Vascular Liver Disorders: Budd-Chiari, Portal Vein Thrombosis & Ischemic Hepatitis

Budd-Chiari syndrome

Definition and presentation. Budd-Chiari syndrome is obstruction of hepatic venous outflow anywhere from the small hepatic veins to the junction of the IVC and right atrium. The usual cause is thrombus. In Asia, membranous webs of the IVC are more frequent. Cardiac congestion and sinusoidal obstruction syndrome are classified separately. The classic triad is RUQ pain, tender hepatomegaly, and ascites. Acute forms can progress to acute liver failure, while chronic forms look like cirrhosis with portal hypertension.

Ascitic fluid. A SAAG ≥1.1 g/dL with total protein ≥2.5 g/dL marks post-sinusoidal congestion, because congested sinusoids leak protein-rich fluid. Cardiac ascites shows the same pattern. Cirrhotic ascites also has a high SAAG, but its protein is low because capillarized sinusoids hold protein back.

Causes. Most patients have at least one prothrombotic condition, and often several:

• myeloproliferative neoplasms, especially JAK2 V617F–positive polycythemia vera (the largest single group)
• paroxysmal nocturnal hemoglobinuria (flow cytometry for CD55/CD59 loss)
• antiphospholipid syndrome, factor V Leiden, prothrombin gene mutation
• oral contraceptives, pregnancy, and the postpartum period
• tumor invasion or compression (HCC, renal cell carcinoma)

Test for JAK2 V617F even when blood counts are normal, because hypersplenism and hemodilution can mask an MPN.

Diagnosis. Doppler ultrasound comes first. It shows absent, reversed, or turbulent hepatic vein flow, thrombus, and intrahepatic "spider-web" collaterals. CT or MR venography then defines the extent. The caudate lobe hypertrophies because its short veins drain directly into the IVC, so it escapes congestion while the rest of the liver atrophies.

Portal vein thrombosis

Causes. Cirrhosis is the most common setting, because portal flow is sluggish. Other causes:

• abdominal inflammation: pancreatitis, diverticulitis, appendicitis
• hypercoagulable states: MPN, factor V Leiden, prothrombin mutation, OCPs
• malignancy: HCC invasion, pancreatic cancer
• procedures: abdominal surgery, splenectomy, umbilical vein catheterization in neonates

Pylephlebitis is septic thrombophlebitis of the portal vein after diverticulitis or appendicitis. It presents with fever and bacteremia, often with Bacteroides fragilis or E. coli, and sometimes liver abscesses. It needs prolonged antibiotics, often combined with anticoagulation.

Acute versus chronic. Acute PVT causes abdominal pain, and extension into the superior mesenteric vein threatens bowel ischemia. In chronic PVT, the occluded vein is replaced by a collateral web (cavernous transformation). The result is prehepatic portal hypertension: splenomegaly and variceal bleeding with normal liver tests and synthetic function, and usually little ascites.

Management. Anticoagulate acute PVT promptly to recanalize the vein and prevent mesenteric extension, and remove triggers such as OCPs. Continue for at least 6 months, and indefinitely if a permanent thrombophilia is present. In chronic PVT, screen for varices and treat them with a nonselective beta-blocker or band ligation. Long-term anticoagulation is reserved for an ongoing prothrombotic state.

Ischemic hepatitis and congestive hepatopathy

Ischemic hepatitis ("shock liver"). Hypotension, cardiac arrest, sepsis, or severe hypoxemia causes centrilobular (zone 3) necrosis, usually in a liver already congested by heart failure. AST and ALT climb into the thousands with a very high LDH. An ALT/LDH ratio <1.5 favors ischemia, whereas viral hepatitis usually exceeds 1.5. Enzymes peak within 1–3 days and fall rapidly toward normal over about 7–10 days, and bilirubin rises later and modestly. The hypotensive episode may be brief and unrecorded. Treatment is restoring cardiac output and perfusion, after which the liver regenerates; prognosis depends on the underlying illness. Exclude acetaminophen toxicity and viral hepatitis.

Congestive hepatopathy. Chronic passive congestion from right heart failure, tricuspid regurgitation, or constrictive pericarditis causes:

• tender hepatomegaly, a pulsatile liver in TR
• JVD with hepatojugular reflux
• high-SAAG, high-protein ascites
• a mild cholestatic pattern on liver tests

Dark, congested zone 3 alternating with paler periportal tissue gives the "nutmeg liver". Years of congestion produce fibrosis that bridges central veins (cardiac cirrhosis). Treatment targets the heart.

Ascites out of proportion to edema, a Kussmaul sign, and a pericardial knock suggest constrictive pericarditis, which pericardiectomy can cure.

Sinusoidal obstruction syndrome

Setting. Sinusoidal obstruction syndrome (SOS), formerly veno-occlusive disease, begins with toxic injury to the sinusoidal endothelium, which then obstructs the sinusoids and terminal hepatic venules. The classic setting is conditioning for hematopoietic stem-cell transplant with cyclophosphamide, busulfan, or total-body irradiation, usually within 21 days. Other causes are oxaliplatin, gemtuzumab or inotuzumab ozogamicin, and pyrrolizidine alkaloids in herbal "bush teas".

Recognition and treatment. SOS presents with painful hepatomegaly, jaundice, and weight gain from fluid retention and ascites. Treat severe SOS with defibrotide plus supportive care. Ursodiol is used for prophylaxis in transplant recipients.