Naga Chalasani1, K Rajender K Reddy2, Robert J Fontana3, Huiman Barnhart4, Jiezhun Gu4, Paul H Hayashi5, Jawad Ahmad6, Andrew Stolz7, Victor Navarro8, Jay H Hoofnagle9. 1. Indiana University School of Medicine, Indianapolis, Indiana, USA. 2. University of Pennsylvania, Philadelphia, Pennsylvania, USA. 3. University of Michigan, Ann Arbor, Michigan, USA. 4. Duke Clinical Research Institute, Duke University, Raleigh, North Carolina, USA. 5. University of North Carolina, Chapel Hill, North Carolina, USA. 6. Mount Sinai School of Medicine, New York, New York, USA. 7. University of Southern California, Los Angeles, California, USA. 8. Einstein Medical Center, Philadelphia, Pennsylvania, USA. 9. Liver Diseases Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
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.
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.
Authors: Robert J Fontana; Paul H Hayashi; Jiezhun Gu; K Rajender Reddy; Huiman Barnhart; Paul B Watkins; Jose Serrano; William M Lee; Naga Chalasani; Andrew Stolz; Timothy Davern; Jayant A Talwakar Journal: Gastroenterology Date: 2014-03-27 Impact factor: 22.682
Authors: Victor J Navarro; Huiman Barnhart; Herbert L Bonkovsky; Timothy Davern; Robert J Fontana; Lafaine Grant; K Rajender Reddy; Leonard B Seeff; Jose Serrano; Averell H Sherker; Andrew Stolz; Jayant Talwalkar; Maricruz Vega; Raj Vuppalanchi Journal: Hepatology Date: 2014-08-25 Impact factor: 17.425
Authors: M Isabel Lucena; Raúl J Andrade; M Carmen Fernández; Ketevan Pachkoria; Gloria Pelaez; José A Durán; Macarena Villar; Luis Rodrigo; Manuel Romero-Gomez; Ramón Planas; Anabel Barriocanal; Joan Costa; Carlos Guarner; Sonia Blanco; José M Navarro; Fernando Pons; Agustin Castiella; Susana Avila Journal: Hepatology Date: 2006-10 Impact factor: 17.425
Authors: Robert J Fontana; Paul B Watkins; Herbert L Bonkovsky; Naga Chalasani; Timothy Davern; Jose Serrano; James Rochon Journal: Drug Saf Date: 2009 Impact factor: 5.606
Authors: David E Kleiner; Naga P Chalasani; William M Lee; Robert J Fontana; Herbert L Bonkovsky; Paul B Watkins; Paul H Hayashi; Timothy J Davern; Victor Navarro; Rajender Reddy; Jayant A Talwalkar; Andrew Stolz; Jiezhun Gu; Huiman Barnhart; Jay H Hoofnagle Journal: Hepatology Date: 2013-12-18 Impact factor: 17.425
Authors: Marwan Ghabril; Jiezhun Gu; Lindsay Yoder; Laura Corbito; Amit Ringel; Christian D Beyer; Raj Vuppalanchi; Huiman Barnhart; Paul H Hayashi; Naga Chalasani Journal: Gastroenterology Date: 2019-07-11 Impact factor: 22.682
Authors: Hans L Tillmann; Ayako Suzuki; Huiman X Barnhart; Jose Serrano; Don C Rockey Journal: Curr Opin Gastroenterol Date: 2019-05 Impact factor: 3.287
Authors: Naga Chalasani; Herbert L Bonkovsky; Jonathan G Stine; Jiezhun Gu; Huiman Barnhart; Elin Jacobsen; Einar Björnsson; Robert J Fontana; David E Kleiner; Jay H Hoofnagle Journal: J Hepatol Date: 2021-12-22 Impact factor: 25.083
Authors: Yi-Ju Li; Elizabeth J Phillips; Andrew Dellinger; Paola Nicoletti; Ryan Schutte; Danmeng Li; David A Ostrov; Robert J Fontana; Paul B Watkins; Andrew Stolz; Ann K Daly; Guruprasad P Aithal; Huiman Barnhart; Naga Chalasani Journal: Hepatology Date: 2021-01 Impact factor: 17.298
Authors: Herbert L Bonkovsky; Huiman X Barnhart; David M Foureau; Nury Steuerwald; William M Lee; Jiezhun Gu; Robert J Fontana; Paul J Hayashi; Naga Chalasani; Victor M Navarro; Joseph Odin; Andrew Stolz; Paul B Watkins; Jose Serrano Journal: PLoS One Date: 2018-10-25 Impact factor: 3.240