Causality assessment of liver injury after chronic oral amiodarone intake†
Corresponding Author
Lucía Llanos MD
Clinical Pharmacology Section, University General Hospital, Alicante, Spain
Clinical Pharmacology Section, University General Hospital, c/Pintor Baeza 12, 03010, Alicante, Spain.Search for more papers by this authorRocío Moreu PhD
Clinical Pharmacology Section, University General Hospital, Alicante, Spain
Search for more papers by this authorAna M Peiró MD, PhD
Clinical Pharmacology Section, University General Hospital, Alicante, Spain
Bioengineering Institute, Miguel Hernández University, Elche, Spain
Search for more papers by this authorSonia Pascual MD, PhD
Liver Unit, University General Hospital, Alicante, Spain
CIBERehd, Carlos III Health Institute, Madrid, Spain
Search for more papers by this authorRubén Francés PhD
Liver Unit, University General Hospital, Alicante, Spain
CIBERehd, Carlos III Health Institute, Madrid, Spain
Search for more papers by this authorJosé Such MD, PhD
Liver Unit, University General Hospital, Alicante, Spain
CIBERehd, Carlos III Health Institute, Madrid, Spain
Search for more papers by this authorJosé F. Horga MD, PhD
Clinical Pharmacology Section, University General Hospital, Alicante, Spain
Bioengineering Institute, Miguel Hernández University, Elche, Spain
Search for more papers by this authorMiguel Pérez-Mateo MD, PhD
Liver Unit, University General Hospital, Alicante, Spain
Search for more papers by this authorPedro Zapater MD, PhD
Clinical Pharmacology Section, University General Hospital, Alicante, Spain
CIBERehd, Carlos III Health Institute, Madrid, Spain
Bioengineering Institute, Miguel Hernández University, Elche, Spain
Search for more papers by this authorCorresponding Author
Lucía Llanos MD
Clinical Pharmacology Section, University General Hospital, Alicante, Spain
Clinical Pharmacology Section, University General Hospital, c/Pintor Baeza 12, 03010, Alicante, Spain.Search for more papers by this authorRocío Moreu PhD
Clinical Pharmacology Section, University General Hospital, Alicante, Spain
Search for more papers by this authorAna M Peiró MD, PhD
Clinical Pharmacology Section, University General Hospital, Alicante, Spain
Bioengineering Institute, Miguel Hernández University, Elche, Spain
Search for more papers by this authorSonia Pascual MD, PhD
Liver Unit, University General Hospital, Alicante, Spain
CIBERehd, Carlos III Health Institute, Madrid, Spain
Search for more papers by this authorRubén Francés PhD
Liver Unit, University General Hospital, Alicante, Spain
CIBERehd, Carlos III Health Institute, Madrid, Spain
Search for more papers by this authorJosé Such MD, PhD
Liver Unit, University General Hospital, Alicante, Spain
CIBERehd, Carlos III Health Institute, Madrid, Spain
Search for more papers by this authorJosé F. Horga MD, PhD
Clinical Pharmacology Section, University General Hospital, Alicante, Spain
Bioengineering Institute, Miguel Hernández University, Elche, Spain
Search for more papers by this authorMiguel Pérez-Mateo MD, PhD
Liver Unit, University General Hospital, Alicante, Spain
Search for more papers by this authorPedro Zapater MD, PhD
Clinical Pharmacology Section, University General Hospital, Alicante, Spain
CIBERehd, Carlos III Health Institute, Madrid, Spain
Bioengineering Institute, Miguel Hernández University, Elche, Spain
Search for more papers by this authorThe contributing authors to this article have declared no conflict of interest.
Abstract
Background/Aim
The number of patients receiving amiodarone will increase in future years. As clinically significant hepatotoxicity associated with oral amiodarone is infrequent and difficult to predict, a new Bayesian-developed model is proposed to help in the causality assessment of amiodarone-induced liver injury.
Methods
Incidence of abnormal liver enzymes in patients receiving amiodarone was obtained from placebo controlled clinical trials. Published case reports of amiodarone-induced hepatotoxicity were identified through a literature search. Maximum number of expected hepatotoxicity cases in amiodarone and placebo-treated patients was calculated using Poisson distribution. The calculated odds ratio was used as a Prior Odds (PrO) to subsequent quantification, using a Bayesian-approach, of individual amiodarone-induced hepatotoxicity likelihood.
Results
PrO of amiodarone-induced hepatotoxicity was 0.48. Thirty nine amiodarone-associated hepatotoxicity case reports were retrieved. Half of published case reports developed an irreversible damage. The amiodarone Bayesian model combining information about latency period and period of remission, together with analytical parameters properly defines the toxicity profile shown in published case reports. The analytical pattern defined by this model is different from the one expected if liver injury in published cases was caused by other etiologies.
Conclusions
A method based on a Bayesian-approach, which links information from clinical trials with clinical hepatotoxicity profile from published case reports can be a useful tool for amiodarone-induced liver injury causality assessment. At present, this method is limited due to scarcity and quality of available data. Further efforts are needed to improve model ability in order to identify amiodarone-induced liver injury. Copyright © 2009 John Wiley & Sons, Ltd.
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