Association of BMI with mortality in drug-induced liver injury.

BACKGROUND: To clarify the associations between BMI and the incidences of all-cause death or liver-related death (LRD)/liver transplantation (LT) in drug-induced liver injury (DILI). METHODS: DILI patients from three hospitals were retrospectively retrieved and follow-up from 2009 to 2021. They were categorized into underweight (BMI < 18.5 kg/m 2 ), normal weight (BMI of 18.5-23.9 kg/m 2 ), overweight (BMI of 24-27.9 kg/m 2 ) and obese (BMI ≥ 28 kg/m 2 ) groups. Cox regression models were conducted to reveal the effect of BMI on all-cause death or LRD/LT. RESULTS: A total of 1469 eligible DILI patients were included: underweight 73 (4.97%), normal weight 811 (55.21%), overweight 473 (32.20%) and obese 112 (7.62%). Eighty-nine patients (6.06%) had all-cause death, of which 66 patients (4.49%) had LRD/LT. The median age was 52 years old, and females were 1039 (70.73%). The associations between BMI and all-cause mortality ( nonlinear test P <  0.01) or liver-related mortality/LT ( nonlinear test P  = 0.01) were J-shaped. Multivariate Cox regression analysis showed that underweight (HR: 3.02, 95% CI: 1.51-6.02) was significantly associated with all-cause mortality after adjusting for age and sex. Furthermore, obese males were significantly associated with liver-related mortality/LT (HR: 3.49, 95% CI: 1.13-10.72) after additional adjustment for serological indices and comorbidities. CONCLUSION: Association between BMI and mortality is a J-shape. The overall mortality was significantly higher in underweight and obese group. Male obesity is independently associated with LRD/LT. These findings indicate that DILI patients with extreme BMI would have a high risk of dismal outcomes, which warrants extra medical care.

Development and validation of a novel model to predict liver-related mortality in patients with idiosyncratic drug-induced liver injury.

BACKGROUND: Early identification of patients with high mortality risk is critical for optimizing the clinical management of drug-induced liver injury (DILI). We aimed to develop and validate a new prognostic model to predict death within 6 months in DILI patients. METHODS: This multicenter study retrospectively reviewed the medical records of DILI patients admitted to three hospitals. A DILI mortality predictive score was developed using multivariate logistic regression and was validated with area under the receiver operating characteristic curve (AUC). A high-mortality-risk subgroup was identified according to the score. RESULTS: Three independent DILI cohorts, including one derivation cohort (n = 741) and two validation cohorts (n = 650, n = 617) were recruited. The DILI mortality predictive (DMP) score was calculated using parameters at disease onset as follows: 1.913 × international normalized ratio + 0.060 × total bilirubin (mg/dL) + 0.439 × aspartate aminotransferase/alanine aminotransferase - 1.579 × albumin (g/dL) - 0.006 × platelet count (109/L) + 9.662. The predictive performance for 6-month mortality of DMP score was desirable, with an AUC of 0.941 (95% CI: 0.922-0.957), 0.931 (0.908-0.949) and 0.960 (0.942-0.974) in the derivation, validation cohorts 1 and 2, respectively. DILI patients with a DMP score ≥ 8.5 were stratified into high-risk group, whose mortality rates were 23-, 36-, and 45-fold higher than those of other patients in the three cohorts. CONCLUSIONS: The novel model based on common laboratory findings can accurately predict mortality within 6 months in DILI patients, which should serve as an effective guidance for management of DILI in clinical practice.

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

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.

Alanine Aminotransferase and Bilirubin Dynamic Evolution Pattern as a Novel Model for the Prediction of Acute Liver Failure in Drug-Induced Liver Injury.

Aims: To develop, optimize, and validate a novel model using alanine aminotransferase (ALT) and total bilirubin (TB) dynamic evolution patterns in predicting acute liver failure (ALF) in drug-induced liver injury (DILI) patients. Methods: The demographics, clinical data, liver biopsy, and outcomes of DILI patients were collected from two hospitals. According to the dynamic evolution of ALT and TB after DILI onset, the enrolled patients were divided into ALT-mono-peak, TB-mono-peak, double-overlap-peak, and double-separate-peak (DSP) patterns and compared. Logistic regression was used to develop this predictive model in both discovery and validation cohorts. Results: The proportion of ALF was significantly higher in patients with the DSP pattern than in the ALT-mono-peak pattern and DOP pattern (10.0 vs. 0.0% vs. 1.8%,p < 0.05). The area under receiver operating characteristic curve (AUROC) of the DSP pattern model was 0.720 (95% CI: 0.682-0.756) in the discovery cohort and 0.828 (95% CI: 0.788-0.864) in the validation cohort in predicting ALF, being further improved by combining with international normalized ratio (INR) and alkaline phosphatase (ALP) (AUROC in the discovery cohort: 0.899; validation cohort: 0.958). Histopathologically, patients with the DSP pattern exhibited a predominantly cholestatic hepatitis pattern (75.0%, p < 0.05) with a higher degree of necrosis (29.2%, p = 0.084). Conclusion: DILI patients with the DSP pattern are more likely to progress to ALF. The predictive potency of the model for ALF can be improved by incorporating INR and ALP. This novel model allows for better identification of high-risk DILI patients, enabling timely measures to be instituted for better outcome.

Systematic review on the reporting quality of randomized controlled trials in patients with hepatitis B or C in China.

BACKGROUND: The numbers of articles reporting randomized controlled trials (RCTs) on viral hepatitis in China have been increasing, but there have been few systematic studies evaluating the reporting quality of RCTs in this field. This study was performed to assess the reporting quality of RCTs on the treatment of hepatitis B and C in China from 1991 to 2015. METHODS: Articles published between January 1991 and December 2015 were identified via the PubMed, MEDLINE, and Embase databases using the key words "randomized clinical trials", "treatment", "therapy", "hepatitis B", "HBV", "hepatitis C", "HCV", "China", and "Chinese". The reporting quality was assessed against the Consolidated Standards of Reporting Trials (CONSORT) checklist. RESULTS: In total, 211 RCTs on the treatment of hepatitis B or C were included. The number of articles focusing on these RCTs increased rapidly over time, while the reporting quality improved steadily over time. Overall, compliance with the key components of the CONSORT checklist was low, with only 8.5%, 3.8%, and 11.4% of the articles fulfilling the reporting requirements of randomization, allocation concealment, and blinding, respectively. CONCLUSIONS: Both the number and the quality of RCT articles were found to have increased steadily over the last two decades. However, compliance with the key components of the CONSORT checklist still needs improvement. It is hoped that the results of this study will lead to improvements in the reporting quality of clinical trials on hepatitis B and C in China.