hepatoportal sclerosis

Hepatoportal sclerosis (HPS) is a rare cause of portal hypertension in children characterized by abnormalities of intra-hepatic portal veins, portal fibrosis, and nodular regeneration.

Hepatoportal sclerosis (HPS) is one of several entities known to cause noncirrhotic portal hypertension. To date, its etiology is unknown.

Etiopathogenesis of these rare disorders remains unclear, but the hypothesis of vascular thrombotic mechanism has been suggested.

Hepatoportal sclerosis (HPS) and nodular regenerative hyperplasia (NRH) are two of several entities that are known to cause portal hypertension in the absence of cirrhosis.

Unlike NRH which has several well-documented causes (medications such as azathioprine, collagen vascular, and myeloproliferative diseases, etc.), HPS, to date, has no known etiology.

In HPS, the primary hepatic lesions are found in the portal tracts which show varying degrees of fibrosis, sclerosis of portal vein radicles, and abnormally formed portal veins.

Synopsis

 abnormalities of intra-hepatic portal veins
 portal fibrosis
 nodular regeneration
 hepatic vascular injury

• microvascular liver injury
•  
   densely fibrotic portal tract
   partial obliteration of the portal vein branch
   foci of inflammatory cells lifting the endothelial lining (venulitis)
   thickened wall of hepatic arteriole
   centrilobular central venulitis

 lobular cholestasis with formation of rosettes (pseudoacinar reaction)
 markedly dilated sinusoids
 dense portal fibrosis with no apparent portal vein branch (phlebosclerosis)

 possible association with nodular regenerative hyperplasia

• condensation of reticulin fibers at the edge of a poorly defined nodule

Associations - Etiology

 Adams-Oliver syndrome (15832360)
 drug-induced hepatic microvascular injury

• 6-thioguanine (in inflammatory bowel disease or acute lymphoblastic leukemia)
• 6-Thioguanine is an antimetabolite akin in structure to nucleoside reverse transcriptase inhibitors such as zidovudine (AZT), stavudine (d4T), and ddI.
• Such drugs may affect the hepatic microvasculature as other antimetabolite medications are known to do, such as azathioprine causing both veno-occlusive disease and NRH.

• anti-HIV didanosine (ddI) (21057809)
  • There are increasing reports of both HPS and NRH as well as noncirrhotic portal hypertension occurring in patients having human immunodeficiency virus (HIV).
  • Several investigators have suggested that the portal hypertension may be related to use of certain highly active anti retroviral therapy (HAART) medications.
  • After reviewing 42 such cases, on January 29, 2010, the FDA issued an advisory regarding the development of portal hypertension occurring in patients with HIV taking didanosine.
  • ddI drug hepatotoxicity and injury to the hepatic microvasculature.

References

 Girard M, Amiel J, Fabre M, Pariente D, Lyonnet S, Jacquemin E. Adams-Oliver syndrome and hepatoportal sclerosis: occasional association or common mechanism? Am J Med Genet A. 2005 Jun 1;135(2):186-9. PMID: 15832360