Cystic fibrosis associated liver disease in children

Table 3 Examples of noninvasive monitoring of liver fibrosis in pediatric cystic fibrosis liver disease

Non-invasive marker	Ref.	Outcome measured	AUC	Sensitivity	Specificity	Comments
Indirect markers of liver fibrosis
APRI	Leung et al[37]	CFLD diagnosis and severe CFLD	0.81	73%	70%	APRI score cut-off > 0.264; Predict CFLD and significant fibrosis in CFLD with a high degree of accuracy
FIB-4	Leung et al[37]	Portal hypertension	0.91	78%	93%	FIB-4 cutoff 0.358
Direct markers of liver fibrosis
TIMP-1	Pereira et al[38]	CFLD diagnosis	0.76	64%	83%	Significantly increased in CFLD vs no-CFLD
Prolyl hydroxylase	Pereira et al[38]	CFLD		60%	91%	Negative correlation between serum TIMP-1 levels and the stage of histological fibrosis; Prolyl hydroxylase useful in distinguishing CFLD patients with early fibrogenesis vs extensive fibrosis; Not able to differentiate CFLD versus no-CFLD
		diagnosis
TIMP-2	Rath et al[38]	CFLD diagnosis	0.69	-	-
m-RNA’s	Cook et al[39]	CFLD diagnosis	0.78	47%	94%	Able to differentiate between CFLD versus no-CFLD but quantify not fibrosis stage; Pathological significance not yet certain, more studies needed
Imaging methods
Transient elastography	Witters et al[40]	Liver stiffness	0.86	63%	87%	Less inter and intra-observer variability; Easy to learn and perform; Regular measurements for serial follow-up feasible
	Rath et al[34]	Liver stiffness	0.68	-	-	Few centres have access to technology
MR elastography	Palermo et al[41]	Liver stiffness	-	100%	100%	Small study, paucity of data; Shear stiffness significantly elevated in CF patients with cirrhosis; Costly with limited availability

AUC: Area under the curve; APRI: Aspartate aminotransferase to platelet ratio index; CFLD: Cystic fibrosis associated liver disease; Fib-4: Fibrosis-4; TIMP: Tissue inhibitor of metalloproteinase; m-RNA: Messenger ribonucleic acid; MR: Magnetic resonance.