Hanouneh Ibrahim A, Feldstein Ariel E, McCullough Arthur J, Miller Charles, Aucejo Federico, Yerian Lisa, Lopez Rocio, Zein Nizar N
Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Liver Transpl. 2008 Sep;14(9):1287-93. doi: 10.1002/lt.21524.
Although hyperinsulinemia and its associated metabolic syndrome (MS) have been implicated in the progression of hepatic fibrosis in hepatitis C virus (HCV) patients, little is known about the consequences of MS after orthotopic liver transplantation (OLT). The aim of this study was to assess the association between MS and fibrosis progression in patients with recurrent HCV after OLT. We identified all OLT/HCV patients (1998-2005) with at least 2 post-OLT liver biopsies. MS was defined with Adult Treatment Panel III criteria at 1 year post-OLT. The Ludwig-Batts scoring system was used to stage all biopsies (408 biopsies from 95 patients). The first biopsy that showed progression post-OLT was used for the time-to-progression analysis. Univariable and multivariable logistic regression analysis was performed to identify factors associated with fibrosis progression. MS was present in 50% of patients. Average follow-up to last available biopsy was 24 +/- 17 months, during which 72% of subjects had fibrosis progression. The overall median rate of fibrosis progression was 0.08 units per month (Q25, Q75: 0.0, 0.17). By univariable analysis, high HCV RNA at 4 months post-OLT (P < 0.001), diabetes (P = 0.046), cytomegalovirus infection (P = 0.006), and MS (P = 0.049) were associated with progression of fibrosis. In multivariable analysis, MS was independently associated with progression of fibrosis beyond 1 year after OLT (odds ratio = 6.3, P = 0.017). A high viral load at 4 months post-OLT (odds ratio = 1.1, P = 0.004) and steroid therapy for acute rejection (odds ratio = 1.9, P = 0.05) were independently associated with fibrosis progression. In conclusion, MS, a potentially modifiable disease, is common and is strongly associated with long-term fibrosis progression in the setting of recurrent HCV after OLT.
尽管高胰岛素血症及其相关的代谢综合征（MS）被认为与丙型肝炎病毒（HCV）患者肝纤维化的进展有关，但关于原位肝移植（OLT）后MS的后果知之甚少。本研究的目的是评估OLT后复发性HCV患者中MS与纤维化进展之间的关联。我们确定了所有在1998年至2005年间接受OLT/HCV治疗且至少有2次OLT后肝脏活检的患者。MS根据OLT后1年的成人治疗小组III标准进行定义。采用路德维希-巴茨评分系统对所有活检标本（来自95例患者的408份活检标本）进行分期。将显示OLT后进展的首次活检用于进展时间分析。进行单变量和多变量逻辑回归分析以确定与纤维化进展相关的因素。50%的患者存在MS。至最后一次可用活检的平均随访时间为24±17个月，在此期间72%的受试者出现纤维化进展。纤维化进展的总体中位速率为每月0.08个单位（第25百分位数，第75百分位数：0.0，0.17）。单变量分析显示，OLT后4个月时高HCV RNA（P<0.001）、糖尿病（P=0.046）、巨细胞病毒感染（P=0.006）和MS（P=0.049）与纤维化进展相关。多变量分析显示，MS与OLT后1年以上的纤维化进展独立相关（优势比=6.3，P=0.017）。OLT后4个月时高病毒载量（优势比=1.1，P=0.004）和急性排斥反应的类固醇治疗（优势比=1.9，P=0.05）与纤维化进展独立相关。总之，MS是一种潜在可改变的疾病，在OLT后复发性HCV的情况下很常见且与长期纤维化进展密切相关。
