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Background The optimal strategy to support primary care practitioners (PCPs) to assess fibrosis severity in nonalcoholic fatty liver disease (NAFLD) and thereby make appropriate management decisions remains unclear. Aims We aimed to examine the feasibility of using a 2-step pathway that combined simple scores (NAFLD Fibrosis Score and Fibrosis-4 Index) with transient elastography (FibroScan®) to streamline NAFLD referrals from a 'routine' primary care population to specialist hepatology management clinics (HMC). Methods The 2-step "Towards Collaborative Management of NAFLD" (TCM-NAFLD) fibrosis risk assessment pathway was implemented at two outer metropolitan primary healthcare practices in Brisbane. Patients aged ≥18 years with a new or established PCP-diagnosis of NAFLD were eligible for assessment. The pathway triaged patients at "high risk" of clinically significant fibrosis to HMC for specialist review, and "low risk" patients to receive ongoing management and longitudinal follow-up in primary care. Results A total of 162 patient assessments between Jun-2019 and Dec-2020 were included. Mean age was 58.7 ± 11.7 years, 30.9% were male, 54.3% had type 2 diabetes or impaired fasting glucose, and mean body mass index was 34.2 ± 6.9 kg/m2 . 122 patients were considered "low risk" for clinically significant fibrosis, two patients had incomplete assessments, and 38 (23.5%) were triaged to HMC. Among 31 completed HMC assessments to date, 45.2% were considered to have clinically significant (or more advanced) fibrosis, representing 9.2% of 153 completed assessments. Conclusion Implementation of the 2-step TCM-NAFLD pathway streamlined hepatology referrals for NAFLD and may facilitate a more cost-effective and targeted use of specialist hepatology resources. This article is protected by copyright. All rights reserved.

BACKGROUND In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2is) have been increasingly used in the treatment of patients with non-alcoholic fatty liver disease (NAFLD). This updated meta-analysis aimed to evaluate the efficacy and safety of SGLT2is for patients with NAFLD. METHODS PubMed, Embase, Cochrane Library, Web of Science, Wan Fang, China National Knowledge Infrastructure and VIP databases were searched for relevant studies from inception to April 30, 2021. Values of weighted mean differences (WMDs) and risk ratios (RRs) were determined for continuous and dichotomous outcomes, respectively. RESULTS A total of 1,498 patients with NAFLD from 20 studies were included for further analysis. Pooled analyses indicated significant improvements in body mass index [WMD: -0.84 kg/m2, 95% CI (-1.09, -0.60)], alanine aminotransferase [WMD: -4.36 U/L, 95% CI (-7.17, -1.54)], aspartate aminotransferase [WMD: -2.94 U/L, 95% CI (-5.33, -0.55)], fasting plasma glucose [WMD: -4.08 mmol/L, 95% CI (-6.21, -1.95)] and fibrosis-4 index [WMD: -0.08, 95% CI (-0.11, -0.05)] following SGLT2i treatment (p

Objective Owing to limited research, the effect of non-alcoholic fatty liver disease (NAFLD) on type 2 diabetes outcomes remains unclear. This study aimed to investigate the association between NAFLD and microvascular complications in hospitalized patients with type 2 diabetes. Methods We included 1982 patients with type 2 diabetes. NAFLD was defined as hepatic steatosis detected by ultrasound without secondary causes of fat accumulation. The diagnosis of diabetic retinopathy (DR), diabetic kidney disease (DKD) and diabetic neuropathy was based on clinical medical records. Risk for advanced liver fibrosis was categorized as “low risk,” “indeterminate risk,” and “high risk,” based on the NAFLD Fibrosis Score (NAFLD-FS). Logistic regression was used to test the association between NAFLD, risk for advanced fibrosis and the presence of DR, DKD, and diabetic neuropathy. Results The prevalence of NAFLD was 61.3%. The presence of DR (odds ratio [OR]: 0.749, 95% confidence interval [CI]: 0.578–0.971), and DKD (OR: 0.667, 95% CI: 0.515–0.864) was inversely associated with NAFLD, after adjusting for covariates. The presence of DR and DKD was higher in the “indeterminate risk” (DR: OR: 1.237, 95% CI: 0.730–2.096; DKD: OR: 1.009, 95% CI: 0.640–1.591, respectively) and “high risk” group (DR: OR: 1.341, 95% CI: 0.730–2.463; DKD: OR: 1.732, 95% CI: 1.021–2.940, respectively) than in the “low risk” group, after adjusting for the same covariates. Only the presence of DKD significantly increased with high NAFLD-FS (P=0.01 for trend). Conclusion The presence of DR and DKD was inversely associated with NAFLD among hospitalized patients with type 2 diabetes. DKD was closely associated with high NAFLD-FS among patients with NAFLD.

The aim of this study was to investigate whether a nutritional intervention motivating increased vegetable consumption would be an effective treatment and diet therapy for patients with non-alcoholic fatty liver disease. We examined 15 patients with this disease (5 men and 10 women). During the 6-month intervention period, all participants received a small amount of vegetables twice a month as a nutritional education tool aimed at increasing vegetable consumption. They also received nutritional counseling and underwent ultrasound and blood biochemical examinations at baseline and 3 and 6 months after initiation of the intervention. Moreover, they were requested to submit dietary records for any 2 days. Green, white, and total vegetable intakes were significantly higher at 3 and 6 months than at baseline in 8 patients. These patients had significantly lower alanine amino­transferase and triglyceride concentrations than those whose vegetable intake did not increase. Additionally, green vegetable intake significantly negatively correlated with weight at 3 and 6 months (r = −0.617, p = 0.032 and r = −0.848, p = 0.008, respectively). These results suggest that our nutritional approach effectively increased vegetable consumption in at least some patients with non-alcoholic fatty liver disease, consequently improving their condition.

Graphical abstract, Introduction Non-alcoholic fatty liver disease (NAFLD) results from increased hepatic total cholesterol (TC) and total triglyceride (TG) accumulation. In our previous study, we found that rats treated with hyperoside became resistant to hepatic lipid accumulation. Objectives The present study aims to investigate the possible mechanisms responsible for the inhibitory effects of hyperoside on the lipid accumulation in the liver tissues of the NAFLD rats. Methods Label-free proteomics and metabolomics targeting at bile acid (BA) metabolism were applied to disclose the mechanisms for hyperoside reducing hepatic lipid accumulation among the NAFLD rats. Results In response to hyperoside treatment, several proteins related to the fatty acid degradation pathway, cholesterol metabolism pathway, and bile secretion pathway were altered, including ECI1, Acnat2, ApoE, and BSEP, etc. The expression of nuclear receptors (NRs), including farnesoid X receptor (FXR) and liver X receptor α (LXRα), were increased in hyperoside-treated rats’ liver tissue, accompanied by decreased protein expression of catalyzing enzymes in the hepatic de novo lipogenesis and increased protein level of enzymes in the classical and alternative BA synthetic pathway. Liver conjugated BAs were less toxic and more hydrophilic than unconjugated BAs. The BA-targeted metabolomics suggest that hyperoside could decrease the levels of liver unconjugated BAs and increase the levels of liver conjugated BAs. Conclusions Taken together, the results suggest that hyperoside could improve the condition of NAFLD by regulating the cholesterol metabolism as well as BAs metabolism and excretion. These findings contribute to understanding the mechanisms by which hyperoside lowers the cholesterol and triglyceride in NAFLD rats.

This study aims to systematically assess the effectiveness and safety of Huazhi Rougan granule in the treatment of non-alcoholic fatty liver.The PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), WanFang databases, VIP databases, Chinese Biomedical Literature Database (SinoMed) were searched to identify the relevant randomized controlled trials, from the establishment of the database to June 7, 2020. The Cochrane risk of bias tool for assessing risk of bias was employed to evaluate the quality of the literatures included. Meta-analyses were performed using RevMan 5.3 software.A total of 23 related literature were retrieved, 9 studies with 1,142 participants were included in the meta-analysis. The overall quality of evidence for this study is low. Meta-analysis results suggest that, Huazhi Rougan granule combined with conventional treatment was significantly superior to the silybin control group in the improvement of liver B-ultrasound, reduction of serological indexes, increase of high-density lipoprotein and total clinical effective rate, which was statistically significant. The improvement of serum lipid parameters included alanine aminotransferase (ALT): [mean deviation (MD) =-10.49, 95% confidence interval (CI): -17.09, -3.90, P0.05], aspartate transaminase (AST): (MD =-9.44, 95% CI: -14.62, -4.26, P0.05), total cholesterol (TC): (MD =-0.77, 95% CI: -0.94, -0.60, P0.05), triglyceride (TG): (MD =-0.40, 95% CI: -0.56, -0.24, P0.05). Reduce low-density lipoprotein cholesterol: (MD =-0.40, 95% CI: -0.56, -0.24, P0.05). Clinical effective rate: [risk ratio (RR) =1.25, 95% CI: 1.16, 1.36, P0.05]. Occurrence of adverse reactions: Of the 9 studies included, 5 reported adverse reactions, of which 3 reported no drug-related adverse reactions. Adverse reactions were reported in 2 cases, all of which were mild adverse reactions.The clinical efficacy of Huazhi Rougan granule combined with conventional basic therapy in the treatment of non-alcoholic fatty liver may be better than that of conventional basic therapy combined with silybin, which may improve the B-ultrasonic grading effect of the liver and reduce the serum lipid parameters of the patients. it may improve the clinical symptoms of non-alcoholic fatty liver, and the incidence of adverse reactions is low, but the number of existing clinical studies is small and the quality is low, in order to further verify the above conclusions. More high-quality clinical RCT trials need to be carried out, and internationally recognized outcome indicators should be selected and uniformly included in the scoring criteria.

Many studies have associated altered intestinal bacterial communities and non-alcoholic fatty liver disease, but the putative effects are inconclusive. The purpose of this network meta-analysis (NMA) was to evaluate the effects of probiotics, prebiotics, and synbiotics on non-alcoholic fatty liver disease through randomised intervention trials. Literature searches were performed until March 2020. For each outcome, a random NMA was performed, the surface under the cumulative ranking curve (SUCRA) was determined. A total of 22 randomised trials comparing prebiotic, probiotic, and synbiotic treatments included 1301 participants. Considering all seven results (aspartate aminotransferase, alanine aminotransferase, body mass index, weight, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) together, the highest SUCRA values are probiotics (94%), synbiotics (61%) and prebiotics (56%), respectively. NMA results provide evidence that probiotics, prebiotics, and synbiotics can alleviate non-alcoholic fatty liver disease. However, due to the lack of high-quality randomised trials, this research also has some limitations.

This study aims to evaluate the effect of non‐alcoholic fatty liver disease (NAFLD) on the susceptibility and consequences of coronavirus disease 2019 (COVID‐19). We retrospectively collected data from 218 adult COVID‐19 patients who showed no evidence of excessive alcohol consumption and underwent abdominal ultrasound examinations. Of these patients, 39.4% patients had been diagnosed with NAFLD, which indicates a much higher prevalence of NAFLD than that reported in the general population. Significantly elevated white blood cell count (p = 0.008), alanine aminotransferase (p = 0.000), aspartate aminotransferase (p = 0.006) and C reactive protein (p = 0.012) were found in the patients with NAFLD. These patients also had significantly higher proportions of hypertension (p = 0.006) and diabetes (p = 0.049) than the non‐NAFLD cases. No significant differences existed in the severity, mortality, viral shedding time and length of hospital stay between patients with or without NAFLD in the sample population. However, subgroup analyses found that in patients with normal body mass index (BMI), NAFLD sufferers were more likely to experience a severe event (30.0% vs 11.5%, p = 0.021). Kaplan‐Meier curve (log‐rank p = 0.017) and Cox regression (HR = 3.26, 95% CI: 1.17–9.04, p = 0.023) analyses confirmed that before and after adjusting for gender, age and comorbidities, NAFLD patients with normal BMI had a higher incidence of suffering severe events. People with NAFLD may have a higher proportion of COVID‐19. NAFLD may be correlated with the severity of COVID‐19 patients in the normal BMI group.

Aim The aim of the study was to explore the experiences of self‐management in patients with non‐alcoholic fatty liver disease (NAFLD). Design The study employed an exploratory descriptive qualitative study using focus group interviews. Methods Twelve participants with NAFLD were recruited from a university hospital in South Korea. The date of data collection was from November–December 2018, and the data were analysed using Braun and Clarke's thematic analysis. Results Three themes and seven subthemes were identified. The themes were (1) facing unexpected obstacles, (2) finding my own path and (3) unmet support needs from healthcare providers. Subthemes included (1) ambiguity in changing lifestyle, (2) confusion caused by inconsistent information overload, (3) not knowing much about the liver nor NAFLD, (4) putting small plans into action every day, (5) getting help from family and friends as care partners, (6) needs for tailored medical help and (7) needs for caring and attentive attitudes.

Summary Background & Aims Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and one of the leading indications for liver transplantation in adults. However, current screening methods are inadequate and are accompanied by several disadvantages. This meta-analysis aims to identify the anthropometrical and biochemical characteristics most commonly appearing in pediatric NAFLD that could contribute to the diagnosis of the disease in the every-day clinical setting. Methods A systematic search was conducted in major electronic databases (MEDLINE, Scopus and Embase) up to 15th of August 2021. Primary outcome was the comparison of the anthropometric characteristics, whereas secondary outcomes were the comparisons of biochemical profile, lipid profile, and metabolic parameters in children with NAFLD compared with age-matched healthy controls. Quality assessment was performed with Newcastle-Ottawa Scale (NOS) and results were expressed as mean differences with 95% confidence intervals. Results Sixty-four studies were included. Two different comparisons were designed regarding the body mass status. Statistically significant differences were demonstrated by comparing children with NAFLD vs lean/normal weighted controls in body weight (23.0 kg, 95% CI: 14.0-31.8, P Conclusions Anthropometrical and biochemical characteristics of children and adolescents with NAFLD are statistically significantly different compared to age-matched controls; these characteristics could be used to identify individuals at risk of developing NAFLD and related comorbidities.

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) has rapidly increased worldwide. The aim of this study was to investigate whether there is an independent relationship between regional fat distribution, especially leg fat mass, and the presence of NAFLD using nationally representative data in Korea.Methods: This cross-sectional study analyzed data from 14,502 participants in the Korea National Health and Nutrition Examination Survey 2008 to 2011. Total fat mass, leg fat mass, and appendicular skeletal muscle mass were measured by dual-energy X-ray absorptiometry. Validated NAFLD prediction models and scoring systems for hepatic fibrosis were used.Results: The leg fat to total fat (LF/TF) ratio showed a negative relationship with many factors, including body mass index, waist circumference, blood pressure, fasting blood glucose, and liver enzyme levels. When the LF/TF ratio and indices of hepatic steatosis were stratified by quartiles, the LF/TF ratio showed a negative correlation with the scoring systems that were used. The LF/TF ratio showed better accuracy in predicting NAFLD than total fat mass or leg fat mass alone. After adjusting for various traditional and lifestyle factors, a low LF/TF ratio remained a risk factor for NAFLD. Among NAFLD subjects, the LF/TF ratio showed a negative relationship with hepatic fibrosis.Conclusion: A lower LF/TF ratio was markedly associated with a higher risk of hepatic steatosis and advanced hepatic fibrosis using various predictive models in a Korean population. Therefore, the LF/TF ratio could be a useful anthropometric parameter to predict NAFLD or advanced hepatic fibrosis.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally and is estimated to affect approximately 25% of the world's population. Data about the prevalence and incidence of NAFLD in Africa are scarce, but the prevalence is estimated to be 13·5% for the general population. This is likely to be an underestimate considering the increasing burden of non-communicable diseases, particularly the rising prevalence of obesity and type 2 diabetes, driven by the overlapping challenges of food insecurity, nutritional transition, and associated increased consumption of calorie-dense foods. Establishing the true prevalence of NAFLD, raising public awareness around the risk factors behind the increase in NAFLD, and proactively addressing all components of metabolic syndrome will be important to combat this silent epidemic, which will have long-term health-care costs and economic consequences for the region.

Background Non-alcoholic fatty liver disease (NAFLD) is a frequently occurring clinical disease, which could be treated by traditional Chinese medicine. However, the effects and mechanisms of xiao-zhi-fang (XZF) alone or in combination with fructooligosaccharides (FOS) on NAFLD remains unclear. Methods This study established the NAFLD mouse model by feeding with a high-fat diet and by administering with XZF and/or FOS. Moreover, the fat content in the liver tissues was evaluated by oil red O and hematoxylin and eosin staining, and the liver function indices were examined using a biochemical analyzer. Changes in the intestinal flora were monitored using 16S rRNA gene sequencing. The results of the current study showed that the alanine aminotransferase, aspartate aminotransferase, total triglyceride, total cholesterol levels, and the amount of lipid accumulation were markedly elevated in NAFLD mice. Results XZF alone or in combination with FOS significantly reduced lipid accumulation in the liver and blood lipid levels in NAFLD mice. Moreover, XZF alone or in combination with FOS notably altered the intestinal flora structure in NAFLD mice. Consequently, 17 operational taxonomic units were decreased and nine were increased in the XZF and/or FOS groups. Conclusions FOS may accelerate the intestinal microecological balance in NAFLD mice after treatment with XZF by promoting intestinal flora growth, thereby enhancing the therapeutic effect of XZF on NAFLD.

The prevalence of non-obese nonalcoholic fatty liver disease (NAFLD) is increasing worldwide with unclear etiology and pathogenesis. Here, we show GP73, a Golgi protein upregulated in livers from patients with a variety of liver diseases, exhibits Rab GTPase-activating protein (GAP) activity regulating ApoB export. Upon regular-diet feeding, liver-GP73-high mice display non-obese NAFLD phenotype, characterized by reduced body weight, intrahepatic lipid accumulation, and gradual insulin resistance development, none of which can be recapitulated in liver-GAP inactive GP73-high mice. Common and specific gene expression signatures associated with GP73-induced non-obese NAFLD and high-fat diet (HFD)-induced obese NAFLD are revealed. Notably, metformin inactivates the GAP activity of GP73 and alleviates GP73-induced non-obese NAFLD. GP73 is pathologically elevated in NAFLD individuals without obesity, and GP73 blockade improves whole-body metabolism in non-obese NAFLD mouse model. These findings reveal a pathophysiological role of GP73 in triggering non-obese NAFLD and may offer an opportunity for clinical intervention., Dysregulation of lipid metabolism and transport contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here the authors identify GP73 as a TBC-domain Rab GTPase-activating protein that regulates very low-density lipoprotein export and promotes NAFLD development in mice.

Sub-Saharan Africa, which has a population of more than 1 billion people, carries 24% of the global burden of disease and spends the least on health care of any region, relying heavily on international development assistance to deliver health care for HIV, tuberculosis, and malaria. The demographic and epidemiological transitions occurring in sub-Saharan Africa, with rising prevalences of obesity and diabetes, enhance the risk of non-alcoholic fatty liver disease (NAFLD), yet this remains an unrecognised complication of metabolic syndrome. There are no guidance documents on NAFLD from sub-Saharan Africa, and non-communicable disease (NCD) guidance documents do not include the associated burden of fatty liver disease. Combating the health and socioeconomic burden of NAFLD requires an integrated liver health approach, with task-shifting to primary health care. Using clear guidance documents to link education and management of HIV, viral hepatitis, NAFLD, and associated NCDs is also crucial to an integrated approach to infectious diseases and NCDs, which requires targeted funding from both governments and international development agencies.

Non-alcoholic fatty liver disease (NAFLD) is currently considered the most common cause of liver disease. Its prevalence is increasing in parallel with the obesity and type 2 diabetes mellitus (DM2) epidemics in developed countries. Several recent studies have suggested that NAFLD may be the hepatic manifestation of a systemic inflammatory metabolic disease that also affects other organs, such as intestine, lungs, skin and vascular endothelium. It appears that local and systemic proinflammatory/anti-inflammatory cytokine imbalance, together with insulin resistance and changes in the intestinal microbiota, are pathogenic mechanisms shared by NAFLD and other comorbidities. NAFLD is more common in patients with extrahepatic diseases such as inflammatory bowel disease (IBD), obstructive syndrome apnea (OSA) and psoriasis than in the general population. Furthermore, there is evidence that this association has a negative impact on the severity of liver lesions. Specific risk characteristics for NAFLD have been identified in populations with IBD (i.e. age, obesity, DM2, previous bowel surgery, IBD evolution time, methotrexate treatment), OSA (i.e. obesity, DM2, OSA severity, increased transaminases) and psoriasis (i.e. age, metabolic factors, severe psoriasis, arthropathy, elevated transaminases, methotrexate treatment). These specific phenotypes might be used by gastroenterologists, pneumologists and dermatologists to create screening algorithms for NAFLD. Such algorithms should include non-invasive markers of fibrosis used in NAFLD to select subjects for referral to the hepatologist. Prospective, controlled studies in NAFLD patients with extrahepatic comorbidities are required to demonstrate a causal relationship and also that appropriate multidisciplinary management improves these patients’ prognosis and survival.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Therapeutic activity of icariin, a major bioactive component of Epimedii Herba, in NAFLD is still unknown. Herein, the C57BL/6J mice were fed with a high-fat diet for 16 weeks to establish a NAFLD model. Mice were assigned to five groups: control group, NAFLD group, and icariin treatment groups. Effects of icariin on blood indices, glucose tolerance, insulin sensitivity, histopathological morphology, cell apoptosis, lipid accumulation, and AMPK signaling were analyzed. In addition, another cohort of mice were assigned to five groups: control group, NAFLD group, dorsomorphin treatment group, icariin treatment group, and dorsomorphin + icariin treatment group. Expression of proteins in liver tissues associated with AMPK signaling, and levels of ALT and AST were evaluated. Icariin attenuated the NAFLD-induced increase of the TG, TC, LDL-C, ALT, AST levels. HDL-C levels were affected neither by NAFLD nor by icariin. Furthermore, icariin treatment (100-200 mg/kg) counteracted the NAFLD-reduced glucose tolerance and insulin sensitivity and modulated histopathological changes, cell apoptosis, and lipid accumulation in liver tissues. Additionally, icariin mitigated the NAFLD-induced up-regulation of the cleaved caspase 3/9, SREBP-1c, and DGAT-2 levels, and enhanced the expression level of CPT-1, p-ACC/ACC, AMPKα1, PGC-1α, and GLUT4. Effects of icariin on the AMPK signaling and levels of AST and ALT could be reversed by AMPK inhibitor, dorsomorphin. This paper investigates the glucose-reducing and lipid-lowering effects of icariin in NAFLD. Moreover, icariin might function through activating the AMPKα1/PGC-1α/GLTU4 pathway.

Summary Background AMP kinase (AMPK) is an energy sensor implicated in regulation of lipid metabolism, inflammation, and insulin sensitivity. We aimed to assess efficacy and safety of PXL770, a novel direct AMPK activator, in patients with non-alcoholic fatty liver disease (NAFLD). Methods STAMP-NAFLD, a randomised, double-blind, placebo-controlled phase 2a study, was done across 15 US clinical sites. Patients aged 18–75 years with liver fat content of at least 10% at baseline when assessed by MRI-proton density fat fraction (MRI-PDFF) were eligible. Patients were randomly assigned (1:1:1:1), via an interactive web response system, to receive oral PXL770 250 mg once daily, 250 mg twice daily, or 500 mg once daily, or matched placebo. Patients were stratified according to type 2 diabetes status and study site. The primary endpoint was relative change in liver fat content from baseline compared with placebo at week 12, assessed by MRI-PDFF. The primary endpoint was analysed in an ANCOVA model with treatment and stratification criteria as factors and baseline liver fat content as a covariate in the modified intention-to-treat population, defined as all as-randomised patients who received at least one dose of study treatment. Safety was analysed in the safety population, defined as all as-treated patients receiving at least one dose of the study treatment. The trial has been completed and the final results are reported. The trial is registered with ClinicalTrials.gov , NCT03763877 . Findings Between March 29, 2019, and March 13, 2020, 387 patients were screened, of whom 120 were included in the modified intention-to-treat and safety analyses (30 in the 250 mg once daily group, 30 in the 250 mg twice daily group, 29 in the 500 mg once daily group, and 31 in the placebo group). The mean relative change from baseline in liver fat content at week 12 was −1·1% in the placebo group, −1·0% in the 250 mg once daily group (mean difference versus placebo 0·1% [95% CI −15·4 to 15·7], p=0·99), −14·3% in the 250 mg twice daily group (−13·1% [–28·1 to 1·8], p=0·084), and −14·7% in the 500 mg once daily group (−13·5% [–28·5 to 1·4], p=0·076). At least one treatment-emergent adverse event occurred in 23 (77%) of 30 patients in the 250 mg once daily group, 20 (67%) of 30 patients in the 250 mg twice daily group, 21 (72%) of 29 patients in the 500 mg once daily group, and 21 (68%) of 31 patients in the placebo group. The most common treatment-emergent adverse event was diarrhoea (five [17%] of patients in the 250 mg once daily group, seven [23%] in the 250 mg twice daily group, six [21%] in the 500 mg once daily group, and none in the placebo group). No life-threatening events or treatment-related deaths occurred. Interpretation PXL770 treatment did not meet the primary outcome of liver fat improvement compared with placebo. Treatment was well tolerated. Given indications that metabolic features improved with PXL770 treatment, AMPK activation might be a promising pharmacological target for patients with type 2 diabetes and NAFLD, and could also be considered for further assessment in patients with non-alcoholic steatohepatitis. Funding Poxel.

Summary Background Studies have reported a significant association between non-alcoholic fatty liver disease (NAFLD) and increased incidence of cardiovascular disease (CVD). However, the magnitude of the risk and whether this risk changes with the severity of NAFLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of incident CVD events. Methods We systematically searched PubMed, Scopus, and Web of Science from database inception to July 1, 2021, to identify eligible observational studies examining the risk of incident CVD events amongst adult (age ≥18 years) individuals with and without NAFLD and in which NAFLD was diagnosed by imaging, International Classification of Diseases codes, or liver biopsy. The primary outcomes were CVD death, non-fatal CVD events, or both. Data from selected studies were extracted, and meta-analysis was performed using random-effects models to obtain summary hazard ratios (HRs) with 95% CIs. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on Open Science Framework, number osf.io/5z7gf. Findings We identified 36 longitudinal studies with aggregate data on 5 802 226 middle-aged individuals (mean age 53 years [SD 7]) and 99 668 incident cases of fatal and non-fatal CVD events over a median follow-up of 6·5 years (IQR 5·0–10·2). NAFLD was associated with a moderately increased risk of fatal or non-fatal CVD events (pooled random-effects HR 1·45, 95% CI 1·31–1·61; I2=86·18%). This risk markedly increased across the severity of NAFLD, especially the stage of fibrosis (pooled random-effects HR 2·50, 95% CI 1·68–3·72; I2=73·84%). All risks were independent of age, sex, adiposity measures, diabetes, and other common cardiometabolic risk factors. Sensitivity analyses did not modify these results. Interpretation NAFLD is associated with an increased long-term risk of fatal or non-fatal CVD events. CVD risk is further increased with more advanced liver disease, especially with higher fibrosis stage. These results provide evidence that NAFLD might be an independent risk factor for CVD morbidity and mortality. Funding None.

Non‐alcoholic fatty liver disease (NAFLD) is an increasingly prevalent and potentially severe liver disease, emphasizing the need for implementation of widely supported care paths for patients at risk for advanced stages of NAFLD. In particular, the distinction of patients with a progressive and/or advanced, fibrotic NAFLD from those with simple steatosis requires improvement, as well as the awareness for NAFLD among health care professionals. Broad acceptance and implementation of interdisciplinary care paths in the near future will bring enhanced identification of those patients that benefit from surveillance, intensive lifestyle management, and empirical or investigational pharmacotherapy and enhance our epidemiological grasp of NAFLD in relation to lifestyle, genetic background, and cardiometabolic comorbidities related to NAFLD.

OBJECTIVE Abdominal obesity is strongly associated with the development of non-alcoholic fatty liver disease (NAFLD). Early identification and intervention may reduce the risk. We aim to improve pediatric NAFLD screening by comparing discriminative performance of six abdominal obesity indicators. METHODS We measured anthropometric indicators (waist circumference [WC], waist-to-hip ratio [WHR], waist-to-height ratio [WHtR]), body composition indicators (trunk fat index [TFI], visceral fat area [VFA]), and endocrine indicator (visceral adiposity index [VAI]) among 1350 Chinese children aged 6-8 years. Using Spearman correlation, receiver operating characteristic (ROC) curves, and Logistic regression, we validated their ability to predict NAFLD. RESULTS All six indicators can predict NAFLD robustly, with area under the curve (AUC) values ranged from 0.69 to 0.96. TFI, WC, and VFA rank in the top three for the discriminative performance. TFI was the best predictor with AUC values of 0.94 (0.92-0.97) and 0.96 (0.92-0.99), corresponding to cut-off values of 1.83 and 2.31 kg/m2 for boys and girls, respectively. Boys with higher TFI (aOR = 13.8), VFA (aOR = 11.1), WHtR (aOR = 3.1), or VAI (aOR = 2.8), and girls with higher TFI (aOR = 21.0) or VFA (aOR = 17.5), were more likely to have NAFLD. CONCLUSION User-friendly body composition indicators like TFI can identify NAFLD and help prevent the progress of liver disease. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn/enIndex.aspx , No. ChiCTR2100044027); retrospectively registered on 6 March 2021. IMPACT Abdominal obesity increases the risk of pediatric non-alcoholic fatty liver disease (NAFLD). This study compared the discriminative performance of multiple abdominal obesity indicators measured by different methods in terms of accuracy and fastidious cut-off values through a population-based child cohort. Our results provided solid evidence of abdominal obesity indicators as an optimal screening tool for pediatric NAFLD, with area under the curve (AUC) values ranged from 0.69 to 0.96. User-friendly body composition indicators like TFI show a greater application potential in helping physicians perform easy, reliable, and interpretable weight management to prevent the progress of liver damage.

Aim This study assessed the diagnostic performance of liver stiffness measurement (LSM) in detecting liver fibrosis in paediatric patients with non-alcoholic fatty liver disease (NAFLD) through meta-analysis. Methods Online database searches of PubMed, EMBASE, the Cochrane Library and the Web of Science were conducted for studies that evaluated the performance of LSM for diagnosing liver fibrosis in paediatric patients with NAFLD until 1 January 2021. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the quality of the included studies. Three measures were used to assess the performance of LSM for detecting liver fibrosis in paediatric patients with NAFLD, including the summary sensitivities and specificities, the summary area under the receiver operating characteristic curves and the summary diagnostic odds ratios. Results Our final data included seven studies with a total of 436 paediatric patients with NAFLD for meta-analysis. The overall prevalence of mild fibrosis, significant fibrosis, advanced fibrosis and cirrhosis was 66.3, 31.5, 14.9 and 1.2%, respectively. The summary sensitivity, specificity and area under the receiver operating characteristic values of LSM were 80, 92 and 0.94 for the prediction of mild fibrosis; 91, 97 and 0.98 for the prediction of significant fibrosis; and 89, 93 and 0.96 for the prediction of advanced fibrosis, respectively. Conclusion Liver stiffness measurement exhibited good diagnostic performance in predicting liver fibrosis and can be used as a non-invasive tool in the management of paediatric patients with non-alcoholic fatty liver disease.

Telomere length has been linked to the prevalence and progression of metabolic disease. However, clinical implications of telomere length in biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients remain unclear. Therefore, this study aimed to investigate the association of telomere length with the histological severity of NAFLD. The cross-sectional data derived from the prospectively enrolled Boramae NAFLD registry (n = 91) were analyzed. The liver tissues and clinical information were obtained from both NAFLD patients and non-NAFLD subjects. Binary logistic regression was performed to identify the independent association between telomere length and the histological severity of NAFLD. A total of 83 subjects with or without biopsy-proven NAFLD were included for analysis: non-NAFLD in 23 (27.7%), non-alcoholic fatty liver in 15 (18.1%), and non-alcoholic steatohepatitis (NASH) in 45 (54.2%). Telomere length measured from liver tissues showed a strong negative correlation (p p p = 0.019) and high-density lipoprotein cholesterol (OR 0.94; 95% CI 0.80–0.99; p = 0.039) were independently associated with significant fibrosis. The age-adjusted telomere length tends to decrease along with the fibrosis stage of NAFLD. In particular, among the histological components of NAFLD, fibrosis severity seems to be related to telomere length in the liver.

Background Sarcopenia is an independent risk factor not only for advanced‐stage non‐alcoholic fatty liver disease (NAFLD) but also for mortality. We investigated the association of sarcopenia and/or NAFLD with mortality among the Korean general population. Methods Individuals aged 35–75 years without any history of cancer, ischaemic heart disease, ischaemic stroke, or secondary causes of chronic liver disease were selected from the Korean National Health and Nutrition Examination Surveys from 2008 to 2015. Their mortality data until December 2018 were retrieved from the National Death Registry. NAFLD and sarcopenia were defined by hepatic steatosis index and appendicular skeletal muscle mass divided by body mass index (BMI), respectively. Results A total of 28 060 subjects were analysed [mean age, 50.6 (standard error, 0.1) years, 48.2 (0.3) % men]; the median follow‐up duration was of 6.8 (interquartile range, 4.8, 8.4) years. NAFLD predicted mortality after adjustment for age, sex, BMI, hypertension, dyslipidaemia, and smoking (HR 1.32, 95% CI 1.03–1.70), but this prediction lost its statistical significance after additional adjustment for diabetes mellitus. In contrast, NAFLD with advanced fibrosis independently increased the risk of mortality after adjustment for all covariates (HR 1.68, 95% CI 1.02–2.79). Stratified analysis revealed that NAFLD and sarcopenia additively increased the risk of mortality as an ordinal scale (HR 1.46, 95% CI 1.18–1.81, P for trend = 0.001). The coexistence of NAFLD and sarcopenia increased the risk of mortality by almost twice as much, even after adjustment for advanced fibrosis (HR 2.18, 95% CI 1.38–3.44). Conclusions Concurrent NAFLD and sarcopenia conferred a two‐fold higher risk of mortality. The observation that NAFLD and sarcopenia additively increase mortality suggests that risk stratification would be helpful in predicting mortality among those with metabolic derangement.

Background Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition associated with aging, insulin resistance, metabolic syndrome, genetic factors and more. Although genetic traits are among the most important risks factors for NAFLD, the understanding of their influence is still quite limited. The present study aimed at identifying novel single nucleotide polymorphisms (SNPs) that may confer a risk for NAFLD in the Han Chinese population. Methods Based on the “two-hit hypothesis”, candidate SNPs, including Sirtuin3 rs28365927, were genotyped by MassARRAY in B-type ultrasonography-proven NAFLD patients (n = 292) and healthy controls (n = 387). Results In a model analysis of individuals matched based on gender and age that compared 223 NAFLD and 223 non-NAFLD patients, the rs28365927 GA + AA genotype was a significant risk factor for the development of NAFLD in a dominant model. Rs28365927 was significantly associated with a higher NAFLD risk in both an additive model (A vs G) and genotypic model (GA vs GG). Among the NAFLD patients, serum levels of total bilirubin (TBIL), DBIL direct bilirubin (DBIL) and glutamic-pyruvic transaminase (ALT) in rs28365927 A allele carriers (GA + AA) were 11.1, 14.7 and 41.5% higher, respectively, than in non-carriers (GG). Furthermore, among the NAFLD patients, the carriers of Rs28365927 allele A were positively correlated with higher ALT levels. Conclusion Sirtuin3 rs28365927 functional variant confers to the high risk of non-alcoholic fatty liver disease in Chinese Han population. The rs28365927 A allele significantly increased the ALT levels of NAFLD patients.

Background and Aim This retrospective study investigated the effect of 48‐week pemafibrate therapy in non‐alcoholic fatty liver disease (NAFLD) with hypertriglyceridemia, as evaluated by the FibroScan‐aspartate aminotransferase (FAST) score. Methods A total of 31 NAFLD patients who were treated with pemafibrate in Gunma Saiseikai Maebashi Hospital and Kusunoki Hospital from September 2018 to April 2020 were included in the current study. We used the FAST score, which is a novel index of steatohepatitis that can be calculated based on the AST value, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM), to evaluate the effect of pemafibrate treatment. Results The median age was 64.0 (interquartile range [IQR] 55.0–75.0) years and 14 patients (45.2%) were male. Median body mass index was 26.8 (IQR 23.8–28.8). Hypertension and diabetes mellitus were detected in 14 (45.2%) and five (16.1%) patients, respectively. Fasting triglyceride and high‐density lipoprotein cholesterol were significantly improved (P, The FibroScan‐aspartate aminotransferase (FAST) score, which stratifies patients with risk of progressive non‐alcoholic steatohepatitis effectively, was significantly improved during pemafibrate treatment. The delta FAST score was correlated with the variations of alanine aminotransferase, which represents the effect of pemafibrate. Pemafibrate may prevent disease progression in non‐alcoholic fatty liver disease patients with hypertriglyceridemia.

Aims/Introduction We aimed to determine whether mean and visit‐to‐visit glycated hemoglobin (HbA1c) variability independently increase the incidence of non‐alcoholic fatty liver disease (NAFLD) across the diabetic continuum from normal glucose tolerance (NGT) to established diabetes. Materials and Methods In a longitudinal cohort study, 21,123 participants underwent five or more annual health screening checkups. Participants were categorized into diabetes (n = 1,635), prediabetes (n = 6,650) and NGT (n = 12,838) groups. Mean, standard deviation (SD) and coefficient of variation data on HbA1c were obtained from three consecutive measurements. The associations between those data and incident NAFLD were analyzed using Cox regressions. Results Over a median follow‐up period of 57 months, 3,860 (18.3%) participants developed NAFLD. The risk of NAFLD increased continuously, with the mean HbA1c beginning at 4.9%, even in the NGT group. We found a significant association between increasing HbA1c variability and incident NAFLD (coefficient of variation, adjusted hazard ratio 1.14, 95% confidence interval 1.01–1.29; standard deviation, adjusted hazard ratio 1.19, 95% confidence interval 1.05–1.36) in the diabetes group, but not in the NGT or prediabetes group. Consistent findings were observed when NAFLD patients with a low possibility of fibrosis were excluded. The association between the coefficient of variation of HbA1c and incident NAFLD in the diabetes group was significant only in those with an increasing trend of post‐baseline HbA1c (adjusted hazard ratio 1.24, 95% confidence interval 1.01–1.52). Conclusions Increased mean HbA1c levels elevated the risk of incident NAFLD, even with NGT. Increases in visit‐to‐visit variability of HbA1c independently elevated the risk of incident NAFLD, but only in the diabetes group., In a cohort comprising individuals with various glucose statuses at baseline (n = 21,123), the risk of non‐alcoholic fatty liver disease continuously increased according to increasing mean HbA1c from 4.9%, even in the normal glucose tolerance group. We found a significant association between increasing HbA1c variability and incident non‐alcoholic fatty liver disease in diabetes, but not in the normal glucose tolerance and prediabetes groups.

Aims/Introduction Non‐alcoholic fatty liver disease, especially with liver fibrosis, is associated with cardiovascular diseases. The Non‐Alcoholic Fatty Liver Disease Fibrosis Score (NFS), a non‐invasive marker of advanced fibrosis, was found to be associated with cardiovascular diseases in different populations. The aim of the present study was to determine whether the NFS is associated with subclinical myocardial remodeling in type 2 diabetes patients. Materials and Methods A cross‐sectional study was carried out in type 2 diabetes patients. The NFS derived from available parameters was calculated, and the participants were divided according to the quartiles of the NFS and grades of the NFS (low, intermediate and high). Fibrosis‐4 and Aspartate Aminotransferase to Platelet Ratio Index, another two liver fibrosis scores, were also calculated. Subclinical myocardial remodeling was examined by echocardiography, and its associations with NFS, Fibrosis‐4 and Aspartate Aminotransferase to Platelet Ratio Index were analyzed. Results A total of 1,878 type 2 diabetes patients were enrolled in the present study. The NFS was independently associated with sex, age, body mass index, low‐density lipoprotein cholesterol and glycated hemoglobin in type 2 diabetes patients. Parameters of subclinical myocardial remodeling including left atrial dimension, interventricular septum thickness, left ventricular end‐diastolic diameter, left ventricular end‐systolic diameter, left ventricular posterior wall thickness (LVPWT) and left ventricular mass index were all gradually increased with the increment of the NFS. Linear regression analysis further showed that the NFS was positively associated with left atrial dimension, interventricular septum thickness, left ventricular end‐diastolic diameter, left ventricular end‐systolic diameter, LVPWT and left ventricular mass index after adjustment for the confounding factors. Similarly, Fibrosis‐4 was associated with left atrial dimension, interventricular septum thickness, LVPWT and left ventricular mass index. In contrast, the Aspartate Aminotransferase to Platelet Ratio Index was only associated with LVPWT. Conclusions Non‐invasive liver fibrosis scores, especially the NFS, are independently associated with subclinical myocardial remodeling in type 2 diabetes patients., The Non‐Alcoholic Fatty Liver Disease Fibrosis Score is independently associated with subclinical myocardial remodeling in type 2 diabetes patients.

Aims/Introduction This study aims to evaluate the prevalence of and factors associated with non‐alcoholic fatty liver disease (NAFLD) in Indian women with prior gestational diabetes mellitus (GDM) diagnosed using International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Materials and Methods This cross‐sectional study (2018–2019) enrolled women with and without prior GDM. Study participants underwent detailed assessments, including relevant medical, obstetric and demographic details; 75‐g oral glucose tolerance test with glucose and insulin estimation at 0, 30 and 120 min; and other relevant biochemical and anthropometric measurements. NAFLD status was defined by ultrasonography. Results We evaluated a total of 309 women (201 and 108 with and without prior GDM, respectively) at a mean age of 31.9 ± 5.0 years and median of 16 months (interquartile range 9–38 months) following the index delivery. The prevalence of NAFLD was significantly higher in women with prior GDM (62.7% vs 50.0%, P = 0.038; grade 2 and 3 disease, 13.9% vs 6.5%). On logistic regression analysis (fully adjusted model), the odds of NAFLD were 2.11‐fold higher in women with prior GDM (95% confidence interval 1.16–3.85, P = 0.014). Overweight/obesity, metabolic syndrome, prediabetes and homeostasis model of assessment of insulin resistance (a measure of insulin resistance) were positively associated with NAFLD, whereas the Matsuda index (a measure of insulin sensitivity) showed a negative association with NAFLD. Conclusions The prevalence of NAFLD is high in women with prior GDM. Such women also have a high burden of cardiometabolic risk factors. Future studies should evaluate the intermediate and long‐term hepatic and cardiovascular risk, and the impact of lifestyle interventions in reducing morbidity in such women., This study evaluated the prevalence and risk factors of non‐alcoholic fatty liver disease in Indian women with prior gestational diabetes mellitus diagnosed using International Association of Diabetes and Pregnancy Study Groups criteria. Ultrasonography of abdomen was used to define non‐alcoholic fatty liver disease status. Prevalence of non‐alcoholic fatty liver disease was significantly higher in women with prior gestational diabetes mellitus (62.7% vs 50.0%, P = 0.038; grade 2 and 3 disease, 13.9% vs 6.5%).

PURPOSE To evaluate the association between severity of hepatic steatosis/fibrosis with clinical, laboratory, and echocardiographic characteristics, including visceral obesity and type 2 diabetes mellitus (T2DM)-related micro- and macrovascular complications in diabetic patients with non-alcoholic fatty liver disease (NAFLD). METHODS We studied 60 consecutive NAFLD outpatients with T2DM, recording several demographic and clinical characteristics, trunk and visceral fat, cardiac ultrasound, and micro- and macrovascular complications of diabetes mellitus including microalbuminuria, diabetic peripheral neuropathy, peripheral vascular disease, and cardiac autonomic function. Severity of steatosis and fibrosis was evaluated with abdominal ultrasound and liver stiffness measurements, respectively. RESULTS Twenty-three (41%) of the patients had grade 1 steatosis and mean liver stiffness was 7.5 ± 3 kPa. After applying Bonferroni correction for multiple comparisons, ferritin concentration was the only factor significantly different between patients with mild (grade 1) compared to those with moderate/severe (grade 2/3) steatosis and showed good discriminative ability for the presence of moderate/severe steatosis (AUC: 0.74, sensitivity 88%, specificity 48%, PPV 74%, and NPV 72%). In addition, waist circumference was the only factor associated with the presence of significant fibrosis (≥ F2) with very good discriminative ability (AUC: 0.77, sensitivity 89%, specificity 45%, PPV 75%, and NPV 70%). CONCLUSION Specific clinical and laboratory characteristics, which may be determined via widely accessible and noninvasive techniques, were associated with severity of diabetics NAFLD, taking into account echocardiographic characteristics, visceral obesity, and T2DM-related systemic complications.

Background Non-alcoholic fatty liver disease (NAFLD) has high morbidity and mortality related to cardiovascular disease (CVD), but statins have been historically underutilised in these patients due to concern for hepatotoxicity. Aims To characterise trends in statin use among individuals with NAFLD and to determine predictors of statin utilisation in this population. Methods Individuals with NAFLD were identified from 2005 to 2018 continuous National Health and Nutrition Examination Survey. Trends in statin use over time were assessed, and predictors of statin under-utilisation for primary prevention were identified. The roles of a known diagnosis of liver disease and disease severity were examined. Results We included 14 113 individuals; 34.6% had NAFLD, of whom 5.4% reported a liver disease diagnosis. There was a significant increase in statin use for primary prevention between 2005 and 2018 (18.1%-25.0%; P = 0.03), but guideline-indicated use for this purpose was low (54.5% between 2005 and 2012; 48.6% between 2013 and 2018). A known NAFLD diagnosis was a negative predictor of statin use during the earlier time period but not more recently. Utilisation did not decrease with increasing liver disease severity. Conclusions In a nationally representative population with NAFLD, statin use for primary prevention has increased over time, but guideline-concordant use remains low. A known liver disease diagnosis was associated with lack of statin use in the earlier time period but not more recently, suggesting a changing perspective of underlying liver disease impacting statin utilisation. Further work to improve guideline-indicated statin use in this high-risk population is needed.

Abstract. Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were

Background Non-alcoholic fatty liver disease (NAFLD) is increasing in recognition as a hepatic condition that is unrelated to significant alcoholic consumption, but has rather, been suggested to constitute cardiovascular risk (irrespective of traditional risk factors and high-risk plaque features). Both coronary artery disease and NAFLD share the same pathophysiology and metabolic profile. NAFLD can theoretically be a source/initiator for coronary artery disease (CAD). We aimed to study the association between NAFLD, CAD, the presence of high-risk plaque features, and the severity of stenosis. Results We recruited 800 patients with suspected obstructive CAD and planned for coronary computed tomography angiography (CCTA), Exclusion criteria: heavy alcohol consumption; contraindications to contrast media; unevaluated coronary-artery segments; other known liver disease; and use of oral corticosteroids and/or amiodarone. Non-enhanced Computed Tomography abdomen was performed before the CCTA to detect NAFLD. To study the association between NAFLD and the presence of CAD, patients were classified as to either have, or not have CAD. The CAD group were then further studied for the presence of high-risk plaque features: napkin ring sign, Positive remodelling, Low Hounsfield unit (HU), and Spotty calcium; and their association with NAFLD. Thirty-two per cent of patients had NAFLD and 45% had CAD. A significant association between NAFLD and CAD was found (OR 4.21, 95% CI (confidence interval) (2.83–6.25), p = 0.000). In CAD patients, significant associations were present between NAFLD and high-risk plaque features: Napkin ring sign, Positive remodelling, Low HU, and Spotty calcium (OR 7.88, 95% CI (4.39–14.12), p p p p 50% stenosis or 3V disease, and Total occlusion, respectively, p Conclusions NAFLD is strongly associated with CAD, high-risk plaque features and higher grade of stenosis.

Background Non-alcoholic fatty liver disease (NAFLD) patients are at a substantial risk for developing cardiovascular disease (CVD). High-density lipoprotein (HDL) is well known to have protective effects against the development of atherosclerotic CVD. One of the major antiatherogenic effects of HDL is its anti-oxidative function. Objectives This study investigated the association of anti-oxidative capacity of HDL with subclinical atherosclerosis in NAFLD and non-NAFLD subjects. Methods A total of 143 subjects including 51 NAFLD and 92 control subjects were included in this case–control study. HDL oxidative index (HOI) was determined spectrophotometrically using a cell-free method in the presence of a fluorescent substrate dichlorofluorescein diacetate (DCFDA). Paraoxonase 1 (PON1) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) plasma levels were assessed in both groups. Results The NAFLD patients with impaired HDL anti-oxidative function (HOI ≥ 1) had higher MDA levels, aspartate amino transferase (AST), liver stiffness (LS), and carotid intima-media thickness (cIMT) values compared to the controls. HDL oxidative index (HOI) was positively correlated with MDA levels and cIMT and negatively correlated with SOD activity. Conclusions Higher circulating levels of MDA were associated with the impaired anti-oxidative function of HDL in NAFLD. The impaired anti-oxidative capacity of HDL might be related to NAFLD severity and subclinical atherosclerosis in NAFLD patients.

BACKGROUND: Essential phospholipids (EPL) are used as adjuvant treatment in people with fatty liver disease and other chronic liver diseases. A new formulation of EPL paste was developed to improve patient compliance. The study was aimed to assess the safety, patient-reported outcomes, and impact on compliance of the new EPL paste formulation in patients with non-alcoholic fatty liver disease (NAFLD) or viral hepatitis. METHODS: The study enrolled 147 patients (48.3% male; mean ± standard deviation (SD) age 44.8 ± 10.5 years) in the intention-to-treat population; 72.8% had NAFLD and 27.9% had viral hepatitis B (HBV) or hepatitis C (HCV). Patients received EPL paste (one 600 mg sachet 3 times daily) for 12 weeks, with 4-, 8-, and 12-week scheduled visits and a 13-week follow-up visit. Patient-reported outcomes were evaluated at 4, 8, and 12 weeks compared with baseline using dedicated Likert scales. Compliance was assessed by comparing actual versus prescribed dosing of the EPL. RESULTS: After 12-week treatment with EPL paste, statistically significant improvements were observed in mean ± SD Global Overall Symptom scores (from 4.21 ± 1.09 to 1.87 ± 0.91; P < .01) and overall Gastrointestinal Symptom scores (from 19.91 ± 5.74 to 11.17 ± 3.57; P < .01), compared to baseline scores. Compliance with prescribed essential phospholipid treatment was 99% throughout the 12-week treatment period. CONCLUSION: Essential phospholipids paste had a favorable safety profile associated with improved gastrointestinal symptoms and with high levels of compliance in patients with NAFLD and viral hepatitis.

Background Pemafibrate is a novel, selective peroxisome proliferator-activated receptor α modulator (SPPARMα). In mice, Pemafibrate improved the histological features of non-alcoholic steatohepatitis (NASH). In patients with dyslipidaemia, it improved serum alanine aminotransferase (ALT). Aims To evaluate the efficacy and safety of Pemafibrate in patients with high-risk, non-alcoholic fatty liver disease (NAFLD). Methods This double-blind, placebo-controlled, randomised multicentre, phase 2 trial randomised 118 patients (1:1) to either 0.2 mg Pemafibrate or placebo, orally, twice daily for 72 weeks. The key inclusion criteria included liver fat content of ≥10% by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF); liver stiffness of ≥2.5 kPa, by magnetic resonance elastography (MRE); and elevated ALT levels. The primary endpoint was the percentage change in MRI-PDFF from baseline to week 24. The secondary endpoints included MRE-based liver stiffness, ALT, serum liver fibrosis markers and lipid parameters. Results There was no significant difference between the groups in the primary endpoint (-5.3% vs -4.2%; treatment difference -1.0%, P = 0.85). However, MRE-based liver stiffness significantly decreased compared to placebo at week 48 (treatment difference -5.7%, P = 0.036), and was maintained at week 72 (treatment difference -6.2%, P = 0.024), with significant reduction in ALT and LDL-C. Adverse events were comparable between the treatment groups and therapy was well tolerated. Conclusions Pemafibrate did not decrease liver fat content but had significant reduction in MRE-based liver stiffness. Pemafibrate may be a promising therapeutic agent for NAFLD/NASH, and also be a candidate for combination therapy with agents that reduce liver fat content. ClinicalTrials.gov, number: NCT03350165.

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide. A strong relationship exists between NAFLD and diabetes mellitus. There is growing evidence of a mechanistically complex and strong association between the two diseases. Current data also shows that one disease actually leads to worsening of the other and vice versa. Understanding of the various pathophysiological mechanisms involved, natural history and spectrum of these two diseases is essential not only for early diagnosis and management but also for prevention of severe disease forms. Despite the tremendous progress made in recent times in acquiring knowledge about these highly prevalent diseases, the guidelines and recommendations for screening and management of diabetics with NAFLD remain ambiguous. An interdisciplinary approach is required to not only raise awareness of the prevalence of NAFLD in diabetics but also for better patient management. This can help attenuate the development of significant complications, such as cirrhosis, decompensation and hepatocellular carcinoma in these patients, thereby halting NAFLD in its tracks. This review focuses on the pivotal role of primary care physicians and endocrinologists in identification of NAFLD in diabetics in early stages and the role of proactive screening for prompt referral to hepatologist.

ObjectiveSome data suggest a positive association between non-alcoholic fatty liver disease (NAFLD) and incident major adverse cardiovascular events (MACEs). However, data are lacking from large cohorts with liver histology, which remains the gold standard for staging NAFLD severity.DesignThis population-based cohort included all Swedish adults with histologically confirmed NAFLD and without cardiovascular disease (CVD) at baseline (1966–2016, n=10 422). NAFLD was defined from prospectively recorded histopathology and categorised as simple steatosis, non-fibrotic steatohepatitis, non-cirrhotic fibrosis and cirrhosis. Patients with NAFLD were matched to ≤5 population controls without NAFLD or CVD, by age, sex, calendar year and county (n=46 517). Using Cox proportional hazards modelling, we calculated multivariable adjusted HRs (aHRs) and 95% CIs for MACE outcomes (ie, ischaemic heart disease (IHD), stroke, congestive heart failure (CHF) or cardiovascular (CV) mortality).ResultsOver a median of 13.6 years, incident MACE was confirmed in 2850 patients with NAFLD and 10 648 controls. Patients with NAFLD had higher incidence of MACE than controls (24.3 vs 16.0/1000 person-years (PY); difference=8.3/1000 PY; aHR 1.63, 95% CI 1.56 to 1.70), including higher rates of IHD (difference=4.2/1000 PY; aHR 1.64, 95% CI 1.54 to 1.75), CHF (difference=3.3/1000 PY; aHR 1.75, 95% CI 1.63 to 1.87), stroke (difference=2.4/1000 PY; aHR 1.58, 95% CI 1.46 to 1.71) and CV mortality (difference=1.2/1000 PY; aHR 1.37, 95% CI 1.27 to 1.48). Rates of incident MACE increased progressively with worsening NAFLD severity (ptrend=0.02), with the highest incidence observed with cirrhosis (difference vs controls=27.2/1000 PY; aHR 2.15, 95% CI 1.77 to 2.61).ConclusionCompared with matched population controls, patients with biopsy-proven NAFLD had significantly higher incidence of MACE, including IHD, stroke, CHF and CV mortality. Excess risk was evident across all stages of NAFLD and increased with worsening disease severity.

Background. Non-alcoholic fatty liver disease (NAFLD) is a leading etiological factor of chronic liver diseases in children in industrialized countries. The high prevalence of small intestinal bacterial overgrowth (SIBO) is common in patients with NAFLD. Therefore, the purpose of our work is to study the impact of SIBO on the structural and functional parameters of the liver in obese/overweight children. Materials and methods. We examined 73 children aged 6 to 17 years, mean age of patients was (11.41 ± 2.68) years. Depending on the presence of overweight/obesity and the results of glucose hydrogen breath test (HBT), patients were divided into 2 groups: group 1 — 30 overweight/obese persons with SIBO, group 2 — 28 overweight/obese children without SIBO. The control group consisted of 15 apparently healthy children with normal weight and without SIBO. The presence of liver steatosis was established by means of transient elastography with controlled attenuation parameter. Additionally, we performed lactose HBT and a biochemical blood test with biochemical hepatogram, determination of lipid and carbohydrate parameters. Results. It was found that 70 % of children in group 1 had NAFLD, compared to 32 % in group 2. Also, erythrocyte sedimentation rate was higher in group 1 than in groups 2 and 3 (p, Актуальность. Неалкогольная жировая болезнь печени (НАЖБП) занимает лидирующие позиции среди хронических заболеваний печени у детей в промышленно развитых странах. Известно, что для пациентов с НАЖБП характерна высокая распространенность синдрома избыточного бактериального роста (СИБР). Цель работы — изучить влияние СИБР на структурно-функциональные показатели печени у детей с избыточным весом и ожирением. Материалы и методы. Обследовано 73 ребенка в возрасте от 6 до 17 лет, средний возраст пациентов составил (11,41 ± 2,68) года. В зависимости от наличия избыточного веса/ожирения и результатов водородного дыхательного теста (ВДТ) с глюкозой пациенты были разделены на 2 группы: 1 группа — 30 детей с избыточным весом/ожирением и наличием СИБР, 2 группа — 28 детей с избыточным весом/ожирением без СИБР. Контрольную группу составили 15 практически здоровых детей с нормальным весом и без СИБР по результатам ВДТ с глюкозой. Наличие стеатоза печени устанавливали при помощи транзиентной эластографии с функцией САР. Дополнительно проводили ВДТ с лактозой и биохимический анализ крови с определением показателей биохимической гепатограммы, липидного и углеводного спектров. Результаты. Установлено, что 70 % детей 1 группы имели сопутствующую НАЖБП по сравнению с 32 % во 2 группе. В 1 группе скорость оседания эритроцитов была выше, чем во 2 и 3 группах (p, Актуальність. Неалкогольна жирова хвороба печінки (НАЖХП) посiдає провідні позиції серед хронічних захворювань печінки в дітей у промислово розвинених країнах. Відомо, що для пацієнтів iз НАЖХП характерна висока поширеність синдрому надмірного бактеріального росту (СНБР). Метою роботи є вивчення впливу СНБР на структурно-функціональні показники печінки в дітей iз надмірною вагою та ожирінням. Матеріали та методи. Обстежено 73 дитини віком від 6 до 17 років, середній вік пацієнтів становив (11,41 ± 2,68) року. Залежно від наявності надмірної ваги/ожиріння i результатів водневого дихального тесту (ВДТ) з глюкозою пацієнти були розподілені на 2 групи: 1 група — 30 дітей iз надмірною вагою/ожирінням та СНБР, 2 група — 28 дітей iз надмірною вагою/ожирінням без СНБР. Контрольну групу становили 15 практично здорових дітей iз нормальною вагою та без СНБР за результатами ВДТ з глюкозою. Наявність стеатозу печінки встановлювали за допомогою транзієнтної еластографії з функцією САР. Додатково проводили ВДТ з лактозою та біохімічний аналіз крові з визначенням показників біохімічної гепатограми, ліпідного й вуглеводного спектрів. Результати. Встановлено, що в 70 % дітей 1 групи була супутня НАЖХП порівняно з 32 % у 2 групі. У 1 групі швидкість осідання еритроцитів була вищою, ніж у 2 і 3 групах (p

Актуальность. Неалкогольная жировая болезнь печени (НАЖБП) охватывает спектр заболеваний, тесно связанных с метаболическими факторами риска. Цель: изучить эффективность терапии с использованием препарата Bifidobacterium infantis (B.infantis) 35624 на динамику проявлений депрессии у больных НАЖБП и сахарным диабетом (СД) 2-го типа. Материалы и методы. Обследовано 56 больных НАЖБП. Больные разделены на 2 группы: больные I группы (n = 26) для коррекции дисбиоза толстой кишки (ДТК) получали комбинированный пробиотик; II группы (n = 30) — препарат B.іnfantis. Нарушение функций центральной нервной системы определяли с помощью таких нейропсихометрических тестов, как шкала самооценки Спилбергера — Ханина, шкала депрессии Бека (BDI), шкала Zung, Торонтская алекситимическая шкала. Результаты. Анализ микробиологического исследования фекалий у обследованных больных обеих групп до лечения указывает на выраженные изменениями в количественном и качественном составе микрофлоры толстой кишки. У больных НАЖБП и СД 2-го типа соматическая патология сопровождается выраженными проявлениями депрессии, тревожности, неуверенности в себе. Продемонстрировано значительное уменьшение выраженности депрессии, тревожности на фоне нормализации микробного состава толстой кишки при длительном приеме B.infantis 35624 у больных НАЖБП и СД 2-го типа. Выводы. У больных НАЖБП и СД 2-го типа установлено ДТК преимущественно II (у 53,3–53,8 % обследованных) и I степеней (у 30,0–30,8 % обследованных). У больных НАЖБП и СД 2-го типа определяются тревожные расстройства, умеренно выраженные проявления депрессии по шкале Спилбергера — Ханина, BDI, шкале Zung и Торонтской шкале, что требует соответствующей коррекции. Курсовой прием B.infantis 35624 у больных НАЖБП и СД 2-го типа является эффективным средством не только для коррекции дисбиоза толстой кишки, но и коррекции проявлений депрессии и тревожных состояний у данных пациентов., Актуальність. Неалкогольна жирова хвороба печінки (НАЖХП) охоплює спектр захворювань, тісно пов’язаних із метаболічними факторами ризику. Мета: визначити ефективність комплексної терапії з використанням препарату Bifidobacterium infantis (B.іnfantis) 35624 на динаміку проявів депресії у хворих на НАЖХП та цукровий діабет (ЦД) 2-го типу. Матеріали та методи. Обстежено 56 хворих з НАЖХП. Хворих розподілено на 2 групи: хворі І групи (n = 26) для корекції дисбіозу товстої кишки (ДТК) отримували комбінований пробіотик; ІІ групи (n = 30) — препарат B.іnfantis. Порушення функції центральної нервової системи визначали за допомогою таких нейропсихометричних тестів, як шкала самооцінки Спілбергера — Ханіна, шкала депресії Бека (BDI), шкала Zung, Торонтська алекситимічна шкала. Результати. Аналіз мікробіологічного дослідження фекалій в обстежених хворих обох груп до лікування вказує на виражені зміни в кількісному і якісному складі мікрофлори товстої кишки. У хворих на НАЖХП та ЦД 2-го типу соматична патологія супроводжується вираженими проявами депресії, тривожності, невпевненості у собі. Продемонстровано значне зменшення вираженості депресії, тривожності на фоні нормалізації мікробного складу товстої кишки при тривалому прийомі B.infantis 35624 у хворих на НАЖХП та ЦД 2-го типу. Висновки. У хворих на НАЖХП та ЦД 2-го типу встановлено ДТК переважно ІІ (у 53,3–53,8 % обстежених) та І ступенів (30,0–30,8 % обстежених). У хворих на НАЖХП та ЦД 2-го типу визначаються тривожні розлади, помірно виражені прояви депресії за шкалою Спілбергера — Ханіна, BDI, шкалою Zung та Торонтською шкалою, а це вимагає корекції. Курсовий прийом B.infantis 35624 хворими на НАЖХП та ЦД 2-го типу є ефективним засобом не тільки для корекції дисбіозу товстої кишки, але і зменшення проявів депресії та тривожних станів у таких пацієнтів., Background. Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases, which are closely associated with metabolic risk factors. The purpose of the research was to determine the effect of comprehensive therapy using Bifidobacterium infantis (B.infantis) 35624 drug on the dynamics of depression manifestations in patients with NAFLD and type 2 diabetes mellitus (T2DM). Materials and methods. Fifty-six patients with NAFLD were examined. They were divided into 2 groups: the first group (n = 26) of patients received a combined probiotic for the correction of colon dysbiosis, the second group (n = 30) received B.іnfantis preparation. Central nervous system disorders were determined using the following neuropsychometric tests (Spielberg-Hanin Self-Rating Scale, Beck Depression Inventory, Zung Self-Rating Depression Scale, Toronto Alexithymia Scale). Results. Analysis of microbiological study of feces in the examined patients of both groups before treatment indicates pronounced changes in the quantitative and qualitative composition of intestinal microflora. In patients with NAFLD and T2DM, somatic pathology is accompanied by marked manifestations of depression, anxiety, self-doubt. The research demonstrated a significant decrease in the severity of depression and anxiety on the background of normalization of the microbial composition of the colon with long-term administration of B.infantis 35624 in patients with NAFLD and T2DM. Conclusions. In patients with NAFLD and T2DM, colon dysbiosis was detected, mainly degrees II (in 53.3–53.8 % of surveyed people) and I (in 30.0–30.8 % of individuals). Patients with NAFLD and T2DM are diagnosed with anxiety disorders, moderate manifestations of depression on the Spielberg-Hanin scale, Beck Depression Inventory, Zung Self-Rating Depression Scale, and Toronto Alexithymia Scale, which requires correction. Course intake of B.infantis 35624 by patients with NAFLD and T2DM is an effective tool not only for the correction of colon dysbiosis, but also for the reduction of the manifestations of depression and anxiety in these patients.

Dietary modification plays a vital role in the treatment of non-alcoholic liver diseases. We investigated the effects of the consumption of a different amount of dehulled adlay, which has hypolipidaemic and anti-inflammatory properties, on non-alcoholic fatty liver disease (NAFLD). We fed rats a high-fat-high-fructose liquid diet for 16 weeks to induce NAFLD. The rats were divided into three groups fed the NAFLD diet only (NN) or a diet containing 44·9 or 89·8 g/l of dehulled adlay (NA and NB groups, respectively). After 8 weeks, the NA and NB groups had lower C-reactive protein levels and improvement in insulin resistance. In addition, the NB group had lower liver weight and hepatic TAG and cholesterol concentrations than did the NN group. Compared with the NN group, the high-dose NB group had improved steatosis, lower hepatic TNF-α, IL-1β and IL-6 levels and lower adipose leptin levels. Our results suggest that a diet containing dehulled adlay can ameliorate NAFLD progression by decreasing of insulin resistance, steatosis and inflammation.

Introduction Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, which is estimated to affect 20-30% of the adult population in Europe. Several studies have shown an association of NAFLD with multiple cardiovascular risk factors such as abdominal obesity, atherogenic dyslipidaemia, hypertension, insulin resistance, and impaired glucose tolerance. Atherosclerosis is a chronic, progressive, inflammatory disease, which begins early in life and follows a long asymptomatic phase. Coronary artery calcification (CAC) is the radiological confirmation of the presence of atherosclerotic coronary artery disease. The predictive value of CAC for future cardiac events is well established. Also, the progression of CAC is strongly associated with the development of cardiovascular events. Aim To assess the association of NAFLD with the progression of subclinical atherosclerotic activity, reflected as the dynamic changes in CAC score over time. Material and methods The databases PubMed/Medline/Embase from inception until 31 December 2020 were searched for observational studies investigating NAFLD and CAC progression in adults. Results In total, 5 studies were included, 4 of which, including 10,060 patients, provided data regarding the association of NAFLD with the progression of CAC. The analysis showed that NAFLD is associated with significant odds of progression of CAC; OR = 1.5, 95% CI: 1.34-1.68, p = 0.001. No publication bias was detected (Egger's test p = 0.6). Meta-regression analyses proved that OR toward CAC progression is not significantly influenced by the time of follow-up (coefficient = 0.0083, Z = 1.14, p = 0.25). Conclusions NAFLD increases the risk toward CAC progression over time.

Background/Aims: Maternal and fetal outcomes in pregnant patients with Non-alcoholic fatty liver disease (NAFLD) have been largely unexplored. To determine the level of evidence associated with maternal and fetal outcomes in pregnant women with NAFLD.Methods: We conducted a comprehensive literature search. The studies included pregnant patients with a previous, current or subsequent diagnosis of NAFLD. We used a random-effects model using odds ratios (OR) with 95% confidence intervals (CI).Results: Twenty-two studies, with 13,641 female NAFLD patients were reviewed. The results highlight that NAFLD patients had a statistically significant increased likelihood of baseline diabetes mellitus (OR, 6.00; 95% CI, 2.21–16.31; P0.05).Conclusions: This meta-analysis provides pooled evidence that NAFLD is associated with a substantial increase in maternal diabetic and hypertensive complications and multiple adverse fetal outcomes. This data is important for clinicians managing these patients before, during and after pregnancy.

Non-alcoholic fatty liver disease (NAFLD) affects about a quarter of the world's population and it is closely linked to hypertension (HT). Pro-inflammatory and anti-inflammatory cytokines play a key role in the pathology progression, and the search for non-invasive biomarkers for the diagnosis of NAFLD remains an important issue. The aim of the study was to determine the diagnostic and prognostic value of IL-1β and IL-10 in assessing the progression of liver parenchyma changes in patients with NAFLD and HT comorbidity. Materials and methods. A study of 115 patients with non-alcoholic steatohepatitis (NASH) was performed. The main group consisted of 63 patients with NASH and HT, 52 patients with isolated NAFLD represented the comparison group. Clinical and laboratory parameters were evaluated, IL-10 and IL-1β levels were measured by ELISA method, ultrasound steatometry and elastography were performed in all patients. Results. The attenuation coefficient and median liver stiffness in NAFLD and HT group significantly exceeded the results in the isolated NAFLD group and in the control group. The IL-1β level in NAFLD and HT group was 17.55 pg/ml, and in isolated NAFLD group the indicator averaged 15.72 pg/ml, which exceeded the control values (8.26 pg/ml). IL-10 level was 12.69 pg/ml and 14.34 pg/ml in patients with comorbid and isolated NAFLD, respectively, while control results averaged 16.19 pg/ml. It were found strong relationship between IL-1β, IL-10 and CRP levels in patients with NAFLD and HT (r=0.61, p=0.024, and r=-0.69, p=0.036, respectively). Inverse correlations were also found between the cytokines IL-1β and IL-10 in NAFLD patients with and without HT (r=-0.61, p

Introduction In parallel with the improvement of living standard, Non-alcoholic fatty liver disease (NAFLD) becomes the most common liver disease around the world. Huazhi Fugan Granules (HZFGG) is a formula which is used to treating of fatty liver, Based on the data we studied, HZFGG may have potential as a therapeutic formula for the alleviation of NAFLD. Objectives The aim of our study was to identifying the improvement of HZFGG on NAFLD and exploring the potential mechanisms. Methods MCD diet fed C57BL/6 mice once a day for 4 weeks to induce NAFLD model, HZFGG (10, 15, 20 g/kg) orally administered simultaneously. The serum levels of TC, TG, ALT, AST were detected. H&E and Oil Red O staining were used to observed the liver sections. TNF-α, IL-1β and Gpx were also detected. The expression levels of TLR4, MyD88, p-NF-κB, NF-κB, p-IκBa were measured by western blotting assay. The apoptosis of the liver tissues were detected by TUNEL assay. Results HZFGG decreased the serum levels of TC, TG, ALT, AST in MCD-diet mice. HZFGG alleviated inflammation by decreasing the levels of TNF-α and IL-1β and ameliorated oxidative stress through increased the level of Gpx. HZFGG Attenuates MCD-induced liver steatosis and injury in mice. Hepatocyte apoptosis was decreased after HZFGG treatment. Furthermore, HZFGG also suppressed the expression levels of TLR4 and MyD88, subsequently, inhibited the phosphorylation of NF-κB and IκBa. Conclusion HZFGG can improved MCD induced hepatic injury through inhibited TLR4/NF-κB signaling pathway in NAFLD model.

To investigate the cross-sectional and longitudinal correlation between sex hormones and non-alcoholic fatty liver disease (NAFLD) in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG). A total of 360 patients with obesity aged 16–48 years (170 men and 190 women) were enrolled between May 2017 and March 2021. Among them, 132 patients (55 men and 77 women) who underwent LSG had follow-up data. Anthropometric parameters, metabolic variables, and sex hormones were measured. NAFLD was assessed by FibroScan with controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). In the preoperative cohort, levels of CAP and LSM were significantly higher in men than women. Lower total testosterone (TT) was associated with higher CAP and LSM in men, whereas higher TT was associated with higher CAP in women. In the postoperative cohort, TT levels and NAFLD were significantly modified after LSG in both genders. Changes in TT levels at 3 months after surgery were negatively correlated with changes in CAP levels in men, and changes in TT levels at 6 months after surgery were positively correlated with changes in CAP levels in women. After adjusting possible confounders, the changes in TT levels were independently correlated with CAP variation in both genders. LSG significantly modified TT levels and NAFLD in both genders. The correlation between TT levels and NAFLD at baseline as well as the changes after surgery suggested TT levels play an important role in the development and regression of NAFLD in both genders.

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)-based therapy is currently considered to be an effective treatment for NAFLD. The present study aimed to determine whether hUC-MSCs-exosomes have a hepatoprotective effect on NAFLD. We constructed NAFLD rat model by high-fat high-fructose feeding. Liver cells (L-O2) were treated with palmitic acid (PA) to mimic NAFLD model. NAFLD rats and PA-treated L-O2 cells were treated with hUC-MSCs-exosomes, and then we determined the influence of exosomes on liver damage and glucose and lipid metabolism in vivo and in vitro. We found that hUC-MSCs-exosomes exhibited an up-regulation of miR-627-5p. Exosomal miR-627-5p promoted cell viability and repressed apoptosis of PA-treated L-O2 cells. Exosomal miR-627-5p also enhanced the expression of G6Pc, PEPCK, FAS and SREBP-1c and suppressed PPARα expression in PA-treated L-O2 cells. Moreover, miR-627-5p interacted with fat mass and obesity-associated gene (FTO) and inhibited FTO expression in L-O2 cells. MiR-627-5p-enriched exosomes improved glucose and lipid metabolism in L-O2 cells by targeting FTO. In vivo, exosomal miR-627-5p ameliorated insulin tolerance, liver damage, glucose and lipid metabolism and reduced lipid deposition in NAFLD rats. Exosomal miR-627-5p also reduced body weight, liver weight, and liver index (body weight/liver weight) in NAFLD rats. In conclusion, these data demonstrate that HUC-MSCs-derived exosomal miR-627-5p improves glucose and lipid metabolism and alleviate liver damage by repressing FTO expression, thereby ameliorating NAFLD progression. Thus, hUC-MSCs-exosomes may be a potential treatment for NAFLD.

This systematic review and meta-analysis aimed to compare the outcomes of curative therapy (resection, transplantation, ablation) for hepatocellular carcinoma (HCC) arising from non-alcoholic fatty liver disease (NAFLD) and non-NAFLD etiologies.A systematic search of PubMed, EMBASE and Cochrane Library was conducted for studies comparing survival, peri- and post-operative outcomes. Quality assessment was performed using the Newcastle-Ottawa scale.Findings for 5579 patients were pooled across 9 studies and examined. Analysis demonstrated improved disease-free survival (DFS; HR 0.85, 95% CI 0.74-0.98, p = 0.03) and overall survival (OS; HR 0.87; 95% CI 0.81-0.93; p 0.0001) in NAFLD-HCC patients undergoing liver resection as compared to non-NAFLD HCC patients. NAFLD-HCC patients undergoing all forms of curative therapy were similarly associated with improved OS (HR 0.96; 95% CI 0.86-1.06; p = 0.40) and DFS (HR 0.85; 95% CI 0.74-0.98; p = 0.03), albeit results being significant only for DFS. Only 2 studies reported higher rates of peri- and post-operative complications in patients with NAFLD-HCC. Significant inter-study heterogeneity precluded further analysis.NAFLD-HCC patients can enjoy long-term survival benefit with aggressive curative therapy. Peri- and post-operative morbidity should be mitigated with pre-operative optimization of comorbidities, and deliberately close post-operative monitoring.

Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease of unknown etiology occurring frequently in individuals with metabolic disturbances. Obesity has been suggested as a potential risk factor for the severity of OPLL. We aimed to investigate whether non-alcoholic fatty liver disease (NAFLD) is associated with OPLL severity. We assessed the severity of NAFLD by a liver-to-spleen (L/S) ratio on computed tomography (CT) scans of 85 symptomatic OPLL patients at a single institution in Japan. We also assessed the severity of OPLL by CT reconstruction sagittal and axial images. The prevalence of NAFLD in middle-aged patients (age