Development and validation of a clinical scale for the diagnosis of drug-induced hepatitis.

Abstract

The objective of this study is to present and validate a clinical scale for the diagnosis of drug-induced liver injury (DILI). Five components were selected to be included in the scale: temporal relationship between drug intake and the onset of clinical picture, exclusion of alternative causes, extrahepatic manifestations, rechallenge or accidental re-exposure, and previous report in medical literature. The relative importance of each component was weighed, and arbitrary scores were attributed. The probability of the diagnosis of DILI was expressed as a final score, which could vary from -6 to 20. Content validity, criterion validity, construct validity, and inter-rater reliability were studied. To analyze validity and reliability, a random sample of 50 cases of suspected DILI was drawn from a series of 120 cases reported to our unit. The classification of the 50 cases by three experts in DILI was used as the external standard in the study of criterion validity. Agreement between the scale and the standard, and agreement between two independent raters (inter-rater reliability) was analyzed by weighted kappa coefficient. There was agreement between the scale and the standard in 42 cases (84%) with a weighted kappa coefficient of 0.90. A good discriminatory capacity of the scale was found when construct validity was studied. Agreement between raters was observed in 86% of the cases, corresponding to the weighted kappa of 0.93. In conclusion, the clinical scale was shown to have a high-level of validity and inter-rater reliability as well as a good discriminatory capacity between different levels of probability. These data suggest that the scale is suitable for use in clinical practice and may contribute to overcome the difficulties in the process of causality assessment in DILI.