TY - JOUR
T1 - Idiosyncratic Drug Induced Liver Injury in African-Americans is Associated with Greater Morbidity and Mortality Compared to Caucasians
AU - Chalasani, Naga
AU - Reddy, K. Rajender K.
AU - Fontana, Robert J.
AU - Barnhart, Huiman
AU - Gu, Jiezhun
AU - Hayashi, Paul H.
AU - Ahmad, Jawad
AU - Stolz, Andrew
AU - Navarro, Victor
AU - Hoofnagle, Jay H.
N1 - Funding Information:
Th e DILIN Prospective Study (NCT 00345930) is conducted by the United States Drug Induced Liver Injury Network which is funded as a cooperative agreement by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health. DILIN consists of 6–8 medical centers, a central data coordinating center and a sample repository. The DILI Prospective Study design, method of causality assessment, and various scoring systems have been described in detail elsewhere ( 5 ). The study was approved by the appropriately convened institutional review boards at the participating clinical centers and data coordinating center as well as by a Data Safety and Monitoring Board appointed for this purpose by the NIDDK. All participants provided written informed consent before enrollment. The DILIN Prospective Study has been the source for multiple publications on topics which ranged from overall patient population characteristics to phenotypes and sub-phenotypes and select implicated agents ( 10–17 ). Participants who form the basis for this report were included in other reports published by the DILIN. All participants completed a questionnaire that captured self-reported racial and ethnic information. Cases of DILI that underwent formal causality assessment and were judged to be definite, highly likely, or probable were eligible for inclusion in this analysis.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Objectives:Idiosyncratic drug induced liver injury (DILI) is a rare but potentially serious liver disorder and a major cause of significant liver injury. Limited data exist on racial differences in DILI incidence, presentation, and course.Methods:We compared the causative agents, clinical features, and outcomes of DILI among self-described African-Americans and non-Hispanic whites (Caucasians) enrolled in the DILIN Prospective Study. Individuals with definite, highly likely, or probable DILI enrolled between September 2004 and February 2016 were included in this analysis.Results:144 African-Americans and 841 Caucasian patients met the eligibility criteria. Causal medications varied by race: trimethoprim/sulfamethoxazole being the most common cause among African-Americans (7.6 vs. 3.6%) followed by methyldopa (4 vs. <1%), phenytoin (5 vs. <1%), isoniazid (4 vs. 4%), and amoxicillin/clavulanate (4.1 vs. 13.4%). The severity of illness, however, tended to be greater in African-Americans than Caucasians as determined by peak mean bilirubin (14.3 vs. 12.8 mg/dl), INR (1.9 vs. 1.6), and DILIN severity score (3.0 vs. 2.6). The frequency of severe cutaneous reactions was significantly higher in African-Americans (2.1 vs. 0.36% in Caucasians, P=0.048). African-Americans also had higher rates of hospitalization (76.7 vs. 57.6%, P<0.001), liver transplantation or liver related death by 6 months (10.2 vs. 5.8%, P=0.02 after controlling for selected covariates), and chronic DILI (24 vs. 16%, P=0.06).Conclusions:The most common DILI causative agents differ between African-Americans and Caucasians. African-Americans are more likely to have severe cutaneous reactions and more severe liver injury leading to worse outcomes, including death and liver transplant.
AB - Objectives:Idiosyncratic drug induced liver injury (DILI) is a rare but potentially serious liver disorder and a major cause of significant liver injury. Limited data exist on racial differences in DILI incidence, presentation, and course.Methods:We compared the causative agents, clinical features, and outcomes of DILI among self-described African-Americans and non-Hispanic whites (Caucasians) enrolled in the DILIN Prospective Study. Individuals with definite, highly likely, or probable DILI enrolled between September 2004 and February 2016 were included in this analysis.Results:144 African-Americans and 841 Caucasian patients met the eligibility criteria. Causal medications varied by race: trimethoprim/sulfamethoxazole being the most common cause among African-Americans (7.6 vs. 3.6%) followed by methyldopa (4 vs. <1%), phenytoin (5 vs. <1%), isoniazid (4 vs. 4%), and amoxicillin/clavulanate (4.1 vs. 13.4%). The severity of illness, however, tended to be greater in African-Americans than Caucasians as determined by peak mean bilirubin (14.3 vs. 12.8 mg/dl), INR (1.9 vs. 1.6), and DILIN severity score (3.0 vs. 2.6). The frequency of severe cutaneous reactions was significantly higher in African-Americans (2.1 vs. 0.36% in Caucasians, P=0.048). African-Americans also had higher rates of hospitalization (76.7 vs. 57.6%, P<0.001), liver transplantation or liver related death by 6 months (10.2 vs. 5.8%, P=0.02 after controlling for selected covariates), and chronic DILI (24 vs. 16%, P=0.06).Conclusions:The most common DILI causative agents differ between African-Americans and Caucasians. African-Americans are more likely to have severe cutaneous reactions and more severe liver injury leading to worse outcomes, including death and liver transplant.
UR - https://www.scopus.com/pages/publications/85028860098
U2 - 10.1038/ajg.2017.215
DO - 10.1038/ajg.2017.215
M3 - Article
C2 - 28762375
AN - SCOPUS:85028860098
SN - 0002-9270
VL - 112
SP - 1382
EP - 1388
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
IS - 9
ER -