Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
1.
Hepatobiliary Pancreat Dis Int ; 20(5): 426-432, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34246549

RESUMO

BACKGROUND: This study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD). METHODS: This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance. RESULTS: Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037-8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388-4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772-9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398-6.210; P = 0.004) after the adjustments of the BMI and diabetes. CONCLUSIONS: Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.

2.
Front Immunol ; 12: 688910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177945

RESUMO

Lactate is an end product of glycolysis. As a critical energy source for mitochondrial respiration, lactate also acts as a precursor of gluconeogenesis and a signaling molecule. We briefly summarize emerging concepts regarding lactate metabolism, such as the lactate shuttle, lactate homeostasis, and lactate-microenvironment interaction. Accumulating evidence indicates that lactate-mediated reprogramming of immune cells and enhancement of cellular plasticity contribute to establishing disease-specific immunity status. However, the mechanisms by which changes in lactate states influence the establishment of diverse functional adaptive states are largely uncharacterized. Posttranslational histone modifications create a code that functions as a key sensor of metabolism and are responsible for transducing metabolic changes into stable gene expression patterns. In this review, we describe the recent advances in a novel lactate-induced histone modification, histone lysine lactylation. These observations support the idea that epigenetic reprogramming-linked lactate input is related to disease state outputs, such as cancer progression and drug resistance.

3.
Health Qual Life Outcomes ; 19(1): 140, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962617

RESUMO

BACKGROUND: Health Related Quality of Life (HRQL) is a multi-dimensional construct that can comprehensively evaluate the patient's health status, including physical, emotional, mental and social well-being. In this study, we aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on HRQL in a Chinese population. METHODS: In this national multicenter cross-sectional survey, patients with NAFLD were enrolled. Chronic Liver Disease Questionnaire (CLDQ)-NAFLD was used to qualify HRQL. Univariate and multivariate analysis were used to identify independent risk factors of HRQL. RESULTS: A total of 5181 patients with NAFLD from 90 centers were enrolled in this study (mean age, 43.8 ± 13.3 years; male, 65.8%). The overall CLDQ score was 5.66 ± 0.89. Multivariate logistic regression analysis showed that body mass index (BMI: HR, 1.642; 95% CI, 1.330-2.026), alanine transaminase (ALT: HR, 1.006; 95% CI, 1.001-1.011), triglyceride (HR, 1.184; 95% CI, 1.074-1.305), disease severity (HR, 3.203; 95% CI, 1.418-7.232) and cardiovascular disease (HR, 4.305; 95% CI, 2.074-8.939) were independent risk factors for overall CLDQ score. In the logistic analyses of individual domain, BMI and triglyceride were independent risk factors of all domains. ALT, disease severity, diabetes, depression and cardiovascular disease were influencing factors for the CLDQ score of several domains. CONCLUSIONS: This national multicenter cross-sectional survey in China indicated that the HRQL in patients with NAFLD was impaired. HRQL was found to be significantly associated with sociodemographic and clinical factors. Attention should be paid to the optimally managing care of patients with NAFLD to improve their HRQL.


Assuntos
Grupo com Ancestrais do Continente Asiático/psicologia , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Nível de Saúde , Hepatopatia Gordurosa não Alcoólica/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários/normas , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
4.
Clin Transl Gastroenterol ; 12(4): e00323, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33848277

RESUMO

INTRODUCTION: To evaluate the diagnostic performance of ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) by FibroTouch for diagnosis of hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We recruited 237 patients undergoing FibroTouch and liver biopsy within 2 weeks. The pathological findings of liver biopsy were scored by Nonalcoholic Steatohepatitis Clinical Research Network, and the diagnostic accuracy of UAP for steatosis and LSM for fibrosis was evaluated by area under the receiver operating characteristic curve (AUROC). The impacts of histological parameters on UAP and LSM were analyzed, and diagnostic performance of FibroTouch UAP and LSM was compared with other noninvasive biomarkers. RESULTS: The success rate of FibroTouch examination was 96.51%. The AUROC of UAP for diagnosis of steatosis ≥S1, ≥S2, and S3 was 0.88, 0.93, and 0.88, and the cutoff values were 244, 269, and 296 dB/m, respectively. The AUROC of LSM for the diagnosis of fibrosis stages ≥F2, ≥F3, and F4 was 0.71, 0.71, and 0.77, and the cutoff values were 9.4, 9.4, and 11 kPa, respectively. Multiple regression analysis showed that LSM was positively correlated with degree of fibrosis and NAFLD activity score. UAP was positively correlated with liver steatosis. The diagnostic performance of UAP for steatosis was significantly superior to that of the hepatic steatosis index. DISCUSSION: FibroTouch has a low failure rate with moderate to high diagnostic performance for discriminating the steatosis degree and fibrosis stage and is suitable for clinical evaluation and monitoring of patients with NAFLD.


Assuntos
Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Ultrassonografia/métodos , Adulto , Área Sob a Curva , Biomarcadores , Biópsia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Biomed Res Int ; 2019: 6272174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467903

RESUMO

Objective: The spectrum of UDP-glucuronyl transferase A1 (UGT1A1) variants in hereditary unconjugated hyperbilirubinemia varies markedly between different ethnic populations. This study evaluated the UGT1A1 genotypes in hyperbilirubinemia patients from southeastern China. Methods: We enrolled 60 patients from southeastern China (44 men and 16 women; age range: 3-76 years) with unconjugated hyperbilirubinemia and performed genetic analysis of the UGT1A1 gene by direct sequencing. Results: For patients with Gilbert syndrome, 85% (47/55) harbored pathogenic variants of UGT1A1⁎60. Both UGT1A1⁎28 and UGT1A1⁎81 were detected in the promoter region of UGT1A1. Additionally, 83% (20/24) of patients with Gilbert syndrome heterozygous for UGT1A1⁎60 had an association with heterozygous variation of UGT1A1⁎28 or UGT1A1⁎81, while 91% (21/23) of Gilbert syndrome patients homozygous for UGT1A1⁎60 had biallelic variations of UGT1A1⁎28 and UGT1A1⁎81. We detected 213 UGT1A1 allelic variants, including six novel variations, with the most frequent allele being the UGT1A1⁎60, followed by UGT1A1⁎28 and UGT1A1⁎6. All of the patients showed multiple sites of variants in UGT1A1; however, variation number was not associated with bilirubin levels (P>0.05). Conclusions: The spectrum of UGT1A1 variants in southeastern Chinese patients was distinct from other ethnic populations. Our findings broaden the knowledge concerning traits associated with UGT1A1 variants and help profile genotype-phenotype correlations in hyperbilirubinemia patients.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Glucuronosiltransferase/genética , Hiperbilirrubinemia/genética , Adolescente , Adulto , Idoso , Alelos , Bilirrubina/genética , Bilirrubina/metabolismo , Criança , Pré-Escolar , China , Feminino , Frequência do Gene , Genética Populacional , Genótipo , Humanos , Hiperbilirrubinemia/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Adulto Jovem
7.
Ann Anat ; 226: 48-56, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31330310

RESUMO

Zebrafish lateral line neuromasts are composed of central hair cells surrounded by supporting cells. Cisplatin is a common anticancer drug, with hair cell disruption being a frequent side effect of this drug. In our study, we observed complete functional hair cell loss after six hours of cisplatin insult in neuromasts, as demonstrated by anti-parvalbumin 3 immunofluorescence staining or YO-PRO1 vital dye staining. Time course analysis of neuromast hair cell regeneration showed that regenerated hair cells first appeared between 12 and 24h after damage, and the abundance of these cells increased stepwise with recovery time. After 72h, 90% of the hair cells were regenerated, and after 84h, the number of regenerated hair cells was comparable to the number of neuromast hair cells before treatment. The expression pattern of slc17a8 also showed that hair cells were regenerated after cisplatin exposure. Meanwhile, peripheral supporting cells moved toward the center of the neuromasts, as shown by the in situ expression pattern of sox21a. Increased hair cell progenitor formation was also observed, as demonstrated by the in situ expression pattern of atoh1a. Furthermore, we detected increased expression of wnt2, wnt3a, and ctnnb1 in sorted supporting cells from the sqet10 transgenic line, which labels neuromast supporting cells specifically. In situ hybridization analysis also showed decreased expression of dkk1a and dkk2. Regenerated hair cells were inhibited by early inhibition of Wnt/ß-catenin signaling. Taken together, the results presented here showed that Wnt/ß-catenin signaling was activated in supporting cells during cisplatin exposure earlier than expected. Our results also indicated that supporting cells enabled hair cell regeneration via Wnt/ß-catenin signaling during cisplatin exposure.


Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Sistema da Linha Lateral/citologia , Sistema da Linha Lateral/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Morte Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Via de Sinalização Wnt/genética , Peixe-Zebra , beta Catenina/efeitos dos fármacos , beta Catenina/genética
9.
J Transl Med ; 16(1): 166, 2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29914513

RESUMO

BACKGROUND: A model was constructed using clinical and serum variables to discriminate between chronic hepatitis B (CHB) patients with and without significant necroinflammatory activity (score 4-18 vs. score 0-3). METHODS: Consecutive CHB patients who underwent liver biopsy were divided into two sequential groups: a training group (n = 401) and a validation group (n = 401). Multivariate analysis identified alanine aminotransferase, γ-glutamyltransferase, prothrombin time and albumin as independent predictors of necroinflammatory activity. RESULTS: The area under the receiver operating characteristic curve was 0.826 for the training group and 0.847 for the validation group. Using a cut-off score of H ≤ 0.375, significant necroinflammatory activity (score 4-18) was excluded with high accuracy [78.2% negative predictive value (NPV), 72% positive predictive value (PPV), and 90.8% sensitivity] in 238 (59.4%) of 401 patients in the training group and with the same certainty (88.1% NPV, 61.2% PPV, and 95.1% sensitivity) among 204 (50.9%) of 401 patients in the validation group. Similarly, applying a cut-off score of H > 0.720, significant necroinflammatory activity was correctly identified with high accuracy (90.8% PPV, 57.7% NPV, and 92.0% specificity) in 150 (37.4%) of 401 patients in the training group and with the same certainty (91.8% PPV, 64.6% NPV, and 95.4% specificity) in 188 (46.9%) of 401 patients in the validation group. CONCLUSIONS: A predictive model based on easily accessible variables identified CHB patients with and without significant necroinflammatory activity with a high degree of accuracy. This model may decrease the need for liver biopsy for necroinflammatory activity grading in 72.1% of CHB patients.


Assuntos
Hepatite B Crônica/patologia , Inflamação/patologia , Fígado/patologia , Modelos Biológicos , Adulto , Biópsia , Estudos de Coortes , Feminino , Hepatite B Crônica/diagnóstico , Humanos , Modelos Logísticos , Masculino , Curva ROC , Reprodutibilidade dos Testes
10.
Exp Ther Med ; 14(5): 4134-4140, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29075339

RESUMO

The aim of the present study was to explore the protective effects of Berberine (BBR) against non-alcoholic steatohepatitis (NASH). Male 4-week-old C57BL/6J Apolipoprotein E-deficient (ApoE-/-) mice were divided into the following three groups, which were given different diets: Normal chow diet (SC group); high-fat high-cholesterol diet (HFHC group); and HFHC diet supplemented with BBR (BBR group). Serum biochemical indicators of hepatic function and histological liver tissue changes were evaluated. The expression of neutrophil elastase (NE) and genes involved in the inflammatory response was measured. ApoE-/- mice fed a HFHC diet for 12 weeks developed NASH, characterized by steatosis and liver inflammation. Body weight, and serum triglyceride and cholesterol levels were markedly reduced by BBR. BBR supplementation significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels in mice with HFHC diet-induced NASH, and significantly downregulated hepatic expression and activity of NE, whereas α1-antitrypsin (α1-AT) expression was significantly recovered by BBR (all P<0.05 vs. the HFHC group). Furthermore, treatment with BBR induced a significant reduction in the expression of key genes, including phospoinositide 3-kinase, nuclear factor-κB and interleukin-8, in the C-X-C chemokine receptor type 4 (CXCR4) signaling pathway (all P<0.05 vs. the HFHC group). These results suggest that BBR alleviates NASH in ApoE-/- mice fed a HFHC diet. Restoration of the balance of NE and α1-AT levels, which in turn facilitate the inhibition of the CXCR4 signaling pathways, may be involved in the hepatoprotective effect of BBR. These results indicate that BBR may be a candidate therapeutic agent for the treatment of NASH.

11.
Diagn Pathol ; 12(1): 61, 2017 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-28814334

RESUMO

BACKGROUND: Abernethy malformation is a rare congenital anomaly characterised by the partial or complete absence of the portal vein and the subsequent development of an extrahepatic portosystemic shunt. Caroli's disease is a rare congenital condition characterised by non-obstructive saccular intrahepatic bile duct dilation. Caroli's disease combined with congenital hepatic fibrosis and/or renal cystic disease is referred to - Caroli's syndrome. The combination of Abernethy malformation and Caroli's syndrome has not been reported previously. CASE PRESENTATION: We present the case of a 23-year-old female who was found to have both type II Abernethy malformation and Caroli's syndrome. Radiological imaging was performed, including computed tomography with three-dimensional reconstruction and magnetic resonance imaging with (magnetic resonance cholangiopancreatography (MRCP), which revealed a side-to-side portocaval shunt, intrahepatic bile duct dilation, congenital hepatic fibrosis, and renal cysts. In addition, PKHD1 (polycystic kidney and hepatic disease 1) gene mutational analysis revealed a paternally inherited heterozygous missense mutation (c.1877A > G, p.Lys626Arg). A liver biopsy confirmed the pathological features of Caroli's syndrome. CONCLUSIONS: To our knowledge, this is the first reported case of a patient with both type II Abernethy malformation and Caroli's syndrome diagnosed using a comprehensive approach that included imaging, mutational analysis, and liver biopsy. Additionally, this is the second reported case to date of an Asian patient presenting with liver and renal disorders with the same paternally inherited PKHD1 missense mutation.


Assuntos
Doença de Caroli/complicações , Doença de Caroli/genética , Veia Porta/anormalidades , Receptores de Superfície Celular/genética , Malformações Vasculares/complicações , Malformações Vasculares/genética , Feminino , Humanos , Mutação , Adulto Jovem
12.
Sci Rep ; 7(1): 4748, 2017 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-28684781

RESUMO

Based on the severity of liver fibrosis, low or high-risk profile of developing end-stage liver disease was present in nonalcoholic fatty liver disease (NAFLD). However, the mechanisms inducing transition from mild to advanced NAFLD are still elusive. We performed a system-level study on fibrosing-NAFLD by weighted gene co-expression network analysis (WGCNA) to identify significant modules in the network, and followed by functional and pathway enrichment analyses. Moreover, hub genes in the module were analyzed by network feature selection. As a result, fourteen distinct gene modules were identified, and seven modules showed significant associations with the status of NAFLD. Module preservation analysis confirmed that these modules can also be found in diverse independent datasets. After network feature analysis, the magenta module demonstrated a remarkably correlation with NAFLD fibrosis. The top hub genes with high connectivity or gene significance in the module were ultimately determined, including LUM, THBS2, FBN1 and EFEMP1. These genes were further verified in clinical samples. Finally, the potential regulators of magenta module were characterized. These findings highlighted a module and affiliated genes as playing important roles in the regulation of fibrosis in NAFLD, which may point to potential targets for therapeutic interventions.


Assuntos
Redes Reguladoras de Genes , Cirrose Hepática/genética , Hepatopatia Gordurosa não Alcoólica/genética , Transcriptoma , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Biomarcadores/metabolismo , Biologia Computacional , Conjuntos de Dados como Assunto , Progressão da Doença , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Fibrilina-1/genética , Fibrilina-1/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Lumicana/genética , Lumicana/metabolismo , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Trombospondinas/genética , Trombospondinas/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-28740538

RESUMO

The aim of this study was to explore the potential beneficial effects of linarin enriched Flos Chrysanthemi extract (Lin-extract) on nonalcoholic steatohepatitis (NASH) induced by high-fat high-cholesterol (HFHC) diet in rats. SD rats received normal diet, HFHC diet, or HFHC diet plus different doses of Lin-extract. The liver content of triglyceride and total cholesterol markedly increased in HFHC diet-fed model rats while middle and high dose of Lin-extract lowered liver cholesterol significantly. The expression of stearoyl-CoA desaturase (SCD1) was upregulated by HFHC diet and further elevated by high dose Lin-extract. High dose of Lin-extract also markedly lowered the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and inhibited the activation of c-Jun N-terminal kinase (JNK) induced by HFHC in livers. The HFHC-increased mRNA levels of hepatic inflammation cytokines, including monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and chemokine (C-X-C motif) ligand 1 (CXCL1), were suppressed by Lin-extract dose-dependently. Furthermore, pathology evaluation showed that high dose Lin-extract greatly improved lobular inflammation. Our results suggest that Lin-extract could attenuate liver injury and inflammation induced by HFHC diet in rats. Its modulatory effect on lipid metabolism may partially contribute to this protective effect.

14.
Cell Physiol Biochem ; 41(1): 239-251, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28214827

RESUMO

BACKGROUND AND AIM: The incidence of nonalcoholic fatty liver disease (NAFLD), ranging from mild steatosis to hepatocellular injury and inflammation, increases with the rise of obesity. However, the implications of transcription factors network in progressive NAFLD remain to be determined. METHODS: A co-regulatory network approach by combining gene expression and transcription influence was utilized to dissect transcriptional regulators in different NAFLD stages. In vivo, mice models of NAFLD were used to investigate whether dysregulated expression be undertaken by transcriptional regulators. RESULTS: Through constructing a large-scale co-regulatory network, sample-specific regulator activity was estimated. The combinations of active regulators that drive the progression of NAFLD were identified. Next, top regulators in each stage of NAFLD were determined, and the results were validated using the different experiments and bariatric surgical samples. In particular, Adipocyte enhancer-binding protein 1 (AEBP1) showed increased transcription activity in nonalcoholic steatohepatitis (NASH). Further characterization of the AEBP1 related transcription program defined its co-regulators, targeted genes, and functional organization. The dynamics of AEBP1 and its potential targets were verified in an animal model of NAFLD. CONCLUSIONS: This study identifies putative functions for several transcription factors in the pathogenesis of NAFLD and may thus point to potential targets for therapeutic interventions.


Assuntos
Hepatopatia Gordurosa não Alcoólica/patologia , Adulto , Idoso , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Carboxipeptidases/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Redes Reguladoras de Genes , Humanos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Repressoras/metabolismo , Índice de Gravidade de Doença , Transcriptoma
15.
Adv Ther ; 33(11): 2069-2081, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27743352

RESUMO

INTRODUCTION: Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD) that can progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Differentiating between non-alcoholic fatty liver (NAFL) and NASH/advanced fibrosis is an important step in the management of NAFLD. Metabolic syndrome (MS) and its components are important risk factors for NAFLD, and NASH is thought to be the hepatic injury of MS. The prevalence of NASH among NAFLD patients with MS is thought to be high. In China, NAFLD is a relatively new public health concern, and the current prevalence of NASH among Chinese liver biopsy-proven NAFLD patients with and without MS is not known. METHODS: This multicenter, cross-sectional study will investigate the prevalence of NASH in approximately 480 Chinese NAFLD patients. Patients will be eligible for enrollment if they have biopsy-proven NAFLD and if their liver biopsies are available for rereading. For our analysis, patients will be stratified according to the presence/absence of MS, and the prevalence of NASH in the subgroups will be compared. Other possible tests that could indicate a risk of NASH, including transient elastography, ultrasonography, cytokeratin-18, liver function tests, and others, will be studied in an effort to derive a practical, noninvasive predictive model for NASH. DISCUSSION: Patients with NAFL who have MS may also have a very high risk of developing NASH. The present study will inform about the risk of NASH in Chinese liver biopsy-proven NAFLD patients with and without MS. TRIAL REGISTRATION: This study registered at http://www.chictr.org.cn (registration number: ChiCTR-OOC-16007902). FUNDING: Sanofi (China) Investment Co., Ltd.


Assuntos
Fígado/patologia , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Adulto , Biópsia/métodos , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Testes de Função Hepática/métodos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Fatores de Risco
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(4): 460-5, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27323620

RESUMO

OBJECTIVE: To observe the effect of Compound Zhajin Granule (CZG) on Toll-like re-ceptor 4 (TLR4) signaling pathway in high-fructose corn syrup induced NASH mice. METHODS: Thirty 6-week-old male C3H mice were divided into the high fat and high fructose (HFHFr) group (n = 20) and the control group (n = 10) according to body weight. Mice in the HFHFr group ate high fat diet and drank 20% fructose water, while those in the control group ate common diet and drank common water. After 8 weeks mice in the HFHFr group were divided into two group according to body weight, the HFHFr group and the CZG group, 10 in each group. Mice in the CZG group were fed with high fat forage and 20% fructose water, and administered with 50 mL/kg 12. 8% CZG (prepared by hawthorn, Radix Curcumae, Alisma Orientale, Fritillaria Thunbergii, Silybum Marianum, peach seed in the ratio of 3:1.5:1.5:2:1.5:2:1) by gastrogavage. Mice in the HFHFr group were fed in the same way and daily administered with equal volume of distilled water by gastrogavage. Sixteen weeks later all mice were sacrificed. Body weight, liver wet weight, liver function, and lipid metabolism were detected. Pathological changes of liver tissues were assessed by HE staining, oil red O staining, and Masson staining. Expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-alpha (TNF-α) were detected using immunohistochemical staining and real-time fluorescent quantitative PCR. RESULTS: Body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST) were obviously lower in the CZG group than in the HFHFr group (P < 0.05); oil red O stained area and density were decreased more in the CZG group than in the control group. HE staining showed ballooning inflammation was reduced more in the CZG group than in the HFHFr group. Masson staining was negative. Positive rates of TLR4 and MyD88 and mRNA expressions were significantly lower in the CZG group than in the HFHFr group (all P < 0.05). CONCLUSION: CZG could significantly inhibit TLR4 signaling pathway of liver in NASH mice.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Dieta Hiperlipídica , Frutose/administração & dosagem , Frutose/efeitos adversos , Inflamação , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C3H , Fator 88 de Diferenciação Mieloide/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Cell Physiol Biochem ; 37(6): 2405-14, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26646705

RESUMO

BACKGROUND/AIMS: Isocitrate dehydrogenase 2 (IDH2) is a mitochondrial NADP-dependent isocitrate dehydrogenase, and has been found to be a tumor suppressor in several types of tumors. However, the roles of IDH2 in hepatocellular carcinoma (HCC) as well as underlying mechanisms remain unknown. METHODS: The IDH2 and matrix metalloproteinase 9 (MMP9) levels in the specimens from 24 HCC patients were investigated by Western blot and ELISA, respectively. Their relationship was examined by correlation analyses. Patient survival with high IDH2 levels and low IDH2 levels was compared. IDH2 levels and MMP9 levels were modified in a human HCC cell line. The effects of IDH2 or MMP9 modulation on the expression of the other were analyzed. The effects of IDH2 on cell invasion were analyzed in a transwell cell invasion assay. The dependence of nuclear factor x03BA;B (NF-x03BA;B) signaling was examined using a specific inhibitor. RESULTS: The IDH2 levels significantly decreased in HCC, and were lower in HCC with metastases, compared to those without metastases. IDH2 levels inversely correlated with MMP9 levels in HCC. HCC patients with Low IDH2 had lower 5-year survival. MMP9 levels did not regulate IDH2 levels, while IDH2 inhibited MMP9 levels in HCC cells, in a NF-x03BA;B signaling dependent manner, possibly through ix03BA;B, to suppress HCC cell invasion. CONCLUSIONS: Down regulation of IDH2 may promote HCC cell invasion via NF-x03BA;B-dependent increases in MMP9 activity. IDH2 may be a potential therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/enzimologia , Isocitrato Desidrogenase/metabolismo , Neoplasias Hepáticas/enzimologia , Metaloproteinase 9 da Matriz/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , NF-kappa B/metabolismo
18.
Liver Int ; 35(11): 2392-400, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25689614

RESUMO

BACKGROUND & AIMS: Controlled attenuation parameter (CAP) is a non-invasive method for evaluating hepatic steatosis. However, larger skin capsular distance (SCD) can affect the accuracy. The aim of this study was to investigate the impact of SCD on the diagnostic performance of CAP and liver stiffness measurement (LSM). METHODS: Of 101 patients with non-alcoholic fatty liver disease (NAFLD) and 280 patients with chronic hepatitis B (CHB) who underwent liver biopsy were prospectively recruited. CAP, LSM and SCD were performed using FibroScan with M probe. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy. The optimal thresholds were defined by the maximum Youden index. RESULTS: SCD (B 30.34, P < 0.001) and hepatic steatosis (B 23.04, P < 0.001) were independently associated with CAP by multivariate analysis. The AUROCs were slightly higher for SCD <25 mm compared to those for SCD ≥25 mm for steatosis ≥5% (0.88 vs. 0.81), >33% (0.90 vs. 0.85) and >66% (0.84 vs. 0.72). For SCD <25 mm, the optimal CAP cut-offs for differentiating steatosis ≥5%, >33% and >66% were 255.0 dB/m, 283.5 dB/m and 293.5 dB/m. However, cut-offs were elevated by approximately 60-70 dB/m for SCD ≥25 mm. When stratified by fibrosis grade, LSM was significantly affected by SCD ≥25 mm for advanced fibrosis (≥F3) in NAFLD, but not in CHB. CONCLUSION: CAP is a promising tool for detecting and quantifying hepatic steatosis. SCD ≥25 mm may cause overestimation of steatosis. Similarly, SCD ≥25 mm affects the detection of advanced fibrosis by LSM in NAFLD patients.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite B Crônica/patologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Pele/patologia , Adulto , Área Sob a Curva , Biópsia , Índice de Massa Corporal , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Curva ROC , Índice de Gravidade de Doença
19.
Clin Exp Pharmacol Physiol ; 41(9): 643-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24837195

RESUMO

The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has emerged as a useful predictor of long-term outcome in NAFLD patients. We evaluated the predictive performance of the NFS for overall mortality in a Chinese population with NAFLD. All NAFLD patients diagnosed ultrasonographically at Xixi Hospital of Hangzhou between 1996 and 2011 were retrospectively recruited to the study. Outcome was determined by interview and causes of death were confirmed by medical records. The area under the receiver operating characteristic curve (AUCROC ) was used to determine the predictive accuracy of the NFS, BARD (body mass index, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, diabetes) score, FIB-4 index and the AST/platelet ratio index (APRI) for mortality. Data from a total of 180 eligible patients (median age 39 years; 96 men) were analysed, with 12 deaths over a median follow-up period of 6.6 years (range 0.5-14.8 years). Using Cox model analysis, the NFS as a continuous variable was identified as the only predictor for all-cause mortality (hazard ratio 2.743, 95% confidence interval (CI) 1.670-4.504). The NFS yielded the highest AUCROC of 0.828 (95% CI 0.728-0.928, P < 0.05), followed by the FIB-4 index, APRI and BARD score (AUCROC 0.806 (P < 0.05), 0.732 (P < 0.05) and 0.632, respectively). The data indicated that the NFS is a useful predictor of 6.6-year all-cause mortality for Chinese patients with NAFLD.


Assuntos
Causas de Morte , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Valor Preditivo dos Testes , Adulto , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , China/epidemiologia , Feminino , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/mortalidade , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Ultrassonografia , Adulto Jovem
20.
Clin Exp Pharmacol Physiol ; 41(7): 482-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24739055

RESUMO

The aim of the present study was to investigate Toll-like receptor-4 (TLR4) signalling at different stages of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat, high-fructose (HFHFr) diet in mice. Both TLR4 wild-type (WT) and mutant (TLR4(mut) ) mice were fed either standard chow (SC) or the HFHFr diet for different periods of time from 4 to 16 weeks. Pathological characteristics and function of the liver were assessed. Simple steatosis, steatohepatitis and hepatic fibrosis occurred sequentially in Week 4, 8 and 16 in WT mice fed with the HFHFr. Expression of TLR4, myeloid differentiation factor 88 (MyD88), interferon regulatory factor (IRF) 3 and IRF7 started to increase at Week 4, peaked at Week 8 and then declined to basal levels at Week 16. This pattern was consistent with changes in inflammation in the liver revealed by haematoxylin and eosin staining. However, lipid accumulation, inflammation and fibrosis in livers of TLR4(mut) mice fed the HFHFr diet were significantly alleviated. In addition, the expression of activin A in WT mice fed the HFHFr diet increased at Week 16. The data suggest that TLR4 signalling mediates non-alcoholic steatohepatitis before fibrosis and that activin A is subsequently involved in NAFLD.


Assuntos
Gorduras na Dieta/toxicidade , Sacarose na Dieta/toxicidade , Frutose/toxicidade , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Receptor 4 Toll-Like/metabolismo , Ativinas/genética , Ativinas/metabolismo , Animais , Gorduras na Dieta/administração & dosagem , Sacarose na Dieta/administração & dosagem , Frutose/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Fator Regulador 7 de Interferon/genética , Fator Regulador 7 de Interferon/metabolismo , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...