Nonalcoholic Fatty Liver Disease Associated With The Quantitative Diagnosis Of Metabolic Syndrome And Serological Indicators Research

BACKGOUND&AIMSAccurate measures of liver fat content are essential for investigating the role of hepatic steatosis in the pathophysiology of multiple metabolic disorder. We aimed to establish and validate a simple and propagable method for quantitative assessment of liver fat content based on the combination of standardized ultrasound hepatic/renal ratio and hepatic attenuation rate, using [1H]-MRS as gold standard.METHODSTotally127participants were recruited from the physical examination centre of Shanghai Zhongshan Hospital. All subjects were examined with both ultrasonography (US) and [1H]-MRS at the same day. Ultrasound hepatic/renal echo-intensity ratio (H/R) and ultrasound hepatic echo-intensity attenuation rate (HA) were obtained from ordinary ultrasound images using computer program. Both parameters were standardized using a tissue-mimicking phantom before analysis.RESULTS1.The study population consisted of71men and56women with an age range of16-75years old. Liver fat content determined by [1H]-MRS ranged from3.0to70.9%(mean20.2%). With the increase of hepatic fat content, US hepatic/renal ratio and US hepatic attenuation rate also increased significantly (P<0.001).2. Both US hepatic/renal ratio and US hepatic attenuation rate were highly positively associated with the hepatic fat content by [1H]-MRS (r=0.884, P<0.001and r=0.711, P<0.001,respectively).3. Multivariate linear regression analysis showed that among all common anthropometric and US quantitative parameters, the greatest contribution to the prediction of liver fat content came from the US H/R ratio, and it could be used independently to calculate liver fat content (adjusted explained variance78.0%, P<0.001). The addition of US hepatic attenuation rate to the US hepatic/renal ratio further improved the explained variance to79.8%. The algorithm derived from the second predictive model was as follows:Liver fat content(%)=62.592X US hepatic/renal ratio+168.076X US hepatic attenuation rate-27.863.4. Patients with liver fat content measured by [1H]-MRS of at least5.56%were diagnosed as hepatic steatosis. Receiver operating characteristic curve ananlysis showed that the optimal cutoff value for ultrasound-estimated liver fat content to diagnose hepatic steatosis was9.15%. The sensitivity and specificity for quantitative US to diagnose hepatic steatosis were95.1%and100%, respectively, better than the qualitative US, whose sensitivity and specificity were82.5and83.3%, respectively. In subjects with liver fat content less than15%, the quantitative US also yielded much higher sensitivity (82.6%) and specificity (100%) than traditional US (sensitivity=47.8%, specificity=83.3%)5. Difference of estimated liver fat contents among different ultrasound machines and operators was reasonably well.91.3%and69.2%patients would have the difference of calculated liver fat contents from different operators or different US machines within the range of±5%liver fat content.6. After adjustment for age, sex and BMI, US hepatic fat content is significantly associated with waist circumference, ALT, AST, triglycerides, HDL-c, APO-E and blood glucose(P<0.05).CONCLUSIONSUltrasound quantitative method is a simple, low-cost, and sensitive analytic tool, and could accurately reflect hepatic fat content in clinical practice. It is especially suitable for large-scale quantitative study on hepatic steatosis, and provide an easy and effective parameter for early diagnosis of mild hepatic steatosis and evaluation of NAFLD treatment efficacy。 BACKGOUND&AIMSNon-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome (MS). Mounting evidence showed that patients with MS were usually accompanied with elevation of liver enzymes. However, the current’normal’limits for liver enzymes often fail to identify patients with metabolic syndrome and its associated NAFLD. The aim of the study was to explore the association of liver enzyme elevation with MS and NAFLD.METHODS:In the present study,1503participants, aged between18and95years, were recruited from the physical examination centre of Shanghai Zhongshan Hospital and Shanghai Changfeng Community Health Centre. A standard interview, anthropometric and laboratory measurement were performed for each participant. Hepatic fat content was determined in237(125men and112women) of1503participants using [1H]-magnetic resonance spectroscopy(MRS).RESULTS:1. Of634men and869women,222(35.0%) and215(24.7%) had MS, respectively. In men, the median levels (in IU/L) of ALT, AST and GGT were22(15-37),22(18-27) and30(21-45), respectively. In women, the median levels (in IU/L) of ALT, AST and GGT were16(12-25),20(17-25) and22(16-32), respectively.2. Spearman partial correlation analysis showed that ALT and GGT were significantly associated with most components of MS in both men and women after adjustment for age, BMI, smoking status and alcohol intake (P<0.05).3. Logistic regression analyses for the presence of MS in relation to the ALT, AST and GGT quintiles revealed that the ORs for MS increased progressively with increasing liver enzyme levels. After adjustment for age, BMI, smoking status and alcohol intake, the ORs for MS significantly increased in both men and women from the third quintile of ALT and GGT, respectively (P<0.001). Female participants with AST levels in the top quintile had the higher prevalence of MS (P=0.001), but increased AST level did not increase the risk of MS in men.4. Cut-off values were calculated for ALT, AST and GGT in association with increase in the prevalence of MS using ROC curve analysis. For men, the cut-off values for a diagnosis of MS were26,25and29IU/L for ALT, AST and GGT, respectively; in women, these values were20,23and21IU/L, respectively.5. Compared with the traditional’normal’limits for liver enzymes, the new liver enzyme cut-off values identified approximately30%more patients with MS, with a specificity of about70%.6. Participants with hepatic fat content not less than5.56%by [1H]-MRS were diagnosed as NAFLD patients. The sensitivity of the new liver enzyme cut-off values for the diagnosis of NAFLD was significantly greater than that of the traditional ’normal’liver enzyme limits, with acceptably high specificity (78.0-90.2%) and positive predictive value (93.7-96.9%).CONCLUSIONS:Slight elevation in liver enzymes, even within the current ’normal’ range, could reflect liver fat deposition and a dysmetabolic state in the absence of known liver disease. The current ’normal’ liver enzyme limits are not appropriate for the identification of patients with metabolic disorders or potential hepatic steatosis. A lowering of normal liver enzyme limits is advisable for early detection of MS and NAFLD in ’healthy’ people who currently have elevated ALT or GGT levels within ’normal’ limits. BACKGROUND&AIMSElevation of serum uric acid levels could independently predict the risks for metabolic syndrome(MS) and non-alcoholic fatty liver disease (NAFLD). However, Uric acid (UA) has a dual role both as a pro-and anti-oxidant, and its function is dependent on the difference of physiochemical circumstances. Thus, there might be a different meaning of hyperuricemia between subjects with diet and metabolism-related UA over-production and those with UA retention due to impaired renal excretion function. The aim of the study was to investigate the assocation of serum uric acid level with MS and NAFLD in a middle-aged and elderly population with normal and impaired renal excretion function, rescpectively.METHODSA cross-sectional study was performed in a community population comprising1141subjects with a median age of62years, enrolled consecutively to the Shanghai Changfeng study from May2010to May2011. A standard interview, anthropometric and laboratory measurement were performed for each participant. Hepatic fat content was determined by a newly-established ultrasound quantitative method.RESULTS1. The study included1141subjects (426men) with a median age of62years.364subjects (31.9%) were diagnosed metabolic syndrome and477(41.8%) fulfilled the diagnosis of NAFLD based on hepatic fat content by quantitative ultrasonography. Hyperuricemia was identified in195participants (17.1%), with a significant higher prevelence of MS (50.3%) and NAFLD (58.5%). There were687subjects (60.2%) with estimated glomerular filtration rate (eGFR)≥90ml/min/1.73m2,423(37.1%) with eGFR60-90ml/min/1.73m2, and31(2.7%) with eGFR<60ml/min/1.73m2.2. Serum UA concentration increased significantly with the increase of number of metabolic syndrome components (P<０.001).3. The univariate correlation analysis showed that ultrasound hepatic fat content was significantly associated with serum uric acid in all participants (r=0.193,P<0.001), and in the subgroup of subjects with GFR≥90ml/min/1.73m2, univariate correlation analysis showed a even stronger correlation (r=0.255, P<０.001), which was weakened but still significant in subjects with eGFR lower than90ml/min/1.73m2(r=0,144, P=0.001).4. All subjects are divided into four subgroups according to sex-specific cutoffs for quartiles of UA. Multivariate logistic regression analysis showed that the ORs for MS increased significantly from Quartile3, after adjustment for age, smoking, drinking, BMI, liver enzymes, APO-A, APO-B and eGFR in subjects with eGFR≥90ml/min/1.73m2, However, no independent association was found between serum uric acid quartiles and MS in subjects with eGFR<90ml/min/１.73m2.5. Multivariate linear stepwise regression analysis showed that UA had an independent quantitative association with hepatic fat content in the subgroup of687subjects with eGFR≥90ml/min/1.73m2(P=0.003). Multivariate logistic regression analysis involving all metabolism-related parameters also revealed that UA was independently associated with the presence of NAFLD in subjects with normal renal function. But there was no independent association between UA and hepatic fat content or NAFLD in subjects with impaired renal excretion function (eGFR<90ml/min/1.73m2).CONCLUSIONSSerum uric acid level was independently associated with the occurrence of MS and NAFLD in a middle-aged and elderly Chinese population with normal renal excretion function, but in patients with renal insufficiency, the elevated serum UA, largely due to the renal retention, showed no independent correlation with MS and NAFLD. Therefore, hyperuricemia independently predicts the risks of metabolic disorders in people with normal renal function, but in patients with renal excretion insufficiency, the meaning of hyperuricemia should be explained with caution.