Idiopathic non-cirrhotic portal hypertension

Idiopathic non-cirrhotic portal hypertension is the clinical diagnosis of exclusion featuring portal hypertension without hepatic cirrhosis, vascular obstruction, schistosomiasis, or a variety of other chronic liver diseases.

Terminology

Prior terms for this entity include non-cirrhotic portal fibrosis, idiopathic portal hypertension, idiopathic portal fibrosis, and Banti syndrome ^5,6. Idiopathic non-cirrhotic portal hypertension was proposed in 2011 as the uniform term ⁵.

As a clinical diagnosis, idiopathic non-cirrhotic portal hypertension encompasses a spectrum of histopathologic entities: nodular regenerative hyperplasia, incomplete septal cirrhosis, obliterative portal venopathy, and less commonly partial nodular transformation. The term hepatoportal sclerosis has also been used in a manner overlapping with obliterative portal venopathy. However, these morphologic alterations can be seen without portal hypertension. The Vascular Liver Disease Interest Group proposed in 2019 the term portosinusoidal vascular disease to encompass all those patients with histologic features historically associated with idiopathic non-cirrhotic portal hypertension, regardless of whether they actually have portal hypertension ⁶.

Epidemiology

The condition is thought to have a prevalence rate of approximately 3% ⁵.

Associations

Many systemic disorders have been described in association ⁵:

• immunological disorders (e.g. systemic sclerosis, systemic lupus erythematosus, primary hypogammaglobulinemia)

• chronic infections (e.g. HIV, bacterial infections of the gut)

• medications and toxins (e.g. azathioprine, 6-thioguanine, arsenic)

• genetic disorders (e.g. Turner syndrome, Adams-Oliver syndrome)

• thrombophilia

Clinical presentation

The diagnosis of idiopathic non-cirrhotic portal hypertension requires at least one clinical sign of portal hypertension ⁵:

• splenomegaly/hypersplenism

• esophageal varices

• ascites (non-malignant)

• increased hepatic venous pressure gradient

• portovenous collaterals

The diagnosis of portosinusoidal vascular disease requires a non-cirrhotic liver biopsy with either of the following ⁶:

• one clinical sign specific for portal hypertension,

• one histological lesion specific for portosinusoidal vascular disease, or

• one clinical sign not specific for portal hypertension and one histologic lesion not specific for portosinusoidal vascular disease

The clinical signs of portal hypertension are as follows ⁶:

• specific

  • gastric, esophageal, or ectopic varices

  • portal hypertensive bleeding

  • portosystemic collaterals at imaging

• not specific

  • ascites

  • platelet count <150,000 per μL

  • spleen size ≥13 cm in largest axis

In idiopathic non-cirrhotic portal hypertension, other chronic liver conditions must be excluded by a combination of liver biopsy, laboratory tests, and imaging ^5,6:

• cirrhosis of any etiology

• chronic viral hepatitis (hepatitis B or hepatitis C)

• nonalcoholic steatohepatitis

• alcoholic steatohepatitis

• autoimmune hepatitis

• hereditary hemochromatosis

• Wilson disease

• primary biliary cholangitis

• congenital hepatic fibrosis

• sarcoidosis

• schistosomiasis

• obstruction of the hepatic or portal veins (e.g. Budd-Chiari syndrome, portal vein thrombosis)

Similarly, the diagnosis of portosinusoidal vascular disease excludes a number of conditions ⁶:

• bone marrow transplantation (eg, sinusoidal obstruction syndrome)

• Budd-Chiari syndrome or hepatic venous outflow obstruction

• schistosomiasis on liver biopsy (positive serology alone does not exclude the diagnosis)

• cardiac failure or Fontan surgery

• Abernethy syndrome

• hereditary hemorrhagic telangiectasia

• chronic cholestatic diseases

• tumor infiltration of the liver

• sarcoidosis

• congenital hepatic fibrosis

Pathology

The pathogenesis is unclear but the portosinusoidal vasculature is typically implicated ⁶. The entity is often considered among the presinusoidal causes of portal hypertension due to the prevalence of the specific finding of obliterative portal venopathy (wall thickening, luminal occlusion, and vanishing of the portal veins), which results in increased portal system resistance ⁵. The other two specific histologic findings are nodular regenerative hyperplasia and incomplete septal fibrosis/cirrhosis ⁶.

Non-specific histological lesions in portosinusoidal vascular disease include portal tract abnormalities (multiplication, arterial dilation, periportal vascular channels, aberrant vessels), architectural disturbance (irregular distribution of portal tracts and central veins), non-zonal sinusoidal dilation, and mild perisinusoidal fibrosis ⁶.

A liver biopsy is required to rule out cirrhosis and some causes of non-cirrhotic portal hypertension, as well as identify the histologic changes associated with portosinusoidal vascular disease. Liver biopsy is usually accomplished with image-guided percutaneous or transjugular approaches. A core at least 20 mm long is required to exclude cirrhosis ⁶.

Radiographic features

Several findings support the presence of portal hypertension:

• esophageal and/or gastric varices or other portosystemic collateral vessels (most specific)

• splenomegaly ⁵

• ascites ⁵

• elevated hepatic venous pressure gradient (>5 mm Hg, measured on fluoroscopy-guided hepatic vein catheterization)

The appearance of the liver in idiopathic non-cirrhotic portal hypertension/portosinusoidal vascular disease is non-specific. The liver surface is typically smooth but it is sometimes nodular due to nodular regenerative hyperplasia, mimicking cirrhosis ^5,6. The combination of segment 4 atrophy and segment 1 hypertrophy seen in cirrhosis is uncommon in non-cirrhotic portal hypertension ⁶. Altered parenchymal perfusion (increased arterial perfusion, diminished subcapsular portal perfusion) is occasionally seen ^7,8.

Patent large hepatic and portal veins have been cited as a requirement for diagnosis ⁵, but intrahepatic and extrahepatic portal vein abnormalities are common in obliterative portal venopathy, including thrombosis, diminished caliber, lack of visibility, and wall thickening ^7,8. The hepatic artery may be enlarged ⁶.

Treatment and prognosis

Thought to have a more favorable outcome than cirrhotic portal hypertension, but treatment strategies currently attempt to control the varices rather than treat the portal hypertension.