Cells of Monocytic Origin as Surrogate Markers for Individual Drug Effects and Hepatotoxicity

Adverse Reaction to Drug, Drug-induced Disorder of Liver

Drug metabolism in the liver is subject to large fluctuations (differences between women and men, people of different ethnic backgrounds, children and adults). These large differences are responsible for very different drug effects and side-effects (and especially liver damage caused by drugs) between individuals. Recent scientific findings suggest that blood derived cells can be used to model individual effects of drugs on the liver reflect inter-individual differences. Since liver damage caused by drugs is a diagnosis of exclusion, the aforementioned cells can be used to identify patients that show higher sensitivity to hepatotoxic side-effects and - in case several drugs are involved - identify the causal agent or possible interactions.

Drug-induced liver injury (DILI), especially its idiosyncratic for is often an unpredictable complication of drug therapy. Until now it is very challenging to predict occurrence, severity and outcome of DILI. Previous data provide evidence that cells from peripheral blood may reflect hepatocellular damage (Fannin RD, Hepatology. 2010). Own research could show that peripheral monocytes are capable to obtain several hepatocyte-like functions while maintaining individual characteristics of the donor, especially cytochrome P450 metabolism (Benesic, Gerbes, et al, Lab Invest 2012). This study investigates the effects of potentially hepatotoxic drugs on cells generated from patient blood in comparison to the clinical presentation. Its aim is the evaluation of in vitro tests using monocyte derived cells for diagnosis and exclusion of DILI and the potential to use the patient derived-cells for mechanistic investigations of DILI. 4 groups are investigated: 1) donors without liver disease 2) patients who will start a therapy with DILI-potential; 3) DILI patients; 4) patients with liver injuries other than DILI. Patient history and clinical data are obtained and a single blood sample will be collected after informed consent.

Australia, Germany, Hong Kong, Japan, South Korea