Author information

• ¹Division 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.
• ²Bicocca Bioinformatics Biostatistics and Bioimaging Centre - B4, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
• ³Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands.
• ⁴Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada.
• ⁵Centre 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.
• ⁶Liver 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.
• ⁷Liver 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.
• ⁸Department 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.
• ⁹Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; IRCCS Negrar, Verona, Italy.
• ¹⁰Department 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.
• ¹¹Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
• ¹²Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas.
• ¹³The Sheila Sherlock Liver Centre and UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom.
• ¹⁴Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
• ¹⁵Division of Gastroenterology and Hepatology, University of Alberta, Edmonton, Canada.
• ¹⁶Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Ghent University Hospital, Ghent, Belgium.
• ¹⁷Liver Institute Northwest, Seattle, Washington; Elson S. Floyd College of Medicine, Washington State University, Seattle, Washington.
• ¹⁸Gastroenterology Unit, Fondazione IRCCS "Casa Sollievo Sofferenza" Hospital, San Giovanni Rotondo (FG), Italy.
• ¹⁹Epatocentro Ticino, Lugano, Switzerland.
• ²⁰Division of Gastroenterology and Hepatology, Ospedali Riuniti University Hospital, Ancona, Italy.
• ²¹ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
• ²²Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.
• ²³Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona; Arizona State University, Phoenix, Arizona.
• ²⁴Toronto 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.
• ²⁵Division 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.

Abstract

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.