Variceal haemorrhage in hereditary haemorrhagic telangiectasia.

Hepatic in involvement in hereditary haemorrhagic telangiectasia can lead to cirrhosis and occasionally to portal hypertension and variceal haemorrhage. The ultrasonographic, arteriographic and histological findings are described in a patient with this complication. Hepatic artery embolisation proved unsuccessful in arresting repeated haemorrhage which was eventually controlled by hepatic artery ligation. Porto-systemic venous shunting, an apparently logical approach to management, would probably have aggravated the problem.     

LIVER FAILURE CAUSED BY HEPATIC ANGIODYSPLASIA IN HEREDITARY HEMORRHAGIC TELANGIECTASIA

Hereditary hemorrhagic telangiectasia is a systemic vascular disease with autosomal dominant inheritance that results in telangiectasia, arteriovenous malformations, and hemangiomas. The liver is one of the organs commonly affected in hereditary hemorrhagic telangiectasia, and hepatic lesions consist of angiodysplasia and fibrosis. A patient with hereditary hemorrhagic telangiectasia and significant impairment of synthetic liver function is reported. Dynamic computed tomography revealed marked enlargement of the common hepatic and intrahepatic arteries, heterogeneous parenchymography, and early opacification of the hepatic veins consistent with telangiectasias and arteriovenous shunting. Overall, the liver was predominantly occupied by vascular structures and scarce residual hepatic parenchyma. Other causes of liver dysfunction, such as viral hepatitis and alcohol abuse, were excluded. In general, hepatic fibrovascular dysplasia seen in hereditary hemorrhagic telangiectasia usually results in only mild liver dysfunction; however, this case shows that hepatic involvement may rarely result in hepatic failure.     

Hepatic telangiectasia and cirrhosis

In a woman with hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu disease) who died of fulminant hepatitis B, autopsy revealed cirrhosis of the liver and diffuse hepatic telangiectasia. Her daughter and grandson also suffered from the hepatic involvement of HHT. Sufficient laboratory investigations were available to exclude known causes of cirrhosis. We review the relationship between Osler-Weber-Rendu disease and liver cirrhosis or fibrosis.     

Unilateral Nevoid Telangiectasia and chronic Liver Disease

Unilateral nevoid telangiectasia was observed on the back of the left hand and wrist in a 19-year old man with chronic liver disease and portal hypertension. Moreover, abnormalities of the elastic fibers of the skin were found. Examination of the liver biopsy showed extensive portal fibrosis with many dilated blood vessels. No usual cause of juvenile cirrhosis was detected. In the comment, the authors suggest that unilateral nevoid telangiectasia and liver disease could be manifestations of a disease involving skin and liver vessels, as in hereditary hemorrhagic telangiectasia.     

Isolated arterioportal fistula presenting with variceal hemorrhage

We report a case of life-threatening hematemesis due to portal hypertension caused by an isolated arterioportal fistula (APF). Intrahepatic APFs are extremely rare and are a cause of presinusoidal portal hypertension. Etiologies for APFs are comprised of precipitating trauma, malignancy, and hereditary hemorrhagic telangiectasia, but these were not the case in our patient. Idiopathic APFs are usually due to congenital vascular abnormalities and thus usually present in the pediatric setting. This is one of the first cases of adult-onset isolated APF who presented with portal hypertension and was successfully managed through endoscopic hemostasis and subsequent interventional radiological embolization.     

Liver involvement in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease with an autosomal dominant inheritance pattern, characterized by widespread telangiectases that can involve the skin, mucous membranes, lung, brain, gastrointestinal tract and/or liver. It has an estimated prevalence of 1 to 2 cases per 10,000. The prevalence of hepatic involvement in HHT had been estimated in 8% to 31% in retrospective studies but in more recent large prospective series the prevalence is higher, ranging between 41% and 78%. Nevertheless, symptoms occur only in 8% of the patients with HHT and liver involvement. Liver involvement by HHT is characterized by widespread diffuse liver vascular malformations that give rise to three types of shunting: arteriovenous (hepatic artery to hepatic vein), arterioportal (hepatic artery to portal vein), and portovenous (portal vein to hepatic vein). The three most common initial clinical presentations are high-output heart failure, portal hypertension and biliary disease. We describe the case of a patient with diagnosis of HHT and hepatic involvement and we review of the literature. A 58-year-old woman with HHT came to consultation with heart failure symptoms and echographic and endoscopic findings of portal hypertension. The multislice computed tomography of the abdomen revealed the presence of multiple telangiectases in the hepatic parenchyma and a shunt from the hepatic artery to the portal vein. We conclude that the symptomatic involvement of the liver in HHT is an extremely infrequent entity. It must be suspected when clinical manifestations and compatible imagenologic findings exist in patients with antecedents of HHT.     

Symptomatic hepatic arterioportal shunt resolved through conservative treatment

Arterioportal shunt in the liver is a rare vascular disorder that may be due to congenital vascular malformation (hereditary hemorrhagic telangiectasia), trauma, iatrogenic causes (after a hepatic biopsy) or neoplasm. Initial treatment consists of transcatheter arterial embolization with different kinds of materials. We present the case of a 64-year-old woman with signs of portal hypertension and severe diarrhea. Doppler ultrasonography, computed tomography and angiography revealed arterioportal fistulae between the hepatic artery and right portal vein. Transcatheter arterial embolization with n-butyl-2-cyanoacrylate surgical glue (Glubran) was successfully performed. After 2 years of follow-up, the patient remains asymptomatic. Transcatheter arterial embolization with Glubran should be considered as a therapeutic option in arterioportal shunts and could be a definitive therapy.     

Liver involvement in hereditary haemorrhagic telangiectasia or Rendu-Osler-Weber disease.

Hereditary haemorrhagic telangiectasia is a genetic disease characterised by the presence of teleangiectases virtually involving every organ. Hepatic involvement is represented by a spectrum of vascular abnormalities, which evolve in a continuum from tiny teleangiectases to substantial vascular malformations, potentially with a progressively greater arteriovenous shunt. Liver involvement in hereditary haemorrhagic telangiectasia is almost always asymptomatic; on the other hand, hepatic vascular malformations can induce severe complications, depending on the predominant venous side of the arteriovenous fistulas-high-output cardiac failure in the case of hepatohepatic fistulas, and portal hypertension in the case of hepatoportal fistulas. Doppler sonography can detect and stage hepatic vascular malformations in subjects with hereditary haemorrhagic telangiectasia; according to Doppler sonographic grading, appropriate advice for follow-up and/or therapy can be given.     

Hypertension portale et maladie de Rendu-Osler-Weber familiale

Background

Rendu-Osler-Weber disease is an autosomal dominant disease, characterized by widespread telangiectasia that can affect the skin, mucous membranes and many organs. The prevalence of liver involvement in patients with Rendu-Osler-Weber disease classically ranges from 8 to 31%, caused by vascular malformations which can be complicated by portal hypertension.

Case report

M. N.Z, a 40-year-old patient with familial and personal hemorrhagic antecedents was hospitalised in 2003 for severe anaemia. The clinical examination found telangiectases in skin and mucous membranes, hepatomegaly, splenomegaly, oedema and ascites. Abdominal sonography showed a homogeneous hepatosplenomegaly, ascites and an enlarged common hepatic artery. Doppler ultrasonography showed the presence of shunting between hepatic artery and portal vein. The ascites was rivalta negative. The upper digestive endoscopy showed stage II oesophageal varices and D1 telangiectasia. The patient received propranolol 160 mg/l and a diuretic. The patient developed refractory ascites and anaemia which required puncture, albuminotherapy and blood transfusions. The patient died six months later.

Discussion and conclusion

Hepatic vascular malformations in Rendu-Osler-Weber disease are generally asymptomatic. However, portal hypertension, as in our case, or severe biliary complications are possible. Doppler ultrasonography enables a diagnosis to be made. Liver transplant is the definitive treatment in cases of cardiac failure, biliary necrosis and/or portal hypertension.     

Liver disease in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is an hereditary disorder that results in fibrovascular dysplasia with the development of telangiectasias and arteriovenous malformations. It predominantly involves the skin, mucous membranes, viscera, lungs, and brain. Hereditary hemorrhagic telangiectasia shows great genetic heterogeneity, and its phenotypes have been classified based on the recently identified mutated genes: endoglin (HHT-1) and activin-like kinase receptor-1 (HHT-2). Other families with phenotypic HHT do not bear these mutations; therefore, other genes are probably involved as well. Liver involvement is reported in up to 30% of persons affected by HHT. Large arteriovenous malformations in the liver can lead to significant complications, including high-output congestive heart failure, portal hypertension, hepatic encephalopathy, biliary ischemia, and liver failure. Embolization of large arteriovenous malformations in the liver remains controversial; however, liver transplantation can successfully eradicate these complications.     

Natural History and Outcome of Hepatic Vascular Malformations in a Large Cohort of Patients with Hereditary Hemorrhagic Teleangiectasia

Background

Hereditary hemorrhagic telangiectasia is a genetic disease characterized by teleangiectasias involving virtually every organ. There are limited data in the literature regarding the natural history of liver vascular malformations in hemorrhagic telangiectasia and their associated morbidity and mortality.

Aim

This prospective cohort study sought to assess the outcome of liver involvement in hereditary hemorrhagic telangiectasia patients.

Methods

We analyzed 16 years of surveillance data from a tertiary hereditary hemorrhagic telangiectasia referral center in Italy. We considered for inclusion in this study 502 consecutive Italian patients at risk of hereditary hemorrhagic telangiectasia who presented at the hereditary hemorrhagic telangiectasia referral center and underwent a multidisciplinary screening protocol for the diagnosis of hereditary hemorrhagic telangiectasia. Of the 502 individuals assessed in the center, 154 had hepatic vascular malformations and were the subject of the study; 198 patients with hereditary hemorrhagic telangiectasia and without hepatic vascular malformations were the controls. Additionally, we report the response to treatment of patients with complicated hepatic vascular malformations.

Results

The 154 patients were included and followed for a median period of 44 months (range 12?C181); of these, eight (5.2%) died from VM-related complications and 39 (25.3%) experienced complications. The average incidence rates of death and complications were 1.1 and 3.6 per 100 person-years, respectively. The median overall survival and event-free survival after diagnosis were 175 and 90 months, respectively. The rate of complete response to therapy was 63%.

Conclusions

This study shows that substantial morbidity and mortality are associated with liver vascular malformations in hereditary hemorrhagic telangiectasia patients.     

Sonographic criteria for the diagnosis of hepatic involvement in hereditary hemorrhagic telangiectasia (HHT)

Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) is highly variable and may lead to severe clinical symptoms such as heart failure. This controlled, prospective study defined sonographic criteria for hepatic involvement in HHT. Color Doppler sonography and pulsed Doppler sonography were used to study 25 patients with HHT and liver involvement, 20 patients with HHT without liver involvement, 25 patients with cirrhosis, and 25 patients without liver disease. The diagnosis of hepatic manifestation was confirmed by computed tomography and/or angiography. Liver size, parenchymal changes of the liver, vessel diameters, and flow velocities of the portal vein and the hepatic artery were determined. Resistance index (RI) and pulsatility index (PI) were calculated. The diameter of the common hepatic artery was significantly dilated without overlap between HHT patients with liver involvement and the 3 control groups (mean 11.3 +/- 2.8 mm [HHT with liver involvement], 4.6 +/- 0.9 mm [HHT without liver involvement], 4.8 +/- 1.0 mm [cirrhosis], and 4.4 +/- 1.0 mm [healthy controls], P <.001). Doppler parameters of the proper hepatic artery differed significantly (all P <.001). In all patients with HHT and liver involvement, areas with intrahepatic hypervascularization caused by dilated intrahepatic arteries were observed in varying intensity. Cardiac output significantly correlated with the diameter of the common hepatic artery (r = 0.53, P =.007) and the portal vein (r = 0.42, P =.05). In conclusion, the diameter of the common hepatic artery (>7 mm) and intrahepatic hypervascularization are suitable sonographic diagnostic parameters of HHT with high sensitivity and specificity. Dilated diameters of the hepatic feeding vessels are indicators for systemic circulatory distress in these patients.     

Akute Gef??komplikationen der Leber

Acute hepatic vascular complications are rare. Acute portal vein thrombosis (PVT) and the Budd-Chiari syndrome (BSC) are the leading causes. Coagulopathy and local factors are present in up to 80% of cases. Diagnosis is established by colour-coded Doppler sonography, contrast-enhanced computed tomography or magnetic resonance imaging. Patients with acute PVT present with abdominal pain and disturbed intestinal motility. In the absence of cirrhosis anticoagulation with heparin is established followed by oral anticoagulation. In severe cases, surgical thrombectomy or transjugular thrombolysis with stent shunt may be necessary. Acute or fulminant BCS may require emergency liver transplantation or a transjugular intrahepatic portosystemic stent shunt, if patients present with acute liver failure. Milder cases receive anticoagulation for thrombolysis of occluded hepatic veins. Sinusoidal obstruction syndrome (SOS) is diagnosed after total body irradiation or chemotherapy, the term SOS replacing the former veno-occlusive disease. The treatment of congenital vascular malformations, complications in the setting of OLTX as well as patients with hepatic involvement of hereditary hemorrhagic telangiectasia requires significant expertise in a multidisciplinary approach.     

Acute hepatic vascular complications

Acute hepatic vascular complications are rare. Acute portal vein thrombosis (PVT) and the Budd-Chiari syndrome (BSC) are the leading causes. Coagulopathy and local factors are present in up to 80% of cases. Diagnosis is established by colour-coded Doppler sonography, contrast-enhanced computed tomography or magnetic resonance imaging. Patients with acute PVT present with abdominal pain and disturbed intestinal motility. In the absence of cirrhosis anticoagulation with heparin is established followed by oral anticoagulation. In severe cases, surgical thrombectomy or transjugular thrombolysis with stent shunt may be necessary. Acute or fulminant BCS may require emergency liver transplantation or a transjugular intrahepatic portosystemic stent shunt, if patients present with acute liver failure. Milder cases receive anticoagulation for thrombolysis of occluded hepatic veins. Sinusoidal obstruction syndrome (SOS) is diagnosed after total body irradiation or chemotherapy, the term SOS replacing the former veno-occlusive disease. The treatment of congenital vascular malformations, complications in the setting of OLTX as well as patients with hepatic involvement of hereditary hemorrhagic telangiectasia requires significant expertise in a multidisciplinary approach.     

Portal vein aneurysm in hereditary hemorrhagic telangiectasia

Both hereditary hemorrhagic telangiectasia (HHT) and portal vein aneurysm are rare disorders. We described the first documented case of HHT associated with portal vein aneurysm. As the portal vein aneurysm in this patient associated with HHT, the pathogenesis in this patient seems to have been a congenital anomaly of the vasculature.     

Liver involvement in hereditary hemorrhagic telangiectasia (HHT)

Liver involvement in hereditary hemorrhagic telangiectasia (HHT) consists of extensive intrahepatic vascular malformations associated with blood shunting (arteriovenous, arterioportal and/or portovenous). It is a rare disorder that nevertheless can result in significant systemic and hepatobiliary abnormalities. Although hepatic vascular malformations are present in a majority of patients with HHT, symptoms occur in a only a minority with a clear predominance for the female gender. Symptoms from liver vascular malformations are often misdiagnosed and this can lead to potentially harmful interventions. In this review article, clinical findings of liver involvement in HHT and their pathophysiology are discussed as well as diagnostic methodologies, therapies used and their outcome. Data presented is based on a review of the literature performed in October 2006 using the following MEDLINE search terms: (hereditary hemorrhagic telangiectasia [ALL] OR Rendu-Osler-Weber [ALL]) AND (liver OR hepatic [ALL]). Papers were considered if they were published in English and if they included specific cases that were sufficiently described.     

Coronary artery ectasia associated with hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) is characterized by a variety of cutaneous, mucosal, and visceral vascular anomalies. A patient with classic hereditary hemorrhagic telangiectasia was shown to have three-vessel coronary artery ectasia without evident atherosclerosis, and association not previously demonstrated. The possibility that coronary artery ectasia may be a manifestation of hereditary hemorrhagic telangiectasia is discussed.     

Severe hemoptysis due to portal hypertension. Responsibility of acquired splenopulmonary shunt and treatment by proximal splenorenal anastomosis]

Hemoptysis is not considered as an hemorrhagic complication of portal hypertension. We report a patient with liver cirrhosis and portal hypertension who developed a hitherto unreported porto-pulmonary transdiaphragmatic collaterality many years after splenectomy. Life threatening hemoptysis complicated this unusual shunt after banal bronchitis. A proximal splenorenal shunt was performed and was completely effective at 26 months.     

A histologically proven case of progressive liver sarcoidosis with variceal rupture

Sarcoidosis is a chronic multi-systemic granulomatous disease,and liver involvement frequently occurs.in most cases,no evidence of liver dysfunction is ob-served,and portal hypertension due to sarcoid liver diseases is a rareoccurrence.Moreover,no case of liver sarcoidosis has ever been reported with confirma-tion of the disease progression.Herein we describe a patient having hepatic sarcoidosis with severe portal hypertension and liver dysfunction.The diagnosis was histologically confirmed from granulomatous status to established liver cirrhosis over 10 years.A 46-year-old woman developed massive hematemesis due to the rupture of gastric cardial varices.She underwent emer-gency endoscopic injection sclerotherapy,and clear evi-dence of chronic hepatic failure.Twelve years ago,she was diagnosed as having sarcoidosis with respiratoryclinicalsymptoms.Liver biopsy revealed asymptomatic incidental granulomas without fibrosis development.After a couple of years,features of liver dysfunction were manifest and progressed.Ten years after the first biopsy,a second liver biopsy was performed,and well established dense fibrosis was revealed.Although significant liver dysfunction with portal hypertension is rarely seen in sarcoidosis,this case indicates that we have to consider the possibility that sarcoidosis may cause end-stage liver cirrhosis.     

Liver involvement in hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease). Report of one case and review of the literature

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia; mutations in at least three genes (ENG, ACVRL1 et MADH4), which are components of transforming growth factor (TGF)-beta, may lead to the clinical picture of HHT. HHT is a multisystemic angiodysplasia, resulting in multiple vascular malformations, involving notably the liver. EXEGESIS: We report the case of a patient with anicteric cholestasis, revealing HHT. Abdominal CT-scan revealed hepatic artery dilation and multiple arteriovenous fistula. At 2-year follow-up, the patient exhibited liver involvement-associated high output cardiac insufficiency. CONCLUSION: Liver involvement is frequent in HHT, occurring in 8-31% of patients; it may lead to life-threatening complications, such as high output cardiac failure, portal hypertension or severe cholangitis. Abdominal Doppler ultrasonography is a non-invasive accurate method, suitable for first-line imaging of the liver in patients with HHT; it should be done in all patients, in order to detect HHT-related hepatic vascular malformations.