Measurement of Gamma Glutamyl Transferase to Determine Risk of Liver Transplantation or Death in Patients With Primary Biliary Cholangitis.


Journal

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
ISSN: 1542-7714
Titre abrégé: Clin Gastroenterol Hepatol
Pays: United States
ID NLM: 101160775

Informations de publication

Date de publication:
08 2021
Historique:
received: 08 05 2020
revised: 14 07 2020
accepted: 03 08 2020
pubmed: 11 8 2020
medline: 10 9 2021
entrez: 11 8 2020
Statut: ppublish

Résumé

Gamma-glutamyltransferase (GGT) is a serum marker of cholestasis. We investigated whether serum level of GGT is a prognostic marker for patients with primary biliary cholangitis (PBC). We analyzed data from patients with PBC from the Global PBC Study Group, comprising 14 centers in Europe and North America. We obtained measurements of serum GGT at baseline and time points after treatment. We used Cox model hazard ratios to evaluate the association between GGT and clinical outcomes, including liver transplantation and liver-related death. Of the 2129 patients included in our analysis, 281 (13%) had a liver-related clinical endpoint. Mean age at diagnosis was 53 years and 91% of patients were female patients. We found a correlation between serum levels of GGT and alkaline phosphatase (ALP) (r = 0.71). Based on data collected at baseline and yearly for up to 5 years, higher serum levels of GGT were associated with lower hazard for transplant-free survival. Serum level of GGT at 12 months after treatment higher than 3.2-fold the upper limit of normal (ULN) identified patients who required liver transplantation or with liver-related death at 10 years with an area under the receiver operating characteristic curve of 0.70. The risk of liver transplantation or liver-related death in patients with serum level of GGT above 3.2-fold the ULN, despite level of ALP lower than 1.5-fold the ULN, was higher compared to patients with level of GGT lower than 3.2-fold the ULN and level of ALP lower than 1.5-fold the ULN (P < .05). Including information on level of GGT increased the prognostic value of the Globe score. Serum level of GGT can be used to identify patients with PBC at risk for liver transplantation or death, and increase the prognostic value of ALP measurement. Our findings support the use of GGT as primary clinical endpoint in clinical trials. In patients with low serum level of ALP, a high level of GGT identifies those who might require treatment of metabolic disorders or PBC treatment escalation.

Sections du résumé

BACKGROUND & AIMS
Gamma-glutamyltransferase (GGT) is a serum marker of cholestasis. We investigated whether serum level of GGT is a prognostic marker for patients with primary biliary cholangitis (PBC).
METHODS
We analyzed data from patients with PBC from the Global PBC Study Group, comprising 14 centers in Europe and North America. We obtained measurements of serum GGT at baseline and time points after treatment. We used Cox model hazard ratios to evaluate the association between GGT and clinical outcomes, including liver transplantation and liver-related death.
RESULTS
Of the 2129 patients included in our analysis, 281 (13%) had a liver-related clinical endpoint. Mean age at diagnosis was 53 years and 91% of patients were female patients. We found a correlation between serum levels of GGT and alkaline phosphatase (ALP) (r = 0.71). Based on data collected at baseline and yearly for up to 5 years, higher serum levels of GGT were associated with lower hazard for transplant-free survival. Serum level of GGT at 12 months after treatment higher than 3.2-fold the upper limit of normal (ULN) identified patients who required liver transplantation or with liver-related death at 10 years with an area under the receiver operating characteristic curve of 0.70. The risk of liver transplantation or liver-related death in patients with serum level of GGT above 3.2-fold the ULN, despite level of ALP lower than 1.5-fold the ULN, was higher compared to patients with level of GGT lower than 3.2-fold the ULN and level of ALP lower than 1.5-fold the ULN (P < .05). Including information on level of GGT increased the prognostic value of the Globe score.
CONCLUSIONS
Serum level of GGT can be used to identify patients with PBC at risk for liver transplantation or death, and increase the prognostic value of ALP measurement. Our findings support the use of GGT as primary clinical endpoint in clinical trials. In patients with low serum level of ALP, a high level of GGT identifies those who might require treatment of metabolic disorders or PBC treatment escalation.

Identifiants

pubmed: 32777554
pii: S1542-3565(20)31083-1
doi: 10.1016/j.cgh.2020.08.006
pii:
doi:

Substances chimiques

gamma-Glutamyltransferase EC 2.3.2.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1688-1697.e14

Informations de copyright

Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.

Auteurs

Alessio Gerussi (A)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Davide Paolo Bernasconi (DP)

Bicocca Bioinformatics Biostatistics and Bioimaging Centre - B4, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

Sarah Elisabeth O'Donnell (SE)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Willem J Lammers (WJ)

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands.

Henk Van Buuren (H)

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands.

Gideon Hirschfield (G)

Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada.

Harry Janssen (H)

Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada.

Christophe Corpechot (C)

Centre de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, Paris, France; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hôpital Saint- Antoine, Paris, France.

Anna Reig (A)

Liver Unit, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hospital Clinic de Barcelona, Barcelona, Spain.

Albert Pares (A)

Liver Unit, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hospital Clinic de Barcelona, Barcelona, Spain.

Pier Maria Battezzati (PM)

Liver and Gastroenterology Unit, ASST Santi Paolo Carlo, University of Milan, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), ASST Santi Paolo e Carlo, Milan, Italy.

Massimo Giovanni Zuin (MG)

Liver and Gastroenterology Unit, ASST Santi Paolo Carlo, University of Milan, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), ASST Santi Paolo e Carlo, Milan, Italy.

Nora Cazzagon (N)

Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Azienda Ospedale - Università Padova, Padova, Italy.

Annarosa Floreani (A)

Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; IRCCS Negrar, Verona, Italy.

Frederik Nevens (F)

Department of Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), University Hospitals Leuven, KU Leuven, Leuven, Belgium.

Nikolaos Gatselis (N)

Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.

George Dalekos (G)

Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.

Marlyn J Mayo (MJ)

Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas.

Douglas Thorburn (D)

The Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom.

Tony Bruns (T)

Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.

Andrew L Mason (AL)

Division of Gastroenterology and Hepatology, University of Alberta, Edmonton, Canada.

Xavier Verhelst (X)

Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Ghent University Hospital, Ghent, Belgium.

Kris Kowdley (K)

Liver Institute Northwest, Seattle, Washington; Elson S. Floyd College of Medicine, Washington State University, Seattle, Washington.

Adriaan van der Meer (A)

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands.

Grazia Anna Niro (GA)

Gastroenterology Unit, Fondazione IRCCS "Casa Sollievo Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy.

Benedetta Terziroli Beretta-Piccoli (BT)

Epatocentro Ticino, Lugano, Switzerland.

Marco Marzioni (M)

Division of Gastroenterology and Hepatology, Ospedali Riuniti University Hospital, Ancona, Italy.

Luca Saverio Belli (LS)

ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.

Fabio Marra (F)

Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.

Maria Grazia Valsecchi (MG)

Bicocca Bioinformatics Biostatistics and Bioimaging Centre - B4, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

Keith D Lindor (KD)

Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona; Arizona State University, Phoenix, Arizona.

Pietro Invernizzi (P)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.

Bettina E Hansen (BE)

Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.

Marco Carbone (M)

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy. Electronic address: marco.carbone@unimib.it.

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