Topical issues of clinical symptoms and diagnostics of septic shock

Abstract

Viral hepatitis remains the most common cause of liver cirrhosis (LC). Monocytes, capable of migrating to the liver and participating in inflammation and fibrogenesis, play an important role in the LC pathogenesis as confirmed by the association of certain monocyte subsets with the disease severity and mortality in alcoholic and biliary LC. However, the clinical and prognostic relevance of monocytes in viral LC remains poorly investigated. This study was aimed to investigate the disturbances in circulating monocytes including classical (CD14++CD16, cMo), intermediate (CD14++CD16+, iMo) and non-classical monocytes (CD14+CD16++, nMo) in patients with viral LC, as well as their correlation with viral characteristics, LC severity and progression of the disease 12 months after combination therapy. A significant increase in iMo and nMo, cMo level tended to decrease, and a two-fold decline in cMo/iMo ratio was revealed in patients with viral LC vs. healthy donors. These changes in monocyte pattern did not depend on the type of virus (HCV vs HBV/HDV) or its replication (replication vs the integrative phase), but were associated with the LC severity. The iMo level was positively correlated with laboratory indicators of liver damage, ChildPugh (rS = 0.57; P = 0.001) and MELD score (rS = 0.41; P = 0.033). ROC analysis showed that the cMo/iMo ratio at 9.5 allowed to predict the risk of LC progression with a sensitivity of 83.3% and a specificity of 76.2%. Of note, in comparison groups patients with alcoholic or biliary/autoimmune LC also demonstrated increased frequencies in iMo and nMo and decreased cMo/iMo ratio. However, in this case, the LC severity was negatively correlated with CD16+monocytes, particularly with the iMo and nMo subset, respectively, in alcoholic and biliary LC, evidencing the protective role of such cell subsets. Thus in viral LC the changes in circulating monocyte profile to increased iMO and nMo as well as decreased cMo are not associated with the virus type and replication; in contrast to the alcoholic and biliary/autoimmune LC, the level of iMo directly correlates with the indicators of liver damage and LC severity; cMo/iMo ratio is a biomarker of therapy response/disease progression.