非酒精性脂肪性肝病患者血清铁代谢指标的变化及临床意义

目的观察非酒精性脂肪性肝病(NAFLD)患者血清铁代谢指标变化及其临床意义。方法收集2014年7月-2016年4月上海市第八人民医院收治的68例NAFLD患者(NAFLD组),另选取健康体检者70例(健康对照组)。68例NAFLD患者中单纯NAFLD患者24例,伴ALT异常者44例。检测所有研究对象的AST、ALT、TC、TG水平及铁代谢指标[血清铁(SI)、血清铁蛋白(SF)、血清铁调素(HEPC)]水平,观察NAFLD患者ALT异常与血清铁代谢指标的相关性。计量资料组间比较采用独立样本t检验,计数资料组间比较采用χ~2检验,两变量间的相关性采用Pearson相关系数分析。结果 NAFLD组患者的BMI、ALT、AST、TC、TG水平均显著高于健康对照组(t值分别为9.8、8.6、8.5、9.2、2.7,P值均0.05);铁代谢指标SI、SF水平显著高于健康对照组[SI:(21.7±7.1)μmol/L vs(18.7±6.9)μmol/L,t=2.3,P=0.02;SF:(340.2±257.6)μg/L vs(119.1±81.2)μg/L,t=6.7,P0.01)],HEPC显著低于健康对照组[(12.2±5.3)μg/L vs(22.2±6.5)μg/L,t=9.9,P0.01)]。伴ALT异常NAFLD患者的血清ALT、SI、SF水平显著高于单纯NAFLD患者[ALT:(89±58)U/L vs(26±8)U/L,t=7.1,P0.01;SI:(23.4±6.2)μmol/L vs(19.6±7.9)μmol/L,t=2.2,P=0.03;SF:(406.2±290.0)μg/L vs(219.4±112.0)μg/L,t=3.7,P0.01),血清HEPC水平显著低于单纯NAFLD患者[(7.4±4.9)μg/L vs(16.1±7.8)μg/L,t=4.7,P0.01)]。Pearson相关性分析结果显示,SF与ALT、AST呈显著正相关(r值分别为0.28、0.34,P值分别为0.02、0.01)。结论 NAFLD患者存在显著铁超载,且在伴ALT异常的NAFLD患者中表现更为明显。SF与ALT、AST呈显著正相关。血清铁蛋白能在一定程度上反映NAFLD患者肝损伤严重程度。     

非酒精性脂肪性肝病患者血清视黄醛结合蛋白4的变化及临床意义

目的观察非酒精性脂肪性肝病(NAFLD)患者视黄醇结合蛋白4(RBP4)的变化及其临床意义。方法收集2016年7月至2018年6月上海市第八人民医院收治的80例NAFLD患者(NAFLD组),另选取健康体检者72例(健康对照组)。80例NAFLD患者中单纯NAFLD患者30例,伴ALT异常的NAFLD患者50例。检测所有研究对象的ALT、AST、TG、TC、FBG、空腹胰岛素水平及RBP4水平,观察NAFLD患者ALT异常、肝纤维化程度、胰岛素抵抗程度与RBP4的相关性。计量资料组间比较采用独立样本t检验,计数资料组间比较采用χ2检验,两变量间的相关性采用Pearson相关系数分析。结果NAFLD组患者的AST、ALT、TG、TC、FBG、HOMA-IR、NAFLDFS水平均显著高于健康对照组(t值分别为8.016、8.581、4.997、10.080、4.877、6.989、5.639,P值均<0.01);RBP4水平显著高于健康对照组[(533.95±197.21)ngl/ml vs(249.09±58.78)ngl/mL,t=11.791,P<0.05]。肝纤维化危险组的FBG、HOMA-IR、RBP4高于无肝纤维化组[FBG:(7.05±2.12)mmol/L vs(5.05±0.33)mmol/L,t=-4.644,P<0.01;HOMA-IR(3.88±1.76)vs(2.36±1.72),t=-4.725,P<0.01;RBP4:(588.23±133.33)ngl/ml vs(463.40±103.20)ngl/mL,t=-4.721,P<0.01]。伴ALT异常NAFLD患者的血清ALT水平显著高于单纯NAFLD患者[ALT:(106.79±59.56)U/L vs(26.90±8.21)U/L,t=-7.081,P<0.01];但RBP4无明显差异[RBP4:(509.80±118.76)ngl/mL vs(520.44±139.93)ngl/mL,t=-0.348,P=0.729]。Pearson相关性分析结果显示,RBP4与HOMA-IR、NAFLDFS呈显著正相关(r值分别为0.430、0.464,P值均<0.01);与ALT(r=-0.061,P=0.593)无相关。结论NAFLD患者存在RBP4高表达,且在胰岛素抵抗、肝纤维化程度高的NAFLD患者中表现更为明显。血清RBP4能在一定程度上反映NAFLD患者胰岛素抵抗、肝纤维化的严重程度。     

非酒精性脂肪性肝病患者肝损伤程度与IL-18、IL-8含量的相关性

目的 探讨非酒精性脂肪性肝病(NAFLD)患者肝损伤程度与白介素(IL)-18、IL-8水平的相关性.方法 分别用酶联免疫吸附分析(ELISA)法及放射免疫分析(RIA)法检测60例NAFLD患者(NAFLD组)[其中非酒精性脂肪肝患者30例(NAFL组),非酒精性脂肪性肝炎患者30例(NASH组)]和30例正常对照组血清IL-18、IL-8的水平;常规方法检测ALT、AST、TG的水平.结果 NAFL组、NASH组与对照组比较血清IL-18、IL-8、TNF-a、ALT、AST、TG水平差异具有非常显著性(P<0.01),NAFL组与对照组及NASH组与NAFL组比较,上述指标差异均具有显著性(P<0.05).结论 IL-18、IL-8水平随肝细胞受损程度加重而增加,并与ALT、TG水平呈正相关.IL-18是T细胞介导肝损伤的必须媒介,IL-8是介导炎症反应中起重要作用的因子,可能在肝损伤起重要作用.血清IL-18、IL-8浓度的高低可用于判断NAFLD患者肝损伤的严重程度及监测疾病变化.     

非酒精性脂肪性肝病患者血清铁蛋白检测的意义

目的了解非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)患者血清铁蛋白(serum ferritin,SF)的检测意义。方法采用微粒子酶免疫分析法(MEIA)测定250例NAFLD患者的血清铁蛋白值,并根据患者首诊时CT片脂肪肝分度分为轻度组(65例)、中度组(98例)和重度组(87例),对3组患者的SF值进行比较分析。结果 250例NAFLD患者中ALT正常者135例,SF平均值为(320.5±167.0)ng/ml;ALT异常者115例,SF平均值为(608.5±254.4)ng/ml,差异有统计学意义(z=10.38,P=0.00)。轻度组、中度组和重度组患者ALT值分别为(87.2±52.0)U/L、(99.4±68.5)U/L、(89.4±78.0)U/L,3组间差异无统计学意义(z=0.18,P=0.43)。3组患者的SF值分别为(330.5±118.0)ng/ml、(350.2±187.5)ng/ml、(509.4±150.8)ng/ml,轻度组和中度组SF无统计学差异,重度组SF显著升高,与轻度组和中度组差异显著(z=8.20、6.39,P值均为0.00)。结论 NAFLD患者SF的升高与肝脏脂肪变程度和肝细胞的损害程度密切相关。     

173例脓毒症患者血清CK-MB、ALT、AST水平与病情严重程度的关系分析

目的探讨磷酸肌酸激酶同工酶(CK-MB)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基酶(AST)在脓毒症患者血清中的水平及意义。方法选取2016年1月至2018年9月在我院治疗的脓毒症患者173例,根据住院期间预后情况分为死亡组(n=61)和存活组(n=112),同时根据入院时APACHEⅡ评分分为轻度组(n=42)、中度组(n=73)和重度组(n=58),检测患者血清CK-MB、ALT和AST水平。结果重度患者血清CK-MB、ALT和AST分别为(190.22±23.32)U/L、(132.29±11.43)U/L和(140.22±15.50)U/L,明显高于中度和轻度患者(P0.05);中度患者血清CK-MB、ALT和AST分别为(150.92±20.05)U/L、(101.22±9.82)U/L和(110.28±12.21)U/L,明显高于轻度[(121.29±21.11)U/L、(86.93±10.02) U/L和(90.33±11.40) U/L]患者(P0.05);死亡患者血清CK-MB、ALT和AST分别为(201.11±25.58)U/L、(129.82±13.29)U/L和(134.40±14.33)U/L,明显高于存活患者[(143.39±30.22) U/L、(100.05±11.22)U/L和(109.28±13.32)U/L](P0.05);APACHEⅡ评分与CK-MB、ALT和AST呈正相关(r=0.483、0.434和0.455,P0.05)。结论脓毒症患者血清CK-MB、ALT和AST明显升高,与病情严重程度及预后有一定关系,CK-MB、ALT和AST水平越高,患者病情越严重,预后越差。     

非经典Wnt信号通路在2型糖尿病大鼠非酒精性脂肪性肝炎发生与发展中的作用

目的 探讨非经典Wnt信号通路在2型糖尿病大鼠非酒精性脂肪性肝炎(NASH)发生与发展中的作用.方法 将雄性SD大鼠24只随机等分为对照组和模型组.对照组喂以基础饲料;模型组喂以高糖高脂饲料.4周后,模型组注射链脲佐菌素(30 mg/kg)诱导2型糖尿病(T2DM).各组继续对应饲料喂养至12周,模型组成功造模为T2DM-NASH模型.取血清及肝脏组织.检测血清葡萄糖、ALT、AST水平;苏木素-伊红及油红O染色观察肝脏病理改变;免疫组织化学、Western blot检测肝脏Wnt5a、NF-κB p65蛋白的表达;实时PCR定量检测肝脏Wnt5a mRNA、NF-κB p65 mRNA的表达,分别与对照组比较.数据以均数土标准差(x-±s)表示,采用t检验和直线相关与回归分析进行统计学分析. 结果 对照组和T2DM-NASH组中,血清葡萄糖分别为(6.25土1.28)mmol/L和(31.21±0.86) mmol/L,t=-36.204;血清ALT分别为(31.00±3.69) U/L和(301.50±8.62)U/L,t=-99.94 ;血清AST分别为(77.58±1.83)U/L和(344.75±1.82) U/L,t=-358.85,P值均＜0.01.苏木素-伊红及油红O染色显示肝细胞脂肪变性及肝组织炎症.免疫组织化学结果显示对照组和TDM-NASH组的Wnt5a表达量(积分吸光度)分别为1.15E4±577.45和4.04E5±2.42E4,t=-56.24;NF-κB p65表达量(积分吸光度)分别为1.28E4±1.59E3和4.21E5±1.68E4,t=-83.895,P值均＜0.01.Western blot结果显示T2DM-NASH组Wnt5a蛋白相对表达量和对照组相比为4.21土0.34比1.00±0.25,t=17.030 ; T2DM-NASH组NF-κB p65蛋白相对表达量和对照组相比为4.93±0.76比1.00±0.13,t=11.438,P值均＜0.01.实时定量PCR结果显示T2DM-NASH组Wnt5a mRNA相对表达量和对照组相比为9.53±0.64比1.04土0.35,t=20.165,P＜0.01 ; T2DM-NASH组NF-κB p65 mRNA表达量和对照组相比为0.60±0.13比0.74±0.10,t=-1.802,P=0.125.相关性分析结果表明T2DM-NASH组肝组织Wnt5a蛋白表达水平分别与血清ALT、AST水平存在正相关性(r=0.64,P＜0.05;r=0.59,P＜0.05).肝组织Wnt5a与NF-κB p65蛋白表达存在正相关性(r=0.58,P＜0.05).结论 Wnt5a可能通过激活NF-κ B介导炎症反应参与到T2DM合并NASH的发生与发展.     

2型糖尿病男性患者血清睾酮水平低下对非酒精性脂肪性肝病的影响

目的研究2型糖尿病(type 2 diabetes mellitus,T2DM)男性患者血清睾酮水平低下对非酒精性脂肪性肝病(non-alcoholic fatty live disease,NAFLD)的影响。方法采用随机数字表法抽取160例广东省湛江市第一中医医院收治的T2DM男性患者进行临床分析,根据是否合并NAFLD分为NAFLD组(75例)非NAFLD组(85例),同时按照超声检查结果将NAFLD组分为中重度组(40例)和轻度组(35例)2个亚组,分析NAFLD与睾酮水平(testosterone,TT)间的关系。结果 NAFLD组患者血清ALT、GGT和TG水平均高于非NAFLD组,HDL-C和TT水平均低于非NAFLD组,差异有统计学意义(P均0.05);两组患者的ALP和AST差异无统计学意义(P0.05)。轻度NAFLD患者的TT值为(3.76±1.56)ng/ml,中重度NAFLD患者的TT值为(3.01±0.97)ng/ml,差异有统计学意义(t=3.697,P0.001)。TT水平与血清ALT、GGT、TG呈负相关(r值分别为-0.619、0.782、0.503,P值分别为0.001、0.001、0.003),与HDL-C呈正相关(r=0.592,P=0.002)。结论对于男性T2DM患者,血清总睾酮水平降低与其发生NAFLD具有相关性,对血清总睾酮水平进行监测可为血清睾酮水平低下2型糖尿病男性患者NAFLD的预防及治疗提供参考。     

IGF1和IGFBP3在非酒精性脂肪性肝病病程中的表达变化

目的比较IGF1、IGFBP3血清水平在单纯性脂肪肝(NAFL)和脂肪性肝炎(NASH)中的表达差异,探讨血清IGF1、IGFBP3水平与非酒精性脂肪性肝病(NAFLD)的疾病进展及与相关代谢参数的关联性。方法选取符合NAFLD诊断标准的患者80例,其中NASH患者50例,30例年龄、性别匹配的NAFL患者,采用酶联免疫分析法(ELISA)测定两组患者血清胰岛素样生长因子1(IGF1)、胰岛素样生长因子结合蛋白3(IGFBP3)表达水平以及相关代谢参数。结果与NAFL组相比,NASH组患者有更高的体质指数(BMI)、腰围、肝酶指标(ALT、AST、γ-GGT)、胰岛素(Insulin)水平、胰岛素抵抗水平(HOMA-IR)、游离脂肪酸水平(FFA),IGF1水平明显下调(149.89+114.94)对(100.78+51.97),(P=0.034);IGFBP3明显上调(10.52+6.44)对(16.66+11.6),(P=0.003)。结论 IGF1、IGFBP3可能与NAFLD疾病进展密切相关。     

血清FGF-21水平与非酒精性脂肪性肝病的相关性

目的探讨成纤维细胞生长因子21(FGF-21)与非酒精性脂肪性肝病(NAFLD)进展的相关性,无创预测诊断非酒精性脂肪性肝炎(NASH)。方法选取NAFLD患者80例,正常健康人群50例作为对照。测量身高、体质量、腰围等生理指标,计算BMI;检测ALT、AST、AST/ALT、ALP、GGT、TC、TG、HDL、LDL等生化指标;双抗夹心法测定血清中FGF-21浓度水平。结果血清FGF-21与AST及低密度脂蛋白胆固醇具有相关性(P0.05),与肝细胞脂肪变性、气球样变、小叶内炎症、汇管区炎症及纤维化程度呈高度相关(P0.01);随NAS评分增高其浓度增大,呈高度正相关(r=0.881,P0.01);NASH患者血清中FGF-21明显高于Non-NASH患者(t=0.127,P0.01),经ROC曲线分析,AUC=0.977,利用Youden指数确定最佳敏感性为97.4%,特异性为91.7%,最佳cut-off值为40.76 ng/L,具有较高的诊断能力。结论 NASH患者血清FGF-21水平明显升高,血清FGF-21可作为评价NASH及其严重程度的独立预测因子,可以作为一个无创性诊断指标对NASH进行诊断。     

非酒精性脂肪性肝病儿童血清25-(OH)D3和IL-17水平变化初步研究

目的调查非酒精性脂肪性肝病(NAFLD)肥胖儿童血清25羟维生素D3[血清25-(OH)D3]和白介素-17(IL-17)水平变化。方法 2014年1月～2017年12月我院诊治的肥胖儿童62例,参照非酒精性脂肪性肝病诊疗指南标准诊断单纯性非酒精性脂肪肝(NAFL)36例,非酒精性脂肪性肝炎(NASH)26例,另选健康儿童30例,采用ELISA法检测血清25-(OH)D和IL-17水平。结果 NAFL儿童血清25-(OH)D3水平为(15.2±2.1) ng/mL,NASH儿童为(9.6±1.3) ng/ml,均显著低于健康儿童的(26.3±2.3) ng/mL,而血清IL-17水平分别为(17.1±7.8)μg/L和(36.2±12.6)μg/L,均显著高于健康儿童的(1.4±0.5)μg/L,差异均有统计学意义(P0.05);中度脂肪变儿童血清ALT和AST水平分别为(54.1±15.4) U/L和(46.5±12.6) U/L,重度组儿童分别为(117.1±37.1) U/L和(78.5±31.0) U/L,均显著高于轻度组的(33.4±4.6) U/L和(30.5±2.9) U/L(P0.05);中度脂肪变儿童血清25-(OH)D3水平为(10.2±1.4) ng/ml,重度组儿童为(8.4±1.1) ng/ml,显著低于轻度组的(15.8±2.0) ng/mL(P0.05),而血清IL-7水平分别为(22.2±6.3)μg/L和(39.6±9.2)μg/L,显著高于轻度脂肪变儿童的(13.5±3.5)μg/L,组间差异均有显著性统计学意义(P0.05)。结论 NAFLD儿童血清25-(OH)D3水平降低,而血清IL-17水平升高,它们的变化可能与肝内脂肪变程度有关,动态监测这些变化,可能对了解病情和防治效果判断起指导作用。     

Non-alcoholic steatohepatitis with normal aminotransferase values

AIM： To investigate the aspects of liver histology in patients with non-alcoholic steatohepatitis （NASH） who had normal aminotransferase levels. METHODS： Thirty-four patients diagnosed with liver steatosis by ultrasonographic examination participated in the study. We compared all non- alcoholic fatty liver disease and NASH cases, according to aminotransferase level, aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio and presence of metabolic syndrome. RESULTS： Sixteen of 25 patients with high aminotransferase levels were diagnosed with NASH and nine with simple fatty liver according to liver histology. Among the nine patients with normal aminotransferase levels, seven had NASH and two had simple fatty liver. The patients with normal and high liver enzyme levels had almost the same prevalence of NASH and metabolic syndrome. Liver histology did not reveal any difference according to aminotransferase levels and AST/ALT ratio. CONCLUSION： Aminotransferase levels and AST/AIT ratio do not seem to be reliable predictors for NASH. Despite numerous non-invasive biomarkers, all patients with fatty liver should undergo liver biopsy.     

Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease

AIM To identify a panel of biomarkers that can distinguish between non-alcoholic fatty liver disease(NAFLD) and non-alcoholic steatohepatitis(NASH), and explore molecular mechanism involved in the process of developing NASH from NAFLD.METHODS Biomarkers may differ during stages of NAFLD. Urine and blood were obtained from non-diabetic subjects with NAFLD and steatosis, with normal liver function(n = 33), from patients with NASH, with abnormal liver function(n = 45), and from healthy age and sex-matched controls(n = 30). Samples were subjected to metabolomic analysis to identify potential non-invasive biomarkers. Differences in urinary metabolic profiles were analyzed using liquid chromatography tandem mass spectrometry with principal component analysis and partial least squares-discriminate analysis.RESULTS Compared with NAFLD patients, patients with NASH had abnormal liver function and high serum lipid concentrations. Urinary metabonomics found differences in 31 metabolites between these two groups, including differences in nucleic acids and amino acids. Pathway analysis based on overlapping metabolites showed that pathways of energy and amino acid metabolism, as well as the pentose phosphate pathway, were closely associated with pathological processes in NAFLD and NASH.CONCLUSION These findings suggested that a panel of biomarkers could distinguish between NAFLD and NASH, and could help to determine the molecular mechanism involved in the process of developing NASH from NAFLD. Urinary biomarkers may be diagnostic in these patients and could be used to assess responses to therapeutic interventions.     

Obesity and non-alcoholic fatty liver disease in chronic hepatitis C

BACKGROUND: Superimposed non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) may affect HCV-related fibrosis. We performed a study to determine the relationship between NAFLD and chronic hepatitis C. METHODS: One hundred and twenty patients with chronic hepatitis C and available liver biopsies were included. Baseline liver biopsies were read by 1 hepatopathologist using Metavir, as well as a fatty liver pathology protocol. Patients' baseline clinical, demographic, and virologic data were associated with the extent of steatosis (>33% vs. < or =33%), the type of fatty liver (no steatosis vs. steatosis only vs. NASH), and the stage of fibrosis seen on the liver biopsy. RESULTS: Seventy percent of patients were men and 80% were white. The mean age was 47.48+/-5.70 years, mean BMI was 29.01 +/-5.01 kg/m, and mean waist to hip ratio (W/H) was 0.90+/-0.08. Patients with higher grade of steatosis had higher BMI (32.83+/-6.26 vs. 28.49+/-4.62, P = 0.034), more likely to have genotype 3 (21.4% vs. 5.7%, P = 0.037) and advanced fibrosis (92.9% vs. 62.3%, P = 0.033) than those with lower grade of steatosis. Of these, only HCV-genotype 3 remained independently associated with higher grade of steatosis. When patients with superimposed NASH (n = 22) were compared with those with only steatosis (n = 49) and those without steatosis (n = 49), patients with superimposed NASH had more evidence of obesity (BMI: 30.64+/-5.23 vs. 29.90+/-5.35 vs. 27.33+/-4.07, P = 0.008; W/H: 0.97+/-0.06 vs. 0.91+/-0.08 vs. 0.87+/-0.07, P < 0.001), more commonly infected with HCV genotype 3 (14% vs. 12% vs. 0%, P = 0.036) and had more advanced fibrosis (95.5% vs. 75.5% vs. 42.9%, P < 0.001). Race, gender, and age did not affect extent of steatosis or presence of superimposed NASH. CONCLUSION: In conclusion, markers of obesity (BMI and W/H) and HCV genotype 3 are associated with the extent of steatosis and type of fatty liver. Higher grade of steatosis and presence of superimposed NASH are both associated with advanced hepatic fibrosis.     

Clinical, biochemical and histological correlations in a group of non-drinker subjects with non-alcoholic fatty liver disease

The correlation between biochemistry, imaging-studies and histology is a matter of controversy in non-alcoholic fatty liver disease (NAFLD) and the major pathophysiology of non-alcoholic steatohepatitis (NASH) is still unknown. We aimed to perform a comparative analysis between clinical, biochemical and histological variables of NAFLD. One-hundred and five NAFLD patients (F/M: 51/54), were studied, all with no-alcohol intake. The groups were followed-up for six months. Necroinflammation and fibrosis were more severe in patients with diabetes (p = 0.002, and p = 0.0001, respectively). In comparing NAFL to NASH, plasma nitric-oxide and malondialdehyde levels were significantly higher (p = 0.05, for-both), and vitamin-E and-C levels were significantly lower in NASH (p = 0.002, and 0.001, respectively). The serum ferritin levels were higher in NASH patients (p = 0.016). While the ultrasonographic grade was significantly higher, the liver-spleen density gradient was significantly lower in NASH group (p = 0.017, and 0.005, respectively). Within a six month period, serum ALT levels dropped into the normal range in 23/76 (30.3%) patients and serum ALT in the 6th month correlated significantly with the severity of steatosis, inflammation and fibrosis in initial biopsy (p = 0.023, 0.035, 0.011, respectively). In conclusion, the probability of severe liver disease is higher in patients with elevated-ALT in NAFLD. Serum ferritin levels have some prognostic significance in liver damage and fibrosis. Overt diabetes is predictive of advanced fibrosis and inflammation. However impaired glucose-tolerance is not. The advice on diet and exercise for six months after diagnosis may be a good strategy in NAFLD. The patients with normal-ALT without hepatomegaly, morbid-obesity and diabetes seem to have a good prognosis, however some of these patients may still require liver biopsy.     

Clinical model for distinguishing nonalcoholic steatohepatitis from simple steatosis in patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) encompasses both simple steatosis and nonalcoholic steatohepatitis (NASH). Differentiation of these two entities requires histopathologic evaluation. The aim of this study was to establish a reliable diagnostic model for differentiating steatosis from steatohepatitis utilizing both clinical characteristics and a panel of biochemical markers of lipid peroxidation and fibrosis. Eighty subjects with biopsy proven NAFLD were enrolled, 39 with simple steatosis and 41 with histopathologic evidence of NASH. Demographic and laboratory data to include serologic testing for 8-epi-PGF(2alpha), transforming growth factor-beta (TGF-beta), adiponectin, and hyaluronic acid (HA) were obtained and compared between the two groups. There were significant differences between the two groups with respect to age (P=0.004), female gender (P=0.024), aspartate aminotransferase (AST) (P=0.028), body mass index (BMI) (P=0.003), fasting insulin (0.018), AST/alanine aminotransferase (ALT) ratio (AAR) (P=0.017), quantitative insulin sensitivity check index (QUICKI) (P=0.002), and HA (P=0.029). A composite index for distinguishing steatosis from NASH was calculated by summing the risk factors of age >or=50 years, female gender, AST>or=45 IU/l, BMI >or=30 mg/kg2, AAR>or=0.80, and HA>or=55 microg/l, and its accuracy was determined by receiver operating characteristic (ROC) analysis to be 0.763 (95% CI: 0.650-0.876). The presence of three or more risk factors had a sensitivity, specificity, PPV, and NPV of 73.7%, 65.7%, 68.2%, and 71.4%, respectively. In addition, HA at a cutoff of 45.3 microg/l was a good predictor of advanced fibrosis. In conclusion, we propose a noninvasive screening model for distinguishing simple steatosis from NASH. Identifying patients at risk for NASH will allow clinicians to more accurately determine who may benefit from liver biopsy.     

代谢综合征与慢性乙型病毒性肝炎及非酒精性脂肪性肝病患者肝纤维化程度的相关性研究

目的 比较慢性乙型病毒性肝炎患者和非酒精性脂肪性肝病患者代谢综合征患病率,以及代谢综合征对慢性乙型病毒性肝炎患者和非酒精性脂肪性肝病患者肝纤维化进展的影响.方法 对2008年1月至2009年6月在我院就诊的136例慢性乙型病毒性肝炎患者和110例非酒精性脂肪性肝病患者进行回顾性分析,调查其代谢综合征的患病率,测定肝功能及病毒学指标,进行肝脏病理学检查.采用t检验和X~2检验进行统计学分析.结果 代谢综合征总的患病率为28.5%,非酒精性脂肪性肝病患者代谢综合征患病率显著高于慢性乙型病毒性肝炎患者(分别为49.1%和11.8%).肝纤维化分期为S_(0～1)、S_(2～4)的慢性乙型病毒性肝炎患者代谢综合征的患病率分别为3.1%和19.7%(P＜0.01),代谢综合征、体重指数、天门冬氨酸转氨酶、γ-谷氨酰转肽酶及炎症程度均与其肝纤维化程度相关.在非酒精性脂肪性肝病患者中,非酒精性脂肪性肝炎患者代谢综合征患者率高于非酒精性脂肪肝(分别为55.4%和40.0%);纤维化分期为S_(0～1)、S_(2～4)的患者代谢综合征的患病率分别为36.2%和70.7%(P＜0.01);代谢综合征、丙氨酸转氨酶、天门冬氨酸转氨酶、γ-谷氨酰转肽酶及明显炎症均与其肝纤维化严重程度相关.结论 非酒精性脂肪性肝病患者代谢综合征的患病率高于慢性乙型病毒性肝炎患者,这两类患者代谢综合征与肝纤维化程度相关.     

Abnormal glucose tolerance is a predictor of steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease

OBJECTIVE: The majority of patients with non-alcoholic fatty liver disease (NAFLD) have simple steatosis. A minority, however, present with non-alcoholic steatohepatitis (NASH), a condition that can lead to advanced fibrosis and cirrhosis. The frequencies of NASH and fibrosis among patients with NAFLD and sustained elevation of liver function tests (LFT) are uncertain. Our aim was to estimate these frequencies. We characterize a population with NAFLD, with special emphasis on insulin resistance and the metabolic syndrome, and study possible predictors for different stages of the disease. MATERIAL AND METHODS: All referred patients with sustained elevation of LFT, radiological evidence or clinical suspicion of fatty liver, and absence of other liver disease, were invited to participate in our study in the period June 2002 to December 2004. RESULTS: Of 129 patients who met the inclusion criteria, 88 underwent liver biopsy. NAFLD was verified in 83 of them. Among these patients, 59 (71%) had the metabolic syndrome, 41 (49%) had NASH and 36 (43%) had fibrosis. Abnormal glucose tolerance (T2DM or impaired glucose tolerance) was the only independent risk factor for NASH (OR: 3.14; 95% CI: 1.20-8.23). Independent predictors for fibrosis were abnormal glucose tolerance (OR: 3.83; 95% CI: 1.29-11.40) and body mass index (OR: 1.20; 95% CI: 1.06-1.36) per kg/m2. CONCLUSIONS: Both NASH and fibrosis are frequently present among patients with NAFLD and sustained elevation of LFT. The probability of these potentially progressive stages of NAFLD increases with the presence of abnormal glucose tolerance.     

Development of steatohepatitis in Ob/Ob mice is dependent on Toll-like receptor 4

Background and aim. The etiology of non-alcoholic fatty liver disease (NAFLD) progression, and why some patients develop non-alcoholic steatohepatitis (NASH) vs. uncomplicated NAFLD, is not well understood. Obesity and NAFLD are thought to be associated with high circulating levels of leptin; however, the role of leptin in NASH has been controversial. Secondly, as ob/ob mice are known to have elevated circulating levels of TLR4-stimulating endotoxin secondary to increased intestinal permeability.Material and methods. We evaluated the long-term effects of steatosis on the livers of aleptinemic (OB) mice and the role of TLR4 in the development of hepatic sequelae in these animals.Results. At 20 weeks of age OB animals displayed grossly steatotic livers, but also features of early stage NASH including hepatocellular ballooning and numerous necroinflammatory foci with associated changes in serum aspartate aminotransferase (AST) and alanine transaminase (ALT). TLR4 KO did not affect the development of obesity or steatosis in ob/ob mice, but protected these animals from hepatitis and liver injury.Conclusions. In conclusion, the data presented here indicate that steatohepatitis develops in the absence of leptin, and that TLR4 is integral to the development NASH secondary to hyperphagia.