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. 2022 Aug 17;17(8):e0272786.
doi: 10.1371/journal.pone.0272786. eCollection 2022.

A logistic regression model based on inpatient health records to predict drug-induced liver injury caused by ramipril-An angiotensin-converting enzyme inhibitor

Phuong Nguyen Thi Thu  1   2 , Mai Ngo Thi Quynh  1 , Hung Nguyen Van  1 , Hoi Nguyen Thanh  2 , Khue Pham Minh  1
Affiliations

A logistic regression model based on inpatient health records to predict drug-induced liver injury caused by ramipril-An angiotensin-converting enzyme inhibitor

Phuong Nguyen Thi Thu et al. PLoS One. .

Abstract

Drug-induced liver injury (DILI) is a rare side effect of angiotensin-converting enzyme inhibitors (ACEIs). Ramipril is a widely used ACE compound because of its effectiveness in the treatment of hypertension and heart failure, as well as its low risk of adverse effects. However, the clinical features of ramipril, and the risk of DILI, have not been adequately studied. A retrospective cohort study was performed based on data from 3909 inpatients to compare the risk of DILI conferred by ramipril and other ACEIs. A logistic regression model was then constructed and validated against data from 1686 patients using ramipril, of which 117 patients were diagnosed with DILI. The use of ramipril increased the risk of DILI by 2.68 times (odds ratio = 2.68; 95% confident interval (CI):1.96-3.71) compared with the group using other ACEIs. The clinical features of DILI in the ramipril group were similar to those from the ACEI group (P>0.05), except that the ALT level was higher (P<0.05). A logistic regression model including Body mass index (BMI), comorbidity, liver disease, daily dose, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) was built and successfully validated for DILI risk prediction, with the area under the receiver operating characteristic curve of the model of 0.82 (95% CI: 0.752-0.888). We recommend that clinicians should be aware of the levels of ALT and ALP as well as BMI, comorbidities, and liver disease before prescribing ramipril to avoid the risk of DILI in patients.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Data processing.
ACEIs: angiotensin converting enzyme inhibitors; DILI: Drug-induced liver injury; MLR: multiple logistic regression.
Fig 2
Fig 2. Variables star schema.
DILI, drug induced liver injury; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; TBIL, total bilirubin.
Fig 3
Fig 3. Impact of independent predictors on the probability of drug induced liver injury on multiple logistic-regressions.
DILI: drug induced liver injury.
Fig 4
Fig 4. Comparison of receiver operating characteristic curve curves of 3 models.
AUC: area under the receiver operating characteristic curve.
See this image and copyright information in PMC

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