Efficacy of 50-week administration of interferon-alfa 2a to 159 chronic hepatitis B patients with or without HBe-antigen was investigated. Patients received 1 to 9 MU/injection of interferon for 26 ...to 50 weeks. 24.7% (23/93) of HBe-antigen-positive patients became HBe-antigen-negative after 24-week treatment with interferon. Those who remained HBe-antigen-positive after 24-week interferon therapy received additional 26-week of interferon and 35.1% (13/37) turned to HBe-antigen-negative. Nornal serum ALT at 12 month after interferon therapy was observed in 56.6% (25/44) of HBe-antigen-negative patients, althouth sustained clearance of serum HBV DNA was obtained in only 4 cases. 18.9% (30/159) dropped out mainly due to adverse effects of interferon. Fifty-week interferon therapy seems to increase the response rate of CH-B, althouth the high prevalence of adverse effects should be considered especially among those who received high-dose interferon.
Cerberovascular accidents in patients with chronic renal failure undergoing hemodialysis can have serious clinical consequences. We describe a 24-year-old male with tuberous sclerosis who had been on ...hemodialysis for 14 months and was admitted to our hospital because of suspected subdural hematoma. He underwent surgical removal of the hematoma. Post operative course was without sequelae by the use of peritoneal dialysis as well as hemodialysis with a reduced heparin dosage. Renal angiography revealed hypervascular tumors and polycystic kidney, He had multiple adenoma sebaceum in his face and periungual f ibromas were noticed on toenails. Ophthalmoscopic examination revealed a phacoma in both eyes, As no tumors nor vascular abnormalities were found around the hematoma at the time of surgery, the possibility of underlying tuberous sclerosis as being the etiologic factor of the subdural hematoma appeared remote. Hemorrhagic tendency associated either with renal insufficiency or anticoagulant used with hemodialysis or head trauma were considered as possibly contributing to the cerebral lesion.
The immunosuppressive effect and other properties of a novel immunosuppressant, FTY720, have been studied mostly in the experimental transplantation of various extrahepatic organs. In this ...experiment, we evaluated the antirejection potency and adverse effects of this agent on liver grafts using a canine liver transplantation model.
Forty-eight orthotopic liver transplantations were performed by the standard technique under a veno-venous bypass. Liver recipients were divided into two studies: a single-dose study with FTY720 at various doses and a combined dose study with conventional immunosuppressants (cyclosporine or tacrolimus) alone and combined with FTY720. Survival, biochemical and hematological tests, blood levels of immunosuppressants, and postmortem histology were determined.
The median survival of untreated control animals was 9 days, whereas treatment with FTY720 at a dose of 0.1 mg/kg/day prolonged graft survival to 49.5 days. FTY720 at 1 mg/kg/day showed a slight but insignificant prolongation to 16 days, but when the dose was increased to 5 mg/kg/day, the graft was rejected at 10 days. The combination of FTY720, 0.1 mg/kg/day, with a subtherapeutic dose of cyclosporine, 5 mg/kg/ day, prolonged median animal survival from 40 days with cyclosporine alone to 74 days. A combination of FTY720 (0.1 mg/kg/day) with tacrolimus (0.5 mg/kg/ day) compromised animal survival, reducing survival from 83.5 days with tacrolimus alone to 30.5 days due to infectious complication and emaciation by overimmunosuppression. No evident drug-induced side effects were observed.
FTY720 has a potent immunosuppressive effect when used alone at 0.1 mg/kg/day in canine liver transplantation. FTY720 is a promising candidate for future clinical application in orthotopic liver transplantation.
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