Tags

Type your tag names separated by a space and hit enter

Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland.
Gastroenterology 2013; 144(7):1419-25, 1425.e1-3; quiz e19-20G

Abstract

BACKGROUND & AIMS

Little is known about the incidence of drug-induced liver injury (DILI) in the general population. We investigated the incidence and the quantitative risk of DILI in a population-based cohort.

METHODS

We performed a prospective study and collected data from 96 individuals diagnosed with DILI in Iceland from 2010 through 2011 (54 women; median age, 55 y). Liver injury was defined based on levels of alanine aminotransferase that were more than 3-fold the upper limit of normal and/or alkaline phosphatase levels more than 2-fold the upper limit of normal. Patients with acetaminophen toxicity were excluded. Drug history and clinical outcome were analyzed. Causality was assessed using the Roussel Uclaf Causality Assessment Method. The patients were registered in prescription databases for outpatients and inpatients.

RESULTS

The crude annual incidence rate of DILI was 19.1 (95% confidence interval [CI], 15.4-23.3) cases per 100,000 inhabitants. DILI was caused by a single prescription medication in 75% of cases, by dietary supplements in 16% of cases, and by multiple agents in 9% of cases. The most commonly implicated drugs were amoxicillin-clavulanate (21 of 96; 22%), diclofenac (6%), azathioprine (4%), infliximab (4%), and nitrofurantoin (4%). The median duration of therapy was 20 days (range, 8-77 days); 26 patients had jaundice (27%) and 22 patients were hospitalized (23%) for a median of 5 days (range, 2-8 days). Overall 35,252 patients received amoxicillin-clavulanate as outpatients, and DILI occurred in 1 of 2350 (43 of 100,000; 95% CI, 24-70). DILI also occurred in 1 of 9480 patients taking diclofenac (11 of 100,000; 95% CI, 4-24), 1 of 133 patients taking azathioprine (752 of 100,000; 95% CI, 205-1914), 1 of 148 patients taking infliximab (675 of 100,000; 95% CI, 184-718), and 1 of 1369 patients taking nitrofurantoin (73 of 100,000; 95% CI, 20-187).

CONCLUSIONS

In a population-based study in Iceland, the incidence of DILI was the highest reported to date. Amoxicillin-clavulanate was the most commonly implicated agent. The highest risk of hepatotoxicity was associated with azathioprine and infliximab, but the actual number of cases attributed to these agents was small.

Authors+Show Affiliations

Department of Internal Medicine, Section of Gastroenterology and Hepatology, National University Hospital, Reykjavik, Iceland. einarsb@landspitali.is

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23419359

Citation

Björnsson, Einar S., et al. "Incidence, Presentation, and Outcomes in Patients With Drug-induced Liver Injury in the General Population of Iceland." Gastroenterology, vol. 144, no. 7, 2013, pp. 1419-25, 1425.e1-3; quiz e19-20.
Björnsson ES, Bergmann OM, Björnsson HK, et al. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144(7):1419-25, 1425.e1-3; quiz e19-20.
Björnsson, E. S., Bergmann, O. M., Björnsson, H. K., Kvaran, R. B., & Olafsson, S. (2013). Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology, 144(7), pp. 1419-25, 1425.e1-3; quiz e19-20. doi:10.1053/j.gastro.2013.02.006.
Björnsson ES, et al. Incidence, Presentation, and Outcomes in Patients With Drug-induced Liver Injury in the General Population of Iceland. Gastroenterology. 2013;144(7):1419-25, 1425.e1-3; quiz e19-20. PubMed PMID: 23419359.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. AU - Björnsson,Einar S, AU - Bergmann,Ottar M, AU - Björnsson,Helgi K, AU - Kvaran,Runar B, AU - Olafsson,Sigurdur, Y1 - 2013/02/16/ PY - 2012/12/05/received PY - 2013/02/07/revised PY - 2013/02/11/accepted PY - 2013/2/20/entrez PY - 2013/2/20/pubmed PY - 2013/7/31/medline SP - 1419-25, 1425.e1-3; quiz e19-20 JF - Gastroenterology JO - Gastroenterology VL - 144 IS - 7 N2 - BACKGROUND & AIMS: Little is known about the incidence of drug-induced liver injury (DILI) in the general population. We investigated the incidence and the quantitative risk of DILI in a population-based cohort. METHODS: We performed a prospective study and collected data from 96 individuals diagnosed with DILI in Iceland from 2010 through 2011 (54 women; median age, 55 y). Liver injury was defined based on levels of alanine aminotransferase that were more than 3-fold the upper limit of normal and/or alkaline phosphatase levels more than 2-fold the upper limit of normal. Patients with acetaminophen toxicity were excluded. Drug history and clinical outcome were analyzed. Causality was assessed using the Roussel Uclaf Causality Assessment Method. The patients were registered in prescription databases for outpatients and inpatients. RESULTS: The crude annual incidence rate of DILI was 19.1 (95% confidence interval [CI], 15.4-23.3) cases per 100,000 inhabitants. DILI was caused by a single prescription medication in 75% of cases, by dietary supplements in 16% of cases, and by multiple agents in 9% of cases. The most commonly implicated drugs were amoxicillin-clavulanate (21 of 96; 22%), diclofenac (6%), azathioprine (4%), infliximab (4%), and nitrofurantoin (4%). The median duration of therapy was 20 days (range, 8-77 days); 26 patients had jaundice (27%) and 22 patients were hospitalized (23%) for a median of 5 days (range, 2-8 days). Overall 35,252 patients received amoxicillin-clavulanate as outpatients, and DILI occurred in 1 of 2350 (43 of 100,000; 95% CI, 24-70). DILI also occurred in 1 of 9480 patients taking diclofenac (11 of 100,000; 95% CI, 4-24), 1 of 133 patients taking azathioprine (752 of 100,000; 95% CI, 205-1914), 1 of 148 patients taking infliximab (675 of 100,000; 95% CI, 184-718), and 1 of 1369 patients taking nitrofurantoin (73 of 100,000; 95% CI, 20-187). CONCLUSIONS: In a population-based study in Iceland, the incidence of DILI was the highest reported to date. Amoxicillin-clavulanate was the most commonly implicated agent. The highest risk of hepatotoxicity was associated with azathioprine and infliximab, but the actual number of cases attributed to these agents was small. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/23419359/Incidence_presentation_and_outcomes_in_patients_with_drug_induced_liver_injury_in_the_general_population_of_Iceland_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(13)00217-5 DB - PRIME DP - Unbound Medicine ER -