Reticuloendothelial activation correlates with disease severity and predicts mortality in severe alcoholic hepatitis

Abstract

Background Overactivation of reticuloendothelial cells lining liver sinusoids – Kupffer cells (macrophages) and sinusoidal endothelial cells – may narrow the sinusoidal lumen, impair perfusion in liver microcirculation and contribute to disease severity in alcoholic hepatitis. Aim The aim of the article was to assess reticuloendothelial activation in patients with severe alcoholic hepatitis (SAH). Methods In SAH patients, we prospectively studied baseline reticuloendothelial activation markers [serum ferritin, sCD163 and plasma von Willebrand factor (VWF) antigen] and Macrophage Activation Syndrome (MAS) criteria, correlated them with disease severity scores [model for end-stage liver disease (MELD) and Sequential Organ Failure Assessment (SOFA) scores] and analyzed their ability to predict survival over a 90-day follow-up period. Results A total of 50 SAH patients [45 (37–49) years, median (interquartile range), 49 males, discriminant function, 76.2 (54.5–106.6); MELD score, 30 (26.2–36)] were studied. 41 SAH patients (82%) had ferritin >500 ng/mL, and all (100%) had markedly raised sCD163 and VWF levels. The median sCD163 level was 10-fold higher than healthy controls and the median VWF level was 5-fold above the upper limit of normal. In total, 37 SAH patients (74%) met MAS criteria. Reticuloendothelial activation markers correlated with MELD and SOFA scores (P < 0.05). VWF was an independent marker to predict mortality in SAH [adjusted hazard ratio, 1.002 (1.000–1.004)]. Conclusions The reticuloendothelial system was markedly activated and correlated with disease severity scores in SAH patients.VWF predicted short-term mortality independent of MELD and sCD163. Further larger multicentric studies are needed to validate these findings.

Plasma Von Willebrand Factor Levels Predict Survival in COVID-19 Patients Across the Entire Spectrum of Disease Severity

“…All patients were triaged as per WHO score for severity of COVID-19 [9], and managed as per institutional protocol. The in-hospital outcome of these patients was noted.…”

“…A recent review, documents raised VWF along-with low ADAMTS13 (VWF cleaving enzyme-a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in COVID-19 patients [7]. CD163 (scavenger receptor for hemoglobin haptoglobin complex), a macrophage specific protein, is also a macrophage activation marker shown to be elevated in inflammatory conditions [8,9].…”

Portal Hypertension in Alcohol-Associated Hepatitis

“…Overactivation of these reticuloendothelial cells in the sinusoids may correlate with disease severity and mortality in patients with severe AH. A prospective study was carried out in 50 severe AH patients (Maddrey’s discriminant function > 32 or MELD > 20) [ 36 ]. Of these, 43 patients (82%) who fell into the category of very severe AH (Maddrey’s discriminant function, 76.23 (55.06–104.35)) showed a marked activation of the reticuloendothelial system with elevated levels of von Willebrand factor (vWF), an indicator of EC activation, as well as increased levels of soluble CD163 and ferritin, markers of macrophage activation.…”

Recognizing Dysfunctional Innate and Adaptive Immune Responses Contributing to Liver Damage in Patients With Cirrhosis

“…Severe alcoholic hepatitis often precipitates ACLF 56 . Markers of reticulo - endothelial activation correlate with liver disease severity and predict death, independent of Model for End-Stage Liver Disease (MELD) scores, in patients with severe alcoholic hepatitis 57 , 58 . Prognostic ability of these indices, suggest that these inflammatory markers may contribute to worsening of severity of liver disease in these patients.…”