Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana.
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Clin Transl Gastroenterol. 2020 Apr;11(4):e00141. doi: 10.14309/ctg.0000000000000141.
Drug-induced liver injury (DILI) is a diagnosis of exclusion, and it can be challenging to adjudicate when there are multiple comorbidities and concomitant medications. In this study, we tested the hypothesis that comorbidity burden impacts the causality adjudication in patients with suspected DILI.
We studied consecutive patients with suspected DILI enrolled in the Drug-Induced Liver Injury Network Prospective Study at 2 centers between 2003 and 2017. The comorbidity burden at presentation was determined using the Charlson Comorbidity Index (CCI). We analyzed the association between significant comorbidity (CCI > 75th percentile) and (i) the adjudication of DILI by expert consensus as definite, highly likely, or probable (high-confidence DILI) and (ii) the Roussel Uclaf Causality Assessment Method (RUCAM) scores.
Our cohort consisted of 551 patients who were classified as "no comorbidity" (54%, CCI = 0), "mild comorbidity" (29%, CCI = 1 or 2), and "significant comorbidity" (17%, CCI > 2). The probability of high-confidence DILI was significantly lower in patients with significant comorbidity compared with those with mild or no comorbidities (67% vs 76% vs 87%, respectively, P < 0.001). The mean RUCAM scores decreased with increasing comorbidity (no comorbidity 6.6 ± 2, mild comorbidity 6 ± 2.4, and significant comorbidity 5.6 ± 2.7, P < 0.001). In the multiple logistic regression, significant comorbidity had an independent inverse relationship with DILI (odds ratio: 0.37, 95% confidence interval: 0.2-0.69, P = 0.001).
Higher comorbidity burden impacts the causality assessment in patients with suspected DILI. Further studies are needed to investigate the utility of comorbidity burden as a variable in the DILI causality instruments.
药物性肝损伤（DILI）是一种排除性诊断，当存在多种合并症和同时使用多种药物时，其因果关系的判断可能具有挑战性。在这项研究中，我们检验了合并症负担会影响疑似 DILI 患者因果关系判断的假设。
我们研究了 2003 年至 2017 年间在两个中心参与药物性肝损伤网络前瞻性研究的连续疑似 DILI 患者。使用 Charlson 合并症指数（CCI）确定就诊时的合并症负担。我们分析了显著合并症（CCI＞第 75 百分位数）与（i）专家共识确定的 DILI 判定（明确、高度可能或可能）和（ii）Roussel Uclaf 因果关系评估方法（RUCAM）评分之间的关联。
我们的队列包括 551 名患者，他们被分为“无合并症”（54%，CCI=0）、“轻度合并症”（29%，CCI=1 或 2）和“显著合并症”（17%，CCI＞2）。与轻度或无合并症患者相比，有显著合并症患者发生高度置信 DILI 的可能性显著降低（分别为 67%、76%和 87%，P＜0.001）。随着合并症的增加，RUCAM 评分降低（无合并症 6.6±2，轻度合并症 6±2.4，显著合并症 5.6±2.7，P＜0.001）。在多变量逻辑回归中，显著合并症与 DILI 呈独立的负相关（比值比：0.37，95%置信区间：0.2-0.69，P=0.001）。
更高的合并症负担会影响疑似 DILI 患者的因果关系评估。需要进一步研究来探讨合并症负担作为 DILI 因果关系工具中一个变量的效用。
