Current guidelines for diagnosis and management of hepatic involvement in hereditary hemorrhagic teleangiectasia

Table 1 Curaçao diagnostic criteria of hereditary hemorrhagic teleangiectasia

Curaçao criteria	Description
Epistaxis	Spontaneous and recurrent
Teleangiectases	Multiple, at characteristic sites: Lips, oral cavity, fingers, nose
Visceral lesions	GI telangiectasia, pulmonary, hepatic, cerebral or spinal AVMs
Family history	A first degree relative with HHT
Number of criteria	HHT diagnosis
3-4	Definite
2	Possible
0-1	Unlikely

AVMs: Arteriovenous malformations; HHT: Hereditary hemorrhagic teleangiectasia.

Table 2 Genes responsible for hereditary hemorrhagic teleangiectasia, phenotypes and liver involvement prevalence

Gene	Protein	Location	Phenotype	Liver involvement prevalence
ENG	Endoglin	9q34.11	HHT1	7.6%-43.0%
ACVLR1	ALK1	12q13.13	HHT2	40.6%-57.6%
MADH4	Smad4	18q21.1	PJ-HHT	33.3%
GDF2	BMP9	10q11.22	HHT-like	Unknown
RASA-1	p120-RasGAP	5q14.3	CM-AVM	Unknown

ACVLR1: Activin A receptor type II-like 1; ALK1: Activin-like receptor kinase 1; BMP9: Bone morphogenetic protein 9; CM-AVM: Capillary malformation–arteriovenous malformation syndrome; GDF2: Growth differentiation factor 2; ENG: Endoglin; MADH4: Mothers against decapentaplegic homolog 4; p120-RasGAP: p120-Ras GTPase activating protein; PJ: Juvenile polyposis; RASA-1: Ras p21 protein activator 1; Smad4: Small mother against decapentaplegic.

Table 3 Clinical Scoring Index for clinical probability of significant liver disease in hereditary hemorrhagic teleangiectasia patients[25]

Criteria		Points
Age at presentation (yr)	> 47	1
	≤ 47	0
Sex	Female	1
	Male	0
Hb at presentation (g/dL)	< 8	3
	8-12	2
	12-16	1
	> 16	0
ALP at presentation (IU/L)	> 300	4
	225-300	3
	150-224	2
	75-149	1
	> 75	0
Clinical Scoring Index	Clinical probability of significant liver disease
≤ 2	Low	(0.4%-3.2%)
3-6	Intermediate	(8.2%-64.1%)
≥ 7	High	(82.9%-93.0%)

ALP: Alkaline phosphatase; Hb: Hemoglobin.

Table 4 Doppler ultrasound grading of hepatic vascular malformations in hereditary hemorrhagic teleangiectasia patients[24]

VMs grade	Doppler US findings
0.5	HA diameter 5-6 mm and/or
	PFV > 80 cm/sec and/or
	HA RI < 0.55 and/or
	Peripheral hepatic hypervascularization
1	HA dilation > 6 mm (only extrahepatic) and
	PFV > 80 cm/sec and/or
	HA RI < 0.55 and/or
2	HA dilation intra- and extrahepatic and
	PFV > 80 cm/sec
	Possible flow abnormality in portal and/or hepatic veins
3	Complex changes in HA and its branches with marked flow abnormalities
	Flow abnormality in portal and/or hepatic veins
4	Decompensation of arteriovenous shunt with dilatation of portal and/or hepatic vein and marked flow abnormalities in both arteries and vein/s

HA: Hepatic artery; PFV: Peak flow velocity; RI: Resistivity index; US: Ultrasound; VMs: Vascular malformations.