Histological Changes In Liver Research Articles

Clinical predictors and noninvasive imaging in Fontan-associated liver disease: A systematic review and meta-analysis

Background: Despite the development of several imaging modalities for diagnosing Fontan-associated liver disease (FALD), there is no optimal protocol for the follow-up of FALD. We conducted a systematic review and meta-analysis to identify factors related to liver fibrosis using biopsy reports and to identify alternative noninvasive modalities that could better reflect liver histological changes in FALD. Methods: A systematic review and meta-analysis were conducted following the PRISMA guidelines Table S2. We searched Embase, PubMed, and Cochrane databases for studies on FALD, focusing on those assessing clinical factors associated with liver fibrosis severity through liver biopsy and noninvasive imaging techniques. Results: A total of 42 studies were identified, of which 12 conducted meta-analyses and subgroup analyses of the severity of liver fibrosis using liver biopsies. Liver biopsy results showed a weak positive correlation between Fontan duration and fibrosis severity (R = 0.36). Subgroup analyses revealed significant differences in hemodynamic parameters, such as Fontan pressure, between patients with mild and severe fibrosis. Platelet count, aspartate aminotransferase to platelet ratio index, and fibrosis-4 index were significantly associated with fibrosis severity, with severe fibrosis showing lower platelet counts and higher aspartate aminotransferase to platelet ratio index and fibrosis-4 index levels. Noninvasive imaging modalities, particularly magnetic resonance elastography and shear wave elastography, demonstrated strong correlations with biopsy-confirmed fibrosis severity. Conclusions: This study identifies key clinical factors, and noninvasive modalities accurately reflect liver fibrosis severity in patients with FALD. Clinical factors such as platelet count, aspartate aminotransferase to platelet ratio index, and fibrosis-4 index may aid in identifying patients at risk for severe fibrosis. In addition, magnetic resonance elastography and shear wave elastography are promising tools for noninvasive assessment in our study. Further research is needed to refine these diagnostic approaches and improve patient management.

Omega-3 fatty acids mitigate histological changes and modulate the expression of ACACA, PFK1 and ET-1 genes in broiler chickens under environmental stress: a pulmonary artery, cardiomyocyte and liver study

The aim of this study was to investigate the effects of omega-3 fatty acids on blood biochemical parameters, histological changes in pulmonary artery, cardiomyocytes, and liver, as well as the expression of ACACA, PFK1, and ET-1 genes in broiler chickens under environmental stress (high stoking density). A total of 420 one-day-old male Ross broilers were used in a 2 × 2 factorial arrangements, with 2 levels of environmental stress (without and with stress; 9 and 17 birds/m2, respectively) and 2 levels of omega-3 fatty acids (low and high; 0.057 and 0.5% of the diet, respectively) in a completely randomized design comprising 4 treatments and 5 replicates per each. The body weight decreased at d 40 because of environmental stress (P ≤ 0.05). The ascites heart index (AHI) in broilers fed high omega-3 fatty acids diets was lower (P = 0.062) than broiler fed low omega-3 fatty acids diet (0.279 vs. 0.316). Stressed birds showed a higher neutrophil: lymphocyte ratio compared to non-stressed birds (P ≤ 0.05). Broiler chickens receiving high omega-3 fatty acids diets exhibited elevated levels of hematocrit (HCT), hemoglobin (HGB), and lymphocytes (P ≤ 0.05). The neutrophil: lymphocyte ratio, and serum concentration of alanine aminotransferase (ALT), and aspartate aminotransferase (AST) decreased in broilers fed high omega-3 fatty acids diets (P ≤ 0.05). In stressed broilers on a high omega-3 diet, pulmonary artery wall thickness decreased (P ≤ 0.05). Additionally, under stress, myocardial cell diameter, hepatocyte and cell nucleus diameter significantly increased (P ≤ 0.05). Stressed broilers showed an increased relative fold change in PFK1 enzyme activity but reduced ET-1 mRNA expression in the liver compared to stressed birds on a high omega-3 diet (P ≤0.05). In conclusion, the results indicate that dietary omega-3 fatty acids have the potential to alleviate the adverse histological changes in the pulmonary artery, cardiomyocytes, and liver, while also modulating the expression of genes ACACA, PFK1, and ET-1 that are influenced by environmental stress in broiler chickens.

A betaine-contained solution reduced cold ischemia damage through inhibiting vacuolar degeneration in livers

A new osmoprotectant-containing multiple saccharide (MS) solution was formulated for this study. The primary objectives were to compare the effects of the MS solution with those of the University of Wisconsin (UW) solution and hypertonic citrate adenine (HCA) solution on liver cold preservation, as well as to investigate the mechanisms underlying osmolarity-induced injury. Rat livers were cold-stored for 18 h at 4 °C using the different solutions and subsequently subjected to 2 h of normothermic machine perfusion (NMP) for functional assessment. The livers were categorized into four groups: HCA, UW, MS, and a control group. Liver function and histological changes were evaluated using biochemical markers such as lactate dehydrogenase (LDH), alongside histopathological analysis. Additionally, the expression of aquaporin 9 (AQP9) and hydrogen peroxide (H2O2) in hepatocytes was examined. Liver damage was significantly reduced in the UW and MS groups (p < 0.05). Histopathological analysis revealed a decrease in hepatic apoptosis and injury scores in the MS group compared to the HCA group (p < 0.05). No significant differences in liver function changes were observed between the MS and UW groups. Furthermore, examination of liver tissue showed increased H2O2 fluorescence intensity and decreased AQP9 protein levels in livers exhibiting vacuolar degeneration. In conclusion, the MS solution demonstrated superior effectiveness in preserving the liver during cold storage by inhibiting vacuolar degeneration caused by intracellular H2O2 accumulation.

Cicer arietinum phytosome ameliorates hepatosteatosis via downregulation of fatty acid synthase and stearoyl-CoA desaturase 1 in rats

Abstract Background Hepatosteatosis is considered a universal problematic health due to bad lifestyle. Thereby, the current study evaluates the influence of the Cicer arietinum polyunsaturated fatty acids (CAP) and newly synthesized C. arietinum polyunsaturated fatty acids phytosome (CAPP) against non-alcoholic fatty liver disease (NAFLD) persuaded through a high-fat diet (HFD) in addition to tamoxifen (TAM) in male albino rats. Forty-eight rats were separated into eight groups (6 rats/group). Rats of the control group were administered distilled water for 45 consecutive days, while phosphatidyl choline (PC), CAP, and CAPP groups administered distilled water (15 days), afterward administered PC, CAP, and CAPP, respectively (500 mg/kg b.wt), orally for 30 days. All the previous groups fed normal diet for the 45 days, while NAFLD rats feed HFD for 45 days and receive TAM (200 mg/kg b.wt, i.p) daily for 15 days, followed by administration of vehicle, PC, CAP, and CAPP orally for another 30 days. Results Hepatosteatosis was appraised biochemically by significant increase in the concentrations of serum AST, ALT, γGT, LDH, ALP, total bilirubin, total lipid, triglycerides, fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD-1), and LDL-cholesterol, as well as hepatic total lipids and triglycerides. In addition, a significant decline in serum total protein, albumin, and HDL-cholesterol concentrations was observed in comparison with the control group. NAFLD induces oxidative stress by noteworthy increase in hepatic MDA, H2O2, and meaningful reduction in hepatic GSH, SOD, GST, GRD, and CAT levels as compared with the corresponding control group. Liver histological changes were noted in the NAFLD group as compared to the control. Interestingly, CAP and CAPP treatments modulate the abnormal effects of NAFLD in all the previous parameters. For the histological changes caused by NAFLD, the liver tissue appeared nearly normal after the treatment with CAP and CAPP. Conclusion CAP and CAPP administration may have a potential role in alleviating hepatosteatosis. This may relate to its downregulation against FAS, SCD-1, and oxidative stress.

Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models

Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disorders, is characterized by hepatic lipid accumulation. MASLD causes alterations in the antioxidant defense system, lipid, and drug metabolism, resulting in impaired antioxidant status, hepatic metabolic processes, and clearance of therapeutic drugs, respectively. In the MASLD pathogenesis, dysregulated epigenetic mechanisms (e.g., histone modifications, DNA methylation, microRNAs) play a substantial role. In this study, the development of MASLD was investigated in mice fed a high-fat, high-fructose, and high-cholesterol (FFC) diet from 2 months of age, mice treated neonatally with monosodium glutamate (MSG) on a standard diet (STD), and mice treated with MSG on an FFC diet at 7 months of age and compared to control mice (C) on STD. Changes in liver histology, detoxification enzymes, epigenetic regulation, and genes involved in lipid metabolism were characterized and compared. The strong liver steatosis was observed in MSG STD, C FFC, and MSG FFC, with significant fibrosis in the latter one. Moreover, substantial alterations in hepatic lipid metabolism, epigenetic regulatory factors, and expressions and activities of various detoxification enzymes (namely superoxide dismutase, catalase, and carbonyl reductase 1) were observed in MASLD mice compared to control mice. miR-200b-3p, highly significantly upregulated in both FFC groups, could be considered as a potential diagnostic marker of MASLD. The MSG mice fed FFC seem to be a suitable model of MASLD characterized by both liver steatosis and fibrosis and substantial metabolic dysregulation.

The possible protective effect of luteolin on cardiovascular and hepatic changes in metabolic syndrome rat model.

The metabolic syndrome, or MetS, is currently a global health concern. The anti-inflammatory, anti-proliferative, and antioxidant properties of luteolin are some of its advantageous pharmacological characteristics. This research was designed to establish a MetS rat model and investigate the possible protective effect of luteolin on cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. Forty adult male albino rats were split into four groups: a negative control group, a group treated with luteolin, a group induced MetS (fed 20% fructose), and a group treated with luteolin (fed 20% fructose and given luteolin). Following the experiment after 8weeks, biochemical, histological (light and electron), and immunohistochemistry analyses were performed on liver and heart tissues. Serum levels of cTnI, CK-MB, and LDH were significantly elevated in response to the cardiovascular effect of MetS. Furthermore, compared to the negative control group, the MetS group showed a marked increase in lipid peroxidation in the cardiac and hepatic tissues, as evidenced by elevated levels of MDA and a decline in the antioxidant defense system, as demonstrated by lower activities of GSH and SOD. The fatty liver-induced group exhibited histological alterations, including disrupted hepatic architecture, dilated and congested central veins, blood sinusoids, and portal veins. In addition to nuclear structural alterations, most hepatocytes displayed varying degrees of cytoplasmic vacuolation, mitochondrial alterations, and endoplasmic reticulum dilatation. These alterations were linked to inflammatory cellular infiltrations, collagen fiber deposition, active hepatic stellate cells, and scattered hypertrophied Kupffer cells, as demonstrated by electron microscopy and validated by immunohistochemical analysis. It is interesting to note that eosinophils were seen between the liver cells and in dilated blood sinusoids. Moreover, the biochemical (hepatic and cardiac) and histological (liver) changes were significantly less severe in luteolin-treated raton a high-fructose diet.These results suggested that luteolin protects against a type of metabolic syndrome that is produced experimentally.

Risk factors for significant histological changes in both HBeAg positive and negative treatment-naive chronic hepatitis B with persistently normal alanine aminotransferase level

BackgroundChronic hepatitis B virus (HBV) infection remains a serious health issue, and determining the optimal time for antiviral therapy is challenging. We aimed to assess liver histological changes in patients with HBeAg-positive chronic hepatitis B (CHB) and those with HBeAg-negative CHB who had persistently normal alanine aminotransferase and to determine the association between significant liver injury and various clinical parameters.MethodsWe retrospectively included, in this study, 339 treatment-naïve patients with chronic HBV infections who had persistently normal alanine aminotransferase and underwent liver biopsy from 2013 to 2023. Histologic assessment was based on the Metavir scoring system to evaluate the association between clinical characteristics and the severity of liver inflammation and fibrosis.ResultsAmong the included participants, 138 were HBeAg-positive and 201 were HBeAg-negative. Lower hepatitis B surface antigen (HBsAg) (P = 0.003) and higher aspartate aminotransferase (AST) (P = 0.002) levels were associated with significant necroinflammation, whereas increasing age (P = 0.004) and lower HBV DNA (P < 0.001) levels were associated with significant fibrosis in HBeAg-positive patients with normal ALT levels. Higher HBV-DNA (P = 0.001) and AST levels(P < 0.001) were associated with significant necroinflammation, and higher AST(P < 0.001) levels were associated with significant fibrosis in HBeAg-negative patients.ConclusionsA substantial proportion of patients with HBV infection who had normal ALT presented significant liver injury. HBsAg and AST were independent predictive factors for evaluating inflammation, while HBV DNA load and age were independent predictive factors for evaluating fibrosis in the HBeAg-positive group. HBV DNA load and AST were independent predictive factors for evaluating inflammation, while AST were independent predictive factors for evaluating fibrosis in the HBeAg-negative group.

Developmental histology of the liver in the Balkan crested newt Triturus ivanbureschi (Caudata: Salamandridae)

The liver, a crucial organ for metabolic processes, has a generally uniform histological structure across amphibian taxa. However, ontogenetic changes, particularly those related to biphasic life cycle and metamorphosis, are less documented. Here, we explored and described the liver histology of an emerging model organism, the Balkan crested newt (Triturus ivanbureschi) at three ontogenetic stages: larval, juvenile (just after metamorphosis) and adult. At the larval stage, the liver is characterized by hepatocytes containing large lipid droplets, poorly developed basement membranes in the blood vessels, and a lack of melanin-rich macrophage centers. Juveniles show transitional characteristics between larvae and adults. Lipid droplets in hepatocytes are abundant, but also, at the juvenile stage the well-developed basement membrane of blood vessels and melanomacrophages are present, as in adults. The presence of lipid droplets in hepatocytes during larval and juvenile stages suggests the liver's role in fat storage and energy provision during development and growth. Melanomacrophages, which synthesize melanin, perform phagocytosis, and neutralize free radicals, have been found in juveniles (after metamorphosis) and increase with age. The biphasic life cycle and liver histology transition in Triturus newts provide an insight in changes in liver histology and make them a suitable model for studying fat deposition regulation and the evolution of the immune system in terrestrial vertebrates.

Protective Effect of Banana, Cassava, and Corn Flours on Hepatotoxicity of Malnourished Male Rats

Background: Malnutrition-induced hepatotoxicity is defined as liver damage caused by insufficient nutrition, which results in oxidative stress and damage to liver cells. Objectives: The present study aimed to investigate the protective effects of banana, cassava, and corn flours on hepatotoxicity induced by malnutrition in male rats. Methods: Twenty-four male rats were divided into six groups (n=4): (1) rats received 30 g/rat normal feed daily for 45 days; (2) rats received 30 g malnutrition feed daily for 45 days; rats received 30 g/rat malnutrition feed daily for 15 days and then treated with normal feed (3), banana flour (4), cassava flour (5), and corn flour (6), for 30 days. The malnutrition groups received a diet with protein deficiency for 15 days, then were treated with a diet according to each treatment group. The liver enzymes were analyzed, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Furthermore, the liver's histopathological changes in each group were evaluated using Hematoxylin eosin staining. Results: The AST levels in malnourished male rats significantly (p&lt;0.05) increased (240.75±67.23 U/L) compared to the control group (170.00±33.52 U/L). While, the ALT levels (66.75±12.69 U/L) were decreased compared to the control group (98.75±26.61 U/L). Furthermore, malnutrition diet in rats caused significant changes in liver histology, including inflammatory cell infiltration, necrosis, congestion of the central vein, cytoplasmic vacuolization, and widened hepatic sinusoid. Interestingly, normalized AST and ALT levels and improved liver histology were observed in malnourished rats after receiving normal feed and flour of banana, cassava, and corn. Conclusions: Banana, cassava, and corn flours exhibited hepatoprotective activity on malnutrition-induced hepatotoxicity in malnourhised male rats.

Effect of Treatment of Malaria and Diabetes with Aqueous Extract of &lt;i&gt;Anthocleista Djalonensis&lt;/i&gt; in Mice

Anthocleista djalonensis is a medicinal plant that has been used to treat malaria, jaundice, abscesses and diabetes. The study assessed the effects of aqueous extract of A. djalonensis leaves on some biochemical indices in the treatment of malaria and diabetes. Twenty-four mice used were randomly assigned into six groups numbering four each and provided with feed and water ad libitum. Group 1 (control) received water and feed only. Groups 2, 3, 4 5 and 6 received 200 mg/kg body weight of extract; 5 mg/kg body weight of chloroquine, 400 mg/kg body weight extract, 2 mg/kg body weight glibenclamide 5 mg/kg body weight chloroquine and 2 mg/kg body weight glibenclamide respectively for seven days. Phytochemical screening of A. djalonensis leaves revealed the presence of alkaloids, phenols, saponins, steroids, flavonoids and tannins at 6.76 ± 0.03, 0.61 ± 0.01, 2.11 ± 0.02, 0.89 ± 0.01, 3.10 ± 0.03 and 1.13 ± 0.01 % respectively. Alanine aminotransferase and aspartate aminotransferase activity of Groups 5 and 6 were significantly (p&lt;0.05) higher compared to the control. There were no visible histological changes in liver and kidney. Results of this study suggest that A. djalonensis is relatively safe for the treatment of diabetes and malaria at the administered doses.

Significant liver histological change is common in HBeAg-positive chronic hepatitis B with normal ALT

Background and aimsNumerous HBeAg-positive chronic hepatitis B (CHB) patients with persistently normal ALT have significant liver histopathology. It is imperative to identify true “immune tolerant” patients. We aimed to evaluate the liver histopathology features of HBeAg-positive CHB patients with normal ALT and the incidence of liver cirrhosis and HCC in CHB patients during follow-up.Methods179 HBeAg-positive CHB patients with normal ALT who performed liver biopsy from 2009 to 2018 were retrospectively analyzed. Liver necroinflammation ≥ G2 and/or liver fibrosis ≥ S2 was defined as significant liver histopathological change.Results57.5% patients were in the indeterminate phase with significant liver histological changes. The proportion of the patients with evident liver necroinflammation was higher in the high-normal ALT group (21-40U/L) when compared with the low-normal ALT group (≤ 20 U/L) (51.3% vs. 30.0%, p < 0.05), and patients aged ≥ 40 years had a higher proportion of significant fibrosis than those aged < 40 years (64.5% vs. 39.9%, p < 0.05). The percentages of patients with ≥ S2 and ≥ G2/S2 in the HBV DNA < 107 IU/mL group were higher than those in the HBV DNA ≥ 107 IU/mL group (72.7% vs. 40.1%, p < 0.01; 81.8% vs. 54.1%, p < 0.05). During follow-up, two of immune tolerant patients and four of indeterminate patients developed into cirrhosis, and one of immune tolerant patients and one of indeterminate patients developed into HCC, respectively.ConclusionsHBeAg-positive CHB patients with high-normal ALT or HBV DNA < 107 IU/mL were tend to be indeterminate. Liver biopsy or noninvasive approaches are recommended to evaluate liver histopathology, and antiviral therapy is recommended for patients with significant liver histopathology.

Effect of Multiple Types of High-fat Diet Induction on Gut Microbiota Profile and Butyrate Levels on NAFLD Rat Model

Dysbiosis, marked by a decline in Firmicutes (such as Clostridium spp.) and a rise in Proteobacteria (such as Escherichia coli), is recognized as a pathway linked to the progression of non-alcoholic fatty liver disease (NAFLD). High-fat food may influence the development of NAFLD. This study investigates the effect of different high-fat diets on gut microbiota composition and butyrate levels in a rat model. Four groups of Rattus norvegicus strain Wistar (n=27) were fed specific diets for 12 weeks: normal diet (ND, n=7), high-fat diet (HFD, n=6), western diet (WD, n=7), and high-fat-high-fructose diet (HFHFD, n=7). Stools were cultured on Eosin Methylene Blue (EMB) for Escherichia coli and Forget Fredette Agar (FFA) for Clostridium spp. Colonies were counted using Total Plate Count (TPC), and butyrate levels were measured with gas chromatography. Liver histology was assessed with the NAFLD activity score (NAS). Gut microbiota were analyzed using Crosstab and Chi-Square tests, and butyrate levels with the Kruskal-Wallis test. Butyrate levels decreased in NAFLD-inducing diet groups (HFD, WD, HFHFD) compared to ND (p=0.021). Escherichia coli colony counts were significantly higher in NAFLD-inducing diet groups (p=0.048), while Clostridium spp. counts were higher in ND (p=0.001). Liver histological changes, particularly in the WD group, resembled NAFLD. These findings imply that different high-fat diets can alter the gut microbiome, potentially influencing NAFLD development.

Histological liver, kidney, and brain changes induced by pregabalin drug in albino rats

Histological liver, kidney, and brain changes induced by pregabalin drug in albino rats

Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase.

Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B (CHB) patients were not previously conducted. To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy. The clinical and laboratory data of 1532 untreated CHB patients were collected, and all patients had least once liver biopsy from January 2015 to December 2021. The significant differences among different phases of CHB infection were compared with t-test, and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis. Among 1532 untreated CHB patients, 814 (53.13%) patients were in the indeterminate phase. Significant liver histological changes (defined as biopsy score ≥ G2 and/or ≥ S2) were found in 488/814 (59.95%) CHB patients in the indeterminate phase. Significant liver histological changes were significant differences among different age, platelets (PLTs), and alanine aminotransferase (ALT) subgroup in indeterminate patient. Multivariate logistic regression analysis indicated that age ≥ 40 years old [adjust odd risk (aOR), 1.44; 95% confidence interval (CI): 1.06-1.97; P = 0.02], PLTs ≤ 150 × 109/L (aOR, 2.99; 95%CI: 1.85-4.83; P < 0.0001), and ALT ≥ upper limits of normal (aOR, 1.48; 95%CI: 1.08, 2.05, P = 0.0163) were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase. Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase, and additional strategies are urgently required for the management of these patients.

Dapagliflozin dampens liver fibrosis induced by common bile duct ligation in rats associated with the augmentation of the hepatic Sirt1/AMPK/PGC1α/FoxO1 axis

Liver fibrosis is considered an epidemic health problem due to different insults that lead to death. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, is one of the newer anti-diabetic drugs used to manage type 2 diabetes mellitus (T2DM). DAPA exerted beneficial effects in many human and rat models due to its antioxidant, anti-inflammatory and antifibrotic activities. AimDue to previously reported capabilities related to DAPA, we designed this study to clarify the beneficial role of DAPA in liver fibrosis triggered by common bile duct ligation (CBL) in male rats. MethodsFor 14 or 28 days after CBL procedures, DAPA was administered to the rats orally at a dose of 10 mg/kg once daily. The effects of DAPA were evaluated by assaying liver enzymes, hepatic oxidant/antioxidant parameters, serum levels of tumor necrotic factor alpha (TNF-α), and AMP-activated protein kinase (AMPK). In addition, we measured the hepatic expression of fibrosis regulator-related genes along with evaluating liver histological changes. Key findingsDAPA successfully decreased hepatic enzymes and malondialdehyde levels, increased superoxide dismutase activity, elevated catalase levels, decreased serum levels of TNF-α, elevated serum levels of AMPK, decreased liver hydroxyproline content, upregulated Sirt1/PGC1α/FoxO1 liver gene expressions, down-regulated fibronectin-1 (Fn-1), collagen-1 genes in liver tissues, and improved the damaged liver tissues. Deteriorated biochemical parameters and histological liver insults associated with CBL were more pronounced after 28 days, but DAPA administration for 14 and 28 days showed significant improvement in most parameters and reflected positively in the histological structures of the liver. SignificanceThe significance of this study lies in the observation that DAPA mitigated CBL-induced liver fibrosis in rats, most likely due to its antioxidant, anti-inflammatory, and antifibrotic effects. These results suggest that DAPA's beneficial impact on liver fibrosis might be attributed to its interaction with the Sirt1/AMPK/PGC1α/FoxO1 pathway, indicating a potential mechanistic action for future exploration.

Exercise improves surrogate measures of liver histological response in metabolic dysfunction-associated steatotic liver disease.

Exercise is recommended for the management of metabolic dysfunction-associated steatotic liver disease (MASLD), yet effects on liver histology remain unknown, especially without significant weight loss. We aimed to examine changes in surrogate measures of liver histological response with exercise training. We conducted a post hoc pooled analysis of three randomised controlled trials (duration: 12-20 weeks) comparing aerobic exercise interventions with controls. The primary outcome measure was a ≥30% relative reduction in (MRI-measured) liver fat, as a surrogate measure of liver histological response (the threshold necessary for fibrosis improvement). Secondary outcome measures were changes in other biomarkers of liver fibrosis, anthropometry, body composition and aerobic fitness. Eighty-eight adults (exercise: 54, control: 34; male: 67%) were included with mean (SD) age 51 (11) years and body mass index 33.3 (5.2) kg/m2. Following the intervention, exercise had ~5-fold (OR [95%CI]: 4.86 [1.72, 13.8], p = .002) greater odds of ≥30% relative reduction in MRI-measured liver fat compared with control. This paralleled the improvements in anthropometry (waist and hip circumference reduction), body composition (body fat, visceral and subcutaneous adipose tissue) and aerobic fitness (V̇O2peak, ventilatory threshold and exercise capacity). Importantly, these effects were independent of clinically significant body weight loss (<3% body weight). Exercise training led to clinically meaningful improvements in surrogate serum- and imaging-based measures of liver histological change, without clinically meaningful body weight reduction. These data reinforce the weight-neutral benefit of exercise training and suggest that aerobic training may improve liver fibrosis in patients with MASLD.

Exploring the therapeutic potential of plasma from intermittent fasting and untreated rats on aging-induced liver damage.

This research aims to investigate the effects of plasma from 12-month-old intermittently fasting rats (IFpls) and untreated rats (Npls) on the liver biomolecules and histological changes in 24-month-old male Sprague-Dawley rats. Fasting rats underwent an 18-h daily fasting period and a 6-h feeding window for 35 days. The plasma was administered bi-daily, and blood samples were examined for specific liver biomolecules. Fourier transform infrared (FTIR) spectroscopy and linear discriminant analysis (LDA) was used to identify molecular profiles. Liver sections were stained for histopathological evaluation, and the expression levels of Notch signalling pathway components were assessed. Distinct molecular profiles were identified across liver biomolecules, lipids, proteins and nucleic acids with high accuracy. Notably, IFpls was found to protect against hepatic instability, microvesicular steatosis and liver fibrosis by decreasing lymphatic infiltration density and Notch pathway expression levels. Both treatments reduced protein oxidation and carbonylation, with Npls showing a pronounced decrease in protein oxidation. Furthermore, Npls increased protein conformation and glycogen/phosphate content, while IFpls increased glucose/protein content. Both IFpls and Npls induce substantial and unique alterations in liver biomolecules. IFpls offers a protective effect on various liver conditions, while Npls exhibits promising results in reducing protein oxidation and altering biomolecule content. These findings offer valuable insights for future research and potential therapeutic approaches.

Hypoglyceamic and Hepatoprotective Potentials of Dichloromethane (DCM) Fraction of Gongronema Latifolium Extract in Streptozotocin-Induced Diabetic Wistar Rats

Diabetes is a chronic health issue with devastating but preventable consequences. The increasing proportion of the aging population, intake of calorie-dense diets, weight problems and sedentary lifestyles have been directly implicated in the increased number of diabetics globally. Furthermore, diabetes confers a huge economic burden due to its management costs, especially in low income countries. This study investigated the hypoglyceamic and hepatoprotective potentials of the dichloromethane (DCM) fraction of G. latifolium stem bark extract on some biochemical parameters in streptozotocin-induced hyperglycemic rats. A total of thirty (30) Wistar rats were randomly assigned into five (5) groups with six (06) animals per group. Type 2 diabetes was induced with intraperitoneal administration of streptozotocin in Groups 2 – 4, with animals in Groups 1 and 2 acting as normal and untreated diabetic controls, respectively. Group 3 rats were treated with the standard drug, metformin, while groups 4 and 5 were orally administered 200 and 400 mg/kg body weight of DCM fraction of G. latifolium stem bark extract. Changes in the body weight, biochemical assays (ALT, AST, total protein, albumin and urea), and expression levels of selected genetic markers, as well as the changes in liver histology, were determined and compared. Data obtained from this study show that the fasting blood glucose levels in hyperglycemic rats were significantly (p &lt; 0.05) reduced, and the body weight steadily increased in rats treated with both doses of the DCM fraction of G. latifolium stem bark extract compared to the untreated diabetic rats. Total protein, AST and ALT levels, but not albumin levels, were significantly (p &lt; 0.05) increased in rats treated with both doses of the extract. In addition, administration of the extracts significantly (p &lt; 0.05) reversed the streptozotocin-induced repression of NRF2 and CAT expression in diabetic rats. Furthermore, histology results show an improvement in the liver architecture in the rats treated with the extract. The results from this study show that the DCM fraction of g. Latifolium stem bark extract possesses hypoglycemic, hepatoprotective and anti-diabetic activities and could be used in the management of diabetes.

Screening impacts of Tilmicosin-induced hepatic and renal toxicity in rats: protection by Rhodiola rosea extract through the involvement of oxidative stress, antioxidants, and inflammatory cytokines biomarkers.

Tilmicosin (TIL) is a semisynthetic macrolide antibiotic with a broad spectrum of activity derived from tylosin. TIL is effective in the treatment of bovine and ovine respiratory diseases caused by different microbes. In parallel, Rhodiola rosea (RHO) is a popular herbal remedy because of its anti-inflammatory and antioxidant qualities. The experiment lasted for 12days. Depending on the experimental group, the animals received either distilled water or RHO root extract dissolved in distilled water for 12days through a stomach tube, and the single subcutaneous injection on day 6 of the experiment of either 500 μL of 0.9% NaCl or TIL dissolved in 500 μL 0.9% NaCl. Samples and blood were collected for serum analysis, gene expression, and immunohistochemistry screening at liver and kidney levels. TIL injection increased serum levels of hepatic and renal markers (ALP, ALT, AST, TC, TG, creatinine, and urea) with decreased total proteins. In parallel, TIL induced hepatic and renal oxidative stress as there was an increase in malondialdehyde levels, with a decrease in catalase and reduced glutathione activities. Of interest, pre-administration of RHO inhibited TIL-induced increase in hepato-renal markers, decreased oxidative stress, and increased liver and kidney antioxidant activities. Quantitative RT-PCR showed that TIL increased the liver's HSP70 (heat shock protein), NFkB, and TNF-α mRNA expression. Moreover, TIL upregulated the expression of desmin, nestin, and vimentin expression in the kidney. The upregulated genes were decreased significantly in the protective group that received RHO. Serum inflammatory cytokines and genes of inflammatory markers were affected in liver tissues (HSP70, NFkB, and TNF-α) and kidney tissues (desmin, nestin, and vimentin)-TIL-induced hepatic vacuolation and congestion together with glomerular atrophy. The immunoreactivity of PCNA and HMGB1 was examined immunohistochemically. At cellular levels, PCNA was decreased while HMGB1 immunoreactivity was increased in TIL-injected rats, which was improved by pre-administration of RHO. RHO administration protected the altered changes in liver and renal histology. Current findings support the possible use of RHO to shield the liver and kidney from the negative effects of tilmicosin.

New progress on diagnosis and treatment for indeterminate-phase chronic hepatitis B virus-infected patients

Authoritative guidelines at home and abroad typically classify chronic hepatitis B virus (HBV) infection into four stages. However, in clinical practice, a considerable number of patients do not meet the guidelines for staging and are called "indeterminate phase" chronic HBV- infected patients. Studies have shown that patients in the indeterminate phase account for about 30%-50% of chronic HBV infection, have significant liver histological changes or even cirrhosis in a large proportion, and are at a higher risk of HCC and death if they do not receive antiviral therapy. Preliminary research shows that patients in the indeterminate phase who receive antiviral treatment have a good virological response and a remarkable reduced HCC risk. To this end, the 2022 publication "Expert Opinions on Expanding Antiviral Treatment for Chronic Hepatitis B" recommends aggressive treatment for patients with an indeterminate phase who have undergone more than a year of follow-up. However, there is still a lack of unified standards to refine the classification, as well as a lack of effective and rapid non-invasive diagnostic methods to identify patients in the indeterminate phase who are at risk for disease progression. This article aims to review the researches on the proportion, clinical characteristics, disease progression, and treatment benefits to further explore how to better manage indeterminate-phase chronic HBV-infected patients.