Elevated bilirubin, alkaline phosphatase at onset, and drug metabolism are associated with prolonged recovery from DILI

Ashby, Kristin; Zhuang, Wei Vivian; González-Jiménez, A.; Álvarez‐Álvarez, Ismael; Lucena, M. Isabel; Andrade, Raúl J.; Aithal, Guruprasad P.; Suzuki, Ayako; Chen, Minjun

doi:10.1016/j.jhep.2021.03.021

Cited by 27 publications

(20 citation statements)

References 31 publications

(62 reference statements)

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“…Some studies have shed light on the outcomes of DILI. Ashby et al [ 36 ] established a multivariate recovery score model to predict prolonged DILI recovery from 294 cases and validated in two external cohorts. Notably, their enrolled patients were acute DILI, and no liver biopsy was performed.…”

Section: Discussionmentioning

confidence: 99%

Prediction of biochemical nonresolution in patients with chronic drug‐induced liver injury: A large multicenter study

Wang

Deng

et al. 2022

Hepatology

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Background and Aims To clarify high‐risk factors and develop a nomogram model to predict biochemical resolution or biochemical nonresolution (BNR) in patients with chronic DILI. Approach and Results Retrospectively, 3655 of 5326 patients with chronic DILI were enrolled from nine participating hospitals, of whom 2866 underwent liver biopsy. All of these patients were followed up for over 1 year and their clinical characteristics were retrieved from electronic medical records. The endpoint was BNR, defined as alanine aminotransferase or aspartate aminotransferase >1.5× upper limit of normal or alkaline phosphatase >1.1× ULN, at 12 months from chronic DILI diagnosis. The noninvasive high‐risk factors for BNR identified by multivariable logistic regression were used to establish a nomogram, which was validated in an independent external cohort. Finally, 19.3% (707 of 3655) patients presented with BNR. Histologically, with the increase in liver inflammation grades and fibrosis stages, the proportion of BNR significantly increased. The risk of BNR was increased by 21.3‐fold in patients with significant inflammation compared to none or mild inflammation (p < 0.001). Biochemically, aspartate aminotransferase and total bilirubin, platelets, prothrombin time, sex, and age were associated with BNR and incorporated to construct a nomogram model (BNR‐6) with a concordance index of 0.824 (95% CI, 0.798–0.849), which was highly consistent with liver histology. These results were successfully validated both in the internal cohort and external cohort. Conclusions Significant liver inflammation is a robust predictor associated with biochemical nonresolution. The established BNR‐6 model provides an easy‐to‐use approach to assess the outcome of chronic DILI.

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Section: Discussionmentioning

confidence: 99%

Prediction of biochemical nonresolution in patients with chronic drug‐induced liver injury: A large multicenter study

Wang

Deng

et al. 2022

Hepatology

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“…The area under the curve (AUC) of the ROC for the training set of recovered DILI vs. chronic DILI is 0.889, with a sensitivity of 73.7% and a specificity of 92.7%, while the AUC for the validation set is 0.888, with a sensitivity of 71.4% and a specificity of 91.3% ( Figure 5B ). We then evaluated the predictive ability of AdA and Asp (‘AdA-Asp model’) with other markers such as TB, DB, ALP and TCA in all the DILI patients, which has been reported to be correlated with DILI chronicity in previous studies ( 11 , 12 , 28 ). The AUC for TB, DB, ALP and TCA were 0.57, 0.55, 0.58, and 0.57, respectively, while AUC for the panel of AdA and Asp was 0.850 ( Figure 5C ).…”

Section: Resultsmentioning

confidence: 99%

“…In our study, serum metabolites were detected by using global metabolic analysis and logistic regression was used to select metabolites in order to establish the prediction model for chronic DILI. An ‘AdA-Asp model’ was developed in our study, showing better predictive ability than biochemical indicators such as TB, DB, ALP ( 28 ) and TCA ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Alteration of Bile Acids and Omega-6 PUFAs Are Correlated With the Progression and Prognosis of Drug-Induced Liver Injury

Zhao

Zhou

et al. 2022

Front. Immunol.

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Background & AimsDrug-induced liver injury (DILI) is one of the leading causes of liver failure with some of the patients progressed to chronic DILI. The mechanisms underlying the severity and chronicity of DILI are poorly elucidated and the biomarkers are limited. Metabolites and gut microbiota played a crucial role in the development of various liver diseases. Herein, a systematic analysis of serum metabolites and gut microbiota was performed in DILI patients, aiming to identify metabolites correlated with the progression and clinical prognosis of DILI.MethodsVarious serum metabolites were quantitated using a metabolite array technology in this prospective study. Gut microbiome compositions and the expression profiles of liver genes were determined in patients with DILI and healthy controls.ResultsMetabolomic analysis revealed that bile acids (BAs) and polyunsaturated fatty acids (PUFAs) were closely related to DILI severity and chronicity respectively. The ratios of serum primary/secondary BAs and omega-6/omega-3 PUFAs were elevated in DILI patients. A model established by adrenic acid (AdA) and aspartic acid (Asp) exerts good performance for predicting the chronicity of DLIL. Hepatic transcriptome revealed enhanced expression of PUFA peroxidation and supressed expression of BA synthesis related genes in DILI patients. In addition, Lactic acid bacteria and BA converting bacteria were increased in gut of DILI patients. Besides, elevated serum malondialdehyde (MDA) and fibroblast growth factor 19 (FGF19) was observed in DILI patients.ConclusionBAs and PUFAs could be potent markers for the severity and chronicity of DILI respectively. The panel of AdA and Asp could be ideal predictive model for the risk of chronicity at the acute stage of DILI. Gut microbiota might act as a negative feedback mechanism to maintain the homeostasis of BAs and PUFAs via FGF19 signalling and PUFA saturation, respectively. Our study revealed novel biomarkers for severe and chronic DILI and provided new therapeutic targets for DILI.

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“…Patient recovery was defined as a return to normal of the patient’s serum biochemical parameters (1 × ULN) ( Ashby et al, 2021 ). As patients with DILI whose liver function did not return to normal for >6 months were considered to have a chronic liver injury ( Yu et al, 2017 ), we set 180 days as the cutoff point for follow-up.…”

Section: Methodsmentioning

confidence: 99%

Impact of pharmacist active consultation on clinical outcomes and quality of medical care in drug-induced liver injury inpatients in general hospital wards: A retrospective cohort study

Dong

et al. 2022

Front. Pharmacol.

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The utility of pharmacist consultation for drug-induced liver injury (DILI) management has not been explored. This retrospective cohort study evaluated the impact of a pharmacist active consultation (PAC) service on the management and outcome in patients with DILI. Consecutive patients meeting clinical biochemical criteria for DILI were enrolled at a tertiary teaching hospital between 1 January 2020 and 30 April 2022. The Roussel Uclaf Causality Assessment Method was used to assess causality between drug use and liver injury for each suspected DILI patient. Included patients were grouped according to whether they received PAC, and a proportional hazard model with multivariate risk adjustment, inverse probability of treatment weighting (IPTW), and propensity score matching (PSM) was used to assess DILI recovery. In the PSM cohort, the quality of medical care was compared between PAC and no PAC groups. A total of 224 patients with DILI (108 who received PAC and 116 who did not) were included in the analysis. Of these patients, 11 (10%) were classified as highly probable, 58 (54%) as probable, and 39 (36%) as possible DILI in the PAC group, while six patients (5%) were classified as highly probable, 53 (46%) as probable, and 57 (49%) as possible DILI in the no PAC group (p = 0.089). During patient recovery, PAC was associated with a ∼10% increase in the cumulative 180-day recovery rate. The PAC group had a crude hazard ratio (HR) of 1.73 [95% confidence interval (CI): 1.23–2.43, p = 0.001] for DILI 180-day recovery, which remained stable after multivariate risk adjustment (HR = 1.74, 95% CI: 1.21–2.49, p = 0.003), IPTW (HR = 1.72, 95% CI: 1.19–2.47, p = 0.003), and PSM (HR = 1.49, 95% CI: 1.01–2.23, p = 0.046). In the PSM cohort, PAC was more likely to identify suspect drugs (90% vs. 60%, p < 0.001) and lead to timely withdrawal of the medication (89% vs. 57%, p < 0.001). Thus, PAC is associated with a better quality of medical care for patients with DILI and can improve patient outcomes.

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Elevated bilirubin, alkaline phosphatase at onset, and drug metabolism are associated with prolonged recovery from DILI

Cited by 27 publications

References 31 publications

Prediction of biochemical nonresolution in patients with chronic drug‐induced liver injury: A large multicenter study

Prediction of biochemical nonresolution in patients with chronic drug‐induced liver injury: A large multicenter study

Alteration of Bile Acids and Omega-6 PUFAs Are Correlated With the Progression and Prognosis of Drug-Induced Liver Injury

Impact of pharmacist active consultation on clinical outcomes and quality of medical care in drug-induced liver injury inpatients in general hospital wards: A retrospective cohort study

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