S3549 Cholestasis Without a Label: A Case of Idiopathic Cholestatic Liver Disease

Introduction: Cholestatic liver disease is characterized by impaired bile formation or flow, typically marked by a disproportionate elevation in alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) compared to aminotransferases (ALT, AST). Common causes include primary biliary cholangitis, drug-induced cholestasis, and biliary obstruction. We present a case of a 44-year-old man presenting with chronic cholestatic hepatopathy and significant jaundice, in the absence of serologic or histologic abnormalities, representing a case of idiopathic cholestatic disease. Case Description/Methods: A 44-year-old male presented with abdominal pain and elevated liver function tests (LFTs): alkaline phosphatase 1,858, ALT 213, AST 260, and total bilirubin 6.7. Serologic and metabolic workup including ASMA, AMA, IgG4, Anti-SP100, Anti-GP210, CA 19-9, and viral hepatitis panels were unremarkable. Computed tomography abdomen and right upper quadrant ultrasound showed only reactive gallbladder wall edema. Magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRCP) revealed mild intrahepatic biliary dilation with pruning appearance of the ducts including areas of wall thickening, suggestive of possible early primary sclerosing cholangitis (PSC). However, endoscopic retrograde cholangiopancreatography (ERCP) with stent placement showed no dominant stricture or typical cholangiopathic changes and failed to improve LFTs. Liver biopsy was consistent with non-specific chronic cholestatic liver disease. Given persistently abnormal LFTs, prednisone was started without improvement in LFTs despite treatment. The patient remained jaundiced but without signs of hepatic decompensation. In the setting of elevated MELD and persistent cholestatic liver injury, the patient was referred for liver transplant evaluation. Discussion: This case, patient presented with a chronic cholestatic pattern of liver injury, yet extensive evaluation failed to reveal a definitive etiology. In idiopathic cases, management is supportive and symptom driven, as specific therapies are limited in the absence of defined underlying disease. Emerging agents targeting bile acid metabolism are under study, but long-term efficacy and safety remain to be established. Until then, the mainstay of care in cases like this remains vigilant management of cholestasis-related complications and timely referral for liver transplant consideration are essential to optimizing patient outcomes.