非酒精性脂肪性肝病与代谢综合征

非酒精性脂肪性肝病(NAFLD)事实上是一个肝脏脂肪性病变的疾病谱,包括单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)、肝纤维化或肝硬化、肝衰竭,甚至部分患者发生肝细胞性肝癌。NAFLD与代谢综合征(MS)密切伴随,并认为是代谢综合征的肝脏表现。胰岛素抵抗可能是二者共同的发病基础。NAFLD已经成为MS、2型糖尿病(T2DM)和心血管疾病(CVD)的重要的独立预测因子,NAFLD成为T2DM和CVD高危人群,因此早期诊断和早期干预NAFLD对预防T2DM和CVD具有重要意义。     

非酒精性脂肪性肝病是糖尿病的并发症吗?

非酒精性脂肪性肝病(NAFLD)虽然是一种肝脏疾病,但越来越受到内分泌学界的重视。糖尿病的代谢状态与NAFLD的病理之间存在复杂的相互作用,促进彼此的发生。在2型糖尿病(T2DM)人群中,脂肪肝伴随率高达57%～80%,合并糖尿病的NAFLD患者可能更容易发生非酒精性脂肪性肝炎(NASH)、肝纤维化等进展性肝病。而NAFLD也促使糖尿病患者糖脂代谢紊乱进一步恶化,以及糖尿病慢性大血管和微血管并发症的发生发展。上述依据支持NASH应被视为T2DM并发症的观点。临床上,一旦T2DM诊断明确,应积极评估NASH或进展性纤维化风险,并积极干预。     

非酒精性脂肪性肝病合并2型糖尿病患者肝组织病理学变化研究

目的 研究非酒精性脂肪性肝病（NAFLD）合并2型糖尿病（T2DM）患者肝脏组织病理学变化。方法 分析240例行肝活检术的NAFLD患者临床资料,比较NAFLD合并T2DM与未合并T2DM患者肝组织病理学表现和评分的差异。结果 在240例NAFLD患者中,合并2型糖尿病者80例（33.3%）,未合并T2DM 者160例（66.7%）;在NAFLD合并T2DM患者中非酒精性脂肪性肝炎（NASH）60例、肝纤维化20例,未合并T2DM患者中分别为68例和92例;在NAFLD合并T2DM患者中检出肝纤维化评分≥2者30例（37.5%）、肝细胞气球样变评分≥2者23例（28.8%）和马洛里小体22例（27.5%）,均显著高于未合并T2DM患者的【20例（12.5%）、22例（13.8%）和30例（18.8%）,P<0.05】;T2DM为发生NASH（OR=3.27,95%CI：1.42~7.55）和肝纤维化（OR=3.35,95%CI：1.55~7.63）的独立危险因素。结论 合并T2DM的NAFLD患者肝组织病理学损伤更趋严重,应注意防治。     

2型糖尿病患者非酒精性脂肪肝及进展肝纤维化与骨质疏松的关系

目的研究2型糖尿病(type 2 diabetes mellitus, T2DM)患者非酒精性脂肪肝(non-alcoholic fatty liver disease, NAFLD)及进展纤维化与骨质疏松(osteoporosis, OP)的关系。方法通过横断面研究方法, 收集2019年9月至2020年9月于南京医科大学附属淮安第一医院内分泌及老年医学科住院的T2DM患者391例。根据肝脏B超分为T2DM合并NAFLD和T2DM未合并NAFLD组。根据肝纤维化指数分为肝脏纤维化低分险组及肝脏纤维化中高风险组。收集患者一般临床特征和病史、实验室及双能X线骨密度检查结果。多因素logistic回归评估T2DM患者NAFLD及进展肝纤维化与OP的关系, 最后根据年龄、性别、体重指数和糖尿病病程进行交互作用和分层分析。结果多因素logistic回归显示T2DM患者罹患OP风险及骨密度下降与NAFLD发生无统计学意义上差异(所有P>0.05)。调整年龄、性别、体重指数和糖尿病病程后, 肝脏纤维化中高风险组T2DM患者髋部骨密度(β为-0.044, 95%CI -0.087～-0.001,...     

关注2型糖尿病合并非酒精性脂肪性肝病的肝脏结局

<正>2型糖尿病(type 2 diabetes mellitus,T2DM)和非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)作为代谢综合征的组分常相伴存在,NAFLD影响糖尿病患者血糖控制难以达标,进而促进慢性并发症的发生。同时,2型糖尿病促使NAFLD向非酒精性脂肪性肝炎(NASH)、肝纤维化、甚至肝细胞癌发展,增加肝脏相关死亡率。就诊内     

T2DM合并非酒精性脂肪性肝病伴进展性肝纤维化患者血清抵抗素和TyG指数变化及其临床意义探讨

目的 探讨2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)患者进展性肝纤维化的血清指标评估方法。方法 2019年3月～2022年2月青海省人民医院收治的204例T2DM合并NAFLD患者,依据NAFLD纤维化评分(NFS)诊断进展性肝纤维化。采用ELISA法检测血清抵抗素水平,常规检测空腹三酰甘油和空腹血糖,计算三酰甘油葡萄糖(TyG)指数,应用多因素Logistic回归分析影响T2DM合并NAFLD患者进展性肝纤维化发生的危险因素,应用受试者工作特征曲线(ROC)下面积(AUC)评估血清抵抗素联合TyG指数的诊断效能。结果 在204例T2DM合并NAFLD患者中,发现存在进展性肝纤维化者31例(15.2%);进展性肝纤维化组年龄、糖尿病病程、HOMA-IR、血清抵抗素和TyG指数显著大于或长于非进展性肝纤维化组(P<0.05),而估算的肾小球滤过率(eGFR)则显著低于非进展性肝纤维化组(P<0.05);多因素Logistic回归分析显示,年龄(OR=2.901,95%CI:1.042～5.238)、血清抵抗素(OR=3.404,95%CI:1.874～9.43...     

肥胖通过不同机制导致脂肪性肝炎和肝细胞癌

<正>非酒精性脂肪性肝病(NAFLD)是肥胖和代谢综合征累及肝脏的病理表现,疾病谱包括单纯性脂肪肝(NAFL)、非酒精性脂肪性肝炎(NASH)及其相关肝纤维化、肝硬化和肝细胞癌(HCC)。随着肥胖在全球的流行,NAFLD已成为全球第一大慢性肝脏疾病,普通成人和肥胖患者NAFLD患病率分别高达25%和50%,肥胖症显著增加NAFLD患者肝硬化和HCC发病风险~([1-2])。临床上,90%以上的丙型肝炎相关HCC和酒精性肝病相关HCC发生在肝硬化的基     

非酒精性脂肪肝研究新进展

非酒精性脂肪性肝病（NAFLD）是代谢综合征表现为一组肝脏病变的总称，包括2型糖尿病（T2DM）、胰岛素耐受、脂质代谢障碍和高血压。NAFLD的特点是大囊泡状脂肪变性，范围从单一的脂肪肝到非酒精性脂肪性肝炎（NASH）；随后由单纯的脂肪变性向炎症／纤维化疾病发展。持续性的肝脏损伤将导致肝脏向纤维化或肝硬化发展。[第一段]     

2型糖尿病合并非酒精性脂肪性肝病患者肝纤维化与血尿酸水平的关系

目的探讨2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)患者肝纤维化与血尿酸水平的关系。方法选取2018年1月-2019年8月在沧州市人民医院就诊的T2DM合并NAFLD患者328例,应用NAFLD纤维化评分(NFS)联合FIB-4评估肝纤维化风险,分为肝纤维化低危组(136例)、肝纤维化中危组(145例)及肝纤维化高危组(47例);另选取资料匹配的T2DM患者141例为对照。比较各组血尿酸水平的差异。计量资料多组间比较采用单因素方差分析或Kruskal-Wallis H检验;计数资料组间比较采用χ~2检验。采用logistic回归法分析肝纤维化的影响因素。绘制受试者工作曲线(ROC)评价危险因素的预测效能。结果与T2DM组相比,T2DM合并NAFLD组血尿酸水平显著升高,差异有统计学意义(265. 00±77. 01 vs 313. 04±100. 90,t=-5. 619,P 0. 001)。与肝纤维化低危组(290. 70±95. 46)和中危组(328. 15±90. 85)相比,肝纤维化高危组患者(392. 77±108. 37)血尿酸水平显著升高(P值均0. 01)。肝纤维化高危组高尿酸血症患病率亦显著高于肝纤维化低危组和中危组(47. 00%vs 11. 72%vs 11. 76%,P值均0. 01)。logistic回归分析显示血尿酸[比值比=1. 133,95%可信区间:1. 064～1. 312]是T2DM合并NAFLD患者发生肝纤维化的独立危险因素。ROC曲线显示血尿酸对肝纤维化有一定预测价值,ROC曲线下面积为0. 745。结论高血尿酸水平是T2DM合并NAFLD患者肝纤维化发生发展的独立危险因素。     

非酒精性脂肪性肝病及其相关炎症纤维化诊断进展

正非酒精性脂肪性肝病(NAFLD)在包括中国的多个亚洲国家的患病率超过25%~([1])。NAFLD疾病谱包括非酒精性肝脂肪变(NAFL)、非酒精性脂肪性肝炎(NASH)及其相关肝纤维化和肝硬化~([2])。肝活检作为诊断NASH和纤维化分期的"金标准"并不完美,因此,影像学检查、血清标志物以及预测模型无创诊断的价值仍引人关注。     

Insulin resistance increases the risk of incident type 2 diabetes mellitus in patients with non‐alcoholic fatty liver disease

Aim

Type 2 diabetes mellitus (T2DM) is a major complication of patients with non‐alcoholic fatty liver disease (NAFLD). The aim of this retrospective study is to determine the risk factors for development of T2DM in patients with biopsy‐proven NAFLD.

Methods

One hundred and sixty two consecutive patients with biopsy‐proven NAFLD who received a 75‐g oral glucose tolerance test were enrolled as the total cohort. Among them, we analyzed 89 patients without T2DM diagnosed by oral glucose tolerance test to estimate the cumulative rate for development of T2DM as the follow‐up cohort.

Results

Of 162 patients, the glucose tolerance pattern were DM in 45 patients (27.8%), impaired glucose tolerance in 68 (42.0%), and normal glucose tolerance in 49 (30.2%). Patients with NAFL tended to be more likely to have normal glucose tolerance than those with non‐alcoholic steatohepatitis (NASH). The serum levels of pre‐ and post‐load insulin were significantly higher in the NASH group. Of 89 patients without T2DM, 13 patients newly developed T2DM during a follow‐up period of 5.2 years. The cumulative rate of T2DM incidence was 8.8% at the end of the 5th year and 23.4% at the end of the 10th year. Multivariate analysis identified homeostasis model of assessment – insulin resistance (≥3.85, hazard ratio 40.1, P = 0.033) as an independent risk factor for development of T2DM.

Conclusions

Patients with NASH have an underlying potential of glucose intolerance. In NAFLD patients, insulin resistance is the most important risk factor for the incidence of T2DM. Appropriate therapy against insulin resistance could be needed for patients with NAFLD to prevent development of T2DM.     

High prevalence of undiagnosed liver cirrhosis and advanced fibrosis in type 2 diabetic patients

Background. Patients with type 2 diabetes mellitus (T2DM) are at risk for developing end-stage liver disease due to nonalcoholic steatohepatitis (NASH), the aggressive form of non-alcoholic fatty liver disease (NAFLD). Data on prevalence of advanced fibrosis among T2DM patients is scarce. Aim. To evaluate prevalence of steatosis, advanced fibrosis and cirrhosis using non-invasive methods in T2DM patients.Material and methods. 145 consecutive T2DM patients (> 55 years-old) were prospectively recruited. Presence of cirrhosis and advanced fibrosis was evaluated by magnetic resonance imaging (MRI) and NAFLD fibrosis score (NFS) respectively. Exclusion criteria included significant alcohol consumption, markers of viral hepatitis infection or other liver diseases. Results are expressed in percentage or median (interquartile range).Results. 52.6% of patients were women, the median age was 60 years old (57-64), mean BMI was 29.6 ± 4.7 kg/m² and diabetes duration was 7.6 ± 6.9 years. A high prevalence of liver steatosis (63.9%), advanced fibrosis assessed by NFS (12.8%) and evidence of liver cirrhosis in MRI (6.0%) was observed. In a multivariate analysis GGT > 82 IU/L (P = 0.004) and no alcohol intake (P = 0.032) were independently associated to advanced fibrosis.Conclusion. A high frequency of undiagnosed advanced fibrosis and cirrhosis was observed in non-selected T2DM patients. Screening of these conditions may be warranted in this patient population.     

The use of statins alone,or in combination with pioglitazone and other drugs,for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement

Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (> 5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without.The use of statins, though considered safe by the guidelines, have very limited use; only 10% in high CVD risk patients are on statins by tertiary centers in the US. There are data from several animal studies, 5 post hoc analyses of prospective long-term survival studies, and 5 rather small biopsy proven NASH studies, one at baseline and on at the end of the study. All these studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and in the clinical studies large reductions in CVD events in comparison with those also on statins and normal liver. Ezetimibe was also reported to improve NAFLD.Drugs currently in clinical trials seem to have potential for slowing down the evolution of NAFLD and for reducing liver- and CVD-related morbidity and mortality, but it will take time before they are ready to be used in everyday clinical practice. The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause of death in NAFLD/NASH patients.     

Novel antidiabetic medications for non‐alcoholic fatty liver disease with type 2 diabetes mellitus

Liver‐related diseases are the leading causes of death in patients with type 2 diabetes mellitus (T2DM) in Japan. Type 2 diabetes mellitus is closely associated with non‐alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Non‐alcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma and hepatic failure. Non‐alcoholic steatohepatitis can be called “diabetic hepatopathy”. There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first‐line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin, weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to lack of clinical evidence. The effects of pioglitazone on NASH histology with T2DM have been extensively proved, but several concerns exist, such as body weight gain, fluid retention, cancer incidence, and bone fracture. In recent years, novel antidiabetic medications have been approved for T2DM, such as glucagon‐like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and sodium/glucose cotransporter 2 inhibitors. A key clinical question for hepatologists is what kinds of antidiabetic medications are the most appropriate for the treatment of NAFLD accompanied by T2DM, to prevent progression of hepatic fibrosis resulting in HCC/liver‐related mortality without increased risk of cardiovascular events. This review focuses on novel antidiabetic agents and future perspectives on the treatment of NAFLD/NASH with T2DM.     

2型糖尿病合并非酒精性脂肪性肝病患者血清视黄醇结合蛋白4水平变化及影响因素的研究

目的 研究T2DM合并非酒精性脂肪性肝病（NAFLD）患者血清视黄醇结合蛋白4（RBP4）水平变化.方法 选取单纯T2DM患者（T2DM） 32例,T2DM合并NAFLD者（T2DM＋NAFLD）31例及正常对照（NC）者34名,测定血清RBP4水平,并计算胰岛β细胞功能指数（HOMA-β）及葡萄糖处置指数（DI）.结果 与其他两组比较,T2DM＋ NAFLD组血清RBP4水平最高（P＜0.05或P＜0.01）,而DI最低（P均＜0.01）.且TG、WC、SBP、DI是RBP4的独立影响因素（P均＜0.05）.RBP4是T2DM合并NAFLD独立危险因素（OR=1.142,P=0.057）.结论 血清RBP4在T2DM＋NAFLD组最高,与胰岛β细胞功能密切相关.     

Glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update

Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver disease worldwide. NAFLD progresses in some cases to non-alcoholic steatohepatitis (NASH), which is characterized, in addition to liver fat deposition, by hepatocyte ballooning, inflammation and liver fibrosis, and in some cases may lead to hepatocellular carcinoma. NAFLD prevalence increases along with the rising incidence of type 2 diabetes mellitus (T2DM). Currently, lifestyle interventions and weight loss are used as the major therapeutic strategy in the vast majority of patients with NAFLD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used in the management of T2DM and do not have major side effects like hypoglycemia. In patients with NAFLD, the GLP-1 receptor production is down-regulated. Recently, several animal and human studies have emphasized the role of GLP-1RAs in ameliorating liver fat accumulation, alleviating the inflammatory environment and preventing NAFLD progression to NASH. In this review, we summarize the updated literature data on the beneficial effects of GLP-1RAs in NAFLD/NASH. Finally, as GLP-1RAs seem to be an attractive therapeutic option for T2DM patients with concomitant NAFLD, we discuss whether GLP-1RAs should represent the first line pharmacotherapy for these patients.     

Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non‐alcoholic fatty liver disease patients

Introduction: Differentiation between steatosis and non‐alcoholic steatohepatitis (NASH) in non‐alcoholic fatty liver disease (NAFLD) is important as NASH progress to cirrhosis. No specific laboratory/imaging technique exists either to diagnose NASH or to select patients for liver biopsy. Patients and methods: We evaluated serum ferritin and the features of metabolic syndrome with respect to histological inflammation and/or fibrosis in NAFLD patients. The Kleiner scoring system was used to classify NAFLD in consecutive liver biopsies. One hundred and eleven patients: median age 52.6, 64 males, obesity 62, diabetes mellitus (DM) 58, arterial hypertension 26 and hyperlipidaemia 40%. Results: Histologically, 40.7 had fatty liver, 30.6% had borderline NASH, 28.7% had NASH and 11% had cirrhosis. Multivariate regression showed that diabetes, serum ferritin concentrations, body mass index (BMI) and AST were independently associated with NASH: together, the areas under the receiver operating characteristic (AUROC) was 0.91 (95% confidence interval 0.86–0.96); fibrosis was associated with ferritin concentrations and BMI: AUROC 0.87, portal inflammation with ferritin and DM: AUROC 0.82, while lobular inflammation was associated with BMI, DM and ferritin: AUROC 0.85. Conclusion: Serum ferritin concentrations and BMI are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients. Both ferritin and BMI are potential discriminant markers to select patients for liver biopsy and are associated with inflammation and fibrosis.     

Body weight loss and glycemic control on the outcomes of patients with NAFLD. The role of new antidiabetic agents

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide affecting a third of adults and 12% of children in Western countries. In around 50–60%% of cases, NAFLD and type 2 diabetes mellitus (T2DM) coexist and act synergistically to increase the risk of adverse hepatic and extra-hepatic outcomes. T2DM is a strong risk factor for rapid progression of NAFLD to nonalcoholic steatohepatitis (NASH), cirrhosis or hepatocellular carcinoma (HCC), which have become frequent indications of liver transplantation.The pathophysiology of NAFLD is complex and its relationship with T2DM is bidirectional, where lipotoxicity and insulin resistance (IR), act as the strongest pillars.To date, no pharmacological treatment has been approved for NAFLD. However, there is an intense research with numerous drugs focused on reversing inflammation and liver fibrosis through modulation of molecular targets without good results.It has been known for some time that weight reduction >10% is associated to histological improvement of NAFLD. Recently, glycemic control has been shown to induce similar results. Diet and physical exercise for weight reduction have limitations, so alternative methods (pharmacologic, endoscopic or surgical) may be required. Currently, new antidiabetic drugs inducing weight loss, have been recently approved for the treatment of obesity. Nevertheless, their therapeutic effects on NAFLD have not been extensively studied.We will review here, recently published data on the effects of weight loss and glycemic control on the histological and metabolic parameters of NAFLD and recent published data on therapeutic studies of NAFLD with new antidiabetic drugs.