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Death and liver transplantation within 2 years of onset of drug‐induced liver injury
Abstract
Drug‐induced liver injury (DILI) is an important cause of death and indication for liver transplantation (fatality). The role of DILI in these fatalities is poorly characterized, particularly when fatalities occur >26 weeks after DILI onset. We analyzed patients in the US Drug‐Induced Liver Injury Network prospective study having a fatal outcome within 2 years of onset. Each case was reviewed by eight network investigators and categorized as DILI having a primary, a contributory, or no role in the fatality. We subcategorized primary role cases as acute, chronic, acute‐on‐chronic, or acute cholestatic liver failure. For contributory and no role cases, we assigned a primary cause of death. Among 1,089 patients, 107 (9.8%) fatalities occurred within 2 years. DILI had a primary role in 68 (64%), a contributory role in 15 (14%), and no role in 22 (21%); 2 had insufficient data. Among primary role cases, 74% had acute, 13% chronic, 7% acute on chronic, and 6% acute cholestatic failure. For the 15 contributory role cases, common causes of death included sepsis, malignancy, and severe cutaneous reactions with multiorgan failure. For the 22 no role cases, malignancies accounted for most fatalities. Higher bilirubin, coagulopathy, leukocytosis, and thrombocytopenia were independently associated with DILI fatalities. New R ratio Hy's law had a higher positive predictive value for overall fatality (14% versus 10%) and a stronger independent association with DILI fatalities within 26 weeks compared to the original version of Hy's law (hazard ratio, 6.2, 95% confidence interval 3.4‐11.1, versus 2.2, 95% confidence interval 1.3‐3.7). Conclusions: DILI leads directly or indirectly to fatality in 7.6% of cases; 40% of these had nonacute liver failure courses. New R ratio Hy's law better identifies risk for death compared to the original Hy's law. (H epatology 2017;66:1275‐1285).
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Amoxicillin-clavulanate is the most common cause of DILI in Europe and North America.
“Amoxicillin-clavulanate is in first place on this list.”
From Drug-induced liver injury. Part I: Classification, diagnosis and treatment (2025) · cites this paper as [5]
The drugs following amoxicillin-clavulanate as common causes of DILI include antituberculosis drugs (isoniazid, pyrazinamide, rifampicin), NSAIDs (diclofenac, ibuprofen), immunosuppressants (azathioprine, infliximab), and other antibiotics (nitrofurantoin, minocycline, azithromycin, levofloxacin).
“It is followed by antituberculosis drugs (isoniazid, pyrazinamide, rifampicin), nonsteroidal antiinflammatory drugs (diclofenac, ibuprofen), immunosuppressants (azathioprine, infliximab) and other antibiotics (nitrofurantoin, minocycline, azithromycin, levofloxacin) [3-5].”
From Drug-induced liver injury. Part I: Classification, diagnosis and treatment (2025) · cites this paper as [5]
Conventional drugs remain the most common cause of DILI in Europe and North America.
“Conventional drugs remain the most common cause of DILI in Europe and North America.”
From Drug-induced liver injury. Part I: Classification, diagnosis and treatment (2025) · cites this paper as [5]
Cases fulfilling Hy's law are associated with increased mortality or need for liver transplantation.
“Studies have shown that approximately 10% of cases that fulfill Hy's law will progress to ALF [5,64], and is associated increased mortality or need for liver transplantation [65][66][67][68].”
From Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update (2024) · cites this paper as [66]
Liver transplantation can significantly increase survival by up to 66.2% in patients with drug-induced acute liver failure or acute-on-chronic liver failure.
“Liver transplantation can significantly increase survival by up to 66.2% [66,211,212].”
From Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update (2024) · cites this paper as [66]
The overall prognosis of drug-induced acute liver failure or acute-on-chronic liver failure is poor, with 24% or 27.1% transplant-free survival.
“The overall prognosis of DI-ALF/ACLF is poor, with 24% or 27.1% transplant-free survival.”
From Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update (2024) · cites this paper as [66]
In its cohort of over 1,000 patients, DILIN demonstrated that the nR Hy's law better identifies risk for death compared to the original Hy's law.
“and also demonstrated in its cohort of over 1,000 patients that the nR Hy's law better identifies risk for death compared to the original Hy's law [31].”
From DILI Differences and Similarities between the US and Europe (2026) · cites this paper as [31]
In 2017, the DILIN group reported that DILI leads directly or indirectly to fatality in 7.6% of cases, and 40% of these had non-acute liver failure courses.
“In 2017, the DILIN group reported that DILI leads directly or indirectly to fatality in 7.6% of cases, and 40% of these had non-acute liver failure courses”
From DILI Differences and Similarities between the US and Europe (2026) · cites this paper as [31]
In the same prospective study, 40% of the patients had non-ALF courses.
“A prospective study investigating the fatalities of patients with DILI reported that 7.6% of patients died mainly or partially due to DILI within 2 years, and 40% of the patients had non-ALF courses.[26]”
From Drug-induced liver injury: Diagnosis, management and the role of liver transplantation (2025) · cites this paper as [26]
Overall, a 10% mortality rate is reported for DILI.
“Overall, a 10% mortality rate is reported for DILI.[25–27]”
From Drug-induced liver injury: Diagnosis, management and the role of liver transplantation (2025) · cites this paper as [26]
Hospitalized patients with DILI with coagulopathy and hepatic encephalopathy have a likelihood of spontaneous recovery <30%.
“Hospitalized patients with DILI with coagulopathy and hepatic encephalopathy should promptly be considered for LT evaluation as their likelihood of spontaneous recovery is <30%.[26,28]”
From Drug-induced liver injury: Diagnosis, management and the role of liver transplantation (2025) · cites this paper as [26]
A prospective study investigating fatalities of patients with DILI reported that 7.6% of patients died mainly or partially due to DILI within 2 years.
“A prospective study investigating the fatalities of patients with DILI reported that 7.6% of patients died mainly or partially due to DILI within 2 years, and 40% of the patients had non-ALF courses.[26]”
From Drug-induced liver injury: Diagnosis, management and the role of liver transplantation (2025) · cites this paper as [26]
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Research works printed but not linked: 21
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Metadata
- Authors
- Hayashi, P. H., Rockey, D. C., Fontana, R. J., Tillmann, H. L., Kaplowitz, N., Barnhart, H. X., Gu, J., Chalasani, N. P., Reddy, K. R., Sherker, A. H., Hoofnagle, J. H., & for the Drug‐Induced Liver Injury Network (DILIN) Investigators
- Venue
- Hepatology
- Published
- 2017-08-26
- Volume
- 66
- Issue
- 4
- Pages
- 1275-1285
- ISSN
- 0270-9139
- 1527-3350
- PMC
- PMC5605419
- Cited by
- 123
- References
- 0
- Language
- en
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