Vascular Diseases of the Liver

Question 1

BUDD-CHIARI SYNDROME

Answer 1

obstruction of hepatic veins or terminal inferior vena cava (IVC)

Question 2

Causes of Budd-Chiari Syndrome

Answer 2

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

Question 3

Pathogenesis

Answer 3

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.

Question 4

Abdominal imaging with Doppler US, CT, or MRI show variable findings in the hepatic veins and IVC including

Answer 4

(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.

Question 5

Additional findings are common

Answer 5

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.

Question 6

CT in a patient with Budd-Chiari syndrome.

Answer 6

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

Question 7

MRI in a patient with Budd-Chiari syndrome

Answer 7

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.

Question 8

A recommended evaluation for the underlying cause

Answer 8

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

Question 9

Treatment

Answer 9

primary BCS should receive anticoagulation and specific therapy for the underlying disease

Question 10

EXTRAHEPATIC PORTAL VEIN OBSTRUCTION

Answer 10

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.

Question 11

Acute PVT

Answer 11

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.

Question 12

Portal cavernoma

Answer 12

is characterized by the disappearance of the normal portal vein and its replacement by a network of portoportal collaterals.

Question 13

Acute Portal Vein Thrombosis in the Absence of Cirrhosis

Answer 13

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.

Question 14

Diagnosis and Natural History of Acute Portal Vein Thrombosis in the Absence of Cirrhosis

Answer 14

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

Question 15

Treatment of Acute Portal Vein Thrombosis in the Absence of Cirrhosis

Answer 15

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.

Question 16

PORTAL VEIN THROMBOSIS IN PATIENTS WITH CIRRHOSIS

Answer 16

extension to the superior mesenteric vein may induce intestinal ischemia

Question 17

Features that suggest malignant invasion

Answer 17

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.

Question 18

PORTAL VEIN THROMBOSIS IN PATIENTS WITH CIRRHOSIS: Two treatment options are available

Answer 18

Two treatment options are available: anticoagulation and TIPS

Question 19

IDIOPATHIC NONCIRRHOTIC PORTAL HYPERTENSION

Answer 19

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.

Question 20

SINUSOIDAL OBSTRUCTION SYNDROME (HEPATIC

VENO-OCCLUSIVE DISEASE)

Answer 20

destruction of sinusoidal endothelial cells predominantly in the central part of the hepatic lobule, with focal obstruction of sinusoidal lumens and resulting congestion.

Question 21

The most common settings for SOS

Answer 21

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.

Question 22

2 major histopathologic features of SOS

Answer 22

Sinusoidal dilatation and a loss of hepatocytes in the centrilobular
area

Question 23

ISCHEMIC HEPATITIS

Answer 23

extreme serum AST elevations (to >3000 U/L), ischemic hepatitis accounts for about half.

The most common cause of ischemic hepatitis is cardiovascular disease

Question 24

Clinical Features and Diagnosis of ISCHEMIC HEPATITIS

Answer 24

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.

Question 25

Treatment of ISCHEMIC HEPATITIS

Answer 25

transient and self-limited.

No specific therapy exists for ischemic hepatitis, and treatment is directed at improving cardiac output and systemic oxygenation.

Question 26

CONGESTIVE HEPATOPATHY

Answer 26

The effects of heart failure on the liver predictably include decreased hepatic blood flow, increased hepatic vein pressure, and decreased arterial oxygen saturation.1

Question 27

CONGESTIVE HEPATOPATHY

Answer 27

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

Question 28

Histopathology of ischemic hepatitis.

Answer 28

demonstrates centrilobular necrosis, loss of hepatocytes, and sinusoidal congestion with red blood cells, but only a scant inflammatory infiltrate.

Perivenular fibrosis is evident.

Question 29

CONGESTIVE HEPATOPATHY

Answer 29

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.

Question 30

Typical CT and US findings in congestive hepatopathy

Answer 30

include hepatomegaly, ascites, dilatation of the IVC and hepatic veins, and, at CT, inhomogeneous hepatic enhancement during the portal phase of contrast administration.

Question 31

Histopathology of cardiac cirrhosis.

Answer 31

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.

Question 32

ISCHEMIC CHOLANGIOPATHY

Answer 32

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.

Question 33

Bile ducts

Answer 33

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

Question 34

ISCHEMIC CHOLANGIOPATHY

Answer 34

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.

Question 35

DIABETIC HEPATOSCLEROSIS

Answer 35

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

Question 36

HEREDITARY HEMORRHAGIC TELANGIECTASIA

Answer 36

HHT, or Osler-Weber-Rendu disease, is a genetic disorder
with autosomal-dominant inheritance and is characterized by
widespread cutaneous, mucosal, and visceral telangiectasias

Question 37

HEREDITARY HEMORRHAGIC TELANGIECTASIA

Answer 37

The abnormal blood vessels in HHT result in a direct artery- to-vein connection.

Question 38

Three types of shunting may occur and coexist

Answer 38

(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.