Interactive Digital Graphic Tool for Drug-induced Hepatotoxicity

by | May 4, 2019 |

Hepatotoxicity is the drug-induced destruction of the liver cells leading to a liver injury. Screening for hepatotoxicity is done as per Hy’s law ie, by checking for the elevated levels of liver enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) and also serum total bilirubin to a specific range. However, the detection of drug-induced hepatotoxicity is difficult as it requires excluding other probable causes of liver injury like alcoholism, viral hepatitis, etc. Due to this, various approved drugs in the market that were found to be hepatotoxic were ultimately withdrawn post-marketing. Therefore, in 2004, Food and Drug Administration (FDA) developed a program known as eDISH (evaluation of Drug-Induced Serious Hepatotoxicity) for graphically evaluating the drug-induced hepatotoxicity. The program plotted the results of biological tests done in cases of liver injury and also allowed for viewing the time course of the biological tests for each case, which allowed for easier identification of drug-induced hepatotoxicity. Since 2004, this program has helped to decrease the drug withdrawals from the market due to hepatotoxicity.

The program is still utilized for detection of drug-induced hepatotoxicity but is limited to static graphs only. However, there is a need for a more interactive graphical display to allow for better detection and evaluation of drug-induced hepatotoxicity. Therefore, ASA-DIA Interactive Safety Graphics working group is developing an interactive modified form of the FDA’s eDISH. The program is under testing and may be available soon as an open-access program. This interactive tool better visualizes and modifies safety data as per requirement, allowing for better detection and evaluation of drug-induced hepatotoxicity. The program, similar to e-DISH, divides the graph into four quadrants of normal range, Hy’s law range, Temple’s corollary range, and isolated hyperbilirubinemia range and disperses the cases in the graph. The program, however, additionally allows for checking the time course and the previous levels of a laboratory evaluation for each case of interest. The program also allows for filtering of data and adjustment of laboratory thresholds to better understand the relatedness of liver damage to the drug. This gives full freedom to a user as the user can easily detect and validate cases of drug-induced hepatotoxicity through the interactive graph.

The group has also provided a workflow for evaluating the relationship between the drug and liver damage on the basis of several evaluations and steps. The workflow is based on current medical literature and practices to help guide the user through the various steps and evaluations that can be done using the interactive program. This allows the user to understand the relation of liver damage to the drug by better interpretation of the results of each evaluation and by providing help in drawing a conclusion after every step. Overall, interactive graphical tools may prove to be the next big step in the evaluation of drug-induced hepatotoxicity; therefore, there is a need to develop other tools like interactive eDISH.

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