Effectiveness of Saroglitazar in MASLD Patients: A Prospective, Real‐World Assessment of Liver and Metabolic Health

INTRODUCTIONNon-alcoholic fatty liver disease (NAFLD) among paediatric population is increasing globally along with the growing obesity epidemic. Fibrosis is an important predictor of advanced liver disease, cardiovascular events and malignancy in adults. This study aims to investigate the relationship between hepatic steatosis, alanine aminotransferase (ALT) and components of the metabolic syndrome with NAFLD among children with obesity and diabetes. METHODOLOGYChildren from paediatric diabetes and obesity clinic in University Malaya Medical Centre were invited to participate in the study between 2016 and 2019. All had transient elastography (Fibroscan, Echosens, Paris). NAFLD was assessed by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). We categorized LSM as 7.0 kPa for fibrosis stage F≥2, 8.7 kPa for F≥3 and 10.3 kPa for F4 (cirrhosis). Mild, moderate and severe steatosis (CAP=1, 2 and 3, respectively) were defined as >248 dB/m,>268 dB/m and>280 dB/m respectively. Data on basic demographics, anthropometric measurements and clinical components of metabolic syndrome were collected. RESULTSA total of 56 children (60.7% male) with ages between 6 to 18 years old (median 13 years) were recruited. There were 64.3% Malays, 19.6% Indians, 12.5% Chinese and 3.6% other ethnicities. ALT levels are positively correlated with LSM values and CAP score (p<0.05). A total of 20 (35.7%) had fibrosis, among which 10 (17.9%) had significant fibrosis (F2), 5 (8.9%) hadadvanced fibrosis (F3) and another 5 (8.9%) had cirrhosis (F4). Among 76.8% (n=43) of patients with steatosis, 2 (3.6%) had mild steatosis, 2 (3.6%) had moderate steatosis and 39 (69.6%) had severe steatosis. There were 18 (32.2%) who had diabetes mellitus, 5 (8.9%) had hypertension, and 23 (41%) fulfilled the criteria for metabolic syndrome. Fibrosis is significantly associated with presence of metabolic syndrome (OR=3.409, 95% CI: 1.089-10.676, p=0.032). CONCLUSIONObese children with metabolic syndrome are more likely to have advanced liver disease compared to those without metabolic syndrome.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is an emerging health problem, that can progress to non-alcoholic steatohepatitis (NASH) and cirrhosis with associated liver morbidity and mortality. The prevalence of NAFLD is...

Introduction and Objective: Type 2 diabetes (T2D) is frequently associated with hepatic complications like fatty liver and fibrosis named Metabolic dysfunction associated steatotic liver disease (MASLD).This study evaluates the demographic profile, Body Mass Index (BMI) and liver health parameters— Fibrosis-4 (FIB-4) score, Controlled Attenuation Parameter (CAP) score and Liver Stiffness Measurement (LSM) Methods: A total of 520 patients were screened and 383 people with T2D were included after exclusion. Data included demographics (age and gender), BMI, FIB-4 score, CAP score, LSM and respective liver fibrosis and fatty liver grades. CAP scores and LSM were assessed using Fibroscan 430 Mini Plus (Echosens, France). Descriptive statistics, Spearman correlation, and ANOVA were utilized to identify significant relationships Results: The cohort had a mean age of 56.2 years, with 61.6% males. The mean BMI was 27.3 kg/m², and the average CAP score was 268.3 dB/m. Mean LSM was 6.64 kPa. BMI showed a moderate positive correlation with CAP (r = 0.30, p < 0.001) and LSM (r = 0.25, p < 0.001). Higher BMI classes were associated with significantly elevated CAP scores (p < 0.01).FIB-4 scores were not significantly correlated with CAP or LSM but increased with advanced fibrosis [F2-F4 (p < 0.001)]. LSM values increased progressively with BMI classification, peaking in the obese category (7.35 kPa) compared to normal weight (6.69 kPa) and overweight individuals (6.87 kPa). F1 and F2 grades being more prevalent in obese compared to normal weight and overweight categories. Missing data included BMI (31.3%), FIB-4 (50.6%), CAP (25.3%) and LSM (25.3%) Conclusion: This study highlights the intricate relationships between BMI, FIB-4, liver fibrosis and fatty liver gradings in T2D. Findings underscore the importance of comprehensive metabolic and hepatic assessments in T2D for better clinical outcomes. Future research should address the role of demographic variables in liver health disparities among T2D populations Disclosure S. Chandel: None. K. Ravi Teja: None.

Objective To investigate the relationship between Fibroscan® data controlled attenuation parameter(CAP), liver stiffness measurement(LSM), and the risk of metabolic syndrome(MS). Methods A total of 817 subjects in this year′s staffs physical checkup screening for fatty liver were recruited. Questionnaires were filled, anthropometries including neck and waist circumferences were collected, and fasting glucose, lipid profiles, insulin, adiponectin levels were measured, CAP and LSM were recorded using FibroScan®. The subjects were divided into MS and control groups. Clinical characteristic parameters were compared, and independent predictors for MS were analyzed. Results There were 231 subjects(28.3%) in the MS group and 586(71.7%) in the control group. As compared to the controls, MS group had significantly higher CAP, LSM, neck circumference, and fasting insulin levels [(277±48 vs 237±44)dB/m, (4.9±2.2 vs 4.1±1.0)kPa, (37.1±3.3 vs 34.1±3.0)cm, (9.3±4.7 vs 5.7±2.9)μIU/ml, all P<0.01], whereas adiponectin levels were lower [(10.6±8.8 vs 18.7±14.9)ng/ml, P<0.01]. With the accumulation of MS components, CAP and LSM increased. When CAP and LSM were divided into quartiles, the number of MS components increased with increasing quartiles, along with proportions and odds ratios for the occurrence of MS, and CAP showed a stronger correlation with MS than LSM. Binary Logistic regression analysis revealed that CAP, age, neck circumference, adiponectin, and fasting insulin levels were independent predictors for MS. Even with no MS component, subjects with CAP≥248 dB/m had elevated body mass index, neck and waist circumference, waist to hip ratio, increased fasting insulin, triglyceride, uric acid and reduced adiponectin levels. Conclusion CAP showed a close relationship with MS. Increased CAP was associated with increased body weight, dyslipidemia, elevated uric acid, and fasting insulin, whereas reduced adiponectin even before the occurrence of MS. Key words: Metabolic syndrome; Transient elastography; Controlled attenuation parameter; Liver stiffness measurement

This study compared the capacity of two different models of HIIT [high-(HC) and low-(LC) compression], with or without the use of berberine (BBR), on NOD-like receptor pyrin domain-containing protein-3 (NLRP3), H19, interleukin (IL)-1β, high-sensitivity C-reactive protein (hs-CRP), and insulin resistance markers. Fifty-four middle-aged men with overweight or obesity and prediabetes [fasting blood glucose (FBG) 110-180 mg/dL] were randomly and equally assigned to the HC, LC, HC + BBR, LC + BBR, BBR, and non-exercising control (CON) groups. The HC (2:1 work-to-rest) and LC (1:1 work-to-rest) home-based training programs included 2-4 sets of 8 exercises at 80%-95% HRmax, twice a week for 8 weeks. Participants in the berberine groups received approximately 1000 mg daily. All exercise interventions led to a significant reduction in hs-CRP, IL-1β, insulin, FBG, and insulin resistance index (HOMA-IR) versus CON. Notably, there was a significant reduction in FBG and HOMA-IR with the BBR group compared to the baseline. Both NLRP3 and H19 experienced a significant drop only with LC in comparison to the baseline. While both exercise protocols were beneficial overall, LC uniquely exhibited more anti-inflammatory effects, as indicated by reductions in H19 and NLRP3. However, the addition of berberine to the exercise programs did not demonstrate additional benefits.

Background and AimNon‐alcoholic fatty liver disease (NAFLD) is common in the United States and China. We compared prevalence of metabolic syndrome (MS), hepatic steatosis and fibrosis, and quantity and quality of body fat between American versus Chinese patients with NAFLD.MethodsNAFLD patients were prospectively recruited from the University of Michigan Health System (UMHS) in the United States and Peking University Health Sciences Center (PUHSC) in China. All patients had baseline computed tomography (CT), laboratory tests and Fibroscan® controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Comparisons were made for overall cohorts and matched cohorts (matched for sex, age, and body mass index [BMI] category). Logistic regression was performed to identify independent predictors of moderate and severe steatosis and lack of advanced fibrosis.ResultsOne‐hundred and one American and One‐hundred and sixty Chinese patients were included. UMHS patients were older, with higher prevalence of MS, had higher LSM and CAP scores, and more fat in liver, visceral, subcutaneous, and muscle compartments than PUHSC patients. Differences in LSM, visceral fat Hounsfield unit, and subcutaneous fat area (SFA) persisted in the matched cohort. NAFLD patients with MS had significantly higher LSM, and more fat in liver, visceral, subcutaneous and muscle compartments than those without. Moderate or severe steatosis was independently associated with MS, visceral fat quality, and SFA, while the absence of advanced fibrosis was associated with Asian race and not having MS.ConclusionAmerican patients with NAFLD had more liver fibrosis than Chinese patients despite having better quality visceral fat and after matching for age, sex, and BMI category.

Hepatic steatosis poses a significant health burden in people with HIV. Fibroblast growth factor 21 (FGF21) production from the liver regulates glucose metabolism. Higher serum levels of FGF21 are associated with hepatic steatosis and liver fibrosis in the general population. Growth differentiation factor 15 (GDF15) secretion from the liver is also upregulated in chronic inflammatory diseases and is associated with cardiovascular dysfunction in people with HIV. Here, we measured serum FGF21 and GDF15 concentrations in people with HIV and hepatic steatosis. A total of 177 people with HIV with no other known cause of liver disease underwent vibration-controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) quantification. Hepatic steatosis was defined as CAP ≥ 263 dB/m and advanced fibrosis as LSM > 12 kPa. Fasting serum total FGF21 and GDF15 concentrations were measured by ELISA. Relationships between biomarkers and hepatic parameters were analysed using a Censored Tobit Model. Participants with hepatic steatosis exhibited significantly higher mean (SD) levels of serum FGF21 (p = 0.002) and GDF15 (p = 0.02) than participants without steatosis. FGF21 levels increased with BMI (p = 0.04). Higher FGF21 and GDF15 levels correlated modestly with higher CAP (FGF21 r = 0.30, p < 0.001; GDF15 r = 0.21, p = 0.01) and LSM scores (FGF21 r = 0.25, p < 0.001; GDF15 r = 0.27, p = 0.01). FGF21 concentrations were 40% higher and GDF15 17% higher in persons with steatosis. Participants with the highest FGF21 levels (quartile 4) showed significantly higher mean CAP and LSM values, and longer mean duration of HIV compared with persons in quartile 1. Similar trends were also seen with GDF15 level quartiles. People with HIV and hepatic steatosis had higher levels of serum FGF21 and GDF15 than those without steatosis, and levels correlated with disease severity. FGF21 and GDF15 may aid in identifying people with HIV at risk of steatotic liver disease.

Background:Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the prevalence of NAFLD among Saudi patients with T2DM using transient elastography.Methods:A total of 490 patients with T2DM who attended diabetes and primary care clinics were recruited. Controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) were obtained via FibroScan to assess steatosis and fibrosis.Results:Of the examined 490 patients with T2DM, 396 (80.8%) had hepatic steatosis (CAP ≥248 dB/m): 326 (66.5%) had severe steatosis (CAP ≥280 dB/m), while 41 (8.4%) and 29 (5.9%) had mild (CAP ≥248 to <268 dB/m) and moderate steatosis (CAP ≥268 to <280 dB/m), respectively. Of the 396 patients with steatosis, only 35 (8.8%) had LSM ≥7.9 kPa, suggesting the presence of fibrosis, while 361 (91%) had LSM <7.9 kPa, indicating the absence of fibrosis. Increased body mass index (BMI), waist circumference, systolic blood pressure (SBP), and alanine aminotransferase (ALT) were positively associated with both steatosis and fibrosis. After adjusting for age and gender, data from logistic regression analysis demonstrated BMI, waist circumference, SBP, ALT, and high-density lipoprotein (HDL) as significant independent factors for steatosis, while SBP was the only significant predictor associated with fibrosis.Conclusions:Our results demonstrate an increase in prevalence of NAFLD in Saudi patients with T2DM, based on transient elastography and CAP score. The risk of NAFLD appears to be higher in T2DM patients with abdominal obesity, elevated SBP, and increased ALT levels, which supports the screening of these conditions in patients with T2DM.

Metabolic syndrome (MetS) is characterized by abdominal obesity, increased blood pressure (BP), fasting blood glucose (FBG) and triglyceride levels, and reduced high-density lipoprotein (HDL) levels. This study aims to investigate the efficacy of the Wharton's jelly mesenchymal stem cells (WJMSCs)-derived small extracellular vesicles' (sEVs) preparations in managing MetS. Twenty-four rats were fed with a high-fat and high-fructose diet to induce MetS for 16 weeks and randomized into three groups (n = 8/group): a MetS Control group treated with normal saline, MetS Low Dose (LD) group treated with a LD of sEVs preparations (3 × 109 particle/rat), and MetS High Dose (HD) group treated with a HD of sEVs preparations (9 × 109 particles/rat). The Control Non-Disease (ND) group was given a standard rat diet and autoclaved tap water with normal saline as treatment. Treatments were given via intravenous injection every three weeks for twelve weeks. Rats were assessed every six weeks for physical measurements, FBG, lipid profiles, CRP, leptin, adiponectin, and BP. Necropsy evaluation was performed on the lungs, liver, spleen, and kidney. Significant reductions in FBG, triglycerides, BP, and increased HDL levels were observed in the treated groups compared to the control group. However, significant abdominal circumference (AC) improvement was not observed in the treated groups. Non-significant associations were found between fasting CRP, leptin, and adiponectin levels with MetS rats after treatment. In addition, sEVs preparations improved inflammation and hemorrhage in the lung and mineralisation in the renal of the treated group. Human fetal WJMSCs-derived sEVs preparations improve all the clusters of MetS in rats except AC and could be further explored as a treatment for MetS.

Background: Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are two prevalent chronic conditions that frequently co-occur in as high as 50–80% of individuals, often complicating management and increasing the risk of cardiovascular disease and liver-related complications. Vitamin E, a potent fat-soluble antioxidant, has emerged as a potential adjunctive therapy for improving liver function and glycemic control in individuals with these coexisting conditions. Aims and Objectives: The aims are to explore the existing evidence on the effects of Vitamin E supplementation on glycemic control in individuals with T2DM and NAFLD, considering its role in oxidative stress modulation, liver health, and overall metabolic management. Materials and Methods: A case–control study was conducted with 100 participants diagnosed with T2DM and NAFLD, divided into two groups: Case group (with Vitamin E supplementation), Vitamin E at a dose of 400 IU once daily for a duration of 6 months and control group (without Vitamin E supplementation). The study assessed various parameters, including fasting blood glucose (FBG), post-prandial blood glucose (PPBG), hemoglobin A1c (HbA1c), liver enzymes (serum glutamic-oxaloacetic transaminase [SGOT], serum glutamic pyruvate transaminase [SGPT]), and the fatty liver index (FLI) before and after 6 months of treatment. Statistical analysis used: Independent samples paired t-test was used to compare the means between two groups. Chi-square test was used to compare the proportions between the groups. P&lt;0.05 was considered statistically significant. The Statistical Package for the Social Sciences, version-26, IBM, Chicago, USA was used in analysis. Results: Vitamin E supplementation resulted in a modest reduction in FBG and PPBG levels in the treatment group. FBG was reduced by 11.32 mg/dL and PPBG by 147 mg/dL. Similar trends were observed in the control group, with a more significant reduction in FBG (37.2 mg/dL) and PPBG (162.1 mg/dL). Both groups showed improvements in liver function, with reductions in SGOT and SGPT levels, and reductions in HbA1c and high-sensitivity C-reactive protein. The FLI also decreased in both groups, though the reduction in the treatment group was more significant. Conclusions: Vitamin E supplementation may offer modest improvements in glycemic control and liver function in individuals with T2DM and NAFLD, particularly in reducing postprandial glucose levels. However, the more significant reductions in the control group suggest that other factors may influence the results, and further research with larger sample sizes and longer durations is needed to confirm these findings.

A daily habit of yogic practice or walking, along with an oral hypoglycemic agent (OHA) could be beneficial for better control of type 2 diabetes mellitus (T2DM). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to find out the efficiency of yoga or walking on glycemic control in T2DM. The present systematic review and meta-analysis were completed according to the PRISMA guidelines. The risk of bias in included studies was evaluated, by using the revised Cochrane risk-of-bias tool for randomized trials. Meta-analysis was implemented using RevMan software. Forest plots were used to illustrate the study findings and meta-analysis results. Sixteen studies were included in this systematic review, where 1820 participants were allocated to one of the following interventions: yoga, walking, and without any regular exercise (control group). Participants were between 17-75 years of age. Compared to the control group, the yoga group had a significant reduction in fasting blood glucose (FBG) by 31.98 mg/dL (95% CI = -47.93 to -16.03), postprandial blood glucose (PPBG) by 25.59 mg/dL (95% CI = -44.00 to -7.18], glycosylated hemoglobin (HbAlc) by 0.73% (95% CI = -1.24 to -0.22), fasting insulin by 7.19 μIU/mL (95% CI = -12.10 to -2.28), and homeostatic model assessment for insulin resistance (HOMA-IR) by 3.87 (95% CI = -8.40 to -0.66). Compared to the control group, the walking group had a significant reduction in FBG by 12.37 mg/dL (95% CI = -20.06 to -4.68) and HbA1c by 0.35% (95% CI = -0.70 to -0.01). Compared to the walking group, the yoga group had a significant reduction in FBG by 12.07 mg/dL (95% CI = -24.34 to - 0.20), HbA1c by 0.20% (95% CI = -0.37 to -0.04), fasting insulin by 10.06 μIU/mL (95% CI = -23.84 to 3.71) and HOMA-IR by 5.97 (95% CI = -16.92 to 4.99). Yoga or walking with OHA has positive effects on glycemic control. For the management of T2DM, yoga has relatively more significant effects on glycemic control than walking.Review registration number: PROSPERO registration number CRD42022310213.

Glucomannan is a dietary fiber that slows the absorption of carbohydrates and suppresses appetite, thereby reducing blood glucose. This meta-analysis sought to examine the effect of glucomannan supplementation on Fasting Blood Glucose (FBG) and Postprandial Glucose (PPG) in adults. We searched PubMed, and SCOPUS databases, and Google Scholar from inception to May 2020, using relevant keywords. All randomized controlled clinical trials (RCTs) that examined the effect of glucomannan supplementation on FBG and PPG in adults were included. Weighted mean differences (WMD) and their 95% confidence interval (CI) were calculated using Stata. Subgroup analysis was used to discern possible sources of heterogeneity. Overall, 6 trials were included, consisting of 124 participants. We found that glucomannan supplementation significantly reduced FBG (WMD): -0.60 mmol/L, 95% CI: -1.16, -0.05; P=0.03, but not PPG (WMD: -2.07mmol/L ; 95% CI: -5.09, 0.95; P=0.18), compared with controls group. We conducted subgroup analysis based on dosage and duration of intervention and health status of the population. Findings from subgroup analysis revealed a significant effect of glucomannan supplementation on FBG in diabetic patients (WMD: -1.28 mmol/L, 95% CI: -2.54, -0.02; P=0.04). Glucomannan supplementation can elicit significant reductions in FBG, but has no significant impact on PPG, in adults. More RCTs may find the exact effect of glucomannan on FBG and PPG. The online version contains supplementary material available at 10.1007/s40200-022-00993-6.

The prognostic importance of changes in vibration-controlled transient elastography (VCTE) parameters, liver stiffness measurement (LSM), and controlled attenuation parameter (CAP), in individuals with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown. A prospective cohort of 288 patients underwent 2 VCTE exams at least 2 years apart, and the relative percentage changes in LSM and CAP were calculated. Outcomes were the occurrence of any liver-related events (LREs), cardiovascular events (CVEs), and all-cause mortality. Multivariable Cox analyses, adjusted for liver and cardiometabolic factors, assessed associations between VCTE parameters changes, both as continuous and dichotomical variables (LSM increase >15% and CAP reduction >10%), and outcomes. During a median follow-up of 6 years, there were 22 LREs, 28 CVEs, and 37 all-cause deaths. For LREs, baseline LSM was the strongest predictor, but LSM increases added further prognostic value (hazard ratio [HR]: 1.5 [1.0-2.1], 1-SD increment). For CVEs, both LSM increase (HR: 1.7 [1.3-2.3]) and CAP reduction (HR: 1.5 [1.0-2.3], 1-SD decrease) were significant predictors. For all-cause mortality, baseline CAP was a protective predictor. When classified into subgroups based on LSM and CAP changes, the subgroup with both increased LSM and reduced CAP had the highest risks for CVEs (HR:5.3 [1.4-19.6]) and all-cause mortality (HR: 3.4 [1.2-9.6]). The highest risk for LREs was observed in the subgroup with increased LSM without CAP reduction (HR: 3.5 [0.9-12.9]). VCTE parameters changes, LSM increase and CAP reduction, provide prognostic information for adverse liver, cardiovascular, and mortality outcomes in individuals with T2D and MASLD.

The pathogenesis involving non-alcoholic fatty liver disease (NAFLD) in the context of chronic HBV (CHB) virus infection requires to be understood for developing improved modalities of diagnosis and treatment. We retrospectively investigated the association between NAFLD and CHB virus infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between years 2013 and 2016, we studied 455 subjects in the current investigation. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the hepatitis B virus (HBV) viral load. Other liver function markers showed a significant positive correlation with both CAP and LSM scores. Plasma IL-13 was independently associated with increased CAP score where every increase of 1 unit of IL-13 was associated with an increase in CAP score by 0.98 unit. CCL11 was independently associated with LSM with every increase of CCL11 by a unit that, in turn, was associated with an increase of LSM score. We found that there was a high concurrence of NAFLD among patients with CHB virus infection. The presence of metabolic syndrome and chronic inflammation in CHB virus-infected patients were two independent factors that led to the progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components.

Background: The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has plagued the general population of the world, which has revised the nomenclature of nonalcoholic fatty liver disease (NAFLD). Transient elastography is one of the key screening methods for MASLD to evaluate the presence of fat and fibrosis in the liver. Materials and Methods: This was a cross-sectional, observational study performed at the single diabetology center of Ahmedabad, in participants aged 18 years and above, and having any one cardio-metabolic risk factors of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, or obesity. Their lipid, sugar, and transient elastography parameters; controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) were recorded. Results: In data of 141 participants, the presence of co-morbid conditions such as obesity (80.14%) was most common, followed by T2DM in 45.4%, while 79.5% had steatosis (&gt; S0) and 27.6% had fibrosis (&gt; F0/F1). Co-morbid conditions like higher weight and history of myocardial infarction (MI) were the major risk factors associated with increased CAP score, whereas higher weight and glycosylated hemoglobin (HbA1c) were the risk factors for increased LSM values. Fibrosis index-4 score has a poor correlation with the LSM and CAP score individually. Conclusion: The distribution of liver fibrosis and steatosis assessed using the CAP and LSM score, in MASLD individuals, is prevalent among patients with a history of MI and excess weight; while higher HbA1c is significantly associated with LSM score only.