Wanyuan He

Standardized Ultrasound Hepatic/Renal Ratio and Hepatic Attenuation Rate to Quantify Liver Fat Content: An Improvement Method

Accurate measures of liver fat content are essential for investigating the role of hepatic steatosis in the pathophysiology of multiple metabolic disorders. No traditional imaging methods can accurately quantify liver fat content. [1H]‐magnetic resonance spectroscopy (MRS) is restricted in large‐scale studies because of the practical and technological issues. Previous attempts on computer‐aided ultrasound quantification of liver fat content varied in method, and the ultrasound quantitative parameters measured from different ultrasound machines were hardly comparable. 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 quantitative parameters, using [1H]‐MRS as gold standard. Totally 127 participants were examined with both ultrasonography (US) and [1H]‐MRS. 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. Standardized ultrasound H/R and HA were positively correlated with the liver fat content by [1H]‐MRS (r = 0.884, P < 0.001 and r = 0.711, P < 0.001, respectively). Linear regression analysis showed ultrasound H/R could modestly predict the amount of liver fat (adjusted explained variance 78.0%, P < 0.001). The addition of ultrasound HA slightly improved the adjusted explained variance to 79.8%. Difference of estimated liver fat contents between different ultrasound machines and operators was reasonably well. Thus, computer‐aided US is a valid method to estimate liver fat content and can be applied extensively after standardization of ultrasound quantitative parameters.

Liver fat content is associated with increased carotid atherosclerosis in a Chinese middle-aged and elderly population: the Shanghai Changfeng study.

BACKGROUND Nonalcoholic fatty liver disease is closely associated with metabolic syndrome and cardiovascular disease (CVD). We investigated whether the liver fat content (LFC) is independently associated with carotid artery intima-media thickness (CIMT) and evaluated the contribution of the LFC to the increased CIMT. METHODS We conducted a community-based study among 1809 participants (682 males and 1127 females) from the Changfeng Study who were at least 45 years old. A standard interview, anthropometrics and laboratory parameters were performed for each participant. The CIMT was determined by ultrasonography. A large CIMT value was defined as 75th percentile of the maximum CIMT. A standardised ultrasonographic hepatic-renal ratio was used to assess the LFC. RESULTS The median LFC value was 6% (interquartile range, 3-14%), and 34% of the subjects had hepatic steatosis based on the criteria for diagnosis of steatosis by quantitative ultrasound. The maximum CIMT, average CIMT and plaque score were strongly associated with the LFC (β = 0.319, 0.324 and 1.361, respectively; all P < 0.05) after adjustment for age, gender, smoking history, low-density lipoprotein cholesterol and metabolic syndrome. The multiple logistic regression analysis showed that a 1 SD increase in the LFC, the OR for having a large CIMT was 1.350 (95% CI 1.180-1.545; P < 0.001) after adjustment for all potential confounders. CONCLUSIONS These results suggest that the LFC is independently associated with carotid atherosclerosis in the Chinese population, and that the risk of atherosclerosis is proportional to the degree of hepatic steatosis.

Quantification of Carotid Plaque Neovascularization Using Contrast-Enhanced Ultrasound With Histopathologic Validation

We sought to evaluate contrast-enhanced ultrasound (CEUS) imaging for the quantification of carotid plaque neovascularization. Seventeen patients underwent carotid endarterectomy after standard ultrasound and CEUS. Semiquantitative and quantitative analyses of contrast enhancement within the plaque were performed using a visual interpretation scale and quantitative analysis software, respectively. Enhancement intensity (dB) was measured at the plaque (EI(plaque)). Each specimen was stained with CD34 and CD68 to assess for microvessels and macrophages, respectively. Semiquantitative CEUS analyses were correlated with neovascularization at histology (r = 0.70, p = 0.002). Quantitative analysis was also correlated with neovascularization at histology (EI(plaque)r = 0.81, p < 0.001). EI(plaque) (r = 0.64, p = 0.01) was correlated with the degree of enhancement as assessed visually. Semiquantitative and quantitative analyses were not correlated with macrophage infiltration at the plaque. Contrast enhancement in the carotid plaque was correlated with neovascularity at the histopathologic exam. Furthermore, semiquantitative and quantitative measurements were highly correlated with each other, suggesting that either can be used to detect intraplaque neovascularization.

A novel simple noninvasive index to predict renal transplant acute rejection by contrast-enhanced ultrasonography.

Purpose This study aimed to evaluate the application of quantitative contrast-enhanced ultrasonography (CEUS) in the assessment of renal allograft dysfunction and to establish a new noninvasive index to predict acute rejection (AR). Methods Fifty-seven renal transplant recipients were enrolled in this prospective study. Before renal allograft biopsy, CEUS examinations were performed. The biopsy results proved 23 cases of AR (AR group), 10 cases of acute tubular necrosis (ATN group), and 24 with normal evolution (stable group). Contrast-enhanced ultrasonography parameters including rising time (RT), time to peak (TTP), and the delta-time among regions of interest (&Dgr;RT and &Dgr;TTP) were analyzed. Results In the AR group, RT and TTP of interlobar artery and medulla (RTi, RTm, TTPi, and TTPm) as well as &Dgr;RT and &Dgr;TTP between medulla and cortex (&Dgr;RTm-c and &Dgr;TTPm-c) were significantly higher compared with those in the stable group. RTm and TTPm as well as &Dgr;RTm-c and &Dgr;TTPm-c were remarkably higher compared with those in the ATN group. &Dgr;RTm-c and estimated glomerular filtration rate (eGFR) were identified as independent predictors by multivariate analysis (P = 0.008 and P = 0.024). On the basis of the multivariate analysis results and area under the receiver operating characteristic curves of individual markers, we constructed a new simple index, P = −0.587 + 0.286 × &Dgr;RTm-c − 0.028 × eGFR; new index = eP/(1 + eP), to discriminate AR, which had better area under the receiver operating characteristic curves than eGFR or individual CEUS parameters. Conclusion Contrast-enhanced ultrasonography parameters are reliable markers for differentiating the perfusion status of transplanted kidneys. Furthermore, the new simple index can easily predict AR with a high degree of accuracy.

I148M variant of PNPLA3 increases the susceptibility to non-alcoholic fatty liver disease caused by obesity and metabolic disorders.

The patatin‐like phospholipase 3 (PNPLA3) rs738409 gene polymorphism is an important genetic determinant of non‐alcoholic fatty liver disease (NAFLD). However, the associations between liver fat and metabolic traits in rs738409 G allele carriers and the allelic influence on this association have not been fully studied.

Liver Fat Content, Evaluated through Semi-Quantitative Ultrasound Measurement, Is Associated with Impaired Glucose Profiles: A Community-Based Study in Chinese

Nonalcoholic fatty liver disease (NAFLD) is closely associated with type 2 diabetes mellitus. We investigated whether the deposition of fat in the liver is associated with glycemic abnormalities and evaluated the contribution of the liver fat content (LFC) to the impaired glucose regulation. We conducted a community-based study among 2836 residents (1018 males and 1818 females) without prior known diabetes mellitus from the Changfeng Study who were at least 45 years old. A standard interview, anthropometrics and laboratory parameters were performed for each participant. The standardised ultrasound hepatic-renal echo-intensity and hepatic echo-intensity attenuation rate were used to assess the LFC. The cohort was stratified according to the quintiles for LFC. Two-hour glucose and fasting blood glucose increased across the LFC quintiles after adjustment for age and gender. LFC increased continuously among glucose categories after adjustment for age and gender (NGT: 7.7±0.3%, IFG: 10.0±0.8%, IGT: 11.8±0.5%, IFG+IGT: 11.7±0.9%, new- DM: 12.4±0.6%, P<0.001). By logistic regression analysis, 1% LFC increment independently predicted prediabetes and diabetes (OR 1.032, 1.019–1.045, P<0.001; 1.021, 1.005–1.037, P = 0.012, respectively) after adjustment for all potential confounders. Furthermore, participants with LFC higher than 10% had higher odds ratios of impaired glucose regulation as compared with those with LFC below 10% in fully adjusted logistic models. These results suggest that the LFC is strongly associated with impaired glucose regulation in the Chinese population, and that an even slightly elevated LFC is associated with increased glucose dysregulation.

Renal function‐dependent association of serum uric acid with metabolic syndrome and hepatic fat content in a middle‐aged and elderly Chinese population

The effect of uric acid (UA) on the pathogenesis of metabolic disorders is highly dependent on its physicochemical properties, and hyperuricaemia associated with different conditions may have different clinical meanings. The aim of the present study was to investigate the association of serum UA levels with metabolic syndrome and non‐alcoholic fatty liver disease (NAFLD) in a middle‐aged and elderly population with normal and impaired renal function. The cross‐sectional study was performed on 1141 participants (426 men, 715 women; mean age 62 years) enrolled from the Shanghai Changfeng community. Each participant underwent a standard interview, with anthropometric and laboratory measurements. Hepatic fat content (HFC) was determined by a newly established quantitative ultrasound method. Univariate correlation analysis showed that serum UA was associated with all components of metabolic syndrome and HFC (r = 0.193, P < 0.001), especially in participants with a normal estimated glomerular filtration rate (eGFR; r = 0.255, P < 0.001). Logistic regression analysis demonstrated an independent association of serum UA with metabolic syndrome and NAFLD in participants with normal renal function, but not in those with eGFR < 90 mL/min per 1.73 m2. Furthermore, multivariate linear analysis showed that UA levels were independently associated with HFC (P = 0.003), but only in participants with normal eGFR. Elevated serum UA is independently associated with metabolic syndrome and NAFLD in patients with normal renal excretory function. However, in those with renal insufficiency, hyperuricaemia has no association with metabolic disorders.

Mean Platelet Volume in Relation to Carotid Atherosclerosis in Normotensive, Euglycemic, and Normolipidemic Chinese Middle-Aged and Elderly Adults

We investigated whether mean platelet volume (MPV) is independently associated with the carotid intima–media thickness (cIMT) in normotensive, euglycemic, and normolipidemic middle-aged and elderly adults. A total of 256 males and 398 females were enrolled from the Changfeng Study. Compared to male patients with MPV in the first quintile, male patients with MPV in the fifth quintile had greater cIMTs and higher prevalence of carotid plaque. After adjusting for conventional cardiovascular disease risk factors, male participants with MPV in the fifth quintile had a 1.669-fold increased risk of carotid plaques relative to those in the lowest quintiles. In female patients, the cIMTs and prevalence of carotid plaque were not significantly different among the groups. These results suggest that MPV is independently associated with carotid atherosclerosis in normotensive, euglycemic, and normolipidemic males. The MPV could be an easily measured marker of atherosclerosis for males.

Low-grade albuminuria is associated with carotid atherosclerosis in normotensive and euglycemic Chinese middle-aged and elderly adults: the Shanghai Changfeng Study.

BACKGROUND Microalbuminuria is associated with cardiovascular disease (CVD). We investigated whether low-grade albuminuria (LGA) is independently associated with the carotid intima-media thickness (CIMT) and carotid plaques in normotensive and euglycemic Chinese middle-aged and elderly adults. METHODS A total of 1341 normotensive and euglycemic participants (489 males and 852 females; mean age, 57.7 years) with normal urinary albumin-to-creatinine ratios (UACRs) (<30 μg/mg) were enrolled from the Changfeng Study. A standard interview, anthropometric measurements and laboratory analyzes were performed for each participant. Bilateral CIMTs were measured using ultrasonography, and the presence of carotid plaques was assessed. The urinary albumin excretion rate was measured using an early morning urine sample to determine the UACR. RESULTS The median UACRs were 4.2 (interquartile range, 2.9-6.0) μg/mg and 5.6 (interquartile range, 4.0-8.2) μg/mg for male and female subjects, respectively. Compared with subjects with UACRs in the first and second tertiles, subjects of both genders with UACRs in the third tertile had greater CIMTs. After adjusting for conventional CVD risk factors and the glomerular filtration rate (GFR), male and female participants with UACRs in the third tertile for each gender had a 1.696-fold and 1.911-fold increased risk, respectively, of carotid plaques relative to those in the lowest tertiles. The logUACR was positively associated with the CIMT (β = 0.068 in males, P = 0.001; and β = 0.034 in females, P = 0.012) after adjusting for conventional CVD risk factors and the GFR. The multiple logistic regression analysis showed that a 1-unit increase in the logUACR corresponded to an odds ratio (OR) of having a carotid plaque that was 1.875 (95% confidence interval (CI) 1.103-3.538; P = 0.022) and 2.389 (95% CI 1.244-4.391; P = 0.01) for male and female subjects, respectively, after adjusting for all potential confounders. CONCLUSIONS These results suggest that the UACR is independently associated with carotid atherosclerosis in normotensive and euglycemic Chinese individuals and that even when well below the current microalbuminuria threshold, LGA contributes to the risk of atherosclerosis.

Assessment of liver fat content using quantitative ultrasonography to evaluate risks for metabolic diseases.

The ultrasound quantitative method for liver fat content (LFC) is a recent established method for non‐invasive assessment of liver steatosis. Its use in clinical practice is further explored by investigating the quantitative relationships between LFC measured by quantitative ultrasonography and metabolic diseases in a middle‐aged and elderly Chinese population.