Significance of C-Reactive Protein and Interleukin-6 as a Marker of Severity of Different Stages of Liver Cirrhosis

Abstract

Liver cirrhosis, the end-stage of various liver diseases, has a poor prognosis, which is determined by deterioration of hepatic functional capacity and consecutive development of hepatic complications. Egypt is a heavily populated country, with a strikingly high hepatitis C virus (HCV) infection prevalence of 26%. The high prevalence of chronic liver diseases in Egypt has led to increasing numbers of Egyptian patients suffering from end-stage liver disease. The severity of cirrhosis is important to assess because it serves as a predictor of patient survival, surgical outcomes, and the risk of complications such as variceal bleeding. Assessment tools commonly used in patients with cirrhosis include the model for end-stage liver disease (MELD), which has a score ranging from 0 to 40; and the Child-Pugh classification system, which has a score ranging from 0-15. C-reactive protein (CRP) is a pleiotropic protein produced predominantly in the liver in response to interleukin 6 (IL-6) stimulus. C-reactive protein is believed to have a variety of functions: enhancement of Summary and Conclusion - 174 - phagocytosis through classical complement activation, increased expression of endothelial adhesion molecules, and up-regulation of proinflammatory (IL-8, tumor necrosis factor α, and plasminogen activator inhibitor 1) and anti-inflammatory (IL-10, interferon γ, and IL-1β) cytokines. Interleukin-6 (IL-6) is a proinflammatory cytokine which plays an important role in the host defence mechanism. Serum IL-6 levels are low in physiological conditions, but increase considerably in pathological conditions such as trauma, inflammation and neoplasia. In tumors, IL-6 may be involved in promoting the differentiation and growth of target cells. In fact, several neoplastic cell lines (such as esophageal cancer, renal cell carcinoma, multiple myeloma, prostate and ovarian cancer) have been shown to produce high in vitro levels of IL-6, and high concentrations of this cytokine are associated in vivo with a poor outcome of the disease in many types of tumours. The value of CRP might be a predictive marker for the evolutionary stages of the liver cirrhosis. Further research is necessary in order to consider the value of CRP as a standard parameter for the prediction of liver cirrhosis evolution. Summary and Conclusion - 175 - It is well established that the life expectancy of patients with liver cirrhosis is closely linked to the degree of liver dysfunction and the occurrence of clinical complications, and powerful prognostic tools such as the Child-Pugh score or the MELD score exist to predict short- and long-term survival. However, alterations in inflammation-related components, such as TNF-α, IL-6 or adhesion molecules like ICAM-1, have been shown to be of prognostic significance in cirrhotic patients. Some studies reported that there is a correlation between serum levels of CRP, IL-6 and liver diseases especially those with liver cirrhosis in whom CRP and IL-6 detected in their serum. This study was designed to assess the association between elevated levels of serum CRP, IL-6 and different stages of liver cirrhosis, also to explore the significance of serum levels of CRP, IL-6 as markers of severity of liver cirrhosis.