TY - JOUR
T1 - Measurement of Gamma Glutamyl Transferase to Determine Risk of Liver Transplantation or Death in Patients With Primary Biliary Cholangitis
AU - Gerussi, Alessio
AU - Bernasconi, Davide Paolo
AU - Italian PBC Study Group and the GLOBAL PBC Study Group
AU - O'Donnell, Sarah Elisabeth
AU - Lammers, Willem J.
AU - Van Buuren, Henk
AU - Hirschfield, Gideon
AU - Janssen, Harry
AU - Corpechot, Christophe
AU - Reig, Anna
AU - Pares, Albert
AU - Battezzati, Pier Maria
AU - Zuin, Massimo Giovanni
AU - Cazzagon, Nora
AU - Floreani, Annarosa
AU - Nevens, Frederik
AU - Gatselis, Nikolaos
AU - Dalekos, George
AU - Mayo, Marlyn J.
AU - Thorburn, Douglas
AU - Bruns, Tony
AU - Mason, Andrew L.
AU - Verhelst, Xavier
AU - Kowdley, Kris
AU - van der Meer, Adriaan
AU - Niro, Grazia Anna
AU - Beretta-Piccoli, Benedetta Terziroli
AU - Marzioni, Marco
AU - Belli, Luca Saverio
AU - Marra, Fabio
AU - Valsecchi, Maria Grazia
AU - Lindor, Keith D.
AU - Invernizzi, Pietro
AU - Hansen, Bettina E.
AU - Carbone, Marco
N1 - Funding Supported by grants of the Italian Ministry of Health in the role of auto-reactive hepatic natural killer cells in the pathogenesis of primary biliary cholangitis (PE-2016-02363915) and in the biocompatible nano-assemblies to increase the safety and the efficacy of steroid treatment against liver inflammation (GR-2018-12367794). This research was partially supported by the Italian Ministry of University and Research (MIUR) - Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic).
Publisher Copyright:
© 2020 AGA Institute
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85096375515&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2020.08.006
DO - 10.1016/j.cgh.2020.08.006
M3 - Article
C2 - 32777554
AN - SCOPUS:85096375515
SN - 1542-3565
VL - 19
SP - 1688-1697.e14
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 8
ER -