Management conference Middle age man with nephrotic syndrome, ascitis and edema Raika Jamali MD Digestive Disease Research Center Tehran University of Medical Sciences • A 49 years old man with progressive bilateral pedal edema and ascitis from 1 month ago. • History of DM for 4 years. • Three months ago during the evaluation for excessive proteinuria inappropriate for diabetic nephropathy ,prolongation of PT was detected before kidney biopsy. • Viral markers requested and was referred for liver function evaluation. EXAM • Vital signs were stable. No fever. • Mild anemia. Ichterus in sclera. • Parallel collaterals in chest and upper abdomen which filled upward. • Tense ascitis. liver span 14 cm. • Moderate splenomegaly . • No signs of chronic liver disease. • Bilateral pedal edema. • • • • WBC=6500 HB=10 PLT=245000 MCV=85 • FBS=180 • TG=200 • AFP =60,92 AST=52 ALT=43 Bili T=5 Bili D=1.3 ALP=508 PT(INR)=2.6 PTT=38 Albumin=2.2 Protein=5.2 • BUN=15 • Cr=0.9 • Uric Acid=4 • U/A: 3+ protein • 24 h urine protein: 7 gr /day • HCV Ab=suspicious • HBs Ag=Neg • HBs Ab=positive • HBc Ab=positive • HBV DNA and HCV RNA Titer : undetectable Ascitic fluid • RBC=20 • WBC=70 • Albumin=0.5 • Cytology=negative for malignancy Sonography • Liver was enlarged with hetrogenous echo pattern. • PV diameter 10 mm. • Severe ascitis. • Moderate splenomrgaly. Color Doppler sonography • IVC and suprahepatic veins were occluded. • Portal vein was occluded with collaterals in hilum. • Renal veins were thrombosed. • Splenic vein was patent. • • • • • • • • • • Activated protein C resistance: 221(120) B2 micro globulin : 10 (0-3) Anti cardiolipin Ab: normal Anti phospholipids Ab: normal Pr C: reduced Pr S: reduced Anti thrombin 3: normal homocysteine: normal Ham, sucrose test: normal CD 55,59: normal Endoscopy • Fundal and esophageal varices were seen. • Snake skin appearance in fundus and body. • mottled appearance to the underperfused liver with collapsed portal veins, • ascites (small arrows) • extensive retroperitoneal varices (large arrow). • enlarged caudate lobe of the liver (large arrowhead) • the collapsed small IVC (small arrowhead). Follow Up • The patient was treated with diuretic and concomitant albumin. • Several abdominal paracentesis were performed. • Heparin started and switched to warfarin. • Proteinuria decreased during F/U. • Ascitis and edema is partially controlled with diuretic. • Hypercoagulability states were checked again which showed normal results. Budd-Chiari syndrome • more common in women • third or fourth decade • most common symptoms is ascites (84%) and hepatomegaly (76%) • obstruction was in the hepatic veins (62%) inferior vena cava (7%) • portal vein thrombosis (14%) • myeloproliferative disorder was present in 23% (polycythemia vera). Major causes of the Budd-Chiari syndrome • • • • • • • • • Myeloproliferative diseases Malignancy (Hepatocellular carcinoma) Infections and benign lesions of the liver Oral contraceptives Pregnancy Hypercoagulable Behcet's disease Membranous webs of IVC Idiopathic • Acute (20%) : (2% with fulminant hepatic failure) • Subacute (40%): (having signs or symptoms for < 6 months and no evidence of cirrhosis) • Chronic (40%): (having signs or symptoms for > 6 months with evidence of cirrhosis) Acute • most commonly in women (during pregnancy ) • pain and hepatomegaly • Jaundice and ascites develop rapidly • Liver function can deteriorate quickly, leading to hepatic encephalopathy • DDx: ischemic, viral, malignant/infiltrative, and toxic hepatitis Subacute and chronic disease • clinical manifestations depend upon the extent of occlusion, and the recruitment of collateral circulation. • Chronic occlusion of the hepatic veins may be associated with hypertrophy of the caudate lobe. • This cause compression of the intrahepatic portion of the IVC, leading to lower extremity edema • cirrhosis may develop in the chronically congested liver, resulting in portal hypertension • encephalopathy is infrequent • Hepatopulmonary syndrome (28%) • liver biochemical tests are usually mildly abnormal DIAGNOSIS • Chronic or subacute Budd-Chiari syndrome should be considered in unexplained liver dysfunction, particularly if ascites is a principal feature, or if risk factors for BuddChiari syndrome exist. Clinical: • Splenomegaly, venous collaterals • Edema of the lower extremities suggests occlusion of the inferior vena cava • Signs of right-sided congestive heart failure (such as jugular venous distension) • Acute : hepatomegaly, RUQ pain, ascites • Accuracy of noninvasive imaging modalities depends upon: duration of disease, location of the clot. • Portal vein thrombosis limits therapeutic options and has a poor prognosis Doppler ultrasonography • • • • • • • • • Screening test hepatomegaly, splenomegaly, ascites, intraabdominal collaterals, caudate lobe hypertrophy, atrophy of other hepatic lobes, compression of IVC Thickening, irregularity, stenosis, or dilation of the walls of the hepatic veins • Abnormal flow in the major hepatic veins or IVC CT scan • Delayed or absent filling of the three major hepatic veins • Patchy flea-bitten appearance of the liver • Rapid clearance of dye from the caudate lobe • Narrowing and/or lack of opacification of the inferior vena cava Magnetic resonance imaging • typical distorted "comma-shaped" intrahepatic collaterals • unremarkable ultrasound examination but in whom the suspicion is high Venography Gold standard for diagnosis plan therapeutic interventions . Determine pressure gradient above and below the entrance of the hepatic veins into the inferior vena cava • Accurately define the extent or characteristics of the hepatic venous flow • Compression of the intrahepatic IVC, leads to sluggish flow in hepatic veins. As a result, the hepatic veins can be undetectable during ultrasound Doppler studies, although they may be patent and amenable to therapy Liver biopsy • Can be diagnostic in the acute or subacute form • Features include centrizonal congestion, necrosis, and hemorrhage • Cirrhosis may be present in the chronic form • Determine prognosis and guide therapy • Cirrhotics are less likely to benefit from revascularization procedures • thrombotic process in Budd-Chiari syndrome may not involve all the hepatic veins. • Thus, the distribution of the typical pathologic findings may be focal or patchy. As a result, some patients require biopsy of both the right and the left lobes of the liver. • laparoscopic approach may be better suited • Perfom Bx when there is confusion regarding the diagnosis and plan treatment accordingly TREATMENT • Prevent the propagation of the clot • Decompress the congested liver • Prevent complications (malnutrition, portal hypertension) _________________________________ • Medical treatment (supportive care, anticoagulation, thrombolysis), • Radiologic procedures (angioplasty, TIPS,) • Surgical intervention (shunting procedures , transplantation). Medical therapy • • • • • Diuretics and a low sodium diet large-volume paracenteses Improve nutritional status Underlying cause should be investigated Myeloproliferative disorder may benefit from treatment with aspirin and hydroxyurea • Anticoagulation alone is unlikely to lead to sufficient recanalization of occluded vessels to avoid the progression of liver disease. • A trend for a benefit of anticoagulation on survival in less severe disease. Medical therapy : • 1) Chronic or subacute Budd-Chiari syndrome with well compensated liver disease at the time of presentation. • 2) When other types of therapy are not feasible • Risk of anticoagulation should also be considered, especially in patients who present with bleeding complications • Patients receiving only medical therapy should be monitored closely for disease progression (liver biopsies annually )and portal hypertension complications (looking for varices) Thrombolytic therapy • In acute form which blood clots are younger than three to four weeks • Do not use thrombolytic agents in: • patients who have extensive clot involving the IVC • or a clot of unknown age. Radiologic treatment • Angioplasty • Stenting • Transjugular intrahepatic portosystemic shunt Surgical therapy • Restore hepatic venous drainage using shunt surgery • Because of the availability of TIPS, few vascular surgeons routinely perform shunt surgery. • Underlying cause of the thrombotic diathesis should be identified and treated prior to considering shunt surgery. • Unlikely to be beneficial in patients who have cirrhosis, Such patients are best managed with liver transplantation. • survival following shunt surgery depends upon the extent of liver damage prior to surgery, and the continued patency of the shunt • Maintenance of shunt patency often requires anticoagulation • deterioration in patients following shunt surgery should be investigated by angiography to determine whether the shunt has thrombosed, which may be corrected by angioplasty. Liver transplantation • who are not candidates for radiologic or surgical decompression • or who have decompensated cirrhosis • protein S, protein C, or antithrombin III deficiency may also be cured of their clotting tendency by liver transplantation, • Survival following OLT depends upon the underlying cause of the Budd-Chiari syndrome and the patients condition at the time of the transplant Budd-Chiari syndrome during nephrotic relapse in a patient with resistance to activated protein C clotting inhibitor • Am J Kidney Dis. • It has long been known that patients with nephrotic syndrome have a hypercoagulable state, which explains the association between nephrotic syndrome, renal vein thrombosis, and thromboembolism. • However, the Budd-Chiari syndrome has never been reported in nephrotic patients. • This is the first report of such an association that, most likely, depended on a primary resistance to activated protein C Budd-Chiari syndrome and inferior vena cava thrombosis in a nephrotic child. • Pediatr Nephrol. • We observed Budd-Chiari syndrome in a boy aged 2 years 6 months with nephrotic syndrome due to hepatic vein and inferior vena cava thrombosis, confirmed by Doppler imaging. • Normal values of the routine hemostatic parameters proved that they are of little predictive value for the thrombotic state. • Immediate heparin infusion was initiated. High doses of heparin up to 59 IU/kg per hour were required for efficient anticoagulation. • A remission of the nephrotic syndrome was achieved with vincristine. • Oral anticoagulation with a vitamin K antagonist was continued for 6 months. • Doppler imaging then indicated full reestablishment of the blood flow through the affected vessels. • The favorable outcome was due to the immediate heparin infusion and prompt remission of the nephrotic syndrome. • Doppler imaging was an important tool for non-invasive diagnosis and follow-up. Thromboembolic complications in children with nephrotic syndrome in Bulgaria (1974-1996). • Pediatr Nephrol. • Over a period of 22 years, 447 children with nephrotic syndrome (NS) have been retrospectively studied for clinically apparent thromboembolic complications (TEC). • The incidence of TEC is 2% (9/447). • TEC were predominantly venous (81% venous vs. 19% arterial). • The most commonly affected vessels were deep leg veins, IVC, SVC, mesenteric artery, and hepatic veins (Budd-Chiari syndrome). Etiology based prevalence of Budd-Chiari syndrome in eastern India • J Assoc Physicians India. • Idiopathic membranous obstruction and stricture of IVC are the commonest cause of BCS in the eastern part of India. • Hepatocellular carcinoma is also a common cause, presenting in the fulminant form. • Ultrasonography may be a helpful screening test for BCS, • IVC and hepatic vein catheterisation is essential for a complete work up of these patients. Budd-Chiari syndrome--a case report • Nepal Med Coll J. • A 21year old male presented with abdominal pain for 2 months and abdominal distension and swelling of lower limbs for 1 month. • US showed coarse echotexture of liver and intraluminal filling defect of IVC • Confirmation of diagnosis was done by inferior venacavography. • The patient had nephrotic syndrome as the risk factor for thrombosis. • The patient underwent portocaval shunt with significant symptomatic relief.