BACKGROUND & AIMS Patients with drug-induced liver injury (DILI) frequently have comorbid conditions, but the effects of non-liver comorbidities on outcomes are not well understood. We investigated the association between comorbidity burden and outcomes of patients with DILI, and developed and validated a model to calculate risk of death within 6 months. METHODS A multiple logistic regression model identified variables independently associated with death within 6 months of presenting with suspected DILI (6-month mortality) for 306 patients enrolled in the Drug-Induced Liver Injury Network prospective study at Indiana University (discovery cohort). The model was validated using data from 247 patients with suspected DILI enrolled in the same study at the University of North Carolina (validation cohort). Medical comorbidity burden was calculated using the Charlson Comorbidity Index-patients with scores higher than 2 were considered to have significant comorbidities. RESULTS Six-month mortality was 8.5% in the discovery cohort and 4.5% in the validation cohort. In the discovery cohort, significant comorbidities (odds ratio, 5.4; 95% confidence interval [CI], 2.1-13.8), Model for End-Stage Liver Disease score (odds ratio, 1.11; 95% CI, 1.04-1.17), and serum level of albumin at presentation (odds ratio, 0.39; 95% CI, 0.2-0.76) were independently associated with 6-month mortality. A model based on these 3 variables identified patients who died within 6 months, with c-statistic values of 0.89 (95% CI, 0.86-0.94) in the discovery cohort and 0.91 (95% CI, 0.83-0.99) in the validation cohort. We developed a web-based calculator for use in the clinic to determine risk of death within 6 months for patients with suspected DILI. CONCLUSIONS We developed and validated a model based on comorbidity burden, Model for End-Stage Liver Disease score, and serum level of albumin that predicts 6-month mortality in patients with suspected DILI.

中文翻译：

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疑似药物引起的肝损伤患者的合并症负担模型（用于计算六个月内的死亡风险）的模型的开发和验证。

背景与目的药物诱发性肝损伤（DILI）患者经常患有合并症，但对非肝脏合并症对预后的影响尚不甚了解。我们调查了合并症负担与DILI患者预后之间的关联，并开发并验证了一种模型以计算6个月内的死亡风险。方法采用多重逻辑回归模型，对306名参加印第安纳大学药物诱发性肝损伤网络前瞻性研究（发现队列）的患者进行疑似DILI表现的6个月内死亡（6个月死亡率）与死亡独立相关的变量。使用来自北卡罗来纳大学同一项研究的247名疑似DILI患者的数据对模型进行了验证（验证队列）。使用Charlson合并症指数计算医疗合并症负担，评分高于2的患者被认为具有重大合并症。结果发现队列的六个月死亡率为8.5％，验证队列的为4.5％。在发现队列中，重大合并症（比值比为5.4； 95％置信区间[CI]为2.1-13.8），终末期肝病评分模型（比值比为1.11； 95％CI为1.04-1.17）和呈现时白蛋白的血清水平（赔率，0.39； 95％CI，0.2-0.76）与6个月死亡率独立相关。基于这三个变量的模型确定了在6个月内死亡的患者，发现队列的c统计量值为0.89（95％CI，0.86-0.94），而验证队列的c统计值为0.91（95％CI，0.83-0.99）。 。我们开发了一种基于网络的计算器，供临床使用，以确定可疑DILI患者在6个月内的死亡风险。结论我们开发并验证了基于合并症负担，终末期肝病评分模型和白蛋白血清水平的模型，该模型可预测可疑DILI患者的6个月死亡率。