Steroid-sparing basiliximab-based immunosuppressive therapy reduced the incidence of biliary leakage, and biliary leakage was the independent factor for biliary stricture. The non-surgical and surgical treatments for biliary complications were satisfactory.
After liver transplantation in HCV-infected patients, the virus load inevitably exceeds pre-transplantation levels. This phenomenon reflects suppression of the host-effector immune responses that control HCV replication by the immunosuppressive drugs used to prevent rejection of the transplanted liver. Here, we describe an adoptive immunotherapy approach, using lymphocytes extracted from liver allograft perfusate (termed herein liver allograft-derived lymphocytes), which includes an abundance of NK/NKT cells that mounted an anti-HCV response in HCV-infected liver transplantation recipients, despite the immunosuppressive environment. This therapy involved intravenously injecting patients 3 days after liver transplantation with liver allograft-derived lymphocytes treated with IL-2 and the CD3-specific mAb OKT3. During the first month after liver transplantation, the HCV RNA titers in the sera of recipients who received immunotherapy were markedly lower than those in the sera of recipients who did not receive immunotherapy. We further explored these observations in human hepatocyte-chimeric mice, in which mouse hepatocytes were replaced by human hepatocytes. These mice unfailingly developed HCV infections after inoculation with HCV-infected human serum. However, injection of human liver-derived lymphocytes treated with IL-2/OKT3 completely prevented HCV infection. Furthermore, an in vitro study using genomic HCV replicon-containing hepatic cells revealed that IFN-γ-secreting cells played a pivotal role in such anti-HCV responses. Thus, our study presents what we believe to be a novel paradigm for the inhibition of HCV replication in HCV-infected liver transplantation recipients.
IntroductionLiver failure and hepatocellular carcinoma (HCC) due to chronic hepatitis C infection are the most common indications for liver transplantation (LT), and the incidences of both have been projected to increase further in the future. Recurrent HCV infection of the allograft is universal, occurs immediately after LT, and is associated with accelerated progression to cirrhosis, graft loss, and death (1, 2). This reflects the suppression of those host-effector immune responses that usually control HCV replication, suggesting that the immunosuppressive environment may play a major role in the rapid progression of recurrent HCV infection after LT (3, 4). Further, the immunosuppressive condition described above is considered to increase the incidence of cancer recurrence after LT in HCC patients. We recently proposed the novel strategy of adjuvant immunotherapy for preventing the recurrence of HCC after LT; this immunotherapy involves intravenously injecting LT recipients with activated liver allograft-derived NK cells (5, 6). Since the immunosuppressive regimen currently used after LT reduces the adaptive immune components but effectively maintains the innate components of cellular immunity (7-9), the augmenta-
Hepatic steatosis is one of the most common hepatic disorders in developed countries. The epidemic of obesity in developed countries has increased with its attendant complications, including metabolic syndrome and non-alcoholic fatty liver disease. Steatotic livers are particularly vulnerable to ischemia/reperfusion injury, resulting in an increased risk of postoperative morbidity and mortality after liver surgery, including liver transplantation. There is growing understanding of the molecular and cellular mechanisms and therapeutic approaches for treating ischemia/reperfusion injury in patients with steatotic livers. This review discusses the mechanisms underlying the susceptibility of steatotic livers to ischemia/reperfusion injuries, such as mitochondrial dysfunction and signal transduction alterations, and summarizes the clinical impact of steatotic livers in the setting of hepatic resection and liver transplantation. This review also describes potential therapeutic approaches, such as ischemic and pharmacological preconditioning, to prevent ischemia/reperfusion injury in patients with steatotic livers. Other approaches, including machine perfusion, are also under clinical investigation; however, many pharmacological approaches developed through basic research are not yet suitable for clinical application.
Background: Splenectomy is gaining increasing importance for cirrhotic patients with hypersplenism. However, its safety and efficacy for patients with chronic liver disease remain unclear. Methods: We retrospectively examined the medical records of 38 consecutive cirrhotic patients who underwent splenectomy or simultaneous hepatectomy and splenectomy for hepatocellular carcinoma. Results: White blood cell and platelet counts significantly increased 3 months after splenectomy. Serum levels of total bilirubin and prothrombin time significantly improved 1 year after splenectomy. Interferon therapy was administered to 25 patients after splenectomy. A sustained viral response was achieved in 8 patients (42%). The total incidence of portal or splenic vein thrombosis (PSVT) detected by postoperative dynamic computed tomography was 13/38 (34.2%). Multivariate analysis revealed preoperative spleen volume (SV) to be the sole independent predictor of postoperative PSVT. Receiver-operator characteristic curve analysis showed that a cut-off SV of 450 ml corresponded to a sensitivity of 85% and a specificity of 56%. Conclusions: Splenectomy improved the liver function and facilitated effective interferon therapy in cirrhotic patients with hypersplenism, although preoperative SV was frequently associated with postoperative PSVT.
The results of CFSE-MLR assays, which could be used for rigorously monitoring rejection, provided evidence of low incidence of acute rejection after LDLT.
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