I. Overview Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is a hereditary disorder of angiogenesis development that can involve the skin, mucous membranes, lungs, gastrointestinal tract, liver, brain and other organs of the body. HHT is an autosomal dominant disorder with two types: the causative gene is ENG ( endoglin, located on the long arm of chromosome 9, 9q33-34), and HHT type 2, in which the causative gene is ALK-1 (activin receptor-like kinase 1, located on the long arm of chromosome 12, 12q13). HHT is a disorder of vascular development, which is characterized by capillary dilation, arteriovenous fistula and aneurysm formation. The lesions are located in the vessel wall and are characterized by a lack of elastic fibers and smooth muscle in the capillary and small arterial walls, or even by a single layer of endothelial cells, degenerative endothelial cell degeneration, defective endothelial cell junctions, and loss of responsiveness to sympathetic nerves and vasoactive substances. The rupture of blood vessels can be triggered by a slight external force or intravascular pressure, and is most common in the skin and mucous membranes, especially on the back of the hands and face. Hereditary hemorrhagic capillary dilation involves the liver in 8-31% of cases, and fewer have early symptoms. With the improvement of diagnostic techniques and understanding of HHT, HHT involving the liver is gradually gaining attention. The main pathological basis of the liver is also capillary dilatation, arteriovenous fistulas and aneurysms. Three-dimensional imaging of blood vessels has demonstrated the presence of hepatic aneurysms, abnormal dilatation of hepatic sinuses, and three types of fistulas in patients with hepatic HHT: hepatic artery-hepatic vein fistula, hepatic artery-portal vein fistula, and hepatic vein-portal vein fistula. Arteriovenous fistulas result in abnormal arteriovenous shunts that cause portal hypertension, liver failure, and hepatic encephalopathy. Arteriovenous fistula shunts also increase cardiac preload, raise cardiac output, produce a hyperdynamic circulatory state, and can be secondary to congestive heart failure. In hereditary hemorrhagic capillary dilation involving the liver, biliary pathology is more important. The blood supply to the biliary system is derived from the peribiliary vascular plexus originating from the hepatic artery. Arteriovenous fistulas may cause hypoperfusion of this vascular plexus, ischemic necrosis of the biliary tract both inside and outside the liver, which in turn leads to stenosis and phasic dilatation of the biliary tract, and can result in ischemic necrosis of the biliary tract. Nodular regeneration of hepatocytes, hepatic fibrosis, and even cirrhosis. These changes are similar to the pathological changes commonly seen in the liver with perfusion chemotherapy and liver transplantation. In cases similar to Caroli’s disease, some scholars believe that the normal development of the biliary tract may be affected by abnormalities in the development of early biliary pegylated vessels, and the coexistence of hereditary hemorrhagic capillary dilatation sign in the liver and polycystic kidney suggests this possibility. Clinical manifestations HHT can occur in all organs of the body, and the most susceptible organs are nose, skin, lung, gastrointestinal tract and brain. Patients can develop epistaxis in childhood, which is characterized by repeated rupture and bleeding of the involved vessels. Patients with skin and mucous membrane involvement may show red spots on the lips, tongue, fingers, face, conjunctiva, trunk, arms, etc. Capillaries or small blood vessels may be nodular, spider nevus-like or hemangioma-like dilated and prone to rupture and bleeding, and patients with HHT may also suffer from hypoxemia and secondary erythrocytosis due to pulmonary arteriovenous fistula, resulting in fatigue, cyanosis and other symptoms of hypoxia. Brain involvement can manifest as migraine, transient ischemic attack, stroke, epilepsy, cerebral hemorrhage, and subarachnoid hemorrhage. Those with gastrointestinal tract involvement may present with symptoms such as vomiting blood and blood in the stool due to gastrointestinal bleeding. In addition, chronic blood loss or frequent and heavy bleeding can lead to iron deficiency anemia. Patients with hereditary hemorrhagic capillary dilatation of the liver have no obvious clinical symptoms in the early stages and may have a combination of these clinical manifestations. As the disease progresses more than half of the patients will develop liver-related clinical symptoms. The main clinical manifestations are congestive heart failure, portal hypertension, and biliary disease. Congestive heart failure is the most common symptom in patients with HHT with liver involvement. The shunt of the arteriovenous fistula causes blood to flow directly from the hepatic artery into the hepatic vein without passing through the hepatic sinusoids and into the body circulation, increasing the preload of the heart, causing high cardiac output and generating a hyperdynamic circulatory state, which leads to secondary congestive heart failure, with varying degrees of dyspnea and edema. Hepatomegaly may occur due to increased blood flow through the hepatic arteriovenous fistula, with pain and tenderness in the hepatic region, and in some patients, a pulsating mass may be palpable, tremulous to touch, and a continuous vascular murmur may be heard. Hepatic arteriovenous fistula shunts can lead to portal hypertension, and patients may develop complications such as ascites and esophagogastric fundic varices. The formation of a hepatic arteriovenous fistula causes biliary ischemia, and patients develop right upper abdominal pain, cholestasis, and cholangitis, and with progression of the disease, patients may also develop biliary necrosis or even hepatic necrosis. A few patients can also develop abdominal colic, hepatic nodular hyperplasia, cirrhosis and even hepatic encephalopathy,. III. Diagnosis Patients with hepatic HHT are mostly detected early during physical examination. Patients may have recurrent episodes of spontaneous epistaxis, dilation and bleeding of skin and mucous membrane capillaries in the lips, tongue, fingers, face, conjunctiva, trunk, arms, and other visceral (lung, gastrointestinal tract, brain, etc.) involvement, and may have a family history of HHT, i.e., a patient with HHT in the immediate family. The diagnosis of hepatic HHT is based on clinical manifestations as well as imaging studies. The diagnosis is easier in those with symptoms of congestive heart failure, portal hypertension, and biliary system. Patients with atypical clinical manifestations rely mainly on imaging examinations, such as ultrasound, CT, multilayer spiral CT angiography (CTA), MRI, and angiography. Ultrasonography is simple and convenient, and is considered an effective means of screening and diagnosis. it mainly shows tortuous dilatation of hepatic arteries in a stepped, worm-like or cystic shape, and some patients may have hemangiomas with sieve-like structures. color Doppler flow imaging can also show abnormal blood flow conditions such as high speed and low resistance. ct shows tortuous dilated vessels around the abdominal aorta, in the hilar region and in the liver, and diffusely dilated capillary network in the liver. Cirrhosis and increase in liver volume are also seen with biliary cyst formation, bile duct dilatation and stenosis. Due to the presence of hepatic arteriovenous fistula, intensive CT is seen in the hepatic arterial phase with significant enhancement of the lesion area. The angiography (DSA) can visually reflect the dilatation of hepatic artery and the formation of intrahepatic arteriovenous fistula, and CTA can visually show the twisting, dilatation and malformed vascular masses in the liver by combining volume reconstruction and maximum density projection techniques, and the multi-phase scan can show the arteriovenous malformation and can observe the position relationship between the vessels from multiple angles. Its combination with CT can more clearly define the liver parenchyma and biliary tract, and it is also a non-invasive operation, avoiding complications such as puncture infection. Therefore, for this part of complex hepatic HHT lesions, CTA is superior to DSA. the diagnostic value of MRI is approximately the same as CT. With the advancement of experimental techniques in molecular biology and molecular genetics, genetic diagnosis has become a feasible diagnostic tool for HHT as an autosomal dominant disorder. Moreover, after comparison, Cohen JH et al. concluded that genetic diagnosis is not significantly more expensive than traditional clinical diagnosis and is more suitable for family screening. IV. Treatment The treatment of hepatic HHT is still controversial, including medical support therapy and surgery, and individualized treatment may be a better choice. Treatment is mainly directed at congestive heart failure, complications of portal hypertension, and biliary lesions. Surgical treatment of hepatic HHT mainly includes hepatic arteriovenous fistula ligation, hepatic artery interventional embolization, and liver transplantation. For asymptomatic and mild patients, they can be followed up and observed or treated symptomatically with drugs. Surgical treatment for hyperperfusion of the hepatic artery, and arteriovenous fistula may prevent complications. In contrast, for patients with more severe and complex hepatic HHT, aggressive surgical intervention should be performed, mainly including hepatic artery ligation, tethering, hepatic artery interventional embolization, and liver transplantation. Liver transplantation is a curative treatment and has been reported in Europe and the United States with a good overall prognosis. However, the shortage of donor livers, the stringent requirements of surgical conditions and techniques, and the high cost of liver transplantation have limited the availability of liver transplantation. Hepatic artery ligation and tethering can achieve the same results as liver transplantation in some patients by reducing hepatic artery blood supply, alleviating hepatic venous fistula blood supply, reducing abnormal shunts, reducing complications, and improving the organism’s condition. Hepatic artery ligation can effectively close the arteriovenous fistula and reduce liver blood theft and cardiac load. Intraoperative preservation of the perihepatic ligament as much as possible, no freeing of the common bile duct, preservation of the perihepatic ligament and arterial collateral circulation can prevent to some extent the ischemia of the intra- and extrahepatic biliary tract caused by hepatic artery ligation. In patients with HHT who already have severe congestive heart failure, pulmonary hypertension, complications of portal hypertension and biliary complications, it may be difficult to change the patient’s pathophysiological condition even with liver transplantation, and symptomatic treatment with medications may improve the quality of life and prolong survival time. V. Prognosis Early diagnosis and treatment of hepatic HHT is more important. Screening and timely diagnosis and treatment of HHT family members, suspected HHT patients and patients with juvenile polyposis can effectively avoid the development of asymptomatic hepatic HHT patients and prevent the occurrence of heart failure, portal hypertension and biliary complications. With the continuous progress of non-invasive examination techniques such as ultrasound and CT, the diagnostic accuracy of HHT imaging has improved significantly, and the examination of patients with pain in the liver area, localized pulsating masses, tremors and continuous vascular murmurs can basically provide a clear diagnosis and can provide a strong basis and support for treatment. genetic diagnosis of HHT is gradually maturing and can be used as a diagnostic tool for hepatic HHT. Patients with asymptomatic and mild lesions can achieve long-term survival, even in complicated patients through hepatic artery ligation (tethering) and liver transplantation.