Idiosyncratic DILI: Immunology in Cases with Evidence Based on RUCAM

Idiosyncratic drug induced liver injury (iDILI) is a multifaceted and fairly well described liver disease, but there is yet some uncertainty on the role of immune systems triggering the liver injury and speculation on the cascade of immune events. Many conclusions were so far based on narratives or cases of iDILI, which did not receive the benefit of a robust causality assessment like by the Roussel Uclaf Causality Assessment Method (RUCAM). This analysis aims to clarify the cascade of immune events that lead to the liver injury by conventional drugs. For this approach, the search focused on iDILI cases with verified diagnosis by RUCAM. Most promising were parameters obtained from the blood as mirror of what happened in the liver during the injurious processes.The focus of this present analysis is on patients with RUCAM based iDILI and concomitant immune-related parameters in the blood. As an example, compelling evidence for a role of immune systems in iDILI was found for circulating mediators in the blood secreted by liver immune cells in patients under a therapy for tuberculosis, detected were also serum anti-cytochrome P450 (CYP) antibodies in patients after anesthesia with sevoflurane or desflurane and thereby reflecting their metabolism by the CYP 2E1 isoform, the occurrence of serum of autoantibodies in patients with drug induced autoimmune hepatitis (DIAIH) due to many drugs, and the role of blood and liver monocytes, which provide direct evidence for the activation of the hepatic innate immune system to the adapted immune system. In essence, patients with RUCAM based iDILI show various immunology features in the blood compatible with the role of the hepatic immune systems in patients with suspected iDILI caused by some but not all drugs.