Adiponectin-leptin ratio for the early detection of lean non-alcoholic fatty liver disease independent of insulin resistance.

BACKGROUND: Lean Non-alcoholic Fatty Liver Disease (NAFLD) shares a similar disease burden to those of their overweight counterparts and should be detected early. We hypothesized that the adiponectin-leptin ratio (AL ratio) could be a good marker for early detection of lean NAFLD independent of insulin resistance. MATERIALS AND METHODS: A total of 575 adults without diabetes were enrolled in a community-based study. The subjects were stratified into the lean controls, lean NAFLD, simple overweight/obesity and overweight/obesity NAFLD groups according to body mass index (BMI) and ultrasonographic fatty liver indicators. Serum adiponectin and leptin levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD in relation to the tertiles of serum AL concentration after adjustment. Receiver operating characteristic (ROC) analyses were applied to evaluate the diagnostic performance of the AL ratio for NAFLD. RESULTS: The mean age of the participants was 42.8 ± 11.5 years. Comparing with the lean controls, the odds of having lean NAFLD for the highest versus the lowest tertile of AL ratio was 0.28(95%CI: 0.12-0.69) after adjustment. Putting AL ratio, BMI, triglyceride, AST/ALT ratio to the diagnosis performance of NAFLD, the ROC was 0.85 (95% CI: 0.82-0.88), 0.83 (95% CI 0.78-0.87) and 0.86 (95% CI 081-0.91) for all NAFLD, NAFLD in women and NAFLD in men, respectively. (p < .001). CONCLUSIONS: The study revealed that the AL ratio could be a good biomarker to early distinguish lean NAFLD patients from lean controls independent of insulin resistance. [AQ3]Key messagesThe prevalence of non-alcoholic fatty liver disease (NAFLD) increases globally and is related to liver diseases and metabolic dysfunctions. Lean subset of NAFLD shares a similar disease burden to those of their overweight counterparts and should be detected early.Adiponectin-leptin ratio were associated with the severity of steatosis and was a predictor of obese NAFLD better than each single adipokine. To date, there is no investigation that explores specifically for the relationship between lean NAFLD and AL ratio.Our study found that adiponectin-leptin ratio is a sole independent marker regardless of insulin resistance in lean NAFLD. Having lean NAFLD for the highest versus the lowest tertile of adiponectin-leptin ratio was 0.28(95%CI: 0.12-0.69) after adjustment of age, sex, current smoking, exercise habits, HOMA-IR and AST/ALT. ROC for the NAFLD performance is good for the early detection (0.85; 95% CI: 0.82-0.88). Further rigorous investigation is necessary and should be promptly performed.

Comparison of transient elastography and Model for End-Stage Liver Disease-sodium to Model for End-Stage Liver Disease-sodium alone to predict mortality and liver transplantation.

OBJECTIVES: Model for End-Stage Liver Disease (MELD) alone and with sodium (MELD-Na) have decreasing predictive capacity as trends in liver disease evolve. We sought to combine transient elastography (TE) with MELD-Na to improve its predictive ability. METHODS: This is a retrospective cohort study comparing the use of TE, MELD-Na, and composite MELD-Na-TE to predict liver transplantation and all-cause mortality, with hepatic decompensation as a secondary outcome. Cox proportional hazards regression was used to measure predictive ability and control for confounders. RESULTS: Of the 214 patients, the mean age was 53 years with 35% being female and 76% being Caucasian. Hepatitis C (59%) and nonalcoholic fatty liver disease (22%) were the most frequent liver disease etiologies. On univariable analysis, MELD-Na [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06-1.2, P < 0.001], TE (HR 1.04, 95% CI 1.03-1.06, P < 0.001) and composite MELD-Na-TE (HR 1.13, 95% CI 1.08-1.19, P < 0.001) were associated with death or transplant. On multivariable analysis, MELD-Na was no longer significant (HR 1.08, 95% CI 0.95-1.22, P = 0.27) after adjusting for TE (HR 1.05, 95% CI 1.03-1.07, P < 0.001) while composite MELD-Na-TE remained significant (HR 1.16, 95% CI 1.09-1.24, P < 0.001). Composite MELD-Na-TE predicts mortality or liver transplant with the highest C-statistic of 0.81. Age (HR 1.05, 95% CI 1-1.09, P = 0.04), TE (HR 1.04, 95% CI 1.03-1.06, P < 0.001) and composite MELD-Na-TE (HR 1.11, 95% CI 1.06-1.15, P < 0.001) were significantly associated with hepatic decompensation. CONCLUSION: Composite MELD-Na-TE better predicts liver transplantation, death, and hepatic decompensation compared to MELD/MELD-Na or TE alone.

Metabolically healthy obesity and risk of non-alcoholic fatty liver disease severity independent of visceral fat.

BACKGROUND AND AIM: Obesity and metabolic conditions may be related to non-alcoholic fatty liver disease (NAFLD). The study assesses the risk of NAFLD according to obesity and metabolic health status in a community-based population. METHODS: A total of 1651 subjects were recruited from the community. Individuals were categorized into four groups according to obesity status (defined as a body mass index ≥ 25 kg/m2 ) and metabolically healthy status: metabolically healthy nonobesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy nonobesity (MUHNO), and metabolically unhealthy obesity (MUHO). NAFLD was diagnosed based on a semiquantitative ultrasonography measurement. Visceral fat was assessed through bioelectrical impedance analysis and is shown by tertile (T1, T2, and T3). A proportional odds model was used to assess the cumulative risk of NAFLD. RESULTS: The NAFLD prevalence was 26.7%, 62.8%, 47.0%, and 76.7% in subjects with MHNO, MHO, MUHNO, and MUHO, respectively (P < 0.0001). After adjustment for age, sex, exercise habits, alcohol consumption, cigarette smoking, and visceral fat, the odds ratios for more severe NAFLD were 2.44 (95% confidence interval [CI]: 1.64-3.65), 2.75 (95% CI: 1.91-3.94), and 7.41 (95% CI: 4.94-11.12) in the MHO, MUHNO, and MUHO groups, respectively, compared with the MHNO group. In addition, the odds ratios for more severe NAFLD significantly increased with the increase in visceral fat level (T2 vs T1: 3.83, 95% CI: 2.65-5.53; T3 vs T1: 9.17, 95% CI: 5.33-15.79). CONCLUSION: Both obesity and metabolically unhealthy status were associated with a higher risk of NAFLD independent of visceral fat level.

Fully automated lesion segmentation and visualization in automated whole breast ultrasound (ABUS) images.

BACKGROUND: The number of breast cancer patients has increased each year, and the demand for breast cancer detection has become quite large. There are many common breast cancer diagnostic tools. The latest automated whole breast ultrasound (ABUS) technology can obtain a complete breast tissue structure, which improves breast cancer detection technology. However, due to the large amount of ABUS image data, manual interpretation is time-consuming and labor-intensive. If there are lesions in multiple images, there may be some omissions. In addition, if further volume information or the three-dimensional shape of the lesion is needed for therapy, it is necessary to manually segment each lesion, which is inefficient for diagnosis. Therefore, automatic lesion segmentation for ABUS is an important issue for guiding therapy. METHODS: Due to the amount of speckle noise in an ultrasonic image and the low contrast of the lesion boundary, it is quite difficult to automatically segment the lesion. To address the above challenges, this study proposes an automated lesion segmentation algorithm. The architecture of the proposed algorithm can be divided into four parts: (I) volume of interest selection, (II) preprocessing, (III) segmentation, and (IV) visualization. A volume of interest (VOI) is automatically selected first via a three-dimensional level-set, and then the method uses anisotropic diffusion to address the speckled noise and intensity inhomogeneity correction to eliminate shadowing artifacts before the adaptive distance regularization level set method (DRLSE) conducts segmentation. Finally, the two-dimensional segmented images are reconstructed for visualization in the three-dimensional space. RESULTS: The ground truth is delineated by two radiologists with more than 10 years of experience in breast sonography. In this study, three performance assessments are carried out to evaluate the effectiveness of the proposed algorithm. The first assessment is the similarity measurement. The second assessment is the comparison of the results of the proposed algorithm and the Chan-Vese level set method. The third assessment is the volume estimation of phantom cases. In this study, in the 2D validation of the first assessment, the area Dice similarity coefficients of the real cases named cases A, real cases B and phantoms are 0.84±0.02, 0.86±0.03 and 0.92±0.02, respectively. The overlap fraction (OF) and overlap value (OV) of the real cases A are 0.84±0.06 and 0.78±0.04, real case B are 0.91±0.04 and 0.82±0.05, respectively. The overlap fraction (OF) and overlap value (OV) of the phantoms are 0.95±0.02 and 0.92±0.03, respectively. In the 3D validation, the volume Dice similarity coefficients of the real cases A, real cases B and phantoms are 0.85±0.02, 0.89±0.04 and 0.94±0.02, respectively. The overlap fraction (OF) and overlap value (OV) of the real cases A are 0.82±0.06 and 0.79±0.04, real cases B are 0.92±0.04 and 0.85±0.07, respectively. The overlap fraction (OF) and overlap value (OV) of the phantoms are 0.95±0.01 and 0.93±0.04, respectively. Therefore, the proposed algorithm is highly reliable in most cases. In the second assessment, compared with Chan-Vese level set method, the Dice of the proposed algorithm in real cases A, real cases B and phantoms are 0.84±0.02, 0.86±0.03 and 0.92±0.02, respectively. The Dice of Chan-Vese level set in real cases A, real cases B and phantoms are 0.65±0.23, 0.69±0.14 and 0.76±0.14, respectively. The Dice performance of different methods on segmentation shows a highly significant impact (P<0.01). The results show that the proposed algorithm is more accurate than Chan-Vese level set method. In the third assessment, the Spearman's correlation coefficient between the segmented volumes and the corresponding ground truth volumes is ρ=0.929 (P=0.01). CONCLUSIONS: In summary, the proposed method can batch process ABUS images, segment lesions, calculate their volumes and visualize lesions to facilitate observation by radiologists and physicians.

Impact of a home health care program for disabled patients in Taiwan: A nationwide population-based cohort study.

The aim of this study was to evaluate the impact of home health care (HHC) for disabled patients.We conducted a nationwide population-based retrospective cohort study. A total of 5838 disabled patients with HHC were identified to match by propensity score with 15,829 disabled patients without HHC receiving tube or catheter care (tracheostomy tube, nasogastric tube, urinary catheter, cystostomy tube, nephrostomy tube) or stage 3 or 4 pressure sore care from the Taiwanese National Health Insurance Research Database between 2005 and 2009. After 1:1 matching, 2901 subjects in the HHC group and 2901 subjects in the non-HHC group were selected and analyzed. Generalized estimating equations (GEEs) were used to compare the risk of health outcomes (rate of hospitalization and emergency services use) and the healthcare expenditure between the 2 groups.Compared to those in the non-HHC group, the patients in the HHC group had significantly higher risk for hospitalization (odds ratio [OR] = 18.43, 95% confidence interval [CI]: 15.62-21.75, P < .001) and emergency services use (OR = 3.72, 95% CI: 3.32-4.17, P < .001) 1 year before the index date. However, 1 year after the index date, the risk for hospitalization (OR = 1.6, 95% CI: 1.41-1.83, P < .001) and emergency services use (OR = 1.16, 95% CI: 1.04-1.30, P < .05) attenuated significantly. Regarding the comparison of total healthcare expenditure 1 year before and after the index date, our study showed an insignificant decrease of US$1.5 per person per day and a significant increase of US$5.2 per person per day (P < .001) in the HHC and non-HHC groups, respectively.The HHC for disabled patients has a potential role to reduce hospitalization and emergency services use. Besides, the improvement of healthcare quality through HHC was not accompanied by increased healthcare expenditure. The clinical impact of HHC emphasizes the importance for public health officials to promote HHC model to meet the needs of disabled patients.

Hepatic Steatosis Assessment with Ultrasound Small-Window Entropy Imaging.

Nonalcoholic fatty liver disease is a type of hepatic steatosis that is not only associated with critical metabolic risk factors but can also result in advanced liver diseases. Ultrasound parametric imaging, which is based on statistical models, assesses fatty liver changes, using quantitative visualization of hepatic-steatosis-caused variations in the statistical properties of backscattered signals. One constraint with using statistical models in ultrasound imaging is that ultrasound data must conform to the distribution employed. Small-window entropy imaging was recently proposed as a non-model-based parametric imaging technique with physical meanings of backscattered statistics. In this study, we explored the feasibility of using small-window entropy imaging in the assessment of fatty liver disease and evaluated its performance through comparisons with parametric imaging based on the Nakagami distribution model (currently the most frequently used statistical model). Liver donors (n = 53) and patients (n = 142) were recruited to evaluate hepatic fat fractions (HFFs), using magnetic resonance spectroscopy and to evaluate the stages of fatty liver disease (normal, mild, moderate and severe), using liver biopsy with histopathology. Livers were scanned using a 3-MHz ultrasound to construct B-mode, small-window entropy and Nakagami images to correlate with HFF analyses and fatty liver stages. The diagnostic values of the imaging methods were evaluated using receiver operating characteristic curves. The results demonstrated that the entropy value obtained using small-window entropy imaging correlated well with log10(HFF), with a correlation coefficient r = 0.74, which was higher than those obtained for the B-scan and Nakagami images. Moreover, small-window entropy imaging also resulted in the highest area under the receiver operating characteristic curve (0.80 for stages equal to or more severe than mild; 0.90 for equal to or more severe than moderate; 0.89 for severe), which indicated that non-model-based entropy imaging-using the small-window technique-performs more favorably than other techniques in fatty liver assessment.

High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance.

OBJECTIVE: Selenium is an essential micronutrient for human health. Although many observational and interventional studies have examined the associations between selenium and diabetes mellitus, the findings were inconclusive. This study aimed to investigate the relationship between serum selenium levels and prevalence of diabetes, and correlated the relationship to insulin resistance and central obesity. RESEARCH DESIGN AND METHODS: This was a hospital-based case-control study of 847 adults aged more than 40 years (diabetes: non-diabetes =1:2) in Northern Taiwan. Serum selenium was measured by an inductively coupled plasma-mass spectrometer. The association between serum selenium and diabetes was examined using multivariate logistic regression analyses. RESULTS: After adjusting for age, gender, current smoking, current drinking, and physical activity, the ORs (95% CI, p value) of having diabetes in the second (Q2), third (Q3), and fourth (Q4) selenium quartile groups were 1.24 (95% CI 0.78 to 1.98, p>0.05), 1.90 (95% CI 1.22 to 2.97, p<0.05), and 5.11 (95% CI 3.27 to 8.00, p<0.001), respectively, compared with the first (Q1) quartile group. Further adjustments for waist circumference and homeostatic model assessment-insulin resistance (HOMA-IR) largely removed the association of serum selenium levels with diabetes but not in the highest quartile (compared with Q1, Q3: 1.57, 95% CI 0.91 to 2.70, Q4: 3.79, 95% CI 2.17 to 6.32). CONCLUSIONS: We found that serum selenium levels were positively associated with prevalence of diabetes. This is the first human study to link insulin resistance and central obesity to the association between selenium and diabetes. Furthermore, the association between selenium and diabetes was independent of insulin resistance and central obesity at high serum selenium levels. The mechanism behind warrants further confirmation.

Association of Non-alcoholic Fatty Liver Disease with Metabolic Syndrome Independently of Central Obesity and Insulin Resistance.

Non-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease that may lead to liver cirrhosis and hepatocellular carcinoma. We aimed to determine the association between the prevalence of metabolic syndrome (MetS) and NAFLD severity using semi-quantitative ultrasonography (US). A total of 614 participants were recruited from the community. NAFLD was evaluated according to the ultrasonographic Fatty Liver Indicator (US-FLI), which is a semi-quantitative liver ultrasound score. Insulin resistance was estimated with the homeostasis model assessment index for insulin resistance (HOMA-IR). NAFLD and MetS were found in 53.7 and 17.3% of the participants, respectively. Linear relationships were found between the severity of NAFLD and waist circumference, fasting glucose, HOMA-IR, triglycerides, HDL-C and blood pressure. After adjusting for confounding factors, i.e., body mass index and HOMA-IR, the odds ratios for MetS were 3.64 (95% confidence interval (CI): 1.5-8.83) for those with mild NAFLD and 9.4 (95% CI: 3.54-24.98) for those with moderate-to-severe NAFLD compared to those without NAFLD. The combination of the HOMA-IR and US-FLI scores better differentiated MetS than the HOMA-IR alone. In addition to obesity, the severity of NAFLD and the HOMA-IR both play important roles in MetS. Whether NAFLD is a component of MetS warrants further research.

The Relationship of Diabetes and Smoking Status to Hepatocellular Carcinoma Mortality.

The relationship of diabetes and smoking status to hepatocellular carcinoma (HCC) mortality is not clear. We aimed to investigate the association of smoking cessation relative to diabetes status with subsequent deaths from HCC.We followed up 51,164 participants (aged 44-94 years) without chronic hepatitis B or C from 1 January 1998 to 31 December 2008 enrolled from nationwide health screening units in a prospective cohort study. The primary outcomes were deaths from HCC.During the study period, there were 253 deaths from HCC. History of diabetes was associated with deaths from HCC for both total participants (adjusted hazard ratio [HR], 2.97; 95% confidence interval [CI], 2.08-4.23) and ever smokers with current or past smoking habits (HR, 1.92; 95% CI, 1.10-3.34). Both never smokers (HR, 0.46; 95% CI, 0.32-0.65) and quitters (HR, 0.62; 95% CI, 0.39-0.97) had a lower adjusted risk of HCC deaths compared with current smokers. Among all ever smokers with current or past smoking habits, as compared with diabetic smokers, only quitters without diabetes had a lower adjusted risk of HCC deaths (HR, 0.37; 95% CI, 0.18-0.78). However, quitters with diabetes were observed to have a similar risk of deaths from HCC when compared with smokers with diabetes. Regarding the interaction between diabetes and smoking status on adjusted HCC-related deaths, with the exception of quitters without history of diabetes, all groups had significantly higher HRs than nondiabetic never smokers. There was also a significant multiplicative interaction between diabetes and smoking status on risk of dying from HCC (P = 0.033). We suggest clinicians should promote diabetes prevention and never smoking to associate with reduced subsequent HCC mortality even in adults without chronic viral hepatitis.