MetaHeps® – A novel method to assess causality in drug-induced liver injury (DILI)

Background: Drug-induced liver Injury (DILI) is the most common reason für acute liver failure. The idiosyncratic form of DILI is still a diagnosis of exclusion and it may be impossible to identify the culprit drug in patients taking several drugs. MetaHeps® are hepatocyte-like cells generated from peripheral blood exhibiting individual hepatocyte-like functions. Therefore, MetaHeps® could be a valuable tool for the positive diagnosis of individual DILI.

Aim: To evaluate in vitro testing using MetaHeps® as a tool to diagnose individual DILI

Methods: MetaHeps® of patients with suspected DILI were generated and treated with the putative causative drugs in vitro. Toxicity was assessed using LDH -release and the RUCAM/CIOMS-Score was calculated for each patient. The clinical data and MetaHeps® results were compared with results from healthy donors and patients with acute liver injury of other origin.

Results: We present several DILI-cases where testing with patient-derived MetaHeps® helped to find the diagnosis: In several patients individual susceptibilty to the suspected drug was confirmed. In one case with a negative in vitro result, further evaluation finally led to the diagnosis of acute viral hepatitis E. In another case two drugs were involved and testing allowed to identify the causative agent.

Conclusion: MetaHeps® allowed to diagnose or exclude DILI in these proof-of-concept cases, as well as the identification of the drugs causative for liver injury. Thus, this proprietary technology could be useful in the diagnosis of drug-induced liver injury.

Supported by GfGB, Exist Technology Transfer and M4 award for Personalized Medicine