Rejection of a liver transplant is a rare but serious event which can be life threatening. T-cells were supposed to be the major, if not the only key player in allograft rejection. However, during recent years B-cell function has regained attention. A chimeric monoclonal antibody against CD20 protein (rituximab) successfully reversed a multi-drug resistant rejection in a liver transplant recipient. Following an uncomplicated postoperative course, the patient showed biopsy-confirmed acute rejection on postoperative day 28. Despite treatment with steroids, increased tacrolimus doses and anti-thymocyte globulin (ATG) the rejection could not be resolved. Repeated biopsies confirmed ongoing acute cellular rejection; however, a humoral component of rejection could not be fully excluded and rituximab treatment was initiated. Liver function showed a subsequent melioration accompanied by convalescence of the patient. No adverse side effects associated to rituximab administration were observed. Promising results with rituximab were reported for heart and kidney transplant recipients suffering from humoral rejection. To our knowledge this is the first report of a successful rescue therapy of a multi-drug-resistant liver allograft rejection with rituximab. The addition of rituximab might be a valuable option to overcome severe, multi-drug-resistant rejection, although humoral nature of rejection is not proven by histology.
Background. Postresectional liver failure (PLF) is a dreaded complication after partial hepatectomy (PH). Data from animal experiments indicate that endogenous ligands (i.e. bile salts) can stimulate liver regeneration and prevent liver injury after PH, via hepatic Fxr and the ileal Fxr-Fgf15 axis. Aim. To investigate whether exogenous activation of the Fxr pathway with the semi-synthetic bile acid derivative obeticholic acid (OCA) could stimulate postresectional liver regeneration in mice. Methods. Twelve weeks old male C57BL6/J mice were pre-treated with OCA (10 mg/kg/day) or vehicle, and after 7 days subjected to 70% PH. Mice were sacrificed at 24, 48 and 72 hrs after PH, and liver injury, secretory function, and regenerative indices were assessed. In a second study, OCA pre-treated mice received oral sucrose supplementation in the postoperative trajectory, and a group of mice receiving intraperitoneal injection of FGF19 was included as a positive control group. Here, mice were sacrificed at 48 hours after PH. Results. No effect could be detected on liver mass recovery after PH, although responses of Cyp7a1, Cyp8b1 and other Fxr target genes implied general effectiveness of OCA treatment. OCA had no consistent effects on the number of Ki-67+ hepatocytes and mitotic figures around the peak of proliferation (i.e. 48 hrs) after PH, having no effect or increasing these regenerative indices in the consecutive experiments. Hepatic bile salt content, an important determinant of PH-induced liver regeneration, at this time point was not affected by OCA. After pre-treatment of mice with FGF19, a reduced expression of ileal bile salt-regulated genes Fgf15 and Slc51b indicating FGF19-mediated repression of bile salt synthesis was seen, but this did not stimulate postresectional liver regeneration in mice. Conclusion. Despite the activation of hepatic and ileal Fxr as shown by induction of target genes, treatment with OCA or FGF19 did not result in accelerated liver regeneration after PH and liver bile salt content was not influenced. We speculate that bile salt homeostasis and endogenous bile salt signaling is already optimal in unaffected livers for proper progression of regeneration after PH. It will be interesting to study the effects of Fxr agonism on liver regeneration after PH, and prevention of PLF in the context of compromised bile salt homeostasis/signaling prior to PH.
Intrahepatic cholangiocarcinoma (ICC) is a fatal disease because of frequent recurrence and poor survival despite curative surgery. We investigated the indications for surgery, borderline, or non-surgeryin patients with advanced ICC. Method: We retrospectively studied 194 patients with ICC who underwent curative surgery between 2000 and 2014. Prognostic factors for survival are evaluated on univariate and multivariate analyses. Result: The 5-year survival rate was significantly higher in patients without intrahepatic metastasis (IM: 53%) than in patients with IM (14%, p<0.0001). The 5-year survival rate was significantly higher in patients without lymph node metastasis (LNM: 55%) than in patients with LN (25%, p<0.0001). IM and LNM showed significant prognostic factor for survival on multivariate analysis (both, p<0.0001). According to the survival rates with IM and/or LNM, the 5-year survival rates were 61% in patients without IM or LNM, 41% in patients with LNM and without IM, 26% in patients with IM and without LNM, and 0% in patients with IM and LNM. Conclusion: Indication of surgery of patients with ICC can determine based on the IM and LNM.
Transplant surgeons are currently faced with the challenge to accept marginal liver transplants due to steatosis or old age. Improving organ quality by implementing a selective organ protective donor management could be the first step towards a graft of enhanced quality. However, the molecular mechanisms of such treatments are still poorly understood. Glucocorticoid medication in donor medicine has been carried out and discussed for a long time. In a recent study published in , Jiménez-Castro et al. [Clin. Sci. (2017) 131, 733-746] demonstrate how liver histology and transplant liver function can be improved by administration of glucocorticoids to brain-dead donor rats with steatotic livers. This work illustrates the need for further trials in order to selectively improve the quality of steatotic livers with a potential for liver transplantation.
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