title: Bevacizumab reverses need for liver transplantation in hereditary hemorrhagic telangiectasia.
abstract: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by mucocutaneous and visceral telangiectasia. Hepatic involvement with vascular malformations may lead to portal hypertension, biliary ischemia, and high-output cardiac failure. Liver transplantation is indicated for life-threatening disease but carries significant risk from surgery and chronic immunosuppression. We report a case of a 47-year-old woman with HHT successfully treated with the vascular endothelial growth factor (VEGF) antibody bevacizumab. The patient was referred for consideration of liver transplantation because of hepatic HHT leading to high-output cardiac failure, diuretic resistant ascites, cholestasis, and malnutrition. As she was considered a high-risk candidate for transplantation, she underwent 6 courses of bevacizumab (5 mg/kg) over 12 weeks. A dramatic improvement in her clinical state was observed after 3 months with reversal of cholestasis, resolution of cardiac failure and ascites, and improvement in nutritional status with a 10% dry weight increase. Treatment induced a marked reduction in liver vascularity and halving of her liver volume from 4807 to 2269 mL over 6 months. This was associated with normalization of her cardiac output from 10.2 to 5.1 L/minute. Correspondingly, she ceased diuretic medications, returned to full-time work, and was delisted as a transplant candidate. She remains well 6 months after completing treatment. In conclusion, antagonism of VEGF receptors led to a dramatic regression of hepatic vascular malformations and reversal of high-output cardiac failure and complications of portal hypertension in this patient with HHT. Bevacizumab may potentially alleviate the need for liver transplantation in this group of patients.
authors.affiliation: Western Australian Liver Transplant Service, Sir Charles Gairdner Hospital, Nedlands, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mitchell
authors.forename: Leon A
authors.initials: LA
authors.lastname: Adams
authors.forename: Gerry
authors.initials: G
authors.lastname: MacQuillan
authors.forename: Jon
authors.initials: J
authors.lastname: Tibballs
authors.forename: Rohan
authors.initials: R
authors.lastname: vanden Driesen
authors.forename: Luc
authors.initials: L
authors.lastname: Delriviere
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001201:Ascites / Q000188:drug therapy / Q000209:etiology / Q000601:surgery; D000068258:Bevacizumab; D016534:Cardiac Output, High / Q000188:drug therapy / Q000209:etiology / Q000601:surgery; D002779:Cholestasis / Q000188:drug therapy / Q000209:etiology / Q000601:surgery; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy / Q000209:etiology / Q000601:surgery; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation; D008279:Magnetic Resonance Imaging; D044342:Malnutrition / Q000188:drug therapy / Q000209:etiology / Q000601:surgery; D008875:Middle Aged; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000150:complications* / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab