Liver Attenuation Research Articles

Non-alcoholic fatty liver disease is a strong predictor of coronary artery calcification in metabolically healthy subjects: A cross-sectional, population-based study in middle-aged subjects.

ObjectivesThis study aims to estimate the relationship between non-alcoholic fatty liver disease (NAFLD) and measures of atherosclerotic cardiovascular disease (ASCVD), and to determine to what extent such relationships are modified by metabolic risk factors.MethodsThe study was conducted in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort (n = 1015, age 50–64 years, 51.2% women). NAFLD was defined as computed tomography liver attenuation ≤40 Hounsfield Units, excluding other causes of liver fat. Coronary artery calcification score (CACS) was assessed using the Agatston method. Carotid plaques and intima media thickness (IMT) were measured by ultrasound. Metabolic status was based on assessments of glucose homeostasis, serum lipids, blood pressure and inflammation. A propensity score model was used to balance NAFLD and non NAFLD groups with regards to potential confounders and associations between NAFLD status and ASCVD variables in relation to metabolic status were examined by logistic and generalized linear regression models.ResultsNAFLD was present in 106 (10.4%) of the subjects and strongly associated with obesity-related traits. NAFLD was significantly associated with CACS after adjustment for confounders and metabolic risk factors (OR 1.77, 95% CI 1.07–2.94), but not with carotid plaques and IMT. The strongest association between NAFLD and CACS was observed in subjects with few metabolic risk factors (n = 612 [60% of all] subjects with 0–1 out of 7 predefined metabolic risk factors; OR 5.94, 95% CI 2.13–16.6).ConclusionsNAFLD was independently associated with coronary artery calcification but not with measures of carotid atherosclerosis in this cohort. The association between NAFLD and CACS was most prominent in the metabolically healthy subjects.

LI-RADS v2017 categorisation of HCC using CT: Does moderate to severe fatty liver affect accuracy?

To compare the sensitivity of Liver Imaging Reporting and Data System (LI-RADS) v2017 for diagnosis of hepatocellular carcinoma (HCC) using multiphasic computed tomography (CT) between patients with and without moderate to severe fatty liver (MSFL). This retrospective study included a total of 106 high-risk patients with 112 pathologically proven HCCs who underwent multiphasic CT. Patients were classified as MSFL (24 men, 2 women; mean age, 59.5 years [range, 38-79 years]) and non-MSFL (64 men, 16 women; mean age, 62.9 years [range, 40-89 years]) groups according to unenhanced CT liver and spleen parenchymal attenuation. Two independent radiologists assigned LI-RADS categories and accessed HCC features on CT. Sensitivities for LR-5 assignment and frequencies of HCC features were compared between the two groups. Sensitivities of LR-5 assignment for diagnosing HCCs were not significantly different between MSFL and non-MSFL groups (65.4% [17/26] vs. 76.7% [66/86] for reviewer 1, p = 0.247; 73.1% [19/26] vs. 76.74% [66/86] for reviewer 2, p = 0.702). No significant differences in the frequencies of arterial hyperenhancement, washout, and capsule were observed between the two groups (96.2% [25/26] vs. 98.8% [85/86], p = 0.412; 80.8% [21/26] vs. 89.5% [77/86], p = 0.308; and 53.8% [14/26] vs. 57% [49/86], p = 0.778, respectively). LI-RADS v2017 using CT showed comparable sensitivity for diagnosing HCC regardless of MSFL. • Using LI-RADS v2017 with CT, diagnosis of HCC in patients with MSFL showed similar sensitivity to that in patients without MSFL. • Frequencies of major HCC features (arterial hyperenhancement, washout, and capsule) on CT between the MSFL and non-MSFL groups were not significantly different. • LI-RADS using CT may be feasible for diagnosing HCC in patients with fatty liver.

Quantification of Liver Fat Content With Unenhanced MDCT: Phantom and Clinical Correlation With MRI Proton Density Fat Fraction.

The purpose of this study was to evaluate the relation between unenhanced CT liver attenuation values and MRI-derived proton density fat fraction (PDFF) for estimation of liver fat content at CT. A CT-MRI phantom was constructed and imaged containing 12 vials with lipid fractions ranging from 0% to 100%. For the retrospective clinical arm, 221 patients (120 men, 101 women; mean age, 54 years) underwent both unenhanced CT and chemical shift-encoded MRI of the liver between 2007 and 2017. Among these patients, 92 had more than one 120-kV CT scan for comparison. CT attenuation and MRI PDFF were derived with coregistered ROI measurements in the right hepatic lobe. The 120-kV subgroup of CT examinations performed within 1 month of MRI PDFF examinations (n = 72) served as the primary cohort for linear correlation. The effects of different tube voltage settings, time intervals between CT and MRI, and iron overload were assessed. Linear least squares regression analysis was performed. Phantom results showed excellent linear fit between CT attenuation and MRI PDFF (r2 = 0.986). In patients, 120-kV CT performed within 1 month of MRI PDFF exhibited strong linear correlation (r2 = 0.828) that closely matched the phantom data, yielding the following clinical CT-MRI conversion formula: MRI PDFF (%) = -0.58 × CT attenuation (HU) + 38.2. Correlation worsened for CT-to-MRI intervals longer than 1 month (r2 = 0.565), and this specific relationship did not apply as well to non-120-kV settings (r2 = 0.554). For patients with multiple scans, correlation progressively worsened over time. CT-based liver fat content was underestimated in several patients with iron overload. The linear correlation between unenhanced CT attenuation and MRI PDFF allows quantification of liver fat content by means of unenhanced CT in clinical practice. As expected, correlation worsened with increasing CT-MRI time interval, variable tube voltage settings, and iron overload.

Hepatic steatosis is highly prevalent across the paediatric age spectrum, including in pre-school age children.

The prevalence of non-alcoholic fatty liver disease (NAFLD) in children is 8% in the general population, and 34% in the context of obesity. There is a paucity of data on the prevalence of hepatic steatosis in healthy children in Ontario. To determine the prevalence of hepatic steatosis using abdominal computed tomography (CT) scans in a cohort of previously healthy children across the paediatric age spectrum in Ontario, Canada, and to determine any association between measures of abdominal adiposity and hepatic steatosis. Retrospective review of the SickKids Trauma Database from 2004-2015. Previously healthy children ages 1-17years having undergone an abdominal CT scan as a part of routine trauma assessment were included, and those with an intra-abdominal injury excluded. Steatosis was defined as a difference between liver and spleen attenuation ≤-25HU. The percentage of the total area occupied by abdominal subcutaneous adipose and visceral adipose tissue was measured. Anthropometrics and baseline demographics were collected. A total of 503 (51% male) children with mean (±SD) age 9.5±4.5years and weight z-score of 0.37±1.05 were studied. Seventy-seven (15%, 95% CI [12%-18%]) had hepatic steatosis; no differences found between sexes or across age quartiles. The abdominal subcutaneous adipose tissue area was greater in those with hepatic steatosis compared to those without (32% [22-42] vs 24% [17-36], P=0.003). The visceral adipose tissue area was significantly greater in older children ≥9.8years with hepatic steatosis (7.7% [5.1-10] vs 6.6% (4.9-8.5), P=0.04). Hepatic steatosis was highly prevalent in previously healthy children in Ontario, including children of pre-school age. We found an association between hepatic steatosis and abdominal subcutaneous adipose tissue, and in older children with visceral adipose tissue.

CT predicts liver fibrosis: Prospective evaluation of morphology- and attenuation-based quantitative scores in routine portal venous abdominal scans.

ObjectivesOur aim was to prospectively determine whether quantitative computed tomography (CT) scores, consisting of simplified indices for liver remodeling and attenuation, may predict liver fibrosis in abdominal CT scans.Materials and methodsThis cross-sectional, prospective study was approved by the local IRB (Kantonale Ethikkommission Bern). Written informed consent was given from all patients undergoing study-MR exams. Between 02/16 and 05/17, four different liver fibrosis scores (CRL-R = caudate-right-lobe ratio, LIMV-, LIMA- and LIMVA-fibrosis score, with “LIM” for liver imaging morphology, “V” for liver vein diameter and “A” for attenuation) were calculated in 1534 consecutive abdominal CT scans, excluding patients with prior liver surgery and liver metastasis. Patients were invited to undergo magnetic resonance (MR) elastography as the non-invasive gold standard to evaluate liver fibrosis. MR elastography shear modulus ≥2.8 kPa was defined as beginning liver fibrosis, while ≥3.5 kPa was defined as significant liver fibrosis (which would correspond to fibrosis stage F2 or higher in histology). Cutoff values, sensitivities and specificities obtained from the receiver operating characteristics (ROC) analysis were then calculated in 141 patients who followed the invitation for MR elastography. To mitigate selection bias, prevalence was estimated in the screened total population (n = 1534) by applying the cutoff values with sensitivities and specificities calculated in the MR elastography sub-group. Positive predictive values (PPV) and negative predictive values (NPV) were then calculated.ResultsFibrosis scores including liver vein attenuation LIMA-FS and LIMVA-FS showed higher areas under the ROC curves (0.96–0.97) than CRL-R (0.82) to detect significant liver fibrosis, while LIMV-FS showed good performance as well (0.92). The prevalence-corrected PPV were 29% for CRL-R, 70% for LIMV-FS, 76% for LIMA-FS and 82% for LIMVA-FS.ConclusionCT fibrosis scores, notably LIMA-FS and LIMVA-FS, may predict significant liver fibrosis on routine abdominal CT scans.

Association of Visceral Fat and Liver Fat, Not Thigh Muscle Area nor Attenuation, with the Incidence of Type 2 Diabetes

Visceral fat, liver, and skeletal muscle are all major target organs of insulin and play key roles in the pathophysiology of type 2 diabetes. Not known is whether visceral fat, liver fat, and thigh skeletal muscle area or fat directly measured by computed tomography (CT) are independently associated with the incidence of type 2 diabetes. In a prospective cohort study, 1228 nondiabetic Japanese men and women were included. Intra-abdominal fat area (IAFA), liver-to-spleen (L/S) attenuation ratio to assess liver fat, and mid-thigh muscle area and attenuation were measured by CT. Low CT attenuation of liver and muscle reflects greater liver and intramuscular lipid content. Insulin resistance was assessed by HOMA-IR. Type 2 diabetes was diagnosed as fasting plasma glucose level ≥126 mg/dL, HbA1c ≥6.5%, or taking oral hypoglycemic medications or insulin. Discrete-time logistic hazard model was used. During the 7686 person-years of follow-up (median follow-up period, 7 years), 95 subjects developed type 2 diabetes. IAFA and L/S ratio, not thigh muscle area, were independently associated with the risk of type 2 diabetes. In multiple-adjusted models that included IAFA, L/S ratio, thigh muscle area, age, gender, family history of diabetes, HOMA-IR, smoking habit, daily alcohol consumption, and regular physical activity, odds ratios of type 2 diabetes for tertile 2 and 3 of IAFA were 2.23 (95% CI, 0.94-5.31) and 3.16 (1.33-7.52), respectively, compared to tertile 1, and those for tertile 1 and 2 of L/S ratio were 2.01 (1.01-3.97) and 2.(1.04-4.08), respectively, compared to tertile 3. However, those of tertile 2 and 3 of thigh muscle area were 0.76 (0.32-1.78) and 0.64 (0.24-1.69), respectively, compared to tertile 1. When thigh muscle attenuation was substituted for its area, results was identical to the above model. In conclusion, both greater amounts of visceral and liver fat, not thigh muscle area nor attenuation, were independently associated with the risk of type 2 diabetes. Disclosure K. Sato: None. S. Uehara: None. M. Shibata: None. Y. Hikita: None. W.Y. Fujimoto: None. E.J. Boyko: None. T. Hayashi: None.

IRGM Gene Variants Modify the Relationship Between Visceral Adipose Tissue and NAFLD in Patients With Crohn's Disease.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized comorbidity in Crohn's disease (CD), but the mechanisms are poorly understood. Autophagy is a highly conserved process regulating innate immunity that contributes to CD susceptibility. Emerging data suggest that variants in the autophagy-governing IRGM gene may contribute to the accumulation of visceral adipose tissue (VAT) and hepatic fat. Our objective was to characterize the relationship between VAT, IRGM gene variants, and NAFLD risk in patients with CD. We included all CD patients in the Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM) without history of alcohol abuse or liver disease. Hepatic fat was quantified by liver attenuation (LA) on computed tomography, with NAFLD defined by the validated liver:spleen (L:S) ratio. NAFLD severity was estimated by the FIB-4 Index and alanine aminotransferase (ALT). Using logistic regression modeling, we examined the relationship between VAT, autophagy gene variants, and NAFLD risk. Among 462 patients, 52% had NAFLD. Increasing VAT quartile was associated with reduced LA (mean change, -7.43; 95% confidence interval [CI], -10.05 to -4.81; Ptrend < 0.0001). In the fully adjusted model, patients in the highest VAT quartile had a 2.2-fold increased NAFLD risk (95% CI, 1.21 to 4.14; Ptrend = 0.032) and a 4.2-fold increased risk of ALT>upper limit of normal (ULN) (95% CI, 1.19 to 14.76; Ptrend = 0.017). The relationship between VAT and NAFLD was modified by IRGM variants rs4958847 and rs13361189 (Pinteraction = 0.005 and Pinteraction < 0.001, respectively). In a large CD cohort, VAT was directly associated with prevalent NAFLD, and this relationship was augmented by functionally annotated IRGM variants associated with impaired autophagy.

Abstract P255: Long-term Associations Between Non-High Density Lipoprotein and Apolipoprotein B in Young Adulthood and Coronary Artery Calcification in Adults With Nonalcoholic Fatty Liver Disease in Middle Age: The CARDIA Study

Background: Cardiovascular disease (CVD) is the leading cause of death in nonalcoholic fatty liver disease (NAFLD). Apolipoprotein B (apoB) and non-high density lipoprotein-C (NHDL-C) are positively associated with NAFLD in small studies. High apoB predicts atherosclerotic CVD even when NHDL-C is low, suggesting that apoB may be the strongest predictor of atherosclerotic risk in adults. Objective: To quantify associations between apoB, NHDL-C and the discordance between apoB and NHDL-C levels in young adulthood with prevalent NAFLD, and coronary artery calcium (CAC) in adults with NAFLD in midlife. Methods: CARDIA recruited young adults ages 18 to 30 years in 1985-86. Participants with complete baseline CVD risk factor data and year 25 (Y25) NAFLD assessment and CAC score were included. NAFLD was defined as noncontrast computed tomography (CT) liver attenuation ≤40 Hounsfield Units after exclusions for other causes of liver fat. Presence of CAC was defined as Agatston score &gt;0 on CT. Baseline NHDL-C or apoB values were divided into tertiles and 4 mutually exclusive concordant/discordant groups, stratified based on being above or below median NHDL-C or apoB levels. Results: Analysis included 2,508 participants (baseline age: 27 ± 4 years; body mass index: 25 ± 4 kg/m 2 ; 58% women; 53% white). Y25 NAFLD prevalence was 10%. Compared with the lowest tertile, higher odds of NAFLD were seen in the middle and high tertiles of both apoB and NHDL-C in separate adjusted models. High NHDL-C and low apoB, but not high apoB and low NHDL-C, discordance was associated with Y25 NAFLD in adjusted models. Among NAFLD participants (n=261), NHDL-C/apoB discordance was not associated with Y25 CAC. Highest odds of CAC were observed in NAFLD participants with high NHDL-C ( TABLE ). Conclusion: High NHDL-C is a strong early risk marker for both NAFLD and atherosclerosis among adults with NAFLD in midlife. Based on our study findings, the additional benefit of measuring apoB levels for risk stratification in adults with NAFLD is not apparent.

Single-energy non-contrast hepatic steatosis criteria applied to virtual non-contrast images: is it still highly specific and positively predictive?

To determine the sensitivity, specificity, and predictive values of single-energy non-contrast hepatic steatosis criteria on dual-energy virtual non-contrast (VNC) images. Forty-eight computed tomography (CT) examinations, which included single-energy non-contrast (TNC) and contrast-enhanced dual-energy CT angiography (CTA) of the abdomen, were enrolled. VNC images were reconstructed from the CTA. Region of interest (ROI) attenuations were measured in the right and left hepatic lobes, spleen, and aorta on TNC and VNC images. The right and left hepatic lobes were treated as separate samples. Steatosis was diagnosed based on TNC liver attenuation of ≤40 HU or liver attenuation index (LAI) of ≤-10 HU, which are extremely specific and predictive for moderate to severe steatosis. The sensitivity, specificity, and predictive values of VNC images for steatosis were calculated. VNC-TNC deviations were correlated with aortic enhancement and patient water equivalent diameter (PWED). Thirty-two liver ROIs met steatosis criteria based on TNC attenuation; VNC attenuation had sensitivity, specificity, and a positive predictive value of 66.7%, 100%, and 100%, respectively. Twenty-one liver ROIs met steatosis criteria based on TNC LAI. VNC LAI had sensitivity, specificity, and positive predictive values of 61.9%, 90.7%, and 65%, respectively. Hepatic and splenic VNC-TNC deviations did not correlate with one another (R2=0.08), aortic enhancement (R2<0.06) or PWED (R2 <0.09). Non-contrast hepatic attenuation criteria is extremely specific and positively predictive for moderate to severe steatosis on VNC reconstructions from the arterial phase. Hepatic attenuation performs better than LAI criteria. VNC deviations are independent of aortic enhancement and PWED.

Hepatic Heterogeneity and Attenuation on Contrast-Enhanced CT in Patients With the Hypovolemic Shock Complex: Objective Classification Using a Contemporary Cohort

When objectively measured on computed tomography (CT), does hepatic heterogeneity or overall liver attenuation predict the presence of shock? This retrospective study included 73 patients (mean age 33 years) with the hypoperfusion shock complex (HSC) on CT (cases) and 100 patients (mean age 43 years) with negative trauma CT scans (controls). Liver heterogeneity was calculated by using consistently sized regions of interest (ROIs) to measure the 2 highest and the 2 lowest areas of hepatic density (in Hounsfield units [HU]). The difference between the means of the 2 highest and 2 lowest ROIs was considered the heterogeneity. Attenuation was calculated using the mean of 3 randomly placed ROIs. Both heterogeneity and attenuation were then compared between cases and controls. Median hepatic heterogeneity was 16.8 HU (IQR: 10.7-23.4) for the HSC group and 9.0 HU (IQR: 7.0-10.4) for the controls (P < 0.001). The area under the curve was 0.79, and a threshold of 30 HU yielded a specificity of 100%. Median hepatic attenuation was not significantly different between the HSC and the control groups, with an area under the curve of 0.56. Increased hepatic heterogeneity may represent an objective marker of the HSC that performs in a similar manner to other established signs. By comparison, overall hepatic hypoattenuation is a poor indicator of the HSC.

Correlation between Non-Alcoholic Fatty Liver Disease and Visceral Adipose Tissue in Non-Obese Chinese Adults: A CT Evaluation.

ObjectiveTo investigate the correlation between non-alcoholic fatty liver disease and visceral adipose tissue in non-obese Chinese adults using computed tomography (CT).Materials and MethodsThe study included 454 subjects undergoing abdominal CT scan. Degree of CT attenuation in liver and spleen, and the degree of fat infiltration in liver were evaluated according to three indices: the attenuation value of liver parenchyma (CTLP), the attenuation ratio of liver and spleen (LSratio) and the attenuation difference between liver and spleen (LSdif). Visceral fat area (VFA) and total fat area (TFA) at L2/3 and L4/5 levels were measured, and the abdominal subcutaneous fat area (SFA) was calculated. Bivariate correlation analysis was carried out to determine the correlation among these factors.ResultsIn men, VFA, SFA and TFA at L2/3 and L4/5 levels showed significant differences in terms of the three indices to distinguish fatty liver from non-fatty liver (all, p < 0.001). In men, all the three indices showed negative correlation with TFA, SFA and VFA (all, p < 0.001). The negative correlation between the three indices and VFA at the L2/3 level was higher than at L4/5 level (r = −0.476 vs. r = −0.340 for CTLP, r = −0.502 vs. r = −0.413 for LSratio, r = −0.543 vs. r = −0.422 for LSdif, p < 0.001, respectively). The negative correlation between LSratio, LSdif and VFA at L2/3 and L4/5 levels was higher than SFA at the corresponding level. In women, all the three indices showed negative correlation with VFA and TFA at L2/3 and L4/5 levels, and the negative correlation between CTLP and VFA was higher at L2/3 level than at L4/5 level (r = −0.294 vs. r = −0.254, p < 0.001).ConclusionIn non-obese Chinese adults, the degree of hepatic fatty infiltration showed a strong correlation with abdominal fat on CT. VFA at L2/3 level was more closely related to fatty liver compared with VFA at L4/5 level.

Self-reported marijuana use over 25years and abdominal adiposity: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

We investigated the association between cumulative lifetime and current marijuana use with total abdominal adipose tissue (AT), visceral AT, subcutaneous AT, intermuscular AT, and mean liver attenuation (LA) at mid-life. Longitudinal and cross-sectional secondary data analysis of participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. CARDIA field centers in Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA, USA. CARDIA participants, aged 18-30years in 1985-1986, who were present at the clinic examination in 2010-2011 (n=2902). Marijuana use was assessed from responses to self-administered questionnaires at 8 CARDIA examinations over 25years, determined as cumulative marijuana-years and current use status. Non-contrast computed tomography imaging of the abdomen was obtained in 2010-2011. In 2010-2011, 84% of participants reported a history of marijuana use with 11% reporting use within the past 30days. Before adjustment, we observed greater cumulative marijuana use was associated with lower total abdominal and subcutaneous AT volume and lower LA and current marijuana use was associated with lower subcutaneous AT. However, after adjustment for age, sex, race, field center, cigarette pack-years and current use, regular alcohol consumption, cumulative drink-years, and physical activity, neither cumulative marijuana use nor current use showed an association with any abdominal adipose depot. Our estimates did not differ by age, sex, or race nor after accounting for cohort attrition. Neither cumulative marijuana use nor current marijuana use is associated with total abdominal, visceral, subcutaneous, or intermuscular adipose tissue, or liver attenuation in mid-life.

Dipeptidyl peptidase 4 inhibitors attenuates the decline of skeletal muscle mass in patients with type 2 diabetes.

Activation of dipeptidyl peptidase 4 has been reported to be associated with impairment of insulin signalling in skeletal muscle, presumably leading to loss of muscle function. This study was aimed to investigate whether the use of dipeptidyl peptidase 4 inhibitors (DPP4i) could attenuate the progressive loss of muscle mass in patients with type 2 diabetes. A total 105 patients with type 2 diabetes (mean age 62±12 years; 39% female) were studied in this retrospective observational study. To reduce the bias due to confounding variables, propensity-score matching analysis was performed. Change in skeletal muscle index measured by the whole body dual-energy X-ray absorptiometry at 1-year follow-up was evaluated. One-year changes in visceral and subcutaneous fat area and liver attenuation index were also determined by abdominal computed tomography. Overall, 37 of 105 (35.2%) patients were treated with DPP4i. The estimated change in skeletal muscle index in patients with DPP4i was significantly higher than that in patients without (0.05±0.06 vs -0.10±0.04 kg, P=.046). In a propensity-matched population (N=48), the same finding was observed (0.04±0.03 in DPP4i versus -0.12±0.03kg in non-DPP4i, P=.033). There were no significant differences in changes of visceral and subcutaneous fat area and liver attenuation index between patients with DPP4i and those without. Our data suggest the potential of DPP4i to prevent the progressive loss of muscle mass with ageing in patients with type 2 diabetes.

Beneficial effect of resveratrol on α‑naphthyl isothiocyanate‑induced cholestasis via regulation of the FXR pathway.

Cholestasis is defined as a functional impairment of bile secretion which results in the accumulation of bile acids (BAs) and other toxic molecules in the blood and liver, however, there are very few effective therapies for cholestasis. The farnesoidX receptor (FXR), as a nuclear receptor for BAs, is important in the regulation of BA levels in enterohepatic circulation. It has previously been demonstrated that activation of the FXR pathway may be a useful strategy with which to treat cholestasis. Resveratrol, one of the important ingredients from grape skins and Chinese medicine Polygonum cuspidatum, resulted in FXR‑activated effects invitro and exhibited a protective effect against α‑naphthylisothiocyanate (ANIT)‑induced cholestasis through FXR regulation invivo. The underlying mechanisms of resveratrol against ANIT‑induced cholestasis may be due to the regulation of BA homeostasis, improvement of liver injury and attenuation of the inflammatory response, which were regulated in a FXR‑dependent manner and in turn contributed to overall cholestasis alleviation. Overall, resveratrol as a FXR agonist may act as a potential compound for the treatment of drug‑induced cholestasis.

An artefact of PET attenuation correction caused by iron overload of the liver in clinical PET-MRI

BackgroundAttenuation correction is one of the most important steps in producing quantitative PET image data. In hybrid PET-MRI systems, this correction is far from trivial, as MRI data are not correlated to PET attenuation properties of the scanned object. Commercially available systems often employ correction schemes based on segmenting the body into different tissue classes (air, lung tissue, fat-, and water-like soft tissue), e.g. by using a dual time-point Dixon sequence. However, several pitfalls are known for this approach. Here a specific artefact of MR-based PET attenuation correction is reported, caused by misidentifying the liver as lung tissue due to iron overload.Case presentationA patient with a history of hematopoietic stem cell transplantation underwent a whole-body [18F]FDG PET-MRI scan. Markedly low liver uptake values were noted in the PET images, seemingly caused by an erroneous assignment of lung tissue attenuation values to the liver. A closer investigation demonstrated markedly low MRI intensity values of the liver, indicative of secondary hemochromatosis (iron overload) most probably due to a history of multiple blood transfusions. Manual assignment of adequate liver attenuation values resulted in more realistic PET images.ConclusionsIron overload of the liver was identified as a cause of a specific attenuation correction artefact. It remains to be seen how frequent this artefact will be encountered; however, this case highlights that attenuation maps should always be checked during PET image interpretation in hybrid PET-MRI.

The Use of Computed Tomography in the Diagnosis of Fatty Liver and Abdominal Fat Distribution among a Saudi Population

BACKGROUND:The pandemic of obesity is striking heavily worldwide and particularly among the affluent Gulf States where it is expected to continue to rise along with its complications.AIM:To examine the link between liver fat infiltration and abdominal fat amount using plain computer-assisted tomography (CT).METHODS:Fifty patients visiting the obesity clinic of “King Fahd Specialist Hospital” or Dr Suliman Alhabeeb Hospital between January 2015 and April 2016 were included. Liver and splenic attenuation dimensions were undertaken with three hepatic regions of interests (ROIs) and two ROIs from the spleen. The liver attenuation indices (LAIs) that were measured liver parenchymal attenuation (CTLP), liver/splenic attenuation ratio (LS ratio)and the (3) difference between liver and splenic attenuation (LS dif) and based on this LS dif The patients were grouped as LS dif greater or less than 5. Abdominal fat was evaluated utilising a 3 mm chop CT scan starting from the umbilicus; then computed by a workstation. The abdominal fat was classified as total fat (TF) and the sub-compartments of visceral adipose (fat) (VF), and subcutaneous fat (SF).RESULTS:Twenty-six of the participants were males. The mean (SD) of the age and BMI was 48 (14.9) years and 32.05 (8.3) kg/m2 respectively. The BMI and body Wt had a moderate negative correlation with the liver attenuation indices CTLP, LS ratio, LS diff (r = -0.417, -0.277, -0.312 and 0.435, -0.297, -0.0297), respectively. A very strong negative correlation between fatty liver, LS ratio and CTLP was found (-0.709, -0.575) respectively.CONCLUSION:Plain computed tomography can reliably be used as a survey device for fatty liver disease.

Body mass index trajectories in young adulthood predict non-alcoholic fatty liver disease in middle age: The CARDIA cohort study.

Non-alcoholic fatty liver disease is an epidemic. Identifying modifiable risk factors for non-alcoholic fatty liver disease development is essential to design effective prevention programmes. We tested whether 25-year patterns of body mass index change are associated with midlife non-alcoholic fatty liver disease. In all, 4423 participants from Coronary Artery Risk Development in Young Adults, a prospective population-based biracial cohort (age 18-30), underwent body mass index measurement at baseline (1985-1986) and 3 or more times over 25years. At Year 25, 3115 had liver fat assessed by non-contrast computed tomography. Non-alcoholic fatty liver disease was defined as liver attenuation ≤40 Hounsfield Units after exclusions. Latent mixture modelling identified 25-year trajectories in body mass index per cent change (%Δ) from baseline. We identified four distinct trajectories of BMI%Δ: stable (26.2% of cohort, 25-year BMI %Δ=3.1%), moderate increase (46.0%, BMI%Δ=21.7%), high increase (20.9%, BMI%Δ=41.9%) and extreme increase (6.9%, BMI%Δ=65.9%). Y25 non-alcoholic fatty liver disease prevalence was higher in groups with greater BMI %Δ: 4.1%, 9.3%, 13.0%, and 17.6%, respectively (P-trend <.0001). In multivariable analyses, participants with increasing BMI%Δ had increasingly greater odds of non-alcoholic fatty liver disease compared to the stable group: OR: 3.35 (95% CI: 2.07-5.42), 7.80 (4.60-13.23) and 12.68 (6.68-24.09) for moderate, high and extreme body mass index increase, respectively. Associations were only moderately attenuated when adjusted for baseline or Y25 body mass index. Trajectories of weight gain during young adulthood are associated with greater non-alcoholic fatty liver disease prevalence in midlife independent of metabolic covariates and baseline or concurrent body mass index highlighting the importance of weight maintenance throughout adulthood as a target for primary non-alcoholic fatty liver disease prevention.

Automated analysis of liver fat, muscle and adipose tissue distribution from CT suitable for large-scale studies

Computed Tomography (CT) allows detailed studies of body composition and its association with metabolic and cardiovascular disease. The purpose of this work was to develop and validate automated and manual image processing techniques for detailed and efficient analysis of body composition from CT data. The study comprised 107 subjects examined in the Swedish CArdioPulmonary BioImage Study (SCAPIS) using a 3-slice CT protocol covering liver, abdomen, and thighs. Algorithms were developed for automated assessment of liver attenuation, visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, thigh muscles, subcutaneous, subfascial (SFAT) and intermuscular adipose tissue. These were validated using manual reference measurements. SFAT was studied in selected subjects were the fascia lata could be visually identified (approx. 5%). In addition, precision of manual measurements of intra- (IPAT) and retroperitoneal adipose tissue (RPAT) and deep- and superficial SAT was evaluated using repeated measurements. Automated measurements correlated strongly to manual reference measurements. The SFAT depot showed the weakest correlation (r = 0.744). Automated VAT and SAT measurements were slightly, but significantly overestimated (≤4.6%, p ≤ 0.001). Manual segmentation of abdominal sub-depots showed high repeatability (CV ≤ 8.1%, r ≥ 0.930). We conclude that the low dose CT-scanning and automated analysis makes the setup suitable for large-scale studies.

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OBJECTIVES/SPECIFIC AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the United States and increases risk for cirrhosis and liver cancer. Identifying modifiable risk factors for NAFLD could allow better targeting of prevention programs. Insulin resistance (IR) plays a significant role in the development and progression of NAFLD. IR is also an important precursor to the development of type 2 diabetes (T2DM). However, the development and duration of IR during young adulthood and its association with NAFLD and T2DM in midlife is unclear. To test whether trajectories of IR using homeostatic model assessment (HOMA-IR) change throughout early adulthood are associated with risk of prevalent NAFLD and T2DM among persons with NAFLD in midlife independent of current or baseline HOMA-IR. METHODS/STUDY POPULATION: Participants from the CARDIA study, a prospective multicenter population-based biracial cohort of adults (baseline age 18–30 years), underwent HOMA-IR measurement (≥8 h fasting and not pregnant) at baseline (1985–1986) and follow-up exam years 7, 10, 15, 20, and 25. At Year 25 (Y25, 2010–2011), liver fat was assessed by noncontrast computed tomography (CT). NAFLD was defined as CT liver attenuation &lt;51 Hounsfield Units after exclusion of other causes of liver fat (alcohol/hepatitis/medications). Latent mixture modeling was used to identify 25-year trajectories in HOMA-IR over time. Multivariable logistic regression models were used to assess associations between HOMA-IR trajectory groups and prevalent NAFLD with adjustment for baseline or Y25 HOMA-IR. RESULTS/ANTICIPATED RESULTS: Among 3060 participants, we identified 3 distinct trajectory groups for HOMA-IR for individuals free from diabetes in middle adulthood: qualitatively low-stable (46.7% of the cohort), moderate-increasing (42.0%), and high-increasing (11.3%) with a NAFLD prevalence at Y25 of: 8.3%, 33.4%, and 63.5%, respectively (p-trend&lt;0.0001). After adjustment for confounders (baseline smoking status, alcohol use, body mass index, physical activity score, systolic blood pressure, antihypertensive medication use, and total/HDL cholesterol ratio) and baseline HOMA-IR, increasing HOMA-IR trajectories were associated with greater NAFLD prevalence compared with the low-stable trajectory group [odds ratio (95% CI): 5.8 (4.3–7.9) and 22.3 (14.2–34.9) for moderate and high, respectively]. These associations were attenuated, but remained significant, even after controlling for current Y25 HOMA-IR [OR=3.6 (2.6–5.0) for moderate and 5.9 (3.4–10.3) for high (referent: low)]. Among participants with NAFLD (n=511), high-increasing HOMA-IR trajectory was associated with greater prevalent [OR=6.5 (1.6–25.7)] and incident [OR=8.7 (2.2–34.4)] T2DM at Y25 independent of confounders and Y25 HOMA-IR (referent: low-stable). DISCUSSION/SIGNIFICANCE OF IMPACT: In this community-based sample of individuals free from diabetes at baseline, an increasing HOMA-IR trajectory through young adulthood was associated with greater NAFLD prevalence in midlife. Knowledge of changes in IR throughout adulthood provides new information on the risk of T2DM among persons with NAFLD in midlife independent of current level of IR. These findings highlight early identification of increasing IR as a potential target for primary prevention of T2DM in the setting of NAFLD.

Alcohol Use and Cardiovascular Disease Risk in Patients With Nonalcoholic Fatty Liver Disease

Cardiovascular disease (CVD) is the leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD). Moderate drinking (vs abstinence) is associated with lower risk of CVD in the general population. We assessed whether alcohol use is associated with CVD risk in patients with NAFLD. We analyzed data from participants in the Coronary Artery Risk Development in Young Adults longitudinal cohort study of 5115 black and white young adults, 18-30 years old, recruited from 4 cities in the United States from 1985 through 1986. Participants self-reported alcohol use at study entry and then again after 15, 20, and 25 years. At year 25 (2010-2011), participants underwent computed tomography examination of the thorax and abdomen and tissue Doppler echocardiography with myocardial strain measured by speckle tracking. Coronary artery calcification was defined as an Agatston score above 0. NAFLD was defined as liver attenuation <51 Hounsfield Units after exclusions. Drinkers reported 1-21 (men) or 1-14 (women) standard drinks/week at years 15, 20, or 25. Nondrinkers reported no alcohol use at years 15, 20, and25. Of the 570 participants with NAFLD (mean age, 50 years; 54% black; 46% female), 332 (58%) were drinkers; significantly higher proportions of drinkers were white, male, and with higher levels of education compared with nondrinkers (P < .05 for all). Higher proportions of drinkers had obesity, diabetes, and metabolic syndrome compared with nondrinkers (P < .01). There was no difference in liver attenuation between groups (P= .12). After multivariable adjustment, there was no association between alcohol use and CVD risk factors (diabetes, hypertension, hyperlipidemia) or subclinical CVD measures (coronary artery calcification, early transmitral velocity/late (atrial) transmitral velocity (E/A) ratio, global longitudinal strain). In a population-based sample of individuals with NAFLD in midlife, prospectively assessed alcohol use is not associated with significant differences in risk factors for CVD or markers of subclinical CVD. In contrast to general population findings, alcohol use may not reduce the risk of CVD in patients with NAFLD.