IL-2 receptor antagonist [basiliximab] is associated with rapid fibrosis progression in patients with recurrent hepatitis c after liver transplantation using serial biopsy specimens

Recurrence of hepatitis C virus [HCV] infection following orthotopic liver transplantation [OLT] is universal. There is paucity of data on the safety and efficacy of interleukin [IL]-2 receptor antagonist [IL-2RA] when added to the standard immunosuppression regimen in OLT recipients with recurrent HCV infection. To evaluate the efficacy of IL-2RA [Basiliximab] in preventing acute cellular rejection [ACR] in patients with recurrent HCV infection after OLT and to assess the impact of IL-2RA in promoting fibrosis progression in post-OLT recurrent HCV infection. Using an electronic pathology database, we identified all OLT/HCV patients with at least 2 post-OLT liver biopsies [1998-2006]. Standard immunosuppression consisted of steroids and calcineurin inhibitor with and without mycophenolate mofetil. All patients who were transplanted after May 2004 received IL- 2RA induction therapy. The Ludwig-Batts system was used to stage all biopsies [593 biopsies from 124 patients]. The first biopsy that showed post-OLT fibrosis or the last follow-up biopsy was used for time- to-progression analysis. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify factors associated with the progression of fibrosis. ACR was significantly [p<0.001] lower in patients who received IL-2RA [20 of 70, 29%] compared to those who did not [33 of 54, 61%]. The median [25%ile, 75%ile] follow-up was 12.1 [6.1, 23.9] months during which 61% of patients had progression of fibrosis. Univariate analysis revealed that a higher HCV RNA load at 4 months post-OLT [p=0.002], cytomegalovirus [CMV] infection [p<0.001], use of steroid therapy for ACR [p=0.043], and use of IL-2RA [p<0.001] were associated with higher hazards for the pro- gression of fibrosis. Viral load at 4 months post-OLT was significantly [p=0.025] higher in patients who had IL-2RA therapy [median [25%ile, 75%ile]: 2.9 [1.0, 5.0] _10[6] vs. 1.4 [1.0, 2.3] _10[6]]. In multivariate analysis, patients who received IL-2RA therapy were 3.1 [95% CI: 1.8-5.3] times more likely to develop fi- brosis than those who did not treated with IL-2RA. Steroid therapy for ACR remained significantly [Hazard Ratio=2.9, p=0.002] associated with the progression of fibrosis. IL-2RA [Basiliximab] decreases the rate of ACR. However, it may be associated with more rapid histological progression of the disease in post-OLT recurrent HCV

Experiences relating to management of biliary tract complications following liver transplantation in 96 cases / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate best diagnosing methods and therapy for patients with biliary tract complications after liver transplantation and analyze related factors.</p><p><b>METHODS</b>A review was made of data collected from 96 patients, and confirmed by retrospective case notes examination.</p><p><b>RESULTS</b>A total of 94 patients (97 grafts) survived more than 2 days after transplantation; of whom, 92 had an end-to-end biliary anastomosis with a T tube. The average follow-up was 5.8 months (range: 0.3 - 10.2 months). Among the 94 patients, eight (8.5%, 8/94) had complications: leakage during T-tube removal (2 patients), leakage at an earlier stage (2), simultaneous stricture and leak (2) and just stricture (2). Six patients with biliary tract complications had predisposing factors including hepatic artery stenosis (2 patients, including one hepatic artery stenosis combined with severe rejection, hepatic artery thrombosis (3), and donor-recipient bile duct mismatch (1). There was no difference in cold ischemic time. With hepatic artery thrombosis and/or stenosis > 50%, five patients were re-transplanted; without hepatic artery thrombosis and/or stenosis < 50%, three patients required endoscopic stenting and radiological percutaneous drainage of bile collection with or without balloon dilation. All patients survived.</p><p><b>CONCLUSIONS</b>Biliary strictures occur later than leaks after surgery. Without hepatic artery thrombosis and/or stricture, there is no need for surgery; with hepatic artery thrombosis and/or stricture > 50%, re-transplantation is needed as early as possible.</p>

Surgical complications of orthotopic liver transplantation / 中国普通外科杂志

Objective　To study the prevention and treatment of postoperative complications of liver transplantation (LT). Methods　According to experience of Thomas E. Starzl Transplantation Institute and the Departments of Surgery University of Pittsburgh Medical Center, we introduce the prevention and treatment of surgical complications. Results and Conclusions　Intra-abdominal hemorrhage, hepatic artery thrombosis, portal vein thrombosis, bile leaks, biliary obstruction, intestinal perforation, gastrointestinal bleeding are the postoperative complications of LT which are related to the surgical technique. Rapid improvement of diagnostic assessment of the alterations from normal postoperative course, and timely intervention are very important to minimize morbidity of surgical complications and mortality .

Liver Non-Parenchymal Cells Induce Apoptosis in Activated T Cells in Vitro / 대한이식학회지

PURPOSE: Liver, unlike heart or skin, allografts transplanted between MHC-disparate mouse strains are spontaneously accepted without any immunosuppressive therapy. Despite the allograft acceptance, the recipients continue to exhibit donor-specific immune responses in vitro (MLR and generation of CTL). High levels of CTL apoptosis evident within tolerated liver grafts have been postulated as a mechanism underlying this 'split' tolerance. METHODS and RESULTS: By using radiometric DNA fragmentation test ("JAM" assay) and TUNEL staining, we present the evidence here that liver nonparenchymal cells (NPC) are quite strong inducers of activated T cell apoptotic death in allogeneic mice. This phenomenon occurs the similar level in activated T cells of syngeneic or third-party mice. Liver cells from gld (FasL-deficient) mice exert similar apoptosis-inducing effect on activated T cells from normal mice. Tumor necrosis factor receptor (TNFR): Fc fusion protein, and concanamycin A, an inhibitor of perforin pathway, fail to inhibit the apoptotic activity. CONCLUSION: These data indicate that liver NPC play important role in causing active apoptosis in graft-infiltratingCTL which favors liver graft acceptance, and liver-induced activated T cell apoptosis may not mediated by Fas, TNF or perforin pathways.

Current problems and perspectives of liver transplantation in Pittsburgh: Retransplantation and Split, Reduced size liver transplantation / 한국간담췌외과학회지

No abstract available.

Liver transplantation for chronic viral hepatitis B and C / 中华肝胆外科杂志

Liver transplantation is considered an effective form of therapy for patients with end-stage liver disease.Unfortunately the results of transplantation for patients with chronic viral hepatitis have not been as promising as for other liver disorders.A high rate of hepatitis recurrence in the allograft leading to a higher incidence of graft and patient loss have led many transplant centers to reconsider the use of orthotopic liver transplantation(OLTX)in these groups.Current strategies to prevent hepatitis B infection focus on identifying groups of hepatitis B virus(HBV)patients with lower risks of reinfection,specifically those with lack of markers for active HBV replication.Trials to convert"high risk"HBV patients to a "low risk"group have recently been initiated in the "high risk"group of patients with the aim to convert their HBV status from replicating to nonor low-replicating states.Antiviral agents or immunostimulatory therapy before and/or after OLTX have been proposed as a means to minimize recurrence of hepatitis B in the liver allograft.While the focus has been specific issues related to prevention or treatment of viral hepatitis in OLTX patients,there are still a number of areas for investigation.For example,immunosuppression is considered to play a role in the recurrence and chronicity of HBV and hepatitis C virus(HCV)in the liver allograft,especially since corticosteroids have been demonstrated to have a biologic effect on HBV by inducing HBV antigen synthesis.Moreover,most of the results to date are based on the use of cyclosporin A as the primary agent of immunosuppression.Tacrolimus(FK506)based immunosuppression may also prove to have a beneficial effect for HBV patients undergoing OLTX.By minimizing or eliminating the need for corticosteroids,FK560 based immunosuppression may lessen the risk of recurrence or the severity of hepatitis in the liver allograft in HBV patients,and ultimately improve patient and graft survival.The controversies in the use of OLTX for HBV and HCV have persisted,in spite of an appreciation for the risks associated with selection,prophylaxis and treatment of candidates with HBV,principally dut to the uncertainties associated with OLTX for HCV.The routine application of OLTX to HBV candidates with low or no levels of HBV replication appears justified,however patients with active HBV replication should undergo OLTX only in a setting where new strategies for prevention, prophylaxis or treatment are being tested.Recently,the U.S.Department of Health and Human Services has approved OLTX for HBV,reflecting the improvements made in the clinical arena.However,further advances are needed for HCV prophylaxis and treatment of recurrent hepatitis following OLTX.