Drug-Induced Idiopathic Portal Hypertension Mimicking “Cryptogenic” Cirrhosis in a HIV Patient

Abstract

Introduction: Drug-induced idiopathic portal hypertension (IPH), which may mimic complications of “cryptogenic” cirrhosis, is an exceedingly rare complication of antiretroviral therapy (ART). Case: A 50-year-old Caucasian man with a 20-year history of stable human immunodeficiency virus (HIV) infection on ART therapy presented with fatigue, new onset ascites, and profound iron-deficiency anemia. Endoscopies revealed only portal congestive gastopathy and grade 3 esopahgeal varices. Esphageal varices were banded and a non-selective beta-blocker and diuretics initiated. Computerized tomography scan of the abdomen and revealed only large amount of ascites, hepatosplenomegaly and patent hepatic and portal veins. Liver biopsy revealed mild chronic hepatitis with pericellular and periportal fibrosis (stage 2 of 4). Patient was referred to our center for management of “cryptogenic” cirrhosis. Medical history was positive only for HIV, hypertension and hyperlipidemia. He denied alcohol consumption, smoking, or family history of liver disease. A comprehensive serologic evaluation for alternative causes of chronic liver disease and diagnostic studies for cardiopulmonary disease were negative. His ART included tenofovir/emtricitabine, didanosine, and darunavir with ritonavir boosting. On exam, he appeared chronically ill, muscle wasted, had marked ascites and mild hepatosplenomegaly. Laboratory studies revealed an albumin 2.2 g/dl, AST 83 U/L, ALT 60 U/L, iron-deficiency anemia, CD4 count >250 cells, and undetectable HIV viral load. Calculated MELD score was 8. Ascites fluid analysis revealed a serum to ascites albumin gradient of >1.1, protein <3.0 g/dl, <250 white blood cells, and negative cytology. Despite dietary sodium restriction and increasing diuretic doses, he required routine large-volume paracenteses and supportive blood transfusions. Mean portal pressure was 17 mmHg. Transjugular intrahepatic portosystemic shunt was placed with improvement, but not resolution, of ascites or anemia. Due to transient increase in HIV viral load, didanosine, darunavir, and ritonavir were discontinued and raltegravir added to tenofovir/emtricitabine. Within 3 months, all complications of portal hypertension resolved. Liver biopsy 2 years after his initial presentation confirmed normal liver histology with no hepatic fibrosis. Conclusion: Drug-induced IPH is a very rare complication of didanosine, either as monotherapy or in combination with other ART drugs. Timely recognition of ART-related IPH is essential to needless diagnostic/herapeutic interventions for portal hypertension and “cryptogenic” cirrhosis as IPH will resolve with discontinuation of the culprit drug.