Cystic Fibrosis–Related Liver Disease in a 12-Year-Old: Important Questions of Portal Hypertension Etiology That Start With Pathology: A Case Presentation

Introduction Cystic fibrosis liver disease (CFLD) has long been postulated to be secondary to dysfunctional cystic fibrosis transmembrane conductance regulator in the apical biliary epithelium, leading to bile stasis and eventually cirrhosis with portal hypertension (PH). We present a considerably young patient with signs of esophageal varices and liver biopsy indicating CFLD with significant obliterative portal venopathy as a result of long-standing portal hypertension. Case Presentation A 12-year-old with CF (diagnosed at 1 year) and pancreatic insufficiency was noted to have chronically elevated liver enzymes with decreasing platelet counts (130,000 K/ µL). These findings prompted an ultrasound, which showed splenomegaly. Upper endoscopy showed grade 1 esophageal varices, and liver needle biopsy performed at this time demonstrated focal neutrophilic lobular inflammation with marked pseudoacinar transformation and biliary metaplasia. Noted was grade 1 macrovesicular steatosis, focal dense fibrosis also known as “focal biliary cirrhosis,” and obliterative portal venopathy. Discussion CF patients with liver fibrosis have significant risk of future morbidity. Of specific interest is identification of PH, and obliterative portal venopathy is a very important feature to distinguish on biopsy as it predicts clinical course. Two recent studies in young adults described obliterative portal venopathy (OPV) and noncirrhotic portal hypertension (NCPH) as the predominant pathophysiology in young adults (median, 22 years) with CFLD. One study found cirrhosis present in only 27% of patients with portal hypertension. In addition, it appears that portal hypertension can precede cirrhotic changes. This unique case in a very young patient with CFLD demonstrates that the underlying pathogenesis of noncirrhotic portal hypertension and CFLD remains to be fully solved. These observations may have important consequences for CFLD management, including opting away from “cholestasis-targeted” treatments and more often considering portosystemic shunting procedures instead of transplant, as liver function remains preserved in numerous CFLD cases.