ABSTRACT
Background: Liver biopsy plays a crucial role in evaluating allograft dysfunction. Comprehensive analysis of the histological spectrum of complications, particularly rejection, in different time zones is lacking. Aim: To evaluate the histological spectrum of rejection, in four time zones, in a large Living donor liver transplant series. Patients and Methods: Retrospective analysis of 313 biopsies for the last 10 years of living donor liver transplantation (LDLT) recipients. 123 of which had rejection as diagnosis, were redistributed in four time zones [1-early (<3), 2-intermediate (3–6), 3 and 4-late (6–12 and > 12) months] and were assessed for sixteen histological parameters. Results: Biopsies in time zone 1 (26.5%), 2 (20.7%), 3 (24.6%), and 4 (28.1%)] were nearly equal. Multiple coexistent complications existed in 12% of the cases. Rejection diagnosed in time zone groups: 1 = 22 (17.9%), 2 = 27 (22%), 3 = 36 (29.3%), and 4 = 38 (30.9%). Portal inflammation mixed type (P < 0.000), portal vein (P = 0.001) and hepatic vein endothelialitis (P < 0.000), portal eosinophils (P = 0.001), and lymphocytic bile duct damage (P = 0.01) were most pronounced in group 1. Perivenulitis without hepatic vein endothelialitis was observed (P = 0.03) in groups 3, whereas bile duct atypia (P = 0.01) and duct loss (P < 0.000) were observed in group 4. Multiple episodes of rejection displayed significant association with central perivenulitis (P = 0.002) and bile duct loss (P < 0.001). Conclusions: Histological analysis in large series of LDLT recipients highlights the spectrum of complications in different time zones. Late acute and chronic rejection occurred as early as 3 months posttransplant. Central perivenulitis and bile duct atrophy were associated with repeated episodes of rejection and deterioration.
ABSTRACT
BACKGROUND: With advances in immunosuppression, graft and patient survival rates have increased significantly, but acute cellular rejection remains an important problem following liver transplantation (LT), and late acute rejection (LAR) occurs in a small percentage of recipients. Some risk factors for LAR have been identified, yet the cause of LAR has not been completely investigated. The efficacy of mycophenolate mofetil (MMF) administered in combination with calcineurin inhibitor (CNI) for reduction of LAR has been demonstrated. METHODS: Between January 2006 and August 2007, adult LT recipients (n=309) were enrolled in this study. Biopsy-proven acute rejection that occurred >6 months after LT was defined as LAR. The immunosuppression regimens, CNI or CNI plus MMF, were used continuously for at least 6 months after LT. The mean follow-up period was 34.8 months (range, 25~46 months). RESULTS: LAR occurred in 17 cases (5.5%). The incidence of LAR in the CNI (n=138) or CNI plus MMF groups (n=171) was 8.6% (n=12) and 2.9% (n=5), respectively (P=0.015). Multivariate Cox regression confirmed that CNI plus MMF versus CNI therapy is associated with a decreased risk of LAR (relative risk, 0.33; P=0.04). CONCLUSIONS: The incidence of LAR in the CNI plus MMF group was significantly lower than the CNI group. Thus, continuous use of CNI plus MMF may represent a better immunosuppression regimen to decrease the rate of LAR in LT recipients.