Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent among people living with severe obesity (body mass index [BMI] ≥ 35 kg/m2). However, it remains unknown how sex and adipose tissue distribution are related to MAFLD onset and progression into metabolic dysfunction-associated steatohepatitis (MASH) or advanced stages of fibrosis. Methodology: We retrospectively studied patients with severe obesity who were eligible for bariatric surgery. Demographic characteristics, biomarkers, and cardiometabolic comorbidities were reported. Anthropometric indices such as BMI, waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), neck circumference (NC), lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), and body roundness index (BRI) were measured or calculated. MAFLD, MASH, and stages of fibrosis (F1-F4) were established from perioperative liver biopsies. Standardized univariate and multivariate logistic regression analyses were used to examine the association between demographic variables, anthropometric indices, cardiometabolic conditions, and the risk of MASH or severe fibrosis (F2-F4). Results: A total of 2091 participants with severe obesity were included in the analyses; BMI 47.9 ± 7.3 kg/m2, age 46.2 ± 11.2 years, and 68.4% females. Overall, MAFLD prevalence was 79.5%, with 44.5% having MASH and 24.4% having severe fibrosis (Stage 2 or higher). No anthropometric indices of adiposity were associated with MASH or fibrosis severity. In this population, female sex was a risk factor for severe fibrosis (OR: 1.27, 95% CI 1.01-1.59, p < 0.05). Conclusions: MAFLD and MASH are highly prevalent in individuals living with severe obesity, but no anthropometric indices or laboratory tests are good predictors of MAFLD or MASH in this population. When MAFLD is diagnosed, our results suggest that females with severe obesity might be at higher risk of advanced stages of fibrosis.

Ultrasonography (US) in patients with obesity allows us to measure different layers of abdominal fat (superficial subcutaneous, deep subcutaneous, preperitoneal, omental, and perirenal), not assessable by DEXA or CT scan. Omental and perirenal fat depots are considered predictors of metabolic complications. Liraglutide is particularly effective in reducing weight in patients with insulin-resistance, but its direct impact on each abdominal fat layer is unknown.

We measured, at the L4 level, all 5 abdominal fat depots in 860 patients with obesity (72.8% women, mean age 56.6 ± 1.5 years, BMI 34.4 ± 4.7 kg/m2, body fat 47 ± 2%, abdominal circumference 105.8 ± 3 cm), before and after 6 months of liraglutide treatment. Laboratory tests for glucose, insulin, and lipid profile were routinely done. T-student was used to compare intraindividual differences.

Weight loss was 7.5 ± 2.8 kg (7.96% from baseline), with no differences by sex/age/BMI. Greater loss was observed in patients with higher dosages and NAFLD. All US-measured fat layers showed a significant reduction (p < 0.05) at 6th months. Preperitoneal fat showed a -26 ± 5.5% reduction and 46% of the patients went below metabolic syndrome (MS) risk cut-off values. Omental fat was reduced by -17.8 ± 5% (67% of the patients below MS risk) and perirenal fat by -22.4 ± 4.4% (56% of the patients below MS). Both omental and perirenal fat reduction correlated with total and LDL cholesterol. Higher perirenal fat reduction (-28%) was seen among patients with obesity and hypertension. Perirenal fat also correlated with blood pressure reduction.

Liraglutide induces greater fat loss in the layers involved with MS. However, the maximal reduction is seen at perirenal fat, which has been recently related with hypertension and could play an important role in modulating kidney's expansion and intraglomerular pressure. US is a reproducible clinical tool to assess pathologic fat depots in patients living with obesity.

Recent advances in perirenal adipose tissue (PAT) highlighted that PAT might involve in the pathogenesis of chronic inflammatory and dysfunctional metabolic diseases. This study assessed the association between perirenal fat thickness (PrFT) and metabolic dysfunction-associated fatty liver disease (MALFD) in type 2 diabetes mellitus (T2DM).

This study comprised 867 eligible participants with T2DM. Trained reviewers collected anthropometric and biochemical measurements. The diagnosis of MAFLD was based on the latest international expert consensus statement. PrFT and fatty liver were evaluated by computed tomography. The visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by bioelectrical impedance analysis. The non-alcoholic fatty liver disease fibrosis score (NFS) and fibrosis-4 (FIB-4) index were used to assess progressive liver fibrosis in MAFLD.

Overall, the prevalence of MAFLD was 62.3% in T2DM. The PrFT in the MAFLD group was statistically increased than in the non-MAFLD group (P < 0.05). Correlation analysis showed that PrFT was significantly correlated with dysfunctional metabolic factors like body mass index, waist circumference, triglycerides, high-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, uric acid, and insulin resistance. Multiple regression analysis revealed that PrFT was positively correlated with NFS (β=0.146, P<0.001) and FIB-4 (β=0.082, P=0.025) in the MAFLD. In contrast, PrFT was negatively correlated with CT_L-S (β=-0.188, P<0.001). Furthermore, PrFT was also significantly associated with MAFLD independent of VFA and SFA, the OR (95% CI) was 1.279 (1.191-1.374). Meanwhile, PrFT also had a good identifying value for MAFLD as VFA. The area under the curve (95% CI) value of PrFT identifying MAFLD was 0.782 (0.751-0.812). The optimal cut-off value of PrFT was 12.6mm, with a sensitivity of 77.8% and specificity of 70.8%.

PrFT was independently associated with MAFLD, NFS, and FIB-4 and showed a similar identifying value for MAFLD as VFA, which suggested that PrFT can be used as an alternative index to VFA.

Type 2 diabetes mellitus (T2DM) is a risk factor for nonalcoholic fatty liver disease (NAFLD).

To determine the prevalence and clinical correlates of NAFLD in a large cohort of patients with T2DM.

Four hundred thirty-seven participants with T2DM who consulted at Meijo Hospital from April 2019 to September 2020 and underwent computed tomography (CT) were assessed. The mean age was 74 ± 13 years, and 269 were men. Hepatic attenuation minus splenic attenuation (CTL-S) less than 1 Hounsfield unit was considered fatty liver. NAFLD was defined as fatty liver in the absence of significant alcohol consumption and hepatitis virus infection. A multiple logistic regression was used to assess the independent factors associated with NAFLD.

NAFLD was identified in 25.2% of the participants. Young age (odds ratio [OR] = -0.945; 95% confidence interval [CI]: 0.922-0.969), higher hemoglobin levels (OR = 1.501, 95%CI: 1.278-1.764), lower high-density lipoprotein (HDL) cholesterol levels (OR = 0.971, 95%CI: 0.953-0.989), and the absence of dialysis (OR = 0.109, 95%CI: 0.014-0.856) were independent predictors of NAFLD.

NAFLD was detected with CT in 25.2% of the participants. NAFLD was associated with younger age, higher hemoglobin levels, lower HDL cholesterol levels, and an absence of dialysis.

Optimal management of cardiovascular disease should start with the identification of subjects at subclinical stages. However, available tools are not always accurate or affordable. We assess the usefulness of ultrasound-guided measurement of abdominal fat layers as a surrogate marker of cardiovascular risk. We performed a cross-sectional, case-control, exploratory, pilot study in 10 people living with HIV (PLWH) and 10 HIV-uninfected subjects (control group) matched for age, sex, and body mass index. All participants were men 45-60 years of age, with no active disease or previous abdominal surgery; the PLWH group had been virologically suppressed for ≥2 years under stable antiretroviral therapy. The thickness of abdominal superficial and deep subcutaneous fat, preperitoneal fat, omental (periaortic) fat, and retroperitoneal (perirenal) fat was compared between both groups. Correlations between fat layers and traditional markers of cardiovascular risk were assessed. The thickness of most layers was always higher among PLWH. The differences were statistically significant for the preperitoneal fat layer (p = .04). The presence of atherosclerotic plaque was correlated with the preperitoneal fat layer in the PLWH group (odds ratio = 1.49, p = .02), and metabolic syndrome was correlated with superficial subcutaneous fat, although this was low (odds ratio = 0.54, p = .02). In the control group, several associations were found between carotid intima media thickness and abdominal fat layers. All abdominal fat layers were thicker in the PLWH group, especially preperitoneal fat, and several associations were found between specific fat layers and traditional cardiovascular risk markers. Our results suggest that the thickness of abdominal fat layers, assessed by ultrasound, could be a marker of cardiovascular risk. However, further studies with larger populations are required to confirm these findings.

Noninvasive measures to estimate liver fibrosis in lieu of biopsy in nonalcoholic liver disease (NAFLD) can broadly differentiate high vs low degrees of condition extent. However, an "indeterminate score" necessitates further clinical investigation and biopsy becomes essential, highlighting the need for identification of other noninvasive factors with accuracy for this midlevel extent and its prognosis. Lean NAFLD cases are of particular interest regarding this issue, as they present as otherwise healthy, and will benefit greatly from the less invasive assessment.

To estimate the agreement of two noninvasive assessment tools in lean NAFLD patients, and assess factors related to indeterminate scores.

Ultrasound-diagnosed NAFLD patients, without sign of other chronic liver disease (n = 1262), were enrolled from a tertiary private medical centre between 2016-2019. After grouping by body mass index (obese, overweight, and lean), each participant underwent FibroScan. NAFLD fibrosis score (NFS) was used for subclassification (lower, higher, and indeterminate). No patient underwent liver biopsy. The kappa statistic was used to assess inter-rater agreement between the three groups on liver fibrosis degree assessed via FibroScan and NFS. Indeterminate score among the three groups was assessed to identify factors that predict its determination.

The NAFLD study cohort was composed of lean (159/1262, 12.6%), overweight (365/1262, 29%) and obese (737/1262, 58.4%) individuals. The lean patients were significantly younger (49.95 ± 15.3 years, P < 0.05), with higher serum high density lipoprotein (52.56 ± 16.27 mg/dL, P < 0.001) and lower prevalences of type 2 diabetes mellitus, hypertension and hyperlipidaemia. All groups showed a predominance of lower fibrosis degree. The lean NAFLD patients showed a significantly lower NFS (P < 0.001). Degree of agreement between FibroScan and NFS was fair between the lean and obese NAFLD categories, and moderate in the overweight category. NFS was predictive of indeterminate score. Age was a factor among all the body mass index (BMI) categories; other associated factors, but with less strength, were serum alanine aminotransferase in the overweight category and BMI in the obese category.

Lean NAFLD patients showed lower degree and prevalence of liver fibrosis by NFS; however, follow-up biopsy is still needed.

Background: Information of the relationships between body mass parameters and the severity of fatty liver is deficient in pediatric nonalcoholic fatty liver disease (NAFLD). Methods: The relationships between body mass parameters (waist circumference [WC], body mass index [BMI], and abdominal subcutaneous fat thickness [ASFT]) and the severity of fatty liver were prospectively evaluated in pediatric patients who are overweight or obese, suffering from NAFLD. Ultrasonography was performed to assess fatty liver and its severity on a three-grade scale (low-grade fatty liver [LGFL], grade 1 or 2; high-grade fatty liver [HGFL], grade 3). Results: A total of 110 subjects (55 LGFL and 55 HGFL) aged 6.2-17.9 years were included. The WC, BMI, and ASFT values were significantly higher in the HGFL group compared to those in the LGFL group (p = 0.00004, 0.01, and 0.04, respectively). WC had the greatest power to predict HGFL under receiver-operating characteristic curve analyses and was positively correlated with the severity of fatty liver in subjects aged 6-12-year old and 13-17-year old (p = 0.007, and 0.0039, respectively). ASFT showed a positive correlation with the severity of fatty liver in subjects aged 13-17-year old (p = 0.04). Conclusions: WC, BMI, and ASFT are predictive of severe NAFLD among children who are overweight and obese; particularly, WC has the most predictive accuracy. Among the parameters, WC and ASFT are predictive in specific age groups.

Abdominal fat ultrasound (US) is a simple clinical tool that may allow measures of fat depots not visible using common dual-energy X-ray absorptiometry (DEXA) or computerized tomography (CT) imaging. The aim of this study was to validate the technique, give measures of superficial and profound subcutaneous, preperitoneal, omental and perirenal (retroperitoneal) fat and correlate them with MS markers.

Sequential US measures of these five abdominal fat layers were done at 397 adults. Blood pressure (BP), body mass index (BMI), waist, body fat %, HOMA-IR index (homeostatic model assessment of insulin resistance), lipid profile and leptin were recorded. Metabolic syndrome (MS) was defined according to Cholesterol education programme adult treatment panel III (ATPIII) criteria.

Subcutaneous and omental fat were increased among people with obesity, whereas preperitoneal and perirenal fat did not show any difference according to BMI or waist. Women showed thicker subcutaneous fat (both superficial and profound), whereas men had bigger omental fat. Both postmenopausal and diabetic patients had changes in omental fat only, whereas patients with fatty liver showed thicker preperitoneal and perirenal fat, as well. MS patients showed both thicker perirenal and omental fat. A cut-off of 54 mm in male (M)/34 mm in female (F) of omental fat and 22.5 mm (M)/12.5 mm (F) of perirenal fat could be predictive of later MS onset.

US is a valid method to measure all different abdominal fat depots. Omental and perirenal fat measures may classify patients at risk for MS. Preperitoneal fat depot may also correlate with fatty liver disease.

Background: Obesity, insulin resistance, and diabetes are major risk factors for nonalcoholic fatty liver disease (NAFLD). This study aims to evaluate the association between different grades of NAFLD and abdominal subcutaneous fat thickness with the homeostasis model assessment of insulin resistance (HOMA-IR). Methods: In this pilot study, 59 obese nondiabetic participants with NAFLD were enrolled. Total cholesterol, Hb_A1c, and HOMA-IR were measured. Abdominal subcutaneous fat thickness in the midline just below the xiphoid process in front of the left lobe of the liver (LSFT) and in the umbilical region (USFT), and the degree of hepatic steatosis, were evaluated by ultrasound scans, and their correlation with the degree of steatosis and the NAFLD Activity Score in liver biopsy was assessed. Results: Of the 59 studied participants, 15 had mild, 17 had moderate, and 27 had severe hepatic steatosis by abdominal ultrasound. The mean ± SD HOMA-IR level in NAFLD patients was 5.41±2.70. The severity of hepatic steatosis positively correlated with body mass index (P<0.001), HOMA-IR (P<0.001), serum triglycerides (P=0.001), LSFT (P<0.001), and USFT (P<0.001). Receiver operating characteristics analysis showed that LSFT at a cut-off of 3.45 cm is the most accurate predictor of severe hepatic steatosis, with 74.1% sensitivity and 84.4% specificity. The best cut-off of USFT for identifying severe hepatic steatosis is 4.55 cm, with 63% sensitivity and 81.3% specificity. Conclusion: Abdominal subcutaneous fat thicknesses in front of the left lobe of the liver and in the umbilical region, together with HOMA-IR, are reliable indicators of the severity of NAFLD in obese nondiabetic individuals.

Fat distribution may have prognostic value in the evaluation of non-alcoholic fatty liver disease. This study was conducted to evaluate associations of magnetic resonance imaging-measured abdominal fat areas with steatosis, steatohepatitis, and fibrosis, assessed histopathologically, in patients with type 2 diabetes.

This prospective study included 66 patients with type 2 diabetes (12 males, 54 females, age 26-68 years), without chronic liver disease of other causes. Axial dual-echo magnetic resonance images were acquired. Visceral, subcutaneous, and preperitoneal fat areas were measured using Osirix software. Liver biopsy specimens were obtained from all patients and examined histopathologically to evaluate steatosis, steatohepatitis, and fibrosis. Linear (for steatosis) and logistic (for steatohepatitis and fibrosis) regression models were fitted for the outcomes. R2 was used as a measure of how much model variance the predictors explained and to compare different predictors of the same outcome.

Visceral and preperitoneal fat areas correlated well with histopathologically determined liver steatosis grade (both P = 0.004) and liver fibrosis (P = 0.008 and P = 0.037, respectively). All fat areas correlated well with steatohepatitis (P ≤ 0.002). Preperitoneal and visceral fat areas were the best predictors of steatohepatitis (R2 = 0.379) and fibrosis (R2 = 0.181), respectively.

Visceral fat area was the best predictor of fibrosis in patients with type 2 diabetes. Preperitoneal fat area was the best predictor of steatohepatitis and is a potential new non-invasive marker for use in the screening of these patients to detect more aggressive forms of non-alcoholic fatty liver disease.