Idiosyncratic Drug Induced Liver Injury in African-Americans is Associated with Greater Morbidity and Mortality Compared to Caucasians

Naga Chalasani, K. Rajender K. Reddy, Robert J. Fontana, Huiman Barnhart, Jiezhun Gu, Paul H. Hayashi, Jawad Ahmad, Andrew Stolz, Victor Navarro, Jay H. Hoofnagle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1382-1388
Number of pages7
JournalAmerican Journal of Gastroenterology
Volume112
Issue number9
DOIs
StatePublished - Sep 1 2017

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Chemical and Drug Induced Liver Injury
African Americans
Morbidity
Mortality
Liver
Chronic Drug-Induced Liver Injury
Methyldopa
Clavulanic Acid
Skin
International Normalized Ratio
Amoxicillin
Isoniazid
Sulfamethoxazole Drug Combination Trimethoprim
Wounds and Injuries
Phenytoin
Bilirubin
Liver Transplantation
Hospitalization
Prospective Studies
Transplants

ASJC Scopus subject areas

  • Gastroenterology

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Idiosyncratic Drug Induced Liver Injury in African-Americans is Associated with Greater Morbidity and Mortality Compared to Caucasians. / Chalasani, Naga; Reddy, K. Rajender K.; Fontana, Robert J.; Barnhart, Huiman; Gu, Jiezhun; Hayashi, Paul H.; Ahmad, Jawad; Stolz, Andrew; Navarro, Victor; Hoofnagle, Jay H.

In: American Journal of Gastroenterology, Vol. 112, No. 9, 01.09.2017, p. 1382-1388.

Research output: Contribution to journalArticle

Chalasani, N, Reddy, KRK, Fontana, RJ, Barnhart, H, Gu, J, Hayashi, PH, Ahmad, J, Stolz, A, Navarro, V & Hoofnagle, JH 2017, 'Idiosyncratic Drug Induced Liver Injury in African-Americans is Associated with Greater Morbidity and Mortality Compared to Caucasians', American Journal of Gastroenterology, vol. 112, no. 9, pp. 1382-1388. https://doi.org/10.1038/ajg.2017.215
Chalasani, Naga ; Reddy, K. Rajender K. ; Fontana, Robert J. ; Barnhart, Huiman ; Gu, Jiezhun ; Hayashi, Paul H. ; Ahmad, Jawad ; Stolz, Andrew ; Navarro, Victor ; Hoofnagle, Jay H. / Idiosyncratic Drug Induced Liver Injury in African-Americans is Associated with Greater Morbidity and Mortality Compared to Caucasians. In: American Journal of Gastroenterology. 2017 ; Vol. 112, No. 9. pp. 1382-1388.
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abstract = "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.",
author = "Naga Chalasani and Reddy, {K. Rajender K.} and Fontana, {Robert J.} and Huiman Barnhart and Jiezhun Gu and Hayashi, {Paul H.} and Jawad Ahmad and Andrew Stolz and Victor Navarro and Hoofnagle, {Jay H.}",
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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.

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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.

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