Anti-gp210 and anti-sp100 antibody status and ursodeoxycholic acid response in primary biliary cholangitis
Abstract
Aims:
Primary biliary cholangitis is a chronic biliary liver disease, for which the prognosis is poorer in patients who do not respond satisfactorily to the mainstay of treatment, ursodeoxycholic acid. Evidence suggests the presence of primary biliary cholangitis specific antinuclear antibodies such as anti-gp210 or anti-sp100 are associated with poorer clinical outcomes, and possibly with non-response to ursodeoxycholic acid. We aimed to analyze the association between these primary biliary cholangitis-specific antinuclear antibodies, anti-gp210 and anti-sp100, and ursodeoxycholic acid response in primary biliary cholangitis.
Material and methods:
A retrospective audit was performed on 92 patients with primary biliary cholangitis for whom specific antinuclear antibody status and ursodeoxycholic acid response data was available. The response to ursodeoxycholic acid, assessed using Barcelona and Paris II criteria, was analyzed according to anti-gp210 and/or anti-sp100 positivity.
Results:
There was a non-significantly lower ursodeoxycholic acid response rate among anti-gp210 positive patients (12/18, 66.7%) compared with anti-gp210 negative patients (57/74, 77.0%, p=0.5439); and in anti-sp100 positive patients (15/21, 71.4%) compared with anti-sp100 negative patients (54/71, 76.1%, p=0.886). On univariate analysis and multivariate analysis, there was no significant change in odds of ursodeoxycholic acid response with either anti-gp210 or anti-sp100 positivity.
Conclusion:
This study found that there was no association between anti-gp210 or anti-sp100 antibody status and response to ursodeoxycholic acid in a European primary biliary cholangitis cohort. This is in contrast to previous literature. However there was a trend towards an association between primary biliary cholangitis-specific antinuclear antibody positivity and lower ursodeoxycholic acid response rates.
Keywords
References
Trivedi P, Hirschfield G. Primary biliary cirrhosis: Renaming primary biliary cirrhosis—clarity or confusion?. Nat Rev Gastro Hepat. 2015; 12:678-679.
Parés A, Caballería L, Rodés J. Excellent Long-Term Survival in Patients With Primary Biliary Cirrhosis and Biochemical Response to Ursodeoxycholic Acid. Gastroenterology. 2006; 130:715-720.
Floreani A, Franceschet I, Perini L, Cazzagon N, Gershwin M, Bowlus C.. New Therapies for Primary Biliary Cirrhosis. Clin Rev Allerg Immu. 2014; 48:263-272.
Nevens F, Andreone P, Mazzella G, Strasser S, Bowlus C, Invernizzi P, Drenth J, Pockros P, Regula J, Beuers U, Trauner M, Jones D, Floreani A, Hohenester S, Luketic V, Shiffman M, van Erpecum K, Vargas V, Vincent C, Hirschfield G, Shah H, Hansen B, Lindor K, Marschall H, Kowdley K, Hooshmand-Rad R, Marmon T, Sheeron S, Pencek R, MacConell L, Pruzanski M, Shapiro D. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. New Engl J Med. 2016; 375:631-643
Corpechot C, Chazouillères O, Rousseau A, Le Gruyer A, Habersetzer F, Mathurin P, Goria O, Potier P, Minello A, Silvain C, Abergel A, Debette-Gratien M, Larrey D, Roux O, Bronowicki J, Boursier J, de Ledinghen V, Heurgue-Berlot A, Nguyen-Khac E, Zoulim F, Ollivier-Hourmand I, Zarski J, Nkontchou G, Lemoinne S, Humbert L, Rainteau D, Lefèvre G, de Chaisemartin L, Chollet-Martin S, Gaouar F, Admane F, Simon T, Poupon R. A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis. New Engl J Med. 2018;378:2171-2181
Carbone M, Mells G, Pells G, Dawwas M, Newton J, Heneghan M, Neuberger J, Day D, Ducker S, Sandford R, Alexander G, Jones D. Sex and Age Are Determinants of the Clinical Phenotype of Primary Biliary Cirrhosis and Response to Ursodeoxycholic Acid. Gastroenterology. 2013; 144:560-569.e7.
Kumagi T, Guindi M, Fischer S, Arenovich T, Abdalian R, Coltescu C, Heathcote E, Hirschfield G. Baseline Ductopenia and Treatment Response Predict Long-Term Histological Progression in Primary Biliary Cirrhosis. Am J Gastroenterol. 2010; 105:2186-2194.
Nakamura M, Kondo H, Tanaka A, Komori A, Ito M, Yamamoto K, Ohira H, Zeniya M, Hashimoto E, Honda M, Kaneko S, Ueno Y, Kikuchi K, Shimoda S, Harada K, Arai K, Miyake Y, Abe M, Taniai M, Saibara T, Sakisaka S, Takikawa H, Onji M, Tsubouchi H, Nakanuma Y, Ishibashi H. Autoantibody status and histological variables influence biochemical response to treatment and long-term outcomes in Japanese patients with primary biliary cirrhosis. Hepatol Res. 2014; 45:846-855.
Valour F, Durupt S, Khenifer S, Durieu I. Diagnostic value of anti-gp210 antibodies in primary biliary cirrhosis: a case-based review. BMJ Case Rep. 2013; 2013:bcr2013009803-bcr2013009803.
Liu H, Norman G, Shums Z, Worman H, Krawitt E, Bizzaro N, Vergani D, Bogdanos D, Dalekos G, Milkiewicz P, Czaja A, Heathcote E, Hirschfield G, Tan E, Miyachi K, Bignotto M, Battezzati P, Lleo A, Leung P, Podda M, Gershwin M, Invernizzi P. PBC Screen: An IgG/IgA dual isotype ELISA detecting multiple mitochondrial and nuclear autoantibodies specific for primary biliary cirrhosis. J Autoimmun. 2010; 35:436-442.
Mytilinaiou M, Meyer W, Scheper T, Rigopoulou E, Probst C, Koutsoumpas A, Abeles D, Burroughs A, Komorowski L, Vergani D, Bogdanos D. Diagnostic and clinical utility of antibodies against the nuclear body promyelocytic leukaemia and Sp100 antigens in patients with primary biliary cirrhosis. Clin Chim Acta. 2012; 413:1211-1216.
Nakamura M, Kondo H, Mori T, Komori A, Matsuyama M, Ito M, Takii Y, Koyabu M, Yokoyama T, Migita K, Daikoku M, Abiru S, Yatsuhashi H, Takezaki E, Masaki N, Sugi K, Honda K, Adachi H, Nishi H, Watanabe Y, Nakamura Y, Shimada M, Komatsu T, Saito A, Saoshiro T, Harada H, Sodeyama T, Hayashi S, Masumoto A, Sando T, Yamamoto T, Sakai H, Kobayashi M, Muro T, Koga M, Shums Z, Norman G, Ishibashi H. Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis. Hepatology. 2006; 45:118-127.
Corpechot C, Chazouillères O, Poupon R. Early primary biliary cirrhosis: Biochemical response to treatment and prediction of long-term outcome. J Hepatol. 2011; 55:1361-1367.
.European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017; 67:145-172.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of cholestatic liver diseases. J Hepatol 2009;51:237-267
Carbone M, Sharp S, Flack S, Paximadas D, Spiess K, Adgey C, Griffiths L, Lim R, Trembling P, Williamson K, Wareham N, Aldersley M, Bathgate A, Burroughs A, Heneghan M, Neuberger J, Thorburn D, Hirschfield G, Cordell H, Alexander G, Jones D, Sandford R, Mells G. The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis. Hepatology 2015;63:930-950
Carbone M, Nardi A, Flack S, Carpino G, Varvaropoulou N, Gavrila C, Spicer A, Badrock J, Bernuzzi F, Cardinale V, Ainsworth H, Heneghan M, Thorburn D, Bathgate A, Jones R, Neuberger J, Battezzati P, Zuin M, Taylor-Robinson S, Donato M, Kirby J, Mitchell-Thain R, Floreani A, Sampaziotis F, Muratori L, Alvaro D, Marzioni M, Miele L, Marra F, Giannini E, Gaudio E, Ronca V, Bonato G, Cristoferi L, Malinverno F, Gerussi A, Stocken D, Cordell H, Hirschfield G, Alexander G, Sandford R, Jones D, Invernizzi P, Mells G, Italian PBC Study Group and the UK–PBC Consortium. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score. The Lancet Gastroenterology & Hepatology. 2018; 3: 626-634
Lammers W, van Buuren H, Hirschfield G, Janssen H, Invernizzi P, Mason A, Ponsioen C, Floreani A, Corpechot C, Mayo M, Battezzati P, Parés A, Nevens F, Burroughs A, Kowdley K, Trivedi P, Kumagi T, Cheung A, Lleo A, Imam M, Boonstra K, Cazzagon N, Franceschet I, Poupon R, Caballeria L, Pieri G, Kanwar P, Lindor K, Hansen B. Levels of Alkaline Phosphatase and Bilirubin Are Surrogate End Points of Outcomes of Patients With Primary Biliary Cirrhosis: An International Follow-up Study. Gastroenterology. 2014; 147:1338-1349.e5.
Lleo A, Jepsen P, Morenghi E, Carbone M, Moroni L, Battezzati P, Podda M, Mackay I, Gershwin M, Invernizzi P.. Evolving Trends in Female to Male Incidence and Male Mortality of Primary Biliary Cholangitis. Sci Rep, 2016; 6: 25906.
Lammert C, Juran B, Schlicht E, Chan L, Atkinson E, de Andrade M, Lazaridis K. Biochemical response to ursodeoxycholic acid predicts survival in a North American cohort of primary biliary cirrhosis patients. J Gastroenterol 2013;49:1414-1420
Talwalkar J, Lindor K. Primary biliary cirrhosis. Lancet. 2003; 362:53-61.
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