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1.
Arq. gastroenterol ; 59(3): 402-407, July-Sept. 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1403501

ABSTRACT

ABSTRACT Background Insulin resistance (IR), assessed by different criteria, is an important factor in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). More recently with the characterization of this metabolic dysfunction-associated fatty liver disease (MAFLD), one of the proposed criteria for this diagnosis has been the determination of the homeostasis model assessment-insulin resistance (HOMA-IR). Objective: The purpose of this study was to evaluate the relationship of HOMA-IR>2.5 with clinical, metabolic, biochemical and histological data obtained in non-diabetic patients diagnosed with NAFLD by liver biopsy. Methods: Cross-sectional, retrospective study was carried out with data from 174 adult individuals of both genders with non-diabetics NAFLD, without obvious signs of portal hypertension. The body mass index (BMI) was classified according to the World Health Organization (1998), and the metabolic syndrome by the criteria of NCEP-ATP-III. Biochemical tests were evaluated using an automated method and insulinemia through immunofluorometric assay. Histological findings were classified according to Kleiner et al. (2005). Results: The mean age of the studied population was 53.6±11.2 years, with 60.3% being female. The average BMI was 30.3 kg/m2 and 75.9% of the patients had increased waist circumference. Among evaluated metabolic parameters, there was a higher prevalence of metabolic syndrome (MS) in patients with HOMA-IR>2.5, with no statistical difference in relation to BMI between studied groups. Values of liver enzymes and serum ferritin were significantly higher in patients with this marker of IR, who had a higher prevalence of non-alcoholic steatohepatitis (NASH) and advanced liver fibrosis. In the multivariate analysis, the clinical diagnosis of MS, hyperferritinemia and the presence of NASH in the liver biopsy were the factors independently associated with the presence of altered HOMA-IR. Conclusion: HOMA-IR values >2.5 identify patients with NAFLD with distinct clinical and metabolic characteristics and with a greater potential for disease progression, which validates this parameter in the identification of patients with MAFLD.


RESUMO Contexto A resistência à insulina (RI), avaliada por diferentes critérios, é um fator importante na patogênese da doença hepática gordurosa não alcoólica (DHGNA). Mas, recentemente, com a caracterização desta disfunção metabólica associada com a doença hepática gordurosa (DGH), um dos critérios propostos para este diagnóstico tem sido a determinação do modelo de avaliação da homeostase-resistência à insulina (HOMA-IR). Objetivo: O objetivo deste estudo foi avaliar a relação do HOMA-IR> 2,5 com dados clínicos, metabólicos, bioquímicos e histológicos obtidos em pacientes não diabéticos diagnosticados com DHGNA por biópsia hepática. Métodos Estudo transversal, retrospectivo, com dados de 174 indivíduos adultos de ambos os sexos com DHGNA não-diabética, sem sinais evidentes de hipertensão portal. O índice de massa corporal (IMC) foi classificado de acordo com a Organização Mundial da Saúde (1998) e a síndrome metabólica pelos critérios do NCEP-ATP-III. Os exames bioquímicos foram avaliados pelo método automatizado e a insulinemia por imunofluorometria. Os achados histológicos foram classificados de acordo com Kleiner et al. (2005). Resultados: A média de idade da população estudada foi de 53,6±11,2 anos, sendo 60,3% do sexo feminino. O IMC médio foi de 30,3 kg/m2 e 75,9% dos pacientes apresentaram circunferência da cintura aumentada. Entre os parâmetros metabólicos avaliados, houve maior prevalência de síndrome metabólica (SM) em pacientes com HOMA-IR >2,5, sem diferença estatística em relação ao IMC entre os grupos estudados. Os valores das enzimas hepáticas e da ferritina sérica foram significativamente maiores nos pacientes com este marcador de RI, que apresentaram maior prevalência de esteato-hepatite não alcoólica (EHNA) e fibrose hepática avançada. Na análise multivariada, o diagnóstico clínico de SM, hiperferritinemia e a presença de EHNA na biópsia hepática foram os fatores independentemente associados à presença de HOMA-IR alterado. Conclusão: Valores de HOMA-IR >2,5 identificam pacientes com DHGNA com características clínicas e metabólicas distintas e com maior potencial de progressão da doença, o que valida esse parâmetro na identificação de pacientes com DHG.

2.
Arq. gastroenterol ; 59(1): 123-128, Jan.-Mar. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1374445

ABSTRACT

ABSTRACT Background Supplementation with probiotics, prebiotics and symbiotics has shown positive effects on clinical markers and risk factors for non-alcoholic fatty liver disease (NAFLD). Objective To evaluate the effect of supplementation with probiotic, prebiotic or symbiotic on intestinal microbiota in NAFLD patients. Methods Two investigators conducted independently search for articles in the Medline databases, via PubMed, Web of Science, Embase, Scopus, Lilacs, Central Cochrane Library, Clinical Trials.gov and on the Ovid platform for the gray literature search. Results A total of 3,423 papers were identified by searching the electronic databases; 1,560 of them were duplicate and they were excluded; 1,825 articles were excluded after reading the title and abstract. A total of 39 articles were select to reading, however only four articles met the eligibility criteria to include in this systematic review. Three of the included studies that used prebiotic or symbiotic supplementation showed that after the intervention there were changes in the intestinal microbiota pattern. Only in one study such changes were not observed. A high risk of bias was observed in most assessments. Conclusion Although there is a possible change in the gut microbiota of individuals with NAFLD after supplementation with symbiotics or prebiotics, a clinical indication as part of NAFLD treatment is not yet possible.


RESUMO Contexto A suplementação com probióticos, prebióticos e simbióticos mostrou efeitos positivos sobre marcadores clínicos e fatores de risco para doença hepática gordurosa não alcoólica (DHGNA). Objetivo Avaliar o efeito da suplementação com probióticos, prebióticos ou simbióticos na microbiota intestinal em pacientes com DHGNA. Métodos Dois pesquisadores realizaram buscas independentes de artigos nas bases de dados Medline, via PubMed, Web of Science, Embase, Scopus, Lilacs, Biblioteca Central Cochrane, Clinical Trials.gov e na plataforma Ovid para busca de literatura cinza. Os títulos e resumos foram lidos para excluir artigos irrelevantes. Em seguida, os artigos selecionados foram lidos na íntegra e avaliados de acordo com os critérios de elegibilidade. O risco de viés foi avaliado de acordo com a Cochrane. Resultados Um total de 3.423 artigos foram identificado por meio de busca nas bases de dados eletrônicas; 1.560 deles eram duplicados e foram excluídos; 1.825 artigos foram excluídos após a leitura do título e do resumo. Um total de 39 artigos foram selecionado para leitura, porém apenas quatro artigos atenderam aos critérios de elegibilidade para inclusão nesta revisão sistemática. Três dos estudos incluídos que utilizaram suplementação de prebióticos ou simbióticos mostraram que após a intervenção ocorreram mudanças no padrão da microbiota intestinal. Apenas em um estudo tais mudanças não foram observadas. Um elevado risco de viés foi observado na maioria das avaliações. Conclusão Embora haja uma possível alteração na microbiota intestinal de indivíduos com DHGNA após a suplementação com simbióticos ou prebióticos, uma indicação clínica como parte do tratamento da DHGNA ainda não é possível.

3.
Rev. Eugenio Espejo ; 16(1): 39-49, 20220111.
Article in Spanish | LILACS | ID: biblio-1352995

ABSTRACT

La hepatopatía crónica más prevalente en el mundo es la esteatosis hepática no alcohólica. Así, se realizó una investigación con el objetivo de determinar los factores asociados a esa patología en pacientes atendidos en el Centro de salud tipo B Chambo, Ecuador, durante 2020. Se realizó un estudio con enfoque cuantitativo, de tipo no experimental, correlacional y retrospectivo. Las historias clínicas seleccionadas aportaron los datos de las variables de interés. La media de la edad de los involucrados fue de 54,43 ± 8,10 años. El 60,38% tenía hipertensión arterial, el 52,83% diabetes mellitus, el 62,26% sobrepeso u obesidad y el 49,06% dislipidemia, determi-nando que estas comorbilidades tuvieron una relación significativa con la enfermedad objeto de estudio, la que resultó más incidente en edades mayores de 50 años. Las personas sedentarias o con bajos niveles de actividad física mostraron de ALT y AST.


The most prevalent chronic liver disease in the world is nonalcoholic fatty liver disease. Thus, research aimed to determine the factors associated with this pathology in patients treated at the Type B Chambo Health Center, Ecuador, during 2020. A study was carried out with a quantitati-ve, non-experimental, correlational, and retrospective approach. The selected medical records provided the information for the variables of interest. The mean age of the population was 54.43 ± 8.10 years of age. 60.38% had arterial hypertension, 52.83% diabetes mellitus, 62.26% overweight or obesity and 49.06% dyslipidemia. It was determined that these comorbidities had a significant relationship with the disease under study, which was more incident in ages older than 50. Sedentary people or those ones with low levels of physical activity showed ALT and AST.


Subject(s)
Humans , Male , Female , Middle Aged , Comorbidity , Abiotic Factors , Liver Diseases , Exercise , Cholesterol , Overweight
4.
Article in Chinese | WPRIM | ID: wpr-936366

ABSTRACT

OBJECTIVE@#To investigate the changes of tetraspanin 8 (TSPAN8) expression levels and its role in lipid metabolism during the development of non-alcoholic fatty liver disease (NAFLD).@*METHODS@#Thirty male C57BL/6J mice were randomly divided into normal diet group and high-fat diet (HFD) group (n=15), and after feeding for 1, 3, and 6 months, the expression levels of TSPAN8 in the liver tissues of the mice were detected with Western blotting. In a HepG2 cell model of NAFLD induced by free fatty acids (FFA), the effect of TSPAN8 overexpression on lipid accumulation was examined using Oil Red O staining and an automated biochemical analyzer, and the mRNA expressions of the key genes involved in lipid metabolism were detected using qRT-PCR.@*RESULTS@#Western blotting showed that compared with that in mice with normal feeding, the expression of TSPAN8 was significantly decreased in the liver tissues of mice with HFD feeding for 3 and 6 months (P < 0.05). In HepG2 cells, treatment with FFA significantly decreased the expression of TSPAN8 at both the mRNA and protein levels (P < 0.01). TSPAN8 overexpression in FFA-treated cells showed significantly lowered intracellular triglyceride levels (P < 0.001) and obviously reduced mRNA expression of fatty acid transport protein 5 (FATP5) (P < 0.01). The expression of FATP5 was significantly increased in FFA-treated cells as compared with the control cells (P < 0.001).@*CONCLUSION@#TSPAN8 is involved in lipid metabolism in NAFLD, and overexpression of TSPAN8 may inhibit cellular lipid deposition by reducing the expression of FATP5.


Subject(s)
Animals , Diet, High-Fat/adverse effects , Fatty Acids, Nonesterified , Lipid Metabolism , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism , RNA, Messenger/metabolism
5.
Article in English | WPRIM | ID: wpr-928963

ABSTRACT

OBJECTIVE@#To evaluate the effect of Shilajit, a medicine of Ayurveda, on the serum changes in cytokines and adipokines caused by non-alcoholic fatty liver disease (NAFLD).@*METHODS@#After establishing fatty liver models by feeding a high-fat diet (HFD) for 12 weeks, 35 Wistar male rats were randomly divided into 5 groups, including control (standard diet), Veh (HFD + vehicle), high-dose Shilajit [H-Sh, HFD + 250 mg/(kg·d) Shilajit], low-dose Shilajit [L-Sh, HFD + 150 mg/(kg·d) Shilajit], and pioglitazone [HFD + 10 mg/(kg·d) pioglitazone] groups, 7 rats in each group. After 2-week of gavage administration, serum levels of glucose, insulin, interleukin 1beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), adiponectin, and resistin were measured, and insulin resistance index (HOMA-IR) was calculated.@*RESULTS@#After NAFLD induction, the serum level of IL-10 significantly increased and serum IL-1β, TNF-α levels significantly decreased by injection of both doses of Shilajit and pioglitazone (P<0.05). Increases in serum glucose level and homeostasis model of HOMA-IR were reduced by L-Sh and H-Sh treatment in NAFLD rats (P<0.05). Both doses of Shilajit increased adiponectin and decreased serum resistin levels (P<0.05).@*CONCLUSION@#The probable protective role of Shilajit in NAFLD model rats may be via modulating the serum levels of IL-1β, TNF-α, IL-10, adipokine and resistin, and reducing of HOMA-IR.


Subject(s)
Adiponectin , Animals , Cytokines , Diet, High-Fat , Glucose , Insulin Resistance , Interleukin-10 , Liver , Male , Minerals , Non-alcoholic Fatty Liver Disease/pathology , Pioglitazone/therapeutic use , Rats , Rats, Wistar , Resins, Plant , Resistin/therapeutic use , Tumor Necrosis Factor-alpha
6.
Journal of Clinical Hepatology ; (12): 439-442, 2022.
Article in Chinese | WPRIM | ID: wpr-920908

ABSTRACT

Nonalcoholic fatty liver disease is a common chronic liver disease with the risk of progression to nonalcoholic hepatitis, liver fibrosis, and hepatocellular carcinoma. Nonalcoholic fatty liver disease has various pathogeneses, among which abnormal metabolism of branched-chain amino acids can induce oxidative stress, autophagy, and mitochondrial dysfunction in hepatocytes and is the most important mechanism in the development and progression of nonalcoholic fatty liver disease. This article reviews related research advances and analyzes the possible role of abnormal metabolism of branched-chain amino acids in the development and progression of nonalcoholic fatty liver disease, in order to improve clinical awareness and diagnosis.

7.
Journal of Preventive Medicine ; (12): 222-226, 2022.
Article in Chinese | WPRIM | ID: wpr-920756

ABSTRACT

Objective@#To investigate the perception about illness and identify its influencing factors among patients with non-alcoholic fatty liver disease ( NAFLD ) , so as to provide insights into the management of NAFLD patients. @*Methods@#NAFLD patients admitted to Hangzhou First People's Hospital Affiliated to Medical School of Zhejiang University from January to June, 2020, were selected as the study subjects, and subjects' demographic features were collected using questionnaires, including gender, age and education level. The perception about illness, coping models and social support were assessed using the Brief Illness Perception Questionnaire (BIPQ), Medical Coping Modes Questionnaire ( MCMQ ) and Social Support Rating Scale ( SSRS ), respectively, and factors affecting the perception about illness were identified using multivariable linear regression analysis among NAFLD patients.@*Results@#The 286 respondents included 151 males ( 52.80% ) and 135 females ( 47.20% ), and had a mean age of ( 55.27±10.39 ) years. The mean illness perception score was 38.55±9.21 among the respondents. The mean SSRS score was 42.90±8.64. The mean coping mode scores of confronce, avoidance and resignation were 23.51±4.30, 17.49±2.82, and 7.12±2.05, respectively. Multivariable linear regression analysis identified education level ( high school, β'=-0.216; diploma and above, β'=-0.355 ), household monthly income per capita ( β'=-0.372 ), regular exercise ( β'=-0.310 ), coping modes ( confronce, β'=-0.326; avoidance, β'=-0.191 ) and social support level ( β'=-0.259 ) as factors affecting the perception about illness among NAFLD patients.@*Conclusion@#Negative perceptions about illness are found among NAFLD patients, and household income, education level, regular exercise and coping modes are factors affecting the illness perception among NAFLD patients.

8.
Journal of Clinical Hepatology ; (12): 201-205, 2022.
Article in Chinese | WPRIM | ID: wpr-913143

ABSTRACT

The incidence rate of nonalcoholic fatty liver disease (NAFLD) is increasing year by year, with limited treatment methods, and its pathogenesis is a research hotspot at present. In order to better clarify its pathogenesis, it is urgent to develop advanced, safe, and effective in vitro or in vivo models to understand and develop treatment strategies for this disease. This article reviews the in vitro models commonly used in the preclinical study of NAFLD and discusses their advantages and disadvantages, so as to provide a theoretical basis for the pathogenesis and treatment of NAFLD.

9.
Journal of Clinical Hepatology ; (12): 196-200, 2022.
Article in Chinese | WPRIM | ID: wpr-913141

ABSTRACT

The incidence rate of nonalcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC) tends to increase worldwide, while its pathogenesis remains unclear. With reference to the literature in recent years, this article summarizes the role of adipose tissue inflammation, oxidative stress, gut microbiota, and insulin resistance in the pathogenesis of NAFLD-HCC and the advances in the prevention and treatment of the above mechanisms, so as to provide new ideas for the treatment of NAFLD-HCC.

10.
Journal of Clinical Hepatology ; (12): 129-134, 2022.
Article in Chinese | WPRIM | ID: wpr-913126

ABSTRACT

Objective To investigate the association of lipid accumulation product (LAP) and visceral fat index (VAI) with nonalcoholic fatty liver disease (NAFLD) and the value of LAP and VAI in predicting the risk of NAFLD. Methods A total of 708 subjects who underwent physical examination in China-Japan Friendship Hospital from September 2018 to May 2019 were enrolled and divided into NAFLD group ( n =426) and non-NAFLD group ( n =282), and the two groups were compared in terms of LAP, VAI, and related biochemical parameters. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups.The chi-square test was used for comparison of categorical data between groups. The Spearman test was used for correlation analysis. The subjects were divided into L1-L4 groups based on LAP and V1-V4 groups based on VAI, and the distribution of NAFLD was compared between groups; a logistic regression analysis was used to calculate the risk of NAFLD at different levels of LAP and VAI, and the receiver operating characteristic (ROC) curves were plotted for LAP, VAI, waist circumference (WC), and body mass index (BMI) in predicting NAFLD in different sex and body weight subgroups, so as to evaluate the value of each index in the prediction and diagnosis of NAFLD. Results Compared with the non-NAFLD group, the NAFLD group had significantly higher age, proportion of male subjects, proportion of subjects with a smoking history, and levels of LAP, VAI, WC, BMI, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, and serum uric acid, as well as a significantly lower level of high-density lipoprotein cholesterol (all P 0.7 in predicting the onset of NAFLD in different sex and body weight subgroups; the AUCs of LAP and VAI in the female subgroup were significantly higher than those in the male subgroup (LAP: 0.886 vs 0.785, P < 0.05; VAI: 0.824 vs 0.748, P < 0.05), and the corresponding sensitivities and specificities of LAP and VAI in the female subgroup were also higher than those in the male subgroup (sensitivity: LAP: 79.8% vs 63.7%; VAI: 77.9% vs 77.0%; specificity: LAP: 85.0% vs 81.1%; VAI: 77.6% vs 62.3%). Conclusion The risk of NAFLD increases with the increase in the levels of LAP and VAI. Both LAP and VAI have a good value in predicting NAFLD in different sex and body weight subgroups, especially in predicting NAFLD in the female population.

11.
Journal of Clinical Hepatology ; (12): 124-128, 2022.
Article in Chinese | WPRIM | ID: wpr-913125

ABSTRACT

Objective To investigate the association of ideal cardiovascular health metrics with the incidence rate of nonalcoholic fatty liver disease (NAFLD), and to provide a basis for the prevention and control of NAFLD. Methods A prospective cohort study was conducted for the data of 50 511 employees of Kailuan Group who participated in physical examination from July 2006 to June 2007, and the onset of NAFLD was observed during follow-up once every two years. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Kruskal-Wallis H test used for comparison of continuous data with skewed distribution between multiple groups; the chi-square test was used for comparison of categorical data between groups. The subjects were divided into four groups according to the quartile of cardiovascular health score (CHS), and person-year incidence rate was used to calculate the incidence rate of NAFLD in each group. Restricted cubic spline (RCS) curve was used to calculate the dose-response relation between continuous variables and outcome events; the Cox proportional hazards model was used to analyze hazard ratio ( HR ) and 95% confidence interval ( CI ) in each group and investigate the effect of ideal cardiovascular health metrics on the incidence rate of NAFLD. Results During the mean follow-up time of 5.58 years, a total of 15 265 cases of NAFLD were observed, and the incidence rate of NAFLD was 77.88/1000 person-year in the Q1 group, 61.33/1000 person-year in the Q2 group, 46.37/1000 person-year in the Q3 group, and 33.69/1000 person-year in the Q4 group. RCS results showed a non-linear relationship between CHS continuous variable and the risk of NAFLD ( P < 0.05). The multivariate Cox proportional risk model analysis showed that compared with the Q1 group in terms of the risk of NAFLD, the Q2, Q3, and Q4 groups had an HR of 0.78 (95% CI 0.74~0.81), 0.57 (95% CI 0.54~0.59), and 0.38 (95% CI 0.36~0.41), respectively, and similar results were observed in subjects stratified by sex and age. The analysis of each component showed that ideal body mass index ( HR =0.37, 95% CI : 0.36~0.39), ideal blood glucose ( HR =0.80, 95% CI : 0.77~0.84), ideal blood pressure ( HR =0.72, 95% CI : 0.69~0.75), ideal cholesterol ( HR =0.86, 95% CI : 0.83~0.89), and ideal diet ( HR =0.94, 95% CI : 0.90~0.99) were protective factors against NAFLD. Conclusion Ideal cardiovascular health metrics are protective factors against NAFLD, and maintaining a healthy lifestyle may help to prevent the onset of NAFLD.

12.
Chinese Journal of Hepatology ; (12): 81-86, 2022.
Article in Chinese | WPRIM | ID: wpr-935912

ABSTRACT

Objective: To evaluate the diagnostic value of transient elastography, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) for liver fibrosis in children with non-alcoholic fatty liver disease (NAFLD). Methods: A retrospective study was conducted on 100 cases of nonalcoholic fatty liver disease in Hunan Children's Hospital between August 2015 to October 2020 to collect liver tissue pathological and clinical data. The receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic value of liver stiffness measurement (LSM), APRI and FIB-4 in the diagnosis of different stages of liver fibrosis caused by NAFLD in children. Results: The area under the ROC curve (AUC) value of LSM, APRI and FIB-4 for diagnosing liver fibrosis (S≥1) were 0.701 [95% confidence interval (CI): 0.579 ~ 0.822, P = 0.011], 0.606 (95%CI: 0.436 ~ 0.775, P = 0.182), and 0.568 (95%CI: 0.397 ~ 0.740, P = 0.387), respectively. The best cut-off values were 6.65 kPa, 21.20, and 0.18, respectively. The AUCs value of LSM, APRI, and FIB-4 for diagnosing significant liver fibrosis (S≥ 2) were 0.660 (95% CI: 0.552 ~ 0.768, P = 0.006), 0.578 (95% CI: 0.464 ~ 0.691, P = 0.182) and 0.541 (95% CI: 0.427 ~ 0.655, P = 0.482), respectively. The best cut-off values were 7.35kpa, 24.78 and 0.22, respectively. The AUCs value of LSM, APRI and FIB-4 for the diagnosis of advanced liver fibrosis (S≥ 3) were 0.639 (95% CI: 0.446 ~ 0.832, P = 0.134), 0.613 (95% CI: 0.447 ~ 0.779, P = 0.223) and 0.587 (95% CI: 0.411 ~ 0.764, P = 0.346), respectively. The best cut-off values were 8.55kpa, 26.66 and 0.27, respectively. Conclusion: The transient elastography technique has a better diagnostic value than APRI and FIB-4 for liver fibrosis in children with NAFLD.


Subject(s)
Aspartate Aminotransferases , Biomarkers , Child , Elasticity Imaging Techniques , Humans , Liver/pathology , Liver Cirrhosis/pathology , Liver Function Tests , Non-alcoholic Fatty Liver Disease/pathology , ROC Curve , Retrospective Studies
13.
Chinese Journal of Hepatology ; (12): 52-56, 2022.
Article in Chinese | WPRIM | ID: wpr-935907

ABSTRACT

Objective: To explore the role of nonalcoholic fatty liver disease (NAFLD) in the development of hepatocellular carcinoma (HCC) in patients with prior hepatitis B virus infection (HBsAg-negative and anti-HBC-positive). Methods: 1605 hospitalized patients who were first diagnosed with HCC at Nanfang Hospital between 2015 to 2017 were retrospectively studied. Patients who developed HCC on the basis of active HBV infection (HBsAg-positive, anti-HBc positive) were used as control. Multivariate logistic regression model was used to analyze the relationship between NAFLD and HCC in patients with prior hepatitis B virus infection. Results: Among HCC patients with both HBsAg and anti-HCV negative, the proportion of prior HBV infection accounted for 86.7%. NAFLD prevalence was higher in patients with HCC based on prior HBV infection than active HBV infection (19.7% vs. 8.5%, P < 0.001). After adjusting for gender, age, hypertension, alanine aminotransferase, and liver cirrhosis, patients with HCC based on prior HBV infection were more likely to develop NAFLD (OR: 2.29, 95% CI: 1.40-3.74), and this phenomenon was observed only in patients with non-cirrhosis (OR: 5.26, 95% CI: 2.53-10.96) and aged≥50 years (OR: 2.36, 95% CI: 1.33-4.20). Conclusion: NAFLD may be a risk factor for HCC in a previously infected patients with HBV, especially in non-cirrhotic and population aged≥50 years.


Subject(s)
Carcinoma, Hepatocellular/epidemiology , Hepatitis B/epidemiology , Hepatitis B Surface Antigens , Hepatitis B virus , Humans , Liver Neoplasms/epidemiology , Middle Aged , Non-alcoholic Fatty Liver Disease/epidemiology , Retrospective Studies , Risk Factors
14.
Chinese Journal of Digestion ; (12): 73-82, 2022.
Article in Chinese | WPRIM | ID: wpr-934134

ABSTRACT

Objective:To investigate the function, mechanism and therapeutic potential of macrophages in non-alcoholic steatohepatitis (NASH).Methods:Eight-week-old male foz/ foz (Alms mutant) mice were fed with a high fat diet (HFD) for 6, 8 and 10 weeks and 8-week-old male C57BL/6 mice were fed with a methionine and choline-deficient (MCD) diet for 7 d, 3 weeks and 4 weeks to establish NASH models. The mice of control group were fed with normal diet or MCD control diet. The expression of F4/80 mRNA level in the livers of mice of NASH model group and control group was detected by fluorescence quantitative polymerase chain reaction. Macrophages in the livers of mice of NASH group and control group were determined by immunofluorescence staining. After transgenic lysM-Cre/DTR mice were fed with MCD diet for 5 weeks, they were divided into transgenic experimental group (ablation of macrophages induced by diphtheria-toxin (DTox) injection) and transgenic control group (phosphate buffer saline injection). The levels of triglyceride and lipid peroxide in the livers of transgenic experimental group and transgenic control group were detected, and the inflammation of the livers of the mice was scored. The mechanism of macrophages regulating inflammation in NASH was investigated by cytokine profiliny analysis and Western blotting. The interaction between hepatocytes and macrophages were determined by co-culturing the conditional medium of hepatocytes AML-12 and macrophages RAW264.7. Macrophages of mice of control group and NASH model group were depleted by liposomal clodronate to confirm its value in NASH prevention. Independent sample t-test was used for statistical analysis. Results:F4/80 mRNA level in the livers of NASH model foz/ foz mice fed with HFD for 6 weeks, 8 weeks and 10 weeks was higher than that of control group (1.49±0.19, 1.70±0.15 and 1.93±0.04 vs.1.05±0.22), and the differences were statistically significant ( t=3.06, 4.92 and 7.92, all P<0.05). The expression of F4/80 mRNA level of the livers of NASH model mice fed with MCD for 7 d and 3 weeks was higher than that of control group (2.70±0.99 and 3.08±1.71 vs.1.00±0.83), and the differences were statistically significant ( t=3.43 and 3.54, both P<0.01). The results of immunofluorescence demonstrated that compared with that of control group, the number of F4/80 + inducible nitric oxide synthase (iNOS) + M1 macrophages were significantly increased, while F4/80 + CD206 + M2 macrophages were significantly decreased in the livers of NASH model mice fed with MCD for 4 weeks. After macrophages depletion, the inflammation score, the levels of triglyceride and lipid peroxide in the liver of transgenic experimental mice were all lower than those of transgenic control mice (0.69±0.32 vs. 1.95±0.74, (43.97±13.24) g/mg vs. (63.09±14.85) g/mg, (24.84±6.21) nmol/mg vs.(37.91±8.91) nmol/mg), and the differences were statistically significant ( t =3.14, 2.72 and 2.41, all P<0.05). The results of cytokine profiling analysis showed that macrophage depletion could lower the levels of interleukin (IL)-12 and macrophages inflammatory protein-1α (the difference between multiples: -3.98, -2.74, both P<0.05). CCAAT/enhancer binding protein β was defected in the nuclear of transgenetic experimental mice. In vitro study showed that RAW264.7 macrophages conditional medium could promote lipid accumulation in AML-12 hepatocytes, while conditional medium from MCD medium-treated AML-12 hepatocytes could promote RAW264.7 macrophages to M1 polarization. After treated with liposomal clodronate, the levels of triglyceride and lipid peroxidation in the liver of control mice were both lower than those of MCD-induced NASH model mice((45.33±14.59) g/mg vs. (63.10±16.02) g/mg, (2.11±0.48) nmol/mg vs. (2.73±0.17) nmol/mg), and the differences were statistically significant ( t=2.84 and 2.73, both P<0.05). The results of Western blotting indicated that after treating with liposomal clodronate, the relative content of phosphorylated protein kinase R-like endoplasmic reticulum kinase, inositol requiring enzyme-1α, protein disulfide isomerase, glucose regulatory protein 78, phosphorylated eukaryotic initiation factor 2α in the liver of NASH model mice were all lower than those of NASH model mice without liposomal clodronate treatment (1.84±0.36 vs. 3.05±0.83, 1.50±0.84 vs. 6.65±1.47, 0.87±0.12 vs. 2.28±0.52, 1.68±0.43 vs. 4.76±1.13, 1.42±0.19 vs. 2.75±0.79), and the differences were statistically significant( t=2.32, 5.28, 4.56, 4.41 and 2.85, all P<0.05). Conclusions:Macrophages are polarized into M1 phenotype in NASH. M1 macrophages contributed to NASH progression by interacting with hepatocyets to promote the secretion of inflammatory cytokines, up-regulation of lipogenic factors, oxidative stress and endoplasmic reticulum stress, resulting in the progression of NASH. Macrophages depletion by liposomal clodronate is a potential noval approach for NASH prevention.

15.
Article in Chinese | WPRIM | ID: wpr-933724

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is a liver disorder related to metabolic syndrome, which is considered to be associated with risk of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). It has been reported that NAFLD may serve as an independent predictive factor for BPH and International Prostate Symptom Score (IPSS). In addition, NAFLD may also contribute to identify the high risk population of PCa, and to predict biochemical recurrence and progression of PCa. The roles of NAFLD in BPH and PCa may be related to insulin resistance and metabolic abnormality that cause aberrant and malignant proliferation in the prostatic gland. Besides, chronic systemic inflammation and Toll-like receptor-associated immunization may also involve in the development of NAFLD-mediated BPH. This article reviews the current research evidence on the role of NAFLD in the development of BPH and PCa, indicating that early intervention of NAFLD may alleviate the progression of BPH and PCa.

16.
Article in Chinese | WPRIM | ID: wpr-933396

ABSTRACT

Objective:To investigate effect and underlying lipid-lowering mechanisms of catalpol in non-alcoholic fatty liver disease(NAFLD).Methods:In vivo model of NAFLD was established with high-fat diet-fed ICR mice for 8 weeks. Low(50 mg/kg), medium(150 mg/kg), and high(300 mg/kg) doses of catalpol were administered, and the body weight, liver weight, hepatic index, and biochemical parameters of the mice were analyzed. Free fatty acid-induced LO2 in human hepatocytes to establish NAFLD cell model. Quantitative realtime PCR reaction to detect fatty acid synthesis-related gene levels. Western blotting assay was adopted to analyze proteins in the endoplasmic reticulum stress(ERS)-mediated protein kinase RNA-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α) signaling pathway. Results:Compared with model mice, body weight [(39.43±1.84)g, (34.01±1.83)g, (32.28±1.11)g vs(42.17±1.37)g, all P<0.001], liver weight [(1.03±0.06)g, (0.79±0.05)g, (0.64±0.04)g vs(1.30±0.13)g, P<0.01 or P<0.001], and liver index [(2.60±0.09)%, (2.32±0.09)%, (1.99±0.11)% vs(3.07±0.30)%, P<0.05 or P<0.001] were reduced in low, medium, and high doses of catapol model. Medium and high doses of catalpol diminished total cholesterol, triglyceride, low density lipoprotein-cholesterol, aspartate aminotransferase, and alanine aminotransferase( P<0.01 or P<0.001), increased high density lipoprotein-cholesterol( P<0.01 or P<0.001). In the cell model, elevated levels of both fatty acid synthesis genes and PERK-eIF2α pathway proteins were attenuated by catalase, and this attenuation was reversed by signaling pathway agonists. Conclusion:The Chinese herb catalpol may play a role in improving NALFD by regulating the ERS-mediated PERK-eIF2α signaling pathway.

17.
Article in Chinese | WPRIM | ID: wpr-933395

ABSTRACT

Objective:To evaluate the effects of berberine on necroptosis of non-alcoholic fatty liver disease in mice and its relationship with adenosine monophosphate-activated protein kinase(AMPK)/ signal transducer and activator of transcription 6(STAT6) pathway.Methods:Twenty-five 8-week-old male C57BL/6N mice were divided into control group, steatotic liver group, berberine treatment group(200 mg·kg -1·d -1), AMPK inhibitor Compound C treatment group(0.2 mg·kg -1·d -1), and STAT6 inhibitor AS1517499 treatment group(10 mg·kg -1·d -1). After 12 weeks of intervention, the mice and liver tissue were weighed, and serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) as well as liver malondialdehyde and superoxide dismutase were measured; liver tissue HE, Masson, and oil red O staining were performed. Western blotting was used to detect the expressions of necroptosis related proteins[receptor interaction protein kinase 3(RIPK3), phosphorylated(p-) mixed lineage kinase domain-like(MLKL)], AMPK, p-AMPK, and p-STAT6. Results:Compared with control group, the steatotic liver group had higher quality of liver and liver index, and higher levels of serum AST, ALT, triglyceride, TNF-α, IL-1β, and oxidative stress( P<0.05); Liver tissue was full of cavity changes and inflammatory cell infiltration, widely distributed red lipid droplets and obvious blue fiber dyeing; The expressions of RIPK3 and p-MLKL were up-regulated ( P<0.05), but the levels of p-AMPK and p-STAT6 were relatively reduced ( P<0.05). Compared with the steatotic liver group, berberine intervention decreased liver quality and liver index, improved liver function, reduced blood lipid levels, pro-inflammatory factor expression and oxidative stress level, and significantly alleviated the degree of liver steatosis and fibrosis, the levels of RIPK3 and p-MLKL ( P<0.05), while the expressions of p-AMPK and p-STAT6 were increased significantly ( P<0.05). As compared with the berberine treatment, AMPK and STAT6 inhibitor treatment could offset the protective effect of berberine on steatotic liver, moreover, the expressions of RIPK3 and p-MLKL were increased ( P<0.05). There was no statistical difference in AMPK total protein content among the five groups ( P>0.05). Conclusion:Berberine can activate AMPK/STAT6 pathway to inhibit the necroptosis of hepatocyte, thus plays a protective role on non-alcoholic fatty liver disease in mice.

18.
Article in Chinese | WPRIM | ID: wpr-933333

ABSTRACT

Objective:To evaluate the effect of melatonin preconditioning on hepatic ischemia-reperfusion (I/R) injury in rats with non-alcoholic fatty liver disease (NAFLD).Methods:Forty-eight SPF male Sprague-Dawley rats, aged 10-12 weeks, weighing 200-230 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (Con group), NAFLD group, NAFLD + hepatic I/R group (NAFLD+ HIR group), and NAFLD + hepatic I/R + melatonin treatment group (NAFLD+ HIR+ MT group). The NAFLD model was developed by a high-fat and high-glucose diet (10% glucose, 10% fat) for 8 consecutive weeks in NAFLD, NAFLD+ HIR and NAFLD+ HIR+ M groups, and rats were fed with common chow and freely drank water in the other groups.Melatonin 10 mg/kg was given intragastrically daily for 2 consecutive weeks before developing the model in group NAFLD+ HIR+ MT.The model of liver I/R injury was developed by clipping the hepatic artery and portal vein for 20 min, opening for 5 min, and re-clamping for 20 min followed by restoration of perfusion.Blood samples from inferior vena cava were collected and liver tissues were obtained at 6 h of reperfusion to detect serum levels of insulin, blood glucose, free fatty acid (FFA), triglyceride (TG), alanine aminotransferase (ALT), aspartate amino transferase (AST) and ferritin, and insulin resistance index was calculated.The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reactive oxygen species (ROS) and Fe 2+ in liver tissues were detected by enzyme-linked immunosorbent assay, the pathological changes of liver tissues were examined with a light microscope after hematoxylin-eosin staining.The expression of nuclear factor E2-related factor 2 (Nrf2), lysophosphatidylcholine acyltransferase 3 (LPCAT3), long-chain fatty acyl-CoA synthase 4 (ACSL4) and glutathione peptide peroxidase 4 (GPX4) was detected by Western blot. Results:Compared with Con group, the levels of serum FFA, TG, ALT, AST and ferritin and insulin resistance index were significantly increased, the levels of ROS and Fe 2+ in liver tissues were increased, the levels of GSH-Px and SOD were decreased, the expression of ACSL4 and LPCAT3 was up-regulated, and the expression of Nrf2 and GPX4 was down-regulated in NAFLD group ( P<0.05). Compared with NAFLD group, the serum levels of FFA, TG, ALT, AST and ferritin and insulin resistance index were significantly increased, the levels of ROS and Fe 2+ were decreased, the levels of GSH-Px and SOD were increased, the expression of ACSL4 and LPCAT3 was up-regulated, and the expression of Nrf2 and GPX4 was down-regulated in NAFLD+ HIR group ( P<0.05). Compared with NAFLD+ HIR group, the serum levels of FFA, TG, ALT, AST and ferritin and insulin resistance index were significantly increased, the levels of ROS and Fe 2+ were decreased, the levels of GSH-Px and SOD were increased, the expression of ACSL4 and LPCAT3 was down-regulated, and the expression of Nrf2 and GPX4 was up-regulated in NAFLD+ HIR+ MT group ( P<0.05). Conclusions:Melatonin preconditioning can alleviate hepatic I/R injury in rats with NAFLD, and the mechanism may be related to activation of Nrf2 signaling pathway, reduction of lipid peroxidation and inhibition of ferroptosis.

19.
Article in Chinese | WPRIM | ID: wpr-932950

ABSTRACT

Objective:To investigate the possible role of non-invasive fibrosis scoring systems for detecting high-risk plaque among patients with non-alcoholic fatty liver disease (NAFLD).Methods:A total of 477 consecutive asymptomatic subjects underwent a health checkup including coronary computed tomography angiography (CTA) and abdominal ultrasonography. Fatty liver was evaluated using ultrasonography, and the NAFLD fibrosis score (NFS) was calculated. Coronary stenosis and plaque were evaluated using coronary CTA.Results:Of the study population, 223 had NAFLD. Among the NAFLD patients, high-risk coronary plaque was more frequent in patients with high or intermediate NFS than those with low NFS (62.5% versus 24.0%, P<0.001). The adjusted odds ratio with 95% confidence interval of high-risk plaque was 3.24 (1.11-9.40) for the highest versus lowest quartile of NFS ( P=0.016). Among those without NAFLD, NFS was not associated with high-risk coronary plaque (C-statistic with NFS versus without NFS, 0.766 versus 0.764, P=0.715). Adding NFS to the traditional cardiovascular disease (CVD) risk model increased the C-statistics by 0.679 to 0.739 ( P=0.031). Conclusions:There was an independent association of NFS with high-risk coronary plaque in patients with NAFLD, suggesting its potential use to optimize management of patients with NAFLD.

20.
Journal of Chinese Physician ; (12): 90-95, 2022.
Article in Chinese | WPRIM | ID: wpr-932032

ABSTRACT

Objective:To study the protective effect and possible mechanism of psoralen corylifolia on non-alcoholic steatohepatitis (NASH) induced by high-fat diet in mice.Methods:The newly weaned female mice in the offspring of C57BL/6J mice fed with normal diet were selected as the control group (gavage of distilled water); the newly weaned female mice in the offspring of C57BL/6J mice fed with high-fat diet were randomly divided into model group (gavage distilled water), low-dose group[psoralen corylifolia 1.125 mg/(g·d)], high-dose group [psoralen corylifolia 2.25 mg/(g·d)] and vitamin E group [vitamin E 0.01 mg/(g·d)]. Six mice in each group were fed continuously for 8 weeks. Automatic biochemical analyzer was used to detect serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), total cholesterol (TC) level in mice; The liver tissue pathological changes were observed by hematoxylin-eosin (HE) and Sirius-red (SR) staining; The level of reactive oxygen species (ROS) in liver tissue was detected by dihydroethidium (DHE) fluorescence probe; the activity of NADPH oxidase was detected by kit; The protein expressions of nuclear factor-κB (NF-κB), phosphatidylinositol 3 kinase (PI3K p85), protein kinase B (Akt), P47 phox and protein kinase C-α (PKC-α) were detected by Western blot.Western blot. Results:The levels of serum ALT, AST, TG, TC and homeostasis model assessment of insulin resistance (HOMA-IR) index in the model group were higher than those in the control group (all P<0.01). After treatment, the levels of serum ALT, AST, TG, TC and HOMA-IR in low-dose group, high- dose group and vitamin E group were lower than those in model group (all P<0.05). HE and SR staining showed that hepatocytes in the model group were swollen, and there were lipid droplets of different sizes, vacuoles and obvious fibrosis. After treatment, hepatocyte steatosis and fibrosis decreased and the contents of ROS and NADPH oxidase in liver decreased(all P<0.05); Western blot showed that the p-p65/p65, p-Akt/Akt, p-PKC-α/PKC-α, PI3K, p85 and P47 phox protein expression in the model group were higher than those in the control group (all P<0.01). After treatment, the protein expression levels of p-p65/p65, p-Akt/Akt, p-PKC-α/PKC-α, PI3K, p85 and P47 phox decreased (all P<0.01). Among the above indexes, the protective effect of high-dose group on liver NASH was better than those of vitamin E group and low-dose group (all P<0.05). Conclusions:Psoralen corylifolia can improve the liver function of NASH model mice, which may be related to the inhibition of oxidative stress, inflammatory reaction and liver fibrosis, which provides a new idea for the prevention and treatment of children with NASH.

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