	81%	0.91	-	-
FIBROspect II[63]	TIMP-1, α2-macroglobulin and hyaluronic acid	0.86	80%	70%	-	-	-
Hepascore[66]	Age, sex, α2-macroglobulin, hyaluronic acid, GGT and total bilirubin	0.79	66%	79%	0.89	72%	86%

¹Based on reference number 49;

²Sensitivity values are presented for the lower cutoff and specificity for the upper cutoff (when multiple cutoffs are presented). ELF: Enhanced liver fibrosis; HCV: Hepatitis C virus; AUROC: Area under the receiver operating characteristic curve; GGT: Gamma-glutamyltransferase; TIMP: Tissue inhibitor of matrix metalloproteinases; PIIINP: Procollagen type III amino-terminal peptide; AST: Aspartate aminotransferase.