Goals of Treatment for Improved Survival in Primary Biliary Cholangitis: Treatment Target Should Be Bilirubin Within the Normal Range and Normalization of Alkaline Phosphatase

被引：90

作者：

Murillo Perez, Carla F. ^{[1
,2
]}

Harms, Maren H. ^{[2
]}

Lindor, Keith D. ^{[3
]}

van Buuren, Henk R. ^{[2
]}

Hirschfield, Gideon M. ^{[1
]}

Corpechot, Christophe ^{[4
]}

van der Meer, Adriaan J. ^{[2
]}

Feld, Jordan J. ^{[1
]}

Gulamhusein, Aliya ^{[1
]}

Lammers, Willem J. ^{[2
]}

Ponsioen, Cyriel Y. ^{[5
]}

Carbone, Marco ^{[6
,7
]}

Mason, Andrew L. ^{[8
]}

Mayo, Marlyn J. ^{[9
]}

Invernizzi, Pietro ^{[6
,7
]}

Battezzati, Pier Maria ^{[10
]}

Floreani, Annarosa ^{[11
]}

Lleo, Ana ^{[12
]}

Nevens, Frederik ^{[13
]}

Kowdley, Kris V. ^{[14
]}

Bruns, Tony ^{[15
,16
]}

Dalekos, George N. ^{[17
,18
]}

Gatselis, Nikolaos K. ^{[17
,18
]}

Thorburn, Douglas ^{[19
]}

Trivedi, Palak J. ^{[20
,21
]}

Verhelst, Xavier ^{[22
]}

Pares, Albert ^{[23
]}

Janssen, Harry L. A. ^{[1
]}

Hansen, Bettina E. ^{[1
,24
]}

机构：

[1] Univ Hlth Network, Toronto Gen Hosp, Toronto Ctr Liver Dis, Toronto, ON, Canada

[2] Erasmus MC, Gastroenterol & Hepatol, Rotterdam, Netherlands

[3] Arizona State Univ, Coll Hlth Solut, Phoenix, AZ USA

[4] Hop St Antoine, Ctr Reference Malad Inflammatoires VoiesBiliaires, Paris, France

[5] Acad Med Ctr, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands

[6] Univ Milano Bicocca, Div Gastroenterol, Dept Med & Surg, Milan, Italy

[7] Univ Milano Bicocca, Dept Med & Surg, Ctr Autoimmune Liver Dis, Milan, Italy

[8] Univ Alberta, Div Gastroenterol & Hepatol, Edmonton, AB, Canada

[9] UT Southwestern Med Ctr, Digest & Liver Dis, Dallas, TX USA

[10] Univ Milan, Dept Hlth Sci, Milan, Italy

[11] Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy

[12] Humanitas Univ, Humanitas Clin Res Ctr IRCSS, Div Internal Med & Hepatol, Milan, Italy

[13] Katholieke Univ Leuven, Univ Hosp Leuven, Dept Hepatol, Leuven, Belgium

[14] Swedish Med Ctr, Liver Care Network, Seattle, WA USA

[15] Friedrich Schiller Univ, Jena Univ Hosp, Dept Internal Med 4, Jena, Germany

[16] Univ Hosp RWTH Aachen, Dept Internal Med 3, Aachen, Germany

[17] Univ Thessaly, Dept Med, Larisa, Greece

[18] Univ Thessaly, Res Lab Internal Med, Larisa, Greece

[19] Royal Free Hosp, Sheila Sherlock Liver Ctr, London, England

[20] Univ Birmingham, Natl Inst Hlth Res, Birmingham Biomed Res Ctr, Birmingham, W Midlands, England

[21] Univ Birmingham, Natl Inst Hlth Res, Ctr Liver Res, Birmingham, W Midlands, England

[22] Ghent Univ Hosp, Dept Gastroenterol & Hepatol, Ghent, Belgium

[23] Univ Barcelona, IDIBAPS, CIBERehd, Liver Unit,Hosp Clin, Barcelona, Spain

[24] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada

来源：

AMERICAN JOURNAL OF GASTROENTEROLOGY | 2020年 / 115卷 / 07期

关键词：

CLINICAL-PRACTICE GUIDELINES; PLACEBO-CONTROLLED TRIAL; URSODEOXYCHOLIC ACID; SERUM BILIRUBIN; AUTOIMMUNE HEPATITIS; BIOCHEMICAL RESPONSE; CIRRHOSIS; PROGNOSIS; MANAGEMENT; REMISSION;

D O I：

10.14309/ajg.0000000000000557

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

INTRODUCTION: In primary biliary cholangitis (PBC), bilirubin and alkaline phosphatase (ALP) are widely established as independent predictors of prognosis. Current treatment goals do not aim for normalization of surrogate markers because their association with survival has not been defined. METHODS: The patient cohort from the GLOBAL PBC Study Group was used, comprising of long-term follow-up data from European and North American centers. Ursodeoxycholic acid-treated and untreated patients with bilirubin levels <= 1 x upper limit of normal (ULN) at baseline or 1 year were included. The association of normal ALP with transplant-free survival was assessed in a subgroup with ALP <= 1.67 x ULN at 1 year. Optimal thresholds of bilirubin and ALP to predict liver transplantation (LT) or death were evaluated. RESULTS: There were 2,281 patients included in the time zero cohort and 2,555 patients in the 1-year cohort. The bilirubin threshold with the highest ability to predict LT or death at 1 year was 0.6 x ULN (hazard ratio 2.12, 95% CI 1.69-2.66, P < 0.001). The 10-year survival rates of patients with bilirubin <= 0.6 x ULN and >0.6 x ULN were 91.3% and 79.2%, respectively (P < 0.001). The risk for LT or death was stable below the bilirubin levels of 0.6 x ULN, yet increased beyond this threshold. Ursodeoxycholic acid-induced reduction in bilirubin below this threshold was associated with an 11% improvement in 10-year survival. Furthermore, ALP normalization was optimal, with 10-year survival rates of 93.2% in patients with ALP <= 1 x ULN and 86.1% in those with ALP 1.0-1.67 x ULN. DISCUSSION: Attaining bilirubin levels <= 0.6 x ULN or normal ALP are associated with the lowest risk for LT or death in patients with PBC. This has important implications for treatment targets.

引用

页码：1066 / 1074

页数：9

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