Comorbidity Burden Predicts 6-Month Mortality in Suspected Drug-Induced Liver Injury

Anatomical models of liver surrounded by six blister packs with white pills inside six-pointed star in corners of image on orange background. Concept art photo for treatment of chronic liver disease
Researchers identified a strong relationship between significant comorbidity burden and outcomes of patients with suspected drug-induced liver injury, and developed and validated a model to calculate risk of death within 6 months.

A model consisting of serum albumin, model of end-stage liver disease (MELD) score, and Charlson comorbidity index (CCI) strongly predicts 6-month mortality in patients with suspected drug-induced liver injury (DILI), according to a study published in Gastroenterology. The researchers also discovered that the medical comorbidity burden is significantly associated with both 6-month and overall mortality in this population.

This multicenter observational study (DILIN; identifier: NCT00345930) was designed to investigate the association between the comorbidity burden of patients with DILI outcomes. The discovery cohort used to create the model consisted of 306 participants enrolled at Indiana University (52% women, mean + SD age 49 ± 19 years). Two hundred and fifty-three participants with CCI <2 were classified as having “none to mild comorbidity,” and 53 participants with CCI >2 (17%) were classified as having “significant comorbidity.” Six-month mortality after suspected presentation of DILI was seen in 26 of 253 (10.3%) of participants with none to mild comorbidity, and in 15 of 53 (28.3%) of participants with significant comorbidity (P <.001).

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The validation cohort used to validate the model used data from 247 patients with suspected DILI enrolled in the same study at the University of North Carolina. Forty participants (16%) were classified as having significant comorbidity by CCI scores.

Six-month mortality was 8.5% in the discovery cohort, compared with 4.5% in the validation cohort. In the discovery cohort, multiple logistic regression analysis found serum albumin (odds ratio [OR], 3.7; 95% CI, 0.2-0.7), MELD score (OR, 1.09; 95% CI, 1.03-1.15), and significant comorbidity (OR, 5.2; 95% CI, 2.1-13.3) were all independently associated with 6-month mortality.

A model based on albumin, MELD, and CCI score successfully identified participant mortality 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. A web-based calculator representing the model was developed and calibrated to determine 6-month mortality risk for clinic patients with suspected DILI, and can be accessed here:

Study limitations included the small, subgroup of patients with significant comorbidities (93 of 593 [15.7%]), data from a single center, and a lack of documentation of all comorbid conditions.

Study investigators concluded, “In summary, we observed that medical comorbidity burden is significantly associated with 6 month and overall mortality in individuals with suspected DILI. A model consisting of Charlson Comorbidity Index, MELD score, and serum albumin strongly predicts 6-month mortality in patients with suspected DILI. It identifies patients in need of closer comprehensive monitoring in the wake of acute liver injury.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Ghabril M, Gu J, Yoder L, et al. Development and validation of model consisting of comorbidity burden to calculate risk of death within 6 months for patients with suspected drug-induced liver injury [published online July 11, 2019]. Gastroenterology. doi:10.1053/j.gastro.2019.07.006