Naga Chalasani1, Herbert L Bonkovsky2, Robert Fontana3, William Lee4, Andrew Stolz5, Jayant Talwalkar6, K Rajendar Reddy7, Paul B Watkins8, Victor Navarro9, Huiman Barnhart10, Jiezhun Gu10, Jose Serrano11. 1. Indiana University School of Medicine, Indianapolis, Indianapolis. 2. Carolinas Health Care System, Charlotte, North Carolina. 3. University of Michigan, Ann Arbor, Michigan. 4. University of Texas at Southwestern, Dallas, Texas. 5. University of Southern California, Los Angeles, California. 6. Mayo Clinic, Rochester, Minnesota. 7. University of Pennsylvania, Philadelphia, Pennsylvania. 8. University of North Carolina, Chapel Hill, North Carolina. 9. Einstein Medical Center, Philadelphia, Pennsylvania. 10. Duke Clinical Research Institute, Raleigh, North Carolina. 11. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
Abstract
BACKGROUND & AIMS: The Drug-Induced Liver Injury Network is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study. METHODS: In an observational longitudinal study, we began collecting data on eligible individuals with suspected DILI in 2004, following them for 6 months or longer. Subjects were evaluated systematically for other etiologies, causes, and severity of DILI. RESULTS: Among 1257 enrolled subjects with suspected DILI, the causality was assessed in 1091 patients, and 899 were considered to have definite, highly likely, or probable DILI. Ten percent of patients died or underwent liver transplantation, and 17% had chronic liver injury. In the 89 patients (10%) with pre-existing liver disease, DILI appeared to be more severe than in those without (difference not statistically significant; P = .09) and mortality was significantly higher (16% vs 5.2%; P < .001). Azithromycin was the implicated agent in a higher proportion of patients with pre-existing liver disease compared with those without liver disease (6.7% vs 1.5%; P = .006). Forty-one cases with latency ≤7 days were caused predominantly by antimicrobial agents (71%). Two most common causes for 60 DILI cases with latency >365 days were nitrofurantoin (25%) or minocycline (17%). There were no differences in outcomes of patients with short vs long latency of DILI. Compared with individuals younger than 65 years, individuals 65 years or older (n = 149) were more likely to have cholestatic injury, although mortality and rate of liver transplantation did not differ. Nine patients (1%) had concomitant severe skin reactions; implicated agents were lamotrigine, azithromycin, carbamazepine, moxifloxacin, cephalexin, diclofenac, and nitrofurantoin. Four of these patients died. CONCLUSIONS: Mortality from DILI is significantly higher in individuals with pre-existing liver disease or concomitant severe skin reactions compared with patients without. Additional studies are needed to confirm the association between azithromycin and increased DILI in patients with chronic liver disease. Older age and short or long latencies are not associated with DILI mortality.
BACKGROUND & AIMS: The Drug-Induced Liver InjuryNetwork is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study. METHODS: In an observational longitudinal study, we began collecting data on eligible individuals with suspected DILI in 2004, following them for 6 months or longer. Subjects were evaluated systematically for other etiologies, causes, and severity of DILI. RESULTS: Among 1257 enrolled subjects with suspected DILI, the causality was assessed in 1091 patients, and 899 were considered to have definite, highly likely, or probable DILI. Ten percent of patients died or underwent liver transplantation, and 17% had chronic liver injury. In the 89 patients (10%) with pre-existing liver disease, DILI appeared to be more severe than in those without (difference not statistically significant; P = .09) and mortality was significantly higher (16% vs 5.2%; P < .001). Azithromycin was the implicated agent in a higher proportion of patients with pre-existing liver disease compared with those without liver disease (6.7% vs 1.5%; P = .006). Forty-one cases with latency ≤7 days were caused predominantly by antimicrobial agents (71%). Two most common causes for 60 DILI cases with latency >365 days were nitrofurantoin (25%) or minocycline (17%). There were no differences in outcomes of patients with short vs long latency of DILI. Compared with individuals younger than 65 years, individuals 65 years or older (n = 149) were more likely to have cholestatic injury, although mortality and rate of liver transplantation did not differ. Nine patients (1%) had concomitant severe skin reactions; implicated agents were lamotrigine, azithromycin, carbamazepine, moxifloxacin, cephalexin, diclofenac, and nitrofurantoin. Four of these patients died. CONCLUSIONS: Mortality from DILI is significantly higher in individuals with pre-existing liver disease or concomitant severe skin reactions compared with patients without. Additional studies are needed to confirm the association between azithromycin and increased DILI in patients with chronic liver disease. Older age and short or long latencies are not associated with DILI mortality.
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: Eric S Orman; Hari S Conjeevaram; Raj Vuppalanchi; James W Freston; James Rochon; David E Kleiner; Paul H Hayashi Journal: Clin Gastroenterol Hepatol Date: 2011-02-26 Impact factor: 11.382
Authors: Naga P Chalasani; Paul H Hayashi; Herbert L Bonkovsky; Victor J Navarro; William M Lee; Robert J Fontana Journal: Am J Gastroenterol Date: 2014-06-17 Impact factor: 10.864
Authors: R Vuppalanchi; P H Hayashi; N Chalasani; R J Fontana; H Bonkovsky; R Saxena; D Kleiner; J H Hoofnagle Journal: Aliment Pharmacol Ther Date: 2010-09-03 Impact factor: 8.171
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: Naga Chalasani; Robert J Fontana; Herbert L Bonkovsky; Paul B Watkins; Timothy Davern; Jose Serrano; Hongqiu Yang; James Rochon Journal: Gastroenterology Date: 2008-09-17 Impact factor: 22.682
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: M Isabel Lucena; Raúl J Andrade; Neil Kaplowitz; Miren García-Cortes; M Carmen Fernández; Manuel Romero-Gomez; Miguel Bruguera; Hacibe Hallal; Mercedes Robles-Diaz; Jose F Rodriguez-González; Jose Maria Navarro; Javier Salmeron; Pedro Martinez-Odriozola; Ramón Pérez-Alvarez; Yolanda Borraz; Ramón Hidalgo Journal: Hepatology Date: 2009-06 Impact factor: 17.425
Authors: Andrew Stolz; Victor Navarro; Paul H Hayashi; Robert J Fontana; Huiman X Barnhart; Jiezhun Gu; Naga P Chalasani; Maricruz M Vega; Herbert L Bonkovsky; Leonard B Seeff; Jose Serrano; Bharathi Avula; Ikhlas A Khan; Elizabeth T Cirulli; David E Kleiner; Jay H Hoofnagle Journal: Aliment Pharmacol Ther Date: 2019-04-01 Impact factor: 8.171
Authors: Vincent Lo Re; Bret Zeldow; Michael J Kallan; Janet P Tate; Dena M Carbonari; Sean Hennessy; Jay R Kostman; Joseph K Lim; Matthew Bidwell Goetz; Robert Gross; Amy C Justice; Jason A Roy Journal: Pharmacoepidemiol Drug Saf Date: 2017-07-19 Impact factor: 2.890