Noncirrhotic Portal Hypertension in a Patient with HIV and Didanosine Exposure

Abstract

Purpose: Prolonged exposure to didanosine (DDI) has been shown to cause noncirrhotic portal hypertension (NCPH) in patients with human immunodeficiency virus (HIV). On January 2010, the FDA released an announcement acknowledging 42 cases of NCPH in patients on DDI. A nucleoside reverse transcriptase inhibitor with documented adverse events of lactic acidosis and hepatomegaly with steatosis, DDI is now known to cause NCPH. A 48 year-old male with HIV, previously treated with DDI, with a past medical history of gallbladder stones, drug induced pancreatitis, type II diabetes, hypercholesterolemia and coronary artery disease presented to our service for evaluation of isolated gastric varices on esophagogastroduodenoscopy. He had no history of alcohol or intravenous drug use. Diagnostic tests showed the following were within normal limits: total serum protein, albumin, total bilirubin, INR, TSH, iron, ceruloplasmin, alpha 1 anti-trypsin and alkaline phosphatase. AST and ALT were mildly elevated at 46 and 44 U/L. Hepatitis A, B, and C serologies were negative. Anti-smooth muscle, antimitochondrial and antinuclear antibodies were negative. Colonscopy showed benign polyps. Abdominal ultrasound with Doppler showed portal hypertension with varices in the mid upper abdomen; abdominal CT showed splenomegaly without splenic vein thrombosis and confirmed the diagnosis of right sided portal hypertension with recanalization of the umbilical vein, splenic hilar and perigastric varices. The patient was sent for a transjugular biopsy, pressure measurements, and TIPS placement. The portal vein pressure and portosystemic gradient before TIPS was 17 and 8 mmHg respectively; the portosystemic gradient after TIPS was 3 mmHg. Biopsy, although fragmented, showed steatohepatitis with severe fatty changes but no fibrosis or nodules, and reticulin stain showed no nodular regenerative hyperplasia. Although the pathophysiology of portal hypertension in patients exposed to DDI is not clear, as in the previously mentioned cases, there were no other identifiable causes of portal hypertension in this patient. The wide spread use of DDI for treatment of HIV in the previous two decades makes it very important to raise awareness of NCPH as a complication of this class of medication. Further studies are necessary to clarify the pathophysiology of the NCPH in these patients in order to identify the best therapeutic approach and management.