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

Alessio Gerussi, Davide Paolo Bernasconi, Italian PBC Study Group and the GLOBAL PBC Study Group, Sarah Elisabeth O'Donnell, Willem J. Lammers, Henk Van Buuren, Gideon Hirschfield, Harry Janssen, Christophe Corpechot, Anna Reig, Albert Pares, Pier Maria Battezzati, Massimo Giovanni Zuin, Nora Cazzagon, Annarosa Floreani, Frederik Nevens, Nikolaos Gatselis, George Dalekos, Marlyn J. Mayo, Douglas ThorburnTony Bruns, Andrew L. Mason, Xavier Verhelst, Kris Kowdley, Adriaan van der Meer, Grazia Anna Niro, Benedetta Terziroli Beretta-Piccoli, Marco Marzioni, Luca Saverio Belli, Fabio Marra, Maria Grazia Valsecchi, Keith D. Lindor, Pietro Invernizzi, Bettina E. Hansen, Marco Carbone*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)1688-1697.e14
JournalClinical Gastroenterology and Hepatology
Issue number8
Publication statusPublished - Aug 2021

Bibliographical note

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).

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© 2020 AGA Institute


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