Reduced Alanine Aminotransferase Research Articles

Hepatoprotective Effect of Antrodia camphorata Mycelium Powder on Alcohol-Induced Liver Damage

Background/Objectives: Antrodia camphorata, also known as “Niuchangchih” in Taiwan, is a unique medicinal mushroom native to Taiwan. It is used in traditional medicine to treat various health conditions. In this study, we investigated the efficacy of A. camphorata mycelia on alcohol-induced liver damage, both in vitro and in vivo, in a Good Laboratory Practice (GLP) facility. Methods: The experimental groups consisted of a normal control group (G1), a negative control group (G2), an A. camphorata mycelium powder 50 mg/kg/day administration group (G3), a 100 mg/kg/day administration group (G4), a 200 mg/kg/day administration group (G5), and a positive control silymarin 200 mg/kg/day administration group (G6), with 10 Sprague Dawley rats assigned to each treatment group. Results: We found that treatment with A. camphorata mycelium powder significantly reduced alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, cholesterol, adiponectin, triglyceride, and malondialdehyde concentrations. Histopathological analysis also revealed that the inflammation score significantly decreased in the A. camphorata-treated groups. Conclusion: Based on these results, we conclude that repeated oral administration of A. camphorata mycelium powder is effective in improving alcoholic liver disease.

Evaluating the Root Extract of Reynoutria ciliinervis (Nakai) Moldenke: An Analysis of Active Constituents, Antioxidant Potential, and Investigation of Hepatoprotective Effects in Rats

Reynoutria ciliinervis (Nakai) Moldenke (R. ciliinervis) root, a traditional Chinese medicine, was found to exhibit remarkable pharmacological properties through a series of comprehensive investigations. Our study commenced with a qualitative phytochemical analysis that identified 12 bioactive compounds within the plant. Subsequently, utilizing ultraviolet-visible spectrophotometry, the methanol extract emerged as the optimal solvent extract, which was abundant in diverse classes of compounds such as carbohydrates, phenolics, steroids, alkaloids, phenolic acids, and tannins. In vitro antioxidant assays underscored the exceptional free radical scavenging, metal ion chelation, hydrogen peroxide scavenging, singlet oxygen quenching, and β-carotene bleaching capabilities of the methanol extract, significantly outperforming other solvent extracts. Further ultra high-performance liquid chromatography–electrospray ionization–quadrupole time of flight–mass spectrometry analysis revealed the presence of 45 compounds, predominantly anthraquinones and phenolics, in the methanol extract. The extract demonstrated robust stability under various conditions, including high temperatures, varying pH levels, and simulated gastrointestinal digestion as well as efficacy in inhibiting the oxidation in edible oils. Acute toxicity tests in mice confirmed the safety of the methanol extract and provided a valuable dosage reference for future studies. Importantly, high-dose methanol extract exhibited a significant pre-protective effect against D-galactosamine-induced liver injury in rats, as evidenced by reduced alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, malondialdehyde levels, and elevated catalase and albumin levels. These findings suggest a potential role for the methanol extract of R. ciliinervis root in treating oxidative stress-related disorders, highlighting the plant’s immense medicinal potential. Our research offers a thorough evaluation of the bioactive components, antioxidant properties, stability, and liver-protecting effects of the methanol extract, setting the stage for deeper investigation and potential clinical applications.

Characterizing Metabolomic and Transcriptomic Changes, and Investigating the Therapeutic Mechanism of Psoralea corylifolia Linn. in the Treatment of Kidney-Yang Deficiency Syndrome in Rats

Kidney-yang deficiency syndrome (KYDS) is characterized by a metabolic disorder stemming from neuroendocrine dysregulation, often associated with hepatic dysfunction. In traditional Chinese medicine, Psoralea corylifolia Linn. (BGZ) is commonly utilized for treating KYDS. However, the specific therapeutic effects of BGZ on liver function regulation remain unclear. To evaluate the protective effects of BGZ against KYDS in rats, organ index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other biochemical indices were analyzed. Hematoxylin and eosin (HE) staining was utilized to assess liver histopathology. Additionally, transcriptomic and metabolomic analyses were conducted to identify potential biomarkers. BGZ treatment led to a significant reduction in ALT and AST levels, accompanied by improvements in liver histopathology in rats with KYDS. Moreover, BGZ induced significant alterations in 92 differentially expressed genes (DEGs) and 20 metabolites in the KYDS rat model. The comprehensive examination of metabolites and DEGs identified potential mechanisms underlying the therapeutic effects of BGZ, highlighting the neuroactive ligand-receptor interaction, cAMP signaling pathway, calcium signaling pathway, and cytokine-cytokine receptor interaction as key mechanisms. Validation of key targets within the cAMP pathway was substantiated through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. The cAMP pathway emerges as a plausible mechanism through which BGZ exerts protective effects against KYDS. The findings of this study contribute to an improved understanding of the therapeutic actions of BGZ and establish a groundwork for further research into the complex pathways involved, as well as the potential for drug-targeted therapies for KYDS.

Inhibitory effects of flavonoids on organic cation transporter 1: Implications for food/herb-drug interactions and hepatoprotective effects

Organic cation transporter 1 (OCT1, gene symbol: SLC22A1) is mainly responsible for the hepatic uptake of various cationic drugs, closely associated with drug-induced liver injury (DILI). Screening and identifying potent OCT1 inhibitors with little toxicity in natural products is of great value in alleviating OCT1-mediated liver injury. Flavonoids, a group of polyphenols commonly found in foodstuffs and herbal products, have been reported to cause transporter-mediated food/herb-drug interactions (FDIs). Our objective was to investigate potential inhibitors of OCT1 from 96 flavonoids, evaluate the hepatoprotective effects on retrorsine-induced liver injury, and clarify the structure-activity relationships of flavonoids with OCT1. Thirteen flavonoids exhibited significant inhibition (>50%) on OCT1 in OCT1-HEK293 cells. Among them, the five strongest flavonoid inhibitors (IC50 < 10 μM), including α-naphthoflavone, apigenin, 6-hydroxyflavone, luteolin, and isosilybin markedly decreased oxaliplatin-induced cytotoxicity. In retrorsine-induced liver injury models, they also reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to different levels, the best of which was 6-hydroxyflavone. The pharmacophore model clarified that hydrogen bond acceptors at the 4,8,5’ position might play a vital role in the inhibitory effect of flavonoids on OCT1. Taken together, our findings would pave the way to predicting the potential risks of flavonoid-related FDIs in humans and optimizing flavonoid structure to alleviate OCT1-mediated liver injury.

Effect of Ginger Supplementation on Liver Enzymes: A Systematic Review and Meta-Analysis

Background: Ginger (Zingiber officinale), as one of the herbal medicines, has high antioxidant activity. It may have protective effects against hepatotoxicity. This study seeks to perform a systematic review and meta-analysis on the impact of ginger on liver enzymes. Methods: The present systematic review and meta-analysis study adhered to the guidelines outlined in the PRISMA 2020 statement. A comprehensive literature search was carried out in the Medline database (PubMed), Google Scholar, Embase, Scopus, Web of Science, and Cochrane Library until the conclusion of February 2021. All interventional animal studies were included. The selected studies were the ones that examined the impact of ginger on serum liver enzymes. Results: Out of 741 articles, 39 studies were incorporated into the systematic review and meta-analysis. The pooled results suggested that ginger significantly reduced alanine aminotransferase (ALT) (standardized mean difference (SMD): 2.52, 95% confidence interval (CI): 2.12 to 2.93), aspartate aminotransferase (AST) (SMD: 3.03, 95% CI: 2.48 to 3.58), and alkaline phosphatase (ALP) (SMD: 2.10, 95% CI: 1.60 to 2.60). Conclusion: Ginger has favorable effects on liver enzymes. It shows potential as a beneficial complementary therapy for higher levels of ALT, AST, and ALP because of its useful effects and negligible side effects.

Effectiveness of Omega-3 Polyunsaturated Fatty Acids in Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder characterized by excessive hepatic fat accumulation without alcohol intake. It can progress to non-alcoholic steatohepatitis, increasing the risk of cirrhosis and liver failure. This study aims to evaluate the efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in treating NAFLD. A systematic review and meta-analysis was conducted including studies published from January 2018 to June 2023. Databases searched included PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. Inclusion criteria comprised randomized controlled trials and cohort studies involving human subjects or animal models with NAFLD. Data were extracted and analyzed to assess the impact of omega-3 PUFAs on liver fat, hepatic enzymes, and serum lipid profiles using RevMan 5.4. A total of 15 studies met the inclusion criteria. Omega-3 supplementation significantly decreased alanine aminotransferase (ALT) (mean difference = -2.12, 95% confidence interval (CI) = -3.36, -0.87) and aspartate aminotransferase (AST) (mean difference = -1.50, 95% CI = -2.59, -0.42). Gamma-glutamyl transferase levels showed a trend toward reduction (mean difference = -0.82, 95% CI = -1.66, 0.02). Serum lipid profiles improved significantly with reductions in triglycerides, low-density lipoprotein, and total cholesterol along with significant reductions in AST, ALT, and alkaline phosphatase in animal models. Omega-3 PUFAs appear to offer beneficial effects on liver enzymes, serum lipid profiles, and anthropometric indices in NAFLD patients. While their impact on liver fat content remains uncertain, omega-3 supplementation could serve as a valuable adjunct treatment for enhancing metabolic profiles and liver function in NAFLD patients.

Enhancing Laying Hens' Performance, Egg Quality, Shelf Life during Storage, and Blood Biochemistry with Spirulina platensis Supplementation.

Enhancing the sustainability of chicken farming involves improving health and productivity and product qualities. This study explores the influence of Spirulina platensis (SP) supplementation on the productivity, egg quality, shelf life during storage, and blood biochemistry of laying hens. A total of 192 thirty-nine-week-old White Leghorn hens were randomly divided into 4 dietary groups: a control group and 3 treatment groups receiving 2.5 g/kg, 5 g/kg, or 10 g/kg of SP, respectively. The study was conducted for six weeks with measuring feed intake, feed conversion ratio, egg production, egg quality, shelf life, and blood biochemistry. The results demonstrated significant enhancements in egg weight (p < 0.05) and egg mass (p < 0.05) in the treatment of SP groups. The SP treated hens showed significant improvements in yolk color (p < 0.05) and Haugh unit scores (p < 0.05). The SP supplementation showed a hepatoprotective effect, as indicated by significant reduction in Alanine aminotransferase (ALT) (p < 0.05) and alkaline phosphatase (ALP) (p < 0.05) levels; however, increases in total protein, albumin, and globulin levels were observed. Furthermore, the egg quality of stored eggs for 21 days linearly increased with increments in the SP levels. In conclusion, it can be speculated that adding SP at 2.5 g/kg and 5 g/kg can significantly improve the productivity of laying hens, eggs' quality, shelf life, and blood biochemistry, thereby contributing to a more sustainable and efficient chicken production.

Licorice and liver function in patients with primary liver disease: A systematic review and meta-analysis of RCTs.

Licorice (Glycyrrhiza spp.) has been a cornerstone of traditional Chinese and Japanese medicine. This systematic review and meta-analysis aimed to evaluate the efficacy of licorice formulations, alone or in combination with other herbs, on liver function enzymes in patients with primary liver disease. We systematically searched MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library up to April 2024. Randomized controlled trials (RCTs) comparing the effects of Glycyrrhiza spp. preparations versus placebo or standard of care controls were included. Standard Cochrane methods were used to extract data and appraise eligible studies. A total of 15 RCTs, involving 1367 participants, were included in the analysis. The studies varied widely in geographical location, duration, and licorice preparations used. Licorice significantly reduced alanine aminotransferase (ALT) by 15.63 U/L (95% CI: -25.08, -6.18; p = 0.001) and aspartate aminotransferase (AST) by 7.37 U/L (95% CI: -13.13, -1.61; p = 0.01) compared to control groups. Subgroup analyses revealed that purified glycyrrhizic acid compounds were particularly effective, showing greater reductions in ALT and AST without significant heterogeneity. Although licorice treatment did not significantly impact gamma-glutamyl transferase and total bilirubin (TBIL) levels overall, specific licorice-herb preparations did show a notable reduction in TBIL. The safety profile of licorice was consistent with known side effects, predominantly mild and related to its mineralocorticoid effects. Despite heterogeneity and potential language bias, the findings suggest that licorice can enhance liver function. Further studies should standardize licorice preparations and explore its role in multifaceted herbal formulations to better understand its hepatoprotective mechanisms.

Growth hormone augmentation in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis of randomized controlled trials.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis and metabolic dysregulation. Growth hormone (GH) augmentation has emerged as a potential therapeutic intervention for treating MASLD. This systematic review and meta-analysis aimed to evaluate the impact of GH augmentation on different parameters of MASLD. A systematic literature search identified randomized controlled trials investigating GH augmentation in MASLD patients. Search results were screened via Covidence and the Risk of Bias 2 tool was used to assess bias in randomized controlled trials. Statistical analysis utilized RevMan v5.3. We combined dichotomous outcomes employing odds ratios and continuous outcomes utilizing mean difference (MD), each with a 95% confidence interval (CI). Statistical significance was indicated by a P-value less than 0.05. Heterogeneity was evaluated using I2 tests. Our results showed that GH augmentation resulted in a significant reduction in both relative (MD: -46.26; 95% CI: -71.52, -21.00; P = 0.0003) and absolute (MD: -5.15; 95% CI: -7.93, -2.37; P = 0.0003) hepatic fat fraction. GH augmentation significantly reduced alanine aminotransferase (MD: -5.97; 95% CI: -10.31, -1.62; P = 0.007) and gamma-glutamyl transferase (MD: -16.18; 95% CI: -30.76, -1.59; P = 0.03) levels. No significant changes were observed in hemoglobin A1c, C-reactive protein, fasting serum glucose, BMI, triglycerides, and low-density lipoprotein cholesterol levels. Our meta-analysis highlights GH augmentation as a promising therapy for reducing liver steatosis and improving liver enzyme levels in MASLD patients. Further large-scale trials are warranted to examine the long-term effects, safety profiles, and potential impact on various measures.

Effect of Intermittent Fasting on Liver Function Tests: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Intermittent fasting (IF) is a diet strategy with alternate intervals of calorie reduction and normal eating. Despite its beneficial effects on weight loss and cardiometabolic risk factors, the effect of IF on liver function tests (LFTs) remains unclear. This study aimed to investigate the effect of IF on LFTs through a systematic review and meta-analysis of randomized clinical trials. An electronic search was performed using predefined search terms in databases including PubMed, Scopus, and ISI Web of Science until February 2023. The studies were selected according to PRISMA guidelines, and the risk of bias was assessed for the randomized controlled trials. The results of this study are reported as weighted mean differences (WMDs) with 95% CIs. Fourteen RCTs were included in the meta-analysis, with a total sample size of 908. IF significantly reduced alanine aminotransferase (ALT) (WMD: -2.88, 95% CI: -4.72 to -1.04, P-value = .002) and aspartate aminotransferase (AST) levels (WMD: -1.67, 95% CI: -3.12 to -0.22, P-value = .024). The results of the subgroup analysis showed that the impact of IF was significant in both the nonalcoholic fatty liver disease and the healthy groups for ALT. The effects of IF on the serum gamma-glutamyl transpeptidase (GGT) level were significant (WMD: -3.19, 95% CI: -6.00 to -0.39, P-value = .026), but there were no significant changes in the alkaline phosphatase (ALP) level (WMD: 1.06, 95% CI: -0.23 to 2.34, P-value = .106). Furthermore, no substantial heterogeneity between studies was reported. IF can improve ALT, AST, and GGT levels but not ALP enzyme levels and may have a benefit on liver function. PROSPERO registration no. CRD42023396211.

Synergistic effects of ursodeoxycholic acid, and quercetin on liver function and systemic inflammation in non-alcoholic fatty liver disease and atrial fibrillation patients

Background. Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) co-occur with signifi­cant clinical implications, necessitating therapeutic strategies that address the multifaceted nature of these conditions. This study evaluated the efficacy of standard treatment alone versus combined treatments with ursodeoxycholic acid (UDCA) and quercetin in patients with NAFLD and AF, focusing on improvements in liver function, lipid profile, systemic inflammation, and fibrosis markers. Aim: to evaluate and compare the efficacy of standard treatment alone versus standard treatment combined with ursodeoxycholic acid with and without quercetin in patients with non-alcoholic fatty liver disease and concurrent atrial fibrillation. Materials and methods. In a prospective, randomi­zed, controlled trial, 127 patients with diagnosed NAFLD and concurrent AF were enrolled. They were divided into three groups: group 1 — standard treatment (n = 42), group 2 — standard treatment plus UDCA (n = 44), and group 3 — standard treatment plus UDCA and quercetin (n = 41). The primary outcomes included changes in liver function tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase, alkaline phosphatase), lipid profile (total cholesterol, low- and high-density lipoprotein cholesterol (HDL-C), triglycerides), and non-invasive liver fibrosis scores (NFS, FIB-4). Secondary outcomes focused on systemic inflammation markers (C-reactive protein, galectin-3, soluble ST2) and fibronectin levels. Results. All treatment groups showed significant improvements in liver function tests and lipid profiles. Group 3 exhibited the most substantial reductions in ALT, AST, and improvements in HDL-C, indicating enhanced hepatoprotective and lipid-modulating effects. Systemic inflammation markers and fibronectin levels decreased significantly in groups receiving UDCA and quercetin, with the most pronounced effects observed in group 3, suggesting potent anti-inflammatory and anti-fibrotic action. Additionally, significant improvements in NFS and FIB-4 scores in group 3 highlight the anti-fibrotic potential of combining UDCA and quercetin with standard treatment. Conclusions. The addition of UDCA and quercetin to standard treatment for patients with NAFLD and AF significantly improves liver function, lipid metabolism, and reduces systemic inflammation and fibrosis, compared to standard treatment alone. These findings suggest a synergistic effect of UDCA and quercetin, offering a promising therapeutic strategy for managing the complex interplay between NAFLD and AF.

Ascertaining variations in the activity of larval midgut enzymes of Helicoverpa armigera by dietary emamectin benzoate through biochemical and in silico docking study

Helicoverpa armigera, a ubiquitous polyphagous pest, poses a significant threat to global agriculture, causing substantial economic losses and demonstrating resistance to synthetic pesticides. This study investigates the potential of emamectin benzoate (EMB), an avermectin derivative, as an effective control agent against H. armigera. The larvae of the NBII-MP–NOC–01 strain of H. armigera were reared on an artificial diet. The impact of dietary EMB was examined on four midgut enzymes; alanine aminotransferase (ALT), aspartate aminotransferase (AST), acid phosphatase (ACP), and alkaline phosphatase (ALP). Results showed a dose-dependent and time-dependent reduction in ALT and AST activity, while an initial increase and subsequent decline in ACP and ALP activity at higher EMB concentrations. Computational modelling of enzyme structures and molecular docking studies revealed differential binding of EMB with the midgut enzymes. The strongest interaction was observed between EMB and ALT residues, contrasting with weakest interactions observed with AST. The study also showed that decreased activity of transaminases in H. armigera caused by EMB may be because of stability-activity trade-off, while in phosphatases reverse may be the case. This research provides crucial insights into the biochemical responses and the intricate insecticide-enzyme interactions in H. armigera caused by EMB exposure. This study lays the foundation for further research aimed at developing environmentally friendly approaches for managing H. armigera, addressing the challenges associated with conventional pesticides.

Protective effect of cinnamon extract against cobalt-induced multiple organ damage in rats.

The role of oxidative stress and inflammation in cobalt (Co) toxicity has been the focus of previous studies. Cinnamon and its main components have been reported to have protective effects in various tissues with antioxidant and anti-inflammatory effects. In this study, the protective effect of cinnamon extract (CE) against possible Co-induced heart, kidney, and liver damage in rats was investigated biochemically. Eighteen albino Wistar-type male rats were categorized into three groups (n = 6 per group): control (CG), CoCL2-administered (CoCL2), and CE + CoCL2-administered (CE + Co) groups. The CE + CoCL2 group was administered CE (100mg/kg), and the CoCL2 and CG groups were administered distilled water orally by gavage. One hour after the administration, Co (150mg/kg) was administered orally to the CE + CoCL2 and CoCL2 groups. This procedure was repeated once daily for 7days. Then, biochemical markers were studied in the excised heart, kidney, and liver tissues. CoCL2 increased oxidants and proinflammatory cytokines and decreased antioxidants in heart, kidney, and liver tissues. Heart, kidney, and liver tissue were affected by Co damage. CE treatment suppressed the CoCL2-induced increase in oxidants and proinflammatory cytokines and decrease in antioxidants in heart, kidney, and liver tissues. CE treatment has been shown to attenuate cardiac damage by reducing serum troponin I (TpI) and creatine kinase-MB (CK-MB), renal damage by reducing creatinine and blood urea nitrogen (BUN), and liver damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Co induced the production of oxidants and proinflammatory parameters and antioxidant depletion in heart, kidney, and liver tissues of rats. Our experimental results show that CE protects heart, kidney, and liver tissues against oxidative and inflammatory changes induced by CoCLl2.

Impact of Synbiotic Intake on Liver Metabolism in Metabolically Healthy Participants and Its Potential Preventive Effect on Metabolic-Dysfunction-Associated Fatty Liver Disease (MAFLD): A Randomized, Placebo-Controlled, Double-Blinded Clinical Trial.

Synbiotics modulate the gut microbiome and contribute to the prevention of liver diseases such as metabolic-dysfunction-associated fatty liver disease (MAFLD). This study aimed to evaluate the effect of a randomized, placebo-controlled, double-blinded seven-week intervention trial on the liver metabolism in 117 metabolically healthy male participants. Anthropometric data, blood parameters, and stool samples were analyzed using linear mixed models. After seven weeks of intervention, there was a significant reduction in alanine aminotransferase (ALT) in the synbiotic group compared to the placebo group (-14.92%, CI: -26.60--3.23%, p = 0.013). A stratified analysis according to body fat percentage revealed a significant decrease in ALT (-20.70%, CI: -40.88--0.53%, p = 0.045) in participants with an elevated body fat percentage. Further, a significant change in microbiome composition (1.16, CI: 0.06-2.25, p = 0.039) in this group was found, while the microbial composition remained stable upon intervention in the group with physiological body fat. The 7-week synbiotic intervention reduced ALT levels, especially in participants with an elevated body fat percentage, possibly due to modulation of the gut microbiome. Synbiotic intake may be helpful in delaying the progression of MAFLD and could be used in addition to the recommended lifestyle modification therapy.

Glucagon-like peptide 1 receptor agonists in the treatment of patients with type 2 diabetes and metabolically-associated steatosic liver disease. Review

In recent years, the prevalence of metabolically‑associated steatosis of the liver (MASLD) in patients with type 2 diabetes mellitus (T2DM) has been increasing significantly. Therefore, there is an urgent need to study new strategies for the treatment of this pathology, in particular, to prevent the progression of liver steatosis and fibrosis and to reduce the mortality associated with liver diseases. A systematic review and meta‑analysis of randomized controlled trials was recently conducted to assess the efficacy and safety of glucagon‑like peptide‑1 receptor agonists (GLP‑1RAs) in the treatment of hepatic steatosis and fibrosis in patients with T2DM s and MASLD. A total of eight trials were included in the review, involving a total of 468 participants with T2DM and MASLD. Analysis of the primary results showed that administration of GLP‑1RAs in patients with T2DM and MASLD significantly reduced the content of intrahepatic fat, subcutaneous adipose tissue, and visceral adipose tissue. Analysis of secondary outcomes showed that GLP‑1RAs caused significant reductions in alanine aminotransferase, aspartate aminotransferase, body weight, body mass index, waist circumference, fasting blood glucose and HbA1c, HoMA‑IR insulin resistance index, total cholesterol and triglycerides compared with the control schemes of treatment. The main adverse events associated with GLP‑1RAs included mild to moderate gastrointestinal discomfort and hypoglycemia, which resolved within several weeks. GLP‑1 RAs have a positive effect in patients with T2DM and MASLD and have a positive effect on inflammatory markers, contribute to reducing of weight, waist circumference, and insulin resistance index. Therefore, GLP‑1RAs can be considered as a potential treatment strategy for patients with type 2 diabetes and MASLD, if there are no contraindications. Further studies are needed to clearly understand the effect of GLP‑1RAs on the course of MASLD and the potential mechanisms by which they exert a therapeutic effect and prevent its progression.

Treatment response and clinical event-free survival in autoimmune hepatitis: A Canadian multicentre cohort study

We sought to identify predictors of outcome for people living with autoimmune hepatitis (AIH). We evaluated the clinical course of people with AIH across 11 Canadian centres. Biochemical changes were analysed using linear mixed-effect and logistic regression. Clinical outcome was dynamically modelled using time-varying Cox proportional hazard modelling and landmark analysis. In 691 patients (median age 49 years, 75.4% female), with a median follow-up of 6 years (25th-75th percentile, 2.5-11), 118 clinical events occurred. Alanine aminotransferase (ALT) normalisation occurred in 63.8% of the cohort by 12-months. Older age at diagnosis (odd ratio [OR] 1.19, 95% CI 1.06-1.35) and female sex (OR 1.94, 95% CI 1.18-3.19) were associated with ALT normalisation at 6 months, whilst baseline cirrhosis status was associated with reduced chance of normalisation at 12 months (OR 0.52, 95% CI 0.33-0.82). Baseline total bilirubin, aminotransferases, and immunoglobulin G (IgG) values, as well as initial prednisone dose, did not predict average ALT reduction. At baseline, older age (hazard ratio [HR] 1.25, 95% CI 1.12-1.40), cirrhosis at diagnosis (HR 3.67, 95% CI 2.48-5.43), and elevated baseline total bilirubin (HR 1.36, 95% CI 1.17-1.58) increased risk of clinical events. Prolonged elevations in ALT (HR 1.07, 95% CI 1.00-1.13) and aspartate aminotransferase (HR 1.13, 95% CI 1.06-1.21), but not IgG (HR 1.01, 95% CI 0.95-1.07), were associated with higher risk of clinical events. Higher ALT at 6 months was associated with worse clinical event-free survival. In people living with AIH, sustained elevated aminotransferase values, but not IgG, are associated with poorer long-term outcomes. Biochemical response and long-term survival are not associated with starting prednisone dose. Using clinical data from multiple Canadian liver clinics treating autoimmune hepatitis (AIH), we evaluate treatment response and clinical outcomes. For the first time, we apply mixed-effect and time-varying survival statistical methods to rigorously examine treatment response and the impact of fluctuating liver biochemistry on clinical event-free survival. Key to the study impact, our data is 'real-world', represents a diverse population across Canada, uses continuous measurements over follow-up, and our findings help inform risk stratification of patients. We provide evidence for treating clinicians, as well as those developing and evaluating new therapies, to seek evidence of good treatment response by keeping aminotransferase activity values within the reference range. Our results challenge the role of IgG as a marker of treatment response and if normalisation of IgG should remain an important part of the definition of biochemical remission. Our analysis further highlights that baseline markers of disease severity may not prognosticate early treatment response. Additionally, the initial prednisone dose may be less relevant for achieving aminotransferase normalisation. This is important for patients and treating clinicians given the relevance and importance of side-effects of treatment for patients.

The beneficial hepatic effects of glucagon‐like peptide 1 receptor agonists in patients with diabetes and metabolic dysfunction‐associated steatotic liver disease are independent of weight loss

AbstractBackgroundMetabolic dysfunction‐associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. Despite resmetirom being recently approved for treatingnon‐cirrhotic MASH patients in the United States of America (but not elsewhere), weight loss and lifestyle remain the first line and mainstay for treating the condition. Glucagon‐like peptide 1 receptor agonists (GLP‐1RAs) have shown promise in MASLD treatment, as they promote significant weight loss.AimsIn this study, we assessed the effect of long‐term GLP‐1 therapy on liver disease severity in a cohort of patients with Type 2 diabetes and MASLD.Materials and methodsIn this retrospective observational study, we included all new MASLD patients seen in the liver clinic (Imperial College Healthcare NHS Trust) from January 2010 to May 2022. Demographic, anthropometric and clinical data were collected at baseline and at the most recent follow‐up.Results779 patients were included. Among those with Type 2 diabetes mellitus (T2DM) (n = 335), 94 (28%) were prescribed a GLP‐1RA for a median period of 38 (1–171.2) months. In those on GLP‐1RA, there was a significant improvement in BMI (33.1 vs. 34.9 kg/m2, p = 0.005), alanine aminotransferase (ALT) (37 vs. 58 IU/L, p = 0.009), HbA1c (58 vs. 61 mmol/lL, p = 0.006) and CAP score (331 vs. 354 dB/m, p = 0.0001) at the end of follow‐up. Finally, among those who were treated with GLP‐1RA, 37 patients had &lt;5% weight loss over a median of 38 (10–134) months. In this group, there was also a significant reduction in ALT (32 vs. 58 IU/L, p = 0.0001), AST (30 vs. 36 IU/L, p = 0.004) and CAP score (329 vs. 349 dB/m, p = 0.05) compared with those who lost &gt;5% weight. In this real‐life cohort of patients with diabetes and MASLD, treatment with GLP‐1RA was associated with greater weight loss and hepatic fat reduction. Of note, a reduction in fat content was observed also in those who did not lose weight.ConclusionTreatment with GLP‐1RA should be favoured when treating patients with co‐existing diabetes and MASLD.

Assessment of hepatoprotective and nephroprotective effects of Vitis vinifera leaf extract on carbon tetrachloride induced toxicity in rats

Background: Vitis vinifera is known for its antimicrobial activity; however, the hepatoprotective activity of aqueous extracts of aerial parts has also been reported, but the nephroprotective and hepatoprotective activity of ethanolic extracts have not yet been evaluated. Objective: To evaluate Vitis vinifera's hepatoprotective and nephroprotective activities against CCl4-induced toxicity in rats. Methods: Two doses of ethanolic extract of Vitis vinifera (100 and 200 mg/kg/day) were evaluated and compared with silymarin 100 mg/kg. Biochemical blood parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Gamma-glutamyltranspeptidase (GGT), bilirubin, urea, uric acid, total protein and creatinine, and histopathologic changes of liver and kidney were studied and evaluated. Results: Vitis vinifera reduced the elevated blood levels of ALT, AST, ALP, urea, and creatinine, with the ethanol extract to 200 mg/kg/day being more effective. The histopathologic evaluation suggested that Vitis vinifera decreased hepatic and renal necrosis induced by CCl4. The more significant dose resulted in reductions in AST, ALT, GGT, ALP, and bilirubin of 54, 27, 56, 36, and 17%, respectively. Ethanolic extract 200 mg/kg/day also shows a reduction in elevated levels of Creatinine, Urea, Uric Acid, and Total Protein by 61%, 58%, 29%, and 9%, respectively. Conclusion: Hepatoprotective and nephroprotective activities of ethanol extract of Vitis vinifera were demonstrated, with ethanol extract to 200 mg/kg/day being the most effective. This presents scientific evidence for using medicinal plants such as Vitis vinifera in managing liver and kidney disorders.

Glucagon-like Peptide-1 Receptor Agonists-A Potential New Medication for Pediatric Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children in the US and, if untreated, may progress to end-stage liver disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown improvement in MASLD markers in adults with type 2 diabetes mellitus (T2DM). Currently, there is a lack of medications available for the treatment of pediatric MASLD. We aimed to provide preliminary data on the effects of GLP-1 RAs on markers of MASLD in a retrospective study, in an effort to bridge this gap in the pharmacotherapies available. Nine patients from a T2DM clinic who met the following inclusion criteria were included in this study: patients diagnosed with pre-diabetes or T2DM, prescribed a GLP-1 RA in the prior 12 months, and having alanine aminotransferase (ALT) elevated to twice the upper limit of the normal range, indicating evidence of MASLD. The average change between baseline and the first measurement after starting a GLP-1 RA was calculated for ALT, hemoglobin A1c, and BMI. ALT decreased by an average of 98 points. A1c decreased by an average of 2.2 points. BMI decreased by an average of 2.4 points. There was greater reduction in ALT and A1c compared to BMI, suggesting that improvement in MASLD may be independent of weight loss. This is a preliminary study that shows potential, and prospective studies are needed to evaluate the effects of GLP-1 RAs in the management of pediatric MASLD.

RESTITUTIVE PROPERTIES OF CURCUMA LONGA ON CYPERMETHRIN INDUCED SWISS-ALBINO MICE (MUS MUSCULUS)

The present investigation delves into the reparative efficacy of Curcuma longa extract in mitigating the deleterious effects induced by varying concentrations of cypermethrin in Swiss albino mice (Mus musculus). A significant increase was observed at the highest dose of cypermethrin (200 mg/kg of body weight of Swiss albino mice) in biochemical parameters namely Aspartate Aminotransferase (AST), 49 % Alanine Aminotransferase (ALT), 58 % Blood Urea Nitrogen (BUN), 108 % Creatinine 247 %. The discernible outcome is evidenced by a gradual recovery in the damage inflicted by cypermethrin. Significant changes were observed, including an approximate 16% decrement in AST, 7% reduction in ALT, substantial 45% decline in BUN levels, and a pronounced 76.16% decrease in creatinine levels. Further, haematological indices demonstrate a commendable recovery pattern, with a 10% resurgence in neutrophils, 3% restitution in lymphocytes, 6% recuperation in basophils, 2% restoration in monocytes, and 10% revival in eosinophils. These findings substantiate a promising therapeutic role for C. longa extract within the realm of pharmaceutical industries, signifying its potential utility in countering cypermethrin-induced physiological disbalance.