| Objective:1,To investigate the risk factors and prognosis of hepatitis B virus(HBV) recurrence after HBV related orthotopic liver transplantation with prophylaxis of combined low-dose hepatitis B immunoglobulin(HBlG) and nucleoside analogues and the prevent stragate of high risks of HBV recurrence patients.2,To investigate the clinical and pathological characteristics of HBV recurrence after HBV related liver transplantation.3,To explore intrahepatic immune in patients with HBV recurrence after liver transplantation.Method:1,This is a analysis of the clinical data of 253 patients who had liver transplantation for HBV related liver disease in our medical department from Apr 2005～Apr 2010 including mortality rate,time and cause of death,and so on.2,All patients received nucleoside analogues therapy formally before entering into the waiting list. And nucleoside analogues combined with low-dose HBIG therapy was prescribed during and after transplantation.Patients were regularly followed up by monitoring the HBV recurrence,survival and prognosis. Univariable analysis was performed to determine whether gender,age,concomitance with HCC,serum positive HBeAg,HBVDNA and YMDD mutants. Parameters with P<0.05 in the univariable analysis were entered into multivariate logistic regression analysis. To investigate the different availability of entecavir and lamivudine in patients with high risks of HBV recurrence.3,To analyse the clinical-pathological datas of 16 patients who had HBV recurrence after liver transplantation.4,Eleven liver biopsies,collected from HBV recurrent patients after OLT were detected with immunohistochemistry for the expression of intrahepatic CD3+,CD4+,CD8+,CD4+CD25+ regulatory T cell (Treg) T lymphocytes,and compared with 11 chronic hepatitis B(CHB) liver biopsies.Result:1,Before Apr 30,2010,29 patients died in the all 253 OLT patients. Mortality rate is 11.46% (29/253).21.21% (21/99) in HCC patients and nearly all cause of death were cancer recurrence. However, the death rate of non-HCC patients is 5.19% (8/154) and many people died around the operation.2,There were 16 HBV recurrence in 253 HBV related OLT patients and the recurrence rate is 6.32%(16/253). The median time of recurrence is 13 months. The first,third and fifth cumulative recurrence rate was respectively 3.81% (9/236),6.58% (15/228) and 7.14%(16/224). HBIG was terminated and nucleoside analogues was modulated in 19 patients who developed HBV. All patients HBVDNA was controlled less than 500IU/ml and liver fuction returned to normal. There was no significant difference in the survival rate between recurrence group and control group. Logistic regression analysis revealed that risk factors for HBV recurrence were HBeAg positive,HBVDNA positive,hepatocellula carcinoma and YMDD mutants. Further stratified analysis showed that patients whose HBVDNA load were over 105IU/ml and who suffered from carcinoma recurrence had a higher incidence of HBV recurrence than those who did not. There were 16 HBV recurrence petients in lamivudine group in which 26 patiences were dead. The recurrence rate is 7.92% (16/202). However, Entecavir group in which 3 patients were dead had no HBVrecurrence. The rate of death and HBVrecurrence was no significant in two groups. Further stratified analysis showed that the rate of HBVrecurrence in entecavir group was lower than in lamivudine group in these patience which had high risk factors for HBV recurrence.3,Chronic hepatitis is clinical manifestations of HBV recurrence after OLT. The histological changes in the transplanted livers were hepatocellular degeneration,necrosis and apoptosis,portal infiltrations and fibrosis. Fibrosing cholestatic hepatitis(FCH) was in serious condition with high mortality. With time after recurrence,it was easier to see hepatitis B virus replication in liver cells,incidence of acute rejection,increases of liver fibrosis and the formation of fibrous septa,even pseudolobule.4,Lymphocyte infiltrate mainly in the portal area. The number of CD3+,CD4+,CD8+ T cells were reduced and the numbers of Treg were increased significantly in HBV recurrent patients after OLT compared with those in CHB(P<0.05). The expression of Treg were associated with pathology grade. The high expression of Treg was associated with the high viral load and the positive immunohistochemical expression of HBsAg,HbeAg were enhanced.Conclution:1,OLT is an effective treatment for the HBV correlated end-stage liver disease. HBV recurrence is not the main cause of graft loss and death under the prophylaxis of nucleoside analogues and low-dose HBIG. The high risk factors for HBV recurrence were HBeAg positive,HBVDNA load over 105IU/ml,hepatocellula carcinoma, carcinoma recurrence and YMDD mutants. Combination of entecavir and intramuscular HBIG as the prophylaxis of HBV recurrence is more effective than the lamivudine and intramuscular HBIG group especially to the patients with the high risks of HBV recurrence.2,Immunosuppression exists in HBV recurrent patients after OLT. With native HBV infection livers, Clinical manifestations and pathological damage is lighter,but fibrosis occurs more early and develop rapidly. The number of virus is closely related to liver necrosis and inflammation.3,Compared with chronic hepatitis B patients,the role of virus itself may be the main reason for the HBV recurrence patients in pathogenic mechanism. Intrahepatic Treg may play important roles in immune suppression, control of liver inflammation and viral replication.
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