Non-alcoholic Fatty Liver Disease Liver Fat Score Research Articles

PREVALENCE OF TRANSAMINITIS AND METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE AMONG YOUNG INDIAN ADULTS - A POPULATION BASED STUDY

BackgroundMetabolic dysfunction-associated Steatotic Liver Disease (MASLD) with onset in youth may be more consequential for adverse outcomes than that detected later in adulthood. Transaminitis in the general population is a marker of prevalence of MASLD. There are no previous community-based studies in Indian youth assessing the prevalence of transaminitis. The purpose of this study was to find out the prevalence of transaminitis, MASLD and elevated FIB-4 (Fibrosis-4) index among young South Indian adults. MethodologyThis was a cross-sectional study done over a period of 1 year from January 2022 among adults aged 18-30 years. Multistage sampling was used to recruit participants with Body Mass Index (BMI) <30 kg/m2 and without moderate to heavy alcohol consumption from 4 different socio-geographic regions. Detailed history, physical examination and investigations including liver enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), platelet count and metabolic workup were carried out. FIB-4 index and Nonalcoholic fatty liver disease-liver fat score (NAFLD-LFS) were calculated. LFS≥-0.64 was used to rule in MASLD. ResultsA total of 2373 (1170 males) participants with mean age of 24±3.5 years were included. Transaminitis (AST or ALT≥35 IU/L) was seen in 25.9% of the cohort. MASLD by NAFLD-LFS was present in 27.4% of the population. FIB-4 index≥1.3 was found in 54 (2.27%) participants. Neck circumference and TMC (Trivandrum Medical College)-adiposity index were associated with transaminitis, MASLD and elevated FIB-4. Blood pressure, triglycerides and LDL cholesterol were higher and HDL cholesterol was lower among participants with transaminitis but they were not different among those with elevated FIB-4 index. BMI and waist hip ratio were not different among participants with and those without transaminitis or MASLD. ConclusionThere is a high prevalence of transaminitis and MASLD in community dwelling young adult Indians. We recommend screening all young adult Indians for MASLD and transaminitis.

Comparison of Non-invasive Liver Fat Scoring Systems as Markers of Metabolic Dysfunction-Associated Liver Disease.

Background Metabolism dysfunction-associated steatotic liver disease (MASLD) is hepatic steatosis along with increased weight or obesity, type 2 diabetes, or metabolic dysregulation and without significant alcohol consumption. The clinical prediction of MASLD using simple, non-invasive indices like Fatty Liver Index (FLI), NAFLD Liver Fat Score (NAFLD LFS), Visceral Adiposity Index (VAI), Steato Test and Hepatic Steatosis Index (HSI) yielded heterogeneous results in different populations. Aim We aimed to compare five scores (Fatty Liver Index, NAFLD Liver Fat Score, Visceral Adiposity Index, Steato Test, Hepatic Steatosis Index) for prediction of liver steatosis. Method Patients with metabolic syndrome and alcohol intake less than 20 grams per day were included in the study. Patients with alcohol intake greater than 20 grams per day and known history of liver or biliary disease, infections, muscle injury, autoimmune diseases, thyroid disorders, underlying secondary diabetes mellitus, secondary hypertension, familial dyslipidemia, intake of medications like steroids, hepatotoxic drugs, chemotherapy or drugs altering liver function tests were excluded. The presence of fatty liver was confirmed on ultrasound. Five indices (Fatty Liver Index, NAFLD Liver Fat Score, Visceral Adiposity Index, Steato Test, Hepatic Steatosis Index) were applied to predict liver steatosis. The correlation of each index with presence of fatty liver was analyzed. Based on the sensitivity of the five scoring systems and prevalence of MASLD as observed in existing literature, with a 95% confidence interval and 20% allowable error, the minimum number of positive cases required is 24 and minimum sample size required is 77. Results Among 100 (100%) patients with metabolic syndrome, MASLD was seen in 65 patients (74% males, 56% females). The mean age of patients with MASLD was 59 years. Fatty Liver Index, NAFLD Liver Fat Score, Visceral Adiposity Index, Steato Test had statistically significant (p<0.005) correlation with fatty liver on ultrasound of abdomen. Fatty Liver Index had the highest Area Under the Receiver Operating Characteristic curve (AUROC) of 0.65 (Sensitivity=63, Specificity=62.9%), followed by NAFLD Liver Fat Score (AUROC=0.63, Sensitivity=64.4%, Specificity=62.9%), Visceral Adiposity Index (AUROC=0.628, Sensitivity=50.8%, Specificity=65.7%) and Steato Test (AUROC=0.61, Sensitivity=46.2%, Specificity=77%). Cut-offs for Fatty Liver Index, NAFLD Liver Fat Score, Visceral Adiposity Index, and Steato Test were 42, 0.5, 4, and 4.5 respectively. MASLD was present in 71.4% (N=35) of patients with type 2 diabetes mellitus and 58.8% (N=30) without type 2 diabetes mellitus. Conclusion Fatty Liver Index, NAFLD Liver Fat Score, Visceral Adiposity Index, and Steato Test were comparable as early markers to predict liver steatosis in patients with metabolic syndrome.

Non-invasive tools for liver steatosis and steatohepatitis predict incidence of diabetes, cardiovascular disease and mortality 20 years later: The ATTICA cohort study (2002–2022)

Background & AimsNon-alcoholic fatty liver disease (NAFLD) or, as recently renamed, metabolic dysfunction-associated steatotic liver disease (MASLD), has common metabolic pathways with diabetes and cardiovascular disease (CVD). Non-invasive tools (NITs) for liver steatosis and steatohepatitis (MASH) were studied as potential predictors of diabetes, cardiovascular disease (CVD) and mortality over a 20-year period. MethodsIn 2001-02, 3,042 individuals from the Attica region of Greece were recruited randomly, and were stratified by subgroups of sex, age and region to reflect the general urban population in Athens, Greece. Validated NITs for hepatic steatosis (Hepatic Steatosis Index (HIS), Fatty Liver Index (FLI), Lipid Accumulation Product (LAP), NAFLD liver fat score (NAFLD-LFS)) and steatohepatitis (Index of non-alcoholic steatohepatitis (ION), aminotransferase-creatinine-clearance non-alcoholic steatohepatitis (acNASH)) were calculated. Incidence of diabetes, CVD and mortality were recorded 5, 10 and 20 years later. ResultsWithin a 20-year observation period, the diabetes and CVD incidence was 26.3% and 36.1%, respectively. All hepatic steatosis and steatohepatitis NITs were independently associated with diabetes incidence. ION and acNASH presented independent association with CVD incidence [(Hazard Ratio (HR)per 1 standard deviation (SD) =1.33, 95% Confidence Interval (95%CI) (1.07, 1.99)) and (HRper 1 SD =1.77, 95%CI (1.05, 2.59)), respectively]. NAFLD-LFS which is a steatosis NIT indicating features of steatohepatitis, was linked with increased CVD mortality (HRper 1 SD=1.35, 95%CI (1.00, 2.30)) and all-cause mortality (HRper 1 SD=1.43, 95%CI (1.08, 2.01). Overall, steatohepatitis NITs (i.e., ION and acNASH) presented stronger associations with the outcomes of interest compared with steatosis NITs. Clinically important trends were observed in relation to diabetes and CVD incidence progressively over time, i.e. 5, 10 and 20 years after baseline. ConclusionsEasily applicable and low-cost NITs representing steatohepatitis may be early predictors of diabetes and CVD onset. More importantly, these NITs increased the attributable risk conveyed by conventional CVD risk factors by 10%. Thus, their potential inclusion in clinical practice and guidelines should be studied further.

Harnessing Metabolic Indices as a Predictive Tool for Cardiovascular Disease in a Korean Population without Known Major Cardiovascular Event.

This study evaluated the usefulness of indices for metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR), as predictive tools for cardiovascular disease in middle-aged Korean adults. The prospective data obtained from the Ansan-Ansung cohort database, excluding patients with major adverse cardiac and cerebrovascular events (MACCE). The primary outcome was the incidence of MACCE during the follow-up period. A total of 9,337 patients were included in the analysis, of whom 1,130 (12.1%) experienced MACCE during a median follow-up period of 15.5 years. The metabolic syndrome severity Z-score, metabolic syndrome severity score, hepatic steatosis index, and NAFLD liver fat score were found to significantly predict MACCE at values above the cut-off point and in the second and third tertiles. Among these indices, the hazard ratios of the metabolic syndrome severity score and metabolic syndrome severity Z-score were the highest after adjusting for confounding factors. The area under the receiver operating characteristic curve (AUC) of the 10-year atherosclerotic cardiovascular disease (ASCVD) score for predicting MACCE was 0.716, and the metabolic syndrome severity Z-score had an AUC of 0.619. The metabolic syndrome severity score is a highly reliable indicator and was closely associated with the 10-year ASCVD risk score in predicting MACCE in the general population. Given the specific characteristics and limitations of metabolic syndrome severity scores as well as the indices of NAFLD and IR, a more practical scoring system that considers these factors is essential to achieve greater accuracy in forecasting cardiovascular outcomes.

DIAGNOSTIC ACCURACY OF THE NON-INVASIVE MARKERS NFLS, NI-NASH-DS, AND FIB-4 FOR ASSESSMENT OF DIFFERENT ASPECTS OF NON-ALCOHOLIC FATTY LIVER DISEASE IN INDIVIDUALS WITH OBESITY: CROSS-SECTIONAL STUDY.

Non-invasive markers have been developed to assess the presence and severity of liver abnormalities related to non-alcoholic fatty liver disease (NAFLD). To analyze the diagnostic accuracy of non-invasive NAFLD markers (NAFLD liver fat score [NLFS], non-invasive non-alcoholic steatohepatitis detection score [NI-NASH-DS] and fibrosis score based on four variables [FIB-4]) in individuals with obesity undergoing bariatric surgery. A descriptive retrospective cross-sectional study was carried out enrolling 91 individuals who underwent bariatric surgery at a tertiary-level public university hospital. Non-invasive NAFLD markers were calculated using laboratory tests, clinical and anthropometric variables and diagnostic accuracy tests were calculated comparing them in relation to the gold-standard test for this analysis (histopathological evaluation). A total of 85.7% of the participants were female and mean age was 39.1±9.8 years. The average body mass index was 38.4±3.6 kg/m2. At histopathological examination, 84 (92.3%) patients presented with steatosis, 82 (90.1%) with some type of fibrosis; 21 (23.1%) patients were diagnosed with NASH according to the NAFLD activity score criteria. The overall accuracy of NLFS score was 58.2% for general hepatic steatosis and 61.5% for moderate to severe steatosis. The overall accuracy of FIB-4 was 95.4% for advanced fibrosis. NI-NASH-DS had a 74.7% overall accuracy for NASH. In a population of individuals with obesity, the FIB-4 score had high overall accuracy in assessing the presence of advanced liver fibrosis, whereas the NFLS and NI-NASH-DS had moderate accuracies for the assessment of steatosis and NASH, respectively.

Натрийуретический пептид при ожирении и неалкогольной жировой болезни печени в молодом возрасте

The purpose — to study the relationship of increased natriuretic peptide (NUP) with obesity and non-alcoholic fatty liver disease (NAFLD) in young people. Material and methods. 142 patients, including 74 men and 68 women aged Me = 35 [31–39] years, were examined at the consulting and diagnostic center of the Aviastroiyelny district of Kazan. The study design is an observational clinical case-control study based on the criterion of constitutional obesity. A questionnaire was conducted, as well as a clinical examination with anthropometry, bioimpedance measurement, assessment of the level of N-terminal cerebral natriuretic peptide (NUP), ultrasound examination of the liver with detection of NAFLD, echocardiography. The indices of liver steatosis Non-Alcoholic Fatty Liver Disease – Liver Fat Score (NAFLD-LFS), Hepatic Steatosis Index (HSI) and Triglyceride and glucose Index (TyG) were calculated. The data is processed in IBM SPSS Statistics 26. Results. According to ultrasound data, NAFLD was found in 12.6% of the examined patients. Patients with NAFLD and exogenous constitutional obesity tended to have a higher incidence of elevated levels of NUP when compared with the group of obese people without NAFLD. The prognostic model results showed that NAFLD, HSI index &gt; 36, as well as female gender were associated with an increase in NUP. At the same time, obesity and male gender reduced the likelihood of NUP increase. Conclusion. NAFLD and obesity have a multidirectional effect on the likelihood of NUP increase among young people without diabetes mellitus and cardiovascular diseases. The presence of NAFLD is associated with an increase in NUP, while exogenous constitutional obesity reduces the likelihood of NUP increase.

Elevated Plasma Copeptin Levels Identify the Presence and Severity of Nonalcoholic Fatty Liver Disease in Obesity

Abstract Background Non-alcoholic fatty liver disease is characterized by excessive fat accumulation in the liver with unclear mechanism may be due to epigenetic changes which take place at the transcriptional level without altering the underlying DNA sequence. this epigenetic alternation are involved in regulation of hepatic lipid metabolism, insulin resistance, mitochondrial damage, oxidative stress response, and the release of inflammatory cytokines, all of which have been implicated in the development and progression of NAFLD. Elevated copeptin, a vasopressin marker, is linked to metabolic disease, and obese rats with lowvasopressin concentration had a decreased risk of liver steatosis. Aim and objectives To Detect the elevation of plasma copeptin in obese patients with nonalcoholic fatty liver disease in relation to general population. Subjects and Methods This is A randomized case control cross sectional study, was carried out at internal medicine and gastroenterology department, Ain Shams University hospitals, on 100 patients above 18 years old with Hepatic Steatosis Index (HSI) and NAFLD-Liver Fat Score (LFS), over a period of 6 months. Result There was high statistically significant difference between the studied groups as regard Serum plasma copeptin. Conclusion Our study demonstrates for the first time that copeptin levels predict the presence of biopsy-proven NAFLD in obese individuals, regardless of body adiposity and the coexistence of other metabolic disorders. Studies with longitudinal design are warranted for exploring the possible involvement of AVP/V1aR system in the development and progression of NAFLD.

Association of non-high-density lipoprotein cholesterol trajectories with the development of non-alcoholic fatty liver disease: an epidemiological and genome-wide association study

BackgroundNon-alcoholic fatty liver disease (NAFLD) shares common risk factors with cardiovascular diseases. Effects of longitudinal trends in non-high-density lipoprotein (non-HDL) cholesterol on NAFLD development are not understood. This study aimed to assess the relationship between non-HDL cholesterol trajectories and the incidence of NAFLD and to identify genetic differences contributing to NAFLD development between non-HDL cholesterol trajectory groups.MethodsWe analyzed data from 2203 adults (aged 40–69 years) who participated in the Korean Genome and Epidemiology Study. During the 6-year exposure periods, participants were classified into an increasing non-HDL cholesterol trajectory group (n = 934) or a stable group (n = 1269). NAFLD was defined using a NAFLD-liver fat score > -0.640. Multiple Cox proportional hazard regression analysis estimated the hazard ratio (HR) and the 95% confidence interval (CI) for the incidence of NAFLD in the increasing group compared with the stable group.ResultsA genome-wide association study identified significant single-nucleotide polymorphisms (SNPs) associated with NAFLD. During the median 7.8-year of event accrual period, 666 (30.2%) newly developed NAFLD cases were collected. Compared with the stable non-HDL group, the adjusted HR (95% CI) for the incidence of NAFLD in the increasing non-HDL cholesterol group was 1.46 (1.25–1.71). Although there were no significant SNPs, the polygenic risk score was highest in the increasing group, followed by the stable and control groups.ConclusionOur study indicates that lifestyle or environmental factors have a greater effect size than genetic factors in NAFLD progression risk. Lifestyle modification could be an effective prevention strategy for NAFLD for people with elevated non-HDL cholesterol.

Gender Differences in the Risk for Incident Non-Alcoholic Fatty Liver Disease According to the Transition of Abdominal Obesity Status: A 16-Year Cohort Study.

Waist circumference (WC) is an important predictor of long-term adverse outcomes. We aimed at assessing the correlation between abdominal obesity (AO) patterns and non-alcoholic fatty liver disease (NAFLD). Data from 4467 adults aged 40-69 years and without NAFLD who participated in the Korean Genome and Epidemiology Study were analyzed. Participants were classified according to two-year WC pattern into four groups: persistent lean WC, improved AO, progressed to AO, and persistent AO. NAFLD was defined as NAFLD-liver fat score >-0.640. Multiple Cox proportional hazards regression analysis revealed that the fully adjusted hazard ratio (HR) (95% confidence intervals (CIs)) for NAFLD in persistent AO, progressed to AO, and improved AO groups compared to the persistent lean WC group was 1.33 (1.13-1.57), 1.73 (1.48-2.02), and 1.06 (0.84-1.33), respectively. Women in persistent AO or progressed to AO groups had significantly higher risk for NAFLD than those in persistent lean WC or improved AO groups. Men who had progressed to an AO event over two years had significantly higher risk for NAFLD than those without any AO event over two years. Maintaining lean WC and improving AO would be successful strategies for preventing NAFLD in women, while maintaining lean WC would be more effective in men.

Close association of PFASs exposure with hepatic fibrosis than steatosis: evidences from NHANES 2017–2018

Multiple animals and in vitro studies have demonstrated that perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure causes liver damage associated with fat metabolism. However, it is lack of population evidence for the correlation between PFAS exposure and nonalcoholic fatty liver disease (NAFLD). A cross-sectional analysis was performed of 1150 participants aged over 20 from the US. Liver ultrasound transient elastography was to identify the participants with NAFLD and multiple biomarkers were the indicators for hepatic steatosis and hepatic fibrosis. Logistics regression and restricted cubic splines models were used to estimate the association between PFASs and NAFLD. PFASs had not a significant association with NAFLD after adjustment. The hepatic steatosis indicators including fatty liver index, NAFLD liver fat score, and Framingham steatosis index were almost not significantly correlated with PFASs exposure respectively. But fibrosis indicators including fibrosis-4 index (FIB-4), NAFLD fibrosis score, and Hepamet fibrosis score were positively correlated with each type of PFASs exposure. After adjustment by gender, age, race, education, and poverty income rate, there was also a significant correlation between PFOS and FIB-4 with 0.07 (0.01, 0.13). The mixed PFASs were associated with FIB-4, with PFOS contributing the most (PIP = 1.000) by the Bayesian kernel machine regression model. The results suggested PFASs exposure appeared to be more closely associated with hepatic fibrosis than steatosis, and PFOS might be the main cause of PFASs associated with hepatic fibrosis. Key messages Current exposure doses of PFAS did not significantly change the risk of developing NAFLD. PFASs exposure appeared to be more closely associated with hepatic fibrosis than steatosis. PFOS might be the main cause of PFASs associated with hepatic fibrosis.

Clinical characteristics and management of patients with nonalcoholic steatohepatitis in a real-world setting: analysis of the Ipsos NASH therapy monitor database

BackgroundNonalcoholic steatohepatitis (NASH) is the more severe, inflammatory type of nonalcoholic fatty liver disease (NAFLD). NASH, a leading indication for liver transplantation, is growing in prevalence. The extent of liver fibrosis, ranging from fibrosis stage (FS) of none (F0) to cirrhosis (F4), is a strong predictor of health outcomes. There is little information on patient demographics and clinical characteristics by fibrosis stage and NASH treatment outside of academic medical centers.MethodsWe conducted a cross-sectional observational study using Ipsos’ syndicated NASH Therapy Monitor database, consisting of medical chart audits provided by sampled NASH-treating physicians in the United States in 2016 (n = 174) and 2017 (n = 164). Data was collected online.ResultsOf 2,366 patients reported on by participating physicians and included in the analysis, 68% had FS F0–F2, 21% had bridging fibrosis (F3), and 9% had cirrhosis (F4). Common comorbidities were type 2 diabetes (56%), hyperlipidemia (44%), hypertension (46%), and obesity (42%). Patients with more advanced fibrosis scores (F3-F4) had higher comorbidity rates than patients with F0-F2. Commonly used diagnostic tests included ultrasound (80%), liver biopsy (78%), AST/ALT ratio (43%), NAFLD fibrosis score (25%), transient elastography (23%), NAFLD liver fat score (22%), and Fatty Liver Index (19%). Most commonly prescribed medications were vitamin E (53%), statins (51%), metformin (47%), angiotensin converting enzyme inhibitors (28%), and beta blockers (22%). Medications were commonly prescribed for reasons other than their known effects.ConclusionPhysicians in this study, drawn from a spectrum of practice settings, relied on ultrasound and liver biopsy for diagnosis and vitamin E, statins, and metformin for pharmacological treatment of NASH. These findings imply poor adherence to guidelines in the diagnosis and management of NAFLD and NASH.Plain language summaryNonalcoholic steatohepatitis (NASH) is a liver disease caused by excess fat in the liver which can lead to liver inflammation and scarring (fibrosis), ranging from stage F0 (no scarring) to F4 (advanced scarring). The stage of liver scarring can predict the likelihood of future health problems, including liver failure and liver cancer. However, we do not fully understand how patient characteristics may vary at different stages of liver scarring. We looked at medical information from physicians treating patients diagnosed with NASH to understand how patient characteristics might differ based on the severity of their liver scarring. The majority (68%) of patients were stage F0-F2, with 30% having advanced scarring (F3-F4). In addition to NASH, many patients also had type 2 diabetes, high cholesterol, high blood pressure, and obesity. Patients with more advanced scarring (F3-F4) were more likely to have these diseases than patients with less severe disease (F0-F2). Diagnosis of NASH by participating physicians was based on tests including imaging (ultrasound, CT scan, MRI), liver biopsy, blood tests, and whether patients had other conditions that would put them at risk for NASH. The medications that the doctors prescribed most often to their patients included vitamin E and drugs to treat high cholesterol, high blood pressure, or diabetes. Medications were frequently prescribed for reasons other than their known effects. By understanding how patient characteristics vary by stages of liver scarring and how NASH is currently managed may help guide the evaluation and treatment of NASH when NASH-specific therapies become available.

Abstract #1413498: Whole Body Digital Twin Technology for Remission of T2DM and Normalization of Glycemic and Fatty Liver Parameters: 1 Year Intent to Treat Analysis of the Prospective Randomized Controlled Clinical Trial

Twin Precision Treatment (TPT) is a novel Whole-Body Digital Twin (WBDT) enabled precision nutrition for reversing diabetes, that uses AI and the Internet of Things, to integrate multidimensional data, from non-invasive sensors, to give precision nutrition and health recommendations via the TPT app and by coaches. We conducted a prospective randomized trial to compare the changes in the glycemic metrics and the fatty liver parameters. The Intent to Treat (ITT) analysis among 233 people with T2DM who underwent WBDT was done at one year. 84 T2DM were provided the standard of care (SC). Remission was defined as an A1C level <6.5% for ≥ six months without diabetes medication use for at least 90 days. Normal values were: BMI <25kg/m2, HbA1c <6.5%, FPG <126 mg/dl, HOMA2-IR <1.22, NAFLD Liver Fat Score (NAFLD-LFS) <-0.64, Fatty Liver Score (FLS) <23, Framingham Steatosis Index (FSI) <23. Of the 233 people with T2DM, 209 subjects completed more than six months of WBDT. 72.7% (152/209) sustained remission at one year. The mean age, duration of diabetes, were 43 years (±9.5, range 17 to 69) and 3.4 years (±2.7, range 0.1 to 8). WBDT (n=233) intervention led to a significant number (p<0.0001) of subjects achieving the normalized values from baseline and at 1 year, for BMI (76 to 133), HbA1c (16 to 184), FPG (57 to 181), HOMA2-IR (48 to 130), NAFLD-LFS (26 to 149), FLI (30 to 120), FSI (29 to 135). ALT (68 to 140). One-year improvement in HbA1C was significantly better for WBDT than SC -3.0 (±1.8) vs. -0.2 (±1.2); p<0.001. Our ITT analysis shows that WBDT enables a high rate of remission of T2DM with a durable benefit, beyond six months for the glycemic control. There is a significant increase in the number of people who achieve the normalised biochemical and clinical values, for glycemic and fatty liver indices, while they remain in T2DM remission, at one year

Indices of hepatic steatosis and fibrosis in prediabetes and association with diabetes development in the vitamin D and type 2 diabetes study

AimsNon-alcoholic fatty liver disease (NAFLD) is a common comorbidity that leads to poor outcomes in people at high risk for development of type 2 diabetes (T2D). Vitamin D is a possible mediator. In the vitamin D and type 2 diabetes study (D2d), we investigated the relationship of baseline indices of NAFLD with incident T2D and whether the effect of vitamin D on diabetes was modified by NAFLD. MethodsCross-sectional associations of indices of NAFLD with glycemia and vitamin D status were assessed in 3972 individuals screened for the D2d study. In those with prediabetes randomized to vitamin D or placebo (n = 2423), we examined longitudinal associations of NAFLD indices with incident T2D. We used validated non-invasive scores to assess steatosis [(hepatic steatosis index (HSI); NAFLD-liver fat score (NAFLD-LFS)] and advanced fibrosis [fibrosis-4 (FIB-4) index; AST to Platelet Ratio Index (APRI)]. ResultsEighty-five percent of screened participants had likely steatosis by HSI and 71 % by NAFLD-LFS; 3 % were likely to have advanced fibrosis by FIB-4 and 1.2 % by APRI. FIB-4 indicated that 20.4 % of individuals require further follow up to assess liver health. Steatosis and fibrosis scores were higher among participants with worse glycemia. The NAFLD-LFS and APRI predicted development of diabetes (hazard ratios [95%CI] 1.35 [1.07, 1.70]; P = 0.012) and 2.36 (1.23, 4.54; P = 0.010), respectively). The effect of vitamin D on diabetes risk was not modified by baseline NAFLD indices. Individuals with likely steatosis had a smaller increase in serum 25-hydroxyvitamin D level in response to vitamin D than those without steatosis. ConclusionsThe predicted high prevalence of steatosis, the need for further fibrosis workup, and the relationship between liver health and incident T2D suggest that routine screening with clinically accessible scores may be an important strategy to reduce disease burden.

Non-invasive Screening of Metabolic Associated Fatty Liver Disease and Affecting Factors in Primary Care.

To identify the presence of MAFLD (metabolic associated fatty liver disease) with some non-invasive screening methods and the factors affecting in patients with metabolic dysfunction. A cross-sectional study. Place and Duration of the Study: University of Health Sciences, Kartal Dr. Lutfi Kirdar City Hospital, Istanbul, Turkiye, from March to June 2021. This study included 233 participants with metabolic disease over the age of 18 who applied to family medicine clinics. The participants' sociodemographic data, chronic disease status, biochemical parameters, waist circumference, weight, height, body mass index, and presence of steatosis by ultrasonography were recorded. The risk of developing hepatic fibrosis and steatosis was calculated with the non-alcoholic fatty liver disease liver fat score (NAFLD-LFS), hepatic steatosis index (HSI), fatty liver index (FLI), fibrosis-4 index (FIB-4), NAFLD fibrosis score (NAFLD-FS), and aspartate aminotransaminase to platelet ratio index (APRI). The conclusions were evaluated with SPSS. According to the diagnostic criteria, MAFLD was detected in 58.4% of the participants. Statistically significant difference was found between FLI, HSI, NAFLD-LFS and MAFLD (p<0.001). According to the steatosis index risk groups of the participants, 64.4% - 89.7% were found to be high-risk. Steatosis was confirmed by ultrasonography in 63.6% - 77.8% of those at high-risk for index steatosis. The statistically significant difference was found between hypertension, diabetes mellitus, hyperlipidemia, metabolic syndrome, obesity, and MAFLD (p=0.039, p<0.001, p<0.001, p<0.001, and p=0.011, respectively). Using non-invasive screening methods for steatosis can be clinically useful in detecting patients at risk for steatosis, and these methods are applicable in predicting MAFLD. NAFLD, Fatty liver ındex, Hepatic steatosis index, MAFLD, Steatosis.

Impaired ketogenesis is associated with metabolic-associated fatty liver disease in subjects with type 2 diabetes.

The ketogenic pathway is an effective mechanism by which the liver disposes of fatty acids (FAs) to the peripheral tissues. Impaired ketogenesis is presumed to be related to the pathogenesis of metabolic-associated fatty liver disease (MAFLD), but the results of previous studies have been controversial. Therefore, we investigated the association between ketogenic capacity and MAFLD in subjects with type 2 diabetes (T2D). A total of 435 subjects with newly diagnosed T2D was recruited for the study. They were classified into two groups based on median serum β-hydroxybutyrate (β-HB) level: intact vs. impaired ketogenesis groups. The associations of baseline serum β-HB and MAFLD indices of hepatic steatosis index, NAFLD liver fat score (NLFS), Framingham Steatosis index (FSI), Zhejian University index, and Chinese NAFLD score were investigated. Compared to the impaired ketogenesis group, the intact ketogenesis group showed better insulin sensitivity, lower serum triglyceride level, and higher low-density lipoprotein-cholesterol and glycated hemoglobin levels. Serum levels of liver enzymes were not different between the two groups. Of the hepatic steatosis indices, NLFS (0.8 vs. 0.9, p=0.045) and FSI (39.4 vs. 47.0: p=0.041) were significantly lower in the intact ketogenesis group. Moreover, intact ketogenesis was significantly associated with lower risk of MAFLD as calculated by FSI after adjusting for potential confounders (adjusted odds ratio 0.48, 95% confidence interval 0.25-0.91, p=0.025). Our study suggests that intact ketogenesis might be associated with decreased risk of MAFLD in T2D.

Association between smoking cessation and non-alcoholic fatty liver disease using NAFLD liver fat score.

Smoking is well known to be associated with a higher prevalence and incidence of liver diseases such as advanced fibrosis. However, the impact of smoking on developing nonalcoholic fatty liver disease remains controversial, and clinical data on this is limited. Therefore, this study aimed to investigate the association between smoking history and nonalcoholic fatty liver disease (NAFLD). Data from the Korea National Health and Nutrition Examination Survey 2019-2020 were used for the analysis. NAFLD was diagnosed according to an NAFLD liver fat score of >-0.640. Smoking status was classified as into nonsmokers, ex-smokers, and current smokers. Multiple logistic regression analysis was conducted to examine the association between smoking history and NAFLD in the South Korean population. In total, 9,603 participants were enrolled in this study. The odds ratio (OR) for having NAFLD in ex-smokers and current smokers in males was 1.12 (95% confidence interval [CI]: 0.90-1.41) and 1.38 (95% CI: 1.08-1.76) compared to that in nonsmokers, respectively. The OR increased in magnitude with smoking status. Ex-smokers who ceased smoking for <10 years (OR: 1.33, 95% CI: 1.00-1.77) were more likely to have a strong correlation with NAFLD. Furthermore, NAFLD had a dose-dependent positive effect on pack-years, which was 10 to 20 (OR: 1.39, 95% CI: 1.04-1.86) and over 20 (OR: 1.51, 95% CI: 1.14-2.00). This study found that smoking may contribute to NAFLD. Our study suggests cessation of smoking may help management of NAFLD.

Exploring the Validity of Available Markers and Indices in the Diagnosis of Nonalcoholic Fatty Liver Disease (NAFLD) in People with Type 2 Diabetes in Saudi Arabia.

Nonalcoholic fatty liver disease (NAFLD) is common among Saudi patients with type 2 diabetes (T2DM). However, recommended clinical procedures to detect it are unavailable in many locations. Therefore, better and more available diagnostic biomarkers for NAFLD are needed. Various serum parameters were suggested, and algorithms that employ routine measurements in clinical practice have been developed for the prediction of fat stores in the liver in different populations. However, no such studies have been conducted on Saudis. We aimed to compare selected biochemical markers and calculated indices in T2DM patients diagnosed with NAFLD and patients without NAFLD to find the best markers associated with NAFLD. A cross-sectional study was employed to recruit 67 people with T2DM from endocrine outpatient clinics at King Abdul-Aziz University Hospital. NAFLD was detected by ultrasonography in 28 patients. Demographic information, anthropometric, and blood pressure (BP) measurements were taken. Fasting blood samples were obtained to measure glucose, glycated haemoglobin, lipid profile, liver function tests, and highly sensitive C-reactive protein. Fatty liver index, hepatic steatosis index, NAFLD-liver fat score, and triglyceride and glucose index were calculated. Following stepwise forward likelihood ratio regression with independent variables included in one model using binary logistic regression with age and waist circumference (WC) entered as covariates, elevated diastolic BP and low high-density lipoprotein- cholesterol remained significantly associated with NAFLD (p = 0.002 and 0.03, respectively). However, none of the investigated indices could be used to diagnose the disease adequately due to low specificity, even after calculating new cut-off values. Investigating novel markers and adjusting existing equations used to calculate indices to improve sensitivity and specificity in our population is needed.

Association of non-alcoholic fatty liver disease with left ventricular changes in treatment-naive patients with uncomplicated hypertension.

Background and aimsCardiac structural and functional changes have been demonstrated in patients with non-alcoholic fatty liver disease (NAFLD). Because of the frequent association of NAFLD with hypertension, we aimed to examine the relationship of liver steatosis with left ventricular (LV) changes in patients with hypertension.Materials and methodsIn a cross-sectional study, we included 360 untreated, essential hypertensive patients who were free of major cardiovascular and renal complications. Liver steatosis was assessed by three different biochemical scores (NAFLD Liver Fat Score, LFS; Fatty Liver Index, FLI; Hepatic Steatosis Index, HSI). Echocardiography was performed with standard B-mode and tissue-Doppler imaging.ResultsLV hypertrophy was present in 19.4% and LV diastolic dysfunction in 49.2% of patients who had significantly higher body mass index (BMI), blood pressure (BP), and homeostatic model assessment (HOMA) index and higher frequency of the metabolic syndrome and liver steatosis that was defined by presence of 2 or more positive scores. LV mass index increased progressively across patients who had none, 1, or 2 or more liver steatosis scores, with associated progressive worsening of LV diastolic function. LV mass index was significantly and positively correlated with age, BMI, BP, HOMA-index, LFS, and HSI. Logistic regression analysis showed that age, BP, and liver steatosis scores independently predicted LV hypertrophy and diastolic dysfunction. Liver steatosis independently predicted LV dysfunction but not LV hypertrophy even after inclusion in analysis of the HOMA-index.ConclusionNAFLD is associated with LV hypertrophy and diastolic dysfunction in untreated patients with hypertension. In hypertension, NAFLD could contribute to LV diastolic dysfunction with mechanisms unrelated to insulin resistance.

Risk Scores for Metabolic Dysfunction-Associated Fatty Liver Disease in Pediatric Obesity

Introduction: Early noninvasive detection of incipient liver damage is crucial to prevent long-term adverse health outcomes. A variety of scores to assess liver status have been proposed, mostly for adult populations. Validation of noninvasive hepatic scores to identify children at risk of metabolic dysfunction-associated fatty liver disease (MAFLD) is a gap in research, particularly in youth with severe obesity considering pubertal stage and sex. Methods: In a well-characterized pediatric population aged 9–19 years (n = 115), 19 published liver scores were analyzed. The area under the receiver operating characteristic curve (AUROC) for determination of MAFLD as assessed by magnetic resonance imaging was calculated. Results: The pediatric indices PNFI, B-AST, and M-APRI and several scores developed in adults significantly differed in children with MAFLD compared to children without, while some established indices did not. Only nonalcoholic fatty liver disease liver fat score (NAFLD-LFS) and the model by Cao et al. [PLoS One. 2013;8(12):e82092] showed acceptable predictive accuracy (AUROC >0.8) independently of pubertal stage and sex. When stratifying for pubertal stage and sex, the GSG-Index was superior in pubertal girls, and NAFLD-LFS performed best in pubertal boys. Conclusion: NAFLD-LFS and the model by Cao et al. [PLoS One. 2013;8(12):e82092] were well suited to predict MAFLD in youth with severe obesity. In pubertal children, GSG-Index and NAFLD-LFS performed best in girls and boys, respectively.

Cutoff Points of Waist Circumference for Predicting Incident Non-Alcoholic Fatty Liver Disease in Middle-Aged and Older Korean Adults.

This study aimed to determine the optimal cutoff value of waist circumference (WC) for predicting incident NAFLD. In this community-based prospective cohort study, we analyzed data from 5400 participants without NAFLD at baseline aged 40–69 years. NAFLD was defined as a NAFLD-liver fat score >−0.640. A Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for an association between body composition and NAFLD incidence. The predictive power of each body composition indicator was assessed by Harrell’s concordance index for Cox models. During a mean follow-up period of 12 years, there were 2366 new-onset NAFLD events. Compared with men with WC < 81 cm, the adjusted HR (95% CI) for incident NAFLD in those with WC ≥ 81 cm was 2.44 (2.23–2.67). Compared with women with WC < 78.5 cm, the adjusted HR (95% CI) for incident NAFLD in those with WC ≥ 78.5 cm was 2.54 (2.25–2.87). WC was the most significant risk factor for predicting incident NAFLD among body composition indicators in middle-aged and older Korean adults. The optimal WC cutoff point for predicting incident NALFD was 81 cm in men and 78.5 cm in women, which might assist in the early detection and prevention of NAFLD.