Worsening Hepatic Function in Paroxysmal Nocturnal Hemoglobinuria (PNH) Leading to Hemolysis, Gallstones, and Progressive Hepatic Fibrosis

Abstract

PNH is a rare type of acquired intravascular hemolysis with a limited number of cases reported in the literature. The clinical course is unpredictable and can vary from severe hemolytic anemia, characterized by episodes of hemoglobinuria and life-threatening venous thrombosis, to asymptomatic periods. One serious complication of PNH is progressive hepatic dysfunction. We present the case of a 62-year-old man with a history of PNH controlled with eciluzimab and aplastic anemia who presented with abdominal pain, jaundice, and dark urine. Laboratory studies revealed elevated aminotransferases and indirect hyperbilirubinemia. Abdominal ultrasound demonstrated patent hepatic vasculature and gallbladder sludge without evidence of cholecystitis. MRCP showed no evidence of choledocholithiasis. After improvement in symptoms, the patient again developed frequent and severe episodes of abdominal pain. Laparoscopic cholecystectomy with intraoperative cholangiography demonstrated filling defects within the CBD. Sludge and multiple dark pigmented stones were found in the resection specimen. Liver biopsy revealed subcapsular portal tract hemosiderosis with fibrosis without mass or hepatocellular carcinoma. The patient underwent ERCP and sphincterotomy with removal of small pigment stones from the CBD. The patient's condition improved and he is currently being evaluated for treatment options to decrease risk of progression to cirrhosis. This case demonstrates the natural history of PNH with cholestatic liver disease and pigment stones. Moreover, this patient had evidence of hepatocellular injury on laboratory data with liver biopsy revealing fibrosis. Hepatic vein thrombosis is the most common cause of liver failure in patients with PNH - interestingly, this was not present, and it is ongoing hemolysis and hemosiderosis leading to fibrosis which is the primary etiology of his hepatic dysfunction. Despite progress in the understanding of the disorder, treatment options are largely supportive other than bone marrow transplantation, which carries substantial morbidity and mortality. Given the limited therapeutic options, it is interesting to postulate whether our patient would benefit from trials of antioxidant medications or antifibrotic therapies that may retard progression of liver fibrosis. In conclusion, we present an unusual case of PNH presenting as cholestasis, gallstones and CBD stones, with ongoing hemolysis leading to hepatic fibrosis.Figure 1Figure 1