Liver Health Research Articles

An Australian Community-Based Metabolic Dysfunction-Associated Steatotic Liver Disease Care Pathway for People with Type 2 Diabetes: Barriers and Considerations.

Although clinical guidelines endorse screening for metabolic dysfunction-associated steatotic liver disease (MASLD) with advanced fibrosis in people with type 2 diabetes (T2D), the feasibility of and barriers and considerations relevant to implementing this approach in the community remain unclear. Sequential adults with T2D attending selected community clinics during 2021-2023 were invited to receive a "liver health check" (n=543). A further 95 participants were referred directly from their general practitioner (GP) or self-referred to the study. A total of 302 participants underwent a point of care assessment of hepatic steatosis and stiffness (FibroScan) and were advised to see their GP to discuss the results. "Template" letters containing key results, their interpretation and advice about management of cardiometabolic risk, patient follow-up and referral criteria, were sent to participants' GPs. Referral to a tertiary liver clinic was advised in GP letters for 45 (15%) participants with an increased risk of clinically significant fibrosis (liver stiffness measurement ≥8), 15 participants with 'red flags' (eg splenomegaly, thrombocytopenia) and 2 with unsuccessful FibroScan examinations. A referral from GPs to the liver clinic was received for 27 (44%) of these 62 participants. Approximately 90% of GPs rated the "template" letters favourably on a Likert rating scale. The low rate of participation in the "liver health check" and liver clinic referral reflects a real-world scenario and may stem from societal under-recognition and engagement with MASLD, competing health priorities or under-appreciation of the link between liver fibrosis severity and mortality risk. Further studies need to address strategies to enhance participation in liver health assessments and determine their impact on liver-related morbidity/mortality and overall survival.

Nationwide survey analysis of esophagogastric varices in portal hypertension based on endoscopic management in China

AbstractAimsThe endoscopic treatment of esophagogastric varices is challenging, and the nationwide application of endoscopic therapies for various types of esophagogastric varices and different clinical scenarios remains unclear. This study investigated the use of endoscopic therapy for portal hypertension in China.MethodsThis study used a questionnaire survey initiated by the Liver Health Consortium in China to investigate the use of endoscopic therapies for portal hypertension. Questionnaires were released online from January 30, 2023 to February 28, 2023 and filled out by chief physicians or senior instructors responsible for endoscopic therapies in participating hospitals across 31 provinces (autonomous regions and municipalities) in China. Comparisons of guideline adherence between primary and referral medical centers were performed using the chi‐square test or Fisher's exact test.ResultsIn total, 836 hospitals participated in the survey. For primary and secondary prophylaxis of esophagogastric variceal bleeding (EGVB), adherence to the national guidelines was 72.5% (606/836) and 39.2% (328/836), respectively. Significant differences were observed in the rate of adherence between the primary and referral centers for primary (79.9% [111/139] vs. 71.0% [495/697], p = 0.033) and secondary prophylaxis (27.3% [38/139] vs. 41.6% [290/697], p = 0.002). Of the hospitals, 78.2% (654/836) preferred endoscopic therapies for acute EGVB, and the timing of endoscopy was usually within 12 h (48.5%, 317/654) and 12–24 h (36.9%, 241/654) after bleeding. Endoscopic therapy was more likely to be the first choice of treatment for acute EGVB in referral centers than in primary centers (82.6% [576/697] vs. 56.1% [78/139], p < 0.001). Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, the most prevalent procedures were cyanoacrylate injection combined with sclerotherapy (48.2% [403/836] and 29.9% [250/836], respectively); however, substantial hospitals preferred clip‐assisted therapies (12.4% [104/836] and 26.4% [221/836], respectively). Nonselective beta‐blockers were routinely used in 73.4% (614/836) of hospitals during the perioperative period of EGVB management, and propranolol (88.8%, 545/614) and carvedilol (37.5%, 230/614) were the most widely used nonselective beta‐blockers.ConclusionsThis survey clarified that various endoscopic procedures have been implemented nationwide in China. Participating hospitals have actively performed emergent endoscopy for acute EGVB; however, these hospitals do not adequately follow recommendations regarding primary and secondary prophylaxis of EGVB. In the future, standardizing the selection of endoscopic procedures and improving compliance with guidelines is crucial.

Accuracy and precision of diets fed to close-up cows on dairy farms and its association with early lactation performance

Ensuring a consistent ration is critical for maximizing lactating cow performance, but this is not known for dry cows. The objectives of this cohort observational study were to: 1) characterize close-up dry cow diets fed on commercial farms in Ontario, Canada, 2) describe the accuracy of the nutrient composition between the formulated close-up diet and the diet offered to the cows, 3) describe the precision of the close-up diets across time, and 4) explore potential associations of that accuracy and precision with blood metabolic parameters and milk yield of cows in early lactation. Forty free-stall dairy farms were visited once every 4 wk, for a total of 6 visits to each farm, from April to October 2022. At each visit, samples of the close-up diet were collected and analyzed for dry matter (DM) content and chemical composition. Close-up diet formulations were also obtained by each farm's nutritionists. During each visit, fresh cows (0 to 14 d in milk [DIM]) had blood samples taken for blood metabolites. The same cows were also monitored for milk yield up to 120 DIM. Multivariable models were used to analyze associations between variability (in relation to the formulated diet and across time) of nutrients in the close-up diet, as measured by coefficient of variation (CV), and outcomes in fresh cows. Corn silage (67.6% of farms) and straw (24.3% of farms) were the predominant primary forage sources used in the close-up dry cow diets. Soybean meal (37.8% of farms) and canola meal (18.9% of farms) were the main ingredients used as primary concentrate sources. Overall, the diets offered did not accurately represent the formulated diets. With the exception of net energy for lactation (NEL), the CVs for the other nutrients were all greater than 5%. Diet variability, both between fed and formulated diets and from visit to visit during the close-up period, was associated with metabolic markers and dairy cow production. Lower variability in non-fiber carbohydrates (NFC) between the fed and formulated diets was associated with better liver health index scores. Visit-to-visit variability in fat% and NFC% were associated with blood β-hydroxybutyrate (BHB) concentrations, while NFC% variability was associated with blood glucose levels. Serum nonesterified fatty acids (NEFA) concentrations were associated with visit-to-visit variability in DM% and CP%. These results underscore the importance of maintaining consistency between diet formulations and feeding practices over time to optimize early-lactation dairy herd performance and health, granted that these diets are correctly formulated to meet the nutritional needs of cows in the close-up period and applied with recommended feeding practices.

Effect of Vernonia Cinerea Water Extract on the Protection of Liver Tissue in Chronic Nicotine-Treated Rats

Nicotine, a highly toxic alkaloid found in tobacco, is known for its addictive properties and systemic side effects, including carcinogenic potential and multi-organ damage. Recent evidence indicates that nicotine can significantly impair liver function and regeneration by promoting fibrogenesis and oxidative stress. This study aimed to investigate the protective effects of Vernonia cinerea (VC) against nicotine-induced liver damage in Wistar rats, focusing on inflammation and pro-fibrosis markers. Thirty male Wistar rats were divided into three groups: a control group, a nicotine group (1 mg/kg/day), and a nicotine plus VC group (1 mg/kg/day nicotine and 100 mg/kg/day VC). Liver tissues were examined using Hematoxylin and Eosin staining, and Masson's trichrome staining to evaluate histological changes. Kupffer cell counts were determined using a Panoramic digital slide scanner. Statistical analyses were conducted to compare the groups. Nicotine exposure led to significant liver damage, characterized by increased inflammation, collagen deposition, and disruption of liver architecture. VC supplementation ameliorated these effects, reducing inflammation and fibrosis markers. Kupffer cell counts were lower in the nicotine plus VC group compared to the nicotine group alone. Conclusion: VC demonstrates a protective role in mitigating nicotine-induced liver damage, highlighting its potential as a therapeutic agent for preventing liver fibrosis and maintaining liver health in nicotine-exposed individuals.

Modulation of liver cholesterol homeostasis by choline supplementation during fibrosis resolution

Liver fibrosis is a critical global health challenge, often leading to severe liver diseases without timely intervention. Choline deficiency has been linked to metabolic dysfunction associated steatohepatitis (MASH) and liver fibrosis, suggesting choline supplementation as a potential therapeutic approach. This study aimed to explore the therapeutic potential of choline supplementation in liver fibrosis resolution and its effects on cholesterol homeostasis using a mouse model with induced liver fibrosis. Our findings reveal that choline supplementation significantly decreases blood lactate dehydrogenase (LDH) and non-high-density lipoprotein cholesterol (non-HDL-C) levels. Transcriptome analysis showed that choline supplementation primarily induces genes related to cholesterol homeostasis, suggesting a significant impact on liver cholesterol synthesis. However, choline supplementation did not significantly alter the expression of fibrosis-related, choline metabolism-related, or epigenetics-related genes. This study provides novel insights into the role of choline in liver health and cholesterol metabolism, potentially informing treatments for liver fibrosis and related conditions.

Effects of Dietary Fish Oil Supplementation on the Growth, Proximate Composition, and Liver Health of Chinese Stripe-Necked Turtle (Mauremys sinensis).

Dietary lipids provide energy for animals and can also be converted into other nutrients (such as non-essential amino acids), which play a role in saving protein. The Chinese stripe-necked turtle is a protected and endangered species that has been bred in captivity; however, basic data on lipid requirements remain unavailable. In this study, 360 Mauremys sinensis (body weight of 65.32 ± 0.15 g) were randomly divided into six groups with three replicates per group; the turtles were fed experimental diets supplemented with various levels of fish oil (i.e., 1% (control group, CG), 3.5% (HF-1), 6% (HF-2), 8.5% (HF-3), 11% (HF-4), and 13.5% (HF-5)) for 10 weeks. The results showed that compared with CG, increasing the fish oil level promoted the growth performance of turtles, and the HF-3 group achieved the best effect. The HF-4 group showed the highest increases in the hepatosomatic index and viscerosomatic index. In addition, increased lipid levels also increased the crude lipid content and reduced the crude protein content in muscle tissue. Oil red O staining showed that the liver lipid content increased with the level of supplemented fish oil, which is consistent with the results of the hepatosomatic index. Compared with CG, triglyceride, total cholesterol, and low-density lipoprotein cholesterol increased significantly in both the liver and serum when fish oil levels exceeded 8.5% (p < 0.05), while high-density lipoprotein cholesterol decreased significantly. Aspartate transaminase and cerealthirdtransaminase levels in serum increased significantly when fish oil levels exceeded 8.5% (p < 0.05). Moreover, the activities of antioxidant enzymes (GSH-Px, SOD, T-AOC, and CAT) and MDA showed similar results, indicating that high fish oil levels (8.5-13.5%) caused liver tissue damage in M. sinensis. Increased fish oil levels significantly upregulated the expression levels of cytokines (IFN-γ, TNF-α, TGF-β1, IL-10, and IL-12) (p < 0.05), downregulated the expression levels of antioxidant enzyme-related genes (cat, mn-sod, and gsh-px), and increased apoptosis of liver cells. Supplementation of the diet with 3.5-6% fish oil improved the growth performance of M. sinensis, and the turtles maintained a beneficial immune status. The results provide a scientific basis for optimizing the commercial feed formula of M. sinensis.

Unveiling the Multifaceted Role of CIDEB: From Apoptosis to Lipid Metabolism and Liver Health

Cell-death-inducing DNA fragmentation factor-alpha (DFFA)-like effector b (CIDEB) was first identified as an apoptosis-inducing protein. Further research revealed a pivotal role in lipid metabolism, regulating very-low-density lipoprotein (VLDL), lipid droplets (LD), sterol response element-binding protein (SREBP), and chylomicrons. Recent studies have uncovered that rare germline variants in CIDEB protect against liver diseases, including MAFLD, cirrhosis, and viral hepatitis. Furthermore, CIDEB influences steps of the hepatitis C virus (HCV) replication cycle. This review summarizes the current knowledge about CIDEB’s roles in apoptosis, lipid metabolism, and viral hepatitis, and highlights its critical role in liver diseases.

Effect of increasing β-mannanase supplementation in diets containing copra meal on growth performance, meat quality, liver health, intestinal morphology, and nutrient utilization in broiler chickens.

The current study aimed to investigate the effect of increasing β-mannanase supplementation in diets containing copra meal (CM) on growth performance, meat quality, liver health, intestinal morphology, and nutrient utilization in broiler chickens. A total of 1,600 3-d-old Ross 308 broiler chickens (initial body weight [BW] ± SD = 43.3 ± 1.08 g) were randomly allotted to 1 of 5 treatment groups with 8 replicates. One group was fed a corn-soybean meal-based diet (control). Other 4 diets were prepared by inclusion of 10% commercial CM in the control diet with 0, 400, 800, and 1,600 U β-mannanase/kg. Experiments lasted for 32 d. Birds fed the control diet had less (p=0.001) feed conversion ratio (FCR) than those fed diets containing 10% CM without β-mannanase supplementation. Increasing supplementation of β-mannanase in diets containing 10% CM had no linear and quadratic effects on body weight gain, feed intake, and FCR in broiler chickens. The control diet had greater (p<0.01) apparent total tract retention (ATTR) of DM, GE, and N as compared to the diets containing 10% CM without β-mannanase supplementation; however, no differences in the ATTR of Ca and P were identified between 2 diets. There were no linear and quadratic effects of increasing supplementation of β-mannanase on the ATTR of DM, GE, N, Ca, and P in broiler diets containing 10% CM. Both inclusion of 10% CM and increasing supplementation of β-mannanase in broiler diets did not affect apparent ME (AME) and N-corrected ME (AMEn) values in treatment diets. The use of 10% CM in broiler diets during growing and finishing period impairs growth performance by decreasing energy and nutrient utilization in diets. Increasing β-mannanase supplementation in diets containing 10% CM has no positive effects on performance, meat quality, liver health, intestinal morphology, and nutrient utilization in broiler chickens.

Protective effect of β-sitosterol against high-fructose diet-induced oxidative stress, and hepatorenal derangements in growing female sprague-dawley rats

BackgroundChronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed.ResultsHigh fructose diet fed rats had increased plasma KIM-1, NGAL (p < 0.001) and MDA levels (p < 0.05). Dietary fructose caused microvesicular and macrovesicular steatosis, and reduced glomerular density, Bowman’s capsule area and urinary space. β-sitosterol protected against the high-fructose diet-induced hepatic steatosis and glomerular disturbances without adverse effects on liver and kidney function.Conclusionsβ-sitosterol, as a dietary supplement, could potentially be exploited to prevent high-fructose diet-induced NAFLD and to protect against high-fructose diet-induced renal tubular injury.

Cascara kombucha potential as a functional food for fasting glucose regulation, cholesterol control, and liver function modulation: in vitro and in vivo study

SummaryUnhealthy dietary patterns are a major contributor to obesity worldwide, leading to various adverse metabolic effects such as elevated liver enzyme levels and increased cholesterol concentrations. This study investigates the potential of cascara kombucha as a functional beverage to provide health benefits in both in vitro and in vivo models. Our results indicate that kombucha fermentation enhances the bioactive compounds in cascara, including polyphenols and flavonoids. The in vitro study found that cascara kombucha effectively decreased free radicals (DPPH and ABTS) levels, α‐amylase, and lipase activity, suggesting its potential to act as an antioxidant and modulate carbohydrate and lipid metabolism. In a mouse model, oral administration of cascara kombucha at a dose of 300 mg/kg body weight for 28 days successfully decreased fasting blood glucose levels, improved liver health by reducing aspartate transaminase and alanine transaminase levels, and lowered serum cholesterol content induced by a fat‐enriched diet compared to the untreated group. The levels of superoxide dismutase and catalase, suppressed by the fat‐enriched diet, were restored to normal. Additionally, cascara kombucha downregulated genes associated with inflammation induced by a fat‐enriched diet, including tnf‐α, IL‐6, IL‐1β, and cox‐2. It also positively affected the balance of intestinal microflora in mice by reducing coliform density and enhancing probiotic populations. These findings highlight the potential of cascara kombucha as a promising approach to addressing health issues caused by poor dietary habits and metabolic imbalances.

Regular Consumption of Green Tea as an Element of Diet Therapy in Drug-Induced Liver Injury (DILI).

The liver is a highly metabolically active organ, and one of the causes of its dysfunction is the damage caused by drugs and their metabolites as well as dietary supplements and herbal preparations. A common feature of such damage is drugs, which allows it to be defined as drug-induced liver injury (DILI). In this review, we analysed available research findings in the global literature regarding the effects of green tea and/or its phenolic compounds on liver function in the context of protective action during prolonged exposure to xenobiotics. We focused on the direct detoxifying action of epigallocatechin gallate (EGCG) in the liver, the impact of EGCG on gut microbiota, and the influence of microbiota on liver health. We used 127 scientific research publications published between 2014 and 2024. Improving the effectiveness of DILI detection is essential to enhance the safety of patients at risk of liver damage and to develop methods for assessing the potential hepatotoxicity of a drug during the research phase. Often, drugs cannot be eliminated, but appropriate nutrition can strengthen the body and liver, which may mitigate adverse changes resulting from DILI. Polyphenols are promising owing to their strong antioxidant and anti-inflammatory properties as well as their prebiotic effects. Notably, EGCG is found in green tea. The results of the studies presented by various authors are very promising, although not without uncertainties. Therefore, future research should focus on elucidating the therapeutic and preventive mechanisms of polyphenols in the context of liver health through the functioning of gut microbiota affecting overall health, with particular emphasis on epigenetic pathways.

Preoperative nonalcoholic steatohepatitis and resolution of metabolic comorbidities after bariatric surgery

BackgroundMost patients undergoing bariatric surgery demonstrate elements of the metabolic syndrome (MetS) and can therefore be diagnosed with metabolically unhealthy obesity (MUO). Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) as hepatic manifestations of the MetS occur in many patients with obesity, but their leverage on postoperative improvement to Metabolic Health (MH), defined as absence of any metabolic comorbidity, remains unclear. ObjectivesThe aim of this study was to assess the influence of liver health status, operative procedure, and sex on postoperative switch from a MUO to an MH phenotype. Secondary objective was weight loss to MH. SettingUniversity Hospital, Germany. MethodsPatients who underwent either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at our obesity surgery center were included in this retrospective study. Liver biopsy was taken and evaluated for presence of NAFLD/NASH. For diagnosis of MH, blood pressure and laboratory values referring to the MetS were assessed preoperatively and at 3, 6, 12, and 24 months’ postoperatively. ResultsOne hundred thirty-three patients (73% female) with a mean body mass index of 52.0 kg/m2 and mean age of 43 years were included in this study. A total of 55.6% underwent RYGB and 44.4% underwent SG. NAFLD was found in 51.1% of patients and NASH in 33.8%. All patients were diagnosed MUO at baseline. Postoperatively, 38.3% patients (n = 51) switched to a MH condition. Mean time to MH was 321 days and mean excess body mass index loss to MH was 63.8%. There were no differences regarding liver health status, operative procedure, or sex. ConclusionsBariatric surgery can resolve MUO independent of liver health status, operative procedure, and sex. However, patients should be closely monitored to ensure sustainable long-term outcomes following the switch to the MH condition.

The protective effect of luteolin on cadmium induced liver intestinal toxicity in chicken by Gut-liver axis regulation

Environmental pollution poses a significant challenge to the poultry industry, leading to substantial losses and adverse effects on the health, production, and performance of avian species. In recent years, there has been growing interest in exploring natural compounds with potential protective effects against cadmium (Cd)-induced toxicity. Luteolin (LUT), a flavonoid found in various plants, has been studied for its antioxidant, anti-inflammatory, and cytoprotective properties. In this study, Su green shell grass chickens were divided into 4 groups: control, LUT (150 mg LUT), Cd (100 mg CdCl2), and Cd + LUT (100 mg CdCl2 + 150 mg LUT) groups for 1 month, respectively. The present study revealed that LUT maintained the morphology and functional activity of the liver and intestine. LUT alleviated Cd-induced impairment in the liver and intestinal biochemical indicators, suppressed Cd-induced liver fibrosis, mitigated liver and intestinal tissue damage. Additionally, LUT reduced oxidative stress and regulated the Cd-induced impairment in trace elements of the liver and intestine. Furthermore, LUT reduced Cd-induced liver inflammation, restored Cd-induced intestinal barrier function, and normalized Cd-induced serum proteins, including changes in the content of glutamyltranspeptidase. Moreover, LUT maintained Cd-induced disruption of gut microbiota and alleviated bacterial dysbiosis. Overall, these findings suggest that LUT holds promise as a potential therapeutic agent for mitigating the adverse effects of Cd-induced toxicity in poultry, by preserving liver and intestinal health, reducing oxidative stress, inflammation, and restoring gut microbiota balance.

Alleviating effects of guar gum on high-fat diet-induced liver injury in common carp (Cyprinus carpio)

This research aimed to determine the effect of dietary guar gum inclusion in high-lipid diets on the liver health of common carp (Cyprinus carpio). Four high-fat diets (10 % crude lipid) containing 0 % (HF), 0.3 % (HFG0.3), 1 % (HFG1), and 3 % (HFG3) of guar gum and a normal-lipid diet (5 % crude lipid; Control) were formulated. The tested diets were evenly and randomly distributed to fifteen tanks, with each tank containing thirty fish (4.53 ± 0.05 g). Fish were fed until apparent satiation for eight weeks. Compared to HF, diets HFG0.3, HFG1, and HFG3 significantly improved feed efficiency, with the HFG0.3 diet enhancing weight gain rate and specific growth rate. The results indicated that HF induced gut dysbiosis, hepatic lipid accumulation, oxidative stress, inflammation, and disturbance in hepatic lipid and cholesterol metabolism. Compared to the HF diet, diets HFG0.3, HFG1, and HFG3 substantially decreased hepatic lipid accumulation and malonaldehyde content, increased catalase activity and the expression of AMP-activated protein kinase (AMPKα2), peroxisomal proliferator-activated receptor alpha (PPARα), cholesterol 7alpha-hydroxylase, and decreased the expression of interleukin-1β (IL-1β). Moreover, the HFG0.3 and HFG1 diets dramatically increased nuclear factor erythroid 2-related factor 2 and liver X receptor expression and decreased protein carbonyl contents and expression of IL-8, nuclear factor kappa B (NF-κB p65), and tumor necrosis factor α. Furthermore, the HFG1 diet significantly increased carnitine palmitoyltransferase 1 and peroxisomal proliferator-activated receptor gamma coactivator 1 expression and reduced expression levels of fibroblast growth factor 19, farnesoid X receptor, and sterol regulatory element-binding protein type 1. The linear discriminant analysis effect size (LEfSe) analysis showed that HFG 0.3 and HFG1 substantially increased the enrichment of beneficial microbiota (e.g., lactic acid bacteria, Cetobacterium, and Fusobacterial) and decreased the enrichment of harmful microbiota (e.g., Proteobacteria, Acinetobacter, and Pseudomonas) compared to HF. These results suggested that guar gum can mitigate high-fat diet-induced liver damage in fish.

Lipopolysaccharide, arbiter of the gut-liver axis, modulates hepatic cell pathophysiology in alcoholism.

Over the last four decades, clinical research and experimental studies have established that lipopolysaccharide (LPS)-a component of the outer membrane of gram-negative bacteria-is a potent hepatotoxic molecule in humans and animals. Alcohol abuse is commonly associated with LPS endotoxemia. This review highlights LPS molecular structures and modes of release from bacteria, plasma LPS concentrations, induction of microbiota dysbiosis, disruption of gut epithelial barrier, and translocation of LPS into the portal circulation impacting the pathophysiology of hepatic cells via the gut-liver axis. We describe and illustrate the portal vein circulation and its distributaries draining the gastrointestinal tract. We also elaborate on the gut-liver axis coupled with enterohepatic circulation that represents a bidirectional communication between the gut and liver. The review also updates the data on how circulating LPS is cleared in a coordinated effort between Kupffer cells, hepatocytes, and liver sinusoidal endothelial cells. Significantly, the article reviews and updates the modes/mechanisms of action by which LPS mediates the diverse pathophysiology of Kupffer cells, hepatocytes, sinusoidal endothelial cells, and hepatic stellate cells primarily in association with alcohol consumption. Specifically, we review the intricate linkages between ethanol, microbiota dysbiosis, LPS production, gut-liver axis, and pathophysiology of various hepatic cells. The maintenance of the gut barrier structural and functional integrity and microbiome homeostasis is essential in mitigating alcoholic liver disease and improving liver health.

Use of a Micronutrient Cocktail to Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Adults with Obesity: A Randomized, Double-Blinded Pilot Clinical Trial.

Background and Objectives: The goal of this study was to assess the impact of supplementation with a combination of nutrients on metabolic-dysfunction-associated steatotic liver disease (MASLD)-related liver parameters, and other parameters related to metabolic syndrome in adults with obesity. These measurements included anthropometric and lipid profiling, and FibroScan technology (controlled attenuation parameter (CAP) and transient elastography (TE) values). Materials and Methods: A double-blind, placebo-controlled pilot clinical trial was conducted over a three-month treatment period. Adults with metabolic syndrome and obesity were allocated to receive either a cocktail of nutrients with defined daily dosages (5-MTHF, betaine, alpha-linolenic acid, eicosapentaenoic acid, choline bitartrate, docosahexaenoic acid, and vitamin B12) or a placebo. The participants were evaluated at the start and the end of the three-month treatment period. Results: A total of 155 participants entered the study, comprising 84 in the treatment group and 71 in the placebo group. The administration of the nutritional supplement resulted in a notable reduction in both CAP and TE scores when compared to the placebo group. The treatment group exhibited a mean reduction in CAP of 4% (p < 0.05) and a mean reduction in TE of 7.8% (p < 0.05), indicative of a decline in liver fat content and fibrosis. Conclusions: The supplementation over a period of three months led to a significant amelioration of liver fibrosis and steatosis parameters in adults with metabolic syndrome and obesity. These findings suggest that this supplementation regimen could be a beneficial adjunct therapy for improving liver health in adults with obesity-induced MASLD.

Clinical Case Series on Assessment of Therapeutic Efficacy of Saroglitazar in MASLD Patients

Objective: This prospective case series aimed to evaluate the efficacy of saroglitazar 4 mg in improving clinical parameters in patients with type 2 diabetes mellitus (T2DM) with steatotic liver disease (SLD), focusing on glycemic control, lipid profile, liver enzymes, and transient elastography parameters (CAP and LSM scores). Materials and Methods: Eight T2DM patients having SLD; defined as Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) were enrolled from a single-center, Dr. Dang’s Clinic, Ghaziabad, Uttar Pradesh India. Saroglitazar 4 mg was administered daily, and various clinical parameters were monitored at baseline, 16 weeks, and 32 weeks. Statistical analysis was performed using paired t-tests to assess changes over time. Results: Saroglitazar treatment significantly reduced HbA1c, Triglycerides (TG), Alanine aminotransferase (ALT), transient elastography parameters (CAP and LSM) along with other lipid and glycemic parameters from baseline to weeks 32. These findings underscore potential role of saroglitazar in managing T2DM and associated SLD by improving metabolic parameters and liver health. Conclusion: Saroglitazar showed significant improvements in glycemic control, lipid profile, liver enzymes, liver fat and fibrosis in MASLD patients, indicating its potential as a therapeutic option for managing metabolic abnormalities and liver complications. Further research is needed to validate these findings.

Effects of oligomeric proanthocyanidins on growth performance, antioxidant capability, immunity, liver and intestinal health of Channa argus

To determine the effects of proanthocyanidins on the growth, antioxidant capability, immunity, intestinal morphology, intestinal microbiota, and liver health of Channa argus (10.12 ± 0.12 g), four experimental diets with various oligomeric proanthocyanidin (OPC) concentrations (0, 200, 400, and 800 mg/kg) were fed to triplicate groups for 8 weeks. The final body weight (FBW), weight gain (WG), feeding rate (FER), protein efficiency ratio (PER), and specific growth rate (SGR) were significantly improved in the 400 and 800 mg/kg OPC-supplemented diets (P < 0.05). The superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione (GSH), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in the liver and intestines were increased significantly, whereas the malondialdehyde (MDA) content exhibited the opposite pattern (P < 0.05). The GST, Cu/Zn superoxide dismutase (Cu/Zn SOD), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (NQO-1), and heme oxygenase 1 (HO-1) mRNA expression levels in the intestines and liver were significantly increased, whereas kelch-like ECH-associated protein 1 (Keap1) expression showed the opposite pattern (P < 0.05). Significant increases were noted in the serum lysozyme (LYS), immunoglobulin M (IgM), complement 3 (C3), and complement 4 (C4) levels, and significant decreases were noted in the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), and total cholesterol (TC) levels (P < 0.05). The interferon gamma (IFN-γ), interleukin-8 (IL-8), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) mRNA expression levels in the liver and intestines were significantly decreased, whereas the expression of interleukin-10 (IL-10) showed the opposite trend (P < 0.05). Compared with the control diet, the 400 and 800 mg/kg OPC-supplemented diets markedly improved liver and intestinal morphology. With increasing OPC concentration, the relative abundance of the beneficial bacteria, namely, Firmicutes increased, whereas the opposite trend was observed for the potential pathogenic bacteria, namely, Proteobacteria, Actinobacteria, Chlamydiae, Bacteroidetes, Cyanobacteria, and Acidobacteria. Therefore, dietary OPC supplementation facilitates growth performance and enhances antioxidant capability and immunity, as well as improves liver health, intestinal morphology, and microbiota composition of C. argus, of which the optimal level is 400 mg/kg.

Trajectories of hepatic steatosis and incidence of cardiovascular disease over a 29-year follow-up.

To examine the dynamic change in hepatic steatosis status during repeated assessments over time, and its potential impact on the risk of developing cardiovascular disease (CVD). We assessed trajectories of hepatic steatosis and other metabolic disorders in 3134 middle-aged adults undergoing longitudinal assessment of ultrasonography during a pre-baseline period (1993-2009) in a population-based cohort study of liver health. Subsequently, we determined the association of hepatic steatosis trajectories with the incidence of CVD among 2185 CVD-free individuals, followed until 2021. Metabolic risk factors and cardiovascular events (including coronary heart disease and stroke) were determined through medical examination and linkage with nationwide health databases. We identified three discrete trajectories of hepatic steatosis according to changing pattern over time through group-based trajectory modeling: "stable, non-steatosis" (n=1298), "intermittent" (n=921), and "persistent steatosis" (n=915). During the pre-baseline period, hepatic steatosis trajectories were associated with trajectories of developing diabetes and hypertension, and persistent steatosis (vs. other trajectories) was associated with higher risks and rapidly progressive disease patterns. At a median 13.6years of follow-up, 629 CVD events occurred. A persistent (vs. non-steatosis: HR 1.44, 95% CI 1.17-1.76), but not intermittent, steatosis pattern predicted the future risk of CVD, after adjustment for age, sex, smoking, and obesity. This association was independent of genetic background, and remained after accounting for pre-baseline body-mass index, other cardiometabolic risk factors, Framingham risk score, medications, and hepatic fibrosis score. The persistence of hepatic steatosis is associated with trajectories of metabolic disorder development and increased risk of CVD. These data have important implications for practice and further research.

Fermented aquatic weed meal (FAWM) as a protein source in Asian Catfish Clarias batrachus diets: Impacts on growth, blood chemistry profile, liver and gut morphology and economic efficiency

The global aquaculture industry is increasingly seeking sustainable alternatives to fishmeal (FM) due to its high price and shortfall in supply. In this context, fermented aquatic weed meal (FAWM) could emerge as a viable plant protein source for aquafeed. Four isoproteic diets [30 % crude protein (CP)] were formulated, incorporating 50 % total protein from FAWM comprising fermented Azolla diet (D1), Pistia diet (D2), and Eichhornia diet (D3). The control diet (D0) did not contain FAWM. At the end of the 90 days feeding trial, their growth performance, whole-body proximate composition, gut microbial load, haemato-biochemical indices, liver and gut health, and economic efficiency were determined. Fish fed with D0 had significantly (p < 0.05) improved growth performance and feed utilization compared to other treatment groups. Meanwhile, the fish supplemented with D1 diet exhibited significantly (p < 0.05) higher final weight (g), specific growth rate (%/day), weight gain (%), total biomass (g), and protein efficiency ratio among the FAWM dietary groups. The D1 group also demonstrated the significantly (p < 0.05) highest whole-body CP (64.27 ± 0.40 %) and lower crude lipid (8.24 ± 0.28 %) compared to other test diets. The total bacteria (TB) and lactic acid bacteria (LAB) in the fish gut were found to be significantly (p < 0.05) higher in D1 group. Furthermore, most of the hemato-biochemical indices of fish were significantly (p < 0.05) affected by FAWM inclusions, with few exceptions. The histological findings indicated that amongst the FAWM groups, D1 fish exhibited improved intestinal health. Nonetheless, the gut of the control fish demonstrated substantially (p < 0.05) lower villi width and crypt depth than other treatments. The D1 and D2 diet groups had significantly improved liver health. Moreover, FAWM inclusion enhanced economic efficiency by considerably reducing farm feed cost (US$/kg) and increasing return on investment (%). In summary, dietary inclusion of fermented Azolla pinnata (D1) protein at 50 % in aquafeed promoted feed utilization, growth, health, and farm economics of Asian catfish fingerlings compared to other FAWM diets.