Benedetta Terziroli Beretta-Piccoli1, Guido Stirnimann2, Joachim Mertens3, David Semela4, Yoh Zen5, Luca Mazzucchelli6, Anja Voreck7, Norbert Kolbus7, Elisabetta Merlo6, Claudia Di Bartolomeo8, Paola Messina8, Andreas Cerny9, Silvia Costantini10, Diego Vergani5, Giorgina Mieli-Vergani11. 1. Epatocentro Ticino, Via Soldino 5, 6900, Lugano, Switzerland. Electronic address: benedetta.terziroli@hin.ch. 2. Department of Visceral Surgery and Medicine, University of Bern, Switzerland. 3. Gastroenterology and Hepatology Department, University Hospital Zurich, Zurich, Switzerland. 4. Gastroenterology and Hepatology Department, Kantonsspital St. Gallen, St. Gallen, Switzerland. 5. Institute of Liver Studies, MowatLabs, King's College London Faculty of Life Sciences & Medicine at King's College Hospital, Denmark Hill, London, SE5 9RS, United Kingdom. 6. Istituto Cantonale di Patologia, Locarno, Switzerland. 7. Thermo Fisher Scientific, Freiburg, Germany. 8. Fondazione Epatocentro Ticino, Lugano, Switzerland. 9. Epatocentro Ticino, Via Soldino 5, 6900, Lugano, Switzerland. 10. Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy. 11. Paediatric Liver, GI and Nutrition Centre, MowatLabs, King's College London Faculty of Life Sciences & Medicine at King's College Hospital, Denmark Hill, London, SE5 9RS, United Kingdom.
Abstract
BACKGROUND & AIM: The diagnosis of primary biliary cholangitis (PBC), an uncommon immune-mediated cholestatic liver disease, is based on positive circulating anti-mitochondrial (AMA) and/or PBC-specific anti-nuclear autoantibodies (ANA), coupled with elevated serum alkaline phopsphatase (ALP) levels. Timely initiation of treatment with ursodeoxycholic acid prevents progression to cirrhosis and liver failure. We aimed at investigating liver histology in patients with normal ALP level and positive AMA and/or PBC-specific ANA. METHODS: We searched the Swiss PBC Cohort Study database, which includes subjects with positive PBC autoimmune serology and normal ALP levels, for patients who underwent a liver biopsy. Histological slides were centrally reviewed by an expert liver pathologist, and sera were centrally re-tested for AMA and ANA. RESULTS: 30 patients were included; 90% females, median age 53 (range 27-72) years. Twenty-four (80%) had liver histology typical for (n = 2), consistent with (n = 16) or suggestive of (n = 6) PBC, including three of four AMA-negative ANA-positive patients. Among 22 ursodeoxycholic acid treated patients, 14 had elevated GGT levels before treatment; a significant decrease of the median GGT level between pre- (1.46 x ULN) and post- (0.43 x ULN) treatment (p = 0.0018) was observed. CONCLUSIONS: In our series, a high proportion of AMA positive patients with normal ALP levels have PBC. For the first time we show histological diagnosis of PBC in AMA-negative/PBC-specific ANA-positive subjects and the potential role of GGT as a biomarker in PBC patients with normal baseline ALP levels. Current guidelines for the diagnosis of PBC do not cover the whole extent of PBC presentation, with important clinical implications in terms of timely treatment initiation.
BACKGROUND & AIM: The diagnosis of primary biliary cholangitis (PBC), an uncommon immune-mediated cholestatic liver disease, is based on positive circulating anti-mitochondrial (AMA) and/or PBC-specific anti-nuclear autoantibodies (ANA), coupled with elevated serum alkaline phopsphatase (ALP) levels. Timely initiation of treatment with ursodeoxycholic acid prevents progression to cirrhosis and liver failure. We aimed at investigating liver histology in patients with normal ALP level and positive AMA and/or PBC-specific ANA. METHODS: We searched the Swiss PBC Cohort Study database, which includes subjects with positive PBC autoimmune serology and normal ALP levels, for patients who underwent a liver biopsy. Histological slides were centrally reviewed by an expert liver pathologist, and sera were centrally re-tested for AMA and ANA. RESULTS: 30 patients were included; 90% females, median age 53 (range 27-72) years. Twenty-four (80%) had liver histology typical for (n = 2), consistent with (n = 16) or suggestive of (n = 6) PBC, including three of four AMA-negative ANA-positive patients. Among 22 ursodeoxycholic acid treated patients, 14 had elevated GGT levels before treatment; a significant decrease of the median GGT level between pre- (1.46 x ULN) and post- (0.43 x ULN) treatment (p = 0.0018) was observed. CONCLUSIONS: In our series, a high proportion of AMA positive patients with normal ALP levels have PBC. For the first time we show histological diagnosis of PBC in AMA-negative/PBC-specific ANA-positive subjects and the potential role of GGT as a biomarker in PBC patients with normal baseline ALP levels. Current guidelines for the diagnosis of PBC do not cover the whole extent of PBC presentation, with important clinical implications in terms of timely treatment initiation.