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Potential benefit and lack of serious risk from corticosteroids in drug-induced liver injury: an international, multicentre, propensity score-matched analysis
Abstract
Summary: Background: The use of corticosteroids to treat patients with idiosyncratic drug‐induced liver injury (DILI) relies on empirical clinical decisions. Aim: To investigate the relationship between corticosteroids and risk of acute liver failure (ALF) in patients with DILI and to assess if corticosteroid therapy was associated with improved outcomes in DILI patients. Methods: We analysed bona fide idiosyncratic DILI cases from the Spanish DILI Registry and Indiana University School of Medicine. Patients treated with corticosteroids were compared to those who did not receive any treatment. Nearest neighbour propensity score matching analyses were conducted. Results: We enrolled 724 patients, 106 under corticosteroid therapy, in whom there was over‐representation of more severe injury and autoimmune features, and 618 who did not receive any treatment. In an analysis of 80 pairs of propensity score‐matched patients, corticosteroid administration was not associated with an increased risk of developing ALF (odds ratio = 0.65; 95% confidence interval [CI]: 0.18–2.40; p = 0.518). Furthermore, in an additional analysis, a Cox regression model that included 41 propensity score‐matched pairs showed that patients receiving corticosteroids had a significantly higher normalisation rate of liver enzymes than untreated patients (hazard ratio [HR] = 1.84; 95% CI: 1.02–3.32; p = 0.043), particularly in patients with serious injury who did not resolve within 30 days (HR = 2.79; 95% CI: 1.20–6.50; p = 0.018). Conclusion: Corticosteroid therapy did not worsen outcome in DILI patients. Indeed, corticosteroid administration was associated with a greater rate of normalisation of liver enzymes in patients with serious DILI.
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Some studies have suggested that corticosteroids ameliorate liver injury, while others have suggested that they increase adverse events without significant benefits.
“While some studies have suggested that corticosteroids ameliorate liver injury [187][188][189][190][191], others have suggested that they increase adverse events without significant benefits [192,193].”
From Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update (2024) · cites this paper as [191]
A prednisone taper of 40-60 mg/d over 1-3 months may improve normalization of liver enzymes for immune-mediated DILI.
“while 40-60 mg/d prednisone taper over 1-3 months may improve normalization of liver enzyme for iDILI [82,191].”
From Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update (2024) · cites this paper as [191]
An international collaborative study of all DILI cases retrieved from two prospective DILI registries using propensity score-matching analysis found that the benefit from steroid therapy (increase in the normalisation rate of liver biochemistry) was more evident in patients with severe DILI (nR-based Hy's law) without disease resolution within 30 days of stopping the implicated drug.
“An international collaborative study of all DILI cases retrieved from two prospective DILI registries using propensity score-matching analysis found that the benefit from steroid therapy (increase in the normalisation rate of liver biochemistry) was more evident in patients with severe DILI (nR-based Hy’s law) without disease resolution within 30 days of stopping the implicated drug.”
From Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report (2023) · cites this paper as [67]
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Citations
Cites
Matching Methods for Causal Inference: A Review and a Look Forward
Stuart, E. A. (2010) · Statistical Science · doi:10.1214/09-sts313 · Cited by 5,478
EASL Clinical Practice Guidelines: Drug-induced liver injury
Andrade, R. J., Aithal, G. P., Björnsson, E. S., Kaplowitz, N., Kullak-Ublick, G. A., Larrey, D., & Karlsen, T. H. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.02.014 · Cited by 1,276
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Self-citationACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury
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Causal inference with observational data: the need for triangulation of evidence
Hammerton, G., & Munafò, M. R. (2021) · Psychological Medicine · doi:10.1017/s0033291720005127 · Cited by 262 · cited 1×
“Hypertension, n (%) 27 (25) 159 (26) −0.”
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Andrade, R. J., Aithal, G. P., de Boer, Y. S., Liberal, R., Gerbes, A., Regev, A., Terziroli Beretta-Piccoli, B., Schramm, C., Kleiner, D. E., De Martin, E., et al. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.04.033 · Cited by 166
Self-citationChinese guideline for the diagnosis and treatment of drug-induced liver injury: an update
Mao, Y., Ma, S., Liu, C., Liu, X., Su, M., Li, D., Li, Y., Chen, G., Chen, J., Chen, J., et al. (2024) · Hepatology International · doi:10.1007/s12072-023-10633-7 · Cited by 62
Metadata
- Authors
- Niu, H., Ma, J., Medina‐Caliz, I., Robles‐Diaz, M., Bonilla‐Toyos, E., Ghabril, M., Lucena, M. I., Alvarez‐Alvarez, I., & Andrade, R. J.
- Affiliations
- Servicios de Aparato Digestivo y Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina‐IBIMA Plataforma BIONAND Universidad de Málaga Málaga Spain
- Division of Gastroenterology/Hepatology, Department of Medicine Indiana University School of Medicine Indianapolis Indiana USA
- ORCID
- Venue
- Alimentary Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2022-12-22
- Volume
- 57
- Issue
- 8
- Pages
- 886-896
- ISSN
- 0269-2813
- 1365-2036
- Cited by
- 37
- References
- 5
- Language
- en
- Funders
- Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (PI‐0310‐2018, POSTDOC_21_00780)
- European Cooperation in Science and Technology (CA17112)
- Instituto de Salud Carlos III (CD20/00083, PI18/00901, PI19/00883, PI21/01248, PT20/000127)
- Agencia Española de Medicamentos y Productos Sanitarios
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