ABSTRACT
Autoimmune hepatitis (AIH) recurs after liver transplantation and significantly impacts graft function and patient survival. In this case report, we present 2 cases of male patients with refractory recurrent AIH after liver transplantation. Each patient lost their first graft due to refractory continuous AIH. We have not noticed a similar refractory course for our female patients with AIH post-transplantation at our center. Based on our single-center experience there appears to be a gender disparity in the aggressive nature of AIH recurrence after transplantation. Despite the aggressive nature of recurrent AIH in both patients, graft loss occurred beyond 3 years for both patients and did not influence the 1- and 3-year patient survival. If these findings are validated, they may have significant impact on post-transplantation immunosuppression management in male patients.
Subject(s)
Hepatitis, Autoimmune/diagnosis , Liver Failure/complications , Liver Failure/therapy , Liver Transplantation/adverse effects , Female , Graft Survival , Hepatitis, Autoimmune/etiology , Hepatitis, Autoimmune/therapy , Humans , Immunosuppressive Agents/therapeutic use , Inflammation , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Liver Cirrhosis/therapy , Liver Transplantation/methods , Male , Middle Aged , Recurrence , Treatment OutcomeABSTRACT
PURPOSE: Protamine reversal of heparin anticoagulation during cardiovascular surgery may cause severe hypotension and pulmonary hypertension. A novel protamine variant, [+18RGD], has been developed that effectively reverses heparin anticoagulation without toxicity in canine experiments. Heretofore, human studies have not been undertaken. This investigation hypothesized that [+18RGD] would effectively reverse heparin anticoagulation of human blood in vitro. METHODS: Fifty patients who underwent anticoagulation therapy during vascular surgery had blood sampled at baseline and 30 minutes after receiving heparin (150 IU/kg). Activated clotting times were used to define specific quantities of [+18RGD] or protamine necessary to completely reverse heparin anticoagulation in the blood sample of each patient. These defined amounts of [+18RGD] or protamine were then administered to the heparinized blood samples, and percent reversals of activated partial thromboplastin time, thrombin clotting time, and antifactor Xa/IIa levels were determined. In addition, platelet aggregation assays, as well as platelet and white blood cell counts were performed. RESULTS: [+18RGD] and protamine were equivalent in reversing heparin as assessed by thrombin clotting time, antifactor Xa, antifactor IIa levels, and white blood cell changes. [+18RGD], when compared with protamine, was superior in this regard, as assessed by activated partial thromboplastin time (94.5 +/- 1.0 vs 86.5 +/- 1.3% delta, respectively; p < 0.001) and platelet declines (-3.9 +/- 2.9 vs -12.8 +/- 3.4 per mm3, respectively; p = 0.048). Platelet aggregation was also decreased for [+18RGD] compared with protamine (23.6 +/- 1.5 vs 28.5 +/- 1.9%, respectively; p = 0.048). CONCLUSIONS: [+18RGD] was as effective as protamine for in vitro reversal of heparin anticoagulation by most coagulation assays, was statistically more effective at reversal than protamine by aPTT assay, and was associated with lesser platelet reductions than protamine. [+18RGD], if less toxic than protamine in human beings, would allow for effective clinical reversal of heparin anticoagulation.
