Puchakayala Bharat K, Verma Siddharth, Kanwar Pushpjeet, Hart John, Sanivarapu Raghavendra R, Mohanty Smruti R
Bharat K Puchakayala, Siddharth Verma, Pushpjeet Kanwar, Raghavendra R Sanivarapu, Smruti R Mohanty, Center for Liver Diseases, Division of Gastroenterology and Hepatology, New York Methodist Hospital at Weill Cornell Medical College, Brooklyn, NY 11215, United States.
World J Hepatol. 2015 Nov 8;7(25):2610-8. doi: 10.4254/wjh.v7.i25.2610.
To study clinical and histopathological features of nonalcoholic fatty liver disease (NAFLD) in patients with and without type 2 diabetes mellitus (T2DM) using updated nonalcoholic steatohepatitis clinical research network (NASH-CRN) grading system.
We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2DM. This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author. The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison. The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist. The updated criteria for type 2 diabetes have been utilized for analysis. Background data of patients with NASH and NAFLD has been included. The mean differences were compared using χ(2) and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.
Patients with NAFLD and T2DM were significantly older (49.9 vs 43.0, P < 0.01), predominantly female (71.4 vs 56.3, P < 0.02), had higher rate of metabolic syndrome (88.7 vs 36.4, P < 0.01), had significantly higher aspartate transaminase (AST)/alanine transaminase (ALT) ratio (0.94 vs 0.78, P < 0.01) and Fib-4 index (1.65 vs 1.06, P < 0.01) as markers of NASH, showed higher mean NAFLD activity score (3.5 vs 3.0, P = 0.03) and higher mean fibrosis score (1.2 vs 0.52, P < 0.01) compared to patients with NAFLD without T2DM. Furthermore, advanced fibrosis (32.5 vs 12.0, P < 0.01) and ballooning (27.3 vs 13.3, P < 0.01) was significantly higher among patients with NAFLD and T2DM compared to patients with NAFLD without T2DM. On multivariate analysis, T2DM was independently associated with NASH (OR = 3.27, 95%CI: 1.43-7.50, P < 0.01) and advanced fibrosis (OR = 3.45, 95%CI: 1.53-7.77, P < 0.01) in all patients with NAFLD. There was a higher rate of T2DM (38.1 vs 19.4, P < 0.01) and cirrhosis (8.3 vs 0.0, P = 0.01) along with significantly higher mean Bilirubin (0.71 vs 0.56, P = 0.01) and AST (54.2 vs 38.3, P < 0.01) and ALT (78.7 vs 57.0, P = 0.01) level among patients with NASH when compared to patients with steatosis alone. The mean platelet count (247 vs 283, P < 0.01) and high-density lipoprotein cholesterol level (42.7 vs 48.1, P = 0.01) was lower among patients with NASH compared to patients with steatosis.
Patients with NAFLD and T2DM tend to have more advanced stages of NAFLD, particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2DM.
使用更新的非酒精性脂肪性肝炎临床研究网络(NASH-CRN)分级系统,研究合并和不合并2型糖尿病(T2DM)的非酒精性脂肪性肝病(NAFLD)患者的临床和组织病理学特征。
我们回顾性分析了235例经活检证实患有或未患有T2DM的NAFLD患者的数据。该数据库曾用于之前发表的由同一通讯作者进行的比较NAFLD种族结局的研究。利用芝加哥大学的病理数据库纳入符合NAFLD标准的连续患者,并获取其详细的临床和组织病理学结果进行比较。患者的相关临床资料在肝活检时从电子病历中收集,组织学结果由一位训练有素的单一组织病理学家解读。采用更新的2型糖尿病标准进行分析。纳入了NASH和NAFLD患者的背景数据。使用χ²检验和t检验以及回归分析比较均值差异,以评估NASH和进展性肝纤维化的预测因素。
与未患T2DM的NAFLD患者相比,合并T2DM的NAFLD患者年龄显著更大(49.9岁对43.0岁,P<0.01),女性占比更高(71.4%对56.3%,P<0.02),代谢综合征发生率更高(88.7%对36.4%,P<0.01),作为NASH标志物的天冬氨酸转氨酶(AST)/丙氨酸转氨酶(ALT)比值显著更高(0.94对0.78,P<0.01)以及Fib-4指数显著更高(1.65对1.06,P<0.01),NAFLD活动评分均值更高(3.5对3.0,P=0.03),肝纤维化评分均值更高(1.2对0.52,P<0.01)。此外,与未患T2DM的NAFLD患者相比,合并T2DM的NAFLD患者中进展性肝纤维化(32.5%对12.0%,P<0.01)和气球样变(27.3%对13.3%,P<0.01)的发生率显著更高。多因素分析显示,在所有NAFLD患者中,T2DM与NASH独立相关(OR=3.27,95%CI:1.43 - 7.50,P<0.01)以及与进展性肝纤维化独立相关(OR=3.45,95%CI:1.53 - 7.77,P<0.01)。与单纯脂肪变性患者相比,NASH患者中T2DM发生率更高(38.1%对19.4%,P<0.01)、肝硬化发生率更高(8.3%对0.0%,P=0.01),同时胆红素均值显著更高(0.71对0.56,P=0.01)、AST显著更高(54.2对38.3,P<0.01)以及ALT显著更高(78.7对57.0,P=0.01)。与单纯脂肪变性患者相比,NASH患者的平均血小板计数更低(247对283,P<0.01),高密度脂蛋白胆固醇水平更低(42.7对48.1,P=0.01)。
与未患T2DM的NAFLD患者相比,合并T2DM的NAFLD患者往往处于NAFLD更晚期阶段,尤其是进展性肝纤维化和气球样变发生率更高。