Supplementary Material for: LKM immunofluorescence is associated with DILI, especially after metamizole intake

Background & Aims:
Drug induced liver injury (DILI) is a rare but potentially serious clinical condition. One phenotype of DILI is termed drug-induced autoimmune like hepatitis (DI-ALH) that presents with laboratory and histological features indistinguishable from autoimmune hepatitis. Liver kidney microsomal antibodies (LKM-antibodies) are common in the diagnosis of AIH but were also described to be associated with halothane-induced DILI. Also, the antigens of anti-LKM-1 and anti-LKM-2 belong to the cytochrome P450 enzyme family that is involved in metabolism various drugs. Therefore, we aimed to study the impact of LKM-antibodies in the diagnostic work-up of suspected DILI in a large cohort of patients with liver injury in a tertiary care centre.
Methods:
We screened a large single centre hospital data base and retrospectively identified 63.300 cases with liver injury as defined: AST or ALT > 3 ULN or AP or TBI > 2 ULN. Of those, 82 cases with LKM immunofluorescence positivity (titre ≥ 1: 160) were identified, of which 64 patients fulfilled the inclusion criteria for this study.
Results:
Positive LKM immunofluorescence was associated with drug-induced autoimmune-like hepatitis (DI-ALH). Metamizole association was identified in half of the patients (n=33, 52%). Eight patients with metamizole associated DI-ALHs required liver transplantation and one patient died.
Conclusion:
DI-ALH, especially after metamizole administration, can be a reason for a positivity in LKM immunofluorescence tests. Metamizole DI-ALH has a high liver-related mortality.