Transhepatic balloon dilation of biliary strictures in liver transplant patients: a 10-year experience.

PURPOSE: The authors report their initial and long-term results using transhepatic balloon dilation to treat biliary strictures in liver transplant patients. PATIENTS AND METHODS: Over a 10-year period, 72 liver transplant patients with biliary strictures underwent 81 balloon dilation treatments. Anastomotic strictures were present in 56 patients; nonanastomotic strictures were present in 16. RESULTS: Initial technical success was achieved in 64 of 72 patients (89%). Balloon dilation failed in eight patients (11%), and they were treated surgically. Complications occurred in nine (12%) patients, and all were successfully treated. Within the first 6 months, five patients (6.9%) required surgical revision. Three patients (4.2%) underwent repeated liver transplantation; and five patients (6.9%) died. Fifty-one patients in whom balloon dilation was initially successful were available for at least a 6-month follow-up. Life-table analysis showed an overall 81% +/- 4.8 success rate at 6 months; it dropped to 70% +/- 6.2 at 6 years. For anastomotic strictures, it was 77% +/- 5.8 at 6 months and 66% +/- 7.3 at 6 years. For nonanastomotic strictures, it was 94% +/- 6.2 at 6 months, which dropped to 84% +/- 10 at 5 years. CONCLUSION: Transhepatic balloon dilation represents an effective and relatively safe treatment for biliary stricture in liver transplant recipients.

FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemia/reperfusion.

Using a rat model, the effect of pre-treatment with FK 506 on hepatic ischemia/reperfusion injury was investigated. All control animals died within 72 h of the ischemia/reperfusion injury. Pre-treatment of the animals with FK 506 (0.3 mg/kg in 0.5 ml saline) administered intravenously improved survival. The most striking protection against fatal ischemia/reperfusion injury was achieved in rats that were given FK 506 6 and 24 h prior to the induction of the hepatic ischemic insult (70% and 80% 10-day survival rates, respectively). The hepatoprotective effect of FK 506 was assessed further in a second experiment in which the serum levels of tumor necrosis factor (TNF) and interleukin 6 (IL-6) were measured. These results suggest that a 60-min period of hepatic ischemia and subsequent reperfusion triggers the release of both TNF and IL-6, and that FK 506 pre-treatment (6 h before the ischemic episode) significantly inhibits the production and/or release of these two cytokines compared to untreated controls. These data provide additional information concerning the immunosuppressive and hepatoprotective activities of FK 506. Based upon these data, it is probable that FK 506 attenuates hepatic ischemia/reperfusion injury, at least in part, by reducing TNF and IL-6 levels.

FK 506 ameliorates the hepatic injury associated with ischemia and reperfusion in rats.

The effect of FK 506 on regeneration of the liver was studied in rats after a two-thirds partial hepatectomy after 60 min of ischemia of the unresected liver. The animals were divided into three distinct groups of 10 rats each. Group 1 (controls) received 0.5 ml saline solution intravenously 30 min after the induction of ischemia. Groups 2 and 3 were injected with FK 506 (0.3 mg/kg) intravenously 30 min after and 24 min before the induction of hepatic ischemia, respectively. The hepatic content of ATP and serum levels of ALT and lactate dehydrogenase were determined on each animal. In addition, the histological appearance and mitotic activity of the remnant liver was determined at regular 24-hr intervals after hepatic ischemia. All 10 control animals died within 72 hr. Treatment with FK 506 resulted in improved survival in groups 2 and 3 (30% and 80%, respectively). The improved survival seen in the FK 506-treated animals was reflected by a restoration of hepatic ATP content, a reduction in the serum levels of ALT and lactate dehydrogenase, an amelioration of hepatic necrosis and neutrophilic infiltration and an increase in the mitotic activity of the liver. These results suggest that FK 506 ameliorates the hepatic injury associated with ischemia/reperfusion and has a potent stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective agent when administered to organ donors before graft harvesting.

FK 506 ameliorates the hepatic injury associated with ischemia.

Ischemic damage of the allograft liver is a major problem in clinical liver transplantation. Therefore the identification of hepatoprotective agents is a high priority at most liver transplantation programs. FK 506, a potent new immunosuppressive agent has been reported to possess hepatotrophic activity. To evaluate the putative hepatotrophic activity of FK 506 on experimental hepatic ischemia, rats were subjected to a subtotal hepatectomy following experimental ischemia and subsequent rat survival was assessed. FK 506 (0.3 mg/Kg) administered intravenously 24 hours prior to the induction of hepatic ischemia, reduced the subsequent mortality rate from 100% among controls given saline to only 20% (P less than 0.001). This observation demonstrates that FK 506 enhances the regenerative response of the liver to ischemic injury and may, in addition to its immunologic activity have hepatotrophic activity as well.