All you should know about vascular diseases of liver 05.05.20

1. VA S C U L A R D I S E A S E S O F T H E L I V E R
P r e s e n t e d b y
Dr. Nikhil Chandra Roy

2. VASCULAR DISEASES OF LIVER
• Primary alternation in the blood or lymphatic vessels
• Primary alternations consist of obstruction, fistula, aneurysms,
absence of small or large vessels (due to agenesis or
disappearance)
• Excludes the vascular changes secondary to parenchymal or
biliary disease

3. Hepatic arterial
disease
• Liver ischemia
• Hepatic artery aneurysm
• Hepatic artery thrombosis
• Ischemic cholangiopathy
Portal venous
disease
• Extra hepatic portal vein
obstruction
• Noncirrhotic portal
hypertension
• Congenital portosystemic
shunt(CPSS)
Hepatic venous
disease
• Budd –Chiari syndrome
• Sinusoidal obstruction
syndrome
• Congestive hepatopathy
• Nodular regenerative
hyperplasia of the liver
• Idiopathic sinusoidal
dilatation
• Pleosis hepatis

4. ISCHEMIC HEPATITIS
• Also called hypoxic hepatitis, ischemic hepatopathy, shock liver
• Most commonly encountered form of vascular liver disease
• Cause: Cardiovascular diseases(acute MI, arrhythmia, heart
failure),sepsis, systemic hypoxia due to respiratory failure
• Acute trauma, hemorrhage, burn and heat stroke can also cause
ischemic hepatitis, but the likelihood is substantially less in the
absence of underlying heart disease

5. • Findings of underlying precipitating medical condition
• Extreme elevations of serum aminotransferase levels (>3000 U/L)
• Profound elevation of serum LDH
• ALT/LDH ratio of less than 1.5 is more typical of ischemic hepatitis
than viral hepatitis.
• PT may be prolonged by 2 or 3 seconds
• Serum bilirubin often mildly increased
• Serum creatinine and BUN levels are often elevated due to ATN
DIAGNOSIS

6. • AST and LDH levels peak at
1 to 3 days.
• Return to normal within 7 to
10 days.
Fig: frequently observed course of serum AST and LDH levels in ischemic
hepatitis

7. DIFFERENTIAL DIAGNOSES
• Acute hepatitis due to
Viral infections
Autoimmunity
Toxins
Medications

8. TREATMENT
• Most cases are transient and self limited.
• No specific therapy.
• Rx is directed at improving cardiac output and systemic oxygenation.
• Overall prognosis depends on severity of underlying predisposing
condition, not the severity of the liver disease.

9. BUDD CHIARI SYNDROME
• Obstruction of hepatic veins or terminal inferior vena cava
• It is a rare disease, occurs in 1/100,000 in general population

10. TYPES
• Primary: arises from a venous anomaly
• Secondary: arises from initial lesion outside the veins
Tumour invasion
 Extraluminal compression by cyst or focal nodular
hyperplasia
Blunt abdominal or thoracic trauma

11. AETIOLOGY
• Hypercoagulable States:
Myeloproliferative disorders,
PNH
Deficiency of protein C ,S
 OCP, pregnancy
Antiphospholipid syndrome
Sickle cell disease
• Malignancy:
Carcinoma of liver, kidney ,adrenals
• Infection:
Liver abcess, hydatid cyst, schistosomiasis,
TB, filariasis
• Others:
IBD, Behcets disease, Laproscopic
cholecystectomy, sarcoidosis, polycystic liver
disease, trauma to abdomen or thorax

12. CLINICAL PRESENTATION
• Presentation may be asymptomatic, acute or chronic liver
disease
• In acute form: Rapid development of upper abdominal pain,
marked ascites with tender hepatomegaly, occasionally acute
liver failure
• In chronic form: Features of chronic liver disease and portal
hypertension

13. INVESTIGATION
• Abdominal imaging: US, CT or MRI
• Doppler US for hepatic vasculature(sensitivity>75%)
Non-visualization, thrombotic or stenotic vein with proximal dilatation
,reverse flow in one or more hepatic vein
• CT or MRI: Occlusion of hepatic veins or IVC, enlarged caudate
lobe, ascites, splenomegaly

14. CT
FIGURE . CT in a patient with Budd-Chiari syndrome. The venous phase of vascular enhancement is shown. The
liver is dysmorphic(better seen in A) 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
(most prominent in B) (arrow).

15. MRI
FIGURE . 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.

16. • Hepatic Venography:
Almost never needed for making diagnosis, but when combined with
venous pressure measurement, venography allows percutaneous therapy.
• Investigations for the underlying causes
Imaging for secondary BCS
Flow cytometry
Lupus anticoagulant etc.

17. STEPWISE THERAPEUTIC ALGORITHM FOR BCS
EASL CPG VDL. J Hepatol 2016;64:179–202
Medical treatment
Angioplasty/stenting/thromboly
sis
TIPS
Liver
transplant

18. MEDICAL TREATMENT
• Prompt anticoagulant therapy is important
• Reduce risk of clot extension
• Reduce risk of new thrombotic episodes
• Specific therapy for the underlying disease
• Medical (or endoscopic ) therapy for manifestations of
PHTN(ascites, variceal bleeding, encephalopathy)

19. ANGIOPLASTY/STENTING/THROMBOLYSIS
• Experience of correcting hepatic venous outflow obstruction with
thrombolysis is limited
• Angioplasty/stenting is the definitive treatment for less than 10% of
western BCS patients
• Consider angioplasty/stenting as the first-line decompressive procedure
in patients with short hepatic vein stenosis or IVC stenosis

20. TIPS
• Surgical shunts have not demonstrated a survival advantage in patients
with BCS
• However, TIPS has a lower morbidity and mortality rate than surgery
and is feasible in most patients with IVC obstruction and in those with
severe IVC stenosis

21. LIVER TRANSPLANTATION
• Liver transplantation is the last therapeutic step
BCS may recur after LTx
Incidence of recurrent BCS after LTx is markedly reduced by early
anticoagulation treatment and lifelong maintenance

22. BUDD–CHIARI SYNDROME AND PREGNANCY
EASL CPG VDL. J Hepatol 2016;64:179–202
• Excellent maternal outcome provided disease is well controlled
• Fetal outcome is less favourable
Pregnancies reaching week 20 of gestation have acceptable prognosis
• Vitamin K antagonists associated with high risk of miscarriage and
congenital malformation
Perform pregnancy test as soon as possible
If positive, switch to LMWH
• Periodic monitoring of anti-Xa activity

23. CONGESTIVE HEPATOPATHY
• Right sided heart failure results in centrilobular congestion and
sinusoidal edema that further decrease oxygen delivery
• Superimposed ischemic hepatitis are common in these patients
• Very rarely, long standing cardiac failure and hepatic congestion
give rise to cardiac cirrhosis.

24. CONGESTIVE HEPATOPATHY
• Right sided heart failure results in centrilobular congestion and
sinusoidal edema that further decrease oxygen delivery
• Superimposed ischemic hepatitis are common in these patients
• Very rarely, long standing cardiac failure and hepatic congestion
give rise to cardiac cirrhosis.

25. DIAGNOSIS
• Symptoms and signs of heart failure are predominant features
• Right quadrant discomfort, Tender hepatomegaly, ascites. Spider telangiectasia
and varices are usually not present, jaundice in <10% patient with severe or
acute heart failure
• Mild elevation of serum bilirubin(<3mg/dl)
• Prothrombin time is prolonged in more than 75%of cases
• Other liver biochemical tests are often normal or mildly elevated
• SAAG - High

26. TREATMENT
• Treatment of underlying heart disease
• Supportive treatment for liver component
• Mortality rate is determined by the severity of underlying cardiac
disease

27. SINUSOIDAL OBSTRUCTION SYNDROME
• Previously called hepatic veno-occlusive disease
• Destruction of sinusoidal endothelial cells predominantly in the central
part of hepatic lobule with focal obstruction of sinusoidal lumen
• Nonthrombotic occlusion of central hepatic vein may also be present

28. PATHOGENESIS
Massive centrilobular & midlobular
congestion, obliteration of terminal hepatic
vein
Toxic agent > damage sinusoidal endothelial cells >
sloughing of sinusoidal endothelial cells > obstruction
around central veins

29. AETIOLOGY
• Conditioning for HSCT
• Chemotherapy with oxaliplatin for metastatic HCC
• Hepatic chemoradiation for abdominal organ malignancy
• Immunosuppressive agents
• Pyrrolizidine alkaloid used to make tea.

30. DIAGNOSIS
• Lack of specific clinical signs or serological diagnostic tools makes
recognition of SOS challenging
• Consider a diagnosis of SOS whenever liver disease occurs in patients
with HSCT, cancer chemotherapy, immunosuppression in solid organ
transplantation or IBD
• Consider SOS in patients with weight gain, associated with or without
ascites, tender hepatomegaly and jaundice. Exclude other common
causes of these symptoms
• In patients who do not meet clinical criteria of SOS or when other
diagnoses have to be excluded, use transjugular liver biopsy

31. SOS: PROPHYLAXIS AND TREATMENT
• Recognition of risk factors is helpful to prevent SOS
• Pre-existing liver disease
• Previous SOS
• High intensity regimen
• Abnormal pre-operative GGT, age, female sex, cycles of chemotherapy, and a short interval
between the end of chemotherapy and surgical liver resection
• Routinely control risk factors for SOS
• Use defibrotide to prevent SOS in patients undergoing HSCT
• Supportive measures for the treatment of complications of established SOS
• Bevacizumab have been reported to protect against oxaliplatin related SOS

32. PORTAL VENOUS DISEASES

33. EXTRAHEPATIC PORTAL VEIN OBSTRUCTION
• EHPVO may or may not extend into the intrahepatic portal veins
• Primary EHPVO: acute PVT and portal cavernoma
• Secondary EHPVO: malignant invasion, compression
• EHPVO is second most important cause of portal HTN and most
important cause of non-cirrhotic portal HTN in third world countries
• In children , the causes are umbilical sepsis, umbilical catheterization,
developmental anomalies, dehydration, multiple exchange transfusion

34. CAUSES OF PVT
• Hypercoagulable State :
• Infections: cholangitis, appendicitis, Diverticulitis, cholecystitis, ,liver
abcess, umbilical vein abcess
• Inflammatory diseases: IBD, Behcet disase, pancreatitis
• Therapeutic intervention: hepatobiliary surgery, Radiofrequency
ablation of hepatic tumor, TIPS, Umbilical Vein catheterization, liver
transplantation
• Impaired portal flow : BCS, Cirrhosis, cholangiocarcinoma, HCC,
Pancreatic carcinoma

35. ACUTE PVT
• Characterized by presence of thrombus in the lumen of portal vein on
imaging
• The recent onset of symptoms should be added to these criteria has
been debated

36. DIAGNOSIS
• Severe abdominal pain
• Fever
• Features of intestinal ischemia(per rectal bleeding, ascites) due
to mesenteric vein thrombosis-may be present
• Physical examination is unremarkable

37. • Blood count may reflect SIRS or underlying blood disease
• Liver biochemical test : no alternations or minor transient
changes
• US: solid material filling the lumen of portal vein
• Doppler US: absence of flow in portal vein – is preferred to US
alone
• Contrast enhanced CT is more accurate for showing filling defect
in portal vein lumen.

38. FIGURE . CT in a patient with acute portal vein thrombosis. The portal venous phase is shown and demonstrates
vascular enhancement. The portal and mesenteric veins are enlarged and lack enhancement(arrowhead).
Dilated veins are seen in the porta hepatis, particularly in the gallbladder wall (arrow).

39. TREATMENT
• Anticoagulation: complete recanalization(40%), partial
recanalization(15%)
• Thrombolysis: Recanalization rates similar to those for
anticoagulation, usually not given
• Surgery

40. ACUTE PORTAL VEIN THROMBOSIS: AIMS OF THERAPY
EASL CPG VDL. J Hepatol 2016;64:179–202
• Prevent extension of thrombosis to mesenteric veins
• Leading to mesenteric venous infarction
• Achieve portal vein recanalization
Abdominal pain and systemic inflammation
and/or thrombophilic factor
Confirm acute PVT on unenhanced
and contrast CT scan
Screen for general
and local cause
Discuss urgent laparotomy with
expert surgeon
1. Close monitoring
2. 6 months anticoagulation with coumarin
Inform radiologist of
PVT suspicion
Start LMWH
• Persisting abdominal pain despite
adequate anticoagulation?
• Organ failure?
• Rectal bleeding?
YES NO
Add antibiotics if
septic thrombophlebitis
Treat cause when accurate

41. ACUTE PORTAL VEIN THROMBOSIS: PROGNOSIS
EASL CPG VDL. J Hepatol 2016;64:179–202
• Recanalization of the portal vein can occur up to 6 months
following treatment
• Recanalization of mesenteric and splenic veins increases steadily
up to 12 months
• Over half (55%) of the patients not achieving recanalization will
develop gastroesophageal varices

42. PORTAL CAVERNOMA
• Following acute thrombosis in the absence of recanalization
• Portal venous lumen obliterates
• Porto-portal collaterals develop
• Portoportal collaterals arise from preexisting veins in porta
hepatis and pancreas.
• This lead to development of portal cavernoma

44. DIAGNOSIS
• GI bleeding related to portal HTN
• Splenomegaly
• Liver biochemical test are normal or near normal
• Thrombocytopenia due to hypersplenism.
• US: numerous tortuous vessel occupying the portal vein bed
• Multiphase CT: numerous vascular structures in the region of
portal vein, which enhance during portal venous phase , not
during arterial phase.

45. Normal portal vein is not seen. Serpiginous
anechoic structure in porta hepatis
Serpiginous structure fills with color indicating
vascular structure

46. CT SCAN

47. TREATMENT
• Patient without esophageal varices and strong risk factor for
thrombosis may benefit from anticoagulation therapy
• Recurrent variceal bleeding – EVL, non selective beta blockers
• Surgical portocaval shunt or TIPS – limited role

48. NONCIRRHOTIC PORTAL HYPERTENSION
• Heterogenous group of disorders of vascular origin, leading to
portal hypertension in absence of cirrhosis
• Often asymptomatic until complications develop

49. CAUSES
Prehepatic: EHPVO, Splenic vein thrombosis, splenomegaly(e.g.,
lymphoma)
Hepatic: Presinusoidal: Idiopathic noncirrhotic Portal HTN,
Schistosomiasis, Sarcoidosis, Sclerosing
Cholangitis, Congenital Hepatic Fibrosis
Sinusoidal: Alcoholic hepatitis, hypervitaminosis A,
Nodular regenerative hyperplasia, arsenic and
vinyl chloride poisoning
Postsinusoidal: BCS, SOS

50. POSTHEPATIC: Inferior Vena caval web, Constrictive
pericarditis, Severe right sided heart failure, Restrictive
cardiomyopathy

51. IDIOPATHIC NONCIRRHOTIC PORTAL HYPERTENSION
• Portal HTN in presence of patent hepatic vein and extrahepatic
portal vein
• Absence of identifiable cause of intrahepatic noncirrhotic portal
HTN(Schistosomiasis, Congenital Hepatic Fibrosis, SOS)
• Absence of Cirrhosis and of a cause of Cirrhosis

52. AETIOLOGY
• Unknown
• Conditions associated with INCPH
(1) prolonged exposure to certain drugs and toxins (e.g.,
azathioprine, arsenic ,oxaliplatin)
(2) immune disorders(e.g., connective tissue diseases,Crohns
disease, HIV infection;
(3) prothrombotic conditions(e.g.,myeloproliferative disorders,
antiphospholipid syndrome, protein C and protein S deficiency)
(4) genetic anomalies(e.g.,Turner syndrome)

53. DIAGNOSTIC CRITERIA OF INCPH
*Splenomegaly must be accompanied by additional signs of portal hypertension in order to fulfil this criterion;
†Chronic liver disease must be excluded since severe fibrosis might be understaged on liver biopsy
EASL CPG VDL. J Hepatol 2016;64:179–202
• All 5 criteria must be fulfilled
2. Exclusion of cirrhosis on liver biopsy
5. Patent portal and hepatic veins
1. 1 clinical sign of portal hypertension
• Splenomegaly*/hypersplenism
• Oesophageal varices
• Ascites (non-malignant)
• Portovenous collaterals
3. Exclusion of CLD causing cirrhosis
or non-cirrhotic portal hypertension†
• Chronic HCV or HBV
• NASH/ASH
• Autoimmune hepatitis
• Hereditary haemochromatosis
• Wilson disease
• Primary biliary cirrhosis
4. Exclusion of conditions causing
non-cirrhotic portal hypertension
• Congenital liver fibrosis
• Sarcoidosis
• Schistosomiasis

54. INCPH: TREATMENT
• Treatment and prophylaxis of variceal GI bleeding
-Endoscopic therapy controls acute variceal bleeding in 95% of patients
and reduces risk of rebleeds
• Despite lack of data, endoscopic band ligation is preferable
-TIPS should be considered in case of uncontrolled bleeding
• Anticoagulation cannot be generally recommended
• Can be considered in patients with clear underlying prothrombotic
conditions or in those who develop PVT
• EASL CPG VDL. J Hepatol 2016;64:179–202
Recommendations
Manage portal hypertension according to the guidelines for cirrhosis B 1
Screen, at least every 6 months, for the occurrence of PVT B 1
Consider liver transplantation in INCPH patients who develop liver failure
or unmanageable portal hypertension-related complications
B 1

55. THANK YOU