INTRODUCTION: Hereditary spherocytosis is a hemolytic anemia that leads to premature cell destruction due to red cell membrane defect. It causes release of unconjugated bilirubin, and subsequent bilirubin gallstone formation occurs. Chronic recurrent choledocholithiasis can cause secondary sclerosing cholangitis (SSC). Hemolysis can lead to chronic vascular injury and portal vein thrombosis, resulting in Nodular Regenerative Hyperplasia (NRH). Here, we report a case of HS causing SSC with concurrent NRH. CASE DESCRIPTION/METHODS: A 37-year-old female with a history of hereditary spherocytosis with thrombocytosis presented to the office for abnormal liver function tests (LFTs). History of splenectomy and cholecystectomy in 2002. Patient was noted to have abnormal LFTs in 2009 (Figure 1). Her LFTs were routinely monitored until 2016 when she presented with epigastric pain, jaundice, and abnormal LFTs. Viral and autoimmune hepatitis serologies were negative. Iron studies were normal. Right upper quadrant (RUQ) ultrasound (US) showed mildly dilated intrahepatic ducts. Magnetic resonance cholangiopancreatography(MRCP) was performed which showed a questionable stricture in the proximal CBD and mild dilatation of the central intrahepatic duct. ERCP showed normal caliber CBD with multiple filling defects. A biliary sphincterotomy was performed and the stone was removed. ERCP performed in 2016 and 2018 revealed multiple stones in the biliary ductal system, which were removed and the CBD was dilated. Liver biopsy showed mild portal and lobular inflammation with mild portal fibrosis and changes suggestive of NRH. DISCUSSION: HS caused the patient's recurrent choledocholithiasis and contributed to SSC. Pathologically, SSC causes inflammation, obliterative fibrosis, stricture formation, and destruction of the biliary tree, which leads to biliary cirrhosis. Although often reversible, outcomes may not be as favorable if it is not recognized quickly, particularly in critical illness induced SSC. NRH is a liver disease characterized by many hyperplastic nodules without separation by fibrotic tissue. It is associated with any systemic disease that causes vascular injury, in this case our patient’s HS. Pathology in our case revealed only “mild” changes suggestive of NRH, so the patient hasn’t yet developed portal hypertension. There are no cases in literature that document HS as a factor contributing to either of these disease states. Early suspicion and liver biopsy are necessary for prompt diagnosis and improved outcomes.