OBJECTIVETo evaluate the effect of perioperative HLA antibody changes on acute allograft rejection in cadaveric liver transplantation.

METHODSTotally 134 patients received modified piggyback liver transplantation and enzyme-linked immunosorbent assay was performed for HLA antibody detection before and the 1, 7, 14 and 30 days after operation. B ultrasound-guided liver biopsy was employed for diagnosis of acute allograft rejection, and the perioperative changes of HLA antibodies were evaluated for their effect on allograft acute rejection.

RESULTSOf the 44 recipients with preoperative positivity for HLA antibodies, acute rejection occurred in 56.8% of the patients, as compared with 25.9% in those negative for HLA antibody (P=0.001). The patients who became positive for HLA antibody postoperatively had a rate of acute rejection of 60%, which was significantly higher than that in those persistently negative for HLA antibody (18.6%, P=0.003).

CONCLUSIONHLA antibody positivity before transplantation may contribute to acute rejection episode in liver transplantation, and persistent posttransplant HLA antibody positivity is closely associated with the occurrence of acute rejection.

Adult ; Aged ; Antibodies ; blood ; Female ; Graft Rejection ; immunology ; HLA Antigens ; immunology ; Humans ; Isoantibodies ; blood ; Liver Cirrhosis ; surgery ; Liver Neoplasms ; surgery ; Liver Transplantation ; immunology ; methods ; Male ; Middle Aged

OBJECTIVETo summarize the treatment experience of long-term surviving patients after combined abdominal organ transplantation.

METHODSFrom October 2001 to January 2005, 19 patients received combined abdominal organ transplantation in Nanfang Hospital, including 6 with simultaneous kidney-pancreas transplantation (SKPT), 12 with combined liver-kidney transplantation (CLKT), and 1 with simultaneous liver-pancreas transplantation (SLPT). The periods of follow up were from 6 months to 3 years and 8 months. Summarize primary diseases of the patients, factors which impacted on patients long-term survival rate, and immunological characteristics of combined abdominal organ transplantation.

RESULTSAll of 19 transplant cases were performed successfully. Among then, 18 were followed up; 16 survived till now; 2 patients undergoing liver-kidney transplantation were dead, one of which died from myocardial infarction in the 18 months after operation, and one died from cytomegalovirus in infection of lung in 13 months; 1 liver-kidney transplantation patient and 2 pancreas-liver transplantation patients experienced acute rejection once; 2 patients were found nephrotoxicity. Among the 18 patients, 4 patients' survival time were over 3 years, 7 over 2 years, 6 over 1 year, 1 over 10 months.

CONCLUSIONSCombined abdominal organ transplantation is effective for treatment of two abdominal organ failure diseases. Factors which impact on patients long-term surviving include choosing suitable recipient, high quality of donated organ, avoidance of surgical complication, the history of myocardial infarction before operation, immunosuppressive regime and virus infection late after transplantation. Combined abdominal organ transplantation has some different immunological characteristics from single organ transplantation.

Adult ; Aged ; Duodenum ; transplantation ; Female ; Follow-Up Studies ; Humans ; Kidney Transplantation ; immunology ; methods ; mortality ; Liver Transplantation ; immunology ; methods ; mortality ; Male ; Middle Aged ; Pancreas Transplantation ; immunology ; methods ; mortality ; Treatment Outcome

OBJECTIVETo study the effect and implication of nonmyeloablative donor specific bone marrow (DSBM) infusion on the immunoreaction of liver allotransplantation.

METHODSOrthotopic liver transplantation model was used in this study. Groups were set as follows: Group I, syngeneic control (Wistar-to-Wistar); Group II, acute rejection (SD-to-Wistar); Group III, acute rejection treated with cyclosporine A (CsA) by intramuscular injection (SD-to-Wistar+CsA); Group IV, bone marrow infusion at 7 d pretransplantation followed by short-term CsA treatment (SD-to-Wistar+DSBM); Another group of short-term CsA treatment preoperatively without bone marrow infusion was also set as control. General characteristics and survival time were observed. Histological grades of rejection were determined by pathological examination. IL-2 and IFN-gamma level in peripheral blood and donor liver were detected respectively by Enzyme-Linked Immuno-Sorbent Assay (ELISA) and Western blot. Chimerism of donor cells was measured by PCR for a male-specific marker (Y-chromosome-specific sequence, Sry).

RESULTSNo signs of rejection were found in Group I. Acute rejection occurred in both Group II and the short-term CsA treated group. All the recipients died at (9-15) d posttransplantation with a median survival time of (10.7+/-0.5) d and (11.2+/-2.4) d, respectively. Only mild rejection could be seen in Group III. In Group IV, 4 out of 6 recipients had long-term survival (>100 d), the histological grade of rejection was significantly lower than that of Group II, so did the expression level of IL-2 and IFN-gamma in both peripheral blood and grafted liver. Y-chromosome-specific sequence (Sry) of male SD rats could be detected in the bone marrow, spleen and thymus of female recipients at 15 d after bone marrow infusion.

CONCLUSIONMild preconditioning nonmyeloablative donor specific bone marrow infusion can enhance chimerism formation in recipients, alleviate the rejection of liver allotransplantation and prolong survival of liver allotransplantation.

Animals ; Bone Marrow Transplantation ; immunology ; methods ; Graft Rejection ; etiology ; immunology ; prevention & control ; Liver Transplantation ; adverse effects ; immunology ; Male ; Rats ; Rats, Inbred Strains ; Rats, Wistar ; Transplantation, Homologous ; adverse effects ; immunology ; Treatment Outcome

OBJECTIVETo evaluate the outcomes of liver transplant recipients who received liver allografts from hepatitis B surface antigen (HBsAg)-positive donors.

METHODSThe medical records of 23 male patients (median age, 42.5 years; range: 29-61) who received HBsAg-(+) liver allografts in our organ transplant center were retrospectively analyzed. All patients had confirmed diagnosis of end-stage liver disease (ESLD) secondary to hepatitis B virus (HBV) infection, including 13 HBsAg(+)/HBeAg(-)/HBcAb(+) cases and 10 HBsAg(+)/HBeAb(+)/HBcAb(+) cases. After transplantation, all patients were administered oral entecavir and intravenous anti-hepatitis B immunoglobulin (HBIG) (2000 IU/d during the first week), along with a steroid-free immune suppression regimen. HBV-related antigen and antibody and HBV DNA were detected on post-transplantation days 1, 7, 14, 21, and 30. The liver allografts were monitored by ultrasound imaging. After discharge, monthly follow-up recorded liver function, renal function, acute rejection, infections, vascular complications, biliary complications, HBV recurrence, cancer recurrence, and patient survival.

RESULTSTwo of the recipients died from severe perioperative pneumonia. The remaining 21 recipients were followed-up for 10 to 38 months, and all 21 patients remained HBsAg(+). One recipient developed biliary ischemia and required a second liver transplantation at five months after the primary transplantation. Three recipients (all primary) died from tumor recurrence at 9, 14, and 18 months post-transplantation, respectively. All other recipients survived and had acceptably low HBV DNA copy levels. Color Doppler imaging showed good graft function and normal texture. The patient and graft survival rates were 78.3% (18/23) and 73.9% (17/23), respectively. The recurrence rate of HBV infection was 100% (23/23). In surviving patients, no liver function abnormality, graft loss, or death was found to be related to the recurrence of HBV infection.

CONCLUSIONLiver transplantation using HBsAg(+) liver grafts was safe for patients with ESLD secondary to HBV infection.

Adult ; End Stage Liver Disease ; surgery ; virology ; Hepatitis B Surface Antigens ; immunology ; Humans ; Liver Transplantation ; immunology ; methods ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Tissue Donors

OBJECTIVETo evaluate the effects of newborn rat hepatocyte intrasplenic transplantation combined with rat augmenter of liver regeneration (rALR) injection in treating rats with acute hepatic failure.

METHODSAcute hepatic failure (AHF) was induced in rats using D-gal (1.2 g/kg). The rats were then randomly divided into 6 groups. Group I received no further treatment and served as blank controls; group II received 1 ml buffered saline once through intrasplenic injection; group III received 1 ml rALR; group IV received 2 x 10(7)/ml hepatocytes; group V received 2 x 10(7) hepatocytes suspended in 1 ml rALR (50 microg/kg) and group VI received 2 x 10(7) hepatocytes in 1 ml cyclosporine A (10 mg/kg). The rats of the various treated groups were sacrificed at day 1, 5 and at week 2 and their livers and spleens were examined histopathologically. Blood samples of the rats were also obtained to determine the levels of TNF alpha and IL-1 beta.

RESULTSThere were no significant differences in survival between group I, II and III rats. 33.3% of the group IV rats survived for 2 weeks. At week 2, the survival rate of group V rats was significantly higher than that of group IV, but there was of no statistical significant increase when compared to that of group VI rats. Hepatocytes transplanted into spleens survived for 5-7 days in the spleens of group IV and VI rats, but they survived at least 2 weeks in group V. The average serum TNF alpha level in group IV was significantly higher than that in groups V and VI on the first postoperative day, but after four days, only the difference between group IV and group VI was significant (P < 0.05). The average serum level of TNF alpha in group II was higher than that in groups IV, V and VI on the first postoperative day (P < 0.05), but there were no significant differences between those in groups IV, V and VI on the 1st and the 5th postoperative days.

CONCLUSIONNewborn rat hepatocyte intrasplenic transplantation combined with rALR is effective in treating acute hepatic function failure induced by D-gal in rats. The transplanted hepatocytes can survive for at least 2 weeks in the spleens. The rALR mixed with the hepatocytes injected into the spleens may be able to facilitate the hepatocyte regeneration, to inhibit liver cell apoptosis and to suppress the cellular immunity.

Animals ; Cell Transplantation ; methods ; Female ; Hepatocytes ; transplantation ; Liver Failure, Acute ; immunology ; surgery ; Liver Regeneration ; Male ; Proteins ; therapeutic use ; Rats ; Rats, Wistar ; Spleen ; surgery

Adult ; Hepatitis B ; prevention & control ; Humans ; Immunity, Active ; Liver Transplantation ; immunology ; methods ; Male ; Postoperative Complications ; prevention & control

OBJECTIVETo explore the role of stem cell mobilization on regeneration of partially grafted livers.

METHODSRats models with cross-sex 50% PLTx (partial liver transplantation) were established. The rats were divided into three groups: PLTx, WLTx (whole liver transplantation) and sham operation groups. Bone marrow and liver samples were collected on days 1, 3, 5, 7 postoperatively (each n = 6). The quantitative variations of the cells with stem cell markers in the bone marrow, including beta2m-/Thy-1.1+, CD45+/CD34+, Flt2/3+ and c-kit+ markers, were detected using flow cytometry. Sry gene positive cells in donor livers were detected by fluorescent in situ hybridization (FISH), and the expressions of CD34, c-kit and Thy-1.1 were detected by immunohistochemistry technique.

RESULTSCompared with the WLTx and sham operation groups, beta2m-/Thy-1.1+, CD45+/CD34+ cells in bone marrows in the PLTx group increased on the first postoperative day and decreased on the following days. The CD34, c-kit and Thy-1.1 positive cells detected in portal tract areas peaked during the 3-5 postoperative days. CD34+/CD45+ positive cells could be detected. The expressions of CD34, c-kit and Thy-1.1 positive cells were rare in the WLTx and sham operation groups. Sry+ cells could be detected in portal tract areas and few Sry+/CD34+ and Sry+/Thy-1.1+cells were detected.

CONCLUSIONIn the PLTx group, the stem cells in the bone marrow were mobilized and stem cells in the liver were activated.

Animals ; Antigens, CD34 ; immunology ; Bone Marrow Cells ; cytology ; immunology ; Female ; Hematopoietic Stem Cell Mobilization ; Leukocyte Common Antigens ; immunology ; Liver Transplantation ; methods ; Male ; Rats ; Rats, Sprague-Dawley ; Stem Cells ; cytology ; immunology ; Thy-1 Antigens ; immunology

Adenoviridae ; genetics ; Animals ; Cell Transplantation ; methods ; Gene Transfer Techniques ; Genetic Therapy ; methods ; Graft Rejection ; prevention & control ; Hepatocytes ; immunology ; transplantation ; Humans ; Liver ; metabolism ; Liver Failure ; surgery ; Simian virus 40 ; genetics ; Transfection ; Transplantation, Homologous

Currently, the most effective treatment for end-stage liver fibrosis is liver transplantation; however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently, mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases. MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immune-modulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality. Despite these advantages, issues remain; MSCs also have fibrogenic potential and the capacity to promote tumor cell growth and oncogenicity. This paper summarizes the properties of MSCs for regenerative medicine and their therapeutic mechanisms and clinical application in the treatment of liver fibrosis. We also present several outstanding risks, including their fibrogenic potential and their capacity to promote pre-existing tumor cell growth and oncogenicity.
Animals ; Cell Differentiation ; Cell Proliferation ; Hepatocytes/immunology/metabolism/pathology/*transplantation ; Humans ; Liver/immunology/metabolism/pathology/physiopathology/*surgery ; Liver Cirrhosis/diagnosis/immunology/metabolism/physiopathology/*surgery ; Liver Regeneration ; *Mesenchymal Stem Cell Transplantation/adverse effects ; *Mesenchymal Stromal Cells/immunology/metabolism/pathology ; Phenotype ; Regenerative Medicine/*methods ; Risk Factors ; Signal Transduction ; Treatment Outcome

OBJECTIVETo observe the therapeutic effect of autologous cytokine-induced killer cells (CIK) on HBV DNA positive patients with liver cirrhosis.

METHODSHBV DNA positive 33 patients with cirrhosis were treated with CIK. Before and after cultured in vitro and post-treatment, CD3+, CD3+CD4+, CD3+CD8+, CD3+CD56+ cells, mDC and pDC were detected by flow cytometry. The indexes of virus and liver function were compared between pre- and post-treatment.

RESULTSCD3+, CD3+CD8+ cells and CD3+CD56+ cells were higher after cultured in vitro and after transfused back than those before culture (91.5 +/- 10.3, 74.4 +/- 9.9 vs. 67.9 +/- 12.8; 60.9 +/- 15.5, 37.3 +/- 15.1 vs. 27.9 +/- 10.9; 18.4 +/- 11.7, 14.5 +/- 7.5 vs. 10.6 +/- 7.1). The percentages of mDC and pDC also increased after-treatment vs. pre-treatment (0.54 +/- 0.18 vs. 0.70 +/- 0.29; 0.26 +/- 0.13 vs. 0.41 +/- 0.25). HBV DNA became undetectable in 12 patients and decrease exceeded 100 times in 4 patients after treatment. HBeAg became undetectable in 10 of 14 patients who were HBeAg positive pretreatment patients, among them 2 patients had HBeAb sero conversion. The liver function was improved after treatment. All patients tolerated the treatment.

CONCLUSIONCIK treatment can increase immune effector cells and has some antiviral effect and is safe.

Adoptive Transfer ; adverse effects ; methods ; Adult ; Aged ; Cells, Cultured ; Cytokine-Induced Killer Cells ; cytology ; immunology ; transplantation ; Fatigue ; etiology ; Female ; Headache ; etiology ; Hepatitis B ; complications ; virology ; Humans ; Liver Cirrhosis ; etiology ; immunology ; therapy ; Male ; Middle Aged ; Transplantation, Autologous ; Treatment Outcome