Macrophage Markers, Soluble CD163 (sCD163) and Soluble CD206 (sCD206) in Paracetamol Overdose

Macrophage Activation, Assessed by Macrophage Markers Soluble CD163 and Soluble CD206, as Indication of Early Liver Cell Damage in Paracetamol Overdose

The Danish Council for Strategic Research, Novo Nordisk A/S, Savværksejer Jeppe Juhl og Hustru Ovita Juhls mindelegat

Paracetamol (PCM) is a widely used over-the-counter analgesic, and overdose with PCM is a condition regularly seen in everyday clinical practice. Identification of the patients with early signs of liver injury that may develop into acute liver failure is important. Previous research has shown that macrophages play a role in the development of liver damage in PCM-induced acute liver failure, making macrophage markers interesting possible biomarkers of this condition. In the present study, the investigators aimed to investigate the extent and timing of macrophage activation in PCM-induced liver injury by measuring levels of macrophage markers sCD163 and sCD206 in patients admitted with PCM overdose. The investigators also hoped to find out whether these markers are valuable as prognostic markers of severe outcome in these patients. Furthermore the investigators examined the possible effect of antidote treatment with N-acetylcysteine on activation and function of macrophages by administering NAC to healthy subjects and measuring levels of sCD163 and sCD206 prior to and after completion of treatment.

The part of the study concerning the patients with PCM overdose was strictly observational with measurement of macrophage markers and no other intervention than the NAC treatment administered in the setting of management of the participants PCM overdose according to best clinical practice. The interventional part of the study which is submitted for registration here concerns only healthy controls who were exposed to NAC treatment in order to assess the direct effects of NAC on macrophages. The participants received NAC treatment according to the same protocol as the PCM overdosed patients, and macrophage activation markers were measured prior to and after 16 hours of NAC treatment. Thus, the involvement of the participants in the study was limited to the 16 hours of NAC treatment.

Healthy individuals received intravenous N-acetylcysteine (NAC) treatment to investigate its actions on macrophage activation assessed by the markers soluble CD163 and CD206

Non-randomized exposure to N-acetylcysteine (NAC) of healthy individuals corresponding to the clinical treatment guidelines for paracetamol-overdosed patients

Change in macrophage activation marker soluble CD163 after treatment of healthy individuals with N-acetylcysteine

Change in macrophage activation marker soluble CD206 after treatment of healthy individuals with N-acetylcysteine