Vascular Liver Diseases PDF

Vascular Liver Diseases Prof. Khaled Farid Marei Mansoura University Budd–Chiari syndrome-Classification  Budd–Chiari syndrome (BCS) results from obstruction to hepatic venous outflow caused by either thrombotic or non-thrombotic occlusion. Classification  BCS is classified according to the f...

Vascular Liver Diseases Prof. Khaled Farid Marei Mansoura University Budd–Chiari syndrome-Classification  Budd–Chiari syndrome (BCS) results from obstruction to hepatic venous outflow caused by either thrombotic or non-thrombotic occlusion. Classification  BCS is classified according to the following: a. The duration of symptoms and signs of liver disease *Acute *Subacute *Chronic b. The site of obstruction *Small hepatic veins, excluding terminal venules *Large hepatic veins *Hepatic inferior vena cava (IVC) c. The cause of obstruction *Thrombosis *Membranous web *Direct infiltration by tumor or metastasis along veins Budd–Chiari syndrome-Etiology  Most patients with BCS have an underlying thrombotic diathesis.  In less than 20% of cases the disorder is idiopathic.  Disorders associated with BCS include the following: a. Hematologic disorders *Polycythemia rubra vera *Myeloproliferative disorder *Paroxysmal nocturnal hemoglobinuria *Antiphospholipid syndrome b. Inherited thrombotic diathesis *Factor V Leiden mutation *Protein C and/or S deficiency c. Pregnancy or high-dose estrogen (oral contraceptives) use d. Chronic infections of the liver as TB e. Tumors as hepatocellular carcinoma f. Chronic inflammatory diseases as inflammatory bowel disease Budd–Chiari syndrome-Clinical features Acute venous occlusion causes the rapid development of upper abdominal pain, marked ascites and occasionally acute liver failure. More gradual occlusion causes gross ascites and often upper abdominal discomfort. The classic triad of hepatomegaly, ascites, and abdominal pain is seen in most patients but is nonspecific. Peripheral edema suggests the possibility of thrombosis or compression of the IVC. The natural history of untreated BCS is progression of symptoms often resulting in death caused by complications of portal hypertension. Untreated, the mortality rate is greater than 50%, except in some patients with membranous webs, in whom symptoms develop slowly. Budd–Chiari syndrome-Investigations  LFTs: vary depending on the presentation; can show features of acute hepatitis when the onset is rapid.  Ascitic fluid characteristics are useful clues to the diagnosis: High protein concentration (greater than 2.0 g/dL) White blood cell count usually lower than 500/mm3 Serum-ascites albumin gradient usually 1.1 or higher  Color-flow Doppler ultrasonography, CT, MRI: may demonstrate occlusion of the hepatic veins and inferior vena cava.  Hepatic venography usually performed in conjunction with therapeutic intervention such as transjugular intrahepatic portosystemic shunt (TIPS).  Liver biopsy shows evidence of high-grade venous congestion. Budd–Chiari syndrome-Diagnosis A high index of suspicion is necessary for diagnosis because clinical manifestations and laboratory results are nonspecific. The diagnostic approach to a patient suspected of having hepatic vein occlusion should begin with color Doppler ultrasonography, followed by three-phase CT or MRI. If imaging is equivocal for BCS, then hepatic venography with inferior vena cavography should be performed to confirm the diagnosis. Liver biopsy may be of value to define the extent of fibrosis but is usually unnecessary. Budd–Chiari syndrome-Treatment Diuretics are useful for relieving ascites but do not alter the long-term outcome. Anticoagulation with heparin followed by warfarin is recommended in all patients, because it prevents repeat thromboses. Where recent thrombosis is suspected, thrombolysis with streptokinase followed by heparin and oral anticoagulation should be considered. Angioplasty of short-segment obstructions such as webs or short hepatic vein stenoses relief obstruction temporary, and repeated treatment is required for long-term management. Placement of a metal stent in the hepatic vein following angioplasty of a short-segment stenosis has been used to improve long-term patency. TIPS can be performed in more than 90% of patients despite occlusion of hepatic veins. Liver transplantation is recommended in patients in whom minimally invasive procedures fail and in selected patients with liver failure or partial portal vein thrombosis. Sinusoidal Obstruction Syndrome-Definition  Sinusoidal obstruction syndrome (SOS) is a rare condition characterized by widespread occlusion of central hepatic veins.  SOS (formerly referred to as veno-occlusive disease) is most often seen: In an acute form following bone marrow transplantation (BMT) or hematopoietic stem cell transplantation. It is thought to result from toxicity from the preparative regimen of high-dose cytoreductive therapy, with or without hepatic irradiation. In a chronic, more indolent form following toxicity of pyrrolizidine alkaloids from plants of theCrotalaria, Senecio, andHeliotropium genera. The alkaloids are ingested in the form of herbal teas, hence the term Jamaican bush tea disease.  Histologic features include the following: Subendothelial sclerosis of terminal hepatic venules Thrombosis secondary to sclerosis Sinusoidal fibrosis, particularly in later stages and with chronic injury Centrilobular hepatocyte necrosis. SOS-Clinical features  SOS following BMT has been defined as the occurrence of two or more of the following characteristics appearing within 20 days after transplantation: Painful hepatomegaly Sudden weight gain of more than 2% of baseline body weight Total serum bilirubin level greater than 2.0 mg/dL  The occurrence of SOS is significantly correlated with the subsequent development of renal insufficiency, pleural effusions, heart failure, pulmonary infiltrates, and bleeding requiring blood transfusions.  The more chronic form of SOS develops in persons who ingest pyrrolizidine alkaloids. Clinical features of this condition are similar to those of hepatic vein occlusion and include tender hepatomegaly, abdominal pain, ascites, and fatigue. SOS-Treatment  Treatment of SOS following BMT is largely supportive: Avoid excessive fluid administration Support with platelet and red blood cell transfusions is often necessary because of the profound cytopenias that accompany BMT. Use of dopamine and other pressors is often necessary to maintain renal perfusion, particularly in the presence of a capillary leak syndrome. Broad-spectrum antibiotics are used to treat presumptive infection.  Defibrotide, may be of benefit in treating severe SOS, with a complete remission rate of 30% to 60%.  TIPS is technically feasible but not recommended in patients with SOS.  Liver transplantation for chronic SOS.  Early cases may be managed with a portosystemic shunt. Portal Vein Thrombosis (PVT)-Classification  Acute PVT Symptoms less than 60 days before presentation. No evidence of underlying cirrhosis or portal hypertension.  Chronic PVT May develop in isolation or as a complication of cirrhosis. Presence of portal vein collaterals (portal cavernoma) and portal hypertension distinguish the chronic from the acute phase.  Splenic vein thrombosis May develop in isolation from thrombosis within the main portal vein. Leads to splenomegaly and isolated gastric varices without esophageal varices. Portal Vein Thrombosis (PVT)-Etiology 1. As many as 70% of patients with PVT have an underlying thrombotic disorder. 2. Following infections within the abdomen presumably result from septic pylephlebitis: Acute appendicitis Acute cholecystitis or cholangitis Pancreatitis 3. Isolated thrombosis of the splenic vein may develop following: Chronic pancreatitis Direct trauma to the abdomen 4. PVT in cirrhosis probably results from a combination of these factors: Diminished blood flow within the portal vein Reduced levels of protein C and protein S Hepatocellular carcinoma PVT-Clinical features 1. Acute PVT Abdominal pain and nausea Intestinal ischemia, which may result particularly when thrombosis also involves the superior mesenteric vein Intestinal infarction, which is uncommon but can be fatal 2. Chronic PVT Gastroesophageal varices Splenomegaly Thrombocytopenia Variceal bleeding, well tolerated in the absence of cirrhosis Ascites, which is rare in the absence of cirrhosis PVT-Investigations  Doppler ultrasonography  CT and MRI can often identify thrombus within the portal vein and are helpful when Doppler ultrasonography results are equivocal.  Liver biochemical test levels are normal except in patients with underlying chronic liver disease.  A thorough evaluation for an underlying thrombotic disorder and hepatocellular carcinoma is warranted. PVT-Treatment  Acute PVT  Anticoagulation with heparin or LMWH is indicated in the acute phase. It may promote recanalization if carried out within the first 30 days. It reduces the risk of complications such as bowel infarction. Long-term anticoagulation in presence of an underlying thrombotic disorder.  Thrombolysis is associated with a high rate of bleeding. Chronic PVT  Long-term use of a beta-blocker has been reported to reduce the risk of variceal bleeding.  Band ligation of varices is safe and effective.  Surgical portosystemic shunts in patients in whom less invasive methods fail.  Splenectomy is effective in treating gastric varices resulting from isolated Splenic VT. Vascular Liver Diseases  Hepatopulmonary syndrome In this condition, patients with cirrhosis and portal hypertension develop resistant hypoxemia because of intrapulmonary shunting through direct arteriovenous communications. Clinical features include finger clubbing, spider naevi, cyanosis and a fall in Sa O2 on standing. It resolves following liver transplantation.  Portopulmonary hypertension This is defined as pulmonary hypertension in a patient with portal hypertension. It is caused by vasoconstriction and obliteration of the pulmonary arterial system and presents with breathlessness and fatigue. Pregnancy and Liver Normal changes during pregnancy Liver diseases in pregnancy Liver diseases specific to pregnancy Intrahepatic cholestasis of pregnancy (IHCP) Reversible form of cholestasis characterized by intense pruritus in pregnancy, elevated serum ALT and fasting serum bile acid levels, and spontaneous relief of symptoms and signs within 4 to 6 weeks after delivery. IHCP is the most common liver disease in pregnancy with prevalence ranging between 0.3 and 5.6%. More common in late second or third trimester, but can occur in any trimester Risk factors include advanced maternal age, a history of cholestasis with oral contraceptives, and a personal or family history of IHCP. Etiology is multifactorial, including genetic, hormonal, and environmental factors. Intrahepatic cholestasis of pregnancy (IHCP) Clinical and laboratory features  Jaundice in 25% of patients and following the onset of pruritus  Elevated serum aminotransferase levels (up to four-fold), serum bile acid levels (30–100x), and occasionally serum cholesterol and triglyceride levels  Fat malabsorption can result in fat-soluble vitamin deficiencies requiring supplementation. Diagnosis:  Clinical presentation and high bile acid level.  Ultrasonography should be performed to exclude cholelithiasis. Intrahepatic cholestasis of pregnancy (IHCP) Treatment  Symptom management: sleeping in a cold room, topical alcohol and camphor menthol lotion, cholestyramine, and ursodeoxycholic acid (UDCA) 10 to 15 mg/kg body weight  Early delivery at 37 weeks is encouraged, because intrauterine death is more common in the last month. Outcome  Maternal outcomes are excellent  Increased risk of preterm delivery (19% to 60%); meconium staining of amniotic fluid (24%); fetal bradycardia (14%); fetal distress (22% to 41%); fetal loss (0.4% on average; 4.1% in severe cases), particularly when fasting serum bile acid levels are greater than 40 μmol/L. Acute fatty liver of pregnancy  A rare life-threatening complication of pregnancy manifested by microvesicular fatty infiltration of the liver and progressive liver failure.  Onset in third trimester (usually after 35th week, but as early as 26 weeks; can occur in the immediate postpartum period).  Incidence: 1 in 10,000 to 15,000 deliveries.  Risk factors: primiparity, multiple gestations, and male fetuses.  Defects in mitochondrial fatty acid beta-oxidation in the mother, caused by fetal deficiency in the long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) enzyme. LCHAD is part of mitochondrial trifunctional protein (MTP) and catalyzes the third step in β-oxidation of long-chain fatty acids.  Abnormal concentrations of fetal long-chain fatty acids enter the maternal circulation and have toxic effects in the mother. Acute fatty liver of pregnancy Clinical and laboratory features  Symptoms include headache, fatigue, malaise, nausea, vomiting, and abdominal pain  Jaundice may follow a prodrome  Progressive liver failure may occur, with coagulopathy, encephalopathy, or renal failure  50% of patients have signs of pre-eclampsia  Serum aminotransferase levels are elevated (usually less than 500 U/L)  Serum alkaline phosphatase and bilirubin levels are mildly to moderately elevated  Hyperuricemia occurs in 80% Acute fatty liver of pregnancy Diagnosis  Abdominal ultrasonography and CT are inconsistent in detecting fatty infiltration  If clinically suspected, emergency liver biopsy should be done. Treatment  Rapid delivery of the infant is critical.  Most women improve, but fulminant hepatic failure may occur, and treatment with liver transplantation has been reported  Screening for a fatty acid oxidation defect is indicated in affected patients Outcome  Maternal mortality rate of 8% to 18%  Fetal mortality rate of 18% to 23% HELLP Syndrome  Hemolysis, elevated liver enzymes, and low platelets  More common in the third trimester (usually at or after 32 weeks)  Incidence: 0.2% to 0.6% of all pregnancies; 4% to 12% in women with pre-eclampsia/ eclampsia Clinical and laboratory features  Epigastric pain (65%), nausea or vomiting (30%), headache (31%), hypertension (85%), visual changes, weight gain, edema  Microangiopathic hemolytic anemia with increased serum lactate dehydrogenase and indirect bilirubin levels and decreased haptoglobin levels  Elevated serum aminotransferase levels (from mild to 10 to 100 times)  Decreased platelet count (may be lower than 10,000/mm3)  Proteinuria  Positive D-dimer test is possibly predictive of HELLP syndrome in pre-eclamptic patients HELLP Syndrome Diagnosis: Hemolytic anemia, elevated aminotransferases, low platelets Treatment  Delivery of the infant is indicated in the presence of maternal or fetal distress or a rapidly dropping platelet count. Coexisting pre-eclampsia or AFLP may dictate early delivery  Hospitalization is indicated for treatment of hypertension, stabilization of DIC, seizure prophylaxis, and fetal monitoring  Corticosteroids are recommended if gestation is less than 34 weeks, to improve fetal lung Maturity Outcome  Maternal mortality rate of 1%  Perinatal infant mortality rate of 7% to 22%