ABSTRACT
<p><b>OBJECTIVE</b>To investigate the pathogenesis of ischemic-type biliary lesions (ITBLs) in post-liver transplant patients and the possible therapeutic mechanisms of sirolimus.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Bile Duct Diseases , Drug Therapy , Forkhead Transcription Factors , Metabolism , Gene Expression Regulation , Interleukin-10 , Metabolism , Interleukin-2 , Metabolism , Ischemia , Diet Therapy , Liver Transplantation , Postoperative Complications , Drug Therapy , Sirolimus , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To research the clinical feasibility of emergency right lobe adult-to-adult live-donor liver transplantation in treating acute liver failure following severe hepatitis.</p><p><b>METHODS</b>Consecutive ten severe hepatitis patients (4 acute-on-chronic severe hepatitis and 6 acute severe hepatitis; 9 caused by HBV and 1 with drug-induced acute liver failure) underwent emergency right lobe adult-to-adult live-donor liver transplantation in our hospital from April 2007 to December 2007. The +/- s of model for end-stage liver disease score was 33.22 +/- 6.55. The outcomes of these recipients were prospectively analyzed.</p><p><b>RESULTS</b>Among them, 8 ABO blood group were identical and 2 compatible. One was Rh sub-group negative. Except 2 recipients died (1 acute renal failure caused by veno cava thrombosis, 1 liver graft lose caused by hepatic artery thrombosis), the rest of recipients (80%) and all donors were safe. The mean graft-to-recipient weight ratio was (1.19 +/- 0.14)%, and graft volume to recipient estimated standard liver volume ratio was (65.13 +/- 8.75)%. Right lobe grafts with middle hepatic vein (MHV) 3 cases, without MHV 4 cases, without MHV but followed by V and VIII hepatic vein outflow reconstruction 3 cases. Encouraging outcome was achieved in this group of recipient: elevated serum creatinine, serum endotoxin, decreased serum prothrombin activity (PTA) and total bilirubin returned to normal about on postoperative day (POD) 3, POD 7, POD 14 and POD 28, respectively.</p><p><b>CONCLUSIONS</b>Outcomes of emergency right lobe adult-to-adult live-donor liver transplantation for acute hepatic failure following severe hepatitis are fairly encouraging and acceptable. emergency right lobe adult-to-adult live-donor liver transplantation is an effective and life-saving modality for acute liver failure following severe hepatitis.</p>