Increased CD163and SCD163Is Associated With Acute-on-Chronic Hepatitis B Liver Failure And Hepatocellular Carcinoma

INCREASED CD163AND SCD163IS ASSOCIATED’ ACUTE-ON-CHRONIC HEPATITIS B LIVER FAIL ABSTRACTHepatitis B virus (HBV) infection is an important health problem worldwide. It is thought to be one of the main causes of liver related chronic and acute diseases. With severe acute exacerbation of the disease, some chronic hepatitis B (CHB) patients may progress to liver failure. We define this progression as acute-on-chronic hepatitis B liver failure (ACHBLF). It constitutes about70%of all ACLF in areas with a high incidence of hepatitis B.ACHBLF has an extremely poor prognosis due to a lack of understanding of its pathogenesis. Thus reducing the morbidity and mortality of hepatic failure patients has become a research hotspot. The search for biomarkers which can predict hepatic failure can strengthen the monitoring and treatment of patients with liver failure and reduce the incidence and mortality of ACHBLF. Current clinical research found that there was very close relationship between the pathogenesis of ACHBLF and strong immune response. Therefore, it is very important to fully understand the immune response of ACHBLF.In recent years, the extensive research in CD163make it possible to be an effective indicator and therapeutic target, which can be detected easily. The research of CD163is still in its infancy. However, their diagnostic and prognostic potential in patients with ACHBLF patients has not been investigated yet. That is the focus and direction of our research.Objective:To study the expression and significance of CD163in ACHBLF patients. We detected the surface CD163in peripheral blood mononuclear cells (PBMCs) and sCD163in peripheral blood in ACHBLF patients. We want to know the relationship between the expression of CD163, sCD163and the prognosis of patients with ACHBLF patients, and their relationship with clinical indexes and clinical significance. Methods:We detected the frequency of CD163+PBMCs using flow cytometry(FCM). We also evaluated the average mean fluorescence intensity (MFI) of CD163+PBMCs using FCM. Real-time transcription-polymerase chain reaction (RT-PCR) was performed to assess relative CD163mRNA levels in PBMCs. We evaluated the plasma levels of sCD163by enzyme linked immunosorbent assay (ELISA).Results:1. CD163positive in PBMCs in patients with ACHBLF is significantly higher than CHB patients and healthy controls(HCs), there were significant differences within three groups. However, there were no significant differences in MFI in CD163+PBMCs within three groups.2. CD163mRNA expression in ACHBLF patients was significantly higher than CHB patients and HCs, there were significant differences within three groups.3. Plasma sCD163expression was significantly elevated in patients with ACHBLF, and was significantly correlated with the prognosis of patients. There were significant differences within three groups.4. Plasma levels of sCD163were positively correlated with MELD score, plasma HBV-DNA levels and negatively correlated with PTA, but had no correlation with TBIL.5. CD163positive in PBMCs in CHB patients was significantly higher than that in HCs.6. CD163mRNA expression in CHB patients was higher than that of HCs, there was no significant difference between two groups.7. Plasma sCD163expression was significantly elevated in patients with CHB, there was significant difference between two groups.Conclusion:As expressed in the macrophage surface specific, CD163plays an important role in patients with ACHBLF and CHB in the pathogenesis.The research suggested that CD163and sCD163can be used as useful biomarkers for ACHBLF. SCD163detection is more simple and direct, with more significant group differences. It is significantly correlated with the severity of the disease. CD163and sCD163can be used as index of prognosis in patients with liver failure, and negatively correlated with the prognosis of the patients. 英文摘要第二部分INCREASED CD163AND SCD163IS ASSOCIATED HEPATOCELLULAR CARCINOMA ABSTRACTPeople who have hepatitis B are prone to have a much higher risk of suffering from hepatocellular caicinoma(HCC). Some scholars think that people who have chronic hepatitis B and liver cirrhosis with hepatitis B may have the probability of suffering from HCC9to10times higher than that of normal people. More than80%of HCC patients have hepatitis B virus infection. In all of the malignant tumors, HCC have mortality rates as high as the fifth. Its five-year survival rate is less than5%. These data show that understanding of the pathogenesis, early diagnosis and risk assessment in patients with HCC are very important. However, we lack of effective early prediction and monitoring method of HCC.It is widely interested that TAMs have an anti-inflammatory function resembling M2macrophages. CD163is a M2macrophages specific marker and macrophage activation marker. Its high expression can promote tumor angiogenesis, restructuring, affecting fibrosis tissue cells, organizing reconstruction process. It plays an important role in the pathological process of tumors and acute or chronic inflammation of the liver diseases.Nevertheless in the former part of experiment, we have found the high levels of CD163expression in patients with ACHBLF. We also found the relationship between the expression of CD163and sCD163and clinical prognosis in acute inflammation process. In this experiment, we selected the patients with HCC as the research object. CD163and sCD163may play an important role in patients with HCC. We are eager to know its relationship between the prognosis and clinical indexes, and look for the new direction of treatment.Objective:To study the expression and significance of CD163in HCC. We evalues the surface CD163on peripheral blood mononuclear cells (PBMCs) and the expression of sCD163in peripheral blood. We would like to understand the relationship between the expression of CD163and sCD163and the prognosis of patients with HCC and their relationship with clinical indexes and clinical significance.Methods:We determined the frequency of CD163+PBMCs using flow cytometry (FCM). We also evaluated the average mean fluorescence intensity (MFI) of CD163+PBMCs using FCM. Real-time transcription-polymerase chain reaction (RT-PCR) was performed to assess relative CD163mRNA levels in PBMCs. We evaluated the plasma levels of sCD163by enzyme linked immunosorbent assay(ELISA).Results:1. CD163+mononuclear cells increased significantly in patients with hepatocellular carcinoma (HCC), compared with liver cirrhosis (LC), chronic hepatitis B (CHB) and healthy controls (HCs) with significant difference. There was significant difference in mean fluorescence intensity(MFI) of CD163+PBMCS within groups.2. In patients with HCC, CD163mRNA expression is much higher than the patients of CHB and HCs.There was significant difference within groups.3. sCD163in plasma increased significantly in patients with HCC, and has close relationship with the prognosis of patients with HCC. There were significant differences within groups.4. CD163+mononuclear cells increased significantly in patients with LC, compared with CHB and HCs with significant difference.5. In patients with LC, CD163mRNA expression is higher than the patients of CHB and HCs. There was significant difference within groups.6. sCD163in plasma increased higher in patients with LC, compared with the patients of CHB and HCs with significant differences. 7. sCD163in plasma increased significantly in patients with HCC had no associations with AFP、HBV-DNA and HBeAg.8. There is no correlation between sCD163concentration and Italian CLIP scores. According to a2002AJCC international staging, namely the TNM staging, sCD163concentration in patients with HCC in phase Ⅲ of distant metastasis and Child C level was higher than patients in the stage Ⅰ, stage Ⅱ, but with no significance.Conclusion:CD163plays an important role in patients with HCC、LC in the pathogenesis. The research suggested that CD163and sCD163can be used as useful biomarkers in the treatment of patients with HCC. SCD163detection is much simpler and direct. It is significantly correlated with the severity of the disease. 英文摘要第三部分CD163REVIEW ABSTRACTForm and structure of CD163Monocytes and macrophages play an important role in the human immune system. Macrophages can be divided into M1subsets and M2subsets, which have proinflammatory and anti-inflammatory effects respectively. CD163only express on the macrophage surface of M2type. It belongs to the scavenger receptor cysteine rich domain family B and is a I type protein with130kD weight. It has5homologous isoforms, with structure containing9scavenger receptor cysteine rich domains. CD163has two forms in vivo:one is a transmembrane molecule existing in the form of mononuclear macrophages; the other one present in the blood or other tissue fluid, soluble, namely sCD163.Role of CD163CD163can specifically recognize haptoglobin hemoglobin complex and is a hemoglobin specific scavenger receptor. Through the clearance of free hemoglobin, it can adjust the body’s immune function. CD163can also identify factor of apoptosis (TWEAK). With its specific binding, it plays an important role in monitoring gram positive bacteria and gram negative bacteria. With inflammation stimulation, it can also promote monocyte adhesion to epithelial cells and induction of inflammatory mediators, such as inflammatory factors IL-10.Relationship between CD163and various diseasesCD163and sCD163have a close relationship with the immune system. Several clinical and laboratory studies found that CD163and sCD163are very closely related with various diseases, such as inflammation, tumor, cardiovascular or cerebrovascular diseases. In severe burns, acute liver failure and other serious inflammatory diseases, CD163increased significantly and related with prognosis. CD163increased significantly in HCC and malignant lymphoma, especially in patients with lymph node metastasis and poor response to therapy. It suggests an important role of CD163in prognosis of tumor patients. CD163and sCD163have been clearly proved to be significantly associated with the prognosis of the diabetes、hyperlipidemia and coronary heart disease.CD163and sCD163play important roles in anti-inflammation and promoting cancers, which make them popular in biological targets for future research and have already achieved initial success.