Liver tumors in children with chronic liver diseases

Table 1 Predisposing factors in developing hepatic tumors in chronic liver diseases

Predisposing factors
Oxidative stress
Dysregulation of protumorigenic growth factors and cytokines
Genetic factors: p53 mutation, telomere shortening, homozygous PiZZ mutation, tumor suppressor kinase-1 expression
Hepatocarcinogenesis: HBV, HCV, HIV
Toxic substances: Tyrosinemia type I (maleyl acetoacetate, fumaryl acetoacetate and succinyl acetone), PFIC type 2 and 3 (bile salt)
Metabolic disturbance: Glycogen storage disease type 1 and 4, obesity and NAFLD
Vascular disruption: Congenital absence of portal vein, noncirrhotic portal hypertension, Budd-Chiari syndrome

HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; NAFLD: Non-alcoholic fatty liver disease; PFIC: Progressive familial intrahepatic cholestasis.

Table 2 Liver tumors identified in chronic liver diseases

Liver disease and main pathogenesis	Tumor type
Genetic or metabolic syndromes
Hereditary tyrosinemia type 1[80-83]	HCC
GSD type 1, 3, 4	HA, HCC, HB
Alagille syndrome	HCC, regenerative nodule
Other familial cholestatic syndromes	HCC
NAFLD	HCC
α-1 antitrypsin deficiency	HCC
Infections
HBV	HCC
HCV	HCC
Vascular
Abernethy	FNH, HCC, HA
Noncirrhotic portal hypertension	NRH
Congenital portosystemic shunt	HCC, HB
Cirrhosis and cholestatic conditions
Biliary atresia	HCC, FNH, pseudotumor
Autoimmune hepatitis	HCC
Wilson disease	HCC
Congenital hepatic fibrosis	HCC
Cryptogenic cirrhosis	HCC

FNH: Focal nodular hyperplasia; GSD: Glycogen storage disease; HA: Hepatic adenoma; HB: Hepatoblastoma; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; NAFLD: Non-alcoholic fatty liver disease; NRH: Nodular regenerative hyperplasia.

Table 3 Typical imaging appearances of liver tumors

Tumors	US with doppler	CT	MRI
HB	Well circumscribed hyperechoic or heterogenous echogenic lesion	Hypoattenuating lesion in non-contrast image with heterogeneous arterial and venous enhancement	T1W; hypointense
			T2W; hyperintense
			Heterogeneous arterial and venous enhancement
HCC	Variable from hypo-, iso-, or hyperechoic from internal fat, necrosis or hemorrhage	Well- or poorly defined, hypoattenuating lesion with arterial hyperenhancement and venous “wash-out” with/without delayed capsular enhancement	T1W; hypointense
			T2W; hyperintense
			Early arterial enhancement and wash-out with relative low signal intensity on venous and delayed phases
		Tumor thrombus enhancement in portal vein	Delayed capsular enhancement
FNH	Homogenous, well-circumscribed	Homogeneous, well-circumscribed iso- to slightly hypoechoic lesion	T1W; iso- to slightly hypointense with hypointense scar
			T2W; iso- to slightly hyperintense with hyperintense scar
		Hypoattenuating scar	Enhancement pattern same as CT
	Internal color flow in the central scar extending to the periphery in a spoke-wheel pattern	Arterial and early portal venous enhancement and becomes isoattenuating to liver in the late portal venous and delayed phases	Normal or increased uptake on delayed hepatobiliary phases of the hepatocyte specific contrast agent
Adenoma	Hyperechoic lesion in the normal liver	Well-circumscribed hypoattenuating lesion with hyperattenuation if hemorrhaging	T1W; hyperintense
			T2W; hyperintense
			Fat component; Signal dropout on opposed-phase or fat suppression images
	Hypoechoic lesion in the background of diffuse fatty infiltration or glycogen storage	Intense arterial enhancement and isoattenuating in venous and delayed phases	Peripheral pseudocapsular enhancement
			Enhancement pattern same as CT
NRH	Multiple tiny and typically isoechoic lesions, difficult to detect.	Slightly hypo- or isoattenuating lesion to liver	T1W; homogenous and slightly hyperintense.
			T2W; variable
		Isoattenuation to liver in both arterial and portal venous phases	Enhancement in portal phase like normal liver parenchyma

CT: Computed tomography; FNH: Focal nodular hyperplasia; HB: Hepatoblastoma; HCC: Hepatocellular carcinoma; MRI: Magnetic resonance imaging; NRH: Nodular regenerative hyperplasia; US: Ultrasonography.