| Background and Objectives:About1million people die from chronic HBV infection related diseases (such as Liver cirrhosis and hepatocellular carcinoma) each year. HBV infection seriously threatens human health. HBV consists of four open reading frames (ORF), including S, P, C and X regions, the X protein (namely HBxAg) which has various sorts of regulative functions is encoded by the smallest X reading frame. HBxAg has the function of trans-acting, it can affect viral transcription and replication, signal transduction and apoptosis through interaction with host factors. As confirmed, HBxAg has a two-way role in cell apoptosis. An important way to induce apoptosis is death receptor-mediated pathway, and the typical death receptor pathway is Fas/Fas-L pathway. The relationship among HBxAg, Fas and Fas-L in HCC patients has been reported. But in HBV Chronic infection, LC and HCC patients, the comparative study among these3indexes is not reported yet. To further investigate the role of HBxAg in disease progression and hepatocarcinogenesis, we studied and explored comparatively HBxAg and Fas/Fas-L proteins in liver tissue of HBV-related liver diseases.Methods:We randomly selected78liver puncture or surgical resection specimens and clinical dates from Jinan infectious hospital ang Shandong Provinical hospital, including38patients of HBV chronic infection (As part of normal liver function patients has inflammatory activity, it is difficult to distinguish HBV carriers from mild hepatitis, so this article channeled for HBV chronic infection),20patients of liver cirrhosis and20patients of hepatocellular carcinoma. Liver inflammation grade and fibrosis stage according to Knodell standard. The expressions of HBxAg, Fas and Fas-L in the liver tissues of3groups were detected by an immunohistochemical staining technique. The experimental results were analyzed with the SPSS17.0software. Count data applicated X2test and Fisher’s exact method, pariwise comparisons between multiple samples applicated x2split method, ranked data applicated rank sum test, the correlation analysis using Spearman rank correlation.Results:1. HBxAg mainly distributed in the cytoplasm and nucleus of liver cells, and no obvious staining was found outside the liver cells. The positive rates of HBxAg in HBV chronic infection, LC and HCC patients were71.1%,60.0%and65.0%respectively, there were no statistical significance in HBxAg positive rates(X2=0.754,P=0.686) and expression intensity(X2=3.070,P=0.215) differences among the3groups.2. Fas can be found in the portal area, liver cells, lymphocytes and monocytes in the interstitial tissue of tumor tissues. The positive rates of Fas in liver cells of HBV chronic infection, LC and HCC patients were28.9%,20.0%and5.0%respectively, there were no statistical significance in positive rates (X2=4.667,P=0.101) and expression intensity(Z=4.000,P=0.135) differences among the3groups. The positive rates of Fas in the lymphocytes of3groups were68.4%,60.0%and90.0%respectively, and no significantly statistical difference (X2=4.861,P=0.088) existed between the3groups. However, the expression intensity differences has statistical significance(X2=17.442, P=0.00016), in which the expression intensity was higher than HBV chronic infection patients(Z=-4.360, P=0.00001).3. In the3groups, Fas-L were not found in intrahepatic lymphocytes.The positive rates of Fas-L in liver cells of3groups were36.8%,45.0%and60.0%respectively, the positive rates(x2=2.988,P=0.225) and expression intensity (x2=4.343,P=0.114)differences among3groups have no statistical significance.4. In the severe inflammation area of LC patients and some HCC patients, we can see HBxAg and Fas-L expression abundantly in the same area.5. In HBV chronic infection and LC patients, the expression of HBxAg was positively correlated with Fas(r=0.304, P=0.02) and Fas-L(r=0.368, P=0.004). The expression of Fas was also positively correlated with Fas-L(r=0.448, P=0.0004). HBxAg has no correlation with inflammation grad(r=0.109, P=0.415) and liver fibrosis grade(r=-0.015, P=0.908).6.38patients of HBV chronic infection,20patients of LC and10patients of HCC(10patients lack serum HBVDNA quantitative test results) serum HBVDNA quantitative results to take logarithmic and divided into3groups:<31og,3-61og and^61og. The results showed that the HBxAg expression increased with increasing viral load, and significantly statistical difference existed among the3groups(X2=17.106,P=0.0002). Compared with<31og group, the positive rate of HBxAg in≥61og group is higher(X2=16.800,P<0.05). The positive rates difference of HBxAg in3-61og and<31og groups has statistical significance (X2=6.930,P<0.05).7. HBxAg has no correlation with sex, age and e antigen state (X2were1.973、0.707and2.649, P>0.05). The positive rate of HBxAg expression in group of ALT>40U/L is higher than that of≤40U/L group (X2=7.736, P<0.01).Conclusions:1. HBxAg plays an important role in various stages of chronic HBV infection. In the early stage, HBxAg mainly induces liver cells apoptosis by up-regulating Fas expression, while in the later stage, HBxAg mainly induce immune escape by up-regulating Fas-L expression in liver cells.2. HBxAg and high HBV load may play key role in development of HBV chronic infection as well as hepatocarcinogenesis. |
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