Association between severity of nonalcoholic fatty liver disease and major adverse cardiovascular events in patients assessed by coronary computed tomography angiography.

BACKGROUND: The effect of nonalcoholic fatty liver disease (NAFLD) on major adverse cardiovascular events (MACEs) can be influenced by the degree of coronary artery stenosis. However, the association between the severity of NAFLD and MACEs in patients who underwent coronary computed tomography angiography (CCTA) is unclear. METHODS: A total of 341 NAFLD patients who underwent CCTA were enrolled. The severity of NAFLD was divided into mild NAFLD and moderate-severe NAFLD by abdominal CT results. The degree of coronary artery stenosis was evaluated by using Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Cox regression analysis and Kaplan-Meier analysis were used to assess poor prognosis. RESULTS: During the follow-up period, 45 of 341 NAFLD patients (13.20%) who underwent CCTA occurred MACEs. The severity of NAFLD (hazard ratio [HR] = 2.95[1.54-5.66]; p = 0.001) and CAD-RADS categories 3-5 (HR = 16.31[6.34-41.92]; p < 0.001) were independent risk factors for MACEs. The Kaplan-Meier analysis showed that moderate to severe NAFLD patients had a worsen prognosis than mild NAFLD patients (log-rank p < 0.001). Moreover, the combined receiver operating characteristic curve of the severity of NAFLD and CAD-RADS category showed a good predicting performance for the risk of MACEs, with an area under the curve of 0.849 (95% CI = 0.786-0.911). CONCLUSION: The severity of NAFLD was independent risk factor for MACEs in patients with obstructive CAD, having CAD-RADS 3-5 categories on CCTA.

Prognostic value of metabolic dysfunction-associated steatotic liver disease over coronary computed tomography angiography findings: comparison with no-alcoholic fatty liver disease.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the proposed name change for non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of cardiovascular disease risk with MASLD and NAFLD in patients who underwent clinically indicated coronary computed tomography angiography (CCTA). METHODS: This retrospective study included 2289 patients (60% men; mean age: 68 years) with no history of coronary artery disease who underwent CCTA. The steatotic liver was defined as a hepatic-to-spleen attenuation ratio of < 1.0 on CT just before CCTA. MASLD is defined as the presence of hepatic steatosis along with at least one of the five cardiometabolic risk factors. Adverse CCTA findings were defined as obstructive and/or high-risk plaques. Major adverse cardiac events (MACE) encompassed composite coronary events, including cardiovascular death, acute coronary syndrome, and late coronary revascularization. RESULTS: MASLD and NAFLD were identified in 415 (18%) and 368 (16%) patients, respectively. Adverse CCTA findings were observed in 40% and 38% of the patients with MASLD and with NAFLD, respectively. Adverse CCTA findings were significantly associated with MASLD (p = 0.007) but not NAFLD (p = 0.253). During a median follow-up of 4.4 years, 102 (4.4%) MACE were observed. MASLD was significantly associated with MACE (hazard ratio 1.82, 95% CI 1.18-2.83, p = 0.007), while its association with NAFLD was not significant (p = 0.070). By incorporating MASLD into a prediction model of MACE, including the risk score and adverse CCTA findings, global chi-squared values significantly increased from 87.0 to 94.1 (p = 0.008). CONCLUSIONS: Patients with MASLD are likely to have a higher risk of cardiovascular disease than those with NAFLD. Concurrent assessment of MASLD during CCTA improves the identification of patients at a higher risk of cardiovascular disease among those with clinically indicated CCTA.

Correlation of alanine aminotransferase levels and a histological diagnosis of steatohepatitis with ultrasound-diagnosed metabolic-associated fatty liver disease in patients from a centre in Nigeria.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is defined as the occurrence of hepatic fat accumulation in patients with negligible alcohol consumption or any other cause of hepatic steatosis. This study aimed to correlate the ultrasound-based diagnosis of MAFLD with the histological diagnosis of nonalcoholic steatohepatitis (NASH) and alanine aminotransferase (ALT) levels in patients with MAFLD. METHODS: This was a hospital-based cross-sectional study of 71 patients with MAFLD diagnosed by ultrasound. Percutaneous liver biopsy was performed for histological evidence of NASH in all patients, regardless of liver function test (LFT) values, provided that they had no contraindications. Liver histology was graded using the NASH Clinical Research Network MAFLD Activity Score. The data obtained were entered into SPSS version 21 and analysed using descriptive and inferential statistics. The significance level was set at < 0.05. RESULTS: A total of 71 patients (26 males and 45 females) with MAFLD were included. Thirty-nine (76.5%) patients with MAFLD and normal ALT levels had NASH, while 14 (82.4%) had elevated ALT levels. There was no statistically significant difference in the histological grade of NASH between patients with normal and elevated ALT levels. A weak correlation was found between the severity of steatosis on ultrasound scan and NASH incidence (p = 0.026). The sensitivity and specificity of ALT levels for predicting NASH according to the area under the receiver operating characteristics (AUROC 0.590) at an ALT cut-off value of 27.5 IU/L were 55.8% and 64.7%, respectively. CONCLUSION: NASH can occur in patients with MAFLD, irrespective of alanine transaminase (ALT) levels, and ultrasound grading of the severity of steatosis cannot accurately predict NASH. Liver biopsy remains the investigation of choice.

FibroScan-aspartate transaminase: A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) with hepatic histological NAFLD activity score ≥ 4 and fibrosis stage F ≥ 2 is regarded as "at risk" non-alcoholic steatohepatitis (NASH). Based on an international consensus, NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), respectively; hence, we introduced the term "high-risk MASH". Diagnostic values of seven non-invasive models, including FibroScan-aspartate transaminase (FAST), fibrosis-4 (FIB-4), aspartate transaminase to platelet ratio index (APRI), etc. for high-risk MASH have rarely been studied and compared in MASLD. AIM: To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH. METHODS: A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital, between January 2012 and December 2020. After screening for MASLD and the exclusion criteria, 279 patients were included and categorized into high-risk and non-high-risk MASH groups. Utilizing threshold values of each model, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV), were calculated. Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve (AUROC). RESULTS: MASLD diagnostic criteria were met by 99.4% patients with NAFLD. The MASLD population was analyzed in two cohorts: Overall population (279 patients) and the subgroup (117 patients) who underwent liver transient elastography (FibroScan). In the overall population, FIB-4 showed better diagnostic efficacy and higher PPV, with sensitivity, specificity, PPV, NPV, and AUROC of 26.9%, 95.2%, 73.5%, 72.2%, and 0.75. APRI, Forns index, and aspartate transaminase to alanine transaminase ratio (ARR) showed moderate diagnostic efficacy, whereas S index and gamma-glutamyl transpeptidase to platelet ratio (GPR) were relatively weaker. In the subgroup, FAST had the highest diagnostic efficacy, its sensitivity, specificity, PPV, NPV, and AUROC were 44.2%, 92.3%, 82.1%, 67.4%, and 0.82. The FIB-4 AUROC was 0.76. S index and GPR exhibited almost no diagnostic value for high-risk MASH. CONCLUSION: FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI, Forns index, ARR, S index, and GPR; FAST is superior to FIB-4.

Dietary inflammatory index in relation to the progression of hepatic steatosis and liver fibrosis: evaluation by elastography/Fibroscan.

One of the proposed mechanisms by which nutrition influences the progression of hepatic steatosis to fibrosis is inflammation. The study investigated how the inflammatory potential of the diet affects the risk of liver damage in patients with nonalcoholic fatty liver disease (NAFLD), a condition where fat accumulates in the liver. This cross-sectional study included 170 outpatients with newly diagnosed NAFLD. This study used a device called Fibroscan® to measure the degree of liver fibrosis, which is the scarring of the liver tissue due to chronic inflammation. The study also used a tool called the Dietary Inflammatory Index (DII) to measure the inflammatory potential of the diet based on the intake of different foods and nutrients. In the findings of the study, patients with more severe fat accumulation in the liver (hepatic steatosis) had higher DII scores, meaning they had more inflammatory diets. The study also found that higher DII scores were associated with higher weight and body mass index (BMI). One standard deviation (SD) increase in DII scores was associated with a 0.29 kilopascal (95% CI: 0.10-0.44; P-value 0.001) increase in the mean liver stiffness, an indicator of liver fibrosis. The study concluded that patients with higher DII scores had a higher risk of developing liver fibrosis than those with lower DII scores, even after adjusting for confounding factors (odds ratio: 5.89; P-value: 0.001). The study suggested that eating less inflammatory foods may help prevent or slow down the progression of hepatic steatosis and liver in patients with NAFLD.

Association between nonalcoholic fatty liver disease and left ventricular diastolic dysfunction: A 7-year retrospective cohort study of 3,380 adults using serial echocardiography.

AIM: Left ventricular diastolic dysfunction (LVDD) has been observed in people with nonalcoholic fatty liver disease (NAFLD) in cross-sectional studies but the causal relationship is unclear. This study aimed to investigate the impact of NAFLD and the fibrotic progression of the disease on the development of LVDD, assessed by serial echocardiography, in a large population over a 7-year longitudinal setting. METHODS: This retrospective cohort study included the data of 3,380 subjects from a medical health check-up program. We defined subjects having NAFLD by abdominal ultrasonography and assessed significant liver fibrosis by the aspartate transaminase (AST) to platelet ratio index (APRI), the NAFLD fibrosis score (NFS), and the fibrosis-4 (FIB-4) index. LVDD was defined using serial echocardiography. A parametric Cox proportional hazards model was used. RESULTS: During 11,327 person-years of follow-up, there were 560 (16.0 %) incident cases of LVDD. After adjustment for multiple risk factors, subjects with NAFLD showed an increased adjusted hazard ratio (aHR) of 1.21 (95 % confidence interval [CI]=1.02-1.43) for incident LVDD compared to those without. The risk of LV diastolic dysfunction increased progressively with increasing degree of hepatic steatosis (P< 0.001). Compared to subjects without NAFLD, the multivariable-aHR (95 % CI) for LVDD in subjects with APRI < 0.5 and APRI ≥ 0.5 were 1.20 (1.01-1.42) and 1.36 (0.90-2.06), respectively (P= 0.036), while other fibrosis prediction models (NFS and FIB-4 index) showed insignificant results. CONCLUSIONS: This study demonstrated that NAFLD was associated with an increased risk of LVDD in a large cohort. More severe forms of hepatic steatosis and/or significant liver fibrosis may increase the risk of developing LVDD.

Relationship between skeletal muscle mass loss and metabolic dysfunction-associated fatty liver disease among Chinese patients with metabolic dysregulation.

OBJECTIVE: The aim of this study was to explore the correlation between skeletal muscle content and the presence and severity of metabolic dysfunction-associated fatty liver disease in patients with metabolic dysregulation in China. METHODS: A cross-sectional study was conducted among patients from the endocrinology outpatient department at Ningbo First Hospital, in Ningbo, China, in April 2021. Adult patients with metabolic dysregulation who accepted FibroScan ultrasound were included in the study. However, those without clinical data on skeletal muscle mass were excluded. FibroScan ultrasound was used to noninvasively evaluate metabolic dysfunction-associated fatty liver disease. The controlled attenuation parameter was used as an evaluation index for the severity of liver steatosis. Bioelectrical impedance analysis was used to measure the skeletal muscle index. RESULTS: A total of 153 eligible patients with complete data were included in the final analysis. As the grading of liver steatosis intensifies, skeletal muscle index decreases (men: Ptrend<0.001, women: Ptrend=0.001), while body mass index, blood pressure, blood lipid, uric acid, aminotransferase, and homeostatic model assessment of insulin resistance increase (Ptrend<0.01). After adjusting for confounding factors, a negative association between skeletal muscle index and the presence of metabolic dysfunction-associated fatty liver disease was observed in men (OR=0.691, p=0.027) and women (OR=0.614, p=0.022). According to the receiver operating characteristic curve, the best cutoff values of skeletal muscle index for predicting the metabolic dysfunction-associated fatty liver disease presence were 40.37% for men (sensitivity, 87.5%; specificity, 61.5%) and 33.95% for women (sensitivity, 78.6%; specificity, 63.8%). CONCLUSION: Skeletal muscle mass loss among patients with metabolic dysregulation was positively associated with metabolic dysfunction-associated fatty liver disease severity in both sexes. The skeletal muscle index cutoff value could be used to predict metabolic dysfunction-associated fatty liver disease.

Non-alcoholic fatty liver disease in Tanzania: prevalence, determinants, and diagnostic performance of triglycerides-glucose index and triglycerides-glucose index -body mass index compared to the hepatic ultrasound in overweight and obese individuals.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), which is closely associated with metabolic syndrome (MetS), is rarely reported in Tanzania, where MetS is prevalent. The purpose of this study was to determine the prevalence and associated factors of this condition in overweight and obese individuals and to correlate standard ultrasound diagnosis with triglyceride-glucose index (TyG) and TyG-body mass index (TyG-BMI). METHODS: A cross-sectional analysis was performed in 181 adult outpatients attending a general medical clinic. The presence of fatty liver was detected by ultrasound. Demographic, clinical, and laboratory data were collected and analyzed using STATA 15. To compare categorical variables, a chi-square test was employed, while a Student's t-test was used to compare continuous variables. Additionally, a multivariate regression analysis was conducted to identify the determinants of NAFLD. A significance level was set at p < 0.05. The discriminatory power of TyG and TyG-BMI for diagnosing NAFLD was evaluated using Receiver Operating Characteristic (ROC) Curve analysis and the Area Under the ROC Curve (AUC) was reported. RESULTS: The overall prevalence of NAFLD was 30.4% (55/181). The prevalence's of NAFLD in patients with class III obesity, class II obesity, class I obesity and overweight were 50.0% (12/24),, 38% (19/50), 23.7% (18/76), and 19.5% (6/31),respectively. NAFLD was strongly predicted by hyperuricemia (≥ 360 µmol/L) (p = 0.04) and TyG ≥ 8.99 (p = 0.003). The best cut-off values of TyG and TyG-BMI to predict NAFLD were 8.99 [AUC 0.735; sensitivity 70.9%, specificity 79.3%] and 312 [AUC 0.711; sensitivity 60% and specificity 75.4%] respectively. CONCLUSIONS: The prevalence of NAFLD is high among people with overweight and obesity in Tanzania. We did not find sufficient evidence to recommend the use of TyG and TyG-BMI as surrogates for hepatic ultrasound in detecting NAFLD, and further evaluation is recommended.

The association between dietary inflammatory index (DII) scores and c-reactive protein (CRP) and nonalcoholic fatty liver disease (NAFLD) in a general population cohort.

BACKGROUND AND AIMS: Although there is extensive literature showing the ability of the dietary inflammation index (DII®) to predict concentrations of plasma inflammatory markers, few studies are testing the association between DII scores and nonalcoholic fatty liver disease (NAFLD). Considering the high prevalence of NAFLD and its complications, we conducted a validation study of DII scores and examined its association with NAFLD in the general adult population of Iran. METHODS: This cross-sectional study was conducted on 3110 adult participants in the Amol Cohort Study (AmolCS) who underwent abdominal ultrasonography to diagnose NAFLD. DII and energy-adjusted DII (E-DII™) scores were computed using data from a valid semi-quantitative 168-item food frequency questionnaire (FFQ). Multivariable logistic regression adjusting for socio-demographic, lifestyle, and health-related factors was used to assess association. RESULTS: The EDII was associated with CRP inflammatory biomarker. Participants in the highest, i.e., most pro-inflammatory tertile had the highest odds of NAFLD by ultrasound in all models [fully adjusted model: OR (95 % CI) tertile3vs.1:1.54 (1.05-2.05); Ptrend = 0.04, and 1.63 (1.19-2.21); Ptrend = 0.03 in women and men, respectively]. The highest tertile had the highest OR for NAFLD by fatty liver index (FLI) only in men [fully adjusted model OR (95 % CI) tertile3vs.1: 1.77 (1.15-2.71); Ptrend = 0.01]. Similar results were also obtained for NAFLD by hepatic steatosis index (HSI) in women [fully adjusted model: OR (95 % CI) tertile3vs.1: 1.70 (1.12-2.58); Ptrend = 0.03]. The results of the fully adjusted multivariable model of liver markers and NAFLD status, stratified by gender and abdominal obesity, revealed that the highest tertiles had the highest OR for NAFLD by ultrasound and NAFLD by FLI only in men without abdominal obesity [fully adjusted model: OR (95 % CI) tertile3vs.1: 1.83 (1.17-2.84); Ptrend = 0.03, and, respectively]. NAFLD by FLI tended to increase strongly with tertile E-DII scores in men without abdominal obesity in crude and three adjusted models [full-adjusted model: OR (95 % CI) tertile3vs.1: 3.64 (1.56-8.46); Ptrend = 0.005]. By contrast, women with abdominal obesity in the highest tertile had the highest OR for NAFLD by ultrasound in all models [full-adjusted model: OR (95 % CI) tertile3vs.1: 1.67 (1.07-2.62); Ptrend = 0.02]. CONCLUSIONS: Our results suggest that diet plays a role in regulating inflammation. Additionally, we observed an inflammatory diet predicts the risk of NAFLD in Iranian adults. However, longitudinal studies are required in order to further substantiate the utility of the DII in the development of more effective dietary interventions among populations at risk of chronic disease.

Nonalcoholic Fatty Liver Disease, Bone and Muscle Quality in Prolactinoma: A Pilot Study.

OBJECTIVE: Hyperprolactinemia has negative impacts on metabolism and musculoskeletal health. In this study, individuals with active prolactinoma were evaluated for nonalcoholic fatty liver disease (NAFLD) and musculoskeletal health, which are underemphasized in the literature. METHODS: Twelve active prolactinoma patients and twelve healthy controls matched by age, gender, and BMI were included. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was used to evaluate hepatic steatosis and magnetic resonance elastography (MRE) to evaluate liver stiffness measurement (LSM). Abdominal muscle mass, and vertebral MRI-PDFF was also evaluated with MRI. Body compositions were evaluated by dual energy X-ray absorptiometry (DXA). The skeletal muscle quality (SMQ) was classified as normal, low and weak by using "handgrip strength/appendicular skeletal muscle mass (HGS/ASM)" ratio based on the cut-off values previously stated in the literature. RESULTS: Prolactin, HbA1c and CRP levels were higher in prolactinoma patients (p<0.001, p=0.033 and p=0.035, respectively). The median MRI-PDFF and MRE-LSM were 3.0% (2.01-15.20) and 2.22 kPa (2.0-2.5) in the prolactinoma group and 2.5% (1.65-10.00) and 2.19 kPa (1.92-2.54) in the control group, respectively and similiar between groups. In prolactinoma patients, liver MRI-PDFF showed a positive and strong correlation with the duration of disease and traditional risk factors for NAFLD. Total, vertebral and pelvic bone mineral density was similar between groups, while vertebral MRI-PDFF tended to be higher in prolactinoma patients (p=0.075). Muscle mass and strength parameters were similar between groups, but HGS/ASM tended to be higher in prolactinoma patients (p=0.057). Muscle mass was low in 33.3% of prolactinoma patients and 66.6 of controls. According to SMQ, all prolactinoma patients had normal SMQ, whereas 66.6% of the controls had normal SMQ. CONCLUSION: Prolactinoma patients demonstrated similar liver MRI-PDFF and MRE-LSM to controls despite their impaired metabolic profile and lower gonadal hormone levels. Hyperprolactinemia may improve muscle quality in prolactinoma patients despite hypogonadism.

Screening the General Population for Non-Alcoholic Fatty Liver Disease: Model Development and Validation.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Screening the general population for this may help to select appropriate diagnostic and preventive measures before disease progression. AIMS: We aimed to develop a screening method to identify patients with NAFLD in the general population. METHODS: We analyzed cross-sectional data from a large Japanese study of NAFLD. Principal component analysis was used to analyze the data. Candidate predictors were patients' demographic, clinical, and laboratory characteristics. The resulting model was externally validated using three data sets from different populations. RESULTS: Of 15,464 (54.5% men) included patients, 2,741 (17.7%) had NAFLD as determined by ultrasonography. An index was calculated as the arithmetic mean of the scaled body mass index and serum triglyceride levels for both men and women. The area under the receiver operating characteristic curve, sensitivity, specificity, and false positive rate were 0.875, 0.824, 0.770, and 17.6%, respectively. The mean index values were significantly different between the patients with and without non-alcoholic fatty liver disease (p <0.001). The odds ratio of the index cutoff was 15.6 (95% confidence interval [CI]:14.05, 17.39). The model yielded areas under the curve of 0.828, 0.851, and 0.836 for a Chinese (N = 2,319), an Iranian (N = 2,160), and a Brazilian (N = 45,029) data set, respectively. CONCLUSIONS: The proposed composite index demonstrated high performance and generalizability, suggesting its potential use as a screening tool for NAFLD in the general population.

Correlation between magnetic resonance imaging proton density fat fraction (MRI-PDFF) and liver biopsy to assess hepatic steatosis in obesity.

Obesity is highly associated with Non-alcoholic fatty liver disease (NAFLD) and increased risk of liver cirrhosis and liver cancer-related death. We determined the diagnostic performance of the complex-based chemical shift technique MRI-PDFF for quantifying liver fat and its correlation with histopathologic findings in an obese population within 24 h before bariatric surgery. This was a prospective, cross-sectional, Institutional Review Board-approved study of PDFF-MRI of the liver and MRI-DIXON image volume before bariatric surgery. Liver tissues were obtained during bariatric surgery. The prevalence of NAFLD in the investigated cohort was as high as 94%. Histologic hepatic steatosis grades 0, 1, 2, and 3 were observed in 3 (6%), 25 (50%), 14 (28%), and 8 (16%) of 50 obese patients, respectively. The mean percentages of MRI-PDFF from the anterior and posterior right hepatic lobe and left lobe vs. isolate left hepatic lobe were 15.6% (standard deviation [SD], 9.28%) vs. 16.29% (SD, 9.25%). There was a strong correlation between the percentage of steatotic hepatocytes and MRI-PDFF in the left hepatic lobe (r = 0.82, p < 0.001) and the mean value (r = 0.78, p < 0.001). There was a strong correlation between MRI-derived subcutaneous adipose tissue volume and total body fat mass by dual-energy X-ray absorptiometry, especially at the L2-3 and L4 level (r = 0.85, p < 0.001). MRI-PDFF showed good performance in assessing hepatic steatosis and was an excellent noninvasive technique for monitoring hepatic steatosis in an obese population.

Relation between non-alcoholic fatty liver disease and carotid artery intimal media thickness as a surrogate for atherosclerosis: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis without heavy alcohol consumption or other chronic conditions, encompasses a spectrum from non-alcoholic fatty liver to non-alcoholic steatohepatitis leading to cirrhosis. This analysis aimed to investigate the correlation between NAFLD and carotid intimal media thickness (C-IMT), a non-invasive surrogate for atherosclerosis. METHODOLOGY: Database searches, including PubMed, EMBASE and Cochrane Library, yielded studies up to April 2023. Included were studies exploring the NAFLD-C-IMT relationship in populations aged >18 years. Exclusions comprised non-English papers, those involving animals or pediatric populations and studies lacking control groups. RESULTS: No statistical significance was noted between mild and moderate NAFLD compared to the control group regarding C-IMT [95% confidence intervals (CI): -0.03, 0.12] and (95% CI: -0.03, 0.21), respectively. There was a statistically significant difference only in the Severe NAFLD group ( P value 0.03). NAFLD with and without metabolic syndrome showed statistically significant differences compared to control regarding C-IMT (95% CI: 0.04, 0.12) and (95% CI: 0.01, 0.07), respectively. Fifty-nine studies were mentioned without classification of NAFLD severity and revealed a high statistically significant difference between NAFLD and controls regarding C-IMT with (95% CI: 0.09, 0.12, P < 0.00001). Stratified analysis according to sex was done in two studies and revealed statistical differences between NAFLD and control regarding C-IMT in both groups. CONCLUSION: This meta-analysis underscores a significant association between NAFLD and increased C-IMT, emphasizing the importance of assessing C-IMT in NAFLD patients to identify cardiovascular risk and tailor therapeutic interventions for improved patient outcomes.

Imaging and prognostic characterization of fat-containing hepatocellular carcinoma subtypes.

PURPOSE: Steatohepatitic hepatocellular carcinoma (SH-HCC) is characterized by intratumoral fat with > 50% inflammatory changes. However, intratumoral fat (with or without inflammation) can also be found in not-otherwise specified HCC (NOS-HCC). We compared the imaging features and outcome of resected HCC containing fat on pathology including SH-HCC (> 50% steatohepatitic component), NOS-HCC with < 50% steatohepatitic component (SH-NOS-HCC), and fatty NOS-HCC (no steatohepatitic component). MATERIAL AND METHODS: From September 2012 to June 2021, 94 patients underwent hepatic resection for fat-containing HCC on pathology. Imaging features and categories were assessed using LIRADS v2018. Fat quantification was performed on chemical-shift MRI. Recurrence-free and overall survival were estimated. RESULTS: Twenty-one patients (26%) had nonalcoholic steatohepatitis (NASH). The median intra-tumoral fat fraction was 8%, with differences between SH-HCC and SH-NOS-HCC (9.5% vs. 5% p = 0.03). There was no difference in major LI-RADS features between all groups; most tumors were classified as LR-4/5. A mosaic architecture on MRI was rare (7%) in SH-HCC, a fat in mass on CT was more frequently depicted (48%) in SH-HCC. A combination of NASH with no mosaic architecture on MRI or NASH with fat in mass on CT yielded excellent specificity for diagnosing SH-HCC (97.6% and 97.7%, respectively). The median recurrence-free and overall survival were 58 and 87 months, with no difference between groups (p = 0.18 and p = 0.69). CONCLUSION: In patients with NASH, an SH-HCC may be suspected in L4/LR-5 observations with no mosaic architecture at MRI or with fat in mass on CT. Oncological outcomes appear similar between fat-containing HCC subtypes.

Comparative study of ultrasound attenuation analysis and controlled attenuation parameter in the diagnosis and grading of liver steatosis in non-alcoholic fatty liver disease patients.

PURPOSE: To assess the diagnostic performance of Ultrasound Attenuation Analysis (USAT) in the diagnosis and grading of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) using Controlled Attenuation Parameters (CAP) as a reference. MATERIALS AND METHODS: From February 13, 2023, to September 26, 2023, participants underwent CAP and USAT examinations on the same day. We used manufacturer-recommended CAP thresholds to categorize the stages of hepatic steatosis: stage 1 (mild) - 240 dB/m, stage 2 (moderate) - 265 dB/m, stage 3 (severe) - 295 dB/m. Receiver Operating Characteristic curves were employed to evaluate the diagnostic accuracy of USAT and determine the thresholds for different levels of hepatic steatosis. RESULTS: Using CAP as the reference, we observed that the average USAT value increased with the severity of hepatic steatosis, and the differences in USAT values among the different hepatic steatosis groups were statistically significant (p < 0.05). There was a strong positive correlation between USAT and CAP (r = 0.674, p < 0.0001). When using CAP as the reference, the optimal cut-off values for diagnosing and predicting different levels of hepatic steatosis with USAT were as follows: the cut-off value for excluding the presence of hepatic steatosis was 0.54 dB/cm/MHz (AUC 0.96); for mild hepatic steatosis, it was 0.59 dB/cm/MHz (AUC 0.86); for moderate hepatic steatosis, it was 0.73 dB/cm/MHz (AUC 0.81); and for severe hepatic steatosis, it was 0.87 dB/cm/MHz (AUC 0.87). CONCLUSION: USAT exhibits strong diagnostic performance for hepatic steatosis and shows a high correlation with CAP values.

Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis. METHODS: Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participants were utilized to evaluate genetically predicted liver fat and volume. Data from the ENIGMA Consortium, comprising 51,665 patients, were used to evaluate the associations between genetic susceptibility, NAFLD risk, liver fat, liver volume, and alterations in cortical thickness (TH) and surface area (SA). Inverse-variance weighted (IVW) estimation, Cochran Q, and MR-Egger were employed to assess heterogeneity and pleiotropy. RESULTS: Overall, NAFLD did not significantly affect cortical SA or TH. However, potential associations were noted under global weighting, relating heightened NAFLD risk to reduced parahippocampal SA and decreased cortical TH in the caudal middle frontal, cuneus, lingual, and parstriangularis regions. Liver fat and volume also influenced the cortical structure of certain regions, although no Bonferroni-adjusted p-values reached significance. Two-step MR analysis revealed that liver fat, AST, and LDL levels mediated the impact of NAFLD on cortical structure. Multivariable MR analysis suggested that the impact of NAFLD on the cortical TH of lingual and parstriangularis was independent of BMI, obesity, hyperlipidemia, and diabetes. CONCLUSION: This study provides evidence that NAFLD causally influences the cortical structure of the brain, suggesting the existence of a liver-brain axis in the development of NAFLD.

Correlation and Performance of three Ultrasound Techniques to Stage Hepatic Steatosis in Nonalcoholic Fatty Liver Disease.

AIMS: There is a need to assess the severity of steatosis caused by Nonalcoholic Fatty Liver Disease (NAFLD). We explored new techniques in which Ultrasound-Guided Attenuation Parameter (UGAP), Liver Steatosis Analysis (LiSA) and Hepatorenal Index (HRI) can be applied to the grading of steatosis. MATERIALS AND METHODS: We enrolled 120 patients with or without NAFLD in this study who underwent UGAP, LiSA, HRI and controlled attenuation parameter (CAP) measurements in our hospital from September 2022 to April 2023. Spearman correlation coefficient was used to calculate the correlation between UGAP, LiSA, HRI and CAP values, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of UGAP, LiSA, and HRI for different grades of steatosis. RESULTS: The cohort was classified into four groups based on means of CAP: S0 (no steatosis): 30/120, S1 (mild): 30/120, S2 (moderate): 15/120, and S3 (severe): 45/120. The cut-off values and areas under the receiver operating characteristic curve (AUC) of UGAP, LiSA and HRI for predicting different grades of steatosis were: S≥S1:227dB/m (AUC=0.904), 241dB/m (AUC=0.873), 1.19 (AUC=0.696); S≥S2:251dB/m (AUC=0.978), 264dB/m (AUC=0.913), 1.37 (AUC=0.770); S=S3:263dB/m (AUC=0.962), 289dB/m (AUC=0.923), 1.45 (AUC=0.809). The diagnostic efficacy of UGAP and LiSA was significantly better than HRI, and there were statistically significant differences (all p<0.05). A strong correlation was found between UGAP, LiSA and CAP values (UGAP: r=0.865; LiSA: r=0.810), moderate correlation between HRI and CAP values (r=0.476). CONCLUSION: Both UGAP and LiSA have a strong correlation with CAP and are more accurate than HRI in diagnosing different grades of hepatic steatosis, which can be widely used in the diagnosis of liver steatosis.

ALT poorly predicts Nonalcoholic Fatty Liver Disease (NAFLD) and liver fibrosis as determined by vibration-controlled transient elastography in adult National Health and Nutrition Examination Survey 2017-2018.

BACKGROUND: Non-alcoholic fatty liver disease is a growing problem in the United States, contributing to a range of liver disease as well as cardiovascular disease. ALT is the most widely used liver chemistry for NAFLD evaluation. We hypothesized that the normal range many laboratories use was too high, missing many patients with clinically important steatosis and/or fibrosis. METHODS: This study utilized 2017-2018 NHANES data including 9254 participants. We compared four different upper limits of normal for ALT with specific measurements of steatosis and liver stiffness as determined by liver elastography with FibroScan®. Liver stiffness was further characterized as showing any fibrosis or advanced fibrosis. After exclusions, our final pool was 4184 for liver stiffness measurement and 4183 for steatosis grade as measured by Controlled Attenuation Parameter (CAP). Using these variables, we performed logistic regression between ALT and CAP, and ALT and fibrosis/advanced fibrosis, and did a Receiver Operating Characteristic curve. RESULTS: Based on three of the most widely used cut off values for ALT, we found that ALT does not reliably rule out NAFLD in over 50% of cases. It also missed 45.9-64.2% of patients with liver fibrosis. CONCLUSIONS: Our study revealed that ALT is an inaccurate marker for NAFLD as measured by FibroScan® with CAP greater than or equal to 300 dB/m. Accuracy improved specific risk factors were considered. These data also showed that ALT was a poor marker for liver fibrosis. We conclude that there is no single ALT level that accurately predicts hepatic steatosis or fibrosis.

Association of Diabetic Retinopathy with Midlife Hepatic Steatosis Diagnosed by Elastography and Hepatic Steatosis Index in Type 2 Diabetes in an Indian Population.

Aims: People with type 2 diabetes mellitus are at increased risk of developing hepatic steatosis. We determined the prevalence of hepatic steatosis in middle-aged patients with and without diabetic retinopathy (DR) in an Indian population. We feel this information is critical, with trends of increasing chronic liver disease-related mortality at younger ages. Method: Institution-based analytical cross-sectional study with 114 middle-aged type 2 diabetes patients; 57 in each group with <15 years of duration of DM and without excessive drinking. Hepatic steatosis was determined by the hepatic steatosis index (HSI), hepatic ultrasonography (USG), and elastography. Result: The HSI in DR (37.9 ± 3.9) was more (P = 0.012) than in without diabetic retinopathy (NODR) (36.3 ± 3.3). There was no difference between two groups in liver span (P = 0.829) or in the prevalence of fatty liver (P = 0.562) as determined by conventional USG. Elastography value (kPa) was more (P = 0.001) in DR (6.51 ± 1.85) than in NODR (5.14 ± 1.60). On elastography, 50.9% in DR had a likelihood ratio (Metavir score for a stiffness value) for stage 2 Metavir score. In DR, 11.8% of those missed by USG had a likelihood ratio for ≥ stage 2 Metavir score on elastography. The presence of DR was independently correlated with kPa value (P < 0.001). Conclusion: A significantly higher prevalence of hepatic steatosis was observed in DR in this population. DR can be a useful biomarker for early hepatic screening in midlife, particularly with hepatic elastography, so that timely diagnosis of hepatic steatosis can be made.

Ultrasonographic findings of metabolic dysfunction-associated fatty liver disease: A comparative study with non-alcoholic fatty liver disease and clinical characteristics.

PURPOSE: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analyzed the ultrasonographic findings of MAFLD and NAFLD. METHODS: We conducted a retrospective cross-sectional study of subjects aged ≥19 years who underwent a health screening examination, including ultrasonography, (n = 17,066). Patients were separated into one of three groups; pure MAFLD (n = 5304), pure NAFLD (n = 579), and both NAFLD & MAFLD (n = 11,183). The outcomes were the degree of fatty liver disease and liver cirrhosis, defined by ultrasonography. In addition, the risk of ultrasonographic cirrhosis was assessed in the MAFLD group based on clinical characteristics. RESULTS: The pure NAFLD group had a lower risk of severe fatty liver disease than the both NAFLD & MAFLD groups (0.9 % vs. 4.4 %, p < 0.001). Cirrhosis was not diagnosed in the NAFLD group. Cirrhosis was more common in the pure MAFLD group than in the both NAFLD & MAFLD group (0.3 % vs. 0.0 %, p < 0.001). In the MAFLD group, multivariable analysis showed that diagnosis by hepatic steatosis index (Odds ratio [OR], 12.39; 95 % confidence interval [CI], 3.40-45.19; p < 0.001) or significant alcohol intake (OR, 9.58, 95 % CI, 1.93-47.61; p = 0.006) was independently associated with risk of liver cirrhosis on ultrasonography. CONCLUSION: Liver cirrhosis was more frequently identified on ultrasonography in patients with MAFLD than in NAFLD. MAFLD diagnosed using the hepatic steatosis index or significant alcohol intake is a risk factor for liver cirrhosis.