Abstract
Background & Aims Little is known about the incidence of drug-induced liver injury (DILI) and risk factors for adverse outcomes. We evaluated short-term outcomes of a large cohort of patients with DILI enrolled in an ongoing multicenter prospective study. Methods Data were collected from 660 adults with definite, highly likely, or probable DILI. Regression methods were used to identify risk factors for early liver-related death or liver transplantation and chronic liver injury. Results Patients' median age was 51.4 years; 59.5% were female and 59.1% required hospitalization. Within 6 months of DILI onset, 30 patients received liver transplants (4.5%; 95% confidence interval [CI], 3.0%-6.1%) and 32 died (5%; 95% CI, 3.2%-6.5%); 53% of the deaths were liver related. Asian race, absence of itching, lung disease, low serum albumin levels, low platelet counts, and high serum levels of alanine aminotransferase and total bilirubin at presentation were independent risk factors for reduced times to liver-related death or liver transplantation (C-statistic = 0.87). At 6 months after DILI onset, 18.9% of the 598 evaluable subjects had persistent liver damage. African-American race, higher serum levels of alkaline phosphatase, and prior heart disease or malignancy requiring treatment were independent risk factors for chronic DILI (C-statistic = 0.71). Conclusions Nearly 1 in 10 patients die or undergo liver transplantation within 6 months of DILI onset and nearly 1 in 5 of the remaining patients have evidence of persistent liver injury at 6 months. The profile of liver injury at presentation, initial severity, patient's race, and medical comorbidities are important determinants of the likelihood of death/transplantation or persistent liver injury within 6 months.
| Original language | English |
|---|---|
| Journal | Gastroenterology |
| Volume | 147 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2014 |
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Keywords
- Acute Liver Failure
- Causality
- Hepatotoxicity
- Transplantation
ASJC Scopus subject areas
- Gastroenterology
Cite this
Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset. / Fontana, Robert J.; Hayashi, Paul H.; Gu, Jiezhun; Reddy, K. Rajender; Barnhart, Huiman; Watkins, Paul B.; Serrano, Jose; Lee, William M.; Chalasani, Naga; Stolz, Andrew; Davern, Timothy; Talwakar, Jayant A.
In: Gastroenterology, Vol. 147, No. 1, 2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset
AU - Fontana, Robert J.
AU - Hayashi, Paul H.
AU - Gu, Jiezhun
AU - Reddy, K. Rajender
AU - Barnhart, Huiman
AU - Watkins, Paul B.
AU - Serrano, Jose
AU - Lee, William M.
AU - Chalasani, Naga
AU - Stolz, Andrew
AU - Davern, Timothy
AU - Talwakar, Jayant A.
PY - 2014
Y1 - 2014
N2 - Background & Aims Little is known about the incidence of drug-induced liver injury (DILI) and risk factors for adverse outcomes. We evaluated short-term outcomes of a large cohort of patients with DILI enrolled in an ongoing multicenter prospective study. Methods Data were collected from 660 adults with definite, highly likely, or probable DILI. Regression methods were used to identify risk factors for early liver-related death or liver transplantation and chronic liver injury. Results Patients' median age was 51.4 years; 59.5% were female and 59.1% required hospitalization. Within 6 months of DILI onset, 30 patients received liver transplants (4.5%; 95% confidence interval [CI], 3.0%-6.1%) and 32 died (5%; 95% CI, 3.2%-6.5%); 53% of the deaths were liver related. Asian race, absence of itching, lung disease, low serum albumin levels, low platelet counts, and high serum levels of alanine aminotransferase and total bilirubin at presentation were independent risk factors for reduced times to liver-related death or liver transplantation (C-statistic = 0.87). At 6 months after DILI onset, 18.9% of the 598 evaluable subjects had persistent liver damage. African-American race, higher serum levels of alkaline phosphatase, and prior heart disease or malignancy requiring treatment were independent risk factors for chronic DILI (C-statistic = 0.71). Conclusions Nearly 1 in 10 patients die or undergo liver transplantation within 6 months of DILI onset and nearly 1 in 5 of the remaining patients have evidence of persistent liver injury at 6 months. The profile of liver injury at presentation, initial severity, patient's race, and medical comorbidities are important determinants of the likelihood of death/transplantation or persistent liver injury within 6 months.
AB - Background & Aims Little is known about the incidence of drug-induced liver injury (DILI) and risk factors for adverse outcomes. We evaluated short-term outcomes of a large cohort of patients with DILI enrolled in an ongoing multicenter prospective study. Methods Data were collected from 660 adults with definite, highly likely, or probable DILI. Regression methods were used to identify risk factors for early liver-related death or liver transplantation and chronic liver injury. Results Patients' median age was 51.4 years; 59.5% were female and 59.1% required hospitalization. Within 6 months of DILI onset, 30 patients received liver transplants (4.5%; 95% confidence interval [CI], 3.0%-6.1%) and 32 died (5%; 95% CI, 3.2%-6.5%); 53% of the deaths were liver related. Asian race, absence of itching, lung disease, low serum albumin levels, low platelet counts, and high serum levels of alanine aminotransferase and total bilirubin at presentation were independent risk factors for reduced times to liver-related death or liver transplantation (C-statistic = 0.87). At 6 months after DILI onset, 18.9% of the 598 evaluable subjects had persistent liver damage. African-American race, higher serum levels of alkaline phosphatase, and prior heart disease or malignancy requiring treatment were independent risk factors for chronic DILI (C-statistic = 0.71). Conclusions Nearly 1 in 10 patients die or undergo liver transplantation within 6 months of DILI onset and nearly 1 in 5 of the remaining patients have evidence of persistent liver injury at 6 months. The profile of liver injury at presentation, initial severity, patient's race, and medical comorbidities are important determinants of the likelihood of death/transplantation or persistent liver injury within 6 months.
KW - Acute Liver Failure
KW - Causality
KW - Hepatotoxicity
KW - Transplantation
UR - http://www.scopus.com/inward/record.url?scp=84901777524&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901777524&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2014.03.045
DO - 10.1053/j.gastro.2014.03.045
M3 - Article
C2 - 24681128
AN - SCOPUS:84901777524
VL - 147
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 1
ER -