Elevated polyreactive immunoglobulin G in immune mediated liver injuries with the need for immunosuppressive therapy

Abstract

AbstractBackground and aimThe distinction of drug-induced liver injury (DILI), drug-induced autoimmune-like hepatitis (DI-ALH) and autoimmune hepatitis (AIH) can be challenging due to overlapping clinical characteristics. Recently, polyreactive immunoglobulin G (pIgG) was identified as a novel biomarker with a higher accuracy for the diagnose of AIH than conventional autoantibodies. This retrospective multicenter study aimed to evaluate the diagnostic accuracy of pIgG to distinguish between AIH, DI-ALH and DILI and thus identify patients in need of immunosuppression.MethodsSamples from 116 patients (AIH=81, DI-ALH=12, DILI=23) were recruited and compared to a control group (non-AIH-non-DILI-LD= 596) from existing biorepositories.ResultsNo patient in the DILI-group but 98% in the AIH-and 92% in the DI-ALH-group received immunosuppressive treatment. pIgG levels were significantly higher in the AIH-group (1.9 normalized arbitrary units (nAU) compared to DILI (1.1 nAU, p<0.001) and non-AIH-non-DILI-LD (1.0 nAU, p<0.001). Median pIgG concentrations of the DI-ALH-group (1.7 nAU) were between AIH (p=.634) and DILI (p=.052). Patients that needed immunosuppressive therapy for remission induction had significantly higher pIgG concentrations compared to those with spontaneous recovery of liver injury (1.8 nAU vs. 1.1 nAU, p<.001). The overall accuracy of pIgG >1.27nAU to distinguish AIH from DILI (74%) and liver injuries with and without the need for immunosuppression (74%) was similar to that of ANA (71/74%) and SMA (74/70%) at cut-offs of ≥1/40.ConclusionPolyreactive IgG can be used to predict AIH in comparison to DILI and indicate the need for immunosuppressive therapy in the work-up of immune mediated or drug-induced liver injuries.