The Usefulness of Extended Inflammation Parameters and Systemic Inflammatory Response Markers in the Diagnostics of Autoimmune Hepatitis

Abstract

(1) Introduction: Autoimmune hepatitis (AIH) is a chronic disease. A persistent autoimmune reaction in the liver is significantly related to the systemic inflammatory response. Extended Inflammation Parameters (EIP) can be used to assess the activation of immune cells such as activated neutrophils (NEUT-RI and NEUT-GI) and activated lymphocytes (RE-LYMP and AS-LYMP) in the phase of active inflammation. The role of the systemic inflammatory response markers should also be emphasised, especially: NLR, PLR, and RLR, which have recently been widely studied as markers in autoimmune skin diseases or liver diseases. (2) Materials and Methods: The study included 30 patients with AIH and 30 healthy volunteers. The parameters of the EIP group (RE-LYMP, AS-LYMP, NEUT-RI, NEUT-GI), calculated haematological indices Red Blood Cell Distribution Width-to-Platelet Ratio (RPR), Mean Platelet Volume-to-Platelet Ratio (MPR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Red Blood Cell Distribution Width-to-Lymphocyte Ratio (RLR), and selected blood morphological and biochemical indices were analysed. The aim of the study was to assess the usefulness of the EIP and systemic inflammatory response markers in the diagnostics of AIH. (3) Results: Compared to the controls, the patients with AIH showed significantly higher EIP values: NEUT-RI (48.05 vs. 43.30), NEUT-GI (152.65 vs. 147.40), RE-LYMP (0.07 vs. 0.03), and the inflammatory response markers: MPR (0.05 vs. 0.04), RPR (0.07 vs. 0.05), and NLR (2.81 vs. 1.42. Among the examined markers, EIP has significant diagnostic potential: NEUT-RI (AUC = 0.86), NEUT-GI (AUC = 0.80), and RE-LYMP (AUC = 0.78), and so do calculated haematological indices, i.e., MPR (AUC = 0.75), PLR (AUC = 1.00), and RLR (AUC = 1.00) Moreover, the importance of NEUT-GI (AUC = 0.89), MPR (AUC = 0.93), PLR (AUC = 0.86), RPR (AUC = 0.91), and FIB-4 (AUC = 0.83) in the detection of liver fibrosis in the course of AIH has also been proven. (4) Conclusions: EIP and systemic inflammatory response markers may turn out to be useful in detecting AIH and in looking for features of already developed liver cirrhosis in its course.

The Gut Microbiome and Autoimmune Hepatitis: Implications for Early Diagnostic Biomarkers and Novel Therapies

“…Biomarkers such as EIP (NEUT-RI, NEUT-GI and RE-LYMP), systemic inflammatory response markers (MPR, PLR, RPR, RLR, and NLR), and lowdensity granulocytes (LDGs) could serve as reliable markers for the early diagnosis and predicting the occurrence and severity of inflammatory disease. [32,33] Additionally, bile acids, growth diferentiation factor 15 (GDF15) as the novel diagnostic biomarkers played a vital role in early stages of AIH has already been reported. Strikingly though, intestinal microbiota was considered as a novel early-diagnosis biomarker of inflammatory diseases that have been confirmed.…”

Neutrophil Reactivity Intensity and misclassification of immature granulocytes

“…6 The parameter was proposed as an early marker of infection and sepsis, [6][7][8] a risk marker of mechanical ventilation during Coronavirus disease 2019 9,10 as well as a marker of autoimmune disease. [11][12][13] The normal level of NEUT-RI in samples without pathology was documented to be 45.4 fluorescence intensity (FI) with a standard deviation of 2.8 FI. 6 In cases where part of a dense IG tail is misinterpreted as part of the mature neutrophil population, the NEUT-RI rises as a result of the higher mean fluorescence signal.…”

“…NEUT‐RI corresponds to the NEUT‐Y value in the Sysmex XE‐series and represents the neutrophil reactivity and metabolic activity expressed by the mean fluorescent signal of the neutrophil population 6 . The parameter was proposed as an early marker of infection and sepsis, 6–8 a risk marker of mechanical ventilation during Coronavirus disease 2019 9,10 as well as a marker of autoimmune disease 11–13 . The normal level of NEUT‐RI in samples without pathology was documented to be 45.4 fluorescence intensity (FI) with a standard deviation of 2.8 FI 6 .…”

Nutritional responsiveness affects novel neutrophil parameters and reduces in-hospital mortality and costs in elective cancer oesophagectomy – a single centre, prospective, observational study

“…Among potential new parameters of chronic inflammation are those related to neutrophil activity, i.e., neutrophil reactivity intensity (NEUT-RI) and neutrophil granularity intensity (NEUT-GI), which are indicative of the activation stage of the neutrophilic granulocytes. This measurement, available in the Sysmex Diagnostic haematology analysers, considers the metabolic activity of neutrophils, the internal structure, and the size of the cell [ 8 ]. The usefulness of NEUT-RI and NEUT-GI as markers of systemic inflammation has previously been demonstrated in autoimmune hepatitis patients compared to healthy volunteers [ 8 ].…”

“…This measurement, available in the Sysmex Diagnostic haematology analysers, considers the metabolic activity of neutrophils, the internal structure, and the size of the cell [ 8 ]. The usefulness of NEUT-RI and NEUT-GI as markers of systemic inflammation has previously been demonstrated in autoimmune hepatitis patients compared to healthy volunteers [ 8 ]. The usefulness of NEUT-RI and NEUT-GI as markers of malnutrition and chronic inflammation in elective surgical patients is yet to be determined.…”