Rituximab Rescue Therapy for Refractory Early Acute Rejection after Liver Transplantation

Abstract

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.

Cholesterol, Cytokines and Diseases

“…Besides their vasoconstructive properties, endothelins stimulate the production of cytokines, growth factors (including vascular endothelial growth factor, VEGF) and extracellular matrix proteins (89)(90)(91)(92). Furthermore, endothelins enhance neutrophil adhesion and platelet aggregation, and are chemotactic for monocytes/macrophages.…”

Antibody‐Mediated Rejection in Adult Liver Transplant Recipients: A Case Series and Literature Review

“…However, none of the studies have proposed a comprehensive management strategy providing detailed information on the dose and duration of treatment. Furthermore, there is no recommendation regarding the treatment of chronic antibody‐mediated rejection 1–4,7–31 …”

“…The proper dose and duration of these medications remains unclear. In the literature, 1 to 4 doses of rituximab (375 mg/m 2 weekly) were used; however, 1 or 2 doses of rituximab were the most commonly used regimens 8,12–15,19,21,24–26,29 . Additionally, 1 to 4 doses of bortezomib (0.7‐1.3 mg/m 2 ) weekly or twice a week were administered in the reported cases in the literature 15,17,19,21 .…”

Atherosclerosis: A Classic Inflammatory Disease

“…Proinflammatory stimuli, including a diet high in saturated fat, hypercholesterolemia, obesity, hyperglycemia, insulin resistance, hypertension, and smoking, trigger the endothelial expression of adhesion molecules, such as P-selectin and vascular cell adhesion molecule-l (YCAM-I), which mediate the attachment of circulating monocytes and lymphocytes (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Interestingly, atherosclerotic lesions often form at bifurcations of arteries, regions characterized by disturbed blood flow, which reduce the activity of endothelial atheroprotective molecules, such as nitric oxide, and favor regional YCAM-l expression (25)(26)(27)(28)(29).…”