Effect of exenatide combined with metformin therapy on insulin resistance,liver function and inflammatory response in patients with type 2 diabetes mellitus combined with NAFLD

Objective: To study the effect of exenatide combined with metformin therapy on insulin resistance, liver function and inflammatory response in patients with type 2 diabetes mellitus combined with NAFLD. Methods: A total of 98 patients with type 2 diabetes mellitus combined with NAFLD who were treated in the hospital between February 2015 and January 2017 were divided into control group and observation group by random number table, each with 49 cases. Control group received metformin therapy, and observation group received exenatide combined with metformin therapy. Serum levels of insulin resistance indexes, liver function indexes and inflammatory factors of two groups of patients were detected before treatment and after 12 weeks of treatment. Results: Before treatment, serum levels of insulin resistance indexes, liver function indexes and inflammatory factors were not significantly different between the two groups of patients;after 12 weeks of treatment, serum INS and HOMA-IR levels as well as AST, ALT, GGT, ALP, hs-CRP, IL-1β and IL-6 contents of observation group were lower than those of control group. Conclusion: Exenatide combined with metformin therapy can effectively reduce insulin resistance, reduce liver function injury and inhibit systemic inflammatory response in patients with type 2 diabetes mellitus combined with NAFLD.

Insulin resistance and steatosis in HBV-HCV co-infected patients: Role of PNPLA3 polymorphisms and impact on liver fibrosis progression

AIM:To evaluate steatosis,insulin resistance(IR)and patatin-like phospholipase domain-containing 3(PNPLA3) and their relation to disease progression in hepatitis B and C viruses(HCV-HBV) coinfected patients.METHODS:Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled:66 had HBV-HCV,66 HBV and 198 HCV infection.Prevalence of steatosis,IR and PNPLA3 polymorphisms and their relation to anthropometric,biochemical,virological and histological parameters were evaluated.RESULTS:Prevalence of steatosis in group HBV-HCV was similar to that in HCV(47.0% vs 49.5%,respec-tively);group HBV showed the lowest steatosis(33.3%).Group HBV-HCV had a lesser degree of steatosis than HCV(P = 0.016),lower HCV RNA levels(P = 0.025) and lower prevalence and degree of IR(P = 0.01).PNPLA3 polymorphisms were associated with steatosis.Group HBV-HCV showed higher levels of liver fibrosis than group HCV(P = 0.001),but similar to that ob-served in HBV group.In HBV-HCV group,liver fibrosis was not associated with steatosis,IR or PNPLA3.HBV infection was the independent predictor of advanced liver fibrosis.CONCLUSION:HBV-HCV co-infected patients have lower degree of hepatic steatosis,IR and HCV RNA than HCV mono-infected;co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance.

Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review

To summarise the literature data on hepatitis C virus (HCV)-infected patients concerning the prevalence of glucose abnormalities and associated risk.METHODSWe conducted a PubMed search and selected all studies found with the key words 'HCV' or 'hepatitis C virus' and 'diabetes' or 'insulin resistance'. We included only comparative studies written in English or in French, published from January 2000 to April 2015. We collected the literature data on HCV-infected patients concerning the prevalence of glucose abnormalities [diabetes mellitus (DM) and insulin resistance (IR)] and associated risk [i.e., severe liver fibrosis, response to antivirals, and the occurrence of hepatocellular carcinoma (HCC)].RESULTSHCV infection is significantly associated with DM/IR compared with healthy volunteers and patients with hepatitis B virus infection. Glucose abnormalities were associated with advanced liver fibrosis, lack of sustained virologic response to interferon alfa-based treatment and with a higher risk of HCC development. As new antiviral therapies may offer a cure for HCV infection, such data should be taken into account, from a therapeutic and preventive point of view, for liver and non-liver consequences of HCV disease. The efficacy of antidiabetic treatment in improving the response to antiviral treatment and in decreasing the risk of HCC has been reported by some studies but not by others. Thus, the effects of glucose abnormalities correction in reducing liver events need further studies.CONCLUSIONGlucose abnormalities are strongly associated with HCV infection and show a negative impact on the main liver related outcomes.

Crosstalk between angiogenesis, cytokeratin-18, and insulin resistance in the progression of non-alcoholic steatohepatitis

AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).METHODS: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively. The correlations of these factors with NASH were elucidated.RESULTS: Significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL and healthy liver. The degree of angiogenesis was almost parallel to liver fibrosis development, and both parameters were positively correlated. Similarly, CK-18expression and HOMA-R were signifi cantly increased in NASH as compared with FL and healthy liver. Furthermore, CK-18 and HOMA-IR were also positively correlated with the degree of neovascularization. CONCLUSION: These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH.

production of extracellular lysophosphatidic acid in the regulation of adipocyte functions and liver fibrosis

Lysophosphatidic acid(LPA), a glycerophospholipid, consists of a glycerol backbone connected to a phosphate head group and an acyl chain linked to sn-1 or sn-2 position. In the circulation, LPA is in submillimolar range and mainly derived from hydrolysis of lysophosphatidylcholine, a process mediated by lysophospholipase D activity in proteins such as autotaxin(ATX). Intracellular and extracellular LPAs act as bioactive lipid mediators with diverse functions in almost every mammalian cell type. The binding of LPA to its receptors LPA1-6 activates multiple cellular processes such as migration, proliferation and survival. The production of LPA and activation of LPA receptor signaling pathways in the events of physiology and pathophysiology have attracted the interest of researchers. Results from studies using transgenic and gene knockout animals with alterations of ATX and LPA receptors genes, have revealed the roles of LPA signaling pathways in metabolic active tissues and organs. The present review was aimed to summarize recent progresses in the studies of extracellular and intracellular LPA production pathways. This includes the functional, structural and biochemical properties of ATX and LPA receptors. The potential roles of LPA production and LPA receptor signaling pathways in obesity, insulin resistance and liver fibrosis are also discussed.

Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients

AIMTo investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy. METHODSA cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR). RESULTSFibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis (F0-F) = 179, moderate fibrosis (F2) = 64, and advanced fibrosis (F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage (P CONCLUSIONOur predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy.

瘦素和多囊卵巢综合征(PCOS)伴非酒精性脂肪肝(NAFLD)相关性的临床观察

目的通过对多囊卵巢综合征(polycystic ovary syndrome,PCOS)人群中伴非酒精性脂肪肝(non-acoholic fatty liver disease,NAFLD)的分析,探讨瘦素与PCOS伴NAFLD之间的关系。方法收集35例PCOS伴有NAFLD的患者为脂肪肝组,同期选择35例PCOS不伴NAFLD的患者为非脂肪肝组,健康女性志愿者20例为对照组。所有受试者进行相关问卷调查建立个人病例档案,测量身高(height,H)、体重(weight,W)、体重指数(body mass index,BMI)、腰围(waist circumference,WC)、臀围(hip circumference,HC)及腰臀比(wasit hip ratio,WHR);检测血清睾酮(testosterone,T)、泌乳素(prolactin,PRL)、卵泡刺激素(folliclestimulating hormone,FSH)、黄体生成素(luteinizing hormone,LH)、雌二醇(estradiol,E2)、瘦素、空腹血糖(fasting blood sugar,FBG)、空腹胰岛素(fasting insulin,FINS)、餐后2h血糖(2hpostprandial blood glucose,2hPBG)、稳态模型胰岛素抵抗指数(homeostatic model assessment for insulin resistance,HOMA-IR)、总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)及丙氨酸转氨酶(alaninetransaminase,ALT)等指标。结果两组PCOS的瘦素、W、BMI、WHR、T、LH、LH/FSH、FINS、PBG、HOMA-IR、LDL-C各项指标均高于对照组(P<0.05),FSH显著低于对照组(P<0.05);而PCOS伴NAFLD的瘦素、W、BMI、WC、HC、WHR、FINS、PBG、HOMA-IR、TG、LDL-C、ALT较不伴NAFLD显著升高(P<0.05),HDL-C显著降低(P<0.05)。脂肪肝组的瘦素水平与年龄、W、BMI、WC、HC、WHR、FINS、HOMA-IR及TG呈均显著正相关性(P<0.01),与HDL-C呈显著负相关性(P<0.01),控制与体脂有关的如W、BMI、WC、HC、WHR,脂肪肝组的瘦素水平与HOMA-IR、TG仍有显著正相关性(P<0.01)。结论瘦素水平异常与PCOS伴NAFLD的形成密切相关,及早重视瘦素干预,对于防治PCOS伴NAFLD有重要意义。

饥饿素(ghrelin)在非酒精性脂肪肝病(NAFLD)中的研究进展

非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)在肝脏疾病谱中占据日益重要的地位,其与胰岛素抵抗和氧化应激密切相关。饥饿素(ghrelin)作为一种新发现的从胃内提取的激素,是第一种生长激素促分泌素的内源性配体,能促进生长激素分泌,同时增强食欲,减少脂肪利用,维持能量正平衡,并在改善胰岛素抵抗、抑制炎性反应、抗纤维化和肿瘤等方面有一定作用,可能对NAFLD起到治疗作用。本文就目前国内外关于饥饿素在NAFLD中的研究作一综述。

艾塞那肽联合二甲双胍治疗对2型糖尿病合并NAFLD患者胰岛素抵抗、肝功能及炎症反应的效应

目的:探讨艾塞那肽联合二甲双胍治疗对2型糖尿病合并非酒精性脂肪肝(NAFLD)患者胰岛素抵抗、肝功能及炎症反应的影响。方法:收集2015年2月~2017年1月间在本院接受治疗的2型糖尿病合并NAFLD患者98例,经随机数表法分为对照组及观察组,各49例。对照组患者接受二甲双胍治疗,观察组患者接受艾塞那肽联合二甲双胍治疗。治疗前、治疗12周后,检测两组患者血清中的胰岛素抵抗指标、肝功能指标、炎症因子水平。结果:治疗前,两组患者血清中胰岛素抵抗指标、肝功能指标、炎症因子的水平无显著性差异;治疗12周后,观察组患者血清中胰岛素(INS)、胰岛素抵抗指数(HOMA-IR)的水平以及天冬氨酸草转氨酶(AST)、丙氨酸转氨酶(ALT)、谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、超敏C反应蛋白(hs-CRP)、白介素-1β(IL-1β)、白介素-6(IL-6)的含量低于对照组患者。结论:2型糖尿病合并NAFLD患者接受艾塞那肽联合二甲双胍治疗,可有效减轻胰岛素抵抗并减轻肝功能损伤,抑制全身炎症反应。

复方甘草酸苷联合阿托伐他汀治疗NAFLD的疗效及对肝纤维化和胰岛素抵抗指标的影响

目的探究复方甘草酸联合阿托伐他汀治疗非酒精性脂肪肝病(NAFLD)的效果及对患者Ⅲ型前胶原肽(PCⅢP)、Ⅳ型胶原(Ⅳ-C)和胰岛素抵抗指数(HOMA-IR)的影响。方法选取衢州市人民医院2016年5月至2018年5月收治的NAFLD患者80例,按照随机数字表法分为对照组和观察组,每组40例。对照组患者口服复方甘草酸苷治疗,观察组在对照组基础上联合阿托伐他汀治疗。对比两组患者的临床疗效,治疗前后ALT、AST、γ-谷氨酰转移酶(γ-GT),血清TC、TG、LDL-C、HDL-C,透明质酸(HA)、PCⅢP、Ⅳ-C,游离脂肪酸(FFA)、空腹胰岛素(FINS)、空腹血糖(FBG)、HOMA-IR,以及不良反应发生情况。结果观察组的治疗有效率明显高于对照组,差异有统计学意义(P<0.05)。治疗后两组ALT、AST、γ-GT、TG、TC、LDL-C、HA、PCⅢP、Ⅳ-C、FFA、FINS、HOMA-IR较治疗前均明显降低(均P<0.05),HDL-C明显升高(均P<0.05),且观察组各指标均明显优于对照组(均P<0.05)。两组患者治疗期间不良反应合计发生率比较差异无统计学意义(P>0.05)。结论复方甘草酸苷联合阿托伐他汀治疗NAFLD能够显著减轻患者肝功能损害,降低血脂水平,减轻肝纤维化和胰岛素抵抗,安全性较高。

丹瓜护脉口服液对痰瘀型2型糖尿病合并NAFLD患者糖脂代谢、胰岛素抵抗及肝纤维化程度的疗效观察

目的:以中成药丹瓜护脉口服液干预痰瘀型2型糖尿病合并非酒精性脂肪性肝病(NAFLD)患者,观察其临床疗效。方法:选取2018年6月1日-12月31日在本科住院的105例痰瘀型T2DM合并NAFLD患者,随机分为对照组50例及治疗组55例。对照组按指南规范给予降糖、降压、降脂及抗血小板等西医治疗;治疗组在此基础上加用丹瓜护脉口服液,疗程6个月。观察两组治疗前后糖代谢(FPG、HbA1c、FINS)、脂代谢(TC、TG、HDL-C、LDL-C)、肝酶学指标(ALT、AST),计算HOMA-IR与NAFLD纤维化评分(NFS)的变化,以及脂肪肝程度的变化。结果:(1)治疗前,两组血糖、血脂、HOMA-IR、肝酶学指标等差异无统计学意义(P>0.05)。(2)治疗组治疗6个月后,组内治疗前后比较显示,糖脂代谢、肝酶指标及计算HOMA-IR、NFS也较治疗前明显下降(P<0.05),而FINS、HDL-C水平无明显变化(P>0.05)。对照组治疗6个月后,上述糖脂代谢、肝酶指标等实验室检查指标较治疗前亦有下降(P<0.05),但HOMA-IR、NFS下降并不明显(P>0.05)。(3)组间治疗后比较,治疗6个月后治疗组不仅糖脂代谢及肝酶指标低于对照组,HOMA-IR、NFS也显著低于对照组(P<0.05)。(4)治疗组脂肪肝治疗的总有效率显著高于对照组(P<0.05)。结论:丹瓜护脉口服液用于痰瘀型T2DM合并NAFLD患者在有效改善糖脂代谢的基础上,可改善胰岛素抵抗,同时降低肝损伤并显著改善脂肪肝程度,从而延缓肝纤维化进展。

疏肝消脂Ⅲ方胶囊对NAFLD模型大鼠脂联素及胰岛素抵抗指数干预作用研究

目的:探讨疏肝消脂Ⅲ方胶囊对大鼠非酒精性脂肪肝(NAFLD)模型脂联素(ADP)及胰岛素抵抗评估指数(HOMA-IRI)的干预作用。方法:采用高脂乳剂灌胃法建立NAFLD大鼠模型,造模成功后,给予疏肝消脂Ⅲ方胶囊灌胃干预4周,观察大鼠一般情况及肝组织病理形态变化;检测血清血糖(FBG)、胰岛素(FINS)含量,计算稳态模型HOMA-IRI;采用ELISA法检测肝组织匀浆ADP的含量。结果:药物组FBG、FINS、HOMA-IRI水平较模型组显著降低(P<0.05),肝组织ADP含量较模型组增高(P<0.05),减轻病理学损伤。结论:疏肝消脂Ⅲ方胶囊治疗NAFLD的机制与提高肝组织ADP表达,改善胰岛素抵抗,减轻肝细胞脂肪变性及炎症浸润有关。

NAFLD患者TE成像特点与其病情严重程度及胰岛素抵抗的关系研究

本研究旨在分析NAFLD(非酒精性脂肪性肝病)患者TE(瞬时弹性成像技术)成像特点与其病情严重程度及胰岛素抵抗的关系。通过选择我院NAFLD患者112例,健康体检的患者108例,对比两组患者基线资料,将NAFLD患者根据病情分组并对比相关资料。研究表明NAFLD组患者肝功能、血清胰岛素、HOMA-IR(胰岛素抵抗指数)显著高于对照组,差异显著(P<0.05)。随着脂肪肝严重程度增加,患者普遍年龄增高,男性多于女性,肝脏硬度、肝功能、胰岛素相关指标均明显上升,差异显著(P<0.05)。ROC曲线分析表明CAP(受控衰减参数)对轻度、中度和重度NAFLD均有较高的诊断价值,灵敏度分别为0.865、0.861、0.931,特异度分别为0.614、0.819、0.822。随着NAFLD病情严重程度的加重,CAP与HOMA-IR值均升高,呈显著正相关(r=0.536,r=0.479)。据此可推断NAFLD患者的TE成像特点与不同程度NAFLD密切相关,胰岛素抵抗可临床辅助诊断NAFLD。

二甲双胍辅助治疗对NAFLD患者肝纤维化和胰岛素抵抗的影响

目的研究二甲双胍辅助治疗对NAFLD患者肝纤维化和胰岛素抵抗的影响。方法选取我院从2016年1月～2017年8月100例非酒精性脂肪性肝病(NAFLD)患者,按照随机数字表法分为两组,对照组50例,给予单纯多烯磷脂酰胆碱治疗;观察组50例,给予多烯磷脂酰胆碱联合二甲双胍治疗。治疗12周后,比较两组患者肝纤维化程度和胰岛素抵抗情况。结果观察组患者的各项肝纤维化指标HA、LN-C、IV-C、PCⅢ等指标水平明显低于对照组,差异有统计学意义(P <0.05);两组患者治疗前胰岛素抵抗稳态指数差异无统计学意义(P> 0.05),治疗后观察组胰岛素抵抗稳态指数明显低于对照组,差异有统计学意义(P <0.05);两组患者在治疗期间无明显不良反应。结论二甲双胍辅助治疗可明显缓解NAFLD患者的肝纤维化程度,改善NAFLD患者胰岛素抵抗程度。

新诊断糖尿病合并NAFLD患者血清高分子量脂联素、HOMA-IR及其比值与肝纤维化的相关性

目的探讨新诊断2型糖尿病合并非酒精性脂肪性肝病(NAFLD)患者血清高分子量脂联素(HMWA)、稳态模型胰岛素抵抗指数(HOMA-IR)及两者比值(A/H)与肝纤维化的相关性。方法回顾性分析2020年5月至2021年5月广州市花都区人民医院收治的279例新诊断2型糖尿病合并NAFLD患者的临床资料,分析其肝纤维化发生情况,并采用单因素分析、多因素logistic回归分析法探讨患者肝纤维化的独立影响因素,判断HMWA、HOMA-IR和A/H比值对肝纤维化的预测价值。结果新诊断2型糖尿病合并NAFLD患者肝纤维化患病率为15.77%(44/279)。肝纤维化患者血清HMWA、HOMA-IR和A/H比值水平分别为1.20(0.91,1.78)mg/L、3.41(2.57,5.70)和0.33(0.18,0.62),非肝纤维化患者血清HMWA、HOMA-IR和A/H比值水平分别为2.74(1.57,3.84)mg/L、2.18(1.61,3.12)和1.21(0.55,2.16)。两组患者血清HMWA、HOMA-IR和A/H比值水平比较,差异均有统计学意义(P<0.05)。除年龄、腰围外,HMWA、HOMA-IR和A/H亦是2型糖尿病合并NAFLD患者发生肝纤维化的独立影响因素(P<0.05),且其对肝纤维化有一定预测价值,A/H的曲线下面积明显大于HMWA和HOMA-IR(Z=2.768,P=0.006;Z=2.491,P=0.013),当A/H比值最佳截断值为0.52时,灵敏度为75.00%,特异度为78.72%。结论HMWA、HOMA-I和A/H与2型糖尿病合并NAFLD患者肝纤维化发生风险独立相关,并具有一定预测价值,A/H的预测效能最佳。

Protective Effects of Chaihu Shugan San(柴胡疏肝散) on Nonalcoholic Fatty Liver Disease in Rats with Insulin Resistance

Objective： To investigate the protective effects of Chinese medicine formulation Chaihu Shugan San（柴胡疏肝散, CHSGS） on nonalcoholic fatty liver disease（NAFLD） in rats with insulin resistance（IR） and its molecular mechanisms. Methods： Male Sprague-Dawley rats were randomly divided into six groups： the control group, the model group, Dongbao Gantai group（东宝肝泰, DBGT, 0.09 g methionine/kg）, CHSGS high-dose group（CHSG-H, 12.6 g crude drug/kg）, CHSGS medium-dose group（CHSG-M, 6.3 g crude drug/kg）, and CHSGS low-dose group（CHSG-L, 3.15 g crude drug/kg）. After establishing the NAFLD rat model and treatment for 8 weeks, total cholesterol（TC）, triglyceride（TG）, high-density lipoprotein cholesterol（HDL-C）, free fatty acid（FFA）, fasting blood glucose（FBG）, fasting insulin（FINS） contents in blood serum, and TC, TG contents in the hepatic homogenate were measured by an automatic biochemical analyzer, and a homeostasis model assessment was applied to assess the status of IR, insulin sensitivity index（ISI）, and homeostasis model assessment for insulin secretion（HOMA-IS）. The expression levels of adiponectin and leptin mRNA in liver tissue were analyzed by reverse transcription polymerase chain reaction. Pathological changes of livers were observed by hematoxylineosin staining of paraffin section. Results： Compared with the model group, the serum levels of TC, TG, FFA, FBG, FINS, IRI, ISI, and the liver levels of TC and TG in CHSG-H, CHSG-M, CHSG-L groups showed significant declines（P〈0.01 or P〈0.05）; the serum levels of HDL-C, HOMA-IS were significantly increased（P〈0.01 or P〈0.05）; the expression of leptin mRNA was dramatically decreased and the expression of adiponectin mRNA was increased in the hepatic tissue（P〈0.01 or P〈0.05）. The fatty deposition of liver cells could also be alleviated. Conclusion： CHSGS could up-regulate the expression of adiponectin mRNA and down-regulate the expression of leptin mRNA on the liver, suggesting the CHSGS had positive therapeutic effect on NAFLD in rats with IR.

Peripheral Artery Disease and Risk of Fibrosis Deterioration in Nonalcoholic Fatty Liver Disease:A Prospective Investigation

Objective Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease(NAFLD).Peripheral artery disease(PAD)and liver fibrosis share many common metabolic dysfunctions.We aimed to explore the association between PAD and risk of fibrosis deterioration in NAFLD patients.Methods The study recruited 1,610 NAFLD patients aged≥40 years from a well-defined community at baseline in 2010 and followed up between August 2014 and May 2015.Fibrosis deterioration was defined as the NAFLD fibrosis score(NFS)status increased to a higher category at the follow-up visit.PAD was defined as an ankle-brachial index of<0.90 or>1.40.Results During an average of 4.3 years’follow-up,618 patients progressed to a higher NFS category.PAD was associated with 92%increased risk of fibrosis deterioration[multivariable-adjusted odds ratio(OR):1.92,95%confidence interval(CI):1.24,2.98].When stratified by baseline NFS status,the OR for progression from low to intermediate or high NFS was 1.74(95%CI:1.02,3.00),and progression from intermediate to high NFS was 2.24(95%CI:1.05,4.80).There was a significant interaction between PAD and insulin resistance(IR)on fibrosis deterioration(P for interaction=0.03).As compared with non-PAD and non-IR,the coexistence of PAD and IR was associated with a 3.85-fold(95%CI:2.06,7.18)increased risk of fibrosis deterioration.Conclusion PAD is associated with an increased risk of fibrosis deterioration in NAFLD patients,especially in those with IR.The coexistence of PAD and IR may impose an interactive effect on the risk of fibrosis deterioration.

内脏脂肪指数对瘦型人群中非酒精性脂肪性肝病的预测价值:一项横断面研究

目的探究内脏脂肪指数(visceral adiposity index,VAI)与瘦型人群中非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的相关性及其预测价值。方法随机纳入2020年6月-2021年5月西安交通大学第二附属医院2576名健康体检者,身体质量指数(BMI)正常(即<24 kg/m^(2)),分为瘦型NAFLD组(n=213)与健康对照组(n=2363),根据VAI四分位数由低到高分为Q 1~Q 4组,比较组间生化指标差异与NAFLD患病情况。采用限制性立方样条分析VAI与瘦型NAFLD之间关系,Logistic回归与受试者工作特征(ROC)曲线探究VAI对瘦型NAFLD的预测价值。结果共纳入2576名体检者,瘦型NAFLD患病率为8.3%(213例)。Q 1~Q 4组平均年龄、男性占比、BMI与腰围(waist circumference,WC)显著增加,且呈明显剂量反应关系(均P<0.001)。与Q 1组相比,Q 2~Q 4组收缩压、舒张压、白细胞计数、血红蛋白浓度、谷丙转氨酶、谷草转氨酶、γ氨基转肽酶、碱性磷酸酶、总胆固醇、三酰甘油、低密度脂蛋白胆固醇、血尿酸与空腹血糖水平均明显增加,直接胆红素与高密度脂蛋白胆固醇水平则逐渐降低,组间差异均具有统计学意义(P<0.001)。Q 1~Q 4组NAFLD的患病率分别为0.6%、3.3%、7.0%、22.2%,呈显著递增(P<0.001)。限制性立方样条图显示随着VAI增加,瘦型人群中NAFLD的患病风险显著增加(P<0.001),两者之间存在非线性关系(P for nonlinear<0.001)。Logistic回归结果显示,在调整各混杂因素后,Q 2、Q 3、Q 4组瘦型NAFLD的患病风险仍分别为Q 1组的2.926倍(95%CI:0.971~8.811)、3.435倍(95%CI:1.154~10.230)与5.920倍(95%CI:1.873~18.719)。ROC曲线显示,VAI对于瘦型NAFLD具有较好的预测价值,曲线下面积为0.815,临界值为1.532,诊断敏感性为77.9%,特异性为72.8%,均优于BMI与WC。结论瘦型体检人群中VAI升高与NAFLD发病风险显著相关,具有良好预测价值,可用于瘦型NAFLD早期筛查与诊断。

Overview and developments in noninvasive diagnosis of nonalcoholic fatty liver disease

High prevalence of non-alcoholic fatty liver disease (NAFLD) and very diverse outcomes that are related to disease form and severity at presentation have made the search for noninvasive diagnostic tools in NAFLD one of the areas with most intense development in hepatology today.Various methods have been investigated in the recent years,including imaging methods like ultrasound and magnetic resonance imaging,different forms of liver stiffness measurement,various biomarkers of necroinflammatory processes (acute phase reactants,cytokines,markers of apoptosis),hyaluronic acid and other biomarkers of liver fibrosis.Multicomponent tests,scoring systems and diagnostic panels were also developed with the purposes of differentiating non-alcoholic steatohepatitis from simple steatosis or discriminating between various fibrosis stages.In all of the cases,performance of noninvasive methods was compared with liver biopsy,which is still considered to be a gold standard in diagnosis,but is by itself far from a perfect comparative measure.We present here the overview of the published data on various noninvasive diagnostic tools,some of which appear to be very promising,and we address as well some of still unresolved issues in this interesting field.

25-(OH)D_3、ADPN水平及IR对NAFLD的临床诊断价值

目的探讨非酒精性脂肪肝(NAFLD)患者血清25羟维生素D_3(25-(OH)D_3)、脂联素(ADPN)水平及胰岛素抵抗(IR)的临床意义。方法选取淄博市中心医院收治的86例非酒精性脂肪肝患者以及同期体检的50名健康志愿者为研究对象,分别将其作为研究组与对照组,采用酶联免疫吸附测定法测定所有研究对象血清25-(OH)D_3、ADPN、IR水平,并分析其与不同程度患者临床指标的关系。结果研究组体重指数(BMI)、腰臀比(WHR)、血尿酸、TC、ALP、LDL-C、FBG水平明显高于对照组(P<0.05)。研究组患者中随着病情的严重程度的增加血清25-(OH)D_3、ADPN水平均降低,IR升高,且组间差异均有统计学意义(P<0.05),多因素logistic回归分析显示BMI、WHR、25-(OH)D_3、ADPN、IR均是影响非酒精性脂肪肝的危险因素。结论低水平25-(OH)D_3、ADPN,高水平IR以及肥胖容易引发非酒精性脂肪肝,通过测定其水平可为临床治疗和预后方案的制定提供参考依据。