A prospective nationwide study of drug-induced liver injury in Korea.
OBJECTIVE
To address a growing concern about drug-induced liver injury (DILI), a nationwide study was performed to investigate the significance of DILI in Korea.


METHODS
From May 2005 to May 2007, cases of DILI (alanine transferase > 3 × upper normal limit or total bilirubin > 2 × upper normal limit) from 17 referral university hospitals were prospectively enrolled. Adjudication by the seven review boards was considered for the confirmation of causality and the Roussel Uclaf Causality Assessment Method (RUCAM) scale was used.


RESULTS
A total of 371 cases were diagnosed with DILI. The extrapolated incidence of hospitalization at university hospital in Korea was 12/100,000 persons/year. The causes included "herbal medications" (102, 27.5%), "prescription or non-prescription medications" (101, 27.3%), "health foods or dietary supplements" (51, 13.7%), "medicinal herbs or plants" (35, 9.4%), "folk remedies" (32, 8.6%), "combined" (30, 8.2%), "herbal preparations" (12, 3.2%), and others (8, 2.2%). Nine cases were linked to acetaminophen. The frequencies of hepatocellular, mixed, and cholestatic types were 76.3, 14.8, and 8.9%, respectively. A total of 234 cases met the criteria for Hy's law. Five patients died or underwent transplantation. Twenty-five cases (21 herbs and 4 medications) did not meet the time-to-onset criteria of the RUCAM.


CONCLUSIONS
DILI appears to be a highly relevant health problem in Korea. "Herbal medications" are the principal cause of DILI. A more objective and reproducible causality assessment tool is strongly desired as the RUCAM scale frequently undercounts the cases caused by herbs owing to a lack of previous information and incompatible time criteria.
Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea.
Ki Tae
KT
Suk
Dong Joon
DJ
Kim
Chang Hoon
CH
Kim
Seung Ha
SH
Park
Jai Hoon
JH
Yoon
Yeon Soo
YS
Kim
Gwang Ho
GH
Baik
Jin Bong
JB
Kim
Young Oh
YO
Kweon
Byung Ik
BI
Kim
Seok Hyun
SH
Kim
In Hee
IH
Kim
Ju Hyun
JH
Kim
Soon Woo
SW
Nam
Yong Han
YH
Paik
Jeong Ill
JI
Suh
Joo Hyun
JH
Sohn
Byung Min
BM
Ahn
Soon Ho
SH
Um
Heon Ju
HJ
Lee
Mong
M
Cho
Myoung Kuk
MK
Jang
Sung Kyu
SK
Choi
Seong Gyu
SG
Hwang
Ho Taik
HT
Sung
Jong Young
JY
Choi
Kwang Hyub
KH
Han
D000082:Acetaminophen / Q000506:poisoning*; D000293:Adolescent; D000328:Adult; D000368:Aged; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D004365:Drugs, Chinese Herbal / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D063487:Prescription Drug Misuse; D015995:Prevalence; D011446:Prospective Studies; D056910:Republic of Korea / Q000453:epidemiology
D004365:Drugs, Chinese Herbal; D000082:Acetaminophen