Real time identification of drug-induced liver injury (DILI) through daily screening of ALT results: a prospective pilot cohort study

• Published in: PloS one Vol. 7; no. 8; p. e42418
• Main Authors: M'Kada, Helmi, Perazzo, Hugo, Munteanu, Mona, Ngo, Yen, Ramanujam, Nittia, Fautrel, Bruno, Imbert-Bismut, Françoise, Ratziu, Vlad, Schuppe-Koistinen, Ina, Leblond, Véronique, Delattre, Jean Yves, Samson, Yves, Caen, Olivier Lyon, Bricaire, François, Khayat, David, Pierrot-Deseilligny, Charles, Herson, Serge, Amoura, Zahir, Tilleul, Patrick, Deckmyn, Olivier, Coriat, Pierre, Delpech, Vincent Nicolas, Boulogne, Philippe, Bonnefont-Rousselot, Dominique, Poynard, Thierry
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14-08-2012; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Alanine Transaminase - biosynthesis; Alanine Transaminase - blood; Algorithms; Biomarkers; Chemical and Drug Induced Liver Injury - diagnosis; Chemical and Drug Induced Liver Injury - metabolism; Cohort analysis; Cohort Studies; Comparative analysis; Consortia; Curie, Marie (1867-1934); Diagnostic systems; Female; Gastroenterology - methods; Hepatitis; Hepatology; Hospital patients; Hospitals; Humans; Informed consent; Internal medicine; Laboratories; Liver; Liver diseases; Male; Medical screening; Medicine; Middle Aged; Necrosis; Neurology; Odds Ratio; Patients; Pharmaceutical industry; Pilot Projects; Prospective Studies; Strategy; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0042418

Identification of drug-induced liver disease (DILI) is difficult, even among hospitalized patients. The aim of this pilot study was to assess the impact of a specific strategy for DILI screening.
We prospectively compared the number of acute DILI cases identified in one week of a proactive strategy based on centralized elevated ALT values to those identified with a standard of care strategy for 24-week period based on referral cases to the hepatology unit. In the centralized strategy, a designated study biochemist identified patients with ALT greater than 3 times the upper limit of normal values (ULN) and notified the designated hepatologists, who then went to the patients' wards, analyzed the charts, and if necessary, interviewed the identified patients. During these two periods, patients with possible DILI were included after signing an informed consent in an ongoing European diagnostic study (SAFE-T consortium).
During the 24-week period of the standard strategy, 12 (0.04%) patients out of a total of 28,145 were identified as having possible DILI, and 11 of these accepted to be included in the protocol. During the one-week proactive period, 7 patients out of a total of 1407 inpatients (0.498%) [odds ratio vs. standard = 12.1 (95% CI, 3.9-32.3); P<0.0001] were identified with possible DILI, and 5 were included in the protocol.
A simple strategy based on the daily analysis of cases with ALT >3 ULN by designated biochemists and hepatologists identified 12 times more acute cases of drug-induced liver disease than the standard strategy. This pilot cohort is registered on the number AP-HP P110201/1/08-03-2011 and AFSSAPS B110346-70.