sirolimus and Bile-Duct-Diseases

The use of sirolimus (SRL) in orthotopic liver transplantation (OLT) has been controversial after experimental data suggested an increased risk of hepatic artery thrombosis (HAT). To assess the safety and efficacy of SRL as de novo immunosuppression in OLT recipients. Outcomes of 252 OLT patients who received SRL were compared with outcomes of 291 OLT recipients who received calcineurin inhibitor in a retrospective study. Primary outcomes of this study were: patient- and graft survivals, vascular, biliary, wound complications and rejection rates. Secondary outcomes were: postoperative infection rate, bone marrow and renal function and changes of lipid levels. Patient- and graft survivals, rejection and infection rates were similar. In the SRL group, HAT occurred in 1.2%, biliary complications in 19.4%, and incisional hernias in 9.1%. In the control group the incidence of HAT was 5.8% (P = 0.004), biliary complications 18.5% (P = NS) and incisional hernias 7.2% (P = NS). Patients on SRL experienced significantly higher levels of serum triglycerides but fewer acute cellular rejections. Bone marrow and renal functions were similar in both the groups. Our findings would suggest that SRL is safe and effective for very selected OLT recipients. Randomized controlled trials are necessary to confirm our results.

Topics: Adult; Bile Duct Diseases; Bone Marrow; Calcineurin Inhibitors; Cohort Studies; Female; Graft Rejection; Graft Survival; Hepatic Artery; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Kidney; Lipids; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Postoperative Complications; Retrospective Studies; Sirolimus; Surgical Wound Infection; Thrombosis; Treatment Outcome

To investigate the pathogenesis of ischemic-type biliary lesions (ITBLs) in post-liver transplant patients and the possible therapeutic mechanisms of sirolimus.. The clinic data of 32 post-liver transplant patients with ITBLs from May 2004 to December 2010 was analyzed. There were including 25 male and 7 female patients with a median age of 46 years (ranging from 19 to 61 years). Patients were divided into those who received sirolimus (sirolimus group) and those who did not (control group). The expression of IL-2, FoxP3, and IL-10 in the portal area, liver function indexes, and bile duct injury score were assessed pre-ITBL, when ITBLs were identified, and after 6 months of sirolimus treatment.. Compared with pre-ITBL optical density (OD) values, there was a significantly increase in IL-2 OD(0.138 ± 0.050 in control group and 0.141 ± 0.052 in sirolimus group), but not FoxP3 and IL-10 OD in both groups at the time ITBLs were diagnosed. After 6 months of treatment, the IL-2, FoxP3, and IL-10 OD values in the control group were not different from those when ITBLs were diagnosed. There was a significant reduction in post-therapy IL-2 OD(0.107 ± 0.043, t = 2.087, P = 0.044), and a significant elevation in FoxP3(0.213 ± 0.039) and IL-10 OD(0.187 ± 0.048) in sirolimus group as compared with those when ITBLs were diagnosed(t = -3.822 and -4.350, both P < 0.01). There was a significant increase in serum levels of ALT, AST, total bilirubin, γ-glutamyl transpeptidase and ALP at the time ITBLs were diagnosed compared with pre-ITBL levels in both groups. After 6 months of treatment, the above indexes had not changed in the control group, but significantly improved in the sirolimus group, and the bile duct injury score in the sirolimus group had significantly decreased(4.4 ± 2.4, Z = -2.568, P = 0.010). The 1-year and 3-year graft survival rates in the control group were 6/13 and 5/13, respectively, and 17/19 and 13/19, respectively, in the sirolimus group (χ(2) = 7.166, P = 0.007; χ(2) = 5.398, P = 0.020, respectively).. Sirolimus can downregulate IL-2 expression and upregulate FoxP3 and IL-10 expression, thereby stimulating FoxP3+ Treg cells, suppressing immunopathological damage, and promoting epithelial repair in bile ducts.

Topics: Adult; Bile Duct Diseases; Female; Forkhead Transcription Factors; Gene Expression Regulation; Humans; Interleukin-10; Interleukin-2; Ischemia; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Sirolimus; Young Adult

Topics: Bile Duct Diseases; Biopsy; Constriction, Pathologic; Cyclosporine; Humans; Liver; Liver Cirrhosis; Liver Failure; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Sarcoidosis; Sarcoidosis, Pulmonary; Sirolimus; Time Factors; Treatment Outcome