Prospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2017; 23(22): 4102-4111
Published online Jun 14, 2017. doi: 10.3748/wjg.v23.i22.4102
Drug-induced liver injury in inflammatory bowel disease: 1-year prospective observational study
Tomas Koller, Martina Galambosova, Simona Filakovska, Michaela Kubincova, Tibor Hlavaty, Jozef Toth, Anna Krajcovicova, Juraj Payer
Tomas Koller, Martina Galambosova, Simona Filakovska, Michaela Kubincova, Tibor Hlavaty, Jozef Toth, Anna Krajcovicova, Juraj Payer, 5th Department of Internal Medicine, Gastroenterology and Hepatology, Comenius University in Bratislava Faculty of Medicine, University Hospital Bratislava Ruzinov, 82606 Bratislava, Slovakia
Author contributions: Koller T drafted the manuscript, designed the protocol and performed data analysis; Galambosova M supervised and participated in data collection; Filakovska S participated in data collection; Kubincova M participated in data collection; Hlavaty T revised the protocol design, assisted with data analysis, participated in patient clinical management; Toth J participated in patient clinical management; Krajcovicova A participated in data collection and assisted at data analysis; Payer J suggested the subject of the study and participated at the discussion, approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the institutional ethics committee board of the University Hospital Bratislava Ruzinov of Slovakia.
Clinical trial registration statement: This study did not include any intervention or patient randomization, therefore clinical trial registration was not done.
Informed consent statement: All study participants, or their legal guardian, provided written informed consent prior to any diagnostic or therapeutic procedure. Informed consent for patient data collection was not required by the institutional ethics committee.
Conflict-of-interest statement: The authors of the manuscript having no conflicts of interest to disclose.
Data sharing statement: There is no additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tomas Koller, MD, PhD, Associate Professor, 5th Department of Internal Medicine, Gastroenterology and Hepatology, Comenius University in Bratislava Faculty of Medicine, University Hospital Bratislava Ruzinov, Ruzinovska 6, 82606 Bratislava, Slovakia. tomas.koller@ru.unb.sk
Telephone: +42-190-5118692 Fax: +42-190-5118692
Received: January 28, 2017
Peer-review started: February 8, 2017
First decision: March 16, 2017
Revised: March 29, 2017
Accepted: May 9, 2017
Article in press: May 9, 2017
Published online: June 14, 2017
Abstract
AIM

To analyze 1-year liver injury burden in inflammatory bowel disease (IBD) patients.

METHODS

During a 6-mo inclusion period, consecutive IBD cases having a control visit at IBD center were included. Basic demographics, IBD phenotype and IBD treatment were recorded on entry. Aminotransferase (AT) activities of ALT, AST, ALP and gamma-glutamyl transpeptidase (GGT) were measured at baseline, 3 mo prior to study entry and prospectively every 3 mo for 1 year. Liver injury patterns were predefined as: Grade 1 in ALT 1-3 × upper limit of normal (ULN), grade 2 in ALT > 3 × ULN, hepatocellular injury in ALT > 2 × ULN, cholestatic injury in simultaneous GGT and ALP elevation > ULN. Persisting injury was reported when AT elevations were found on > 1 measurement. Risk factors for the patterns of liver injury were identified among demographic parameters, disease phenotype and IBD treatment in univariate and multivariate analysis. Finally, implications for the change in IBD management were evaluated in cases with persisting hepatocellular or cholestatic injury.

RESULTS

Two hundred and fifty-one patients were included having 917 ALT and 895 ALP and GGT measurements. Over one year, grade 1 injury was found in 66 (26.3%), grade 2 in 5 (2%) and hepatocellular injury in 16 patients (6.4%). Persisting hepatocellular injury was found in 4 cases. Cholestasis appeared in 11 cases (4.4%) and persisted throughout the entire study period in 1 case. In multivariate analysis, hepatocellular injury was associated with BMI (OR = 1.13, 1.02-1.26), liver steatosis (OR = 10.61, 2.22-50.7), IBD duration (1.07, 1.00-1.15) and solo infliximab (OR = 4.57, 1.33-15.7). Cholestatic liver injury was associated with prior intestinal resection (OR = 32.7, 3.18-335), higher CRP (OR = 1.04, 1.00-1.08) and solo azathioprine (OR = 10.27, 1.46-72.3). In one case with transient hepatocellular injury azathioprine dose was decreased. In 4 cases with persisting hepatocellular injury, fatty liver or alcohol were most likely causes and IBD treatment was pursued without change. In the case with persisting cholestatic injury, no signs of portal hypertension were identified and treatment with infliximab continued.

CONCLUSION

Liver injury was frequent, mostly transient and rarely changed management. Infliximab or azathioprine were confirmed as its risk factors indicating the need for regular AT monitoring.

Keywords: Drug-induced liver injury, Risk factors, Inflammatory bowel disease, Infliximab, Adalimumab, Azathioprine

Core tip: We evaluated liver injury in consecutive inflammatory bowel disease (IBD) patients followed for one year in whom aminotransferase activities (AT) were measured at baseline and at 3 mo intervals. We found AT elevations frequently, but they were mostly mild and transient. Even persisting abnormalities had rarely an effect on IBD management. However, ALT elevations and cholestasis appeared more commonly among patients treated with infliximab (ALT) or azathioprine (cholestasis). This finding points to their potential for hepatotoxicity and the need for regular AT monitoring.