Pathological Features Of Liver Tissue And Immune Mechanism Of Liver Injury In Patients With Chronic Active Epstein-barr Virus Infection

Part one: The clinical and pathological features of patients with chronic active Epstein-barr virus infectionObjective: To analyze and summarize the clinical and pathological features of patients with chronic active Epstein-Barr virus infection(CAEBV)at our hospital,and to improve the early diagnosis and treatment of CAEBV.Methods: Five patients with CAEBV at our hospital was included.Their data were analyzed the data retrospectively,including general condition,medical history,laboratory test results and pathological examinations.The pathological characteristics were analysed by examination of liver bisospy.Results:1.Clinical characteristics: Most of the patients were young(male:female=4:1),the median age was 16 years old.The most common clinical manifestations were persistent fever,liver dysfunction,hepatosplenomegaly,and even giant spleen in some patients(3/5).Some patients also had manifestations in nervous system,respiratory system and other extrahepatic systems.2.Laboratory test characteristics:All patients had reduced blood cell counts,including reduced white blood cell,platelets and CD8+T lymphocytes.All patients experienced liver dysfunction with elevated GGT,ALP and TBIL.3.Pathological characteristics:Diffuse bullous steatosis of the liver(5/5),infiltration of lymphcytes and monocyte in the liver lobules and the portal area,enriched Kupffer cells in the liver sinus,the ‘string' alignment of the lymphocytes,mild hyperplasia of fibrous tissue in the portal area and intrahepatic cholestasis.4.Poor prognosis:Five patients were treated with liver-protecting drugs,antiviral agents(ganciclovir or acyclovir)and immunity-regulating drugs.Two patients died within 3 years(40%).Conclusion:1.The clinical manifestations and signs of patients with chronic active Epstein-Barr virus infection were diverse.The main clinical manifestations were persistent fever,liver dysfunction,hepatosplenomegaly and giant spleen.It is refractory to current treatments and the mortality is high.2.The pathological features of CAEBV were bullous steatosis of the liver,infiltration of inflammatory cells and intrahepatic cholestasis.Part two:Detection and analyzation of the immune cells in liver tissue of patients with chronic active Epstein-barr virus infectionObjective: To investigate the immune risk factors for the liver injury in patients with CAEBV by observing the expression of immune cell types,perforin and granzyme B in the liver tissue of CAEBV patients.Methods:The CAEBV patients were included in the study group.Their liver tissues were harvested.Patients with pathologically confirmed hepatic hemangioma were included in the control group.Immunohistochemistry were used to detect the expression of CD3+,CD4+,and CD8+T lymphocytes,CD56 + NK cells,CD20+ B lymphocytes,perforin and granzyme B in the liver tissue of the two groups.Results:1.The general data: The age and sex between CAEBV group and control group had no significant difference(z=1.162,p=0.343),respectively.ALT(64.9(49,384)U / L vs 17.75(12,38.6)U / L,p=0.029),AST(219.25(59,328)U / L vs 21.6(15,24.7)U / L,p =0.029),liver inflammatory activity score(1(1,2)vs 0(0,1),p=0.029)and steatosis degree score(2(1,3)vs 0(0,0),p=0.029)had significant difference between theCAEBV group and the control group.2.CD8+T lymphocytes:The numbers of CD8 + T cells in the liver tisse of CAEBV patients was significantly higher than those in the control group(z=2.309,p=0.029).3.CD3+T lymphocytes,CD4+T lymphocyte,CD56+ NK cells,CD20+B lymphocytes:The CD3+T lymphocytes(z=2.201,p=0.057),CD4+T lymphocyte(z=0.866,p=0.486),CD56+ NK cells(z=1.899,p=0.057)and CD20+ B lymphocytes(z=0.145,p=0.886)had no significant difference between the CAEBVgroup and the control group.4.The expression of perforin and granzyme B: Only one patient was positive for the expression of granzyme B and perforin in the CAEBV group.The expression of perforin and granzyme B in the control group was negative.Conclusions: The numbers of CD8+ T lymphocytes in CAEBV patients was higher than those in the control group,suggesting that CD8 + T lymphocytes played a role in the liver injury of CAEBV patients.The roles of perforin and granzyme B in CAEBV liver injury remained to be further studied.Part three:Expression and Significance of Complement components in Patients with Chronic Active Epstein-Barr Virus InfectionObjective:To observe the expression of complement components in the liver tissue of patients with chronic active EB virus infection and to explore the role of humoral immune response in the liver damage in patients with chronic active EB virus infectMethods: The inclusion criteria were same as those in Part Two.C1 q,C3d,C4 d were detected using immunohistochemistry assay.Results:1.The age and sex between the CAEBV group and the control group had no significant difference(z=1.162,p=0.343).ALT(64.9(49,384)U/ L vs 17.75(12,38.6)U/L,p=0.029),AST(219.25(59,328)U/L vs 21.6(15,24.7)U/L,p=0.029),liver inflammatory activity score(1(1,2)vs 0(0,1),p=0.029)and steatosis degree score(2(1,3)vs 0(0,0),p=0.029)had significant difference between the CAEBV group and the control group.2.Complement:(1).C1q:C1q deposition was observed in the liver tissue of four CAEBV patients,which was in the subendothilial area of the hepatic sinusoid and the Gission capsule.However,C1 q was not found in the liver tissue of the control group.The difference of C1 q in the subendothilial area of the hepatic sinusoid(c(17)=4.5,p=0.029)and the Gission capsule(c(17)=4.5,p=0.029)between the two groups were statistically significant.(2).C3d: C3 d deposition was observed in the liver tissue of all four patients in the CAEBV group,which was in the subendothilial area of the hepatic sinusoid(4/4,100%)and the Gission capsule(4/4,100%).No C3 d depositionwas found in the subendothilial area of the hepatic sinusoid but was observed in the Gission capsule(2/4,50%)of the patients in the control group.There was significant difference between the two groups in the subendothilial area of the hepatic sinusoid(c(17)=4.5,p=0.029).But there was no significant difference between the two groups in the Gission capsule(c(17)=0.667,p=0.429).(3)C4d: C4 d deposition was not found in the liver tissue of the paitents in either the CAEBV group or the control group.Conclusion: The C1 q and C3 d expression can be found in the liver tissue of patients in the CAEBV group.It is suggested that humoral immune response may play a role in the mechanism of liver injury in CAEBV patients.