Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study

Naga Chalasani; Herbert L. Bonkovsky; Robert Fontana; William Lee; Andrew Stolz; Jayant Talwalkar; K. Rajendar Reddy; Paul B. Watkins; Victor Navarro; Huiman Barnhart; Jiezhun Gu; Jose Serrano; Jawad Ahmad; Nancy Bach; Meena Bansal; Huiman X. Barnhart; Kimberly Beavers; Francisco O. Calvo; Charissa Chang; Hari Conjeevaram; Gregory Conner; Jama Darling; Ynto De Boer; Douglas Dieterich; Frank Dipaola; Francisco A. Durazo; James E. Everhart; Robert J. Fontana; Marwan S. Ghabril; David Goldstein; Vani Gopalreddy; Priya Grewal; Paul H. Hayashi; Jay Hoofnagle; Neil Kaplowitz; Suthat Liangpunsakul; Steven Lichtman; Lawrence Liu; Victor J. Navarro; Joseph Odin; Simona Rossi; Mark Russo; Thomas Schiano; Averell H. Sherker; Raj Vuppalanchi; Steven Zacks; Amanda Balasco; Kristin Chesney; Audrey Corne; Sherrie Cummings; Gale Groseclose; Alex Hammett; Judy Hooker; Varun Kesar; Sophana Mao; Kenari Marks; Regina McFadden; Yolanda Melgoza; Sherif Mikhail; Susan Milstein; Wendy Morlan; Val Peacock; Nidia Rosado; Tracy Russell; Maricruz Vega; Manisha Verma; Patricia Walker; Rachana Yalamanchili; Michelle McClanahan-Crowder; Katherine Galan; Tuan Chau; Kowsalya Ragavan; Hoss Rostami; Carmel Puglisi-Scharenbroich; Rebecca J. Torrance; Rebekah Van Raaphorst

doi:10.1053/j.gastro.2015.03.006

Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study

Naga Chalasani, Herbert L. Bonkovsky, Robert Fontana, William Lee, Andrew Stolz, Jayant Talwalkar, K. Rajendar Reddy, Paul B. Watkins, Victor Navarro, Huiman Barnhart, Jiezhun Gu, Jose Serrano, Jawad Ahmad, Nancy Bach, Meena Bansal, Huiman X. Barnhart, Kimberly Beavers, Francisco O. Calvo, Charissa Chang, Hari ConjeevaramGregory Conner, Jama Darling, Ynto De Boer, Douglas Dieterich, Frank Dipaola, Francisco A. Durazo, James E. Everhart, Robert J. Fontana, Marwan S. Ghabril, David Goldstein, Vani Gopalreddy, Priya Grewal, Paul H. Hayashi, Jay Hoofnagle, Neil Kaplowitz, Suthat Liangpunsakul, Steven Lichtman, Lawrence Liu, Victor J. Navarro, Joseph Odin, Simona Rossi, Mark Russo, Thomas Schiano, Averell H. Sherker, Raj Vuppalanchi, Steven Zacks, Amanda Balasco, Kristin Chesney, Audrey Corne, Sherrie Cummings, Gale Groseclose, Alex Hammett, Judy Hooker, Varun Kesar, Sophana Mao, Kenari Marks, Regina McFadden, Yolanda Melgoza, Sherif Mikhail, Susan Milstein, Wendy Morlan, Val Peacock, Nidia Rosado, Tracy Russell, Maricruz Vega, Manisha Verma, Patricia Walker, Rachana Yalamanchili, Michelle McClanahan-Crowder, Katherine Galan, Tuan Chau, Kowsalya Ragavan, Hoss Rostami, Carmel Puglisi-Scharenbroich, Rebecca J. Torrance, Rebekah Van Raaphorst

Research output: Contribution to journal › Article › peer-review

637 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1340-1352.e7
Journal	Gastroenterology
Volume	148
Issue number	7
DOIs	https://doi.org/10.1053/j.gastro.2015.03.006
State	Published - Jun 1 2015

Keywords

DILI
DILIN
Idiosyncratic
Medication
Toxicity

ASJC Scopus subject areas

Hepatology
Gastroenterology

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10.1053/j.gastro.2015.03.006

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Chalasani, N., Bonkovsky, H. L., Fontana, R., Lee, W., Stolz, A., Talwalkar, J., Reddy, K. R., Watkins, P. B., Navarro, V., Barnhart, H., Gu, J., Serrano, J., Ahmad, J., Bach, N., Bansal, M., Barnhart, H. X., Beavers, K., Calvo, F. O., Chang, C., ... Van Raaphorst, R. (2015). Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study. Gastroenterology, 148(7), 1340-1352.e7. https://doi.org/10.1053/j.gastro.2015.03.006

Chalasani, N, Bonkovsky, HL, Fontana, R, Lee, W, Stolz, A, Talwalkar, J, Reddy, KR, Watkins, PB, Navarro, V, Barnhart, H, Gu, J, Serrano, J, Ahmad, J, Bach, N, Bansal, M, Barnhart, HX, Beavers, K, Calvo, FO, Chang, C, Conjeevaram, H, Conner, G, Darling, J, De Boer, Y, Dieterich, D, Dipaola, F, Durazo, FA, Everhart, JE, Fontana, RJ, Ghabril, MS, Goldstein, D, Gopalreddy, V, Grewal, P, Hayashi, PH, Hoofnagle, J, Kaplowitz, N, Liangpunsakul, S, Lichtman, S, Liu, L, Navarro, VJ, Odin, J, Rossi, S, Russo, M, Schiano, T, Sherker, AH, Vuppalanchi, R, Zacks, S, Balasco, A, Chesney, K, Corne, A, Cummings, S, Groseclose, G, Hammett, A, Hooker, J, Kesar, V, Mao, S, Marks, K, McFadden, R, Melgoza, Y, Mikhail, S, Milstein, S, Morlan, W, Peacock, V, Rosado, N, Russell, T, Vega, M, Verma, M, Walker, P, Yalamanchili, R, McClanahan-Crowder, M, Galan, K, Chau, T, Ragavan, K, Rostami, H, Puglisi-Scharenbroich, C, Torrance, RJ & Van Raaphorst, R 2015, 'Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study', Gastroenterology, vol. 148, no. 7, pp. 1340-1352.e7. https://doi.org/10.1053/j.gastro.2015.03.006

@article{538a3136f6f543f7bf132b2079f93a6c,

title = "Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study",

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.",

keywords = "DILI, DILIN, Idiosyncratic, Medication, Toxicity",

author = "Naga Chalasani and Bonkovsky, {Herbert L.} and Robert Fontana and William Lee and Andrew Stolz and Jayant Talwalkar and Reddy, {K. Rajendar} and Watkins, {Paul B.} and Victor Navarro and Huiman Barnhart and Jiezhun Gu and Jose Serrano and Jawad Ahmad and Nancy Bach and Meena Bansal and Barnhart, {Huiman X.} and Kimberly Beavers and Calvo, {Francisco O.} and Charissa Chang and Hari Conjeevaram and Gregory Conner and Jama Darling and {De Boer}, Ynto and Douglas Dieterich and Frank Dipaola and Durazo, {Francisco A.} and Everhart, {James E.} and Fontana, {Robert J.} and Ghabril, {Marwan S.} and David Goldstein and Vani Gopalreddy and Priya Grewal and Hayashi, {Paul H.} and Jay Hoofnagle and Neil Kaplowitz and Suthat Liangpunsakul and Steven Lichtman and Lawrence Liu and Navarro, {Victor J.} and Joseph Odin and Simona Rossi and Mark Russo and Thomas Schiano and Sherker, {Averell H.} and Raj Vuppalanchi and Steven Zacks and Amanda Balasco and Kristin Chesney and Audrey Corne and Sherrie Cummings and Gale Groseclose and Alex Hammett and Judy Hooker and Varun Kesar and Sophana Mao and Kenari Marks and Regina McFadden and Yolanda Melgoza and Sherif Mikhail and Susan Milstein and Wendy Morlan and Val Peacock and Nidia Rosado and Tracy Russell and Maricruz Vega and Manisha Verma and Patricia Walker and Rachana Yalamanchili and Michelle McClanahan-Crowder and Katherine Galan and Tuan Chau and Kowsalya Ragavan and Hoss Rostami and Carmel Puglisi-Scharenbroich and Torrance, {Rebecca J.} and {Van Raaphorst}, Rebekah",

note = "Publisher Copyright: {\textcopyright} 2015 AGA Institute.",

year = "2015",

month = jun,

day = "1",

doi = "10.1053/j.gastro.2015.03.006",

language = "English (US)",

volume = "148",

pages = "1340--1352.e7",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders Ltd",

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TY - JOUR

T1 - Features and outcomes of 899 patients with drug-induced liver injury

T2 - The DILIN prospective study

AU - Chalasani, Naga

AU - Bonkovsky, Herbert L.

AU - Fontana, Robert

AU - Lee, William

AU - Stolz, Andrew

AU - Talwalkar, Jayant

AU - Reddy, K. Rajendar

AU - Watkins, Paul B.

AU - Navarro, Victor

AU - Barnhart, Huiman

AU - Gu, Jiezhun

AU - Serrano, Jose

AU - Ahmad, Jawad

AU - Bach, Nancy

AU - Bansal, Meena

AU - Barnhart, Huiman X.

AU - Beavers, Kimberly

AU - Calvo, Francisco O.

AU - Chang, Charissa

AU - Conjeevaram, Hari

AU - Conner, Gregory

AU - Darling, Jama

AU - De Boer, Ynto

AU - Dieterich, Douglas

AU - Dipaola, Frank

AU - Durazo, Francisco A.

AU - Everhart, James E.

AU - Fontana, Robert J.

AU - Ghabril, Marwan S.

AU - Goldstein, David

AU - Gopalreddy, Vani

AU - Grewal, Priya

AU - Hayashi, Paul H.

AU - Hoofnagle, Jay

AU - Kaplowitz, Neil

AU - Liangpunsakul, Suthat

AU - Lichtman, Steven

AU - Liu, Lawrence

AU - Navarro, Victor J.

AU - Odin, Joseph

AU - Rossi, Simona

AU - Russo, Mark

AU - Schiano, Thomas

AU - Sherker, Averell H.

AU - Vuppalanchi, Raj

AU - Zacks, Steven

AU - Balasco, Amanda

AU - Chesney, Kristin

AU - Corne, Audrey

AU - Cummings, Sherrie

AU - Groseclose, Gale

AU - Hammett, Alex

AU - Hooker, Judy

AU - Kesar, Varun

AU - Mao, Sophana

AU - Marks, Kenari

AU - McFadden, Regina

AU - Melgoza, Yolanda

AU - Mikhail, Sherif

AU - Milstein, Susan

AU - Morlan, Wendy

AU - Peacock, Val

AU - Rosado, Nidia

AU - Russell, Tracy

AU - Vega, Maricruz

AU - Verma, Manisha

AU - Walker, Patricia

AU - Yalamanchili, Rachana

AU - McClanahan-Crowder, Michelle

AU - Galan, Katherine

AU - Chau, Tuan

AU - Ragavan, Kowsalya

AU - Rostami, Hoss

AU - Puglisi-Scharenbroich, Carmel

AU - Torrance, Rebecca J.

AU - Van Raaphorst, Rebekah

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

KW - DILI

KW - DILIN

KW - Idiosyncratic

KW - Medication

KW - Toxicity

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Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study

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