PDF(Pubmed)
Abstract：
UNASSIGNED: We have previously demonstrated high rates of chronic allograft hepatitis and fibrosis in liver transplant patients on long-term cyclosporine monotherapy. We subsequently changed practice to add low-dose prednisolone to maintenance treatment with tacrolimus post-transplant. The aim of the study was to assess the impact of the immunosuppression change on graft histopathology.
UNASSIGNED: Patients treated in this era (Tac + Pred, 2000-2009, N = 128) were compared to a historical cohort, who had been maintained on a steroid-free, cyclosporine-based regime (CSA-Only, 1985-1996, N = 129). Protocol liver biopsies and laboratory tests were performed five- and ten-years post-transplant in both groups.
UNASSIGNED: Compared to CSA-Only, the Tac + Pred cohort had significantly lower rates of chronic hepatitis (CH) at five (20% vs. 44%, p < 0.001) and ten (15% vs. 67%, p < 0.001) years post-transplant, with similar trends observed in inflammation and fibrosis at five years. The Tac + Pred cohort also had significantly lower hepatic transaminases and IgG levels and was less likely to be autoantibody positive at both time points. However, the degree of graft fibrosis at ten years did not differ significantly between eras (p = 0.356).
UNASSIGNED: Increased immunosuppression effectively reduced chronic allograft hepatitis and fibrosis at five years, suggesting it is an immunologically driven variant of rejection. However, there was no significant reduction in the degree of fibrosis at ten years, indicating a multifactorial origin for long term graft fibrosis.
UNASSIGNED: Patients treated in this era (Tac + Pred, 2000-2009, N = 128) were compared to a historical cohort, who had been maintained on a steroid-free, cyclosporine-based regime (CSA-Only, 1985-1996, N = 129). Protocol liver biopsies and laboratory tests were performed five- and ten-years post-transplant in both groups.
UNASSIGNED: Compared to CSA-Only, the Tac + Pred cohort had significantly lower rates of chronic hepatitis (CH) at five (20% vs. 44%, p < 0.001) and ten (15% vs. 67%, p < 0.001) years post-transplant, with similar trends observed in inflammation and fibrosis at five years. The Tac + Pred cohort also had significantly lower hepatic transaminases and IgG levels and was less likely to be autoantibody positive at both time points. However, the degree of graft fibrosis at ten years did not differ significantly between eras (p = 0.356).
UNASSIGNED: Increased immunosuppression effectively reduced chronic allograft hepatitis and fibrosis at five years, suggesting it is an immunologically driven variant of rejection. However, there was no significant reduction in the degree of fibrosis at ten years, indicating a multifactorial origin for long term graft fibrosis.
摘要：
■我们先前已证明长期环孢素单药治疗的肝移植患者中慢性同种异体肝炎和纤维化的发生率很高。随后，我们改变了做法，在移植后使用他克莫司维持治疗中添加低剂量泼尼松龙。该研究的目的是评估免疫抑制变化对移植物组织病理学的影响。
■在这个时代接受治疗的患者(Tac+Pred，2000-2009，N=128)与历史队列进行了比较，一直保持在无类固醇状态，基于环孢菌素的方案(仅CSA，1985-1996年，N=129)。两组移植后五年和十年进行了方案肝活检和实验室检查。
■与仅CSA相比，Tac+Pred队列慢性肝炎（CH）的发病率明显较低（20％vs.44%,p<0.001)和10(15%与67%,p<0.001)移植后年，在五年的炎症和纤维化中观察到类似的趋势。Tac+Pred队列还具有显著较低的肝转氨酶和IgG水平,并且在两个时间点都不太可能是自身抗体阳性。然而,10年时移植物纤维化程度在不同时代之间没有显著差异(p=0.356).
■增加的免疫抑制在五年内有效地减少了慢性同种异体移植肝炎和纤维化，这表明它是一种免疫驱动的排斥反应。然而,十年时纤维化程度没有显著降低，表明长期移植物纤维化的多因素起源。
■在这个时代接受治疗的患者(Tac+Pred，2000-2009，N=128)与历史队列进行了比较，一直保持在无类固醇状态，基于环孢菌素的方案(仅CSA，1985-1996年，N=129)。两组移植后五年和十年进行了方案肝活检和实验室检查。
■与仅CSA相比，Tac+Pred队列慢性肝炎（CH）的发病率明显较低（20％vs.44%,p<0.001)和10(15%与67%,p<0.001)移植后年，在五年的炎症和纤维化中观察到类似的趋势。Tac+Pred队列还具有显著较低的肝转氨酶和IgG水平,并且在两个时间点都不太可能是自身抗体阳性。然而,10年时移植物纤维化程度在不同时代之间没有显著差异(p=0.356).
■增加的免疫抑制在五年内有效地减少了慢性同种异体移植肝炎和纤维化，这表明它是一种免疫驱动的排斥反应。然而,十年时纤维化程度没有显著降低，表明长期移植物纤维化的多因素起源。
