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Significant Medical Comorbidities Are Associated With Lower Causality Scores in Patients Presenting With Suspected Drug-Induced Liver Injury.

ABSTRACT: INTRODUCTION: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. METHODS: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. RESULTS: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). DISCUSSION: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.

SUBMITTER: Ghabril M

PROVIDER: S-EPMC7263658 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Significant Medical Comorbidities Are Associated With Lower Causality Scores in Patients Presenting With Suspected Drug-Induced Liver Injury.

Ghabril Marwan M Gu Jiezhun J Yoder Lindsay L Corbito Laura L Dakhoul Lara L Ringel Amit A Beyer Christian D CD Vuppalanchi Raj R Barnhart Huiman H Hayashi Paul H PH Chalasani Naga N

Clinical and translational gastroenterology 20200401 4

<h4>Introduction</h4>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.<h4>Methods</h4>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 com ...[more]

PMID: 32251016

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Project description:Purpose: Drug-induced liver injury (DILI) is a common adverse reaction in the clinic; however, there are relatively few reports of DILI in critically ill newborns and children. Making use of the Pediatric Intensive Care database (PIC), this study identifies which drugs are related to DILI in neonates and children in China. Methods: Using the PIC, we screened for patients whose liver was suspected of being injured by drugs during hospitalization. The medicine they used was then assessed by the Roussel Uclaf Causality Assessment Method (RUCAM). At the same time, we also collated drug combinations that may affect CYP (Cytochrome P) enzyme metabolism, which may cause DILI. Results: A total of 13,449 patients were assessed, of whom 77 newborns and 261 children were finally included. The main type of liver injury in neonates was mixed (83.1%), while the hepatic injury types of children were mostly distributed between hepatocellular (59.4%) and cholestatic (28.4%). In terms of the RUCAM assessment, the drugs that were most considered to cause or be associated with hepatic injury in newborns were medium and long chain fat emulsions (17%), sodium glycerophosphate (12%), and meropenem (9%); while omeprazole (11%), methylprednisolone sodium succinate (10%), and meropenem (8%) were the primary culprits of DILI in children. Drug combinations frequently seen in neonates that may affect CYP enzyme metabolism are omeprazole + budesonide (16.9%), dexamethasone + midazolam (10.4%), and midazolam + sildenafil (10.4%). In children, the commonly used drug combinations are fentanyl + midazolam (20.7%), ibuprofen + furosemide (18.4%), and diazepam + omeprazole (15.3%). Conclusions: In this study, medium and long chain fat emulsions and sodium glycerophosphate have been strongly associated with DILI in newborns, while omeprazole and methylprednisolone sodium succinate play an important role in the DILI of children. Also, attention should be paid to the effect on CYP enzymes when using multiple drugs at the same time. In future DILI cases, it is advisable to use the latest RUCAM for prospective study design so that complete case data and high RUCAM scores can be collected.

Project description:Functional and structural liver abnormalities may be found in patients with advanced heart failure (HF). The Model of End-Stage Liver Disease Excluding INR (MELD-XI) score allows functional risk stratification of HF patients on and off anti-coagulation awaiting heart transplantation (HTx), but these scores may improve or worsen depending on bridging therapies and during time on the waiting list. Liver biopsy is sometimes performed to assess for severity of fibrosis. Uncertainty remains whether biopsy in addition to MELD-XI improves prediction of adverse outcomes in patients evaluated for HTx.Sixty-eight patients suspected of advanced liver disease underwent liver biopsy as part of their HTx evaluation. A liver risk score (fibrosis-on-biopsy + 1) × MELD-XI was generated for each patient.Fifty-two patients were listed, of whom 14 had mechanical circulatory support (MCS). Thirty-six patients underwent transplantation and 27 patients survived ?1 year post-HTx (74%, as compared with 88% average 1-year survival in HTx patients without suspected liver disease; p < 0.01). Survivors had a lower liver risk score at evaluation for HTx (31.0 ± 20.4 vs 65.2 ± 28.6, p < 0.01). A cut-point of 45 for liver risk score was identified by receiver-operating-characteristic (ROC) analysis. In the analysis using Cox proportional hazards models, a liver risk score ?45 at evaluation for HTx was associated with greater risk of death at 1 year post-HTx compared with a score of <45 in both univariable (HR 3.94, 95% CI 1.77-8.79, p < 0.001) and multivariable (HR 4.35, 95% CI 1.77-8.79, p < 0.001) analyses. Patients who died <1 year post-HTx had an increased frequency of acute graft dysfunction (44.4% vs 3.7%, p = 0.009), longer ventilation times (55.6% vs 11.1%, p = 0.013) and severe bleeding events (44.4% vs 11.1%, p = 0.049). The liver risk score at evaluation for HTx also predicted 1-year mortality after HTx listing (p < 0.001).Patients with HF and advanced liver dysfunction are high-risk HTx candidates. Liver biopsy in addition to MELD-XI improves risk stratification of patients with advanced HF and suspected irreversible liver dysfunction.

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Significant Medical Comorbidities Are Associated With Lower Causality Scores in Patients Presenting With Suspected Drug-Induced Liver Injury.

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Significant Medical Comorbidities Are Associated With Lower Causality Scores in Patients Presenting With Suspected Drug-Induced Liver Injury.

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