Management conference Middle age man with nephrotic syndrome, ascitis and edema

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Management conferenceMiddle age man with
nephrotic syndrome, ascitis and edema

• Raika Jamali MD
• Digestive Disease Research Center
• Tehran University of Medical Sciences

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• 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.

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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.

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AST52ALT43Bili T5Bili D1.3ALP508PT(INR)
2.6PTT38Albumin2.2Protein5.2

• WBC6500
• HB10
• PLT245000
• MCV85
• FBS180
• TG200
• AFP 60,92

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• BUN15
• Cr0.9
• Uric Acid4
• U/A 3 protein
• 24 h urine protein 7 gr /day

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• HCV Absuspicious
• HBs AgNeg
• HBs Abpositive
• HBc Abpositive
• HBV DNA and HCV RNA Titer undetectable

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Ascitic fluid

• RBC20
• WBC70
• Albumin0.5
• Cytologynegative for malignancy

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Sonography

• Liver was enlarged with hetrogenous echo pattern.
• PV diameter 10 mm.
• Severe ascitis.
• Moderate splenomrgaly.

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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.

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• 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

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Endoscopy

• Fundal and esophageal varices were seen.
• Snake skin appearance in fundus and body.

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• 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).

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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.

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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).

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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

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• Acute (20)
• (2 with fulminant hepatic failure)
• Subacute (40)
• (having signs or symptoms for lt 6 months and no
  evidence of cirrhosis)
• Chronic (40)
• (having signs or symptoms for gt 6 months with
  evidence of cirrhosis)

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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

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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

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• 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

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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 Budd-Chiari 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)

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• 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

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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

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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

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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

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• 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

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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

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• 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

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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).

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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

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• 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

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• 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)

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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.

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Radiologic treatment

• Angioplasty
• Stenting
• Transjugular intrahepatic portosystemic shunt

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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.

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• 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.

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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

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Budd-Chiari syndrome during nephrotic relapse in
a patient with resistance to activated protein C
clotting inhibitor

• Am J Kidney Dis.

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• 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

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Budd-Chiari syndrome and inferior vena cava
thrombosis in a nephrotic child.

• Pediatr Nephrol.

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• 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.

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• 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
  re-establishment of the blood flow through the
  affected vessels.

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• 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.

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Thromboembolic complications in children with
nephrotic syndrome in Bulgaria (1974-1996).

• Pediatr Nephrol.

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• 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).

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Etiology based prevalence of Budd-Chiari syndrome
in eastern India

• J Assoc Physicians India.

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• 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.

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Budd-Chiari syndrome--a case report

• Nepal Med Coll J.

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• 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.