Clinical application of the leukocyte migration test and new diagnostic criteria for identifying causative agents in patients with drug-induced liver injury.
OBJECTIVE
We examined the usefulness of the leukocyte migration test (LMT) in the identification of agents causing drug-induced liver injury (DILI).


METHODS
In 14 patients who were tentatively diagnosed as having DILI in Kitasato Institute Hospital, pharmacists collected and evaluated drug information and patients' medication histories to identify causative agents. Simultaneously, LMT and drug lymphocyte stimulation test (DLST) were performed. Furthermore, scoring was performed according to the diagnostic criteria established by the International Consensus Meeting (ICM) and the Digestive Disease Week-Japan 2004 (DDW-J).


RESULTS
LMT-positive agents showed a higher ICM score compared to DLST-positive agents. The rate of LMT-positive agents was examined with respect to ICM assessment, and 0%, 25%, 33%, and 100% of agents regarded as unrelated/unlikely, possible, probable, and highly probable showed positive reactions on LMT, respectively; the rate of LMT-positive agents increased with the degree of the agent's involvement. When the results of LMT were applied to the DDW-J criteria, there was a correlation with the ICM criteria in comparison to scoring based on the results of DLST.


CONCLUSIONS
LMT may be useful for identifying agents causing DILI. Furthermore, the collection and evaluation of drug and patient information and in vitro testing in the identification of causative agents may support more reliable diagnosis.
Usui
Kensuke
K
Center for Clinical Pharmacy and Clinical Sciences, School of Pharmacy, Kitasato University, Tokyo, Japan. usuik@pharm.kitasato-u.ac.jp
Oda
Yoshisada
Y
Kubota
Rie
R
Negishi
Kenichi
K
Uno
Katsuji
K
Tsunematsu
Satoshi
S
Kumagai
Naoki
N
Komiyama
Takako
T
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D054441:Cell Migration Assays, Leukocyte / Q000379:methods*; D002465:Cell Movement; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000293:injuries*; D008107:Liver Diseases / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome