Non-Classical Autoimmune Cholangiopathy Associated With Non-Cirrhotic Portal Hypertension

INTRODUCTION: Autoimmune cholangiopathy (cholangitis; AIC) is a chronic inflammation of the liver that is considered a variant syndrome of autoimmune hepatitis. At times, AIC is used to describe AMA-negative primary biliary cholangitis (PBC), small duct primary sclerosing cholangitis (PSC), and IgG4 sclerosing cholangitis as well as overlap syndrome. Here, we present a case of AIC that did not fit into any of the known nomenclature or phenotype. CASE DESCRIPTION/METHODS: 41-year-old woman was recognized to have abnormal liver tests (alkaline phosphatase [ALP] 340 U/L, ALT 107 U/L, AST 61 U/L), thrombocytopenia (68k /cumm) and splenomegaly. Ultrasound and magnetic resonance cholangiopancreatography confirmed the presence of splenomegaly without any biliary abnormalities suggestive of PSC. Liver stiffness on transient elastography indicated F2-F3 stage of fibrosis (LSM 11.2 kPa). Serologic workup was negative for viral and autoimmune hepatitis (negative ANA, SMA, Anti-LKM, AMA), and serum IgG was low (669mg/dL). A liver biopsy showed bile ductular reaction with bile duct loss suggestive of chronic biliary disease with parenchymal distortion suggestive of nodular regenerative hyperplasia. A trichrome stain showed periportal fibrosis. A short course of prednisone was associated with minimal improvement in liver tests. Ursodiol was started, but when she developed worsening liver tests with jaundice (Total bilirubin 3.8 mg/dL, ALP 291 U/L), she was initiated on budesonide and mycophenolate mofetil with a biochemical response. Due to variceal bleed despite primary prophylaxis with endoscopic band ligation (EBL) and carvedilol, further evaluation with a trans-jugular liver biopsy with portal pressure measurements showed hepatic vein pressure gradient of 16 mm Hg and a vaguely nodular architecture, chronic cholestasis, ductopenia with bridging fibrosis (Figures 1 and 2). The portal tracts were expanded by mild chronic inflammatory cell infiltrate predominantly composed of lymphocytes. Reticulin stain revealed regenerative plates and focal regenerative nodules. IgG 4 stain was negative. DISCUSSION: This case has several unusual features (negative autoantibodies, non-cirrhotic portal hypertension, low serum Ig levels with negative IgG4 staining, and response to immunosuppression) that make it a diagnostic challenge and at best described as non-classical autoimmune cholangiopathy associated with non-cirrhotic portal hypertension.Figure 1.: Immunohistochemistry with Anti Cytokeratin7 Antibody: Ductular reaction & staining of periportal hepatocytes indicating chronic cholestasis.Figure 2.: Hematoxylin and Eosin staining: Portal tract expansion with evidence of ductular reaction and lymphocytic inflammation.