Search Results (54)

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become a worldwide health concern. Soy protein isolate (SPI) is a plant-derived protein with high nutritional value and has shown promising effects in regulating lipid metabolism and inflammation. Objectives: This study aimed to investigate the effects of an α-subunit-deficient SPI (α-lack-SPI) on MASLD and the underlying molecular mechanisms. Methods: Rats were fed with a high-fat, high-cholesterol diet (HFD) to induce MASLD. Results: The results showed that α-lack-SPI significantly reduced the levels of hepatic TG and TC, serum ALT, AST, TC, and LDL-C, and increased serum HDL-C in rats with HFD-induced MASLD. α-lack-SPI significantly attenuated hepatic steatosis and hepatocyte ballooning revealed by histopathological analysis. Meanwhile, α-lack-SPI markedly downregulated the mRNA expressions of Srebf1, Acaca, Fasn, Pcsk9, and Hmgcr, while significantly upregulating Pparα. Additionally, α-lack-SPI treatment significantly reduced the mRNA expressions of hepatic pro-inflammatory cytokines (Tnf-α, Il-1β, Il6), chemokine (Ccl2), and inflammasome component (Nlrp3), as well as the protein expression of COX-2. Conclusions: In conclusion, α-lack-SPI alleviated MASLD in HFD-fed rats probably via improving hepatic lipid metabolism and mitigating hepatic inflammation. These findings indicate that α-lack-SPI may serve as a promising nutritional intervention for MASLD management. Full article

Kupffer cells (KCs) play a pivotal role in the progression of metabolic-associated steatohepatitis (MASH). This study evaluated the impact of short-term KC depletion induced by gadolinium chloride (GdCl₃) in a rat model of MASH. The intervention with GdCl₃ effectively reduced KC markers CD68 and Clec4f, together with pro-inflammatory cytokines (IL-1β, TNFα, NOS2), without affecting anti-inflammatory markers (IL-10, MRC1). Histologically, GdCl₃ reduced hepatocyte ballooning and NAS despite persistent steatosis. KC depletion was associated with decreased oxidative stress markers (TBARS, 3-nitrotyrosine) and antioxidant enzyme activity (SOD, catalase). Additionally, markers of endoplasmic reticulum stress (ATF4, GRP78, CHOP, P58^IPK) and apoptosis (BAX/BCL2 ratio, cleaved caspase-3) were diminished. Despite these improvements, GdCl₃ had no effect on lipid or glucose metabolism in the liver, associated with persistent elevation of PTP1B expression induced by SRD intake. KC depletion, however, increased FGF21 expression. GdCl₃ treatment improved systemic insulin sensitivity and reduced fasting glucose and NEFA serum levels. In white adipose tissue, the treatment decreased adipocyte size, restored insulin signaling, and inhibited lipolysis (ATGL expression) without altering macrophage infiltration (IBA) or thermogenic protein levels (UCP1) in SRD rats. These findings suggest that KC depletion modulates liver-to-adipose tissue crosstalk, potentially through FGF21 signaling, contributing to improved systemic metabolic homeostasis of SRD animals. Full article

Background: Early-life stress and dietary habits are key determinants of metabolic health. This study investigates the combined effects of maternal separation (MS) and a post-weaning high-fat diet (HFD) on liver morphology in male C57BL/6 mice. Methods: Male mice were subjected to MS during early postnatal life or kept unmanipulated (UM). After weaning, animals were assigned to either a control diet (CD) or an HFD, forming four groups: UM-CD, UM-HFD, MS-CD, and MS-HFD. Liver histology, collagen deposition, and both morphometric and stereological parameters were assessed following 16 weeks of dietary intervention. Results: MS and HFD independently altered liver structure, while the combination of both factors intensified these changes. The MS-HFD group exhibited pronounced steatosis, mixed inflammatory infiltrates, and hepatocellular ballooning, with a significantly higher NAFLD Activity Score (NAS). No significant differences were observed in liver fibrosis. Morphometric analysis revealed increased body mass in HFD-fed groups and elevated liver mass in MS-HFD. Liver volume was higher in MS-HFD, though not significantly. Liver stereology revealed reduced numerical density of hepatocytes (Nv_hep) and increased surface density (Sv_hep) in MS groups, with the most pronounced effects in MS-HFD. Conclusions: Maternal separation amplifies the hepatic alterations induced by HFD, promoting early inflammatory and steatotic changes. These findings highlight the significance of early-life stress as a factor increasing susceptibility to diet-induced liver damage. Full article

Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) lacks effective therapies. This study aimed to evaluate the therapeutic potential of compound 3d, a novel elafibranor derivative, focusing on its dual mechanisms of PPAR pathway activation and p38 MAPK signaling inhibition. Methods: Integrated in vitro and in vivo approaches were employed. In vitro, free fatty acid (FFA)-induced lipid accumulation in L02 hepatocytes and lipopolysaccharides (LPSs)-stimulated inflammatory responses in RAW264.7 macrophages were used to evaluate lipid metabolism and anti-inflammatory effects. In vivo, a high-fat diet (HFD)-induced MASH model in C57BL/6 mice assessed serum biochemical parameters (triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor-α (TNF-α), nitric oxide (NO), and interleukin-6 (IL-6)), liver histopathology (H&E, Oil Red O, Masson staining), and proteomic profiling. Gut microbiota composition was analyzed via 16S rRNA sequencing. Western blotting quantified PPAR isoforms (γ/δ), downstream targets (Acox1, EHHADH, Acaa1), and p38 MAPK pathway proteins (p-p38, caspase-8, Bcl-2). Results: In vitro, 3d significantly reduced lipid accumulation (reduction in TG, p < 0.01) and inflammation (decrease in ALT activity, p < 0.05) in hepatocytes, while suppressing LPSs-induced TNF-α (63% reduction), NO (51% decrease), and IL-6 (48% reduction) in macrophages (p < 0.01). In vivo, 3d (30 mg/kg) lowered serum TG (39% decrease), TC (32% reduction), LDL-C (45% decline), and TNF-α (57% reduction) in HFD-fed mice (p < 0.05 vs. model), normalized AST/ALT levels, and ameliorated hepatic steatosis, ballooning, and fibrosis. Proteomics demonstrated PPARγ/δ activation (2.3–3.1-fold upregulation of Acox1, EHHADH, Acaa1; p < 0.001) and p38 MAPK pathway inhibition (54% reduction in p-p38, 61% decrease in caspase-8; 1.8-fold increase in Bcl-2; p < 0.01). Gut microbiota analysis revealed enrichment of beneficial taxa (Lactobacillus: 2.7-fold increase; Bifidobacterium: 1.9-fold rise) and reduced pathogenic Proteobacteria (68% decrease, p < 0.05). Conclusions: Compound 3d alleviates MASH via PPAR-mediated lipid metabolism enhancement and p38 MAPK-driven inflammation/apoptosis suppression, with additional gut microbiota modulation. These findings highlight 3d as a multi-target therapeutic candidate for MASH. Full article

Polygonatum sibiricum polysaccharides (PSPs), plant-derived polysaccharides widely used in the pharmaceutical field, exhibit various biological activities, including anti-inflammatory and antioxidant effects. However, research on their application in chicks remains limited. Therefore, the aim of this study is to investigate the protective mechanism of PSP against liver injury in chicks using an LPS-induced inflammatory model. A total of 200 one-day-old Hy-Line Brown laying chicks were randomly assigned to five groups (40 chicks each): a control group (CON) fed a basal diet, an LPS group, and three PSP groups receiving low (250 mg/L), medium (500 mg/L), and high (1000 mg/L) doses of PSP (PSP250_LPS, PSP500_LPS, and PSP1000_LPS, respectively). The experiment lasted 21 days. During this period, the LPS and PSP groups were intraperitoneally injected with 1500 μg/kg LPS on days 14, 16, 18, and 20, while the CON group received normal saline. On day 21, organs were collected for analysis. The results indicated that PSP treatment significantly reduced the liver and kidney indices that were elevated by LPS (p < 0.05) without affecting the indices of the spleen, thymus, or bursa of Fabricius (p > 0.05). Histological analysis revealed that PSP alleviated LPS-induced ballooning degeneration and cell swelling in hepatocytes. Furthermore, PSP treatment decreased the levels of ALT and AST and significantly mitigated increases in the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α while enhancing the level of the anti-inflammatory cytokine IL-10 (p < 0.05). Transcriptome sequencing of liver samples revealed that LPS significantly altered the expression of 10 genes in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which were regulated by PSP intervention. qPCR validation supported these findings. Furthermore, biochemical analyses of liver tissue showed that PSP alleviated oxidative stress by affecting levels of SOD, MDA, NADPH, ROS, and H₂O₂. In conclusion, PSP may alleviate LPS-induced liver injury in chicks by modulating the PPAR signaling pathway. These findings provide valuable insights for promoting healthy chick rearing and ensuring the safe supply of poultry products. Full article

Emerging evidence indicates a close relationship between gut microbiota and fatty liver disease. It has been suggested that gut microbiota modulation with probiotics ameliorates fatty liver disease in rodents and humans, yet it remains unclear whether the same results will also be obtained in poultry. The aim of this study was to investigate whether a mixture of probiotics supplemented after hatching can prevent CORT-induced fatty liver disease in broilers, and to determine how such effects, if any, are associated with hepatic de novo lipogenesis and gut microbiota composition. Ninety-six one-day-old green-legged chickens were divided into a control group (CON) and probiotic group (PB). At 28 days of age, fatty liver was induced in 16 broilers that were randomly selected from the CON or PB group. At the end of the experiment, broilers from four groups, (i) the control group (CON), (ii) corticosterone group (CORT), (iii) probiotic group (PB), and (iv) PB plus CORT group (CORT&PB), were slaughtered for sampling and analysis. The results showed that probiotic administration significantly prevented CORT-induced body weight loss (p < 0.05) but did not alleviate the weight loss of immune organs caused by CORT. Compared to CON, the broilers in the CORT group exhibited a significant increase in triglyceride (TG) levels in plasma and liver (p < 0.01), as well as severe hepatocytic steatosis and hepatocellular ballooning, which was accompanied by the upregulation of hepatic lipogenesis gene expression. However, probiotic supplementation markedly decreased the intrahepatic lipid accumulation and steatosis histological score, which was associated with the downregulation of sterol regulatory element-binding protein-1 (SREBP1) and acetyl-CoA carboxylase (ACC) mRNA (p < 0.05) and the expression of its protein (p = 0.06). The cecal microbiota composition was determined by 16S rRNA high-throughput sequencing. The results showed that CORT treatment induced distinct gut microbiota alterations with a decrease in microbial diversity and an increase in Proteobacteria abundance (p < 0.05). In contrast, probiotic supplementation increased the beta diversity, the community richness, and the diversity index (p > 0.05), as well as the abundance of Intestinimonas (p < 0.05). Our results indicate that CORT treatment induced severe fatty liver disease and altered the gut microbiota composition in broilers. However, post-hatching probiotic supplementation had a beneficial effect on alleviating fatty liver disease by regulating lipogenic gene expression and increasing gut microbiota diversity and the abundance of beneficial bacteria. We demonstrate for the first time that the supplementation of probiotics to chicks had a beneficial effect on preventing fatty liver disease through regulating lipogenic gene expression and improving the gut microbial balance. Thus, our results indicate that probiotics are a potential nutritional agent for preventing fatty liver disease in chickens. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of hepatocellular carcinoma and end-stage liver transplantation. Characterized by hepatic steatosis, lobular inflammation, and hepatocyte ballooning, there is a dire need to develop therapeutic strategies to mitigate MASH alongside the subsequent fibrosis and cirrhosis. For years, therapeutic development for the treatment of MASH had been considered a graveyard, with various pharmacotherapies failing to achieve clinical efficacy. However, the recent Food and Drug Administration (FDA) approval of Madrigal Pharmaceuticals’ Resmetirom in the United States provides a positive step in the collective effort to eradicate MASH. Granted, with much about Resmetirom’s long-term efficacy and safety still to be determined and with the multi-factorial nature of MASH pathogenesis, continuing to evaluate alternative therapeutic options remains in the best interest of the field. Currently, therapeutics previously approved for other ailments, alongside novel therapeutics developed specifically for the treatment of MASH, are being evaluated in late-phase clinical trials. However, considering the complex nature of the disease and varying clinical outcomes to assess treatment efficacy, achieving regulatory approval as a MASH therapeutic continues to be a rigorous endeavor. In this review, we summarize notable therapeutics of various mechanistic backgrounds having achieved, or actively undergoing, late-phase clinical trials for the treatment of MASH and offer our perspectives on anti-MASH therapeutic development. Full article

Alcohol-associated liver disease (ALD) is a common non-communicable chronic liver disease characterized by a spectrum of conditions ranging from steatosis and alcohol-associated steatohepatitis (AH) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of ALD involves a complex interplay of various molecular, biochemical, genetic, epigenetic, and environmental factors. While the mechanisms are well studied, therapeutic options remain limited. Alpinetin, a natural flavonoid with antioxidant and anti-inflammatory properties, has shown potential hepatoprotective effects, though its efficacy in ALD remains unexplored. This study investigated the hepatoprotective effects of alpinetin using a Lieber–DeCarli ethanol liquid diet model of ALD in C57BL/6 mice. Mice were divided into three groups: the control group, the ethanol group, and the ethanol group treated with alpinetin. Serum activity of ALT, AST, γ-GT, and ALP was measured to assess liver function, along with antioxidative and oxidative/nitrosative stress markers in liver tissue. Pro-inflammatory cytokines and endoplasmic reticulum (ER) stress parameters in liver tissue were also evaluated. Histological assessment of disease activity was performed using the SALVE grading and staging system. Treatment with alpinetin significantly reduced serum levels of ALT, AST, γ-GT, and oxidative/nitrosative stress markers while increasing antioxidative markers. The levels of pro-inflammatory cytokines and ER stress parameters were significantly decreased. Histological analysis demonstrated reduced steatosis, hepatocyte ballooning, and inflammation. These findings suggest that alpinetin holds promise as a potential therapeutic agent for managing ALD. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic lipid accumulation, and echinacoside (ECH) has demonstrated antioxidant and anti-inflammatory effects across multiple conditions, it has demonstrated hepatoprotective effects. Ferroptosis represents a novel mechanism of cell demise, differing from apoptosis and autophagy. Emerging research indicates that ferroptosis in hepatocytes plays a role in the development of alcoholic liver disease. This study aimed to reveal the effect and potential mechanism of ECH on MASLD. Methods: The effect of ECH on the viability, lipid deposition, lipid peroxidation, mitochondrial of OA/PA-treated HepG2 cells were evaluated by Cell Counting Kit-8 assay, JC-1 and immunofluorescence assay. Meanwhile, the mechanism of ECH was assessed using transmission electron microscopy and immunofluorescence analysis. Moreover, db/db mice, a spontaneous type 2 diabetes mode, were intragastrically administered ECH by 300 mg/kg or an equivalent volume of saline. Body weight, lipids, and liver function were measured. liver pathology was performed. The mechanism of ECH in vivo was analyzed using Western blot and immunofluorescence analysis in db/db mice. Results: ECH attenuated lipid deposition, lipid peroxidation and ferroptosis induced by OA/PA in HepG2 cells. Mitochondrial morphology and function in HepG2 cells were also preserved by ECH. In db/db mice model of MASLD, ECH markedly ameliorated liver hepatocellular ballooning, inflammatory cell infiltration in the portal area, and fibrous tissue proliferation. ECH also increased the expression of Nrf2, HMOX-1, SLC7A11, and GPX4, and decreased the expression of ACSL4 in liver tissues. Mechanically, ECH repressed ferroptosis by activating the Nrf2/HO-1 signaling pathway. Conclusions: Our research revealed that ECH has the capability to modulate ferroptosis via the Nrf2-HMOX1pathway, consequently mitigating the progression of MASLD. This suggests that ECH has a potential role in the treatment of MASLD. Full article

The aim of this study was to explain the mechanism underlying the liver injury of juvenile largemouth bass Micropterus salmoides in response to high-starch diet intake. Three diets were formulated with different starch levels, being abbreviated as treatment LS (low starch, 8.13% starch), MS (medium starch, 14.1% starch), and HS (high starch, 20.1% starch), respectively. Fish were fed with their respective diets to apparent satiation for 56 days. The results showed that growth retardation of the HS fish was associated with the reduction in feed intake rather than feed utilization. Histological evaluation of the livers showed that vacuolization was the most prevalent characteristic in the MS fish, while ballooning degeneration, apoptosis, fibrosis, and inflammation were observed in the HS fish. Transcriptome profiling suggested that liver inflammation was mediated by Tlr signal transduction, which activated the Pi3k/Akt/Nfκb signaling axis to promote the release of proinflammatory factors including Il-8 and Ip-10. Hepatocyte apoptosis was mediated by the extrinsic pathway through death receptors including Fas and Tnfr, which coordinately activated the Fadd/caspase-8 death signaling axis. An autonomous inhibition program was identified to counteract the apoptosis signal, and the PI3K/Akt signaling pathway might play an important role in this process through regulating the expression of iap and diablo. Liver fibrosis was mediated through the Tgf-β and Hh signaling pathways. Upon secretion, Tgf-β1/3 bound to TgfβrI/II complex on the liver cell membrane, which induced the phosphorylation of downstream Smad2/3. When Hh interacted with the membrane receptor Ptc, Smo was activated to initiate signaling, driving the activation of Gli. The activation of both Smad2/3 and Gli promoted their nuclear translocation thereby regulating the transcription of target genes, which resulted in the activation and proliferation of HSCs. The activated HSCs constantly expressed colla1 and ctgf, which facilitated substantial accumulation of ECM. It should be noted that the molecular mechanism of liver injury in this study was speculated from the transcriptome data thus further experimental verification is warranted for this speculation. Full article

Background: Hepatocyte ballooning (HB) is a significant histological characteristic linked to the advancement of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Although clinicians now consider liver biopsy the most reliable method for identifying HB, its invasive nature and related dangers highlight the need for the development of non-invasive diagnostic options. Objective: This study aims to develop a novel methodology that combines deep learning and machine learning techniques to accurately identify and measure hepatobiliary abnormalities in liver ultrasound images. Methods: The research team expanded the dataset, consisting of ultrasound images, and used it for training deep convolutional neural networks (CNNs) such as InceptionV3, ResNet50, DenseNet121, and EfficientNetB0. A hybrid approach, combining InceptionV3 for feature extraction with a Random Forest classifier, emerged as the most accurate and stable method. An approach of dual dichotomy classification was used to categorize images into two stages: healthy vs. sick, and then mild versus severe ballooning.. Features obtained from CNNs were integrated with conventional machine learning classifiers like Random Forest and Support Vector Machines (SVM). Results: The hybrid approach achieved an accuracy of 97.40%, an area under the curve (AUC) of 0.99, and a sensitivity of 99% for the ‘Many’ class during the third phase of evaluation. The dual dichotomy classification enhanced the sensitivity in identifying severe instances of HB. The cross-validation process confirmed the strength and reliability of the suggested models. Conclusions: These results indicate that this combination method can decrease the need for invasive liver biopsies by providing a non-invasive and precise alternative for early identification and monitoring of NAFLD and NASH. Subsequent research will prioritize the validation of these models using larger datasets from multiple centers to evaluate their generalizability and incorporation into clinical practice. Full article

Metabolic dysfunction-associated Steatohepatitis (MASH), is a prominent cause for liver cirrhosis. MASH-cirrhosis is responsible for liver complications and there is no specific treatment. To develop new therapeutic approaches, animal models are needed. The aim of this study was to develop a fast animal model of MASH-cirrhosis in rats reflecting the human disease. Carbon tetrachloride (CCl₄) injections in combination with a high-fat Western diet (WD) were used to induce MASH-cirrhosis. To accelerate liver injury, animals received phenobarbital (PB) in their drinking water using two different regimens. Rats developed advanced MASH-cirrhosis characterized by portal hypertension, blood biochemistry, hepatic ballooning, steatosis, inflammation and fibrosis. Importantly, rats receiving low-dose PB for the long term (LT) showed ascites after 6 weeks, whereas rats with high-dose short-term (ST) PB developed ascites after 8 weeks. ST- and LT-treated rats showed increased portal pressure (PP) and decreased mean arterial pressure (MAP). Of note, hepatocyte ballooning was only observed in the LT group. The LT administration of low-dose PB with CCl₄ intoxication and WD represents a fast and reproducible rat model mimicking decompensated MASH-cirrhosis in humans. Thus, CCl₄ + WD with LT low-dose phenobarbital treatment might be the preferred rat animal model for drug development in MASH-cirrhosis. Full article

This study aimed to investigate the immunogenicity of the hepatitis B virus (HBV) vaccine by applying a normal and high-dose hepatitis B virus vaccination program in the mice modeling of non-alcoholic fatty liver disease (NAFLD). NAFLD was induced in mouse livers via diet. At the 10-week mark, both groups were divided into 3 subgroups. While the standard dose vaccination program was applied on days 0, 7, and 21, two high-dose programs were applied: one was applied on days 0 and 7, and the other was applied on days 0, 7, and 21. All mice were euthanized. Blood samples from anti-HB titers; T follicular helper, T follicular regulatory, CD27⁺, and CD38⁺ cells; and the liver, spleen, and thymus were taken for histopathologic evaluation. NAFLD subgroups receiving high doses showed higher hepatocyte ballooning scores than normal-dose subgroup. There were differences in CD27⁺ and CD27⁺CD38⁺ cells in animals fed on different diets, without any differences or interactions in terms of vaccine protocols. In the NAFLD group, a negative correlation was observed between anti-HB titers and T helper and CD27⁺ cells, while a positive correlation was observed with CD38⁺ cells. NAFLD induced changes in immune parameters in mice, but there was no difference in vaccine efficacy among the applied vaccine protocols. Based on this study’s results, high-dose vaccination protocols are not recommended in cases of NAFLD, as they do not enhance efficacy and may lead to increased liver damage. Full article

As gut dysbiosis has been implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH), probiotic supplementation might be a potential treatment for this condition. The aim of this study was to evaluate the effects of single- and mixed-strain probiotics on the severity of NASH induced by a high-fat, high-fructose (HFHF) diet and their mechanisms of action. Male Sprague–Dawley rats were divided into four groups (n = 7 per group): control group, NASH group, NASH + single-strain group, and NASH + mixed-strain group. In the single-strain and mixed-strain groups, rats received Lactobacillus plantarum B7 and Lactobacillus rhamnosus L34 + Lactobacillus paracasei B13 by oral gavage once daily, respectively. The duration of the study was 6 weeks. Liver tissue was used for histopathology, hepatic fat content was assessed by Oil Red O staining and hepatic free fatty acid (FFA), and hepatic TLR4 and CD14 expression were assessed by immunohistochemistry. Fresh feces was collected for gut microbiota analysis. Liver histology revealed a higher degree of fat accumulation, hepatocyte ballooning, and lobular inflammation in the NASH group, which improved in probiotics-treated groups. The amounts of hepatic fat droplets and hepatic FFA levels were more pronounced in the NASH group than in the control and treatment groups. Serum TNF- α levels were significantly higher in the NASH group than in control and probiotic groups. The expression of CD14 and TLR4 increased in the NASH group as compared with the control and probiotics-treated groups. Alpha diversity was reduced in the NASH group, but increased in both treatment groups. The relative abundance of Lactobacillus significantly decreased in the NASH group, but increased in both treatment groups. The relative abundance of Akkermansia significantly increased in the NASH group, but decreased in both treatment groups. In conclusion, both single-strain and mixed-strain probiotics could improve NASH histology by suppressing inflammatory responses in the liver, with this improvement potentially being associated with changes in the gut microbiota. Full article

Nonalcoholic fatty liver disease (NAFLD), or metabolic dysfunction-associated steatotic liver disease (MASLD), is a liver condition that is linked to overweight, obesity, diabetes mellitus, and metabolic syndrome. Nonalcoholic steatohepatitis (NASH), or metabolic dysfunction-associated steatohepatitis (MASH), is a form of NAFLD/MASLD that progresses over time. While steatosis is a prominent histological characteristic and recognizable grossly and microscopically, liver biopsies of individuals with NASH/MASH may exhibit several other abnormalities, such as mononuclear inflammation in the portal and lobular regions, hepatocellular damage characterized by ballooning and programmed cell death (apoptosis), misfolded hepatocytic protein inclusions (Mallory–Denk bodies, MDBs), megamitochondria as hyaline inclusions, and fibrosis. Ballooning hepatocellular damage remains the defining feature of NASH/MASH. The fibrosis pattern is characterized by the initial expression of perisinusoidal fibrosis (“chicken wire”) and fibrosis surrounding the central veins. Children may have an alternative form of progressive NAFLD/MASLD characterized by steatosis, inflammation, and fibrosis, mainly in Rappaport zone 1 of the liver acinus. To identify, synthesize, and analyze the scientific knowledge produced regarding the implications of using a score for evaluating NAFLD/MASLD in a comprehensive narrative review. The search for articles was conducted between 1 January 2000 and 31 December 2023, on the PubMed/MEDLINE, Scopus, Web of Science, and Cochrane databases. This search was complemented by a gray search, including internet browsers (e.g., Google) and textbooks. The following research question guided the study: “What are the basic data on using a score for evaluating NAFLD/MASLD?” All stages of the selection process were carried out by the single author. Of the 1783 articles found, 75 were included in the sample for analysis, which was implemented with an additional 25 articles from references and gray literature. The studies analyzed indicated the beneficial effects of scoring liver biopsies. Although similarity between alcoholic steatohepatitis (ASH) and NASH/MASH occurs, some patterns of hepatocellular damage seen in alcoholic disease of the liver do not happen in NASH/MASH, including cholestatic featuring steatohepatitis, alcoholic foamy degeneration, and sclerosing predominant hyaline necrosis. Generally, neutrophilic-rich cellular infiltrates, prominent hyaline inclusions and MDBs, cholestasis, and obvious pericellular sinusoidal fibrosis should favor the diagnosis of alcohol-induced hepatocellular injury over NASH/MASH. Multiple grading and staging methods are available for implementation in investigations and clinical trials, each possessing merits and drawbacks. The systems primarily used are the Brunt, the NASH CRN (NASH Clinical Research Network), and the SAF (steatosis, activity, and fibrosis) systems. Clinical investigations have utilized several approaches to link laboratory and demographic observations with histology findings with optimal platforms for clinical trials of rapidly commercialized drugs. It is promising that machine learning procedures (artificial intelligence) may be critical for developing new platforms to evaluate the benefits of current and future drug formulations. Full article