Vascular Diseases of the Liver Flashcards
BUDD-CHIARI SYNDROME
obstruction of hepatic veins or terminal inferior vena cava (IVC)
Causes of Budd-Chiari Syndrome
HYPERCOAGULABLE STATES
Antiphospholipid syndrome
Antithrombin deficiency
Factor V Leiden mutation
Methylenetetrahydrofolate reductase C677T polymorphism Myeloproliferative neoplasm*
Oral contraceptives
Paroxysmal nocturnal hemoglobinuria Postpartum thrombocytopenic purpura Pregnancy
Protein C deficiency
Protein S deficiency
Prothrombin gene mutation G20210A Sickle cell disease
INFECTIONS Aspergillosis Filariasis Hydatid cysts (Echinococcus granulosus or E. multilocularis) Liver abscess (amebic or pyogenic) Pelvic cellulitis Schistosomiasis Syphilis TB
MALIGNANCIES
Adrenal carcinoma HCC Leiomyosarcoma Leukemia
Lung cancer Myxoma
Renal carcinoma Rhabdomyosarcoma
MISCELLANEOUS
Behçet disease Celiac disease Dacarbazine therapy IBD
Laparoscopic cholecystectomy Membranous obstruction of the vena cava Polycystic liver disease
Sarcoidosis
Trauma to abdomen or thorax
Pathogenesis
The pattern and speed of the occlusive process varies among the major veins and from patient to patient.
Following initial thrombosis, a vein may transform into a fibrous cord or undergo wall thickening, a process that affects a variable length of the vein and causes varying degrees of narrowing. Short-length stenosis may simulate a membrane.
he occlusion predominates at the ostia of a major hepatic vein into the IVC and the adjacent portion of the IVC.
Abdominal imaging with Doppler US, CT, or MRI show variable findings in the hepatic veins and IVC including
(1) lack of visibility,
(2) dilatation upstream due to a complete or partial obstruction of the terminal portion,
(3) diffuse narrowing and irregularity, and
(4) transformation into a cord-like remnant.
Collateral veins draining peripheral segments of a venous territory into another vein, either hepatic or extrahepatic, are usual.
Additional findings are common
1) a combination of liver sectorial atrophy and hypertrophy, including segment I enlargement;
(2) ascites, portosystemic collaterals, and enlargement of the spleen;
(3) patchy enhancement in the arterial and portal phases, which disappears at the late phase, a pattern indicating decreased portal perfusion due to stasis; and
(4) a marked nodular enhancement in the arterial phase with disappearance in the portal and late phases, without washout, corresponding to regenerative macronodules, some of which have a central scar although some regenerative nodules may show washout.
CT in a patient with Budd-Chiari syndrome.
The venous phase of vascular enhancement is shown. The liver is dysmorphic and enhances in an inhomogeneous fashion. Ascites is present. The hepatic veins are visible as slender, unenhanced structures converging toward an enhanced patent inferior vena cava
MRI in a patient with Budd-Chiari syndrome
Numerous regenerative macronodules less than 2 cm in diameter are hyperintense in the T1-weighted sequence and hypointense in the T2-weighted sequence. Marked enhancement of the nodules is seen in the arterial phase, with isointensity in the portal venous phase.
A recommended evaluation for the underlying cause
general examination for a systemic disease, imaging for secondary BCS, a CBC, assessment for the JAK2 V617F mutation, and calreticulin gene mutations (in a patient with a spleen height >16 cm, platelet count >200,000/mm3, and undetectable JAK2 V617F mutation), flow cytometry of blood cells for paroxysmal nocturnal hemoglobinuria, factor V Leiden and prothrombin G20210A gene mutations, and a lupus anticoagulant and anti-β2-glycoprotein I antibodies for antiphospholipid syndrome
Treatment
primary BCS should receive anticoagulation and specific therapy for the underlying disease
EXTRAHEPATIC PORTAL VEIN OBSTRUCTION
secondary EHPVO may be caused by malignant invasion, compression, or encasement of the portal vein.
Primary EHPVO is comprised of acute PVT and portal cavernoma.
Acute PVT
is characterized by the presence of a thrombus, shown on imaging as solid material in the lumen of the portal vein, in the absence of a cavernoma.
The subsequent transformation of an acutely thrombosed portal vein into a portal cavernoma has frequently been referred to as chronic PVT.
Portal cavernoma
is characterized by the disappearance of the normal portal vein and its replacement by a network of portoportal collaterals.
Acute Portal Vein Thrombosis in the Absence of Cirrhosis
Local factors associated with PVT can be classified into 3 main categories:
(1) inflammatory foci, particularly acute pancreatitis,as well as bacterial cholangitis, appendicitis, and diverticulitis
(2) injury to the portal, splenic, or mesenteric veins (e.g., splenectomy, blunt abdominal trauma);
(3) stasis of blood in the portal venous bed due to cirrhotic or noncirrhotic intrahepatic block.
Diagnosis and Natural History of Acute Portal Vein Thrombosis in the Absence of Cirrhosis
Abdominal imaging usually shows the thrombus as solid material filling the lumen of the portal vein and extending variably into portal vein branches or to the splenic and superior mesenteric veins
Doppler US shows the absence of flow in the portal vein and is preferred to US alone
Treatment of Acute Portal Vein Thrombosis in the Absence of Cirrhosis
Recanalization of the portal vein is unlikely to occur beyond 6 months of the initiation of anticoagulation, if it has not already been achieved.
Splenic or mesenteric veins may continue to recanalize after at least 1 year of anticoagulation.
Thrombolytic therapy, usually given after anticoagulation has failed, has achieved recanalization rates similar to those for anticoagulation.
PORTAL VEIN THROMBOSIS IN PATIENTS WITH CIRRHOSIS
extension to the superior mesenteric vein may induce intestinal ischemia
Features that suggest malignant invasion
are a markedly increased diameter of the vein, a contiguous tumor in the liver, endoluminal enhancement in the arterial phase of imaging or arterial signals recorded on Doppler US or contrast-enhanced US, and malignant cells detected on biopsy specimens of the endoluminal material.
PORTAL VEIN THROMBOSIS IN PATIENTS WITH CIRRHOSIS: Two treatment options are available
Two treatment options are available: anticoagulation and TIPS
IDIOPATHIC NONCIRRHOTIC PORTAL HYPERTENSION
Conditions associated with INCPH can be classified into 4 categories
: (1) prolonged exposure to certain drugs and toxins, including purine analogs (e.g., didanosine, azathioprine, 6-thio- guanine) and oxaliplatin;
(2) immune disorders including connective tissue diseases, common variable immunodeficiency, and HIV infection;
(3) prothrombotic conditions including myeloproliferative disorders, antiphospholipid syndrome, and protein S deficiency; and
(4) genetic disorders including Turner syndrome, telomerase disease, Adams-Oliver syndrome, and familial obliterative portal venopathy, the gene for which is located on chromosome 4.
SINUSOIDAL OBSTRUCTION SYNDROME (HEPATIC
VENO-OCCLUSIVE DISEASE)
destruction of sinusoidal endothelial cells predominantly in the central part of the hepatic lobule, with focal obstruction of sinusoidal lumens and resulting congestion.
The most common settings for SOS
are conditioning for hematopoietic cell transplantation (HCT), chemoradiation for abdominal organ malignancy, immunosuppression with thiopurine derivatives, and chemotherapy with oxaliplatin for metastatic colorectal cancer to the liver.
2 major histopathologic features of SOS
Sinusoidal dilatation and a loss of hepatocytes in the centrilobular
area
ISCHEMIC HEPATITIS
extreme serum AST elevations (to >3000 U/L), ischemic hepatitis accounts for about half.
The most common cause of ischemic hepatitis is cardiovascular disease
Clinical Features and Diagnosis of ISCHEMIC HEPATITIS
Laboratory studies show extreme elevations of the aminotransferase levels (>3000 U/L). The serum LDH level is profoundly elevated, often more so than the ALT, and an ALT/LDH ratio of less than 1.5 is more typical of ischemic hepatitis than of viral hepatitis.
The prothrombin time may be prolonged by 2 or 3 seconds, and the serum bilirubin level is often mildly increased, with peak levels seen after the aminotransferase levels peak.
Serum creatinine and blood urea nitrogen levels are often elevated because of acute tubular necrosis.
Characteristically, serum aminotransferase levels peak 1 to 3 days after the hemodynamic insult and return to normal within 7 to 10 days.
Treatment of ISCHEMIC HEPATITIS
transient and self-limited.
No specific therapy exists for ischemic hepatitis, and treatment is directed at improving cardiac output and systemic oxygenation.
CONGESTIVE HEPATOPATHY
The effects of heart failure on the liver predictably include decreased hepatic blood flow, increased hepatic vein pressure, and decreased arterial oxygen saturation.1
CONGESTIVE HEPATOPATHY
Right-sided heart failure results in transmission of increased central venous pressure from the heart directly to the hepatic sinusoids.
The result is centrilobular congestion and sinusoidal edema that further decrease oxygen delivery
Histopathology of ischemic hepatitis.
demonstrates centrilobular necrosis, loss of hepatocytes, and sinusoidal congestion with red blood cells, but only a scant inflammatory infiltrate.
Perivenular fibrosis is evident.
CONGESTIVE HEPATOPATHY
Mild elevation of the serum bilirubin level (to <3 mg/dL) is common, and jaundice is seen in fewer than 10% of patients, occurring in those with severe or acute heart failure.
The prothrombin time is prolonged in more than 75% of cases and usually is resistant to therapy with vitamin K.
Typical CT and US findings in congestive hepatopathy
include hepatomegaly, ascites, dilatation of the IVC and hepatic veins, and, at CT, inhomogeneous hepatic enhancement during the portal phase of contrast administration.
Histopathology of cardiac cirrhosis.
portal tract in the center of a regenerative nodule and fibrotic bands bridging central veins.
The size of the scar and the presence of the nodule attest to the long-term course of the fibrotic process.
the bland nature of the cirrhosis is apparent. No inflammatory cells are evident. The sinusoids are dilated and congested.
ISCHEMIC CHOLANGIOPATHY
designation for the biliary changes that result from impaired arterial blood flow.
Circumstances in which arterial blood supply to the bile ducts is compromised are mostly iatrogenic and include LT, surgery on the liver and bile ducts, arterial chemo- therapy, and embolization.
Bile ducts
receive blood almost exclusively from arteries, many of which are branches of the common hepatic artery; others (e.g., diaphragmatic branches) penetrate the liver through the capsule, away from porta hepatis
ISCHEMIC CHOLANGIOPATHY
The initial stage of IC consists of ischemic necrosis of the biliary mucosa, which leads to biliary cast formation.
Subsequently, full-thickness ischemia of the bile duct wall occurs and may result in necrosis with extravasation of bile and formation of collections (bilomas) in the liver parenchyma or porta hepatis.
Later, ischemic areas undergo fibrous transformation, resulting in biliary strictures.
DIABETIC HEPATOSCLEROSIS
NASH, Mauriac syndrome, and glycogenic hepatopathy are known liver-related complications of diabetes mellitus.
Diabetic hepatosclerosis (DHS) refers to diabetic vascular disease of the liver that may be found in patients with long-standing insulin-requiring diabetes mellitus with a frequency of up to 12% at autopsy.
severe growth retardation and delayed puberty. It is a form of diabetic microangiopathy that affects the liver in which hyaline thickening of small hepatic artery branches and perisinusoidal basement membrane deposition occurs and is distinct from NASH
HEREDITARY HEMORRHAGIC TELANGIECTASIA
HHT, or Osler-Weber-Rendu disease, is a genetic disorder
with autosomal-dominant inheritance and is characterized by
widespread cutaneous, mucosal, and visceral telangiectasias
HEREDITARY HEMORRHAGIC TELANGIECTASIA
The abnormal blood vessels in HHT result in a direct artery- to-vein connection.
Three types of shunting may occur and coexist
(1) hepatic artery-to-hepatic vein shunting can induce a decrease in systemic vascular resistance and high cardiac output, eventually evolving to heart failure;
(2) hepatic artery-to-portal vein shunting can produce portal hypertension; and
(3) portal vein-to-hepatic vein shunting, the rarest form, may lead to hepatic encephalopathy.
