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Comparison of the prognostic models for mortality in idiosyncratic drug-induced liver injury

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Abstract

Background

Several models have been proposed to predict acute liver failure/death in patients with drug-induced liver injury (DILI), but the predictive performances of them have not been systematically compared. We aim to compare the current models for their predictive potency of mortality at DILI onset.

Methods

DILI patients hospitalized at both Beijing Friendship Hospital and the Fifth Medical Center of PLA General Hospital were categorized into death/liver transplantation (LT) or survival without LT group. Predictive potency of 28-day, 90-day, 6-month and 12-month death/LT outcomes of Hy's Law, nHy's Law, Robles-Diaz Model, drug-induced liver toxicity (DrILTox ALF) Score, Model for End-stage Liver Disease (MELD) Score, and Ghabril Model was compared by Delong method.

Results

A total of 6.3% (83/1314) patients died or received LT within 12 months after DILI onset. The area under receiver operating characteristic of Hy's Law, nHy's Law, and Robles-Diaz Model was all lower than 0.750 for the prediction of within 12 months’ mortality. DrILTox ALF Score, MELD Score and Ghabril Model showed better predictive potency of 28-day [0.896 (0.878–0.912), 0.934 (0.919–0.947), 0.935 (0.921–0.948), respectively], 90-day [0.883 (0.864–0.899), 0.951 (0.938–0.962), 0.952 (0.939–0.963), respectively], 6-month [0.820 (0.799–0.841), 0.905 (0.888–0.921) and 0.908 (0.891–0.923), respectively] and 12-month [0.801 (0.779–0.823), 0.882 (0.863–0.899) and 0.885 (0.866–0.902), respectively] mortality.

Conclusion

Despite the difference of clinical characteristics and implicated-drug categories between China and industrialized countries, we demonstrate that MELD Score and Ghabril Model have the best predictive performance in the prediction of mortality within 12 months after DILI onset.

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Abbreviations

ALF:

Acute liver failure

ALP:

Alkaline phosphatase

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AUROC:

Area under receiver operating characteristic

BMI:

Body mass index

CCI:

Charlson comorbidity index

CI:

Confidence interval

Cr:

Creatinine

DILI:

Drug-induced liver injury

DILIN:

Drug-induced liver injury network

DrILTox:

Drug-induced liver toxicity

GGT:

Gamma glutamyl transferase

HDS:

Herbal and dietary supplements

HGB:

Hemoglobin

INR:

International normalized ratio

LT:

Liver transplantation

MELD:

Model for end-stage liver disease

nHy’s Law:

New Hy’s Law

NSAIDs:

Non-steroidal anti-inflammatory drugs

PLT:

Platelets

RUCAM:

Roussel Uclaf Causality Assessment Method

TBA:

Total bile acid

TB:

Total bilirubin

ULN:

Upper limit of normal

WBC:

White blood cell

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Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 81900526).

Author information

Author notes

  1. Yan Wang and Cailun Zou share co-first authorship.

Authors and Affiliations

  1. Liver Research Center, Key Laboratory On Translational Medicine On Cirrhosis, National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Xi-cheng District, Beijing, China

    Yan Wang, Cailun Zou, Zikun Ma, Tiantian Guo, Yu Wang, Jidong Jia & Xinyan Zhao

  2. Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Aileen Wee

  3. Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada

    Jimin Liu

  4. Department of Clinical Epidemiology and EBM, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China

    Min Li

  5. Fourth Department of Liver Disease (Difficult and Complicated Liver Diseases and Artificial Liver Center), Beijing You’an Hospital, Capital Medical University, Beijing, China

    Liwei Liu

  6. Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China

    Zhengsheng Zou

Authors
  1. Yan Wang
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Contributions

Study concept and design: XZ and ZZ. Acquisition and interpretation: YW, CZ, ZM, TG, YW, LL. Drafting and revision of the manuscript: YW, CZ, XZ, AW, JL, JJ. Statistical analysis: YW, ML. Study supervision: XZ.

Corresponding authors

Correspondence to Zhengsheng Zou or Xinyan Zhao.

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Conflict of interest

Yan Wang, Cailun Zou, Aileen Wee, Jimin Liu, Zikun Ma, Tiantian Guo, Min Li, Yu Wang, Liwei Liu, Jidong Jia, Zhengsheng Zou, and Xinyan Zhao declare that they have no competing interests.

Ethical approval

The protocol was reviewed and approved by the Institutional Review Board with waiver for informed consent (No.2020-P2-300-01).

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Wang, Y., Zou, C., Wee, A. et al. Comparison of the prognostic models for mortality in idiosyncratic drug-induced liver injury. Hepatol Int 17, 488–498 (2023). https://doi.org/10.1007/s12072-022-10405-9

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  • DOI: https://doi.org/10.1007/s12072-022-10405-9

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