Noninvasive diagnosis of periportal fibrosis in schistosomiasis mansoni: A comprehensive review

Table 1 Major advantages and limitations of noninvasive periportal fibrosis markers in Schistosomiasis mansoni infected patients

Feature	Liver biopsy		Serum markers	Imaging techniques
	Wedged	Percutaneous		US	pSWE	TE
Invasiveness	High	High	Minimal	None	None	None
Post-procedural risk	Possible	Possible	Minimal	None	None	None
Accuracy for PPF prediction	High	Low	Medium to high	High	Good	Good
Sensitivity	High	Low	Medium	High	Medium	Medium
Interpretation	Subjective	Subjective	Objective	Subjective	Objective	Objective
Observer variability	High	High	Low	High	Not yet evaluated	Not yet evaluated
Costs	High	Medium	Depends	Medium	Medium	Medium
Limitations by anthropometric features	High	High	None	Medium	Medium	Medium
Suitability for monitoring PPF	Low	Low	High	High	High	High

PPF: Periportal fibrosis; pSWE: Point shear wave elastography; TE: Transient elastography; US: Ultrasound.

Table 2 Major advantages and limitations of noninvasive periportal fibrosis markers in Schistosomiasis mansoni infected patients

PFF markers	Advantages	Limitations
Direct markers
PICP	Elevated levels in patients not treated yet with praziquantel and related to the stage of fibrosis and necroinflammation	Not reliable for establishing fibrosis grade
P3NP	Use for complicated patients who developed hypertension and with more severe liver diseases	Low sensitivity in mild cases
Serum type VI collagen	Correlated with liver fibrosis, splenomegaly, portal vein dilatation and the presence of portosystemic collaterals	Low sensitivity
Hyaluronic acid	Marker for the initial phase of liver fibrosis and it is able to assess the severity of liver disease	High levels in different etiologies of liver disease, barely accessible
Indirect markers
APRI	Low cost, good sensitivity, high diagnostic accuracy for cirrhosis	Interference of hepatic comorbidities
Blood platelet count	Low cost and sensitive marker. It is a marker of portal hypertension and inversely correlated with advanced PPF and the diameter of the spleen	Interference of coagulopathies, some drugs and other live disorders
GGT	Low cost. Correlated with more advanced PPF, faster fibrosis progression rate and indicates intrahepatic alterations	Interference of hepatobiliary alterations
Coutinho Index	Simplicity of calculation and low cost	Requires more tests for use in mild and moderate fibrosis

HA: Hyaluronic acid; PICP: Procollagen type I carboxy-terminal peptide; P3NP: Procollagen type III amino-terminal peptide; PPF: Periportal fibrosis; APRI: Aspartate aminotransferase to platelet ratio index; GGT: Gamma glutamyl transferase.

Table 3 Performance of indirect periportal fibrosis markers in Schistosomiasis mansoni infected patients

Marker	Parameters	Performance in S. mansoni infected patients
		Severe PPF			Mild/significant PPF
		Cut-off	Sn (%)	Sp (%)	Cut-off	Sn (%)	Sp (%)
Platelet count[17,26]	Platelet count/mm3	141000[17]	78.5	60	171000[17], 108500[26]	80, 91	91.7, 85
APRI[17,26]	(AST/ULN)/platelet count	1.066	58.5	71.1	0.349[17], 0.440[26]	90, 96	83.3, 85
GGT[17]	GGT/ULN	> 1.55	60.0	75.6	> 0.84	74.6	83.3
Coutinho index[29,30]	(ALP/ULN)/platelet count	≥ 0.330[29], ≥ 0.316[30]	98, 67.4	94.7, 68.3	≥ 0.300, ≥ 0.228	70.8, 68.6	89.5, 46.3

APRI: Aspartate aminotransferase to platelet ratio index; ALP: Alkaline phosphatase; GGT: Gamma glutamyl transferase; PPF: Periportal fibrosis; Sn: Sensitivity; Sp: Specificity; ULN: Upper limit of normality; S. mansoni: Schistosomiasis mansoni.

Table 4 Image pattern classification of periportal fibrosis according to the World Health Organization[37]

IP	Description
A	Normal
B	Diffuse echogenic foci (“starry sky”), minimal wall thickening of portal and segmental branches
C	Ring echoes around vessels in cross-section; pipe-stems parallel with portal vessels
D	Echogenic ruff around portal bifurcation and main stem; main portal vessel wall thickening
E	Hyper-echogenic patches expanding into parenchyma
F	Echogenic bands and streaks extending from main portal vein and its bifurcatin to liver surface; may retract the surface of the organ
X	Cirrhosis
Y	Fatty liver
Z	Other hepato-biliary diseases

IP: Image pattern.

Table 5 Performance reported in the literature of noninvasive periportal fibrosis imaging techniques in Schistosomiasis mansoni infected patients

Marker	Parameters	Performance in schistosoma infected patients
		Severe PPF		Mild/significant PPF
		Cut-off		Cut-off
		HS	HSS	HIS
US[37]	Image interpretation (Niamey sonographic protocol)	D	E/F	-
TE[20,51,53,57]	Wave propagation speed (kPa)	-	9.6 kPa[57], 8.9 kPa[51], 9.7 kPa[20], 9.5 kPa[53]	-
Pswe[19,51,42]	Wave propagation speed (m/s; kPa)	1.33 m/s[51]	1.39 m/s[19], 1.53 m/s[52]	1.11 m/s[19], 1.29 m/s[52]
2D-SWE[54]	Wave propagation speed (m/s; kPa)	-	14.9 kPa[54]	-

HIS: Hepatointestinal schistosomiasis; HS: Hepatic schistosomiasis; HSS: Hepatosplenic schistosomiasis; PPF: Periportal fibrosis; pSWE: Point shear wave elastography; TE: Transient elastography; US: Ultrasound.

Table 6 Advantages and limitations of noninvasive periportal fibrosis techniques frequently used in clinical practice with regard to Schistosomiasis mansoni infected patients

Techniques	Advantages	Limitations
Blood Platelet Count	Low cost, routine laboratory test, easy access	Difficult to diagnose patients with initial PPF
APRI	Low cost, based on routine laboratory tests, easy access	More frequently used to diagnose patients with portal hyperpertension and esophageal varices, less sensitive for PPF
Coutinho index	Low cost, based on routine laboratory tests (alkaline phosphatase and platelet count), easy access, lets advanced PPF be identified	These tests need to be validated in other centers
Ultrasound	Low cost, safe and based on the Niamey-WHO protocol	Operator dependent
MRI/CT	MRI is more sensitive than ultrasound at diagnosing PPF	Expensive, use of radiation, not available in endemic areas, no relation with the Niamey-WHO protocol
Liver elastography	Good accuracy, distinguishes mild from significant PPF	Expensive, not available in endemic areas
Spleen elastography	Related to portal hypertension	Expensive, not available in endemic areas, needs further studies
Wedge liver biopsy	Gold standard used to diagnose Symmers fibrosis	Only for surgical patients
Percutaneous liver biopsy	Can be used in differential diagnosis between schistosomiasis and other liver diseases	Insufficiently sensitive and so may fail to diagnose PPF

CT: Computer tomography; PPF: Periportal fibrosis; MRI: Magnetic resonance imaging; WHO: World Health Organization.