Rescue of a living donor with liver transplantation.

Postoperative liver failure is a rare complication after living donor liver resection. This is a case report of a 22-year-old healthy donor who was rescued with liver transplantation 11 days after right hemihepatectomy. Nine months later the patient is alive, and has fully recovered from his multiple organ failure. According to a review of the literature, there are four additional living liver donors, who received a liver transplant. Our own patient is the only survivor, so far. This case demonstrates that even in supposedly healthy living donors postoperative complications cannot be completely prevented. Although liver failure is rare in these patients, timely transplantation may need to be considered as the only life-saving treatment.

A multicenter, randomized, double-blind, placebo-controlled trial of recombinant human interleukin-10 in HIV-infected subjects.

OBJECTIVE: To determine the effect of multiple subcutaneous doses of recombinant human interleukin (rhuIL)-10 on plasma HIV RNA levels and CD4 T-cell counts, and to evaluate its safety and tolerability in HIV-infected subjects. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. SUBJECTS: Thirty-nine HIV-infected subjects with CD4 T-cell counts > 200 x 10(6)/l, plasma HIV RNA concentrations > or = 3.18 log10 copies/ml and on stable antiretroviral therapy were recruited from six centers. INTERVENTION: Subjects received (subcutaneously) rhuIL-10 1 microg/kg daily, 4 microg/kg daily, 8 microg/kg three times per week, placebo daily or placebo three times per week for 4 weeks. MAIN OUTCOME MEASURES: Prospectively defined outcomes included safety and tolerability, plasma HIV RNA levels and CD4 T-cell counts. Outcomes were assessed at baseline, weeks 1, 2, 3 and 4 during treatment and weeks 2 and 4 following completion of therapy. RESULTS: Baseline characteristics were similar in all groups. Compared to baseline, no significant change in plasma HIV RNA concentrations or CD4 T-cell counts was observed in any of the groups. RhuIL-10 was generally well tolerated. Two patients receiving rhuIL-10 4 microg/kg required discontinuation due to thrombocytopenia. One patient receiving rhuIL-10 4 microg/kg who had chronic hepatitis B and C infections discontinued drug because of elevated liver function tests. One patient receiving placebo discontinued study drug because of depression. CONCLUSION: The lack of a demonstrable virological benefit, as assessed by plasma viral load, with 4 weeks of rhuIL-10 does not support the development of this immune-based therapy for treatment of HIV infection.

Clinical, hematologic, and immunologic effects of interleukin-10 in humans.

We conducted a double-blind, placebo-controlled study to investigate the safety, pharmacokinetics, and immunological properties of interleukin-10 (IL-10) administration in healthy humans. Volunteers received a single intravenous bolus injection of recombinant human IL-10 (1, 10, or 25 micrograms/kg) or placebo. Cytokine production in whole blood and peripheral blood mononuclear cells (PBMC) was assessed before and 3, 6, 24, and 48 hr after the injection. Peak serum concentrations of IL-10 (15 +/- 1.1, 208 +/- 20.1, and 505 +/- 22.3 ng/ml) occurred after 2-5 min for 1, 10, and 25 micrograms/kg IL-10, respectively. The terminal-phase half-life was 3.18 hr. A transient leukocytosis (24-63% above baseline) was observed 6 hr after injection, which coincided with a dose-dependent decrease (12-24%) in neutrophil superoxide generation. There was a marked inhibition (60-95%) of endotoxin-induced IL-6 production from whole blood in each group receiving IL-10. Production of IL-8 in endotoxin-stimulated blood was reduced in the 10 micrograms/kg group. In PBMC stimulated with phytohemagglutinin and phorbol ester, there was a decrease (72-87%) in interferon-gamma (IFN gamma) production 6 hr after IL-10 with a return to pre-IL-10 levels after 24 hr. This reduction was only partially associated with a decrease in the number of CD2-bearing cells. We conclude that IL-10 administration into humans is without significant side effects, and a single injection reduces ex vivo production of IL-6, IL-8, and IFN gamma.