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Volume: 17 Issue: 1 February 2019

FULL TEXT

CASE REPORT
De Novo Vascular Lesions After Liver Transplant in a Case With Hereditary Hemorrhagic Telangiectasia and Fibropolycystic Liver Disease: Long-Term Follow-Up With Magnetic Resonance Imaging and Magnetic Resonance Angiography

We report a case of a 62-year-old woman who received a liver transplant 19 years previously for end-stage liver disease due to hereditary hemorrhagic telan­giectasia and fibropolycystic liver disease. During long-term follow-up 8 years after the liver transplant, de novo vascular lesions were detected with magnetic resonance imaging and magnetic resonance angiography. Hepatic vascular lesions had slowly progressed, despite no symptoms. To our knowledge, there are few reports in the English literature of de novo vascular lesions after liver transplant in patients with hepatic telangiectasias.


Key words : Fibropolycystic disease, Hepatic telangiectasia, Osler-Weber-Rendu disease

Introduction

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder that affects the lungs, gastrointestinal tract, liver, and brain. The disease is characterized by recurrent epistaxis, cutaneous telangiectasia, and visceral arteriovenous malformations. At least 3 of the 4 Curaçao criteria are required to establish a definite diagnosis: (1) spontaneous, recurrent epistaxis; (2) telangiectasia; (3) a positive family history; and (4) visceral lesions.1 Hepatic involvement, which is characterized by a spectrum of arteriovenous malformations within the liver, occurs in up to 74% of patients with HHT.2 Liver involvement seems to be more frequent in women, who may also experience a more severe disease course and a higher rate of clinically relevant complications.3 Fortunately, most HHT patients are asymptomatic, and less than 5% to 15% of patients present with symptoms.4 Intrahepatic shunts may cause high-output cardiac failure, biliary ischemia, portal hypertension, encephalopathy, and/or mesenteric ischemia.5

We report a case of a 62-year-old woman who received liver transplant for end-stage liver disease due to HHT and fibropolycystic liver disease. De novo vascular lesions after liver transplant were detected during long-term follow-up with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). To our knowledge, there are few reports in the English literature on the possible relapse of hepatic telangiectasias.5,6

Case Report

A 62-year-old female patient with a history of HHT and fibropolycystic liver disease underwent liver transplant due to end-stage liver disease in 1996. Magnetic resonance imaging, magnetic resonance cholangiography, and computed tomography (CT) of the abdomen before transplant had shown multiple hepatic cysts and intrahepatic biliary dilatation, with no apparent communication between the cysts and the biliary system, and also polycystic kidneys. She was followed at our institution from 1998 to 2004 with MRI and MRA for hepatic artery aneurysm, biliary stasis, and dense biliary sludge with stabilized liver and renal functions. Two new vascular liver lesions were shown in 2004, but these lesions were stable in size, as shown during further follow-up MRI and MRA performed in 2006 (Figure 1). The patient was subsequently lost to follow-up until 2013; at which time, 17 years after the transplant, we detected multiple vascular lesions consistent with arteriovenous malformations in the liver with control MRI and time-resolved MRA with interleaved stochastic trajectory technique examinations (Figure 2A). In addition, an aneurysm of the right hepatic artery was seen, which had increased in size compared with that shown in the prior imaging performed in 2006. The hepatic artery aneurysm was treated with coil embolization. Control MRI performed in 2015 showed no change in the size and number of the liver lesions (Figure 2B). The patient is still being followed and so far is showing normal liver functions.

Discussion

Hereditary hemorrhagic telangiectasia, also known as Osler-Weber-Rendu disease, is a rare, autosomally inherited disorder with an incidence of 1 to 2 per 100 000 individuals, a prevalence of 1 to 2 per 10 000, and a clinical penetrance of 97%.7 The presentation is usually subtle with telangiectasia, epistaxis, or gastrointestinal bleeding and a family history of similar complaints. The more severe consequences are shunting of blood through arteriovenous malformations, leading to hyperdynamic circulation and cardiac overload.

Osler-Weber-Rendu disease is genetically hetero­geneous. Mutations of 2 genes have been identified to be associated with HHT: HHT type 1 results from mutations in the endoglin gene on chromosome 9 that encodes endoglin, and HHT type 2 results from mutations in activin A receptor type II-like 1 on chromosome 12, which encodes activin receptor-like kinase 1. Recently, additional HHT-causing genes have been mapped in chromosomes 5 and 6.8 Hepatic involvement is frequently associated with HHT type 2 and mutations of the activin receptor-like kinase 1 gene.5

Hepatic involvement is associated with micro­scopic telangiectasias and direct arteriovenous and portovenous shunts. Vascular lesions show pro­gressive enlargement and form multiple macroscopic intrahepatic shunts detectable by imaging modal­ities. Three types of clinical presentations can be distinguished in symptomatic HHT with liver involvement: high-output heart failure, portal hypertension, and biliary disease.9

Detection of liver involvement depends on imaging studies such as color Doppler ultrasono­graphy, multislice CT, and/or MRI. For the diagnosis of liver involvement, there are different types of Doppler ultrasonography criteria, established by Caselitz and associates,10 Buscarini and associates,11 and Buonamico and associates.2 Color Doppler ultrasonography is a highly accurate, noninvasive method, which has no discomfort for the patient and is less expensive than CT and MRI. However, it is user dependent, and its interpretation can be difficult in the presence of obesity or abdominal bloating due to bowel gas. Multislice CT enables detection and characterization of complex anatomic and pathologic changes in the liver with high sensitivity; thus it is the most preferred imaging modality for the diagnosis and evaluation of the different intrahepatic shunts. However, it requires exposure to ionizing radiation and iodinated intravenous contrast agents. With CT, arteriovenous shunts are present in nearly all HHT patients with liver involvement and these shunts are easily detected during the early arterial phase because of enhancement of the abnormal portal vein (arterioportal shunt) or the hepatic vein (arteriosystemic shunt).8 Abnormal parenchymal perfusion areas, telangiectasias, and large confluent vascular masses are other vascular abnormalities that are frequently identified with CT. Use of MRI and MRA permits evaluations of hepatic involvement in HHT patients. In previously reported small patient series, MRI and MRA have been shown to detect accurately parenchymal abnormalities such as telangiectases, perfusion disorders, focal nodular hyperplasia, biliary tract disorders such as strictures and dilatations of main bile ducts, rarefaction of peripheral intrahepatic bile ducts, and large vessel malformations, including hepatic artery dilatation, tortuosity or anatomic variants, and arteriovenous shunts.12 For our patient, MRI and MRA were preferred during follow-up due to coexisting poly­cystic kidney disease, even though kidney functions were normal, to lower the risk of nephrotoxicity.

Treatment is not usually necessary for asymp­tomatic patients with liver involvement. These patients should be followed periodically. The treatment choices for symptomatic patients include treating complications, administering procedures to reduce shunting, and performing liver transplant. Liver transplant is the only curative possibility and should be reserved for patients with symptomatic and progressively worsening liver disease despite supportive medical therapy.8 The main indications for liver transplant are existence of obstinate heart failure, severe biliary disease complicated by recurrent episodes of cholangitis, development of spontaneous biliary necrosis occurring either during or after hepatic artery embolization or ligation, and presence of portal hypertension not responding to conventional therapeutic procedures.3

The presented patient was reported in 1998 after liver transplant due to the rarity of HHT and fibropolycystic disease co-existence by Saxena and associates.13 Before the transplant procedure, the patient had presented with worsening liver functions, ascites, pleural effusion, wasting, and extreme fatigue. She was at the time also severely cholestatic. A liver biopsy at the time of surgery had shown telangiectasia and portal fibrosis. The patient had a regular postoperative course after the liver transplant procedure, which had been complicated by severe bleeding during surgery. The histology of the explanted liver showed liver involvement in accordance with Osler-Weber-Rendu disease and associated biliary tract disease, which was a combination of ischemic bile duct changes and fibropolycystic disease.13 The patient showed no symptoms during follow-up examinations. However, 2 new vascular liver lesions were shown by MRI 6 years after liver transplant (in 2004), with these beings stable as shown in control MRI and MRA examinations performed in 2006. The patient presented with multiple hepatic vascular lesions and increased sizes of the previous lesions as shown by time-resolved MRA and MRI examinations in 2013 and 2015. The patient is still being followed with no symptoms 17 years after transplant. The patient also had polycystic kidneys, but her renal function has been stable with creatinine clearance within normal limits.

Hepatic telangiectasias relapse has become a topic for discussion in a series reported by Dupuis-Girod and associates.5 From contrast ultrasonography and liver biopsy findings, the group suggested that focal vascular dilatations may be caused by peliosis hepatis. Peliosis hepatis is an uncommon vascular disorder caused by several agents. This condition has also been described in recipients of renal and liver allografts.14 Confirmation of a diagnosis of peliosis hepatis requires a comprehensive macroscopic study of the hepatic anatomy. The radiologic features are similar to those shown in 2 patients previously reported by Sabba and associates.6 In that report, identical hepatic vascular malformations were demonstrated in the transplanted livers of 2 related asymptomatic HHT patients evaluated 10 and 8 years after transplant. In the first patient, focal vascular dilatations throughout the liver were demonstrated by a celiac and mesenteric arteriography; in the other patient, CT scan and hepatic arteriography revealed focal vascular dilations in the transplanted liver. No liver biopsies were performed in these patients. Similarly, we also did not perform a biopsy in our patient. Sabba and associates stated that it is difficult to determine whether the focal vascular dilatations were due to a true relapse of hepatic telangiectasia or due to peliosis hepatis. They suggested that the relapse of telangiectasia in the transplanted liver could be related to a systemic lack or increase in plasmatic factors involved in angiogenetic processes15 or, alternatively, could indicate a renewed vascu­larization of the transplanted liver by host endothelial cells, most likely from bone marrow-derived circulating progenitor endothelial cells.16

In conclusion, HHT patients undergoing liver transplant should have regular and long-term follow-up with noninvasive radiologic imaging to detect any de novo hepatic vascular pathologies.


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Volume : 17
Issue : 1
Pages : 115 - 118
DOI : 10.6002/ect.2016.0024


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From the 1Department of Radiology, Acibadem University School of Medicine; and the 2Memorial Hospital Department of Gastroenterology and Hepatology, Istanbul, Turkey
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Sila Ulus, Acibadem University School of Medicine, Department of Radiology, Kerem Aydinlar Kampusu, Kayisdagi Cad. No:32, 34752 Atasehir, Istanbul Turkey
Phone: +90 216 500 4296
E-mail: silaulus@hotmail.com