非酒精性脂肪性肝病合并2型糖尿病患者血浆促甲状腺激素水平变化及其临床意义*

目的 研究非酒精性脂肪性肝病（NAFLD）合并2型糖尿病（T2DM）患者血清促甲状腺激素（TSH）水平的变化及其临床意义。方法 纳入NAFLD合并T2DM患者43例和T2DM患者40例,比较两组年龄、性别、身高、体质指数（BMI）、血压和血生化指标及血清糖化血红蛋白（HbAlc）、空腹胰岛素（FINS）、游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）等指标的差异,采用Logistic回归分析影响NAFLD患者发生T2DM的独立危险因素。结果 NAFLD合并T2DM患者体质指数（BMI）为（28.4±3.8） kg/m²,显著大于T2DM患者的（23.8±3.1） kg/m²,P<0.05）; NAFLD合并T2DM患者血清ALT、AST、GGT、TG、HOMA-IR和TSH水平显著高于T2DM患者（P<0.05）;不同血清TSH的NAFLD患者血清TC、TG、LDL-C和FT3水平存在显著性差异（P<0.05）;经Logistic回归分析显示,BMI（RR=1.720,95%CI为1.154~3.015）、HOMA-IR（RR=2.632,95%CI为1.010~3.654）、血清TSH（RR=2.577,95%CI为1.214~3.689）和TG水平（RR=1.538,95%CI为1.240~2.658）是影响NAFLD患者发生T2DM的独立危险因素。结论 了解NAFLD患者发生T2DM的危险因素有助于早期预防和干预,检测血清TSH水平可能对筛查合并T2DM的NAFLD患者有一定的临床意义。     

恩替卡韦治疗慢性乙型肝炎合并非酒精性脂肪性肝病患者疗效及其对肝组织脂肪变的影响*

目的 探讨恩替卡韦治疗慢性乙型肝炎（CHB）合并非酒精性脂肪性肝病（NAFLD）患者疗效及其对脂肪肝的影响。方法 25例CHB患者接受恩替卡韦治疗96 w。经肝穿组织学检查行脂肪变分级,使用磁共振氢质子波谱成像（¹H -MRS）检测脂水比（LWR）以判断肝脂肪变变化。采用自行设计的健康问卷调查表调查生活习惯并予以量化。结果 25例CHB患者经组织病理学检查,发现脂肪变≥F1者16例（64.0%）,被认为合并脂肪肝;治疗96 w末,21例（84.0%）患者达到完全病毒学应答;治疗前后血清HBsAg和HBV DNA水平差异有统计学意义（P<0.05）,而血清TBIL、ALT、体质指数、腰臀比、低密度脂蛋白胆固醇等无统计学意义的变化（P>0.05）;根据治疗前后LWR变化,发现治疗后脂肪变变重者8例,未变者13例,改善者4例,而脂肪肝改善患者治疗后腰臀比显著下降（P<0.05）;对生活习惯得分分析发现,每日主食量对脂肪肝的影响比较大（P<0.05）,即每日主食量大者会加重脂肪肝。结论 恩替卡韦治疗未能改善CHB合并NAFLD患者肝脏脂肪变程度,而这些患者在抗病毒的同时控制主食,降低腰臀比或许能减轻肝脂肪变程度。     

2型糖尿病合并非酒精性脂肪性肝病、进展性肝纤维化的危险因素及其预测效能

目的 分析2型糖尿病（T2DM）合并非酒精性脂肪性肝病（NAFLD）、进展性肝纤维化的危险因素及其预测效能。方法 431例T2DM患者根据腹部超声结果分为T2DM合并NAFLD 316例（合并组）、单纯T2DM 115例（单纯组），316例T2DM合并NAFLD患者再根据NAFLD纤维化评分（NFS）分为进展性肝纤维化39例（进展组）、可疑肝纤维化122例（可疑组）、除外肝纤维化155例（除外组），采用单因素分析法和多因素Logistic回归分析法分析T2DM合并NAFLD、进展性肝纤维化的影响因素和危险因素，采用ROC曲线评估相关危险因素对T2DM合并NAFLD、进展性肝纤维化的预测效能。结果 合并组和单纯组年龄、BMI、WBC、LY、AST、ALT、GGT、Alb、SUA、TC、TG、HDL-C、UHR、FIns、FC-P、HOMA-IR比较，P均<0.05；多因素Logistic回归分析结果显示，BMI、AST、Alb、TG、UHR、FC-P是T2DM合并NAFLD的独立危险因素；当BMI预测临界值为24.87 kg/m2时，其诊断T2DM合并NAFLD的灵敏度为77.5%...     

非酒精性脂肪性肝病患者血清载脂蛋白B水平及其临床意义探讨*

目的 研究非酒精性脂肪性肝病（NAFLD）患者血清载脂蛋白B（ApoB）水平变化及其临床意义。方法 2015年2月~2017年11月在我院体检人群1451例,经超声和 FibroTouch检查诊断NAFLD,采用免疫比浊法测定血清ApoB水平。结果 在1451例体检人群中,发现NAFLD患者360例（24.8%）;NAFLD组血清ApoB水平为（1.07±0.24） g/L,显著高于1091例对照组【（0.88±0.27） g/L,P<0.01】;把血清ApoB水平分为263例Q1（<0.73 g/L）、364例Q2（0.73~0.85 g/L）、321例Q3（0.86~0.99 g/L）、300例Q4（1.0~1.16 g/L）和203例Q5（≥1.17 g/L）组,其NAFLD检出率分别为4.2%、9.9%、19.0%、25.0%和34.5%,显示随着血清ApoB水平的升高,NAFLD患病率也显著上升（P<0.05）;同样,随着血清ApoB水平升高,代谢综合征各临床表型发生率也显著升高;多因素Logistic回归分析结果显示,性别、舒张压、体质指数、血清TC、HDL、FPG和ApoB是发生NAFLD的危险因素。结论 血清ApoB水平升高是发生NAFLD的危险因素,发现血清ApoB水平升高者,应及时行相关检查以明确NAFLD的存在,对于临床上早期干预可能具有重要的意义。     

非酒精性脂肪性肝病合并2型糖尿病患者血清铁蛋白变化及其临床意义

目的 探讨非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)患者血清铁蛋白(SF)的变化及其临床意义。方法 本文纳入633例NAFLD合并T2DM、163例T2DM和163例NAFLD患者,检测血清SF和其他血清指标,应用二分类Logistic多元回归分析。结果 NAFLD合并T2DM患者血清SF水平为(293.5±206.4)ng/ml,显著高于T2DM组[(122.1±108.8)ng/ml,P<0.01]或NAFLD组[(202.5±127.6)ng/ml,P<0.01];血清尿酸(UA)水平为(401.2±91.5)μmol/l,显著高于T2DM组[(345.7±88.227)μmol/l,P<0.01];血清C反应蛋白(CRP)水平为(2.4±1.9)mg/dl,显著高于T2DM组[(1.3±1.7)mg/dl,P<0.01]或NAFLD组[(1.6±1.4)mg/dl,P<0.01];二分类Logistic多元回归分析显示SF和UA是NAFLD合并T2DM的独立预测因素(P＜0.05)。结论 检测血清铁可以预测NAFLD患者合并2型糖尿病,应该及时进行相关检查,以早期发现和处理。     

超声定量评估非酒精性脂肪性肝病患者肝脏ARFI值对显著NASH的诊断价值分析

目的 探讨采用声辐射力脉冲成像技术（ARFI）定量评估非酒精性脂肪性肝病（NAFLD）患者肝脏炎症的应用价值。方法 在经肝活检病理学检查诊断的非酒精性单纯性脂肪肝（NAFL）患者31例、明显非酒精性脂肪性肝炎（NASH）患者31例和显著NASH患者31例及健康人31例,使用超声检测左肝和右肝4 cm、6 cm和8 cm位点ARFI值变化。结果 健康人、NAFL、明显NASH和显著NASH患者左肝4 cm、6 cm和8 cm位点ARFI平均值分别为（1.32±0.15） m/s 、（1.25±0.12） m/s 、（1.18±0.11） m/s 和（1.05±0.10） m/s,右肝ARFI平均值分别为（1.08±0.09） m/s、（0.94±0.08） m/s、（0.89±0.09） m/s 和（0.84±0.07） m/s,左右肝ARFI平均值分别为（1.19±0.10） m/s、（1.10±0.09） m/s、（1.02±0.08） m/s和（0.93±0.08） m/s,显示显著性NASH患者ARFI值显著降低（P<0.05）;四组左肝在8 cm位点ARFI值分别为（1.18±0.14）m/s、（1.02±0.13） m/s、（0.87±0.15） m/s 和（0.71±0.11） m/s,右肝在6 cm位点 ARFI值分别 为（1.06±0.10） m/s、（0.95±0.09） m/s、（0.90±0.08） m/s和（0.85±0.07） m/s,右肝在8 cm位点ARFI值分别为（1.02±0.07） m/s、（0.91±0.06） m/s、（0.81±0.08） m/s和（0.72±0.05） m/s,显示显著NASH患者ARFI值显著降低（P<0.05）。结论 ARFI技术定量评估NAFLD患者肝脏损害程度有助于对显著NASH患者的诊断,可能具有一定的临床意义。     

白藜芦醇对非酒精性脂肪性肝炎大鼠肝组织SIRT3表达的影响*

目的 研究非酒精性脂肪性肝炎(NASH)大鼠肝组织沉默交配型信息调节因子2同源蛋白3（SIRT3）的表达变化,探讨其在NASH发病中的作用及白藜芦醇对其的影响。方法 60只SD大鼠被随机分为正常对照组、NASH模型组和白藜芦醇处理组,每组20只。采用高脂饲料喂养建立NASH大鼠模型。制备新鲜肝组织匀浆,检测肝组织内活性氧（ROS）含量和超氧化物歧化酶（SOD）活性。常规检查肝组织病理学变化和超微结构的变化。采用免疫组化法分析SIRT3蛋白的亚细胞定位,采用Western Blot定量检测SIRT3蛋白的表达。结果 模型组大鼠肝指数、血清ALT、AST、TG、TC、LDL-C含量和氧化应激水平显著高于对照组（P<0.01）,药物处理组显著低于模型组（P<0.01）;模型组大鼠非酒精性脂肪性肝病活动性评分（NAS）为（6.83±0.41）分,显著高于对照组[（0.24±0.08）分,P<0.01],处理组为（3.27±0.29）分,显著低于模型组（P<0.01）;模型组大鼠肝细胞线粒体半定量评分为（3.24±0.21）分,显著高于对照组[（0.17±0.03）分,P<0.01],处理组为（1.39±0.12）分,显著低于模型组（P<0.01）;免疫组化检测显示SIRT3蛋白在细胞核和细胞质中均有表达,模型组SIRT3蛋白相对表达量为（0.24±0.03）,显著低于对照组[（0.58±0.02）,P<0.01],而处理组为（0.46±0.03）,显著高于模型组（P<0.01）。结论 NASH大鼠肝组织SIRT3表达量下降,白藜芦醇干预可通过上调SIRT3的表达改善NASH病理学变化。     

慢性乙型肝炎患者临床和肝组织病理学特点及影响肝纤维化因素分析*

目的 分析HBeAg阴性与阳性慢性乙型肝炎（CHB）患者临床和肝组织病理学特点,探讨影响CHB患者发生明显肝纤维化的危险因素。方法 回顾性分析250例CHB患者血清HBV DNA水平、Fibroscan检测肝脏硬度（stiffness）值和肝穿刺组织病理学特点,应用多因素Logistic回归模型分析影响CHB患者发生明显肝纤维化的独立危险因素。结果 160例HBeAg阴性患者血清HBV DNA ≥1×10⁵ copies/ml者所占比例显著低于HBeAg阳性组（66.9%对99.4%,P<0.05）;HBeAg阴性组血清ALT和AST水平显著低于HBeAg阳性组（P<0.05）;血清HBeAg阴性组与阳性组肝组织炎症分级和纤维化分期总体分布差异无统计学意义（P>0.05）;多因素Logistic回归分析结果显示年龄≥40岁、HBV DNA水平高、PTA低和Stiffness水平高为CHB患者存在明显肝纤维化的独立危险因素。结论 血清HBeAg阴性与阳性CHB患者存在一些临床和肝组织病理学特征的差异,血清HBeAg阴性患者可能存在更为严重的临床和预后问题,需要给予特别的关注和管理。     

颅内出血患者合并非酒精性脂肪性肝病情况分析

目的 回顾颅内出血(ICH)患者合并非酒精性脂肪性肝病(NAFLD)情况并分析其危险因素。方法 2010年1月～2020年6月我院收治的ICH患者146例,使用超声检查诊断脂肪性肝病,采用单因素和多因素Logistic回归分析,明确合并NAFLD的危险因素。结果 在本组146例ICH患者中,经超声检查发现NAFLD者52例(35.6%);合并NAFLD组2型糖尿病(T2DM)发生率为32.7%,显著高于非NAFLD组的12.8%(P<0.05),NAFLD组BMI为(25.4±2.4)kg/m²,显著高于非NAFLD组【(23.1±2.7)kg/m²,P<0.05】,NAFLD组血清高密度脂蛋白(HDL)为(1.4±0.5)mmol/L,甘油三酯(TG)为(4.2±1.6)mmol/L,与非NAFLD组【分别为(1.8±0.5)mmol/L和(2.2±1.1)mmol/L】比,差异具有统计学意义(P<0.05),NAFLD组血肿量＞30ml的比率为75.0%,显著高于未合并NAFLD组的39.4%(P<0.05),NAFLD组格拉斯哥昏迷(GCS)评分≤10分的比率为67.3%,显著高于非NAFLD组的37.2%(P<0.05),而两组合并高血压、吸烟、心血管疾病、血管畸形、血清FPG、ALT、AST和感染的比率无统计学差异(P>0.05);多因素Logistic回归分析结果提示合并T2DM、血肿量大和GCS评分低是ICH患者伴有NAFLD的独立危险因素,而血清HDL则是ICH患者不伴有NAFLD的保护性因素(P<0.05)。结论 NAFLD人群可能更容易发生ICH,可能与合并存在的高脂血症、糖尿病和血管病变有关。因此,应该加强对NAFLD人群的筛查和监测,以防止心脑血管疾病的发生,提高生存质量。     

血清AST水平与非酒精性脂肪性肝病的进展性肝纤维化有关

目的探讨我国成人非酒精性脂肪性肝病（NAFLD）进展性肝纤维化的预测因素。方法通过分析2005年1月—2009年3月经病理学证实的NAFLD患者的人口学、生化学及病理学资料,研究与组织学进展性肝纤维化相关的危险因素。非酒精性脂肪性肝炎（NASH）定义为肝组织G2以上炎症或出现BruntNASH病理标准中的肝纤维化,进展性肝纤维化定义为2期以上肝纤维化。结果总计有108例NAFLD患者纳入研究,其中单纯性脂肪肝、NASH、NASH相关肝硬化分别有67例（62.04%）、39例（36.11%）、2例（1.85%）。男性90.7%、平均年龄（36.6±11.1）岁、体质量指数（BMI）（26.34±3.38）kg/m^2、收缩压（120.13±11.17）mmHg、舒张压（76.61±8.93）mmHg。肝脏病理学结果显示,肝纤维化分期S055例（50.5%）、S128例（25.9%）、S215例（13.9%）、S38例（7.4%）、S42例（1.9%）,与S0-1组（83例）患者相比,S2-4组（25例）BMI、血清ALT和AST水平更高（P〈0.05）,年龄、血清总胆红素水平更低（P〈0.05）。Logistic逐步回归分析表明,仅血清AST增高与进展性肝纤维化相关（P=0.027,OR=3.536,CI=1.159～10.790）,ROC曲线下面积为0.724（CI=0.600～0.849,P=0.002）。结论血清AST水平增高是NAFLD出现进展性肝纤维化的重要预测因素,但准确性欠佳。     

PNPLA3 and TM6SF2 polymorphisms in Brazilian patients with nonalcoholic fatty liver disease

BACKGROUND Nonalcoholic fatty liver disease(NAFLD) is becoming the most common chronic liver disease worldwide, with significant morbidity associated with nonalcoholic steatohepatitis(NASH). Genome-wide association studies demonstrated that the variants rs738409 C/G in the PNPLA3 and rs58542926 C/T in the TM6 SF2 genes are determinants of inter-individual and ethnicity-related differences in hepatic fat content and NAFLD progression.AIM To investigate PNPLA3 and TM6 SF2 genotype frequency and their association with NAFLD development and progression in Brazilian patients.METHODS This cross-sectional case-control study enrolled 285 individuals from the Gastroenterology and Hepatology clinics at a university hospital in Brazil. The case patients(n = 148) were confirmed to have NAFLD by the identification of hepatic steatosis on ultrasonography and exclusion of other causes of liver disease. According to the clinical protocol, patients underwent liver biopsy when at high risk for NASH and/or advanced fibrosis(n = 65). Steatohepatitis was confirmed in 54 patients. Individuals who did not have biopsy indication or NASH on histology were considered to have simple steatosis(n = 94). The control group(n = 137) was selected among patients that attended the Intestinal Disease clinic and was composed of subjects without abnormalities on abdominal ultrasonography and normal liver biochemical tests. All individuals underwentPNPLA3 and TM6 SF2 genotype analysis.RESULTS PNPLA3 CC, CG and GG genotype frequencies were 37%, 44% and 19%, respectively, in NAFLD patients and were 58%, 31% and 10% in controls(P 0.001). In a model adjusted for gender, age, body mass index and type 2 diabetes mellitus, the G allele increased the chance of NAFLD(OR = 1.69, 95%CI: 1.21-2.36, P = 0.002) and NASH(OR = 3.50, 95%CI: 1.84-6.64, P 0.001). The chance of NASH was even higher with GG homozygosis(OR = 5.53, 95%CI: 2.04-14.92, P = 0.001). No association was found between G allele and the features of metabolic syndrome. In histological assessment, PNPLA3 genotype was not associated with steatosis grade, although GG homozygosis increased the chance of significant NASH activity(OR = 17.11, 95%CI: 1.87-156.25, P = 0.01) and fibrosis(OR = 7.42, 95%CI: 1.55-34.47, P = 0.01) in the same adjusted model. TM6 SF2 CC, CT and TT genotype frequencies were 83%, 15% and 0.7%, respectively, in NAFLD patients and were 84%, 16% and 0.7% in controls(P = 0.78). The T allele presence was not associated with NAFLD or NASH, and was not associated with histological features.CONCLUSION PNPLA3 may be involved in susceptibility and progression of NAFLD and NASH in the Brazilian population. More advanced histological liver disease was associated with the G allele. The TM6 SF2 genetic variants were not associated with NAFLD susceptibility and progressive histological forms in the population studied, but further studies are required to confirm these findings.     

2型糖尿病患者合并非酒精性脂肪肝及脂肪肝纤维化的危险因素分析

目的：探讨2型糖尿病（T2DM）患者合并非酒精性脂肪肝（NAFLD）及脂肪肝纤维化的危险因素。方法采集2008年5月至2009年12月期间,上海交通大学附属第六人民医院内分泌科住院的1109例T2DM患者的病史资料、生化指标、肝脏超声检查结果,根据B超检查结果将患者分为T2DM组和T2DM合并NAFLD组,采用非酒精性脂肪肝纤维化评分（NAFLDFS）的高诊断阈值（＞0.676）、低诊断阈值（＜-1.455）将T2DM合并NAFLD组分为纤维化亚组、不确定亚组、无纤维化亚组进行分析。结果（1）T2DM合并NAFLD患者体质量指数（BMI）、腰围（WC）、臀围（HC）、腰臀比（WHR）、舒张压（DBP）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、谷氨酰转肽酶（GGT）、总胆红素（TBIL）、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、尿酸（UA）、空腹血糖（FPG）、餐后2h血糖（2hPBG）、空腹C肽（FCP）、FCP代替胰岛素改良稳态模型指数（HOMA-C肽）均更高（P＜0.01或P＜0.05）,而年龄、糖尿病病程、高密度脂蛋白胆固醇（HDL-C）则显著低于T2DM患者（P＜0.01,表1）。（2）逐步logistic回归提示BMI[比值比（OR）＝1.325,95%CI 1.249～1.406]、ALT（OR＝1.025,95%CI 1.013～1.038）、TG（OR＝1.283,95%CI 1.105～1.490）是T2DM合并NAFLD的危险因素,HDL（OR＝0.532,95%CI 0.286～0.989）则是保护因素。（3） T2DM合并NAFLD患者中,纤维化亚组占13.4%。与无纤维化及不确定两亚组比较,年龄、病程、BMI、WC、HC、收缩压（SBP）、AST/ALT、GGT、糖化血红蛋白（HbA1c）显著增加（P＜0.01）,然而ALT、白蛋白（ALB）、TG、血小板（Plt）显著减少（P＜0.01或P＜0.05）,差异具有统计学意义。（4）有序多因素logistic回归提示,年龄、BMI、ALB、AST/ALT、Plt是T2DM合并NAFLD肝纤维化的危险因素。结论住院T2DM合并NAFLD患者比例较大,与BMI     

Association of non-alcoholic fatty liver disease with thyroid function: A systematic review and meta-analysis

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. The relationship of NAFLD with thyroid function parameters and hypothyroidism remains controversial.AimTo clarify the effect of thyroid function parameters and hypothyroidism on the development of NAFLD and progression to nonalcoholic steatohepatitis (NASH).MethodsPubMed, EMBASE, and Cochrane library databases were searched. Study quality was assessed. Weighted mean difference (WMD) and odds ratio (OR) with 95% confidence interval (CI) were calculated.ResultsTwenty six studies involving 61,548 participants were eligible, most of which were of high quality. NAFLD/NASH patients had significantly higher TSH levels than controls in adults (NAFLD versus health: WMD = 0.105, 95%CI = 0.012–0.197; NAFLD versus euthyroidism: WMD = 0.100, 95%CI = 0.005–0.194; NASH versus NAFLD: WMD = 0.540, 95%CI = 0.136–0.944) and children/adolescents (NAFLD versus lean controls: WMD = 1.039, 95%CI = 0.104–1.973; NAFLD versus overweight/obese controls: WMD = 0.485, 95%CI = 0.267–.703). Unclassified hypothyroidism was positively associated with the risk of NAFLD/NASH in adults (NAFLD versus health: OR = 1.605, 95%CI = 1.180–2.183; NASH versus NAFLD: OR = 2.317, 95%CI = 1.425–3.768) and children/adolescents (NAFLD versus overweight/obese controls: OR = 2.015, 95%CI = 1.246–3.258). However, the statistical results were inconsistent among the subgroup meta-analyses of subclinical and overt hypothyroidism. Association of NAFLD with FT3 and FT4 levels was heterogeneous among population.ConclusionTSH level may be an important risk factor for the development and progression of NAFLD, independent of thyroid hormones.     

空腹C肽评估NAFLD合并T2DM患者肝纤维化进展价值分析*

目的 探讨空腹C肽对非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)患者肝纤维化进展的评估价值。方法 在456例NAFLD合并T2DM患者中,经肝脏硬度检测(LSM),发现非进展性肝纤维化组415例和进展性肝纤维化组41例。采用Logistic回归分析影响肝纤维化进展的因素,并采用受试者工作特征曲线(ROC)评价空腹 C 肽对进展性肝纤维化的诊断价值。结果 进展性肝纤维化患者血清HDL-C、PLT计数、AST、空腹C肽和糖化血红蛋白(HbA1c)分别为(1.5±0.2)mmol/L、(259.3±50.3)×10⁹/L、(39.3±5.1)U/L、(2.7±0.8)ng/ml和(10.7±1.0)%,与非进展性肝纤维化组比,差异显著【分别为(1.4±0.3)mmol/L、(267.1±48.2)×10⁹/L、(26.1±4.1)U/L、(2.1±0.7)ng/ml和(8.1±1.1)%,P<0.05】;经Logistic回归分析发现,年龄【OR=0.915,95 %CI:0.841～0.995,P=0.038】、性别(OR=1.250,95% CI:1.005～1.554,P=0.045)、BMI(OR=1.117,95% CI:1.011～1.235,P=0.030)、HbA1c水平(OR=1.117,95% CI:1.011～1.235,P=0.030)和空腹C肽水平(OR=1.206,95% CI:1.068～1.361,P=0.003)是进展性肝纤维化发生的独立影响因素;经ROC曲线分析发现,空腹 C 肽诊断进展性肝纤维化的ROC下面积(AUC)为0.7(95% CI:0.7～0.81,P<0.05),即当空腹C肽水平为2.36 ng/mL时,其诊断的灵敏度为73.2%,特异度为67.0%。结论 利用空腹 C 肽水平诊断NAFLD合并T2DM患者进展性肝纤维化具有一定的诊断价值,值得临床进一步研究。     

Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic (type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease

AIM: 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.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.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 χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM 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 T2 DM.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 T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM 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.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.     

老年男性2型糖尿病患者非酒精性脂肪性肝病临床病理研究

目的 研究老年男性2型糖尿病患者(T2DM)非酒精性脂肪性肝病(NAFLD)发生率及肝脏病理组织学改变的特点.方法 从858例成人尸检材料中,选择病程在10年以上T2DM患者89例为T2DM组,对照组48例,观察各组肝脏组织病理学改变,同时进行组织化学(Masson三色、过碘酸雪夫染色、唾液酶消化-过碘酸雪夫染色、Van Greson氏染色、网状纤维染色)及免疫组织化学(CK8/18)染色.结果 T2DM组89中符合NAFLD诊断44例(49.4%/),非酒精性脂肪性肝炎(NASH)13例(14.6%),对照组48例诊断NAFLD为11例(22.9%),NASH 2例(4.2%),两组间比较差异有统计学意义(P＜0.01、P＜0.05).T2DM组诊断NASH患者均伴有肝纤维化,对照组2例中有1例伴有肝纤维化.T2DM组1例出现肝硬化,对照组未见肝硬化病例.结论 与非糖尿病组相比,老年男性T2DM组NAFLD疾病发生率高,肝损伤程度重;T2DM组NASH患者肝纤维化发生率高;NAFLD患者进展为肝硬化比率低.     

非酒精性脂肪性肝病患者粪便钙卫蛋白检测及其意义*

目的 探讨粪便钙卫蛋白（FC）评估非酒精性脂肪性肝病（NAFLD）患者肠道炎症状态的应用价值。方法 纳入NAFLD和健康人,采用酶联免疫吸附试验检测粪便钙卫蛋白水平,并收集两组研究对象的一般资料和血生化指标。结果 91例正常人和81例NAFLD患者体质指数（BMI）分别为（22.6±2.4） kg/m²和（28.5±4.0） kg/m²,腰围分别为（80.9±7.9） cm和（91.6±9.5） cm,血清谷草转氨酶（AST）分别为（19.3±4.8） u/L和（33.7±18.7） u/L,谷丙转氨酶（ALT）分别为（17.5±7.1） u/L和（55.0±44.5） u/L,甘油三酯（TG）分别为（0.9±0.3） mmol/L和（2.4±2.3） mmol/L,总胆固醇（TC）分别为（4.3±0.6） mmol/L和（5.1±1.3） mmol/L,差异均有统计学意义（P<0.05）;NAFLD组FC水平为43.0（18.8~87.0）μg/g,显著高于正常人的11.4（4.6~24.4）μg/g,差异有统计学意义（P<0.00）;NAFLD组和正常人FC水平大于50 μg/g者分别为48例（59.3%）和6例（6.6%）,两者构成比差异具有统计学意义（x²=55.178,P<0.001）;相关性分析显示,NAFLD患者FC水平与BMI、腰围、血清GGT、TC水平呈正相关（r=0.725,r=0.570,r=0.292,r=0.400,P值均<0.05）;多因素分析发现,低水平的HDL、高水平的TG、BMI和TC是NAFLD发病的独立危险因素（OR=0.011,OR=13.558,OR=1.821,OR=3.086,P值均<0.01）。结论 NAFLD患者粪便FC水平升高,反映肠道可能存在一定的炎症。     

Dietary vitamin E and C intake is inversely associated with the severity of nonalcoholic fatty liver disease

Background & aimsAlthough antioxidants have a protective potential in nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), there is limited evidence regarding the role of dietary intake of antioxidants. The aim was to test the association between dietary vitamins E and C intake and NAFLD, NASH and fibrosis markers.MethodsCross-sectional study of a large cohort of subjects undergoing colonoscopy. The presence of NAFLD was evaluated by ultrasonography. The level of steatosis was defined using SteatoTest, moderate-severe NASH using new quantitative NashTest and borderline-significant fibrosis ≥ F1–F2 using FibroTest. Nutritional intake was measured by food frequency questionnaire (FFQ).ResultsOverall, 789 subjects were included (52.6% men, age 58.83 ± 6.58 years), 714 had reliable FibroMax. Adjusting for BMI, dietary and lifestyle factors, the upper tertile of vitamin E intake/1000 Kcal was associated with lower odds of NASH (OR = 0.64, 0.43–0.94, P = 0.024). There was an inverse association between reaching the recommended vitamin E intake and NASH (OR = 0.48, 0.30–0.77, P = 0.002). The upper tertile of vitamin C intake/1000 Kcal was associated with lower odds of NAFLD and NASH (OR = 0.68, 0.47–0.99, P = 0.045; OR = 0.57, 0.38–0.84, P = 0.004, respectively). Both vitamins were related with the level of steatosis according to SteatoTest.ConclusionVitamin E and C intake may be protective from NAFLD-related liver damage.     

Histopathological stages of nonalcoholic fatty liver disease in type 2 diabetes: prevalences and correlated factors

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM). However, data regarding the prevalence and correlates of its histopathological stages are scarce. The aim was to investigate the prevalence and correlates of the more severe histopathological features of NAFLD, nonalcoholic steatohepatitis (NASH) and advanced fibrosis, in T2DM. Methods: From 125 patients with ultrasonographic evidence of NAFLD, 98 patients underwent liver biopsies, which were examined by two independent pathologists regarding the presence of NASH and graded according to the NASH Clinical Research Network scoring system. Agreement between pathologists was assessed by weighted κ coefficients and independent correlates of NASH and advanced fibrosis (grade ≥2) by multivariate logistic regression. Results: Ninety‐two (94%) patients presented histological NAFLD. Interobserver agreement was substantial to excellent for NASH diagnosis (κ=0.82) and steatosis grading (κ=0.76), and moderate for the NAFLD activity score (κ=0.58) and fibrosis grading (κ=0.52). The prevalence of NASH was 78%, and its independent correlates were hypertriglyceridaemia (P=0.034), high alanine aminotranferase level (P=0.044) and low serum high‐density lipoprotein‐cholesterol (P=0.079). The prevalence of advanced fibrosis ranged from 34% in the best scenario (lowest fibrosis score) to 60% in the worst scenario (highest score). Its independent correlates were a high serum γ‐glutamyl transferase (P=0.002), older age (P=0.022) and male gender (P=0.064). No diabetes‐related clinical characteristic was associated with NASH or advanced liver fibrosis. Conclusions: The prevalence of the severe features of NAFLD is high in T2DM patients. Liver biopsy shall be considered in all diabetic patients with ultrasonographic evidence of NAFLD.