A new and simple score to predict adequate and deep response to ursodeoxycholic acid in patients with primary biliary cholangitis: the ALP-A score.
Journal
European journal of gastroenterology & hepatology
ISSN: 1473-5687
Titre abrégé: Eur J Gastroenterol Hepatol
Pays: England
ID NLM: 9000874
Informations de publication
Date de publication:
01 May 2024
01 May 2024
Historique:
medline:
31
3
2024
pubmed:
31
3
2024
entrez:
31
3
2024
Statut:
ppublish
Résumé
Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), but a significant proportion of patients do not respond adequately, leading to increased risk of adverse outcomes. This study aims to develop a new and straightforward predictive score to identify PBC patients likely to achieve a complete response to UDCA. A logistic regression analysis was conducted using a derivation cohort of PBC patients to identify pre-treatment variables associated with response to UDCA. This analysis led to the development of the ALP-A score, calculated as: Age at diagnosis divided by (alkaline phosphatase at diagnosis/upper limit of normal). ALP-A score accuracy was evaluated using the area under the ROC curve, validated with a large external cohort from Brazil. Additionally, the correlation between the ALP-A score and the previously validated UDCA response score (URS) was assessed. ALP-A score had good predictive power for adequate (AUC 0.794; 95% CI, 0.737-0.852) and deep (0.76; 95% CI, 0.69-0.83) UDCA response at 1 year of treatment. A cutoff score of 17 and 23 points was determined to be the optimal threshold for distinguishing adequate and deep responders, respectively, from non-responders. ALP-A score demonstrated a sensitivity of 73%, specificity of 71%, positive predictive value of 65%, negative predictive value of 78%, and overall accuracy of 72% for biochemical response. The URS displayed similar discriminative ability (AUC 0.798; 95% CI, 0.741-0.855). ALP-A score performs comparably to URS but offers the great advantage of simplicity for routine clinical use. It serves as a valuable tool to identify PBC patients less likely to respond to UDCA treatment, facilitating early consideration of alternative therapeutic approaches.
Sections du résumé
BACKGROUND
BACKGROUND
Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), but a significant proportion of patients do not respond adequately, leading to increased risk of adverse outcomes. This study aims to develop a new and straightforward predictive score to identify PBC patients likely to achieve a complete response to UDCA.
METHODS
METHODS
A logistic regression analysis was conducted using a derivation cohort of PBC patients to identify pre-treatment variables associated with response to UDCA. This analysis led to the development of the ALP-A score, calculated as: Age at diagnosis divided by (alkaline phosphatase at diagnosis/upper limit of normal). ALP-A score accuracy was evaluated using the area under the ROC curve, validated with a large external cohort from Brazil. Additionally, the correlation between the ALP-A score and the previously validated UDCA response score (URS) was assessed.
RESULTS
RESULTS
ALP-A score had good predictive power for adequate (AUC 0.794; 95% CI, 0.737-0.852) and deep (0.76; 95% CI, 0.69-0.83) UDCA response at 1 year of treatment. A cutoff score of 17 and 23 points was determined to be the optimal threshold for distinguishing adequate and deep responders, respectively, from non-responders. ALP-A score demonstrated a sensitivity of 73%, specificity of 71%, positive predictive value of 65%, negative predictive value of 78%, and overall accuracy of 72% for biochemical response. The URS displayed similar discriminative ability (AUC 0.798; 95% CI, 0.741-0.855).
CONCLUSION
CONCLUSIONS
ALP-A score performs comparably to URS but offers the great advantage of simplicity for routine clinical use. It serves as a valuable tool to identify PBC patients less likely to respond to UDCA treatment, facilitating early consideration of alternative therapeutic approaches.
Identifiants
pubmed: 38555601
doi: 10.1097/MEG.0000000000002744
pii: 00042737-202405000-00017
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
628-635Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Références
Hirschfield GM, Chazouillères O, Cortez-Pinto H, Macedo G, de Lédinghen V, Adekunle F, et al. A consensus integrated care pathway for patients with primary biliary cholangitis: a guideline-based approach to clinical care of patients. Expert Rev Gastroenterol Hepatol. 2021; 15:929–939.
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, 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.
Poupon RE, Balkau B, Eschwège E, Poupon R. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. N Engl J Med. 1991; 324:1548–1554.
Angulo P, Batts KP, Therneau TM, Jorgensen RA, Dickson ER, Lindor KD. Long-term ursodeoxycholic acid delays histological progression in primary biliary cirrhosis. Hepatology. 1999; 29:644–647.
Poupon RE, Poupon R, Balkau B. Ursodiol for the long-term treatment of primary biliary cirrhosis. N Engl J Med. 1994; 330:1342–1347.
Cançado GGL, Braga MH, Ferraz MLG, Villela-Nogueira CA, Terrabuio DRB, Cançado ELR, et al.; Members of the Brazilian Cholestasis Study Group Consortium. Clinical features and treatment outcomes of primary biliary cholangitis in a highly admixed population. Ann Hepatol. 2022; 27:100546.
Lammers WJ, van Buuren HR, Hirschfield GM, Janssen HLA, Invernizzi P, Mason AL, et al.; Global PBC Study Group. 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; 147:1338–49.e5; quiz e15.
Shah RA, Kowdley KV. Current and potential treatments for primary biliary cholangitis. Lancet Gastroenterol Hepatol. 2020; 5:306–315.
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.
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.
Kumagi T, Guindi M, Fischer SE, Arenovich T, Abdalian R, Coltescu C, et al. Baseline ductopenia and treatment response predict long-term histological progression in primary biliary cirrhosis. Am J Gastroenterol. 2010; 105:2186–2194.
Corpechot C, Abenavoli L, Rabahi N, Chrétien Y, Andréani T, Johanet C, et al. Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis. Hepatology. 2008; 48:871–877.
Cançado GGL, Couto CA, Terrabuio DRB, Cançado ELR, Villela-Nogueira CA, Ferraz MLG, et al.; Members of the Brazilian Cholestasis Study Group Consortium. Response to ursodeoxycholic acid may be assessed earlier to allow second-line therapy in patients with unresponsive primary biliary cholangitis. Dig Dis Sci. 2023; 68:514–520.
Kuiper EMM, Hansen BE, de Vries RA, den Ouden-Muller JW, van Ditzhuijsen TJM, Haagsma EB, et al.; Dutch PBC Study Group. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology. 2009; 136:1281–1287.
Carbone M, Nardi A, Flack S, Carpino G, Varvaropoulou N, Gavrila C, et al.; 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. Lancet Gastroenterol Hepatol. 2018; 3:626–634.
Murillo Perez CF, Harms MH, Lindor KD, van Buuren HR, Hirschfield GM, Corpechot C, et al.; GLOBAL PBC Study Group. Goals of treatment for improved survival in primary biliary cholangitis: treatment target should be bilirubin within the normal range and normalization of alkaline phosphatase. Am J Gastroenterol. 2020; 115:1066–1074.
Corpechot C, Lemoinne S, Soret PA, Hansen B, Hirschfield G, Gulamhusein A, et al.; Global & ERN Rare-Liver PBC Study Groups. Global & ERN Rare-Liver PBC Study Groups. Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain? Hepatology. 2024; 79:39–48.
Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2021 practice guidance update from the American Association for the Study of Liver Diseases. Hepatology. 2022; 75:1012–1013.
Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2018 practice guidance from the american association for the study of liver diseases. Hepatology. 2019; 69:394–419.
Harms MH, van Buuren HR, Corpechot C, Thorburn D, Janssen HLA, Lindor KD, et al. Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis. J Hepatol. 2019; 71:357–365.
Carbone M, Mells GF, Pells G, Dawwas MF, Newton JL, Heneghan MA, et al.; UK PBC Consortium. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology. 2013; 144:560–569.e7; quiz e13.
Cheung AC, Lammers WJ, Murillo Perez CF, van Buuren HR, Gulamhusein A, Trivedi PJ, et al.; Global PBC Study Group. Effects of age and sex of response to ursodeoxycholic acid and transplant-free survival in patients with primary biliary Cholangitis. Clin Gastroenterol Hepatol. 2019; 17:2076–2084.e2.
Chazouillères O, Wendum D, Serfaty L, Montembault S, Rosmorduc O, Poupon R. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology. 1998; 28:296–301.
Gerussi A, Bernasconi DP, O’Donnell SE, Lammers WJ, Van Buuren H, Hirschfield G, et al.; Italian PBC Study Group and the GLOBAL PBC Study Group. Measurement of gamma glutamyl transferase to determine risk of liver transplantation or death in patients with primary biliary Cholangitis. Clin Gastroenterol Hepatol. 2021; 19:1688–1697.e14.
Cortez-Pinto H, Liberal R, Lopes S, Machado MV, Carvalho J, Dias T, et al. Predictors for incomplete response to ursodeoxycholic acid in primary biliary cholangitis. Data from a national registry of liver disease. United European Gastroenterol J. 2021; 9:699–706.
Gordon SC, Wu K-HH, Lindor K, Bowlus CL, Rodriguez CV, Anderson H, et al.; FOLD Investigators. Ursodeoxycholic acid treatment preferentially improves overall survival among african americans with primary biliary Cholangitis. Am J Gastroenterol. 2020; 115:262–270.
Levy C, Naik J, Giordano C, Mandalia A, O’Brien C, Bhamidimarri KR, et al. Hispanics with primary biliary cirrhosis are more likely to have features of autoimmune hepatitis and reduced response to ursodeoxycholic acid than non-Hispanics. Clin Gastroenterol Hepatol. 2014; 12:1398–1405.
Gazda J, Janicko M, Drazilova S, Grgurevic I, Kanizaj TF, Koller T, et al. External validation of UDCA response score in Slovak and Croatian patients with primary biliary cholangitis. Can J Gastroenterol Hepatol. 2021; 2021:9928065.
Li J, Lu M, Zhou Y, Bowlus CL, Lindor K, Rodriguez-Watson C, et al.; FOLD Investigators. Dynamic risk prediction of response to ursodeoxycholic acid among patients with primary biliary cholangitis in the USA. Dig Dis Sci. 2022; 67:4170–4180.
Chang J-I, Kim JH, Sinn DH, Cho J-Y, Kim KM, Oh JH, et al. Clinical outcomes and validation of ursodeoxycholic acid response scores in patients with korean primary biliary cholangitis: a multicenter cohort study. Gut Liver. 2023; 17:620–628.
Chen J, Xue D, Gao F, Tao L, Li Y, Zhang Q, et al. Influence factors and a predictive scoring model for measuring the biochemical response of primary biliary cholangitis to ursodeoxycholic acid treatment. Eur J Gastroenterol Hepatol. 2018; 30:1352–1360.
Shu Y, Song Y, Bai T, Pan X, Shang H, Yang L, et al. Predictive model of ursodeoxycholic acid treatment response in primary biliary cholangitis. J Clin Transl Hepatol. 2021; 9:187–193.
Cristoferi L, Calvaruso V, Overi D, Viganò M, Rigamonti C, Degasperi E, et al.; Italian PBC Registry. Accuracy of transient elastography in assessing fibrosis at diagnosis in naïve patients with primary biliary cholangitis: a dual cut-off approach. Hepatology. 2021; 74:1496–1508.
Corpechot C, Carrat F, Gaouar F, Chau F, Hirschfield G, Gulamhusein A, et al.; Global & ERN Rare-Liver PBC Study Groups. Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis. J Hepatol. 2022; 77:1545–1553.
Cançado GGL, Couto CA, Terrabuio DRB, Cançado ELR, Villela-Nogueira CA, Ferraz MLG, et al.; Members of the Brazilian Cholestasis Study Group Consortium. Members of the brazilian cholestasis study group consortium. response to ursodeoxycholic acid may be assessed earlier to allow second-line therapy in patients with unresponsive primary biliary cholangitis. Dig Dis Sci. 2023; 68:514–520.