Overlap Syndrome of Autoimmune Hepatitis, Primary Biliary Cholangitis, and Primary Sclerosing Cholangitis in a Patient with Systemic Lupus Erythematosus: A Case Report of Complex Autoimmune Liver Disease

Abstract

Introduction: Overlap syndrome is a spectrum of clinical manifestations between Autoimmune hepatitis (AIH), Primary Biliary Cholangitis (PBC), and Primary Sclerosing Cholangitis (PSC). Overlap syndromes between AIH-PBC and AIH-PSC are well recognized. Overlap between PBC-PSC has only been reported in a few patients. To our knowledge, it is extremely rare for PBC, PSC and probable AIH overlap syndrome to occur in the same patient.Figure 1Figure 2Case report: The patient is a 48-year old Hispanic male with liver cirrhosis and SLE. His cirrhosis was complicated by esophageal varices, thrombocytopenia, coagulopathy, hypoalbuminemia, and chronic portal vein thrombosis. His biochemical profile revealed elevated ALT (2X upper limit of normal (ULN)) and AST (4X ULN), persistently elevated alkaline phosphatase (3X ULN) and elevated bilirubin (2X ULN). Investigations for etiology of cirrhosis included a detailed social history were done. Viral hepatitis serology, iron studies, celiac panel, ceruloplasmin and alpha-1 antitrypsin level were unremarkable. Anti-nuclear antibody (ANA) was positive with a titer of 1:320, anti-smooth muscle antibody (ASMA) was positive with a serum level of 20 (Normally < 20) and P-ANCA was positive. Anti-Soluble liver antigen (anti-SLA) and anti-liver kidney microsomal 1 antigen (Anti-LKM1) were negative. Gamma globulin level was elevated at 2501 mg/dL (normal range 694-1617). Anti-mitochondrial antibody (AMA) was positive with a level of 71.9 units (Normally < 20). The more specific antibody for PBC, AMA-M2, was also positive as well. He also had a positive anti-dsDNA. The patient met criteria for AIH-PBC overlap syndrome based on Paris Criteria. He was on prednisone for autoimmune thrombocytopenia and was started on oral Ursodeoxycholic acid. We also performed an ERCP with cholangiography which showed segmental irregularities of intrahepatic bile ducts with beaded appearance suggestive of sclerosing cholangitis. Based on patient's liver enzymes profile, autoimmune markers, and ERCP findings; he was diagnosed with AIH-PBC-PSC overlap syndrome. We wanted to obtain a liver biopsy, however it could not be done as patient deceased due to septic shock. Conclusion: We are presenting a case with complex clinical spectrum of autoimmune liver diseases which include AIH, PBC, and PSC. To our knowledge, this is only the second reported case of all these diseases overlapping in the same patient; and the first reported case in a patient with SLE.