Relationship Between Hepatic Pathology And Cellular Immune Status Of Patients With Chronic Hepatitis B Virus In Immune Tolerant Phase

AIM: To investigate the relationship between Hepatic pathology and cellular immune status of patients with chronic hepatitis B virus in immune tolerant phase. Method: Analysis the features of liver pathology and clinics in 98 cases of patients with chronic HBV in immune tolerance phase. 30 of them were also detected several items in peripheral blood and liver. Blood tests included T lymphocyte subsets quantity, mDC/ pDC amount and surfactant CD86 and CD83 expression, CD4~+ and CD8~+ T lymphocyte intracellular cytokine (IFN-γ, IL-4) staining and serum IL-10 and IL-12 testing by flow cytometry. Liver test including CD4~+ and CD8~+ T lymphocytes, CD83~+ Dendritic dendritic cells and IL-10 expression by immunohistochemistry.Result:1. 94.9% (93/98) of patients with HBV infection in immune tolerant phase existed liver inflammation, which were G1 (65.31%) and G2 (29.59%); 42.86% of patients existed liver fibrosis, which were 23.47% for S1,14.29% for S2, 5.1% for S3, no cirrhosis were found. Liver inflammation in patients with ALT≤ 20IU/L were lower than those with ALT ranged from 20 to 40 IU/L, showing no significant difference between these two groups (p> 0.05), the liver fibrosis stage in group of ALT ranged from 20 to 40 IU/L were severer than group of ALT ≤ 20IU/L, showing significant difference between these two groups(p <0.05).2. peripheral blood CD8~+ T cells quantities were higher and the ratio of CD4~+ /CD8~+ were lower in immune tolerant patients than healthy people and patients in immune clearance phase, showing significant difference(p <0.05, p <0.01, respectively), peripheral blood mDC quantities in immune tolerant patients were lower than healthy people, but higher than immune clearance patients, showing significant difference(p <0.05, p <0.01, respectively); The percentage of peripheral blood mDC in immune tolerant patients were lowerthan healthy people, but higher than immune clearance patients, showing significant difference(p<0.05, p <0.01, respectively); the expression percentage of CD86 which on the surface of mDC in immune tolerant patients were higher than healthy people, but lower than clearance patients, showing no significant difference (p>0.05 ) . The percentage of peripheral blood pDC in immune tolerant patients were similar to clearance patients, but lower than healthy people, showing significant difference(p <0.01).The expression percentage of CD86 which on the surface of pDC in immune tolerant patients were higher than healthy people and clearance patients, showing no significant difference (p>0.05 ) . The expression percentage of CD83 on pDC and mDC in immune tolerant patients were very low, and similar to each other group, showing no significant difference (p>0.05 ). Peripheral blood Th1 and Th2 in immune tolerant patients were higher than healthy people, but markedly lower than clearance patients, showing significant difference (p<0.01) ; Peripheral blood Tc1 and Tc2 in immune tolerant patients were lower than clearance patients, but showing no significant difference( p>0.05 ). The serum level of IL-12 in immune tolerant patients were higher than healthy people, but markedly lower than clearance patients, showing significant difference (p <0.05 ) ; The serum level of IL-10 in immune tolerant patients were higher than healthy people and clearance patients, but showing no significant difference (p>0.05 ) .3. The quantities of liver CD4~+ and CD8~+ T lymphocytes in immune tolerant patients were higher than healthy people, but markedly lower than clearance patients, showing significant difference(p<0.05); The ratio of CD4~+/CD8~+ in liver in immune tolerant patients were higher than healthy people and clearance patients, showing significant difference to compared with clearance patients (p<0.01) ; Mature DC in liver which express CD83 in immune tolerant patients were similar to the healthy people, but markedly lower than clearance patients, showing significant difference (p<0.05 ) ; Liver IL-10 in immune tolerant patients were slightly lower than healthy people, but higher than clearance patients, showing no significant difference (p>0.05) .Conclusion:1. Most of patients in immune tolerant phase exist mild liver inflammation, some of them have already appeared different stage of fibrosis, so it is limited to determine whether there is liver inflammation by ALT level alone. Patients which ALT are relatively high levels but within the normal range are more like to have fibrosis, ALT does not seem to be a sensitive indicator to determine liver injury, doctors should try to mobilize transhepatic checked and followed up.2. The increased quantities of intrahepatic CD8~+ T lymphocytes in immune tolerant patients suggest their bodies exist immune response against HBV, but because of some unclear reasons, the response are weak and insufficient to removal HBV, but it can lead to sustained liver damage, so liver disease may progress stealthily.3. The decrease of peripheral blood DC subsets and their surface costimulatory molecules in immune tolerant patients may be one of the mechanisms of the tolerant pathogenesis. The mature DCs in liver are not lack in different chronic HBV patients, especially in clearance patients. These results suggest that the reduction of peripheral DCs is more likely attributable to the re-distribution to liver. Liver mature DCs in tolerant patients were similar to healthy people, although there are lots of HBV antigens, therefore suggest a lack of mature DC in liver may be one of important reasons to weakened CTL response.4. According to the results of Thl/Th2 responses and serum cytokines level, Th1-type responses in immune clearance patients are stronger than tolerant patients, and tolerant patients are preferred to Th2 responses. The results of liver IL-10 show that liver microenvironments in tolerant patients were similar to healthy people. This microenvironments are preferred to immune tolerance, and are not conducive to the maturity of DC, and also are not conducive to stimulate cellular immunity. But meanwhile, it may be the self-protection strategy to avoid extensive liver injury when to clean a large number of HBV antigens.5. The results of blood and liver CD4+ and CD8+ T lymphocytes and dendritic show that immune tolerant patients does exist liver inflammation. In themeanwhile, the lack of mature DC in livers and higher levels of IL-10 in liver micro-environment tend to inhibit the inflammatory response. Therefore, most of the chronic HBV patients in immune tolerant phase show liver inflammation, but mainly are mild inflammation.6. From the results of comparing the liver and peripheral immune indicators, we know that although the related peripheral immune indexes are not representative of the actual situation in the liver, But some of them are similar to liver (such as IL-10), some of them (such as CD8~+ T lymphocytes, mDC, pDC) may indirectly speculation liver. So part of peripheral blood indicators may be presentative the status of liver, they have clinical value.