Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide and poses serious harm to human health. There is growing evidence suggesting that the administration of specific supplements or nutrients may slow NAFLD progression. Silymarin is a hepatoprotective extract of milk thistle, but its efficacy in NAFLD remains unclear. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrails.gov, and China National Knowledge Infrastructure and were screened according to the eligibility criteria. Data were analyzed using Revman 5.3. Continuous values and dichotomous values were pooled using the standard mean difference (SMD) and odds ratio (OR). Heterogeneity was evaluated using the Cochran's Q test (I2 statistic). A P<0.05 was considered statistically significant. RESULTS: A total of 26 randomized controlled trials involving 2,375 patients were included in this study. Administration of silymarin significantly reduced the levels of TC (SMD[95%CI]=-0.85[-1.23, -0.47]), TG (SMD[95%CI]=-0.62[-1.14, -0.10]), LDL-C (SMD[95%CI]=-0.81[-1.31, -0.31]), FI (SMD[95%CI]=-0.59[-0.91, -0.28]) and HOMA-IR (SMD[95%CI]=-0.37[-0.77, 0.04]), and increased the level of HDL-C (SMD[95%CI]=0.46[0.03, 0.89]). In addition, silymarin attenuated liver injury as indicated by the decreased levels of ALT (SMD[95%CI]=-12.39[-19.69, -5.08]) and AST (SMD[95% CI]=-10.97[-15.51, -6.43]). The levels of fatty liver index (SMD[95%CI]=-6.64[-10.59, -2.69]) and fatty liver score (SMD[95%CI]=-0.51[-0.69, -0.33]) were also decreased. Liver histology of the intervention group revealed significantly improved hepatic steatosis (OR[95%CI]=3.25[1.80, 5.87]). CONCLUSIONS: Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in NAFLD patients. However, the effects of silymarin will need to be confirmed by further research.

Late-onset Wilson Disease in a Patient Followed-up for Nonalcoholic Fatty Liver Disease.

A 73-year-old woman was referred to our hospital for persistent liver dysfunction. When the patient was 45 years old, her youngest sister had been diagnosed with Wilson disease (WD). The patient therefore underwent several family screening tests, all of which were unremarkable. She had an annual medical checkup and was diagnosed with liver dysfunction and fatty liver at 68 years old. A liver biopsy and genetic testing were performed, and she was diagnosed with WD; chelation therapy was then initiated. In patients with hepatic disorders and a family history of WD, multiple medical examinations should be conducted, as the development of WD is possible regardless of age.

Chronic hepatitis B with concurrent metabolic dysfunction-associated fatty liver disease: Challenges and perspectives.

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has increased among the general population and chronic hepatitis B (CHB) patients worldwide. Although fatty liver disease is a well-known risk factor for adverse liver outcomes like cirrhosis and hepatocellular carcinoma, its interactions with the hepatitis B virus (HBV) and clinical impacts seem complex. The presence of hepatic steatosis may suppress HBV viral activity, potentially leading to attenuated liver injury. In contrast, the associated co-morbidities like diabetes mellitus or obesity may increase the risk of developing adverse liver outcomes. These findings implicate that components of MAFLD may have diverse effects on the clinical manifestations of CHB. To this end, a clinical strategy is proposed for managing patients with concurrent CHB and MAFLD. This review article discusses the updated evidence regarding disease prevalence, interactions between steatosis and HBV, clinical impacts, and management strategies, aiming at optimizing holistic health care in the CHB population.

Comparative efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists, pioglitazone and vitamin E for liver histology among patients with nonalcoholic fatty liver disease: systematic review and pilot network meta-analysis of randomized controlled trials.

INTRODUCTION: There is no conclusive evidence comparing the efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists to the other guidelines recommended pharmacotherapy for nonalcoholic fatty liver disease (NAFLD). Therefore, we aim to compare the effects of GLP-1 receptor agonists, pioglitazone and vitamin E in patients with NAFLD. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Library up to 11 April 2022. Randomized clinical trials (RCTs) comparing GLP-1 receptor agonists, pioglitazone and vitamin E against placebo or other active controls in patients with NAFLD were included. RESULTS: Nine RCTs including 1482 patients proved eligible. GLP-1 receptor agonists ranked first in steatosis, ballooning necrosis, γ-glutamyl transferase, body weight, body mass index, and triglycerides. Administration of GLP-1 receptor agonists, as compared with placebo, was associated with improvement in liver histology [steatosis (OR = 4.11, 95% CI: 2.83, 5.96), ballooning necrosis (OR = 3.07, 95% CI: 2.14, 4.41), lobular inflammation (OR = 1.86, 95% CI: 1.29, 2.68), fibrosis (OR = 1.52, 95% CI: 1.06, 2.20)]. CONCLUSIONS: GLP-1 receptor agonists were as effective as pioglitazone and vitamin E for liver histology among patients with NAFLD. GLP-1 receptor agonists might be considered as an alternative or complementary treatment in the future clinical practice. [Figure: see text].

What do we know about nutrient-based strategies targeting molecular mechanisms associated with obesity-related fatty liver disease?

Obesity is a risk factor for developing nonalcoholic fatty liver disease (NAFLD), and the associated molecular mechanisms could be targeted with nutrient-based strategies. Therefore, it is necessary to review the current mechanisms to propose further treatments. Obesity facilitates the onset of insulin resistance, lipidic abnormalities, hepatic fat accumulation, lipid peroxidation, mitochondrial dysfunction, excessive reactive oxygen species (ROS) production, and inflammation, all related to further steatosis progression and fibrosis. Microbiota alterations can also influence liver disease by the translocation of pathogenic bacteria, energy extraction from short chain fatty acids (SCFAs), intestinal suppression of the expression of fasting-induced adipose factor (FIAF), reduction of bile acids, and altered choline metabolism. There are also genetic polymorphisms in metabolic proteins that predispose to a higher risk of liver diseases, such as those found in the patatin-like phospholipase domain-containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) or also known as lysophosphatidylinositol acyltransferase 1 (LPIAT1), transmembrane channel-like 4 genes (TMC4), fat mass and obesity-associated protein (FTO), the b Klotho (KLB) and carboxylesterase (CES1). No clear dietary guidelines target all mechanisms related to NAFLD development and progression. However, energy and carbohydrate intake restriction, regular physical exercise, supplementation of antioxidants, and restoration of gut microbiota seem to have beneficial effects on the new proposed features of NAFLD.

The effectiveness of web-based interventions on non-alcoholic fatty liver disease (NAFLD) in obese children: A study protocol for a randomized controlled trial.

Aim: Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent liver disease in the world, increasing the risk of cirrhosis and hepatocellular carcinoma, and contributing to the development of type 2 diabetes, cardiovascular disease, and chronic kidney disease. This study aims to carry out a web-based continuum of a care intervention model to provide comprehensive care interventions for obese children with NAFLD, to improve the effectiveness of treatment of children with NAFLD. Design: A 1-year single-blinded randomized clinical trial in hospital in Zhejiang Province. Methods: Eighty subjects will implement the program in a randomized order. The interventions for the control group mainly consisted of the routine distribution of health education materials and health education by holding health-themed lectures, and the preliminary proposed interventions including establishing management teams, regularly delivering related health knowledge, daily uploading of health intervention records, regular supervision and mutual encouragement, home visiting and psychological guidance. The primary outcomes are serum biomarkers such as alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), aspartate aminotransferase, and imaging (liver ultrasound and magnetic resonance imaging). Second outcomes are: BMI, waist-to-hip ratio and quality of life. In addition, socio-demographic characteristics such as age, gender and ethnicity will be recorded. Children aged 7-18 years old and diagnosed with NAFLD will be included, patients will be not eligible if they do not agree to participate or are participating in other health intervention programs. This study was registered on ClinicalTrials.gov (NCT05527938). Results: Over the past 30 years, NAFLD has been recognized as one of the most common liver diseases in adults and children. The current studies have focused on promoting lifestyle changes in children with NASH by providing some education and advice to children and their families to improve the histological features of NASH and lose weight. Because of the convenience and efficiency of the internet can provide some new strategies and ways for lifestyle interventions for children with NAFLD. In addition, we have designed a high-quality RCT based on the SPIRIT guidelines, which also provides strong evidence in this area.

MAFLD, patient-centred care, and APASL.

Asian-Pacific nations are home to more than half the world's population and similar to other global super regions, metabolic dysfunction associated fatty liver disease (MAFLD) is the principal cause for chronic liver disease. To address the challenges ahead for tackling the disease at-scale, the Asian Pacific Association for the Study of the Liver (APASL) was the first pan-national society to endorse and lead the process for redefining the disease and adopting the more appropriate term "MAFLD" with its accompanying set of positive diagnostic criteria. As with this initiative, APASL and Hepatology International will continue to strive to lead the field and work with sister societies towards full adoption of MAFLD. This will advance the science and practice of Hepatology and help incorporate MAFLD within multidisciplinary care teams. Ultimately, it will lead to more cogent clinical trials built on innovative design platforms that include patients with any disease related to metabolic dysfunction. For our patients, an outcome of these endeavours will be the provision of holistic person-centred care for this disease that is so common in our region.

The effect of sesame oil consumption compared to sunflower oil on lipid profile, blood pressure, and anthropometric indices in women with non-alcoholic fatty liver disease: a randomized double-blind controlled trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in the world. There is strong evidence that dyslipidemia and other cardio-metabolic disorders are highly prevalent in patients with NAFLD. This trial aimed at examining the effect of sesame oil (SO) in the context of a weight loss program on lipid profile, blood pressure, and anthropometric indices in women with NAFLD. METHODS: This randomized, double-blind, controlled trial was carried out on 60 women with NAFLD. Subjects were randomly assigned to the SO group (n = 30) and sunflower oil (SFO) group (n = 30), each person consuming 30 g of oil per day for 12 weeks. All the participants received a hypocaloric diet (- 500 kcal/day) during the study. Lipid profile, blood pressure, and anthropometric indices were assessed at pre- and post-intervention phases. RESULTS: In total, 53 participants completed the study. Following 12 weeks of intervention, anthropometric indices (p < 0.001) and systolic blood pressure (SBP) (p < 0.05) were significantly decreased in both groups and diastolic blood pressure (DBP) was significantly decreased in So group (p = 0.03). There was no significant change in lipid profile in both groups (p > 0.05). After adjusting for confounders, DBP (p = 0.031) and total cholesterol (TC) divided by high-density lipoprotein cholesterol (HDL-C) (p = 0.039) in the SO group were significantly reduced compared to the SFO group (p < 0.05). CONCLUSIONS: The present clinical trial revealed that SO and SFO may not differently affect anthropometric indices, SBP, and lipid profile except for TC/HDL-C. In addition, SO may be effective in improvement of DBP and TC/HDL-C compared to the SFO group. TRIAL REGISTRATION: Ethical approval of this trial was obtained at Isfahan University of Medical Sciences with the reference number of IR.MUI. RESEARCH: REC.1399.548 ( https://ethics. RESEARCH: ac.ir/ProposalCertificateEn.php?id=158942&Print=true&NoPrintHeader=true&NoPrintFooter=true&NoPrintPageBorder=true&LetterPrint=true ), and it was registered before the start of the patient recruitment on December 12th, 2020 in the Iranian Registry of Clinical Trials (IRCT) with the registration number of IRCT20140208016529N6 .

Effect of resveratrol supplementation on hepatic steatosis and cardiovascular indices in overweight subjects with type 2 diabetes: a double-blind, randomized controlled trial.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are prone to develop non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD). We aimed to investigate whether the resveratrol supplementation improves novel hepatic and cardiovascular indices in these patients. METHODS: We conducted a double-blind, randomized controlled trial for 8 weeks. Seventy-six patients with T2DM were randomly assigned to receive 1000 mg/day resveratrol or placebo. Levels of lipid accumulation product (LAP), visceral adiposity index (VAI), Castelli risk index I (CRI-I), CRI-II and atherogenic coefficient (AC) were measured at the beginning and after intervention. RESULTS: A total of 71 participants completed the trial. After adjusting for confounding factors including medications, diabetes duration, energy intake and physical activity, no significant difference was found between the intervention group and the control group in LAP (mean change: - 2.46 ± 23.3 vs. 1.43 ± 14.3; P = 0.43), VAI (mean change: - 0.25 ± 1.1 vs. - 0.02 ± 0.6; P = 0.47), CRI-I (mean change: - 0.25 ± 0.9 vs. - 0.09 ± 0.5; P = 0.79), CRI-II (mean change: - 0.23 ± 0.7 vs. - 0.06 ± 0.6; P = 0.38) and AC (mean change: - 0.25 ± 0.9 vs. - 0.09 ± 0.5; P = 0.79). CONCLUSIONS: Resveratrol supplementation had no effect on hepatic steatosis and cardiovascular indices. Further clinical trials, especially among subjects with dyslipidemia are needed to reach a firm conclusion. In addition, taking all medications should be controlled in future studies. Trial registration The protocol was registered on 29/12/2017 at the Iranian clinical trials website (IRCT20171118037528N1) with URL: https://en.irct.ir/trial/27734 .

Efficacy of omega-3-rich Camelina sativa on the metabolic and clinical markers in nonalcoholic fatty liver disease: a randomized, controlled trial.

OBJECTIVE: Recently, omega-3 fatty acids and antioxidants co-supplementation was considered as alternative treatment in the management of nonalcoholic fatty liver disease (NAFLD). This trial evaluated effects of Camelina sativa oil (CSO) as a rich source of omega-3 fatty acids and antioxidants on anthropometric indices, lipid profile, liver enzymes, and adiponectin in NAFLD patients. PARTICIPANTS AND METHODS: This triple-blind, placebo-controlled, randomized clinical trial was conducted on 46 NAFLD patients who were randomly assigned to either a CSO supplement or placebo for 12 weeks. Both groups received a loss weight diet. Levels of liver enzymes, adiponectin, lipid profile, atherogenic index, and anthropometric indices were assessed for all patients at baseline and post-intervention. RESULTS: CSO caused significant differences in weight, BMI, waist circumference, waist-to-hip ratio, triglyceride, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), TC/HDL-c, LDL-c/HDL-c, atherogenic index, alanine aminotransferase, and adiponectin concentrations in the CSO group compared with the placebo group (P < 0.046 for all). No significant differences were found in hip circumference, neck circumference, HDL-c, and other liver enzymes in the CSO group compared with the placebo group (P = 0.790, P = 0.091, P = 0.149, P < 0.159 for liver enzymes, respectively). DISCUSSION AND CONCLUSION: This study showed that CSO supplementation for 12 weeks causes significant changes in all of anthropometric indices (except hip circumference and neck circumference), ALT, lipid profile (except HDL-c), atherogenic index, and adiponectin in NAFLD patients.

The Association Between Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease Diagnosis Varies by Race.

Objectives: This study investigated how the association between metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) diagnosis varies between non-Hispanic African American and white patients. Methods: A retrospective cohort study was performed using electronic medical records from an integrated health care system (2010-2018). Adults with records for all MetS measurements (body mass index, lipids, blood pressure, and blood glucose) in 2011, who did not have a NAFLD diagnosis before their last MetS measurement, were included. Results: The study cohort consisted of 139,336 patients (age 56.1 ± 15.2 years, 57.9% female, 79.4% non-Hispanic white). The rate of NAFLD diagnosis was higher in MetS patients compared with non-MetS patients [adjusted hazards ratio (AHR) = 1.99, 95% CI = 1.91-2.09] with a significant interaction by race (AHR = 2.05, 95% CI = 1.95-2.15 in non-Hispanic whites vs. AHR = 1.76, 95% CI = 1.58-1.96 non-Hispanic African Americans, P = 0.017). Secondary analyses revealed that the relative NAFLD diagnosis rate was higher in non-Hispanic whites with MetS compared with non-Hispanic African Americans with MetS among females and patients 18-39 years of age and 40-59 years, but not among males and those ≥60 years of age. Conclusions: Non-Hispanic white patients with MetS, particularly females and those <60 years of age, may be at increased risk of NAFLD compared with non-Hispanic African American MetS patients and may benefit from extra attention regarding NAFLD screening.

The Myristic Acid:Docosahexaenoic Acid Ratio Versus the n-6 Polyunsaturated Fatty Acid:n-3 Polyunsaturated Fatty Acid Ratio as Nonalcoholic Fatty Liver Disease Biomarkers.

It is well established that diets containing an increased omega-6 polyunsaturated fatty acid (n-6 PUFA) to omega-3 polyunsaturated fatty acid (n-3 PUFA) ratios are linked to inflammation and chronic diseases such as nonalcoholic fatty liver disease (NAFLD). However, the influence of an elevated n-6 PUFA:n-3 PUFA ratio in the tissues requires clarification. Herein, we identified primary experimental and clinical studies where it is possible to compare the performance of the myristic acid (Myr):docosahexaenoic acid (DHA) and n-6 PUFA:n-3 PUFA ratios in the liver and/or serum as potential NAFLD biomarkers. Articles were included if quantitative values of n-6 PUFA, n-3 PUFA, Myr, DHA, and information about liver inflammation or liver disease progression parameters were provided. Overall, most experimental (91.6%) and clinical studies (87.5%) reported higher Myr:DHA ratios associated with inflammation and/or NAFLD progression than the n-6 PUFA:n-3 PUFA ratio. We conclude that the Myr:DHA ratio represents a better biomarker of NAFLD than the n-6 PUFA:n-3 PUFA ratio. Future studies are necessary for verifying this observation.

A Meta-Analysis on the Global Prevalence, Risk factors and Screening of Coronary Heart Disease in Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Cardiovascular disease remains the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Studies examining the association of coronary heart disease (CHD) and NAFLD are cofounded by various cardiometabolic factors, particularly diabetes and body mass index. Hence, we seek to explore such association by investigating the global prevalence, independent risk factors, and influence of steatosis grade on manifestation of CHD among patients with NAFLD. METHODS: Two databases, Embase and Medline, were utilized to search for articles relating to NAFLD and CHD. Data including, but not limited to, continent, diagnostic methods, baseline characteristics, prevalence of CHD, CHD severity, NAFLD severity, and risk factors were extracted. RESULTS: Of the 38 articles included, 14 reported prevalence of clinical coronary artery disease (CAD) and 24 subclinical CAD. The pooled prevalence of CHD was 44.6% (95% confidence interval [CI], 36.0%-53.6%) among 67,070 patients with NAFLD with an odds ratio of 1.33 (95% CI, 1.21%-1.45%; P < .0001). The prevalence of CHD was higher in patients with moderate to severe steatosis (37.5%; 95% CI, 15.0%-67.2%) than those with mild steatosis (29.6%; 95% CI, 13.1%-54.0%). The pooled prevalence of subclinical and clinical CAD was 38.7% (95% CI, 29.8%-48.5%) and 55.4% (95% CI, 39.6%-70.1%), respectively. CONCLUSION: Steatosis was found to be related with CHD involvement, with moderate to severe steatosis related to clinical CAD. Early screening and prompt intervention for CHD in NAFLD are warranted for holistic care in NAFLD.

Healthcare practitioners' diagnostic and treatment practice patterns of nonalcoholic fatty liver disease in Poland: a cross-sectional survey.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) awareness is low. NAFLD diagnosis and management by gastroenterologists (GEs) and general practitioners (GPs) in Poland were evaluated. METHODS: RESTORE was an observational, noninterventional, retrospective cross-sectional survey performed among GEs and GPs with at least 3 years' experience. Computer-assisted web interviews were completed. GEs provided information from patient records. RESULTS: Mean experience was 14.2 (95 GEs) and 22.6 (115 GPs) years. Mean patient numbers with liver disorders consulted per month were 36 (13%; GEs) and 51 (6%; GPs); ~50% were patients with NAFLD. All GEs/GPs used ultrasound; most evaluated transaminases and gamma-glutamyl transferase. More GEs used other imaging techniques and a larger spectrum of laboratory tests than GPs. Physician-identified NAFLD key symptoms were similar for GEs/GPs. GEs noticed less obvious symptoms (abdominal discomfort, drowsiness, fatigability, lack of energy) vs. GPs (abdominal pain/discomfort, dyspepsia). Common comorbidities in NAFLD were similar in GE/GP responses. NAFLD interventions by GEs/GPs (% patients) were diet/lifestyle/pharmacological interventions (54%/59%), diet/lifestyle changes alone (41%/31%) or pharmacological interventions alone (5%/10%). The top three criteria for supportive pharmacological selection were efficacy, tolerability and quality of life improvement for GEs/GPs. The five supportive treatments most commonly prescribed by GEs/GPs were essential phospholipids, ursodeoxycholic acid, timonacic, silybinin/silymarin and ornithine + choline. Information from patient records (n = 380) confirmed GEs responses. CONCLUSIONS: NAFLD is not a silent disease as physicians and patients reported many, albeit nonspecific, symptoms. This cross-sectional survey provides important insights into clinical management of NAFLD by GEs and GPs in Poland.

Liver Disease: Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of fatty infiltration, inflammation, and fibrosis of the liver caused by metabolic factors. It is projected to become the leading cause of cirrhosis and need for liver transplantation in the United States. Guidelines from the American Association for the Study of Liver Diseases (AASLD) do not recommend routine screening of patients at high risk of NAFLD. European guidelines recommend testing for certain high-risk patients. Hepatic steatosis and nonalcoholic steatohepatitis (NASH) are difficult to diagnose and often go unrecognized until patients have advanced fibrosis or cirrhosis. Noninvasive methods are used to assess fibrosis, such as fibrosis scores and vibration-controlled transient elastography. Liver biopsy remains the reference standard for NASH diagnosis and fibrosis staging. The mainstays of treatment for NAFLD, NASH, and fibrosis are weight loss and a healthy diet. Currently, no drugs have been approved by the Food and Drug Administration (FDA) for management of these conditions. Drugs for diabetes management (eg, glucagon-like peptide 1 receptor agonists, pioglitazone) can be useful in patients with diabetes and NASH. Among patients with NAFLD, cardiovascular disease is a common cause of mortality. Thus, the AASLD guidelines recommend consideration of omega-3 fatty acids for hypertriglyceridemia management in patients with NAFLD, and statins for hyperlipidemia management in most patients with NAFLD and NASH.

Omega-3 mechanism of action in inflammation and endoplasmic reticulum stress in mononuclear cells from overweight non-alcoholic fatty liver disease participants: study protocol for the "Brazilian Omega Study" (BROS)-a randomized controlled trial.

The low-grade inflammation is pivotal in obesity and its comorbidities; however, the inflammatory proteins are out of target for traditional drug therapy. Omega-3 (ω3) fatty acids can modulate the downstream signaling of Toll-like receptor (TLR) and tumor necrosis factor-α receptor (TNFα) through GPR120, a G-protein-coupled receptor, a mechanism not yet elucidated in humans. This work aims to investigate if the ω3 supplementation, at a feasible level below the previously recommended level in the literature, is enough to disrupt the inflammation and endoplasmic reticulum stress (ER-stress), and also if in acute treatment (3 h) ω3 can activate the GPR120 in peripheral blood mononuclear cells (PBMC) and leukocytes from overweight non-alcoholic fatty liver disease (NAFLD) participants. The R270H variant of the Ffar4 (GPR120 gene) will also be explored about molecular responses and blood lipid profiles. A triple-blind, prospective clinical trial will be conducted in overweight men and women, aged 19-75 years, randomized into placebo or supplemented (2.2 g of ω3 [EPA+DHA]) groups for 28 days. For sample calculation, it was considered the variation of TNFα protein and a 40% dropout rate, obtaining 22 individuals in each group. Volunteers will be recruited among patients with NAFLD diagnosis. Anthropometric parameters, food intake, physical activity, total serum lipids, complete fatty acid blood profile, and glycemia will be evaluated pre- and post-supplementation. In the PBMC and neutrophils, the protein content and gene expression of markers related to inflammation (TNFα, MCP1, IL1ß, IL6, IL10, JNK, and TAK1), ER-stress (ATF1, ATF6, IRE1, XBP1, CHOP, eIF2α, eIF4, HSP), and ω3 pathway (GPR120, ß-arrestin2, Tab1/2, and TAK1) will be evaluated using Western blot and RT-qPCR. Participants will be genotyped for the R270H (rs116454156) variant using the TaqMan assay. It is hypothesized that attenuation of inflammation and ER-stress signaling pathways in overweight and NAFLD participants will be achieved through ω3 supplementation through binding to the GPR120 receptor. TRIAL REGISTRATION: ClinicalTrials.gov #RBR-7x8tbx. Registered on May 10, 2018, with the Brazilian Registry of Clinical Trials.

Reenvisioning Traditional to Regenerative Therapeutic Advances in Managing Nonalcoholic Fatty Liver Disease in Diabetes Mellitus.

Reports indicate the increasing prevalence of liver disorders in diabetes mellitus (DM) patients. Clinically, it has also been revealed that the existence of nonalcoholic fatty liver disease (NAFLD) enhances the incidence of type 2 diabetes mellitus (T2DM), while T2DM exacerbates NAFLD to extremely severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. This implies the coexistence and bidirectional nature of NAFLD and T2DM, which function synergistically to drive adverse consequences in clinical practice. For treatment of such comorbid state, though the existing practices such as lifestyle management, traditional Chinese medicines (TCM), and pharmaceuticals have offered somewhat relief, the debate continues about the optimal therapeutic impacts. Recent developments in the field of tissue engineering have led to a renewed interest in novel biomaterial alternatives such as stem cells. This might be attributable to their differentiation potential towards hepatic and pancreatic lineage. These cellular therapies could be further complemented by platelet-derived biomaterials, TCM formulations, or any specific drug. Based on these abovementioned approaches, we aimed to comprehensively analyze various preclinical and clinical studies from traditional to regenerative therapeutic approaches in managing concomitant NAFLD and T2DM.

Effect of Lycium barbarum polysaccharide supplementation in non-alcoholic fatty liver disease patients: study protocol for a randomized controlled trial.

BACKGROUND: Non-alcohol fatty liver disease (NAFLD) is the most common chronic liver disease in the world, with a high incidence and no effective treatment. At present, the targeted therapy of intestinal microbes for NAFLD is highly valued. Lycium barbarum polysaccharide (LBP), as the main active ingredient of Lycium barbarum, is considered to be a new type of prebiotic substance, which can improve NAFLD by regulating the gut microbiota. The purpose of this study is to evaluate the safety and efficacy of LBP supplementation in modulating gut microbiota for NAFLD patients. METHODS: This randomized, double-blind, placebo-control study will be conducted in the physical examination center of the Ningxia Hui Autonomous Region People's Hospital. A total of 50 patients with NAFLD confirmed by abdominal ultrasound, laboratory tests, and questionnaire surveys will be recruited and randomly assigned into the control group (maltodextrin placebo capsules) and the intervention group (LBP supplementation capsules) for 3 months. Neither patients, nor investigators, nor data collectors will know the contents in each capsule and the randomization list. The primary outcome measure is the level of ALT concentration relief after the intervention. Secondary outcomes include gut microbiota abundance and diversity, intestinal permeability, patient's characteristic demographic data and body composition, adverse effects, and compliance from patients. DISCUSSION: LBPs are potential prebiotics with the property of regulating host gut microbiota. Our previous studies have documented that LBP supplement can improve the liver damage and the gut microflora dysbiosis in NAFLD rats. This treatment would provide a more in-depth understanding of the effect of this LBP supplementation. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000034740 . Registered on 17 July 2020.

Etiology Exploration of Non-alcoholic Fatty Liver Disease From Traditional Chinese Medicine Constitution Perspective: A Cross-Sectional Study.

Background: From the traditional Chinese medicine (TCM) constitution theory perspective, the phlegm-dampness constitution is thought to be closely related to the occurrence of non-alcoholic fatty liver disease (NAFLD). However, this viewpoint still lacks rigorous statistical evidence. This study aimed to test the association between the phlegm-dampness constitution and NAFLD. Methods: We conducted a cross-sectional study. Participants were residents living in Chengdu, China, undergoing health checkups at the health management center of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between December 2018 and September 2020. TCM constitution type was diagnosed by DAOSH four examinations instrument, NAFLD was diagnosed according to the liver ultrasonography and medical history. Multivariate logistic regression and propensity score matching (PSM) were used to analyze a total of 1,677 qualified data. Results: 1,037 participants had biased constitution(s), 67.8% of which had mixed constitutions (with at least two constitutions). Among 1,677 participants, the phlegm-dampness constitution was associated with the yang-deficiency, yin-deficiency, dampness-heat, qi-depression, and blood-stasis constitutions. The correlation coefficients were 0.11, 0.32, 0.42, 0.20, 0.14, respectively. Between the phlegm-dampness constitution and NAFLD, the odds ratio (OR) and the 95% confidence interval (CI) was 2.05 (1.57-2.69) in the crude model. After adjusting for age, gender, Body mass index (BMI), other biased constitutions, smoking, high blood pressure, diabetes, and dyslipidemia, the OR reduced to 1.51 (1.04-2.18). The associations of seven other biased TCM constitutions and NAFLD were not statistically significant in the fully adjusted model. The PSM analysis showed consistent results with the logistic regression. Conclusions: Among eight biased TCM constitutions, the phlegm-dampness constitution is independently associated with NAFLD. We speculate the phlegm-dampness constitution is a risk factor of NAFLD. Longitudinal studies are needed to confirm this causal relationship in the future. In addition, inconsistent with some TCM practitioners' experience, we disagree that the blood-stasis constitution is associated with NAFLD.