Can a patient have Hereditary Hemorrhagic Telangiectasia (HHT) without hepatic Arteriovenous Malformations (AVMs)?

Can a Patient Have HHT Without Hepatic AVMs?

Yes, a patient can absolutely have HHT without hepatic AVMs—in fact, the majority of HHT patients do not have liver involvement. Hepatic vascular malformations occur in only 44-74% of HHT patients, and only 5-8% of those with hepatic VMs are symptomatic 1, 2.

Understanding Hepatic Involvement in HHT

Prevalence and Clinical Significance

• Hepatic AVMs are not required for HHT diagnosis and their absence does not exclude the disease 1.
• The diagnosis of HHT is established using the Curaçao criteria, which requires 3 of 4 clinical features: spontaneous/recurrent epistaxis, multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose), visceral lesions (pulmonary, hepatic, cerebral, or spinal AVMs or GI telangiectasias), and first-degree relative with HHT 1, 3.
• Hepatic AVMs represent only one possible visceral manifestation among several organ systems that can be affected 1.

Genotype-Phenotype Correlation

• HHT2 (ACVRL1/ALK-1 mutations) shows substantially higher prevalence of hepatic VMs compared to HHT1 (ENG mutations), with marked female predominance 1.
• Patients with HHT1 (ENG mutations) are more likely to have pulmonary and cerebral AVMs rather than hepatic involvement 4, 5.
• The mean age of patients with hepatic VMs is 52 years, indicating that hepatic involvement is age-dependent and may not be present at diagnosis 1.

Screening Recommendations for Hepatic AVMs

When NOT to Screen

Screening for liver involvement in HHT patients is NOT recommended except in specific circumstances 1:

• The prevalence of liver involvement is high but most patients are asymptomatic (only 8% symptomatic) 1.
• There is no effective treatment for asymptomatic hepatic VMs, making routine screening of limited clinical utility 1.
• Screening should be avoided unless the patient has clinical evidence suggesting liver involvement 1.

When TO Screen

Screen for hepatic VMs only when 1:

• The presence of liver vascular malformations would be decisive in establishing a "definite" HHT diagnosis in patients who meet only 1-2 Curaçao criteria 1.
• Genetic testing is inconclusive or unavailable and additional visceral involvement would confirm diagnosis 1.
• The patient has clinical signs suggesting liver involvement: thrill/bruit in right upper quadrant, high-output heart failure, portal hypertension, biliary ischemia symptoms, or unexplained cholestasis 1.

Diagnostic Approach When Screening Is Indicated

Imaging Modality

• Doppler ultrasonography is the first-line imaging for suspected hepatic involvement 1, 3.
• Key diagnostic findings include: enlarged hepatic artery (>6 mm), intrahepatic hypervascularization, peak flow velocity >80 cm/sec, and resistivity index <0.55 1.
• Multiphase CT or angiography can be used as alternatives, showing markedly dilated hepatic artery and heterogeneous hepatic enhancement pattern 1.

Critical Pitfall to Avoid

Never perform liver biopsy in patients with proven or suspected HHT 1, 3:

• Liver biopsy is dangerous due to hemorrhage risk from the vascular malformations 1.
• Biopsy findings are often misinterpreted and provide less information than imaging studies 1.
• The liver may appear nodular due to nodular regenerative hyperplasia (NRH), which can be mistaken for cirrhosis 1.

Clinical Implications

Other Organ Screening Takes Priority

For patients with confirmed or suspected HHT without hepatic involvement, focus screening efforts on:

• Pulmonary AVMs (present in 70-90% of HHT patients with pulmonary involvement): screen with contrast echocardiography or chest CT, as these can cause stroke, brain abscess, or hemorrhage through paradoxical embolization 3, 4, 5, 6.
• Cerebral AVMs (more common in HHT1): screen with brain MRI, particularly in patients with family history of cerebral hemorrhage or stroke 3, 4, 7.
• Gastrointestinal telangiectasias: evaluate with upper endoscopy if unexplained anemia disproportionate to epistaxis 3.

Prognosis Without Hepatic Involvement

• Life expectancy is normal when HHT patients are systematically screened for organ involvement and treated appropriately in HHT centers of excellence 6.
• The absence of hepatic AVMs does not diminish the need for comprehensive screening of other organ systems, as pulmonary and cerebral AVMs pose significant morbidity and mortality risks 3, 4, 6.