S3590 PSC-PBC Overlap Syndrome Presenting With Elevated Lipase and Predominantly Hepatocellular Liver Injury

Introduction: Primary Sclerosing Cholangitis (PSC) and Primary Biliary Cirrhosis (PBC) are progressive cholestatic diseases. Their overlap syndrome can manifest with atypical features, posing diagnostic challenges. Case Description/Methods: A 59-year-old woman with a history of hypertension, presented with 4-5 days of abdominal pain radiating to her back/chest, nausea, and non-bilious, non-bloody vomiting; she denied alcohol use. She admitted had chronic abdominal pain for over 3 years. Examination revealed generalized abdominal tenderness and hyperpigmented, excoriated plaques on her shins; BMI 30.1 kg/m². Initial labs showed: lipase 188 U/L (ref <60 U/L), ALP 130 U/L, ALT 1355 U/L, AST 1522 U/L, and normal total bilirubin. Viral hepatitis serologies were negative. Abdominal ultrasound showed a mildly distended gallbladder and common bile duct (CBD) without calculi. She reported chronic pruritus, generalized weakness, and weight loss. Magnetic resonance cholangiopancreatography (MRCP) revealed minimal prominence of intrahepatic bile ducts with segments of irregularity/beaded appearance and focal narrowing at the hilar confluence, suggestive of PSC. Serology was significant for anti-mitochondrial antibody (AMA) at 111.2 U/mL (ref 0-25 U/mL), antinuclear antibodies 1:40, and anti-smooth muscle antibody (ASMA) at 22 U/mL (ref <20 U/mL). IgG4 antibody negative. Severe iron deficiency anemia (Hb 6.2 g/dL) was noted, requiring transfusion; However, colonoscopy did not identify a bleeding source. Discussion: This case of PSC-PBC overlap syndrome, supported by characteristic magnetic resonance cholangiopancreatography (MRCP) findings for PSC and a positive high-titer AMA for PBC, highlights an atypical presentation. The initial severe hepatocellular injury pattern with only mildly elevated ALP could represent an acute exacerbation or an early-stage manifestation where hepatocellular damage precedes marked cholestasis. While direct pancreatic involvement by PSC/PBC is not clearly established, theocratically, pancreatitis could be secondary to biliary obstruction from sludge or microlithiasis due to cholestasis and common bile duct changes, even without ultrasonographically visible stones. The severe iron deficiency anemia, with a negative colonoscopy, warrants close colonoscopy follow up, as potentially related to inflammatory bowel disease (IBD), a known association with PSC. Clinicians should consider these cholestatic liver diseases in patients with unexplained pancreatitis or atypical liver enzyme elevations, prompting comprehensive biliary imaging and autoimmune workup.