Systemic therapy with bevacizumab in patients with hereditary hemorrhagic telangiectasia (HHT)

Background: Frequent epistaxis, the hallmark of hereditary hemorrhagic telangiectasia (HHT) significantly affects quality of life. Hepatic involvement may be associated with capsular pain, abdominal angina, high-output cardiac failure and portal hypertension with ascites and variceal bleeding. Liver transplantation as well as hepatic artery embolization as invasive treatment options for hepatic involvement are both associated with a certain morbidity and mortality. Patients and methods: Three patients with HHT and symptomatic hepatic involvement prospectively underwent off-label systemic treatment with the vascular endothelial growth factor (VEGF)-inhibitor Bevacizumab in 6 cycles. Clinical symptoms and cardiac output were assessed before as well as 3 months after therapy. Results: At 3 months follow-up, capsular pain and abdominal angina were significantly reduced in two of the three patients (Numerical Rating Scale (NRS) grade 4 and 5 changed to grade 2). Cardiac output, which was initially raised in both patients, normalized and was associated with an improvement in the signs and symptoms of cardiac insufficiency by one stage according to the NYHA classification in both patients. Symptoms however returned back gradually to pre-therapeutic levels after 9 months in one of these two patients. In the third patient with a normal cardiac status prior to therapy, a marked subjective improvement in the performance status, fatigability and quality of life was noted. Grade 2 nasal bleeding reduced to grade 0-1 in all three patients; this clinical improvement was persistent at 3, 7 and 9 months follow-up. No significant lasting complications were observed. Conclusions: Sytemic Bevacizumab therapy could become an important therapy option in the non-invasive medical treatment of patients with HHT. Further studies to document long-term results, to determine the appropriate drug dosage as well as to evaluate the necessity of a maintenance drug regime are warranted.