S2969 Distinction Between Mitochondrial Antibody Positive and Negative Primary Biliary Cholangitis: Case Report and Literature Review

Abstract

Introduction: Anti-mitochondrial antibody-positive primary biliary cholangitis (AMA-pos PBC) is an autoimmune disorder in which monoclonal antibodies are produced against epitopes with in the mitochondrial membranes of biliary epithelial cells, resulting in progressive non-suppurative biliary cholangitis. Up to 5 % of PBC patients lack these auto antibodies, termed as anti-mitochondrial antibody negative (AMA-neg) PBC. This is a somewhat new entity and a variant of AMA-pos PBC but not an overlap syndrome. There have not been good studies describing this phenomenon or associated terminology in the literature. Case Description/Methods: An 87-year-old woman was referred to our clinic after her medical oncologist found elevated isolated levels of serum alkaline phosphatase (714 units/L). She reported fatigue but denied any other symptoms. The physical examination was benign, except for bilateral lower extremity swelling secondary to lymphedema. Her serum alkaline phosphatase level decreased to 413 units/L after an initial dose of prednisone 40 mg daily, and she was maintained on 10 mg daily. Her antinuclear antibody titer was greater than 1:2560 in a centromere pattern. Anti- mitochondrial antibody was not detected. Total IgG level was 871 mg/dL (normal, < 1600 mg/dL), serum anti-smooth muscle antibody was negative, and the hepatitis panel was normal. Computed tomography of the abdomen and pelvis without contrast showed normal liver parenchyma and no acute intra-abdominal pathology. Histopathological examination indicated florid duct lesions. Background parenchyma showed no significant steatosis, and the inflammatory changes were limited primarily to the portal areas. Periodic acid-Schiff staining highlighted the intact hepatic parenchyma and architecture. The patient was diagnosed with AMA-neg PBC and responded well to Urosdeoxycholic acid therapy. (Figure) (Table). Discussion: This case highlights the importance of recognizing AMA-neg PBC as a variant of AMA-pos PBC and being able to differentiate them. Autoimmune cholangitis is a vague and imprecise term that cannot be used in this context. All AMA-negative PBC patients should be tested for other PBC-specific autoantibodies. Although prognosis and bile duct damage and loss are worse in AMA-neg PBC for unknown reasons, treatment remains the same for both.Figure 1.: A: The position of AMA-neg PBC in the spectrum of autoimmune hepatobiliary cholangiopathy PBC, primary biliary cholangitis; ANA, antimitochondrial antibody; IgM, immunoglobulin M; UDCA, ursodeoxycholic acid; AMA-neg, antimitochondrial antibody negative; ANA, antinuclear antibodies; IgG, Immunoglobulin G; ASMA, anti-smooth muscle antibody; anti-LKM-1, anti-liver kidney microsomal antibodies; Anti-LC-1, anti-liver cytosol antibodies; anti-SLA/LP antibodies, anti-soluble liver antigen/liver pancreas antibodies; MRCP, magnetic resonance cholangiogram; ERCP, endoscopic retrograde cholangio-pancreatogram. B and C:Two photomicrographs showing histologic features typical of the florid duct lesion seen in primary biliary cholangitis.. The portal areas show granulomatous inflammation and lymphocytic cholangitis of the bile ducts (pointed yellow arrows) (hematoxylin and eosin stain, 200X original magnification). Table 1. - Diagnostic criteria of AMA-Pos PBC The diagnosis of AMA-pos PBC can be established when two of the criteria listed in Table 1 are met[5] Evidence Criteria 1) Biochemical evidence of cholestasis Elevated alkaline phosphatase levels 2) Serological:AMA-Pos PBCAMA-Neg PBC Mitochondrial antibody positiveMitochondrial antibody negative/Presence of other PBC specific autoantibodies i.e., sp100 or gp210 3) Histopathological Nonsuppurative destructive cholangitis and destruction of interlobular bile ducts.