title: Elevated liver enzymes in inflammatory bowel disease: the role and safety of infliximab.
abstract: BACKGROUND
  Abnormal liver enzymes are frequently encountered in inflammatory bowel disease (IBD) patients. Infliximab has been implicated in inducing drug-induced liver injury, autoimmune hepatitis or reactivation of hepatitis B virus. We aimed to clarify the role of infliximab in liver impairment in an IBD cohort.
  
  
  METHODS
  A total of 305 patients with IBD, without evidence of chronic liver disease, were included in the study and retrospectively evaluated. Laboratory and clinical data were retrieved from a prospectively acquired database. In all, 176 consecutive patients treated with infliximab during the last 5 years were compared with a matched population of 129 patients who did not receive any antitumour necrosis factor treatment.
  
  
  RESULTS
  Elevation of alanine transaminase (ALT) was frequent in the entire population (36.4%) and it was not significantly associated with the use of infliximab (P=0.284). Elevations more than 3 upper limit of normal were observed in 7.9% and these resolved spontaneously in 83%. The use of immunomodulators was the only factor that was significantly associated with liver enzyme abnormalities in multivariate analysis [odds ratio (OR) 2.666, 95% confidence interval (CI) 1.576-4.511, P<0.005]. Overall, 39% of patients on infliximab had elevated liver enzymes and this was associated with increased ALT before starting infliximab (OR 3.854, 95% CI 1.800-8.251, P=0.001) and with longer duration of infliximab treatment (OR 1.030, 95% CI 1.013-1.047, P=0.001).
  
  
  CONCLUSIONS
  Elevated liver enzymes are frequently found in IBD patients and they usually resolve spontaneously. The use of immunomodulators was independently associated with increased ALT. Infliximab is relatively safe in terms of liver impairment and discontinuation of treatment is rarely required in the setting of modest elevations of ALT.
authors.affiliation: aSheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute of Liver and Digestive Health bDepartment of Gastroenterology, Royal Free Hospital, London, UK cDepartment of Gastroenterology, Theageneio Hospital, Thessaloniki, Greece dGastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico and Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Parisi
authors.forename: James
authors.initials: J
authors.lastname: O'Beirne
authors.forename: Roberta E
authors.initials: RE
authors.lastname: Rossi
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tsochatzis
authors.forename: Pinelopi
authors.initials: P
authors.lastname: Manousou
authors.forename: Eleni
authors.initials: E
authors.lastname: Theocharidou
authors.forename: Mark
authors.initials: M
authors.lastname: Hamilton
authors.forename: Charles
authors.initials: C
authors.lastname: Murray
authors.forename: Owen
authors.initials: O
authors.lastname: Epstein
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Burroughs
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology*; D004796:Clinical Enzyme Tests / Q000379:methods; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D015415:Biomarkers; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000410:Alanine Transaminase