高效抗反转录病毒治疗相关性脂肪代谢综合征

自1996年高效抗反转录病毒治疗(HAART)应用于临床以来,艾滋病的发病率和死亡率已经大大降低。但HAART治疗需长期或终身服药,因此,药物的毒副作用容易导致患者的依从性下降。其中脂肪代谢综合征就是HAART用药过程中的一个比较常见的远期不良反应之一。HAART药物中与脂肪代谢有关的主要是蛋白酶抑制剂(PIs)和核苷类逆转录酶抑制剂(NRTIs),可以引起各种代谢异常和内分泌紊乱综合征。其具体的发病机制目前尚不清楚。本文就脂肪代谢综合征的发病机制、检测及治疗进行了阐述。

左旋卡尼汀治疗非酒精性脂肪肝伴代谢综合征临床疗效分析

目的探讨左旋卡尼汀治疗非酒精性脂肪肝伴代谢综合征的临床效果。方法 90例非酒精性脂肪肝伴代谢综合征患者,随机分为对照组和观察组,各45例。对照组接受门冬氨酸钾镁片治疗,观察组接受左旋卡尼汀治疗,对比两组患者的临床效果及代谢综合征指标。结果观察组治疗后其临床效果明显好于对照组,差异有统计学意义(P<0.05)。治疗后观察组患者的代谢综合征指标变化也明显优于对照组(P<0.05)。结论左旋卡尼汀治疗非酒精性脂肪肝伴代谢综合征其临床效果显著,能有效改善患者的血糖以及血脂代谢,无不良反应发生,在临床上具有重要的意义。

清热解毒方药对艾滋病抗病毒治疗后脂肪代谢障碍综合征的临床研究

目的探讨运用清热解毒方药对艾滋病抗病毒治疗后脂肪代谢障碍综合征患者作用的临床疗效及安全性。方法将105例艾滋病抗病毒治疗后出现脂肪代谢障碍综合征的患者随机分为治疗组A、治疗组B与对照组C。治疗组A予清热解毒方组,治疗组B予健脾化湿方组,对照组C予安慰剂。3组均治疗12周,观察治疗前后3组患者血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)、B超影像学表现等指标的变化及中医症状的改善情况。结果治疗12周时治疗组A/B患者中医临床症状、血清TC、TG、LDL和HDL、腹部B超影像学表现的改善情况明显优对照组C,而治疗组A/B血清TC和B超影像学表现的比较,差异有统计学意义。结论采用清热解毒方药对艾滋病抗病毒治疗后脂肪代谢障碍综合征患者的近期临床疗效在一定程度上优于常规健脾化湿方药治疗。

从痰瘀论治HAART致脂肪代谢障碍综合征

脂肪代谢障碍综合征是艾滋病患者使用抗逆转录病毒治疗后常见的副反应,它涉及脂肪重新分布和代谢障碍等内容,脂肪重新分布又包括脂肪沉积和脂肪萎缩两部分内容,代谢障碍即代谢综合征或X综合征主要指胰岛素抵抗、高血脂等。中医从痰、瘀角度来认识此病,气机郁滞、痰凝水聚、瘀血阻痹是主要病机变化过程,痰浊、瘀血贯穿在整个病理变化过程中。治疗当从祛痰化瘀、疏肝解郁、益气解毒之法,并注意顾护胃气。

Liver histology according to the presence of metabolic syndrome in nonalcoholic fatty liver disease cases

AIM:To investigate the histologic features of the liver in nonalcoholic fatty liver disease (NAFLD) cases according to the presence of metabolic syndrome or its individual components. METHODS:We enrolled 81 patients (40 male,41 fe-male) who were diagnosed with fatty liver by ultraso-nographic scan and fulfi lled the inclusion criteria. First anamnesis,anthropometric,clinical,laboratory and imaging features of all participants were recorded and then liver biopsy was performed after gaining consent from patients. Diagnosis of metabolic syndrome was dependent on patients having 3 or more out of 5 risk criteria defined by the WHO. Biopsy specimens were assessed according to Brunt et al's classification. RESULTS:Sixty-nine of the 81 patients had nonalco-holic steatohepatitis (NASH),11 had simple fatty liver and 1 had cirrhosis according to histologic evaluation. Comparisons were made between two groups of NASH patients,those with and without metabolic syndrome. We did not detect statistically significant differences in liver histology between NASH patients with and wit-hout metabolic syndrome. CONCLUSION:NASH can progress without metabolic risk factors or the presence of metabolic syndrome.

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 overweight and obesity likely explains the NAFLD epidemic worldwide.NAFLD is strongly associated with abdominal obesity,type 2 diabetes,and dyslipidemia,and most patients have evidence of insulin resistance.Thus,NAFLD shares many features of the metabolic syndrome(MetS),a highly atherogenic condition,and this has stimulated interest in the possible role of NAFLD in the development of atherosclerosis.Accumulating evidence suggests thatNAFLD is associated with a significantly greater overall mortality than in the general population,as well as with increased prevalence of cardiovascular disease(CVD),independently of classical atherosclerotic risk factors.Yet,several studies including the pediatric population have reported independent associations between NAFLD and impaired flow-mediated vasodilatation and increased carotid artery intimal medial thickness-two reliable markers of subclinical atherosclerosis-after adjusting for cardiovascular risk factors and MetS.Therefore,the rising prevalence of obesity-related MetS and NAFLD in childhood may lead to a parallel increase in adverse cardiovascular outcomes.In children,the cardiovascular system remains plastic and damage-reversible if early and appropriate interventions are established effectively.Therapeutic goals for NAFLD should address nutrition,physical activity,and avoidance of smoking to prevent not only end-stage liver disease but also CVD.

Non-alcoholic fatty liver disease:An early mediator predicting metabolic syndrome in obese children?

AIM:To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome,and if liver B-ultrasound can be used for its diagnosis.METHODS:We classified 861 obese children (6-16 years old) into three subgroups:group 0 (normal liver in ultrasound and normal transaminases);group 1 (fatty liver in ultrasound and normal transaminases);and group 2 (fatty liver in ultrasound and elevated transaminases).We measured the body mass index,waist and hip circumference,blood pressure,fasting blood glucose,insulin,homeostasis model assessment of insulin resistance (HOMA-IR),whole-body insulin sensitivity index (WBISI),lipid profile and transaminases in all the participants.The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination.RESULTS:Among the 861 obese children,587 (68.18%) were classified as having NAFLD,and 221 (25.67%) as having MS.The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587),which was much higher than that in non-NAFLD group (group 0,12.04%) (P < 0.01).There were significantly higher incidences concerning every component of MS in group 2 compared with group 0 (P < 0.05).The incidence of NAFLD in MS patients was 84.61% (187/221),which was significantly higher than that of hypertension (57.46%,127/221) and glucose metabolic anomalies (22.62%,50/221),and almost equal to the prevalence of dyslipidemia (89.14%,197/221).Based on the B-ultrasound scales,the presence of moderate and severe liver fatty infiltration carried a high risk of hypertension [odds ratio (OR):2.18,95% confidence interval (95% CI):1.27-3.75],dyslipidemia (OR:7.99,95% CI:4.34-14.73),impaired fasting glucose (OR:3.65,95% CI:1.04-12.85),and whole MS (OR:3.77;95% CI:1.90-7.47,P < 0.01).The state of insulin resistance (calculated by HOMA-IR and WBISI) deteriorated as the degree of fatty infiltration increased.CONCLUSION:NAFLD is not only a liver disease,but also an early mediator that reflects metabolic disorder,and liver B-ultrasound can be a useful tool for MS screening.

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.

Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome

AIM:To clarify the efficiency of the criterion of metabolic syndrome to detecting non-alcoholic fatty liver disease(NAFLD).METHODS:Authors performed a cross-sectional study involving participants of a medical health checkup program including abdominal ultrasonography.This study involved 11 714 apparently healthy Japanese men and women,18 to 83 years of age.NAFLD was defined by abdominal ultrasonography without an alcohol intake of more than 20 g/d,known liver disease,or current use of medication.The revised criteria of the National Cholesterol Education Program Adult Treatment PanelⅢ were used to characterize the metabolic syndrome.RESULTS:NAFLD was detected in 32.2%(95%CI:31.0%-33.5%)of men(n=1874 of 5811)and in 8.7%(95%CI:8.0%-9.5%)of women(n=514 of 5903).Among obese people,the prevalence of NAFLD was as high as 67.3%(95%CI:64.8%-69.7%)in men and 45.8%(95%CI:41.7%-50.0%)in women.Although NAFLD was thought of as being the liver phenotype of metabolic syndrome,the prevalence of the metabolic syndrome among subjects with NAFLD was low both in men and women.66.8%of men and 70.4%of women with NAFLD were not diagnosed with the metabolic syndrome.48.2%of men with NAFLD and 49.8%of women with NAFLD weren't overweight[body mass index(BMI)≥25 kg/m2].In the same way,68.6%of men with NAFLD and 37.9%of women with NAFLD weren't satisfied with abdominal classification(≥90 cm for men and≥80 cm for women).Next,authors defined it as positive at screening for NAFLD when participants satisfied at least one criterion of metabolic syndrome.The sensitivity of the definition"at least 1 criterion"was as good as 84.8%in men and 86.6%in women.Separating subjects by BMI,the sensitivity was higher in obese men and women than in non-obese men and women(92.3%vs 76.8%in men,96.1%vs 77.0%in women,respectively).CONCLUSION:Authors could determine NAFLD effectively in epidemiological study by modifying the usage of the criteria for metabolic syndrome.

Protective effect of alcohol consumption for fatty liver but not metabolic syndrome

AIM:To investigate the effect of alcohol on the metabolic syndrome (MS) and fatty liver in Japanese men and women.METHODS:A cross-sectional study was conducted in a medical health checkup program at a general hospital.This study involved 18 571 Japanese men and women,18-88 years of age,with a mean body mass index of 22.6 kg/m 2.A standardized questionnaire was administered.The total amount of alcohol consumed per week was calculated,and categorized into four grades.Fatty liver was examined by ultrasound modified criteria of the revised National Cholesterol Educa-tion Program Adult Treatment Panel Ⅲ and the new International Diabetes Federation.RESULTS:The prevalence of fatty liver decreased in men and women with light to moderate alcohol consumption,whereas the prevalence of MS was not so changed.The prevalence of fatty liver of any grade in men was lower than that in those with no or minimal alcohol consumption.In women with light to moderate alcohol consumption,prevalence of fatty liver was lower than that in women with no or minimal alcohol consumption.By logistic regression analysis,the odds ratio (OR) for MS in women with light alcohol consumption was decreased to < 1.0,but this change was not clear in men.The OR for fatty liver was clearly < 1.0 in men with any level of alcohol consumption and in women with light to moderate consumption.CONCLUSION:Light to moderate alcohol consumption has a favorable effect for fatty liver,but not for MS in Japanese men and women.

Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease(NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis(NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

Clinical implications of fatty pancreas:Correlations between fatty pancreas and metabolic syndrome

AIM:To investigate the clinical implications of lipid deposition in the pancreas(fatty pancreas). METHODS:The subjects of this study were 293 patients who had undergone abdominal computed tomography(CT)and sonography.Fatty pancreas was diagnosed by sonographic findings and subdivided into mild,moderate,and severe fatty pancreas groups comparing to the retroperitoneal fat echogenicity. RESULTS:Fatty pancreas was associated with higher levels for visceral fat,waist circumference,aspartate aminotransferase(AST),alanine aminotransferase (ALT),total cholesterol,triglyceride,high density lipoprotein,free fatty acid,γ-GTP,insulin,and the homeostasis model assessment of insulin resistance (HOMA-IR)than the control group(P<0.05).HOMAIR,visceral fat,triglyceride,and ALT also tended to increase with the degree of fat deposition in the pancreas on sonography.In a multivariate logistic regression analysis,HOMA-IR,visceral fat,and ALT level were independently related to fatty pancreas after adjustment for age,body mass index,and lipid profile.The incidence of metabolic syndrome in the fatty pancreas group was significantly higher than in the control group,and the numbers of metabolic syndrome parameters were significantly higher in the fatty pancreas group(P<0.05).CONCLUSION:Sonographic fatty pancrease showed higher insulin resistance,visceral fat area,triglyceride, and ALT levels than normal pancreases.Fatty pancreas also showed a strong correlation with metabolic syndrome.

The relation between epicardial fat thickness and metabolic syndrome

To the editor We read the article Usefulness of the epicardial fat tissue thickness as a diagnostic criterion for geriatric patients with metabolic syndrome by Kaya, et al. The authors aimed to evaluate the epicardial fat tissue thickness （EFT） as a diagnostic criterion for geriatric patients with metabolic syndrome （MetS）. They concluded that EFT levels were higher in geriatric patients with MetS and can therefore be used as a diagnostic criterion for MetS.

Usefulness of the epicardial fat tissue thickness as a diagnostic criterion for geriatric patients with metabolic syndrome

Objective To evaluate the epicardial fat tissue thickness （EFTT） as a diagnostic criterion for geriatric patients with metabolic syn- drome （MetS）. Methods Sixty geriatric patients over 65 years of age were recruited for the study. Patients were divided into two groups： Group 1 （n = 30） consisted of patients with MetS; Group 2 （n = 30） consisted of patients without MetS. Echocardiography was used to measure EFTT in all patients, and blood samples were analyzed for biochemical parameters. Results Compared to Group 2, EFTT levels of Group 1 were statistically higher （P 〈 0.05）. In a binary logistic regression analysis, EFTT levels served as the independent factor for meta- bolic syndrome 03 = 17.35, SE = 4.93, Wald = 12.36, P 〈 0.001）. Receivers operating characteristic Curve （ROC-curve） analysis revealed that EFTT predicted MetS with 96.7% sensitivity and 86.7% specificity above the level of 7.3 mm [area under the curve = 0.969; 95% con- fidence interval （CI）： 0.928-1.00]. Conclusions The present study demonstrated that serum EFTT levels were higher in geriatric patients with MetS and can therefore be used as a diagnostic criterion for MetS.

Cytokeratin-18 fragments and biomarkers of the metabolic syndrome in nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease(NAFLD)remains a leading cause of chronic liver disease.In the context of NAFLD,the presence of nonalcoholic steatohepatitis (NASH)portends an adverse prognosis with greater risk of liver fibrosis and cirrhosis.Although liver biopsy is the keystone of patient management in NAFLD,it is also increasingly clear that such evaluation has its limitations.The availability of biochemical markers of NAFLD and NASH has tremendous potential to radically alter management strategies for these conditions,as well as to monitor disease activity.Our article provides an overview of biomarker discovery and selection in the setting of NAFLD and highlights future directions in the field.

Fatty Acid Synthase Inhibitors from Plants and Their Potential Application in the Prevention of Metabolic Syndrome

Fatty acid synthase （FAS） attracts more and more attention recently as a potential target for metabolic syndrome,such as cancer, obesity, diabetes and cerebrovascular disease. FAS inhibitors are widely existed in plants, consisting of diversiform compounds. These inhibitors exist not only in herbs also in many plant foods, such as teas, allium vegetables and some fruits. These effective components include gallated catechins, theaflavins,flavonoids, condensed and hydrolysable tannins, thioethers,pentacyclic triterpenes, stilbene derivatives, etc, and they target at the different domains of FAS, showing different inhibitory mechanisms. Interestingly, these FAS inhibitor-contained herbs and plant foods and their effective components are commonly related to the prevention of metabolic syndromes including fatreducing and depression of cancer. From biochemical angle,FAS can control the balance between energy provision and fat production. Some studies have shown that the effects of those effective components in plants on metabolic syndromes are mediated by inhibiting FAS. This suggests that FAS plays a critical role in the regulation of energy metabolism, and the FAS inhibitors from plants have significant potential application value in the treatment and prevention of metabolic syndromes.

Non-alcoholic fatty liver disease and metabolic syndrome in obese children

I read with great interest the article of Fu et al who investigated whether non-alcoholic fatty liver disease(NAFLD)is an early mediator for prediction of metabolic syndrome,and whether liver B-ultrasound could be used for its diagnosis,in a study involving 861 obese children(6-16 years old).In this study,it was reported that NAFLD is not only a liver disease,but also an early mediator that reflects metabolic disorder,and that liver B-ultrasound can be a useful tool for metabolic syndrome(MS)screening.The authors reported that NAFLD and MS were present in 68.18%and 25.67%of obese children,respectively.Moreover,they observed that the prevalence of MS in NAFLD children was 37.64%,which was much higher than that in the non-NAFLD group.Criteria analogous to those of the Adult Treatment PanelⅢdefinition for MS were used for children in this study.The reported prevalence data on MS in the young has varied markedly,in large part because of disagreement among the variously proposed definitions of MS.Therefore,in my opinion,a study aiming to assess the association between MS components and NAFLD in obese children has to take into account a simple,easy-to-apply clinical definition proposed by the international diabetes federation for MS.Interpretation of the results of the Fu et al study are limited byanother major caveat:that the diagnosis or exclusion of NAFLD was based on liver enzymes and ultrasound imaging,but was not confirmed by liver biopsy.Indeed,it is known that liver enzymes may be within the reference interval in up to 70%of patients with diagnosed NAFLD and that the full histopathological spectrum of NAFLD may be present in patients with normal liver enzymes,which therefore cannot be reliably used to exclude the presence of NAFLD.