Current treatment options for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease is the leading cause of liver disease in western society. It is a cause of end-stage liver disease, with increased mortality secondary to cirrhosis and its complications. It is also recognized that cardiovascular disease is a significant cause of death in these patients. Significant work evaluating various treatments has been performed in recent years; however, to date, no ideal therapy exists. Lifestyle modification remains the cornerstone of management. The present article reviews the current status of various treatment modalities evaluated in nonalcoholic fatty liver disease.     

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)包括单纯性脂肪肝以及由其演变的脂肪性肝炎和肝硬化.代谢综合征(MS)是心血管病的多种代谢危险因素在个体内集中的状态,NAFLD常与MS相伴,其发病与MS的各组分密切相关.很多研究表明,肥胖、胰岛素抵抗、血脂紊乱、糖代谢异常、高血压是NAFLD发病的危险因素,而在NAFLD人群中MS的患病率明显增高.因此NAFLD与MS关系密切,具有共同的发病基础,二者的预后、治疗原则相似.     

Relationship between nonalcoholic fatty liver disease and metabolic syndrome

OBJECTIVE: The aim of this study was to investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in subjects who underwent a routine health checkup. We intended to establish a clinical association between NAFLD and MS as well as to compare the diagnostic criteria of MS based on the definitions set forth by the International Diabetes Federation (IDF), the US National Cholesterol Education Program Adult Treatment Panel III (2001) (NCEP/ATP‐III) and the Metabolic Syndrome Study Group of Chinese Diabetes Society (CDS). METHODS: Weight, height, waist circumference, hip circumference, percentage of body fat, blood pressure and ultrasound of liver were performed on subjects undergoing routine health checkup. Serum triglyceride, total cholesterol, high density lipoprotein cholesterol and fasting plasma glucose level were measured. RESULTS: A total of 2394 subjects were included in this analysis and 437 had NAFLD. The prevalence of MS in the whole sample according to IDF, NCEP/ATP‐III and CDS definitions was 11.11%, 8.48% and 5.30%, respectively. The total degree of agreement between IDF, NCEP/ATP‐III and CDS definition was 87.76%. The prevalence of MS in NAFLD subjects is much higher than that in non‐NAFLD subjects. The prevalence of NAFLD in MS subjects is also much higher than that in non‐MS subjects. CONCLUSION: The prevalence of MS varied depending on the diagnostic criteria used. NAFLD was strongly associated with the MS, although it remains unknown whether NAFLD is a cause or effect of MS.     

非酒精性脂肪性肝病与代谢综合征关系研究进展

非酒精性脂肪性肝病的发病与胰岛素抵抗及其表型有关。胰岛素抵抗和代偿性高胰岛素血症是代谢综合征的中心环节。非酒精性脂肪性肝病是代谢综合征的临床疾病谱之一。非酒精性脂肪性肝病与动脉粥样硬化性心血管疾病、2型糖尿病及代谢综合征临床症候群的关系密切,本文就非酒精性脂肪肝与代谢综合征的关系作一综述。     

Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease

OBJECTIVES: To explore associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease (NAFLD). DESIGN AND PATIENTS: In a cross-sectional study, we enrolled 60 consecutive NAFLD patients and 60 age-, sex- and body mass index (BMI)-matched healthy controls. MEASUREMENTS: NAFLD (by liver biopsy), plasma adiponectin concentrations, insulin resistance (by homeostasis model assessment, HOMA-IR) and metabolic syndrome (MetS) features. RESULTS: NAFLD patients had a marked decrease in plasma adiponectin concentration (6.1 +/- 2.8 vs. 13.6 +/- 3.8 microg/ml, P < 0.001) compared with matched controls. MetS, as defined by the Adult Treatment Panel III (ATP III) criteria, and its individual components were more frequent among NAFLD patients. The marked differences in adiponectin concentrations that were observed between the groups were little affected by adjustment for age, sex, BMI, HOMA-IR score and MetS components. Notably, decreased adiponectin levels were closely associated with the degree of hepatic steatosis, necroinflammation and fibrosis (P < 0.001 for all) among NAFLD patients. By logistic regression analysis, low adiponectin levels independently predicted hepatic steatosis [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.5-5.8, P < 0.001] and necroinflammation (OR 3.1, 95% CI 1.9-7, P < 0.001), but not fibrosis (P = 0.07), after adjustment for age, sex, BMI, HOMA-IR and MetS components. CONCLUSIONS: NAFLD patients have markedly lower plasma adiponectin concentrations than control subjects. Low adiponectin levels are strongly associated with the severity of liver histology, thus further supporting the hypothesis that adiponectin might be involved in the development of NAFLD.     

他汀类药物在治疗非酒精性脂肪肝病中的研究进展

近年来,非酒精性脂肪肝病逐渐成为国内肝病相关死亡率的主要因素。非酒精性脂肪肝病的发病机制主要与代谢综合征相关,其危险因素主要包括肥胖、2型糖尿病、脂代谢异常等,这些危险因素与心血管疾病密切相关,心血管疾病死亡率也成为非酒精性脂肪肝病首要的死亡原因。他汀类药物是最主要的降脂药物,有证据表明,非酒精性脂肪肝病患者使用他汀类药物降脂治疗不仅能有效降低肝脏转氨酶水平,降低心血管疾病病死率,而且能有效减轻肝脏脂肪变性程度,同时可能对延缓肝脏纤维化有一定的疗效。     

Associations between nonalcoholic fatty liver disease and ischemic stroke

Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and affects a considerab-le proportion of the general population. NAFLD is independently associated with increased risk for cardiovascular events, particularly coronary heart disease. Importantly, even though NAFLD is more prevalent in patients with major cardiovascular risk factors(e.g., type 2 diab-etes mellitus, ob-esity and hypertension), the association b-etween NAFLD and cardiovascular disease appears to b-e independent of these risk factors. However, NAFLD also appears to increase the risk for ischemic stroke, a leading cause of mortality and long-term disab-ility worldwide. It also appears that nonalcoholic steatohepatitis is more strongly related to the risk of ischemic stroke than isolated hepatic steatosis. Moreover, emerging data suggest that patients with NAFLD experience more severe ischemic stroke and have more unfavorab-le prognosis after an acute ischemic stroke in terms of functional dependency and short-and long-term mortality. These associations have major pub-lic health implications, since ischemic stroke is the second leading cause of death worldwide and an important cause of long-term disab-ility. The aim of the present review is to summarize the current knowledge regarding the relationship b-etween NAFLD and ischemic stroke incidence, severity and outcome. Given these associations, it might b-e useful to evaluate patients with acute ischemic stroke for the presence of NAFLD and to manage those with NAFLD more aggressively.     

Carotid lesions in outpatients with nonalcoholic fatty liver disease

AIM： To ascertain whether carotid lesions are more prevalent in outpatients with incidental findings of nonalcoholic fatty liver disease （NAFLD） at abdominal ultrasound （US）. METHODS： One hundred and fifty-four consecutive outpatients （age range 24-90 years, both sexes） referred by general practitioners for abdominal US, and drinking less than 20 g alcohol/day, underwent carotid US for an assessment of carotid intima-media thickness （c-IMT） and carotid plaque prevalence. Hepatic steatosis, visceral fat thickness and subcutaneous fat thickness were also assessed at ultrasonography. RESULTS： Higher c-IMT values were found in the presence of NAFLD （90 patients）, even after adjustment for indices of general and abdominal obesity and for the principal cardiovascular risk factors （0.84 ± 0.10 mm vs 0.71 ± 0.10 mm, P 〈 0.001）. The prevalence of carotid plaques was 57.8% in the patients with NAFLD vs 37.5% in the patients without this condition （P = 0.02）. The adjusted relative risk of having carotid plaques for patients with NAFLD was 1.85 （95% CI： 1.33-2.57, P 〈 0.001）.CONCLUSION： An incidental finding of hepatic steatosis may suggest the presence of silent carotid atherosclerotic lesions.     

Associations between obesity and metabolic health with nonalcoholic fatty liver disease in elderly Chinese

Background: Nonalcoholic fatty liver disease(NAFLD) is closely associated with obesity. However, this association could be influenced by the coexisting metabolic abnormalities. This study aimed to investigate the role of obesity and metabolic abnormalities in NAFLD among elderly Chinese. Methods: A cross-sectional study was performed among elderly residents who took their annual health checkups during 2016 in Keqiao District, Shaoxing, China. Results: A total of 3359 elderly adults were retrospectively included in this study. The overall prevalence of NAFLD was 28.7%. The prevalence of NAFLD were 7.14%, 27.92%, 34.80%, and 61.02% in participants with metabolically healthy normal weight(MHNW), metabolically abnormal normal weight(MANW), metabolically healthy obese(MHO), and metabolically abnormal obese(MAO), respectively. NAFLD patients in MHO group had more unfavorable metabolic profiles than those in MHNW group. Logistic regression analysis showed that sex, body mass index(BMI), fasting blood glucose, and serum uric acid were the risk factors of NAFLD. Conclusions: Both obesity and metabolic health were significantly associated with NAFLD in elderly Chinese. Screening for obesity and other metabolic abnormalities should be routinely performed for early risk stratification of NAFLD.     

Cholecystectomy is independently associated with nonalcoholic fatty liver disease in an Asian population

AIM: To investigate the relationship between gallstone disease and nonalcoholic fatty liver disease(NAFLD) in a large Asian population. METHODS: A cross-sectional study including 17612 subjects recruited from general health check-ups at the Seoul National University Hospital, Healthcare System Gangnam Center between January 2010 and December 2010 was conducted. NAFLD and gallstone disease were diagnosed based on typical ultrasonographic findings. Subjects who were positive for hepatitis B or C, or who had a history of heavy alcohol consumption( 30 g/d for men and 20 g/d for women) or another type of hepatitis were excluded. Gallstone disease was defined as either the presence of gallstones or previous cholecystectomy, and these two entities(gallstones and cholecystectomy) were analyzed separately. Clinical parameters including body mass index, waist circumference, hypertension, diabetes, smoking status, and regular physical activity were reviewed. Laboratory parameters, including serum levels of gamma-glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase, fasting glucose, fasting insulin, total cholesterol, triglycerides, and high-density lipoprotein, were also reviewed.RESULTS: The mean age of the subjects was 48.5± 11.3 years, and 49.3% were male. Approximately 30.3% and 6.1% of the subjects had NAFLD and gallstone disease, respectively. The prevalence of gallstone disease(8.3% vs 5.1%, P 0.001), including both the presence of gallstones(5.5% vs 3.4%, P 0.001) and a history of cholecystectomy(2.8% vs 1.7%, P 0.001), was significantly increased in the NAFLD group. In the same manner, the prevalence of NAFLD increased with the presence of gallstone disease(41.3% vs 29.6%, P 0.001). Multivariate regression analysis showed that cholecystectomy was associated with NAFLD(OR = 1.35, 95%CI: 1.03-1.77, P = 0.028). However, gallstones were not associated with NAFLD(OR = 1.15, 95%CI: 0.95-1.39, P = 0.153). The independent association between cholecystectomy and NAFLD was still significant after additional adjustment for insulin resistance(OR = 1.45, 95%CI: 1.01-2.08, P = 0.045). CONCLUSION: This study shows that cholecystectomy, but not gallstones, is independently associated with NAFLD after adjustment for metabolic risk factors. These data suggest that cholecystectomy may be an independent risk factor for NAFLD.     

非酒精性脂肪性肝病与代谢综合征指标变化的相关性分析

目的探讨中老年人群中非酒精性脂肪性肝病(NAFLD)与代谢综合征相关指标变化的关系。方法收集2010—2011年暨南大学附属第一医院40岁以上体检人群腹部B超检查的数据,用多因素Logistic回归分析体重指数(BMI)、空腹血糖(FBG)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)、丙氨酸转氨酶(ALT)、血尿酸(UA)的变化值与NAFLD变化的关系。结果 2年内男性组和女性组NAFLD检出率都在增加,男性新增NAFLD总检出率为13.7%,明显高于女性新增NAFLD检出率7.5%(P<0.05);男性和女性的NAFLD消减率都是5.5%,且峰值都在60岁年龄组;BMI变化值与新增NAFLD密切正相关,BMI变化值的OR=1.474(95%CI 1.184～1.811),而TG和FBG的变化值与新增NAFLD无相关性;TG和BMI的变化值与NAFLD的消减呈负相关,TG变化值的OR=0.653(95%CI 0.508～0.838),BMI变化值的OR=0.628(95%CI 0.460～0.857),而FBG变化值未发现与NAFLD消减有相关性。结论 BMI变化值与NAFLD发生有密切相关性,TG和BMI的变化值与NAFLD的消减呈负相关,是影响NAFLD变化的重要因素之一。     

Crosstalk between nonalcoholic fatty liver disease and cardiometabolic syndrome

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by fat accumulation combined with low‐grade inflammation in the liver. A large body of clinical and experimental data shows that increased flux of free fatty acids from increased visceral adipose tissue and de novo lipogenesis can lead to NAFLD and insulin resistance. Thus, individuals with obesity, insulin resistance, and dyslipidaemia are at the greatest risk of developing NAFLD. Conversely, NAFLD is a phenotype of cardiometabolic syndrome. Notably, researchers have discovered a close association between NAFLD and impaired glucose metabolism and focused on the role of NAFLD in the development of type 2 diabetes. Moreover, recent studies provide substantial evidence for an association between NAFLD and atherosclerosis and cardiometabolic disorders. Even if NAFLD can progress into severe liver disorders including nonalcoholic steatohepatitis (NASH) and cirrhosis, the majority of subjects with NAFLD die from cardiovascular disease eventually. In this review, we propose a potential pathological link between NAFLD/NASH and cardiometabolic syndrome. The potential factors that can play a pivotal role in this link, such as inflammation, insulin resistance, alteration in lipid metabolism, oxidative stress, genetic predisposition, and gut microbiota are discussed.     

Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk

Nonalcoholic fatty liver disease(NAFLD) encompasses a range of liver histology severity and outcomes in the absence of chronic alcohol use.The mildest form is simple steatosis in which triglycerides accumulate within hepatocytes.A more advanced form of NAFLD,nonalcoholic steatohepatitis,includes inflammation and liver cell injury,progressive to cryptogenic cirrhosis.NAFLD has become the most common cause of chronic liver disease in children and adolescents.The recent rise in the prevalence rates of overweig...     

Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease

BACKGROUND/AIMS: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion. METHODS AND RESULTS: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe. In nondiabetic subjects, a progressive (P < 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome. Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P < 0.01) compared with those with homeostasis model of insulin resistance below the median. CONCLUSIONS: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.     

Effects of nonalcoholic fatty liver disease on the development of metabolic disorders

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) is considered to be the liver component of metabolic syndrome. However, the impact of NAFLD on metabolic syndrome is unclear. The aim of this study was to explore the influence of NAFLD on the development of metabolic disorders. Methods: Patients with NAFLD and an age, sex, and occupation‐matched control group were recruited from employees of Bao‐Steel Group (Shanghai, China) who had received medical check‐ups biennially between 1995 and 2002. Anthropometric and laboratory data, and incidence of metabolic disorders were assessed at baseline and at follow‐up of at least 4 years. SPSS 11.5 was used for statistical analysis. Results: The study consisted of 358 patients (326 men and 32 women) and 788 matched controls (711 men and 77 women) with a similar mean age of 39.0 years and median follow‐up of 6 years. At the end of follow‐up, incidence of obesity (47.6% vs 19.5%), hypertension (69.6% vs 16.3%), hypertriglyceridemia (39.1% vs 16.3%), hypercholesterolemia (24.5% vs 17.3%), impaired fasting glucose (IFG) (25.1% vs 11.6%), diabetes mellitus (20.3% vs 5.2%) and multiple metabolic disorders (MMD) (56.3% vs 16.3%) were significantly higher in the fatty liver group than the control group. Interestingly, the mean alanine aminotransferase (ALT) level in patients with fatty liver significantly decreased at follow‐up compared with baseline (28.56 ± 18.86 vs 31.51 ± 18.34 U/L, P < 0.05). To separate the effects of obesity from fatty liver, the subjects were re‐classified according to the presence of obesity and fatty liver at baseline. The incidence of hypertension (61.1% vs 41.3%), hypertriglyceridemia (38.1% vs 15.0%), hypercholesterolemia (29.9% vs 16.6%), IFG (21.3% vs 10.0%) and diabetes (11.1% vs 4.3%) were significantly higher in the fatty liver group without obesity (n = 84) than in the group with without fatty liver or obesity (n = 614). In addition, the incidence of hypertension (72.9% vs 57.4%), hypertriglyceridemia (39.4% vs 22.7%) and diabetes (23.2% vs 8.4%) was higher in the group with fatty liver and obesity (n = 274) than in the group with obesity alone (n = 174). Conclusions: The presence of NAFLD might predict the development of metabolic disorders due to insulin resistance, rather than obesity itself. ALT levels decreased over time in patients with fatty liver.