LIVER TRANSPLANTATION FOR SEVERE INTRAHEPATIC NON- CIRRHOTIC PORTAL HYPERTENSION

 

Susan C. Abraham, M.D., Emma E. Furth, M.D., and Alyssa M. Krasinskas, M.D. Departments of Pathology, Mayo Clinic, Rochester, MN, USA (SCA), University of Pennsylvania, PA, USA (EEF), and University of Pittsburgh, PA, USA (AMK)

 

Background: Intrahepatic causes of non-cirrhotic portal hypertension are diverse and may be idiopathic or associated with known toxic, developmental, vascular, or biliary tract diseases. Most patients are successfully managed medically or with shunting procedures. In some cases, the manifestations of portal hypertension are sufficiently severe to warrant orthotopic liver transplantation (OL T); in other patients, OL T is performed with the mistaken diagnosis of end-stage cirrhosis.

 

Design: We studied the clinical features, gross and microscopic liver explant pathology, and post-transplant course in 12 patients who underwent OL T for severe intrahepatic, non-cirrhotic portal hypertension. By definition, cases of post-sinusoidal (Budd-Chiari syndrome) and pre-hepatic (occlusive portal vein thrombosis) disease were excluded. Results: There were 7 men and 5 women, with a mean age of 53 years (range, 33 -64 years). Clinical manifestations included gastrointestinal varices (n=9), ascites (n=7), encephalopathy (n=2), and hepatopulmonary syndrome (n=2). Non-occlusive portal vein thrombi were seen radiologically in 2 patients. Low albumin and low platelet levels were present in 8 and 8 patients, respectively, and at least one LFT >1.5-fold elevated was present in 6 patients. Cirrhosis was diagnosed on clinical grounds, radiology, and/or liver biopsy histology in 7, 5, and 1 patients, respectively. Time between presentation and

OLT ranged from 1- 6 years, with a mean of 3 years. Grossly, liver explant weights ranged from 639 g- 1550 g (mean, 1180 g), gross nodularity was described in 8 cases, and intrahepatic portal thrombi were seen in 3 cases. Histologically, 11 livers showed portal tract venopathy, 11 showed incomplete septal cirrhosis, and 11 showed nodular regenerative hyperplasia (NRH). Focal nodular hyperplasia(s) were also present in 2 cases. Causes or known associations for non-cirrhotic portal hypertension were present in 8 patients and included myelodysplasia, lymphoproliferative disease, rheumatoid arthritis (n=2), Imuran toxicity, anti-cardiolipin antibody syndrome, and early-stage chronic biliary tract disease (n=2). Post-OL T, one patient died of pneumonia at 5 months. A total of35 allograft biopsies were examined in 9 patients, and mild histologic features of NRH were noted in 2 patients at 11 months and 5 years, although there were no known symptoms of portal hypertension.

 

Conclusions: A subset of patients with intrahepatic non-cirrhotic portal hypertension have severe manifestations of their disease requiring OL T.  Accurate pre-OL T diagnosis

is frequently difficult at advanced stages of the disease; 7 of 12 patients carried a clinical diagnosis of cirrhosis. Histopathologically, almost all (11 of 12) explanted livers showed incomplete septal cirrhosis with or without NRH, and most showed associated portal abnormalities including portal tract venopathy, mild chronic inflammation and bile ductular proliferation; on small biopsy specimens, these features could easily be misinterpreted as cirrhosis in the setting of other chronic liver diseases. Finally, most patients undergoing OLT for intrahepatic non-cirrhotic portal hypertension have good long-term graft function, although mild histologic features of NRH were noted in two liver allograft biopsies.

 

 

 

 

 

 

LIVER TRANSPLANTATION FOR SEVERE INTRAHEPATIC NON- CIRRHOTIC PORTAL HYPERTENSION

 

Susan C. Abraham, M.D., Emma E. Furth, M.D., and Alyssa M. Krasinskas, M.D. Departments of Pathology, Mayo Clinic, Rochester, MN, USA (SCA), University of Pennsylvania, PA, USA (EEF), and University of Pittsburgh, PA, USA (AMK)

 

 

Please direct correspondence to:

Susan C. Abraham, MD

Department of Pathology

Mayo Clinic

Hilton 11

220 First Street SW

Rochester, MN 55905

Tel: 507-284-8772

Fax: 507-284-1599

email: abraham.susan@mayo.edu