Non-alcoholic fatty liver disease among patients undergoing ultra-sonography abdomen and its associated factors in a tertiary care hospital, Kakinada

Background: Non-alcoholic fatty liver disease (NAFLD) presents a growing global health concern, characterized by the accumulation of hepatic lipids in the absence of significant alcohol consumption. Its prevalence has surged worldwide, including in India, where it has reached alarming levels. Despite its silent progression, NAFLD can lead to severe complications, including liver cirrhosis and hepatocellular carcinoma. Objectives of the study to assess prevalence and its associated factors, which are essential for effective management and prevention strategies. Methods: An observational, analytical cross-sectional study was conducted in a tertiary care hospital in Kakinada, Andhra Pradesh, from June to July 2022. Among 100 subjects, chosen through the simple random sampling. Ethical approval was granted before conducting study. Data on demographics, lifestyle risk factors, anthropometry, and ultrasound findings were collected using a pretested and validated case record form. Statistical analysis was carried out using SPSS software, employing appropriate tests to explore associations between NAFLD and various variables. Results: Among 100 participants, the prevalence of NAFLD was found to be 41%. Significant associations were observed between NAFLD and variables such as BMI (p=0.034), waist-hip ratio (p=0.002), and history of diabetes mellitus (p=0.000). Lifestyle factors, including increased cooking oil consumption, were identified as significant risk factors. Conclusions: The study highlights the high prevalence of NAFLD among subjects undergoing ultrasound abdomen in Kakinada. Significant associations were observed with BMI, waist-hip ratio, and diabetes mellitus history. Promoting healthy behaviours is crucial for NAFLD prevention and management.

Evaluación del desempeño de tres puntajes no invasivos para el diagnóstico de fibrosis avanzada en una población con hígado graso no alcohólico / Evaluation of the performance of three non-invasive scores for the diagnosis of advanced fibrosis in a population with non-alcoholic fatty liver disease

Introducción. La enfermedad hepática grasa no alcohólica (EHGNA) es la hepatopatía crónica más común en el mundo, y en aproximadamente el 10 % de los casos progresará a cirrosis o a carcinoma hepatocelular. La presencia de fibrosis hepática es el mejor predictor de esta progresión, pero su diagnóstico mediante biopsia hepática es invasivo y con riesgo de complicaciones (alrededor del 2,5 %). Existen puntajes no invasivos que se han desarrollado y validado para estadificar la fibrosis, pero no conocemos su rendimiento en la población colombiana. El objetivo de este estudio fue evaluar el desempeño de los puntajes fibrosis-4 (FIB-4), la relación AST/ALT y el índice AST/plaquetas (APRI) para la detección de fibrosis avanzada en pacientes colombianos con EHGNA. Metodología. Estudio observacional tipo transversal de pacientes con EHGNA, que entre 2008 y 2022 tuvieran disponible el resultado de una biopsia hepática. Se hizo una descripción demográfica básica y se calculó el FIB-4, la relación AST/ALT y el APRI con los laboratorios más recientes previos al procedimiento. Posteriormente se calcularon valores de sensibilidad, especificidad, valores predictivos, razones de verosimilitud y área bajo la curva-característica operativa del receptor (AUC-ROC) para los puntos de corte evaluados previamente en la literatura. Resultados. Se incluyeron 176 pacientes, de los cuales el 14,3 % tenían fibrosis avanzada. El FIB-4 presentó el mejor rendimiento con un valor AUC-ROC de 0,74 para el punto de corte de 1,30 y 2,67. En segundo lugar, estuvo la relación AST/ALT con un valor AUC-ROC de 0,68 con el punto de corte de 0,8, y finalmente el APRI con valor AUC-ROC 0,62 con el punto de corte de 1. Conclusión. En la población analizada los tres puntajes tienen menor rendimiento diagnóstico comparado a los resultados reportados en Europa y Japón. El FIB-4 es el único que alcanza una AUC-ROC con rendimiento razonable, con la limitación que 27,4 % obtuvieron un resultado indeterminado.

Introduction. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide, with approximately 10% of cases progressing to cirrhosis or hepatocellular carcinoma. Liver fibrosis presence is the best predictor of this progression, yet its diagnosis through liver biopsy is invasive and poses risk of complications. Although non-invasive scoring systems have been developed and validated for fibrosis staging, their performance remains unexplored in the Colombian population. This study aims to assess the efficacy of the fibrosis-4 (FIB-4) score, AST/ALT ratio, and AST to platelet ratio index (APRI) in detecting advanced fibrosis among Colombian NAFLD patients. Methods. This cross-sectional observational study included NAFLD patients with available liver biopsy results from 2008 to 2022. Basic demographic characteristics were described, and FIB-4, APRI, and AST/ALT ratio were calculated using the latest laboratory data before the procedure. Subsequently, sensitivity, specificity, predictive values, likelihood ratios, and the area under the receiver operating characteristic curve (AUC-ROC) were computed for previously assessed cutoff points. Results. A total of 176 patients were included, among whom 14.3% had advanced fibrosis. FIB-4 demonstrated superior performance with an AUC-ROC value of 0.74 for cutoff points of 1.30 and 2.67. Following was the AST/ALT ratio with an AUC-ROC value of 0.68 for cutoff point of 0.8, and finally, APRI with an AUC-ROC of 0.62 for the cutoff point of 1. Conclusion. All three scores have lower diagnostic efficacy compared to results reported in Europe and Japan. FIB-4 is the only one that achieves an acceptable AUC-ROC performance with the limitation that an indeterminate result was obtained in 27,4% of the sample.

COMMON HUB GENES AND DRUG CANDIDATES FOR DIABETIC KIDNEY DISEASE AND NON-ALCOHOLIC FATTY LIVER DISEASE: A COMPREHENSIVE BIOINFORMATIC STUDY

Diabetes mellitus (DM) is one of the most prevalent diseases responsible for worldwide morbidity and mortality. The kidney and liver are the most commonly affected organs resulting in diabetic kidney disease (DKD) and non-alcoholic fatty liver disease (NAFLD). However, pathophysiological mechanisms that may be common to both DKD and NAFLD have not been elaborated despite having a common underlying cause. This study aimed to identify the hub genes that are common to both DKD and NAFLD and explore the potential drugs for their treatment. Gene expression datasets for DKD and NAFLD from the gene expression omnibus database were analyzed to identify differentially expressed genes (DEGs). A functional enrichment analysis of the DEGs was done to reveal pathways important in the etiology of DKD and NAFLD. Protein-protein interaction (PPI) network was constructed and hub genes were identified. The hub genes were further analyzed to identify potentially viable drug candidates after screening. A total of 89 DEGs were found to be common between DKD and NAFLD. Functional enrichment of said DEGs found Ppar, FoxO signaling and hepatocellular carcinoma pathways to be most prevalent in DKD and NAFLD. From the PPI network, 32 common hub genes were identified. The hub genes were analyzed for interacting drugs. Finally, 9 drugs were identified as potential candidates for the treatment of both diseases. The hub genes identified can provide new insights into the common etiology of DKD and NAFLD. The potentially viable drugs may be repurposed for the treatment of both DKD and NAFLD.

Efecto del confinamiento por COVID-19 en la prevalencia de la enfermedad hepática esteatósica asociada a disfunción metabólica / Effect of COVID-19 lockdown on the prevalence of metabolic dysfunction-associated steatotic liver disease

Introducción. La enfermedad hepática esteatósica asociada a disfunción metabólica (MASLD) es una condición clínica frecuente, relacionada con el sobrepeso, la dislipidemia y la diabetes. Como estos factores de riesgo están a su vez asociados al sedentarismo y la ganancia de peso, se esperaría un impacto como resultado del confinamiento por COVID-19 en la prevalencia de dicha condición. Metodología. Estudio longitudinal retrospectivo en un panel de datos de 132 pacientes de 2017 a 2022, en donde fueron incluidos pacientes con una ecografía hepática y una valoración médica y paraclínica 1,5 años antes y después del periodo de confinamiento (25 de marzo de 2020 a 28 de febrero de 2021). El desenlace primario fue un cambio significativo en la prevalencia de la MASLD, y se utilizó un modelo exploratorio de regresión logística de efectos fijos con panel de datos para hallar los predictores de cambio. Resultados. En un total de 132 pacientes analizados, la prevalencia global de la MASLD antes (31 %; IC95%: 23-39) y después (35,6 %; IC95%: 27,4-43,8) del confinamiento por COVID-19 no cambió significativamente, sin embargo, en las mujeres sí hubo un aumento significativo (RR: 4; IC95%: 1,0004-16). Se encontró una marcada diferencia de prevalencia entre sexos (17 % en mujeres y 46 % en hombres; p=0,001). El confinamiento se asoció a incrementos en la masa corporal (diferencia: +1 kg; IC95%: 0,1-1,9), el colesterol LDL (diferencia: +9,7 mg/dL; IC95%: 4,9-14,4) y al diagnóstico de prediabetes (RR: 2,1; IC95%: 1,4-3,1). La MASLD se asoció positivamente a la preferencia nutricional por la comida rápida (p=0,047). Solo el índice de masa corporal resultó predictor independiente de MASLD (RR: 1,49; IC95%: 1,07-1,93). Conclusión. La prevalencia global de la MASLD no varió después del confinamiento por COVID-19, pero sí se incrementó en mujeres, y algunos de sus factores de riesgo también aumentaron significativamente. Se encontró equivalencia numérica entre la MASLD y la definición previa de la enfermedad. Se requiere un estudio local más grande para desarrollar y validar un mejor modelo predictor del cambio de la MASLD a través del tiempo.

Introduction. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common clinical condition, related to overweight, dyslipidemia and diabetes. As these risk factors are in turn associated with sedentary lifestyle and weight gain, an impact as a result of the COVID-19 confinement on the prevalence of MASLD would be expected. Methodology. Retrospective longitudinal study in a data panel of 132 patients from 2017 to 2022. Patients with a liver ultrasound and a medical and paraclinical assessment 1.5 years before and after the confinement period (March 25, 2020 to February 28, 2021) were included. The primary outcome was a significant change in the prevalence of MASLD, and an exploratory fixed-effects logistic regression model with panel data was used to find predictors of change. Results. In a total of 132 patients analyzed, the overall prevalence of MASLD before (31%, 95%CI: 23-39) and after (35.6%, 95%CI: 27.4-43.8) confinement by COVID-19 did not change significantly, however, in women there was a significant increase (RR: 4, 95%CI: 1.0004-16). A marked difference in prevalence was found between sexes (17% in women and 46% in men; p=0.001). Confinement was associated with increases in body mass (difference: +1 kg, 95%CI: 0.1-1.9), LDL cholesterol (difference: +9.7 mg/dL, 95%CI: 4.9-14.4) and the diagnosis of prediabetes (RR: 2.1, 95%CI: 1.4-3.1). MASLD was positively associated with nutritional preference for fast food (p=0.047). Only body mass index was an independent predictor of MASLD (RR: 1.49, 95%CI: 1.07-1.93). Conclusion. The overall prevalence of MASLD did not change after the COVID-19 lockdown, but it did increase in women, and some of its risk factors also increased significantly. Numerical equivalence was found between MASLD and the previous definition of the disease. A larger local study is required to develop and validate a better predictor model of MASLD change over time.

Mechanism of Astragaloside Ⅳ on db/db Mice with Type 2 Diabetes Mellitus and Non-alcoholic Fatty Liver Disease Based on AMPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the mechanism of astragaloside Ⅳ （AS Ⅳ） on db/db mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD） based on network pharmacology and experimental validation. MethodA total of 24 db/db mice were randomly divided into four groups： model group， metformin group， and low-dose and high-dose AS Ⅳ groups. Six C57 mice were used as the blank group. The low-dose and high-dose AS Ⅳ groups were given AS Ⅳ of 0.015 and 0.030 g·kg-1 by gavage， and the metformin group was given 0.067 g·kg-1 by gavage. The blank and model groups were given equal volumes of distilled water by gavage. After intragastric administration， fasting blood glucose （FBG） was detected， and an oral glucose tolerance test was performed. Serum lipid level and liver histopathology were detected. The target and enrichment pathway of AS Ⅳ for treating T2DM and NAFLD were predicted by network pharmacology， and the main enrichment pathway was verified by molecular biology techniques. The protein expressions of AMPK， p-AMPK， sterol regulatory element-binding protein-1 （SREBP-1）， and fatty acid synthetase （FAS） in liver tissue were detected by Western blot. ResultCompared with the blank group， the levels of body mass， liver weight coefficient， fasting blood glucose， serum total cholesterol， triglyceride， and low-density lipoprotein cholesterol in mice treated with AS Ⅳ were decreased （P<0.05， P<0.01）. The pathology of liver tissue showed significant improvement in lipid accumulation， and imaging results showed that the degree of fatty liver was reduced after AS Ⅳ therapy. Network pharmacological prediction results showed that vascular endothelial growth factor α （VEGFA）， galactoagglutinin 3 （LGALS3）， serine/threonine kinase B2 （Akt2）， RHO-associated coiled-coil protein kinase 1 （ROCK1）， serine/threonine kinase B1 （Akt1）， signaling and transcriptional activator protein （STAT3）， and messtimal epidermal transformation factor （MET） were key targets in "drug-disease" network. The results from the Kyoto encyclopedia of genes and genomes （KEGG） enrichment showed that the AMP-dependent protein kinase （AMPK） signaling pathway was strongly associated with T2DM and NAFLD. Western blot results showed that compared with the blank group， the expression levels of p-AMPK/AMPK in the model group were significantly down-regulated， while those of SREBP-1 and FAS proteins were significantly up-regulated （P<0.01）. Compared with the model group， the expression levels of p-AMPK/AMPK in the metformin group and high-dose AS Ⅳ group were significantly up-regulated， while those of SREBP-1 and FAS proteins were significantly down-regulated （P<0.05， P<0.01）. ConclusionAS Ⅳ regulates the expression of lipid proteins by activating the AMPK signaling pathway， thereby improving lipid metabolism.

An excerpt of an international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease （2023） / 临床肝胆病杂志

In 2020， an international expert panel proposed to replace nonalcoholic fatty liver disease with metabolic associated fatty liver disease （MAFLD）. Recent studies have shown that there is a higher risk of chronic kidney disease （CKD） in the MAFLD population and that MAFLD is an independent risk factor for CKD. However， up to now， there are still no guidelines on the prevention and treatment of MAFLD-related CKD. Based on the Delphi method， the authors led a multidisciplinary team of 50 authoritative experts from 26 countries to reach a consensus on some open-ended research issues about the association between MAFLD and CKD， which can help to clarify the important clinical association between MAFLD and the risk of CKD and improve the understanding of the epidemiology， pathogenesis， management， and treatment of MAFLD and CKD， so as to establish a framework for the early prevention and management of these two common and interrelated diseases.

Role of salidroside in a mouse model of non-alcoholic fatty liver disease： A study based on nicotinamide phosphoribosyltransferase / 临床肝胆病杂志

ObjectiveTo investigate the protective effect of salidroside against nonalcoholic fatty liver disease （NAFLD） and its mechanism of action. MethodsA total of 24 male KM mice were randomly divided into normal group， HFD group， HFD+blank control group， and HFD+salidroside group， with 6 mice in each group. The mice in the normal group were given normal diet， and those in the other groups were given high-fat diet. After 14 weeks of modeling， the mice were given salidroside 100 mg/kg/day by gavage， and related samples were collected at the end of week 22. Enzyme-linked immunosorbent assay was used to measure the serum levels of related biochemical parameters including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C）； HE staining and NAFLD activity score （NAS） were used to observe the liver histopathology of mice； Western blot was used to measure the changes in the expression of NAMPT， Sirt1， AMPKα， and SREBP1 in liver tissue. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal group， the HFD group had obvious steatosis and extensive large lipid droplets in liver tissue， with significant increases in NAS score （P<0.01） and the content of AST， ALT， TG， TC， and LDL-C in peripheral blood （all P<0.05） and a significant reduction in the content of HDL-C （P<0.05）， as well as significant reductions in the expression levels of NAMPT， AMPKα， and Sirt1 in liver tissue （all P<0.05） and a significant increase in the expression level of SERBP1 （P<0.01）. Compared with the HFD group and the HFD+blank control group， the HFD+salidroside group had reductions in the distribution of vacuolar lipid droplets and intralobular inflammation in liver tissue， alleviation of the ballooning degeneration of hepatocytes， significant reductions in NAS score （P<0.01） and the content of AST， ALT， TG， and LDL-C in peripheral blood （all P<0.05）， and a significant increase in the content of HDL-C （P<0.05）， as well as significant increases in the expression levels of NAMPT， AMPKα， and Sirt1 in liver tissue （all P<0.05） and a significant reduction in the expression level of SERBP1 （P<0.01）. ConclusionSalidroside can significantly improve the pathological state of mice with NAFLD induced by high-fat diet and exert a protective effect against NAFLD by increasing the expression of NAMPT， Sirt1， and AMPKα and reducing the expression of SERBP1.

The mechanism of action of mitochondrial dysfunction in the development of non-alcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） has gradually become the main reason affecting human liver health， and many factors are involved in the development and progression of NAFLD. Mitochondria， as the “energy factory” of cells， plays an important role in maintaining normal physiological functions. Studies have shown that hepatic mitochondrial dysfunction promotes the development and progression of NAFLD. This article briefly introduces the latest research advances in the basic characteristics and physiological function of liver mitochondria and reviews new research findings in the association of mitochondrial dysfunction with obesity， simple fatty liver disease， and nonalcoholic steatohepatitis， in order to provide new ideas for the research on targeted mitochondrial therapy for NAFLD.

Using Mendelian randomization to explore the causal association between gut microbiota and nonalcoholic fatty liver disease / 安徽医科大学学报

Objective To explore the causal association between gut microbes and non-alcoholic fatty liver disease(NAFLD)by Mendelian randomisation analysis.Methods Genetic instrumental variables for gut microbiota were identified from a gene-wide association study of 18 340 participants,and summary statistics for NAFLD were ob-tained from the FinnGen database,which provided data on 894 NAFLD cases and 217 898 controls using the IVW method as the primary analysis.In order to test the robustness of the results,MR-Egger method,WM method,Simple Mode method,Weighted Mode method were used for Mendelian randomisation analysis,and heterogeneity test,sensitivity analysis,and multiplicity analysis were performed.Results class Gammaproteobacteria IVW re-sults showed(OR=0.621,95％CI=0.412～0.934,P=0.022);family Enterobacteriaceae IVW results showed(OR=1.481,95％CI=1.069～2.053,P=0.018);genus Lachnospiraceae IVW results showed(OR=1.405,95％CI=1.036～1.904,P=0.029);genus Prevotella7 IVW results showed(OR=0.834,95％CI=0.714～0.974,P=0.021);genus Prevotella9 IVW results showed(OR=1.251,95％CI=1.025～1.527,P=0.027);order Desulfovibrionales IVW results showed(OR=0.714,95％CI=0.519～0.982,P=0.038);or-der Enterobacteriales IVW results showed(OR=1.481,95％CI=1.069～2.053,P=0.018).And there was no heterogeneity in the heterogeneity test,and the sensitivity analyses all showed robustness and no pleiotropy was found.Conclusion This study implicates class Gammaproteobacteria,family Enterobacteriaceae,genus Lachno-spiraceae,genus Prevotella7,genus Prevotella9,order Desulfovibrionales,order Enterobacteriales seven species of gut microorganisms have a causal relationship with NAFLD.

Research progress in clinical management of nonalcoholic fatty liver disease / 重庆医学

Nonalcoholic fatty liver disease(NAFLD),also known as metabolic associated fatty liver disease(MAFLD),is one of the most common chronic liver diseases characterized by the fat accumulation in the liver and hepatocellular damage.Patients with NAFLD can manifest as simple fatty liver or non-alcoholic steatohepatitis(NASH)in the early stage,and can progress to hepatic fibrosis,hepatic cirrhosis,hepatic fail-ure,and hepatic carcinoma in the late stage.NAFLD has become the most common chronic liver disease,af-fecting more than 30%of the population worldwide,posing a threat to human health that cannot be ignored.However,the current research on NAFLD is still incomplete,and there is no ideal medication for the treat-ment of NAFLD.The clinical management of NAFLD lacks unified standards and evidence-based evidence,and the multiple comorbidities bring challenges to the clinical management of NAFLD.This article was aimed to review the research progress in the clinical management of NAFLD,including the diagnosis and non-invasive examination methods,evaluation and commonly used tools,treatments methods,advantages and disadvanta-ges,so as to provide a reference for the clinical management of NAFLD.

Chaihu Guizhi Ganjiang Decoction Improves Non-alcoholic Fatty Liver in Rats Through RIP1/RIP3/MLKL Pathways Inhibiting Necrotic Apoptosis / 广州中医药大学学报

Objective To investigate the therapeutic effect and mechanism of Chaihu Guizhi Ganjiang Decoction on non-alcoholic fatty liver disease(NAFLD)rats.Methods The experiment was conducted in five groups:normal group,model group,low-and high-dose groups of Chinese medicine(Chaihu Guizhi Ganjiang Decoction)and GSK872[receptor interacting protein kinase(RIP)3 inhibitor]group.Except for the normal group,the NAFLD rat model was constructed using high-fat chow feeding method in the remaining groups,respectively.At the end of treatment,hepatocyte apoptosis was observed by terminal transferase uridyl nick end labeling(TUNEL)method,and serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),lipids[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)],and the levels of inflammatory factors tumor necrosis factor α(TNF-α)and interleukin 1β(IL-1β)in liver tissues were measured by enzyme-linked immunosorbent assay(ELISA);and the levels of phosphorylation of RIP1,RIP3,and mixed lineage kinase structural domain-like protein(MLKL)were detected in liver tissues by Western Blot.Results Compared with the normal group,the apoptotic index of rat hepatocytes in the model group was elevated,ALT and AST in serum were significantly elevated,TC,TG and LDL-C levels were significantly elevated,and HDL-C level was significantly reduced,and the contents of TNF-α and IL-1β as well as the phosphorylated expression levels of RIP1,RIP3 and MLKL were significantly elevated in the liver tissues(P＜0.05);compared with the model group,the apoptotic index of hepatocytes in rats in the low-and high-dose groups of Chinese medicine and GSK872 group was reduced,the serum levels of ALT and AST were significantly reduced,the levels of TC,TG and LDL-C were significantly reduced,the level of HDL-C was significantly increased,and the contents of TNF-α and IL-1β and the phosphorylated expressions of RIP1,RIP3 and MLKL in the liver tissues were significantly reduced(P＜0.05);there was no significant difference in the above-mentioned indexes between the low-dose and high-dose groups of Chinese medicine and the GSK872 group(P＞0.05).Conclusion Chaihu Guizhi Ganjiang Decoction can effectively improve NAFLD in rats,and its mechanism may be related to the inhibition of RIP1/RIP3/MLKL signaling pathway activation,which in turn inhibits necrotic apoptosis.

Research progress on the role of ferroptosis in the pathogenesis of non-alcoholic fatty liver disease / 基础医学与临床

Ferroptosis is a new type of cell death proposed in recent years,and its main characteristics are iron overload and lipid peroxidation.Ferroptosis is involved in the occurrence and development of non-alcoholic fatty liv-er disease(NAFLD).Iron overload can generate a large amount of reactive oxygen species through the Fenton reac-tion.Under the action of lipoxygenase,the unsaturated fatty acids on the liver cell membrane undergo lipid peroxi-dation,which induces liver cell death and leads to the occurrence of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.Blocking ferroptosis may provide one of the therapeutic strategies to protect liver cells.

The Association of Intestinal Flora Metabolite TMAO with Non-alcoholic Fatty Liver Disease / 昆明医科大学学报

Objective To explore the role of TMAO from gut microbiota in non-alcoholic fatty liver disease(NAFLD),we detected the serum level of TMAO and its precursor metabolites in NAFLD,as well as the expression level of Eubacterium rectum,Bacteroidetes multiforme,Lactobacillus and bifidobacterium in the intestinal flora.Methods We collected 118 subjects and divided into NAFLD group(86 cases)and healthy control group(32 cases)randomly.We also detected the serum level of TMAO and its precursor metabolites in subjects by high performance liquid chromatography tandem mass spectrometry detection(LC-MS),and the expression of target bacterial DNA was detected by qRT-PCR.Results Serum TMAO,TMA and choline levels were significantly increased in NAFLD(P<0.05),and liver fat content was positively correlated with TMAO(P<0.05).The expression level of Lactobacillus and Eubacterium rectum in NAFLD group were increased(P<0.05);the expression level of Bifidobacterium and Bacteroides multiform were decreased(P<0.05).The serum TMAO level was positively correlated with Eubacterium rectum(r=0.280,P<0.05),and negatively correlated with Bifidobacterium(r=-0.332,P<0.05).Conclusion The level of TMAO in serum shows a positive correlation with NAFLD.The structure of intestinal flora in individuals with NAFLD is altered and linked to TMAO.This suggests that the intestinal flora may have a significant impact on the development of NAFLD through TMAO.

Research progress in the treatment of AMPK regulating lipid accumulation in the treatment of nonalcoholic fatty liver disease / 实用医学杂志

Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease and has posed significant challenges to global public health and medical care.Due to the unclear pathogenesis of NAFLD,lipid accumulation plays a key role in its development.AMPK,as a crucial molecule in lipid metabolism regulation,can improve lipid accumulation caused by NAFLD.This article describes the specific mechanisms of AMPK-related molecules in improving lipid accumulation and treating NAFLD,and lists the current experimental and therapeutic drugs related to AMPK.The potential of AMPK-related drugs in improving lipid accumulation and treating NAFLD is demonstrated,providing ideas and references for future research on AMPK-related drugs for treating NAFLD.

Research progress on serological markers of non-alcoholic fatty liver disease / 中国综合临床

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing year by year, and it has become a serious public health problem that threatens human health.NAFLD patients can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), liver fibrosis, and even cirrhosis without intervention. Therefore, early diagnosis and treatment are particularly important.Liver biopsy is the gold standard for diagnosing NAFLD, but its limitations such as invasion, bleeding, and high cost limit its widespread clinical application. There is an urgent need for sensitive and convenient non-invasive diagnostic methods to achieve early diagnosis and treatment of NAFLD.This article provides a review of the progress in serological diagnostic methods for NAFLD both domestically and internationally in recent years.

Therapeutic effect of low-carbohydrate diet and lifestyle intervention on patients with lean nonalcoholic fatty liver disease / 临床肝胆病杂志

ObjectiveTo investigate the therapeutic effect of low-carbohydrate diet and online lifestyle intervention on patients with lean nonalcoholic fatty liver disease （NAFLD）. MethodsThis study was conducted among 53 patients with lean NAFLD who attended Department of Infectious Diseases in Peking University Shenzhen Hospital and Shenzhen Qianhai Shekou Free Trade Zone Hospital from December 2019 to March 2021， and the patients were given low-carbohydrate diet for calorie restriction ［total calorie intake was calculated based on basal metabolic rate （BMR） and physical activity level （PAL） and was restricted within （BMR×95%×PAL-1 000） kcal to （BMR×95%×PAL-500） kcal， and carbohydrate ratio fluctuated between 10% and 55%］ and lifestyle interventions for 8 weeks. An online software was used for supervision and follow-up， and the patients were observed in terms of treatment outcome and safety. The patients were compared in terms of controlled attenuation parameter （CAP）， liver stiffness measurement （LSM）， Anthropometric parameters， blood biochemistry， urinary protein， and urine ketone body before and after intervention. The patients were followed up after 1 year to measure body weight and body mass index （BMI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the paired-sample Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous； the chi-square test was used for comparison of categorical data between groups. ResultsAfter 8 weeks of intervention， CAP decreased from 304.47±31.91 db/m to 242.43±26.74 db/m， LSM decreased from 7.43±2.41 kPa to 6.36±1.79 kPa， and body weight decreased from 64.29±7.37 kg to 60.24±7.08 kg （t=11.25，3.72， and 14.07， all P<0.001）. Of all patients， 25 （47.2%） had disappearance of fatty liver， and abnormal LSM in 12 patients （63.2%） returned to normal； 52 patients （98.1%） had a mean reduction of 4.05±2.32 kg in body weight. The degree of reduction in CAP increased with the degree of reduction in body weight. After intervention， there were significant reductions in BMI， waist circumference， hip circumference， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， uric acid， fasting blood glucose， triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein （LDL） and a significant increase in high-density lipoprotein （t=12.85， 13.77， 10.28， 7.64， 6.21， 8.35， 6.83， 6.31， 7.4， 4.97， 5.95， and -2.21， all P<0.05）. The patients with abnormal ALT， AST， GGT， uric acid， fasting blood glucose， TG， TC， and LDL at baseline which returned to normal after intervention accounted for 75%， 100%， 81.8%， 57.1%， 100%， 66.7%， 73.5%， and 85.3%， respectively. There were no significant changes in blood urea nitrogen， serum creatinine， urine protein， and urine ketone body （all P>0.05）. There was no rebound in body weight and BMI after 1 year of follow-up （P>0.05）. There were no gastrointestinal reactions during intervention or follow-up. ConclusionLow-carbohydrate diet and lifestyle intervention can improve liver fat content， liver function， and blood lipid parameters in patients with lean NAFLD， with good safety.

Effect of NOD‑like receptor family pyrin domain containing 3 knockdown on a mouse model of nonalcoholic steatohepatitis induced by high-fat high-carbohydrate diet / 临床肝胆病杂志

ObjectiveTo investigate the effect of NOD-like receptor family pyrin domain containing 3 （NLRP3） knockdown on a mouse model of nonalcoholic steatohepatitis （NASH） induced by high-fat high-carbohydrate （HFHC） diet. MethodsA total of 44 mice were randomly divided into normal diet group （CON group） with 20 mice and HFHC group with 24 mice. At the end of week 14 of modeling， 4 mice were randomly selected from the HFHC group for the pre-experiment of adeno-associated virus （AAV） by tail vein injection， and NLRP3 knockdown was verified after 4 weeks. After NLRP3 knockdown was verified at the end of week 18， the remaining 40 mice were given a single tail vein injection of AAV， and then they were divided into CON+NLRP3 knockdown negative control group （CON+NLRP3-NC group）， CON+NLRP3 knockdown group （CON+NLRP3-KD group）， HFHC+NLRP3-NC group， and HFHC+NLRP3-KD group， with 10 mice in each group. At the end of week 24， the activation of NLRP3 inflammasome was observed； related indicators were measured， including body weight， liver weight， liver index， and glucose metabolism （fasting blood glucose， fasting insulin， and Homeostasis Model Assessment of Insulin Resistance ［HOMA-IR］ index）； the indicators of liver lipid content （liver triglyceride ［TG］ and oil red O staining）， liver inflammation （serum alanine aminotransferase ［ALT］ activity， HE staining， and inflammation-related genes）， and liver fibrosis （Sirius Red staining and fibrosis-related genes） were measured. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the CON+NLRP3-NC group based on the results of Western Blot， the HFHC+NLRP3-NC group had significant increases in the protein expression levels of NLRP3， pro-Caspase1， Caspase1， ASC， and IL-1β， while the HFHC+NLRP3-KD group had significant reductions in these levels （all P<0.05）. The HFHC+NLRP3-NC group showed varying degrees of increase in body weight， liver weight， liver index， and glucose metabolism indicators， while the HFHC+NLRP3-KD group showed significant improvements in these indicators （all P<0.05）. As for hepatic fat deposition， compared with the CON+NLRP3-NC group， the HFHC+NLRP3-NC group had a significant increase in liver TG， with a large number of red lipid droplets shown by oil red O staining， and the HFHC+NLRP3-KD group had significant reductions in liver TG and the number of lipid droplets in the liver （all P<0.01）. In terms of liver inflammation， compared with the CON+NLRP3-NC group， the HFHC+NLRP3-NC group had significant increases in serum ALT， NAFLD activity score， and inflammation-related genes， while the HFHC+NLRP3-KD group had significant reductions in these indicators （all P<0.01）. As for liver fibrosis， compared with the CON+NLRP3-NC group， the HFHC+NLRP3-NC group had significant increases in collagen fiber area and fibrosis-related genes， and the HFHC+NLRP3-KD group had significant reductions in fibrosis-related genes （all P<0.05） and a tendency of reduction in collagen fiber area （P>0.05）. ConclusionNLRP3 knockdown can significantly improve hepatic fat deposition and inflammation in a mouse model of HFHC-induced NASH.

Protective effect and mechanism of Hirudo on mice with non-alcoholic fatty liver disease / 中国药房

OBJECTIVE To explore the protective effects and potential mechanisms of Hirudo on mice with non-alcoholic fatty liver disease （NAFLD） in mice. METHODS The male ApoE－/－ mice were randomly divided into the model group and Hirudo low- dose and high-dose groups （0.45， 0.9 g/kg）， with 10 mice in each group； another 10 wild-type male C57BL/6J mice were chosen as the control group. The control group was fed with basal maintenance chow and the remaining groups were fed with high-fat chow for 12 weeks to establish the NAFLD model. Each administration group was given corresponding solution intragastrically， once a day， for 8 consecutive weeks. In the 13th week， the body weight and liver weight of mice in each group were measured after the last medication， and the liver index was calculated； the serum levels of nuclear factor-κB （NF-κB）， tumor necrosis factor-α （TNF- α）， interleukin-1β （IL-1β）， IL-6， total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） were detected； the liver pathomorphological changes were observed； the protein expressions of peroxisome proliferator-activated receptor γ（PPARγ） and silence information regulator type 1 （SIRT1） were detected. RESULTS Compared with the control group， the liver tissue of mice in the model group showed more fat vacuoles and infiltration of inflammatory cells， with significant lipid accumulation； the body weight， liver weight and liver index of the mice， and serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C significantly increased， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissues significantly decreased （P＜0.01）. Compared with the model group， the pathological changes in liver tissue of mice were all relieved in Hirudo low-dose and high-dose groups； the body weight， liver weight and liver index， the serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C decreased significantly， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissue all increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Hirudo can regulate liver lipid metabolism and inhibit inflammation by activating the protein expressions of PPARγ and SIRT1， thus having a significant ameliorative effect on NAFLD.

Risk factors of non-alcoholic fatty liver disease in children / 中国儿童保健杂志

Non-alcoholic fatty liver disease(NAFLD) has become the main cause of chronic liver disease in children worldwide, and the incidence of NAFLD shows an increasing trend year by year. The risk factors leading to the onset of NAFLD in children are diversified and different from those in adults. At present, most medical institutions still pay little attention to NAFLD in children. This paper summarizes the risk factors and mechanisms for NAFLD in children, including gene polymorphism, maternal and fetal conditions, diet and living habits, environmental exposure, metabolic syndrome, endocrine-related mechanisms and intestinal microecology, in order to provide reference for the prevention and management of childhood NAFLD.

Intervention effect and mechanism of Wuwei baogan pill on mice with non-alcoholic fatty liver disease / 中国药房

OBJECTIVE To investigate the intervention effect and mechanism of Wuwei baogan pill on mice with non- alcoholic fatty liver disease （NAFLD）. METHODS The mice were given high-fat and high-sugar diet for 19 weeks to induce NAFLD model. The model mice were randomly grouped into model group， positive control group （polyene phosphatidylcholine capsules， 23.30 mg/kg）， Wuwei baogan pill low-dose， medium-dose and high-dose groups （0.11， 0.23， 0.45 g/kg）， with 8 mice in each group； the normal group was additionally set up without modeling. Administration groups were given relevant medicine intragastrically， and model group and normal group were given constant volume of normal saline， once a day， for consecutive 4 weeks. After the last administration， glucose metabolism （including fasting blood glucose， fasting insulin， insulin resistance index）， liver function [liver index， alanine aminotransferase （ALT）， aspartate aminotransferase （AST），liver tissue pathological score]， lipid metabolism [triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high- density lipoprotein cholesterol （HDL-C）] were measured； the pathological morphology of liver tissue， as well as fibrosis， lipid droplet formation， and glycogen synthesis were observed； the levels of free fatty acid （FFA） in serum and inflammatory factors in liver tissue [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β] were detected； the expressions of insulin receptor substrate/phosphoinositide 3-kinase/protein kinase B/ glycogen synthase kinase 3β （IRS/PI3K/AKT/GSK3β） signaling pathway-related protein in liver tissue were investigated. RESULTS After intervention with high-dose Wuwei baogan pill， liver index of NAFLD mice， serum levels of ALT， AST， FFA， TC， TG and LDL-C， the levels of TNF-α， IL-6 and IL-1β in liver tissue， fasting blood glucose， fasting insulin， insulin resistance index， liver tissue pathological score， proportions of fibrotic staining area and lipid droplet staining area all significantly decreased （P＜0.05）； the level of HDL-C， proportion of glycogen staining area， the phosphorylation of IRS1， PI3K， AKT and GSK3β protein increased significantly （P＜0.05）； the degree of liver cell necrosis and steatosis was reduced， and the fibrotic lesions were alleviated. The above indexes of mice were improved in Wuwei baogan pill low-dose and medium-dose groups， but there was no statistically significant difference in some indexes. CONCLUSIONS Wuwei baogan pill can regulate lipid and glucose metabolism disorders in the liver of NAFLD mice， and improve liver injury， the mechanism of which may be associated with the activation of IRS/PI3K/AKT/GSK3β signaling pathway.