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Tools for causality assessment in drug-induced liver disease

Tillmann, Hans L.a,b; Suzuki, Ayakoc,d; Barnhart, Huiman X.e; Serrano, Josef; Rockey, Don C.g

Current Opinion in Gastroenterology: May 2019 - Volume 35 - Issue 3 - p 183–190
doi: 10.1097/MOG.0000000000000526
LIVER: Edited by Don C. Rockey

Purpose of review There are three liver-specific causality assessment tools currently available to guide clinical diagnosis of Drug-Induced Liver Injury (DILI): Roussel-Uclaf Causality Assessment Method (RUCAM), Digestive-Disease-Week Japan 2004 scale (DDW-J), and Clinical Diagnostic Scale (CDS). The purpose of this review is to assess these tools and discuss how to improve the causality assessment process as a whole.

Recent findings Existing DILI-specific causality assessment tools are surprisingly similar and exhibit only minor differences in point allocation. But difference in threshold for likelihood of being DILI. We reviewed the literature on currently used causality assessment tools, identified areas for future improvement, and herein propose approaches for refinement. Opportunities to improve current models, as well as the assessment process, in general, include in particular provision of more precise clinical detail and to perhaps add new components to scoring systems. For example, the incorporation of drug-specific clinical signature patterns, accounting for a drug's inherent hepatotoxicity potential, and/or incorporation of other drug properties to scoring systems may allow enhancement. Further, more systemic exclusion of competing diagnoses is needed. Finally, causality assessment processes will likely benefit from a data-driven and computer-assisted approach.

Summary Current tools used for DILI adjudication are imperfect. Avenues to improve these tools are described.

aDepartment of Medicine, Division of Gastroenterology, East Carolina University

bGreenville VA Healthcare Center, Greenville

cDivision of Gastroenterology, Duke University

dDurham VA Medical Center

eDuke Clinical Research Institute, Duke University Medical Center, Durham

fNIDDK, Liver Research Branch, Division of Digestive Diseases and Nutrition, Bethesda

gDepartment of Medicine, Medical University South Carolina, Charleston, USA

Correspondence to Hans L. Tillmann, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Vidant Medical Center, Suite 338, Mail Stop, 734 East Carolina University, Greenville, NC 27834, USA. Tel: +1 252 744 5681; fax: +1 252 744 8426; e-mail:

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