Liver Attenuation Research Articles

Relations of liver fat with prevalent and incident chronic kidney disease in the Framingham Heart Study: A secondary analysis.

Prior studies demonstrated an association between non-alcoholic fatty liver disease and chronic kidney disease (CKD), though data are conflicting. We examined the association between liver fat and prevalent and incident CKD in the Framingham Heart Study (FHS). We included FHS participants who underwent computed tomography (CT) from 2002 to 2005 (n=1315). After excluding heavy alcohol use (n=211) and missing covariates (n=117), the final sample included 987 participants. For the incident CKD analysis, we excluded 73 participants with prevalent CKD. Liver fat was measured by the average liver attenuation on CT. Estimated glomerular filtration rate (eGFR) was obtained using the CKD Epidemiology Collaboration Creatinine-Cystatin C equation, and CKD was defined as eGFR<60ml/min/1.73m2 . Microalbuminuria was defined by sex-specific urinary albumin-creatinine ratio cut-offs. Multivariable-adjusted regression models were performed to determine the association between liver fat and CKD. The prevalence of hepatic steatosis and CKD were 19% and 14% respectively (55.9% women, mean age 60±9years). After adjusting for covariates, we observed no significant associations between liver fat and CKD, microalbuminuria or eGFR in cross-sectional analyses. We observed positive associations between liver fat, incident microalbuminuria and reduced eGFR in age- and sex-adjusted models; these relationships were not significant in multivariable-adjusted models. In this community-based cohort study, we did not observe significant associations between liver fat and prevalent or incident CKD with a median follow-up time of 12.5years. The association between NAFLD and CKD may be accounted for by shared risk factors; confirmatory studies are needed.

Feasibility of non-enhanced CT for assessing longitudinal changes in hepatic steatosis.

To evaluate the feasibility of computed tomography (CT) in the assessment of the change in hepatic steatosis (HS) in longitudinal follow-up by employing pathological HS as the reference standard.We retrospectively evaluated 38 living liver donor candidates (27 men and 11 women; mean age, 29.5 years) who underwent liver biopsy twice and had liver CT scans within 1 week of each biopsy. Four readers independently calculated CTL-S index by subtracting spleen attenuation from liver attenuation on non-enhanced CT images. The changes in pathological HS (ΔHS) and CTL-S (ΔCTL-S) between the 1st and 2nd examinations were assessed. The correlation between ΔHS and ΔCTL-S was assessed using the linear regression analysis. Inter-observer measurement error for ΔCTL-S among the 4 readers was assessed using the repeatability coefficient.ΔCTL-S showed a significant correlation with ΔHS in all readers (r = 0.571–0.65, P < .001). The inter-observer measurement error for ΔCTL-S was ±8.9. The ΔCTL-S values beyond the measurement error were associated with a consistent change in HS in 83.3% (13/15) to 100% (15/15), with sensitivities of 47.8 to 79.9% and specificities of 86.7 to 100% for detecting an absolute change of ≥10% in HS among the 4 readers. However, ΔCTL-S values within the measurement error were associated with a consistent change in HS in 43.5% (8/19) to 61.5% (16/26).The change in CTL-S roughly reflects the change in HS during longitudinal follow-up. A small change in CTL-S should not be considered meaningful, while a larger change in CTL-S beyond the measurement error strongly indicates a true change in HS.

Attenuation of high-fat diet-induced fatty liver through PPARα activation by stevioside

Abstract This study aimed to investigate the effect of stevioside on fatty liver. Rats with hyperlipidemic fatty liver were treated with 75–150 mg/kg stevioside for 6 weeks. After oral administration of stevioside, the levels of serum and hepatic lipids and degree of hepatic steatosis were decreased. Stevioside treatment increased the expressions of hepatic peroxisome proliferator-activated receptor (PPAR)α and carnitine palmitoyltransferase-1A proteins and decreased the expressions of hepatic sterol regulatory element-binding protein-1c, fatty acid synthase and diacylglycerol acyltransferase proteins. Following treatment of oleic acid-stimulated hepatocytes with 100–400 μM stevioside, the intracellular lipids were also decreased. In the hepatocytes of PPARα gene silence, the lipid-lowering effect of stevioside was abolished, and its regulatory effects on PPARα-mediated target proteins were reversed. These findings demonstrated that stevioside was effective in treating fatty liver, and its mechanisms were associated with the increment of hepatic PPARα expression and subsequent modulation of its target gene expressions.

Insulin Resistance Exacerbates Genetic Predisposition to Nonalcoholic Fatty Liver Disease in Individuals Without Diabetes.

The accumulation of excess fat in the liver (hepatic steatosis) in the absence of heavy alcohol consumption causes nonalcoholic fatty liver disease (NAFLD), which has become a global epidemic. Identifying metabolic risk factors that interact with the genetic risk of NAFLD is important for reducing disease burden. We tested whether serum glucose, insulin, insulin resistance, triglyceride (TG), low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, body mass index (BMI), and waist‐to‐hip ratio adjusted for BMI interact with genetic variants in or near the patatin‐like phospholipase domain containing 3 (PNPLA3) gene, the glucokinase regulatory protein (GCKR) gene, the neurocan/transmembrane 6 superfamily member 2 (NCAN/TM6SF2) gene, and the lysophospholipase‐like 1 (LYPLAL1) gene to exacerbate hepatic steatosis, estimated by liver attenuation. We performed association analyses in 10 population‐based cohorts separately and then meta‐analyzed results in up to 14,751 individuals (11,870 of European ancestry and 2,881 of African ancestry). We found that PNPLA3‐rs738409 significantly interacted with insulin, insulin resistance, BMI, glucose, and TG to increase hepatic steatosis in nondiabetic individuals carrying the G allele. Additionally, GCKR‐rs780094 significantly interacted with insulin, insulin resistance, and TG. Conditional analyses using the two largest European ancestry cohorts in the study showed that insulin levels accounted for most of the interaction of PNPLA3‐rs738409 with BMI, glucose, and TG in nondiabetic individuals. Insulin, PNPLA3‐rs738409, and their interaction accounted for at least 8% of the variance in hepatic steatosis in these two cohorts. Conclusion: Insulin resistance, either directly or through the resultant elevated insulin levels, more than other metabolic traits, appears to amplify the PNPLA3‐rs738409‐G genetic risk for hepatic steatosis. Improving insulin resistance in nondiabetic individuals carrying PNPLA3‐rs738409‐G may preferentially decrease hepatic steatosis.

SAT-LB017 Anthropometric Imaging and Biological Markers of Adiposity and Aldosterone among African Americans: The Jackson Heart Study

Serum aldosterone increases risk of cardiometabolic disease. Pre-clinical studies suggest adipocytes produce aldosterone, independent of adrenal synthesis. Human studies have linked obesity and aldosterone, but mixed results exist between body fat distribution and aldosterone (1, 2). Body fat distribution varies by race with African Americans (AAs) having more subcutaneous adipose tissue (SAT) than visceral adipose tissue (VAT) compared to whites adjusted for total body fat (3). Thus, we examined the association of anthropometric, imaging and biological markers of adiposity with aldosterone among AAs. We used data from Exams 1 (2000-2004) and 2 (2005-2008) of the Jackson Heart Study, a large prospective study of AA adults. Descriptive statistics were obtained for demographic and clinical characteristics including mean and standard deviation (SD) for the continuous variables and frequencies for the categorical variables. Aldosterone, adiponectin, and leptin were log-transformed due to skewed distribution. Multivariable linear regression models were used to assess the associations of adiposity markers at Exam 1 (body mass index [(BMI]), waist circumference [(WC)], waist-to-height ratio [(WHR)], leptin, adiponectin) and at Exam 2 (VAT, SAT and liver attenuation [liver fat]) with aldosterone levels assessed at Exam 1. Models were adjusted for age, sex, education, occupation, systolic blood pressure, smoking and physical activity. Among 4994 adults (mean age 55.1 years ± 12.8, 63% female), the average BMI was 31.8 ± 7.3 kg/m2. After full adjustment, a 1 unit increase in WC (cm) and BMI (kg/m2) were associated with a 0.5% and 0.8% higher aldosterone, respectively (both p<0.01). A 1% increase in adiponectin was associated with a 0.15% lower aldosterone (p<0.01); whereas, a 1% increase in leptin was associated with a 0.15% higher aldosterone (p<0.01). Compared to the highest BMI category (≥30 kg/m2), the 25-30 and <25 categories showed a 7.2% and 19% lower aldosterone, respectively (both p<0.01). A 1% increase in VAT was associated with a 0.18% increase in aldosterone and a 1% increase in liver attenuation was associated with a 0.34% decrease in aldosterone (both p<0.01), but no significant association was found with SAT. In conclusion, anthropometric measures of obesity, VAT and leptin were positively associated with serum aldosterone, while adiponectin and liver attenuation were negatively associated with serum aldosterone. These data suggest that adiposity may play a role in aldosterone levels among AAs. 1. O’Seaghdha et al, BMC Endocr Disord 12: 3, 2012; 2. Harada et al, Clin. Endocrinol. (Oxf.) 79, 510-516 (2013); 3. Katzmarzyk, et al. Am. J. Clin. Nutr. 91, 7-15 (2010). Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Comparison of the prevalence, severity, and risk factors for hepatic steatosis in HIV-infected and uninfected people

BackgroundHepatic steatosis is prevalent in Western countries, but few studies have evaluated whether the frequency and severity of steatosis are greater in the setting of HIV infection. We compared the prevalence and severity of hepatic steatosis between HIV-infected (HIV+) and uninfected persons and identified factors associated with greater steatosis severity within both groups.MethodsWe performed a cross-sectional study among participants without cardiovascular disease who participated in a substudy of the Veterans Aging Cohort Study. Hepatic steatosis was defined by noncontrast computed tomography (CT) liver-to-spleen (L/S) attenuation ratio < 1.0. Multivariable linear regression was used to: 1) evaluate the association between HIV infection and severity of hepatic steatosis, as measured by absolute liver attenuation, and 2) identify factors associated with greater severity of steatosis, by HIV status.ResultsAmong 268 participants (median age, 55 years; 99% male; 79% black; 23% obese; 64% HIV+ [91% on antiretroviral therapy]), the overall prevalence of steatosis was 7.8% and was similar between HIV+ and uninfected individuals (13 [7.6%] versus 8 [8.2%], respectively; p = 0.85). Participants with HIV, the majority of whom received antiretroviral therapy, had a higher mean absolute liver attenuation (mean difference, 5.68 Hounsfield units; p < 0.001), correlating with lesser hepatic steatosis severity, compared to uninfected participants. After adjusting for covariates, only advanced hepatic fibrosis was associated with greater severity of steatosis in HIV+ persons (p = 0.03) and uninfected individuals (p < 0.001).ConclusionsIn this sample of participants without cardiovascular disease, the prevalence of hepatic steatosis by noncontrast abdominal CT was not different by HIV status. Increasing severity of steatosis was independently associated with advanced hepatic fibrosis in both groups.

Virtual monoenergetic dual-energy CT for evaluation of hepatic and splenic lacerations.

To evaluate the utility of virtual monoenergetic imaging in assessing hepatic and splenic lacerations and to determine the optimal energy level to maximize injury contrast-to-noise ratio. We retrospectively examined 49 contrast-enhanced abdominal CT studies performed on a dual-source dual-energy CT (DECT) scanner with reported liver and/or splenic lacerations. All studies included portal venous phase imaging acquired simultaneously at low (80 or 100kVp) and high (140kVp with tin filtration) energy levels. Conventional 120kVp-equivalent images were generated for routine review by blending the low and high energy acquisitions. Virtual monoenergetic reconstructions were retrospectively generated in 10keV increments from 40 to 90keV. Liver or splenic laceration attenuation, background parenchymal attenuation, and noise were measured on each set of monoenergetic and conventional images. Injury-to-parenchyma contrast and contrast-to-noise ratios (CNR) were calculated. Differences between CNR of monoenergetic series and conventional images were assessed with a paired t test. Liver laceration was identified in 28 patients, and splenic laceration in 22 patients. Background noise was lower at higher monoenergetic levels, with the lowest noise seen at 90keV, less than that of conventional images (stddev 8.0 for 90keV and 8.5 for conventional based on noise of uninjured liver/spleen parenchyma, p < 0.001). For both liver and splenic lacerations, injury-to-parenchyma contrast was greater at lower monoenergetic levels, with maximum at 40keV. Contrast at 40-70keV was significantly greater than that of conventional images (p < 0.001). Injury-to parenchyma CNR was also greater at 40-70keV than that of conventional images and with statistical significance. CNR was highest at 40keV for both liver (6.5 for 40keV and 5.4 for conventional, p < 0.001) and splenic lacerations (7.5 vs. 5.8, p < 0.001). DECT virtual monoenergetic imaging at low keV improves injury-to-parenchyma CNR of hepatic and splenic lacerations compared with traditional polyenergetic reconstructions. Specially, the optimal energy level for assessing both was 40keV.

AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rats.

BACKGROUND:The cannabinoid receptor 2 (CB2) plays a pleiotropic role in the innate immunity and is considered a crucial mediator of liver disease. Cannabinoid CB2 receptor activation has been reported to attenuate liver fibrosis in CCl4 exposed mice and also plays a potential role in liver regeneration in a mouse model of I/R and protection against alcohol-induced liver injury.AIM:In this study, we investigated the impact of CB2 receptors on the antifibrotic and regenerative process associated with cholestatic liver injury.METHODS:Twenty-six rats had bile duct ligation co-treated with silymarin and AM1241 for 3 consecutive weeks. Serum hepatotoxicity markers were determined, and histopathological evaluation was performed.RESULTS:Following bile duct ligation (BDL) for 3 weeks, there was increased aminotransferase levels, marked inflammatory infiltration and hepatocyte apoptosis with induced oxidative stress, as reflected by increased lipid peroxidation. Conversely, following treatment with the CB2 agonist, AM-1241, BDL rats displayed a reduction in liver injury and attenuation of fibrosis as reflected by expression of hydroxyproline and α-smooth muscle actin. AM1241 treatment also significantly attenuated lipid peroxidation end-products, p53-dependent apoptosis and also attenuated inflammatory process by stimulating IL-10 production. Moreover, AM1241 treated rats were associated with significant expression of hepatic progenitor/oval cell markers.CONCLUSION:In conclusion, this study points out that CB2 receptors reduce liver injury and promote liver regeneration via distinct mechanisms including IL-10 dependent inhibition of inflammation, reduction of p53-reliant apoptosis and through stimulation of oval/progenitor cells. These results suggest that CB2 agonists display potent hepatoregenrative properties, in addition to their antifibrogenic effects.

Measured power law attenuation of shear waves in swine liver

To characterize the attenuation and dispersion behavior of shear waves in excised swine liver samples, the complex shear modulus was measured with a Rheospectris C500 + from 10 Hz to 2000 Hz. The shear wave attenuation and shear wave speed were calculated from the complex modulus measurements. A power law fit was evaluated for the shear wave attenuation, and a power law fit with and without a constant offset was evaluated for the shear wave speed. The power law closely matches the measured shear wave attenuation over most of the frequency range evaluated, although some differences are observed in several of the samples below 400 Hz. The power law without the constant offset closely matches the measured shear wave speed above 200 Hz in all measurements, where the addition of the constant offset achieves a much closer fit in all measurements that contain discrepancies below 200 Hz. The results demonstrate that shear wave attenuation in swine liver follows a power law and that a power law with a constant offset is an effective model for the shear wave speed in swine liver. [Work supported in part by NIH Grants DK092255, EB023051, and EB012079.]

Abdominal CT evaluation of the liver and spleen for staging mast cell tumors in dogs yields nonspecific results

Canine mast cell tumor staging is commonly performed using abdominal ultrasonography and fine-needle aspiration cytology of masses, lymph nodes, and hepatic and splenic parenchyma. Computed tomography is used for abdominal, thoracic, or whole body imaging in staging mast cell tumors in the authors' institution enabling evaluation of multiple body areas in one examination. The aim of this study was to compare the CT examinations acquired for staging of mast cell disease to their subsequent liver and spleen cytology findings. Medical records of dogs with primary mast cell tumors that underwent abdominal CT and concurrent liver and spleen aspirates were reviewed. The CT examinations were evaluated for attenuation, size, and margination of the liver and spleen. The relationship between CT findings and cytology results was analyzed. Forty-nine dogs matched the inclusion criteria: five of forty-nine dogs with cutaneous mast cell tumors were positive for metastasis from liver and/or spleen aspirates. Of the five dogs with cytological evidence of liver or spleen metastasis, four had normal CT liver attenuation and size, one dog had concurrent primary hepatocellular neoplasia, four dogs had abnormal splenic parenchyma (two nodular and two diffuse heterogeneity), and one dog had a normal attenuation of the spleen. In four dogs, the spleen was subjectively enlarged. Computed tomographic evaluation of the liver showed no consistent pattern associated with mast cell metastasis and did not predict cytology results. Multifocal splenic hypoattenuating lesions more commonly coincided with mast cell metastasis. Sampling of the liver and spleen remains to be considered in the absence of abnormal CT findings for full staging.

Differing Associations between Fatty Liver and Dyslipidemia According to the Degree of Hepatic Steatosis in Korea.

ObjectiveFatty liver is associated with insulin resistance-related diseases, such as dyslipidemia, obesity, and type 2 diabetes. The aim of this study was to evaluate the association of dyslipidemia with fatty liver and assess the differences in these associations according to the degree of hepatic steatosis.MethodsA total of 2,462 subjects (1,679 men and 783 women) who underwent a comprehensive health check-up (including abdominal computed tomography) from January 2010 to December 2013 were enrolled at Samsung Changwon Hospital Healthcare Center. The liver attenuation index (LAI), defined as the difference between mean hepatic and splenic attenuation, was used to assess the degree of hepatic steatosis. An LAI below 5 Hounsfield units was defined as fatty liver.ResultsWe found that 32.2% of the study subjects had fatty liver. Serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG), and fasting blood glucose concentrations and glycated hemoglobin (HbA1c percentage) were significant greater in the fatty liver group compared with the non-fatty liver group, while serum high-density lipoprotein cholesterol (HDL-C) was significantly lower in the fatty liver group. Subjects with fatty liver had 1.7-fold greater risk of dyslipidemia than those without fatty liver after adjusting for age, sex, body mass index (BMI), and HbA1c. When individuals with fatty liver were analyzed by tertiles of LAI values, LDL-C, TG, fasting glucose, BMI, and HbA1c concentrations increased while HDL-C decreased with decreasing LAI tertiles. Compared with LAI tertile 3, the risk for dyslipidemia significantly increased with adjusted odds ratios of 1.42, and 1.81 in tertiles 2 and 1, respectively.ConclusionFatty liver was significantly associated with dyslipidemia and this association varied according to the degree of hepatic steatosis.

Non-invasive assessment of liver steatosis

Liver steatosis is a major health problem since 20-30% of the population is affected with non-alcoholic fatty liver disease (NAFLD). NAFLD comprises a wide range of liver injury, from simple steatosis to steatohepatitis, progressive fibrosis and eventually cirrhosis with its complications. Liver biopsy is considered the gold standard for steatosis grading. However, it is an invasive procedure with some risks of complications, and cannot be used as a screening procedure. On the other hand, steatosis severity may change within weeks of therapeutic intervention; thus, liver biopsy is unsuitable for monitoring changes over short periods of time. For the assessment of liver steatosis several imaging techniques are available. Conventional B-mode ultrasound (US) is the imaging modality most widely used. It gives a subjective estimate of the fat content in the liver and has a low sensitivity for detecting mild steatosis. The presence of underlying chronic liver disease may reduce the accuracy of US in the diagnosis of hepatic steatosis. The use of computed tomography is limited by the radiation exposure. Moreover, the technique has a low accuracy for mild steatosis, and the presence of other underlying diffuse liver disease may alter liver attenuation values. Magnetic resonance imaging–derived proton density fat fraction (MRI-PDFF) is a technique that accurately quantifies the hepatic fat content and has been proposed as an alternative to the histological assessment of liver steatosis in patients with NAFLD. MRI-PDFF is not influenced by confounding factors and is operator-independent. However, it may have applicability limitations due to claustrophobia, metal implants or pacemakers, or inability to suspend respiration for image acquisition. Moreover, the availability and the costs should be taken into account when it is used for screening purpose. Controlled Attenuation Parameter (CAP) is available on the FibroScan device. CAP measures the attenuation, in decibel/meter, of the US beam that traverses the liver tissue. The performance of the CAP has been assessed in cohort of patients and in a meta-analysis with individual patient's data, taking the histologic grading of steatosis as the reference. Other new ultrasound-based techniques are nowadays available and their performance is under evaluation. These techniques are based on the quantification of the ultrasound attenuation in the tissue or the estimation of the speed of sound within soft tissues, that varies slightly with fat content: an increase in fat content leads to a decrease in the speed of sound.

The novel myokine irisin: clinical implications and potential role as a biomarker for sarcopenia in postmenopausal women.

To clarify the association of circulating irisin with muscle, liver and bone, and to evaluate irisin as a biomarker for sarcopenia in postmenopausal women. Quadriceps cross-sectional area (QcCSA), bone mineral density (BMD), liver attenuation (measured in Hounsfield units (HU)) were assessed using quantitative computed tomography in 153 postmenopausal women, mean age of 72.20 ± 5.96 years. Muscle strength and physical performance were evaluated by handgrip test and short physical performance battery, respectively. Serum irisin was measured by an enzyme-linked immunosorbent assay kit. In addition, 147 young women were recruited as a reference group to define cut-off values for sarcopenia. Circulating irisin was positively correlated with QcCSA/body weight (BW) and liver HU even after adjusting for multiple covariates, and the serum level was significantly lower in the sarcopenia group (QcCSA/BW<-2SD of the mean values for young women) than in the presarcopenia (-2SD≤QcCSA/BW<-1SD) or control groups (1SD≤QcCSA/BW<2SD). Logistic regression models showed that the relationship between circulating irisin and prevalence of sarcopenia remained significant after adjusting for confounding factors (per 1.0 ng/mL decrease of irisin, odds-ratio = 1.95, 95% confidence interval 1.33-2.87, p-value = 0.001). In postmenopausal women, serum irisin may be used as a biomarker for sarcopenia, and we showed the potential for the development of irisin-based early screening and staging tool for sarcopenia.

Diffusely decreased liver attenuation on post-mortem computed tomography: Comparison with ante-mortem computed tomography and autopsy findings

Abstract We present two cases of diffusely decreased liver attenuation on post-mortem computed tomography (CT) which is lower than that on ante-mortem CT. Cases include a 37-year-old female whose cause of death was related to myelodysplastic syndrome (Case #1) and an 88-year-old female whose cause of death was related to malignant lymphoma (Case #2). We compared post-mortem CT (PMCT) liver attenuations with those on ante-mortem CT (AMCT). For Case #1, average AMCT values of the right/left liver were 46.1/50.0 Hounsfield Units (HU) 2 days ante-mortem and PMCT values of the right/left liver were 33.9/38.4 HU 3 h post-mortem. For Case #2, average AMCT values were 61.4/54.9 HU 5 days ante-mortem and PMCT values of the right/left liver were 38.2/40.6 HU 2 h post-mortem. In both Case # 1 and #2, decreased liver attenuations were found on PMCT. Further, autopsy revealed diffuse hepatocellular hemorrhage, deficits, and necrosis in Case #1, and liver infiltration of lymphoma in Case #2. These pathological findings were considered to be related to diffusely decreased liver attenuation on PMCT in conjunction with remarkable deterioration of hepatobiliary function before death. The observed decreases in liver attenuation on PMCT may be attributed mainly to hepatic pathological changes just prior to death. PMCT liver attenuation does not necessarily reflect the ante-mortem state some time before death, and it is therefore necessary to be careful when presuming the ante-mortem hepatic pathological conditions from only PMCT. This attenuation change should be taken into account during PMCT interpretation.

The impact of abdominal fat on abdominal aorta calcification measured on non-enhanced CT.

Cardiovascular (CV) morbidity, atherosclerosis, and obesity are all targets of clinical concern and vast research, as is the association between them. Aim of this study is to assess the impact of adipose tissue (including visceral and subcutaneous fat) on abdominal aorta calcification measured on non-enhanced computed tomography (CT). We retrospectively included 492 patients who underwent non-enhanced CT scans during workup for clinically suspected renal colic. All scans were reviewed for abdominal aorta calcification, liver attenuation, and thickness of visceral and subcutaneous fat. Multivariate general linear regression models were used to assess the association between abdominal aorta calcium score and adiposity measures. In the model that included only adiposity measures; visceral fat thickness had statistically significant direct association with abdominal aorta calcium score (B = 67.1, P <.001), whereas subcutaneous pelvic fat thickness had a significant inverse association with abdominal aorta calcium score (B = −22.34, P <.001). Only the association of subcutaneous pelvic fat thickness with abdominal aorta calcium score remained statistically significant when controlling for age, sex, smoking, hypertension, diabetes mellitus, and hyperlipidemia (B = −21.23, P <.001). In this model, the association of visceral fat remained statistically significant in females (B = 84.28, P = .001) but not in males (B = 0.47, P = .973). Visceral fat thickness and subcutaneous pelvic fat thickness were found to have opposing associations with abdominal aorta calcium score. This suggests that while visceral fat may have a lipotoxic effect on aortic atherosclerotic processes, subcutaneous pelvic fat may have a protective role in these processes.

Liver Fat Is Associated With Markers of Inflammation and Oxidative Stress in Analysis of Data From the Framingham Heart Study

Nonalcoholic fatty liver disease is an inflammatory condition that results in progressive liver disease. It is unknown if individuals with hepatic steatosis, but not known to have liver disease, have higher serum concentrations of markers of systemic inflammation and oxidative stress. We collected data from 2482 participants from the Framingham Heart Study (mean age, 51 ± 11 y; 51% women) who underwent computed tomography and measurement of 14 serum markers of systemic inflammation. Heavy alcohol users were excluded. The liver:phantom ratio (a continuous parameter of liver attenuation relative to a calibration phantom) was used to identify individuals with radiographic evidence of liver fat. Primary covariates included age, sex, smoking, alcohol, aspirin use, hypertension, dyslipidemia, diabetes, and cardiovascular disease. Body mass index and visceral fat were secondary covariates. We used multivariable linear regression models to assess the association between liver fat and systemic inflammatory markers. In multivariable-adjusted models, liver fat was associated with the following inflammatory markers: high-sensitivity C-reactive protein (P < .001), urinary isoprostanes (P < .001), interleukin 6 (P < .001), intercellular adhesion molecule 1 (P < .001), and P-selectin (P= .002). Additional adjustment for body mass index or visceral fat attenuated the results slightly, although all associations remained statistically significant (P for all ≤ .01). In a community-based cohort, individuals with hepatic steatosis without known liver disease had higher mean serum concentrations of systemic markers of inflammation. Studies are needed to determine whether treatment of hepatic steatosis reduces systemic inflammation.

Adaptogens in chemobrain (Part III): Antitoxic effects of plant extracts towards cancer chemotherapy-induced toxicity - transcriptome-wide microarray analysis of neuroglia cells

BackgroundToxicity of chemotherapeutics is a serious problem in cancer therapy. Adaptogens are known to increase adaptability and survival organisms. AimThe aim of this study was to assess the effects of selected adaptogenic herbal extracts on FEC (fixed combination of 5-fluorouracil, epirubicin and cyclophosphamide) induced changes in transcriptome-wide microarray profiles of neuroglia cells. Another task of the study was to identify those genes, which are associated with FEC-induced hepato-, cardio– and nephrotoxicity to predict potential effects of andrographolide (AND), Andrographis herb, Eleutherococcus roots genuine extracts (ES), their fixed combination (AE) and the combination of Rhodiola roots, Schisandra berries and Eleutherococcus roots (RSE) on the organismal level. MethodsGene expression profiling was performed by transcriptome-wide mRNA microarray in the human T98G neuroglia cells after treatment with adaptogens. Interactive pathways downstream analysis was performed with data sets of significantly up- or down-regulated genes and predicted effects on cellular functions and diseases were identified by Ingenuity IPA database software. ResultSignificant differences of transcriptome-wide microarray profiles were observed after treatment of T98G cells with FEC and after co-incubation with adaptogens.FEC induced deregulation of certain genes with suggested toxicity associated with liver fibroses, necrosis and congenital heart diseases. Co-incubation of AE with FEC prevented FEC-induced deregulation of 66 genes increasing organismal death, 37 genes decreasing cell survival, 37 genes decreasing DNA repair, 37 genes decreasing viral infection and some other functions, indicating on potential beneficial effects of AE. Furthermore, FEC-induced hepato-, nephro- and cardiotoxicity related to deregulation of genes was predictably attenuated by AE. Moreover, co-incubation of AE with FEC caused differential expression of genes, which presumably are beneficial for an organism during chemotherapy. They include predicted activation of DNA repair, activation of movement of antigen presenting cells and inhibition of muscle cells death.The main active constituent of AE is AND. Co-incubation of FEC only with AND results in deregulation of 10 genes causing death of breast cancer cells, decrease of liver toxicity and attenuation of organismal death. Co-incubation of ES extract with FEC showed that ES suppressed FEC-induced deregulation of genes, which inhibit organismal death and fertility. Co-incubation of FEC with RSE indicated potential hepatoprotective effect against FEC-induced apoptosis of liver cells presumably due to suppression of FEC-induced expressions of genes, which increased liver cell apoptosis. Simultaneously, RSE activated expression of genes inhibiting tumor growth.Though, microarray analysis did not provide final proof that the genes induced by the AE, AP and ES are responsible for the physiological effects observed in human patients following their oral administration, it provided insights into putative genes and directions for future research and possible implementation into practice. ConclusionApplication of cytostatic drugs in combination with adaptogenic plant extracts induced significant changes in transcriptome-wide microarray profiles of neuroglial cells. These changes indicate on potential beneficial effects of adaptogens on FEC induced adverse events in cancer chemotherapy.

Longer lactation duration is associated with decreased prevalence of non-alcoholic fatty liver disease in women

Lactation lowers blood glucose and triglycerides, and increases insulin sensitivity. We hypothesized that a longer duration of lactation would be associated with lower prevalence of non-alcoholic fatty liver disease (NAFLD), which is the leading cause of chronic liver disease in the United States. Participants from the Coronary Artery Risk Development in Young Adults cohort study who delivered ≥ 1 child post-baseline (Y0: 1985-1986), and underwent CT quantification of hepatic steatosis 25 years following cohort entry (Y25: 2010-2011) were included (n = 844). The duration of lactation was summed for all post-baseline births, and NAFLD at Y25 was assessed by central review of CT images and defined by liver attenuation ≤ 40 Hounsfield Units after exclusion of other causes of hepatic steatosis. Unadjusted and multivariable logistic regression analyses were performed using an a priori set of confounding variables; age, race, education, and baseline body mass index. Of 844 women who delivered after baseline (48% black, 52% white, mean age 49 years at Y25 exam), 32% reported lactation duration of 0 to 1 month, 25% reported >1 to 6 months, 43% reported more than 6 months, while 54 (6%) had NAFLD. Longer lactation duration was inversely associated with NAFLD in unadjusted logistic regression. For women who reported >6 months lactation compared to those reporting 0-1 month, the odds ratio for NAFLD was 0.48 (95% CI 0.25-0.94; p = 0.03) and the association remained after adjustment for confounders (adjusted odds ratio 0.46; 95% CI 0.22-0.97; p = 0.04). A longer duration of lactation, particularly greater than 6 months, is associated with lower odds of NAFLD in mid-life and may represent a modifiable risk factor for NAFLD. A longer duration of breastfeeding has been associated with multiple potential health benefits for the mother including reduction in heart disease, diabetes and certain cancers. In this study we found that breastfeeding for longer than 6 months was associated with a lower risk of non-alcoholic fatty liver disease in mid-life.

Opportunistic Screening for Hereditary Hemochromatosis With Unenhanced CT: Determination of an Optimal Liver Attenuation Threshold.

The purpose of this study was to assess whether a specific liver attenuation threshold for unenhanced CT allows both sensitive opportunistic detection of unsuspected hereditary hemochromatosis and low overall screening test-positive rates. We used a standard ROI placement method on unenhanced CT studies of 3357 consecutive adults (mean age, 57.0 years) with no symptoms of liver disease who underwent colorectal screening. Hepatic attenuation (in HU) was measured to assess test-positive rates at various liver attenuation thresholds. To assess sensitivity, unenhanced hepatic CT attenuation was also measured in 12 patients with hereditary hemochromatosis (mean age, 48.3 years), who were homozygous for the HFE C282Y mutation. All scans were obtained at 120 kV. Serum ferritin levels were recorded for the hereditary hemochromatosis cohort. Mean liver attenuation ± SD among screened adults was 59.4 ± 12.7 HU, compared with 78.7 ± 13.1 HU (range, 59-105 HU) in the hereditary hemochromatosis cohort (p < 0.001). Screening test-positive rates were 30.6% (n = 1028) at 65 HU, 8.2% (n = 275) at 70 HU, 1.2% (n = 39) at 75 HU, and 0.2% (n = 7) at 80 HU. Corresponding sensitivities for hereditary hemochromatosis at these thresholds were 83.3% (10/12) at 65, 70, and 75 HU; and 50.0% (6/12) at 80 HU. Serum ferritin levels were elevated in all patients with hereditary hemochromatosis (mean, 1678 ng/mL; range, 477-3991 ng/mL). An unenhanced CT liver attenuation threshold of 75 HU was sensitive (83.3%) for hereditary hemochromatosis while maintaining an acceptably low screening test-positive rate (1.2%). An unexplained liver attenuation of 75 HU or more on unenhanced CT should trigger appropriate laboratory investigation for iron overload; early intervention with phlebotomy can limit or prevent organ damage in patients with hemochromatosis.

Impact of body mass index on CT attenuation of adrenal adenoma

ObjectiveTo investigate whether lipid metabolism-related factors regulate unenhanced CT attenuation in adrenal adenoma (AA). Materials and MethodsThirty-six patients with surgically proven AAs were enrolled in this study. The patients’ underlying diseases were the following: primary aldosteronism (n = 24), Cushing’s syndrome (n = 8), subclinical Cushing’s syndrome (n = 3) and non-functioning AA (n = 1). Unenhanced CT attenuation of AAs and liver was measured. Pathologically, clear cell ratio (CCR) constituting each AA was qualitatively assessed. Clinical data including tumor diameter, body mass index (BMI), hemoglobin A1c, triglyceride, total cholesterol, blood cortisol and plasma aldosterone levels were also obtained. Simple and multiple linear regression analyses were performed to evaluate the radiological and clinicopathological factors associated with CT attenuation of AAs for all patients and separately for 25 patients with primary aldosteronism or non-functioning AA. ResultsFor all patients, there was a significant correlation between CT attenuation and each of CCR, BMI and blood cortisol levels (p < 0.05). For patients with primary aldosteronism or non-functioning AA, there was also a significant correlation between CT attenuation and CCR or BMI (p < 0.05). ConclusionIn addition to pathological factors, lipid-metabolism-related factors including BMI and blood cortisol levels can affect unenhanced CT attenuation of AA.