TY - JOUR
T1 - Recognizing Drug-Induced Liver Injury
T2 - CurrenT Problems, Possible Solutions
AU - Lee, William M.
AU - Senior, John R.
N1 - Funding Information:
The Acute Liver Failure Study Group has been supported by FDA grant FD-R-001661, NIH grant R03 DK52827, NIH grant R01 DK58369, the Stephen B. Tips Fund of Northwestern Medical Foundation, and the Jeanne Roberts Fund of the Southwestern Medical Foundation.
PY - 2005/1
Y1 - 2005/1
N2 - Currently there are three major problems in understanding drug-induced liver injury (DILI): (1) reliably establishing whether the liver disease was caused by the drug, or by another process; (2) determining the true incidence of and clinical risk factors for drug-induced hepatotoxicity; and (3) elaborating the mechanisms by which injury occurs to hepatocytes and other liver cells. We have focused here on the first two problems, as issues that may be amenable to actions in the near future, but the third may take substantially longer to work out. The first problem requires sufficient information for medical differential diagnosis. There are no pathognomonic indicators of DILI; even liver biopsy is not diagnostic. Making the correct attribution of causality requires analyzing the temporal relationship of drug exposure to illness and excluding all other possible causes. The second problem, determining incidence, cannot be done entirely adequately using currently available methods, whether by clinical trials, by spontaneous adverse event reports, or by retrospective epidemiologic studies. There is need for prospective safety studies to establish the true incidence of DILI caused by a drug, to identify risk factors for it, and to collect biologic materials for analytic studies toward better understanding mechanisms of DILI.
AB - Currently there are three major problems in understanding drug-induced liver injury (DILI): (1) reliably establishing whether the liver disease was caused by the drug, or by another process; (2) determining the true incidence of and clinical risk factors for drug-induced hepatotoxicity; and (3) elaborating the mechanisms by which injury occurs to hepatocytes and other liver cells. We have focused here on the first two problems, as issues that may be amenable to actions in the near future, but the third may take substantially longer to work out. The first problem requires sufficient information for medical differential diagnosis. There are no pathognomonic indicators of DILI; even liver biopsy is not diagnostic. Making the correct attribution of causality requires analyzing the temporal relationship of drug exposure to illness and excluding all other possible causes. The second problem, determining incidence, cannot be done entirely adequately using currently available methods, whether by clinical trials, by spontaneous adverse event reports, or by retrospective epidemiologic studies. There is need for prospective safety studies to establish the true incidence of DILI caused by a drug, to identify risk factors for it, and to collect biologic materials for analytic studies toward better understanding mechanisms of DILI.
KW - Causality attribution
KW - diagnosis of exclusion
KW - hepatotoxicity mechanisms
KW - information required
KW - prospective safety study
KW - risk factors
KW - true incidence
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U2 - 10.1080/01926230590522356
DO - 10.1080/01926230590522356
M3 - Article
C2 - 15805067
AN - SCOPUS:13444273562
SN - 0192-6233
VL - 33
SP - 155
EP - 164
JO - Toxicologic Pathology
JF - Toxicologic Pathology
IS - 1
ER -