Is liver disease a threat to patients with metabolic disorders?

The association of metabolic disorders with liver disease is receiving increasing attention in the gastroenterological community. Cohort studies have shown that advanced liver disease may stem from metabolic disorders, via fatty liver, non-alcoholic steatohepatitis, cryptogenic cirrhosis, and eventually hepatocellular carcinoma. In both obesity and diabetes, deaths from cirrhosis are higher than expected, mainly in subjects with no or moderate alcohol consumption, but high rates of fatty liver disease have been associated with all features of the metabolic syndrome. Also the risk of hepatocellular carcinoma is higher than normal, being dependent on body mass index (BMI) in obesity, and independent of age, BMI, gender and race in diabetes. Finally, metabolic liver disease may interact with hepatitis C virus infection, increasing the risk of steatosis and liver disease progression, as well as reducing the chances of an effective antiviral treatment. There is evidence that treatments aimed at reducing insulin resistance are also effective in improving liver histology. Although cardiovascular disease remains the major cause of increased morbidity and excess mortality in metabolic disorders, the risk of progressive liver disease should no longer be underestimated, being a threat to millions of people at risk in the present epidemics of obesity and diabetes, and therapeutic strategies need to be tested.     

Chronic liver disease and arteriosclerosis

The liver is the main metabolic organ of the body and is strongly associated with lifestyle-related diseases in which abnormal metabolism of glucose and lipid are the main manifestations. Recently, the prevalence of nonalcoholic fatty liver disease(NAFLD), including nonalcoholic steatohepatitis (NASH), has been increasing due to a higher rates of obesity. It has been reported that the presence of NAFLD/NASH and associated liver dysfunction are predictors for cardiovascular disease. In addition, attention has been paid to the link between chronic hepatitis C and lifestyle-related diseases such as obesity and insulin resistance. Atherosclerosis is an important risk factor for cardiovascular disease and is associated with lifestyle-related diseases. Thus, chronic liver disease seems to be strongly associated with atherosclerosis. Cardiovascular disease induced by atherosclerosis should be attended to along with liver cirrhosis and hepatocellular carcinoma, and medications for lifestyle-related diseases are needed in patients with chronic liver disease.     

棕色脂肪治疗代谢相关性脂肪肝病及影像学评估研究进展

代谢相关性脂肪肝病（MAFLD）目前已成为全球第一大肝病,MAFLD不仅能够进展为肝硬化、肝细胞癌,而且还与肥胖、2型糖尿病、心血管疾病等代谢性疾病的发生发展密切相关。目前,尚无已批准用于临床治疗MAFLD的高效药物。近年来,棕色脂肪（BAT）在MAFLD中的潜在作用逐渐受到关注,但两者间的关联及BAT在MAFLD治疗中的作用机制仍需进一步的探索和研究。该文分析了近年来BAT在MAFLD的疾病发展及治疗研究中的概况,并讨论相关影像学检查的新进展,以利于进一步深入探索BAT与MAFLD的关联,探讨BAT作为治疗MAFLD新靶点的可行性。     

健康体检人群体重指数与血脂水平及非酒精性脂肪肝关系的研究

目的探讨体重指数与血脂水平及非酒精性脂肪肝(non-alcoholic fatty liver disease, NAFLD)的关系。 方法对2012年1月至2013年1月于安徽省立医院参加健康体检,病史及饮酒史资料完整的10000名体检者的人体质量指数(BMI)与其相关临床指标进行统计分析。按照BMI将人群分组,不同体重指数人群间血脂水平及NAFLD检出率差异采用χ²检验。 结果(1)所有体检人群中超重及肥胖者5996例,占60%,正常体重者3829例,占38.3%;(2)超重和肥胖在不同年龄组人群中的构成比差异有统计学意义(χ²＝161.733,P＝0.000;(3)除高密度脂蛋白(HDL-C)外,超重组和肥胖组的甘油三脂(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)水平均明显高于体重正常组;(4)NAFLD和高脂血症的发生率随BMI水平升高而逐渐增加;(5)性别(男性)、BMI、TG、TC为NAFLD发生的独立危险因素,HDL-C为保护因素;(6)ROC曲线分析BMI预测NAFLD发生的最佳切点为(男性：24.85或24.95;女性24.95)。 结论超重及肥胖是发生NAFLD和高脂血症的危险因素,应加强对体重的干预,以改善脂代谢和降低NAFLD的发生。     

Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations

The global increase in the prevalence of obesity has heralded a rise in associated liver injury namely NAFLD (non-alcoholic fatty liver disease). It is estimated that 20-30% of adult populations in developed countries have NAFLD and, although high quality data is currently lacking, the condition is clearly increasing in children also. NAFLD should be suspected in those with commonly available simple clinical signs and biochemistry consistent with insulin resistance. A small number of individuals with NAFLD, often considered a relatively benign condition, will progress to more severe stages of liver disease including NASH (non-alcoholic steatohepatitis) with or without fibrosis, cirrhosis and occasionally hepatocellular carcinoma. NAFLD is also commonly associated with an increased risk of developing Type 2 diabetes and treatable features of insulin resistance such as dyslipidaemia and dysglycaemia. Histological examination of liver tissue remains the only proven method to distinguish between simple steatosis and NASH, a condition far more likely to progress to cirrhosis. Identification of an imaging technique or non-invasive marker to achieve this distinction is therefore much sought after and would allow larger clinical trials and better clinical assessment. Case series and pilot studies of lifestyle advice, insulin sensitizers and other medications have shown improvements in liver histology and serum liver enzymes but robust randomized controlled studies are needed. Furthermore, the cost/benefit ratio of any new therapies, and any potential harms, must be evaluated carefully before being clinically advocated.     

2型糖尿病合并脂肪肝88例相关因素分析

目的 探讨Ⅱ型糖尿病合并脂肪肝与肥胖、血压、血糖、胰岛素抵抗指数、血脂水平的关系.方法 随机取201例住院病人,分为糖尿病合并脂肪肝88例(A组),糖尿病无脂肪肝113例(B组),测定体质指数(BMI)、空腹血糖(FBG)、胰岛素抵抗指数(IR)、血脂等.结果 2型糖尿病并脂肪肝组与无脂肪肝组比较,BMI、IR、三酰甘油(TG)、仅密度脂蛋的胆固醇(LDL-C)、载脂蛋的B(Apo)-B均明显升高(P＜0.05).结论 Ⅱ型糖尿病并脂肪肝患者存在超重、胰岛素抵抗、脂代谢紊乱.     

2型糖尿病合并非酒精性脂肪肝的临床研究

【目的]探讨影响2型糖尿病（T2DM）合并非酒精性脂肪肝的危险因素。【方法】分析T2DM伴有非酒精性脂肪肝组26例,T2DM不伴脂肪肝组31例多项指标。【结果】T2DM病伴有脂肪肝组体重指数、腰围、腰臀比、体脂百分比、甘油三酯、胰岛素敏感指数较T2DM不伴有脂肪肝组显著增高（P〈0．05）。【结论】T2DM患者合并非酒精性脂肪肝的独立危险因素是肥胖、高甘油三酯血症和胰岛素抵抗。     

2型糖尿病非酒精性脂肪肝患者危险因素及与代谢综合征的相关性研究

目的研究2型糖尿病非酒精性脂肪肝的危险因素及其与代谢综合征的关系。方法选择2型糖尿病非酒精性脂肪肝患者358例,按有无脂肪肝分组进行临床分析。结果2型糖尿病脂肪肝组肥胖和高脂血症的发生率高于无脂肪肝组,且脂肪肝组代谢综合征的患病率明显升高。结论肥胖和脂代谢异常是2型糖尿病非酒精性脂肪肝患者的相关因素,且其发生率与代谢综合征相关。     

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) refers to the accumulation of hepatic steatosis not due to excess alcohol consumption. The prevalence of NAFLD is up to 30% in developed countries and nearly 10% in developing nations, making NAFLD the most common liver condition in the world. The pathogenesis of NAFLD is related to insulin resistance and, thus, it is frequently found in individuals who have central obesity or diabetes. Insulin resistance and excess adiposity are associated with increased lipid influx into the liver and increased de novo hepatic lipogenesis, promoting hepatic triglyceride accumulation. Defects in lipid utilization via mitochondrial oxidation and lipid export may also contribute to hepatic lipid build-up. Adipocytokine alterations, lipotoxicity from saturated fatty acids and fructose have been all been implicated in causing hepatocyte injury in NAFLD through pathways involving oxidative and endoplasmic reticulum stress. Clinically, NAFLD is commonly asymptomatic and frequently detected incidentally by blood liver function tests or imaging performed for other reasons. Subjects with NAFLD have a higher mortality rate than the general population and are at increased risk of developing cardiovascular disease and diabetes in the future. Histologically, NAFLD occurs as a spectrum from mild hepatic steatosis only, to non-alcoholic steatohepatitis (NASH) characterized by hepatocellular injury and inflammation, to cirrhosis. A diagnosis of NASH with associated fibrosis heralds a more significant prognosis as it is more likely to progressive to cirrhosis with complications of hepatic failure and hepatocellular carcinoma. Currently, the diagnosis of NASH requires a liver biopsy, however, serum based markers of hepatocyte apoptosis such as cytokeratin-18 fragments offer promise as accurate non-invasive diagnostic tests. Treatment of NAFLD revolves around addressing concomitant metabolic risk factors and improving insulin resistance through weight loss measures and exercise. Insulin sensitizing agents such as pioglitazone and anti-oxidant agents such as vitamin E show some promise in improving liver histology in patients with NASH, however, the long-term benefit of these medications has not been demonstrated.     

Fatty liver index predicts incident risk of prediabetes,type 2 diabetes and non-alcoholic fatty liver disease (NAFLD)

AimsTo investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up.MethodsAt baseline (in 2001) 2020 participants, males and females, aged 24–39 years, were stratified according to body mass index (BMI), normal weight (<25 kg/m²), overweight (≥25–<30 kg/m²), or obese (≥30 kg/m²) and FLI (as high FLI ≥60 or low FLI <60). We examined the incidence of prediabetes/type 2 diabetes and NAFLD (ultrasound assessed) over 10 years to 2011 to determine the relative impact of FLI and BMI.Results514 and 52 individuals developed prediabetes and type 2 diabetes during follow-up. Such individuals were older, with higher BMI, serum glucose, insulin, alanine aminotransferase (ALT) and triglyceride (TG) concentrations than those who did not develop prediabetes or type 2 diabetes (n = 1454). The additional presence of high FLI significantly increased the risk of developing prediabetes and type 2 diabetes above the risk of being overweight/obese. Compared with normal weight, low FLI participants, the odds of prediabetes were ∼2-fold higher and the odds of type 2 diabetes were 9–10-fold higher respectively in the overweight/obese, high FLI group. No difference was observed between normal weight, low FLI and overweight/obese and low FLI groups.ConclusionsAn increased FLI significantly increases the odds of incident prediabetes, type 2 diabetes and NAFLD in individuals with overweight/obese highlighting the contributory role of liver fat accumulation in the pathophysiology of prediabetes/type 2 diabetes.

Key messages

• Obesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes.
• Additionally, NAFLD is more prevalent in people with prediabetes and type 2 diabetes when compared to age- and BMI-matched individuals.
• The presence of a raised fatty liver index (FLI) confers a significantly increased risk of developing prediabetes, type 2 diabetes and NAFLD above that conferred by being overweight/obese.
• The degree of elevation of FLI can risk stratify for incident prediabetes and type 2 diabetes in people with obesity.

     

Cirrhosis: diagnosis, management, and prevention

Cirrhosis is the 12th leading cause of death in the United States. It accounted for 29,165 deaths in 2007, with a mortality rate of 9.7 per 100,000 persons. Alcohol abuse and viral hepatitis are the most common causes of cirrhosis, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary care physicians share responsibility with specialists in managing the most common complications of the disease, screening for hepatocellular carcinoma, and preparing patients for referral to a transplant center. Patients with cirrhosis should be screened for hepatocellular carcinoma with imaging studies every six to 12 months. Causes of hepatic encephalopathy include constipation, infection, gastrointestinal bleeding, certain medications, electrolyte imbalances, and noncompliance with medical therapy. These should be sought and managed before instituting the use of lactulose or rifaximin, which is aimed at reducing serum ammonia levels. Ascites should be treated initially with salt restriction and diuresis. Patients with acute episodes of gastrointestinal bleeding should be monitored in an intensive care unit, and should have endoscopy performed within 24 hours. Physicians should also be vigilant for spontaneous bacterial peritonitis. Treating alcohol abuse, screening for viral hepatitis, and controlling risk factors for nonalcoholic fatty liver disease are mechanisms by which the primary care physician can reduce the incidence of cirrhosis.     

老年原发性高血压合并非乙醇性脂肪肝的患病情况及危险因素分析

目的探讨老年高血压患者非乙醇性脂肪性肝病的患病率和危险因素。方法 621例老年高血压患者住院期间经腹部超声检查和采集病史筛查非乙醇性脂肪性肝病(NAFLD),观察其患病率、肝功酶学异常的比例及其危险因素。结果 NAFLD患者发病率为39.1%(243/621)。NAFLD组糖尿病,冠心病,代谢综合征发生率、超重率、三酰甘油、ALT水平高于非NAFLD组,HDL-C低于非NAFLD组,差异有统计学意义(P<0.05)。糖尿病、冠心病、超重和三酰甘油水平是老年高血压患者NAFLD的独立危险因素。结论老年高血压伴NAFLD患者与代谢综合征等多代谢异常密切相关。     

代谢性炎症综合征的概念及临床意义

代谢产物,如游离脂肪酸（FFA）、脂多糖（LPS）等常诱发慢性低度炎症,称代谢性炎症,后者参与并导致动脉粥样硬化、2型糖尿病（T2DM）、非酒精性脂肪肝及肥胖等代谢性疾病的发生。我们在国内外首次提出“代谢性炎症综合征（metabolic inflammatory syndrome,MIS）”的概念及诊断思路,建议将伴有2个及2个以上上述代谢性疾病的患者诊断为MIS。在T2DM人群中,MIS的检测率及预测冠心病的相对危险度明显高于代谢综合征（MS）。 提示MIS的概念较MS更适合于代谢性疾病的早期筛查、预防和研究。如果患者有MIS的 4个组分中的1个,应筛选其他组分,特别是动脉粥样硬化。MIS的概念将促进异病同防和异病同治的临床实践。     

肥胖与高脂血症、脂肪肝、胆囊疾患相关性的研究

目的　探讨肥胖与高脂血症、脂肪肝、胆囊疾患的关系。方法　对 6 6 0名具有高级职称教师 (高职教师 )进行检测身高、体重、血脂及腹部B超检查 ,并对结果进行统计分析。结果　超重及肥胖现患率分别为 2 6 36 %和 36 0 6 %,男性肥胖现患率明显高于女性 (P <0 0 1) ;TC、TG数值随着BMI的增大而上升 ;男女肥胖组并发高TG、脂肪肝的患病率均明显高于对照组 (P <0 0 1或P <0 0 5 ) ,女性肥胖组并发胆囊结石的患病率亦明显高于对照组 (P <0 0 1) ;肥胖组且高TG并发脂肪肝、胆囊结石的患病率明显高于对照组 (P <0 0 1)。结论　肥胖是导致高脂血症、脂肪肝、胆囊结石的主要因素 ,高TG与脂肪肝、胆囊结石关系密切。     

糖尿病合并非酒精性脂肪肝老年患者代谢及血管病变特点

目的:评估老年2型糖尿病(T2DM)伴发非酒精性脂肪肝(NAFLD)患者代谢及血管病变的特点,探讨T2DM和NAFLD对健康的综合影响。方法:将268例老年T2DM患者分为观察组102例(合并NAFLD)和对照组166例(无合并NAFLD),比较2组患者的血清学指标、血管影像学指标及临床并发症,同时行Logistic回归分析相关危险因素。结果:观察组BMI,HOMA-IR,糖化血红蛋白A1c(GHbA1c),ALT、HS-CRP和颈动脉内中膜厚度明显高于(或厚于)对照组(P<0.05～P<0.01),冠状动脉狭窄及冠状动脉粥样硬化性心脏病发生率亦明显高于对照组(P<0.01)。Logistic回归分析示冠状动脉狭窄的危险因素包括甘油三酯、GHbA1c和ALT。结论:T2DM合并NAFLD不仅是简单的伴随现象,而涉及更严重的全身性代谢紊乱,血管并发症发生风险亦增高。     

Evaluation of obesity and diagnostic criteria of obesity as a disease for Japanese

Obesity causes many undesirable health disorders such as diabetes mellitus, hyperlipidemia, hypertension and so on. Recently, those life style-affecting diseases is increasing, especially the increment of diabetes mellitus is prominent. In 2000, Japan obesity society issued the new standard of the evaluation of obesity and new diagnostic criteria of obesity as a disease for Japanese. According to this issue, obesity was evaluated by body mass index(BMI). And, 18.5 < BMI < 25 is normal, 25 < BMI < 30 is obese 1, 30 < BMI < 35 is obese 2, 35 < BMI < 40 is obese 3, and 40 < is obese 4. Obesity as a disease is defined by two cases. The first category is composed of two items; one is BMI > 25, and the other is having one disease worsen by obesity, such as diabetes mellitus, hyperlipidemia, hypertension, hyperuricemia, coronary heart disease, cerebral infarction, sleep apnea syndrome, fatty liver, deformative arthritis. The second category is the visceral type of obesity with BMI > 25, which was diagnosed by west size, over 85 cm for men, and over 90 cm for women, and by visceral fat area over 100 cm2 in abdominal CT.     

NASH in children

It has long been recognized that hepatic steatosis (fatty liver) occurs in obese children as in adults. Steatosis of any etiology can be associated with the development of necro-inflammation and fibrosis, so called steatohepatitis, and even cirrhosis. Nonalcoholic steatohepatitis (NASH) has been proposed as a component of insulin resistant syndrome and exists in pediatric population. The other etiology of NASH in children has not been clearly understood. In addition to obesity, adipose tissue distribution also appears to influence metabolic complications. Subjects with visceral fat adiposity appear to be at risk for fatty liver because of their ability to transport free fatty acids directly into the portal vein for conversion to triglycerides within the liver. A stronger relationship of serum ALT to visceral adiposity than BMI was demonstrated. Many metabolic diseases such as Wilson's disease, NICCD, OTC deficiency, carnitine deficiency have steatohepatitis and cirrhosis. It may play the important role to reveal the mechanism of progress to NASH.     

Nonalcoholic Fatty Liver Disease: Evidence-Based Management and Early Recognition of Nonalcoholic Steatohepatitis

Nonalcoholic fatty liver disease is the most prevalent liver disease in the world. Metabolic syndrome and obesity are associated risk factors. The inflammatory subtype, nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis, is predicted to become the primary indication for liver transplantation within the next decade. Although there are no approved medications for NASH, there are ongoing multicenter trials aimed at targeting aspects of fat accumulation, inflammation, and fibrosis throughout the disease process. Nurse practitioners should focus on identifying patients at risk for NASH, while using guidelines for the management of nonalcoholic fatty liver disease and the comorbidities contributing to disease progression.     

2型糖尿病并发脂肪肝80例临床分析

目的　探讨2型糖尿病患者空腹血糖、血脂、体重指数与脂肪肝的关系。方法　对2型糖尿病并发脂肪肝患者进行空腹血糖、血脂水平及身高、体重的测定,计算体重指数(BMI),并以76例2型糖尿病无脂肪肝患者作对照。结果　2型糖尿病并发脂肪肝组与未并发脂肪肝组相比BMI、甘油三酯、低密度蛋白胆固醇及空腹血糖均升高(均为P<0. 05)。结论　2型糖尿病患者合并脂肪肝与血脂代谢紊乱、血糖偏高及肥胖等有关。     

老年人群代谢综合征调查分析

目的：调查老年体检人员代谢综合征（MS）及其相关疾病的患病情况。方法：检测559例体检人员的身高、体重、腰围、血压、心率、体重指数（BMI）、空腹血糖、总胆固醇、甘油三脂、高密度脂蛋白等指标，并对调查结果进行统计分析。结果：老年男性MS发病率为14．15％，60-70岁组的MS发病率为最高，达22．41％；老年女性MS发病率为20．56％，80岁以上的发病率较高，达30．43％。在MS各种组合中，男性和女性均以肥胖＋高血压＋高血脂这种组合比例最大，占40％以上。MS患者伴发脂肪肝、糖尿病、高血压的比例均高于非代谢综合征的患者（P〈0．05，P〈0．01）。脂肪肝（OR=4．287，95％CI：1．737～10．583，P=0．002）、腰围（OR=3．783，95％CI：1．019～14．050，P=0．047），脂肪肝和腰围与MS密切相关。结论；本次调查显示老年人MS发病率有增高趋势，最多见的表现形式为肥胖＋高血压＋高血脂组合，MS合并脂肪肝、糖尿病、高血压的比例亦有增高，脂肪肝和腰围对MS具有显著危险性。