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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.
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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.
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Objective: Non-alcoholic fatty liver disease is common worldwide, and lifestyle modifications are key to its treatment. This study aimed to identify the barriers to lifestyle modifications in patients with non-alcoholic fatty liver disease and to organize the results using the Capability Opportunity Motivation-Behavior (COM-B) model.Materials and Methods: The framework of Arksey and O’ Malley was used in this scoping review. We searched PubMed, Scopus, and the Cochrane Library without language restrictions for reports published up to September 11, 2022, including peer-reviewed literature reporting barriers to lifestyle modifications in patients with non-alcoholic fatty liver disease. Patient-reported barriers were analyzed inductively and organized into the components (capability, opportunity, and motivation) of the COM-B model.Results: The literature search yielded 583 articles, of which seven qualitative studies, four quantitative studies, and one mixed-methods study met the inclusion criteria. Lack of time, lack of information on the diagnosis and management of non-alcoholic fatty liver disease, negative perceptions of the prescribed exercise and diet, physical symptoms interfering with the behavior, presence of comorbidities, and lack of family cooperation were frequently reported as barriers.Conclusion: The results of this study may contribute to the development of appropriate care and education strategies to promote behavioral changes in patients with non-alcoholic fatty liver disease.
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objectiveTo investigate the differences in clinical indices and lipid metabolism between the patients with nonalcoholic fatty liver disease （NAFLD） and healthy individuals in the overweight population. MethodsIn this study， body mass index （BMI）>23 kg/m2 was defined as overweight. A total of 62 overweight patients with NAFLD who were admitted to Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2020 to April 2021 were enrolled as overweight NAFLD group， and 50 overweight individuals who underwent physical examination during the same period of time were enrolled as control group. Clinical information and blood biochemical parameters were recorded for all subjects. Ultra-performance liquid chromatography-tandem mass spectrometry was used to analyze serum lipidomic profile， and principal component analysis and orthogonal partial least squares-discriminant analysis were used to perform the multivariate statistical analysis of lipidomic data. The chi-square test was used for comparison of categorical data between two groups， and the independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups. ResultsThe overweight NAFLD group had a significantly higher BMI than the overweight control group （Z=-2.365， P=0.018）. As for serological markers， compared with the overweight control group， the overweight NAFLD group had significantly higher levels of red blood cells， hemoglobin， hematocrit， uric acid， total protein， globulin， alkaline phosphatase， gamma-glutamyl transpeptidase， alanine aminotransferase， aspartate aminotransferase， cholinesterase， low-density lipoprotein， total cholesterol， triglyceride， apolipoprotein B， and blood glucose （all P<0.05）. The lipidomic analysis showed that there was a significant difference in lipid metabolism between the two groups， and a total of 493 differentially expressed lipids were identified （VIP value>1， P<0.05）， among which 143 lipids were significantly upregulated and 350 lipids were significantly downregulated in the overweight NAFLD group. The mean total fatty acid content in the overweight NAFLD group was 3.6 times that in the overweight control group. Compared with the overweight control group， the overweight NAFLD group had a significant reduction in the content of triglyceride with>3 unsaturated bonds （P<0.001） and a significant increase in the content of triglyceride with ≤3 unsaturated bonds （P<0.001）. ConclusionCompared with healthy overweight individuals， overweight NAFLD patients tend to have significant abnormalities in some biochemical parameters and lipid metabolites， with significant increases in the content of fatty acid in blood and the types of saturated fat chains in triglycerides.
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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.
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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.
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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.
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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.
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Objective To study the change of lipidomics in chronic cadmium-exposed mice,thereby screening out lipid subclasses,lipid molecules and enriched metabolic pathways with significant differences.Methods Twelve SPF male C57BL/6J mice(8 weeks old)were randomly divided into the control group(normal water feeding)and the experimental group[cadmium water(0.6 mg/L of CdCl2)feeding],with 6 mice in each group.Mice were sacrificed after 6 months of cadmium exposure,and fresh liver tissues were collected immediately.Lipid oil red O staining and lipidomics analysis were performed on liver tissue.Results Compared with the control group,the liver tissue of mice in the experimental group did not appear red after lipid oil red O staining.Seventeen lipid subclasses with significant differences and 144 lipid molecules with significant differences were screened out by lipidomics.These lipid molecules with significant differences were enriched in glycerophospholipid metabolism,linoleic acid metabolism,alpha-linolenic acid metabolism,glycosylphosphati-dylinositol biosynthesis,glycerolipid metabolism and arachidonic acid metabolism by KEGG.Conclusion This study reveals that chronic cadmium exposure can induce the disorder of lipid subclasses and lipid metabolites in the liver of mice,which provides a basis for understanding the non-alcoholic fatty liver disease caused by chronic cadmium exposure.
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Objective To explore the value of ultrasonic quantitative measurement of hepatorenal index(HRI)for diagnosing non-alcoholic fatty liver disease(NAFLD)in children.Methods Abdominal ultrasound and upper abdominal MRI data of 70 obese children were retrospectively analyzed.ROI with different sizes and shapes of liver and right kidney were delineated on longitudinal and transverse ultrasound images,respectively,and the echo intensity of ROIs were measured to obtain HRIsmall ROI on longitudinal section,HRIsmall ROI on transverse section,HRIlarge ROI on longitudinal section and HRIlarge ROI on transverse section,i.e.HRI1,HRI2,HRI3,HRI4,while the gray,skewness and kurtosis of liver ultrasound image were recorded.Liver proton density fat fraction(PDFF)were measured based on MRI,and NAFLD was diagnoses taken PDFF≥6%as standard.The correlations of HRI with PDFF and liver ultrasound image related parameters were analyzed.Taken MRI as the standard,receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic efficacy of HRI for NAFLD.Multivariate logistic regression analysis was performed taken age,sex,body mass index(BMI)percentile,HRI3 and liver ultrasound image related parameters as independent variables and MRI diagnosis of NAFLD as dependent variable to screen the predictors of MRI diagnosis of NAFLD.Results HRI1,HRI2,HRI3 and HRI4 obtained with ultrasound was 1.89±0.52,1.88±0.55,1.97±0.51 and 1.92±0.55,respectively.PDFF obtained with MRI was(12.53±3.14)%,and diagnosed NAFLD in 34 cases.HRI and PDFF had moderate positive correlation(r=0.51-0.61,all P＜0.01).The correlation between HRI3 and PDFF was the strongest(r=0.61),and HRI3 was weakly correlated with liver gray3(r=-0.270,P=0.020),with area under the curve(AUC)for diagnosing NAFLD of 0.93(P＜0.01).BMI percentile(OR=1.06),HRI3(OR=34.20)and liver gray3(OR=0.79)were all predictive factors for MRI diagnosis of NAFLD.Conclusion Ultrasonic quantitative measurement of HRI had high clinical value for diagnosing NAFLD in children.
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AIM:To improve the success rate of experimental modeling of non-alcoholic fatty liver(NAFLD)in rats by high-fat diet through comparing three different formulations of high-fat diets in con-structing non-alcoholic fatty liver rats model,so as to provide a reliable animal model for the study of non-alcoholic fatty liver disease.METHODS:SPF-grade male SD rats were divided into four groups randomly:control group,high-fat diet group1(HFD1),high-fat diet group2(HFD2),high-fat diet group3(HFD3).Each group was given the corre-sponding feed for 8 weeks while modeling.The da-ta on general observation,body weight changes,and ingestion of the rats were recorded during the modeling period.After 8 weeks'feeding,liver ultra-sound,CT and MRI examination were performed for the rats of each group to check the status.Blood and liver samples were collected.Changes in liver function(ALT,AST),blood lipids(TC,TG,HDL-C,LDL-C),and inflammatory indexes(IL-1β,IL-6,TNF-α)were detected.The morphology of the liv-ers was observed with the naked eyes,and the liv-er index and Lee's index were calculated at the end of 8 weeks.The effects of different high-fat diets on the establishment of NAFLD model in SD rats were comprehensively evaluated by comparing the difference of above indexes among the groups.RE-SULTS:Compared with the control group,rats in the HFD1,HFD2 and HFD3 groups showed poor mental deterioration,decreased activity,severe hair loss,decreased food intake,increased body weights,and significantly increased liver index and Lee's in-dex,along with increased liver volume,blunt edge,steatosis and lipid deposition,and the trend was even more pronounced in the HFD3 group.Com-pared with the control group,the serum levels of ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α were significantly increased,while the contents of HDL-C was significantly decreased in the HFD1,HFD2 and HFD3 group,especially in the HFD3 group.Com-pared with the control group,the B ultrasonogra-phy showed an enlarged liver with enhanced paren-chymal echo and pipe unsharpness,CT showed that the liver and spleen CT ratio decreased obvi-ously,and the MRI images showed obvious differ-ence of liver signal intensity between in/out of phase image in the HFD1,HFD2 and HFD3 group,and the most significant imaging changes was ob-served in the HFD3 group.CONCLUSION:The above three kinds of high-fat diets can establish NAFLD model in SD rats after 8 weeks'feeding,the models induced by HFD3 was better than those in-duced by the other two groups.NAFLD lesion is rel-atively serious and expected to last longer in HFD3 group,which are more suitable for investigating the underlying mechanisms of non-alcoholic fatty liver disease and development of lipid-lowering drugs.
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Objective:To analyze the application value of non-invasive inflammation diagnosis model in the diagnosis of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) combined with hepatitis B virus (HBV) infection.Methods:A total of 98 patients with NAFLD complicated with HBV infection admitted to some coastal China Coast Guard Hospital of People′s Armed Police from June 2019 to October 2021 were selected. Their liver stiffness (LSM), aspartate aminotransferase to platelet ratio (APRI), γ-glutamyltranspeptidase to platelet ratio (GPR), and fibrosis index based on factor 4 (FIB-4) were measured, The receiver operating characteristic (ROC) curve was used to analyze its clinical diagnostic efficacy for liver fibrosis caused by NAFLD combined with HBV infection.Results:Among 98 patients, there were 7 cases in S0 stage, 47 cases in S1 stage, 21 cases in S2 stage, 14 cases in S3 stage, and 9 cases in S4 stage; Including 35 cases of obvious liver fibrosis and 9 cases of cirrhosis. There was no statistically significant difference in gender and body mass index (BMI) among patients in different stages (all P>0.05). Age: the S0 group<the S1 group<the S2 group<the S3 group<the S4 group ( P<0.05); LSM, APRI, FIB-4: S0 group<S1 group<S2 group<S3 group<S4 group (all P<0.05); The GPR of the S0 and S1 groups was significantly lower than the other groups ( P<0.05), and the S2 group<the S3 group<the S4 group ( P<0.05). The sensitivity and specificity of LSM in diagnosing obvious liver fibrosis were 71.6% and 83.1%, respectively; The sensitivity and specificity of APRI were 61.4% and 80.9%, respectively; The sensitivity and specificity of GPR were 82.3% and 66.8%, respectively; The sensitivity and specificity of FIB-4 were 66.2% and 69.5%, respectively. The sensitivity and specificity of LSM in diagnosing liver cirrhosis were 86.1% and 67.5%, respectively; The sensitivity and specificity of APRI were 77.4% and 75.2%, respectively; The sensitivity and specificity of GPR were 79.6% and 75.3%, respectively; The sensitivity and specificity of FIB-4 were 81.2% and 60.4%, respectively. Conclusions:Patients with NAFLD combined with HBV infection show a significant increase in LSM, APRI, GPR, and FIB-4 as liver fibrosis worsens. These non-invasive inflammatory diagnostic models have certain diagnostic value for liver fibrosis, with LSM and GPR having higher diagnostic efficacy.
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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.
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Objective To observe the effects of Jianpi Liqi Huashi Prescription on hepatocyte injury,oxidative stress and nitrative stress in mice with non-alcoholic steatohepatitis(NASH);To explore its mechanism in the treatment of NASH.Methods Totally 32 male C57BL/6J mice were randomly divided into control group,model group and TCM low-and high-dosage groups,with 8 mice in each group.The control group was fed with ordinary diet,and the other groups were fed with high-fat diet,for consecutive 16 weeks.Starting from the 13th week,the control group and model group were given 0.4%CMC-Na solution by intragastric administration and the TCM groups were given corresponding doses of drugs by intragastric administration,respectively.Biochemical instrument was used to detect serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)contents,HE staining and oil red O staining were used to detect liver histopathology,triglyceride(TG)content and myeloperoxidase(MPO)activity in liver tissue were detected through test kit.immunofluorescence staining was used to detect positive expression of CD11b in liver tissue,the mRNA expressions of NOX1 and NCF1 were detected by RT-PCR,and the protein expressions of inducible nitric oxide synthase(iNOS)and 3-nitrotyrosine(3-NT)in liver tissue were detected by Western blot.Results Compared with the control group,the hepatocytes in the model group showed diffuse steatosis,hepatocyte swelling and inflammatory cell infiltration;a large number of fat droplets were formed by oil red O staining;serum ALT and AST contents significantly increased(P<0.05),the TG content and MPO activity in liver tissue significantly increased(P<0.05);the positive expression of CD11b in liver tissue increased;the mRNA expressions of NOX1 and NCF1 in liver tissue significantly increased(P<0.05);the expressions of iNOS and 3-NT protein in liver tissue significantly increased(P<0.05).Compared with the model group,the degree of liver steatosis,the level of inflammatory cell infiltration and the number of lipid droplets in TCM groups decreased significantly;serum ALT and AST contents significantly decreased(P<0.05);the TG contents and MPO activity in liver tissue significantly decreased(P<0.05);the positive expression of CD11b in liver tissue decreased;the mRNA expressions of NOX1 and NCF1 in liver tissue significantly decreased(P<0.05);the expression of 3-NT protein in liver tissue significantly decreased(P<0.05);the expression of iNOS protein in liver tissue of mice in TCM high-dosage group significantly decreased(P<0.05).Conclusion Jianpi Liqi Huashi Prescription may relieve liver cell damage,lipid deposition and inflammation in NASH mice by alleviating oxidative stress and nitrative stress in the liver,and play a role in the treatment of NASH.
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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.
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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.
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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.
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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.
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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.
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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.