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1.
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
2.
J Dig Dis ; 22(6): 363-372, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33844454

RESUMO

OBJECTIVE: To investigate the potential therapeutic role of porous SiO2 -coated ultrasmall selenium particles nanospheres (Se@SiO2 nanospheres) pretreatment in acute pancreatitis (AP) and to investigate the related mechanism. METHODS: C57BL/6 mice were randomized to the normal control (CON) group, the AP (induced by cerulein injection) (CAE) group, and AP pretreated with Se@SiO2 nanocomposites at 1 and 2 mg/kg (CAE + 1 or 2 mg/kg Se@SiO2 ) groups, respectively. Serum levels of amylase and lipase, inflammatory cytokines (interleukin [IL]-6, IL-1ß and tumor necrosis factor [TNF]-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were measured, and histopathology was performed to examine the tissue samples of the pancreas, lungs, kidneys and liver. Immunofluorescence assay of reactive oxygen species (ROS), myeloperoxidase (MPO) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling were conducted, and levels of MPO, malondialdehyde, superoxide dismutase and glutathione were evaluated. Finally, Western blot analysis was used to evaluate protein expressions of Nrf2, HO-1, NQO1, TLR4, MyD88 and p-p65 in pancreatic tissue. RESULTS: Se@SiO2 nanospheres alleviated pathological damage to the pancreas, and reduced pancreatic enzymes and inflammatory cytokines. Injury to other organs such as the liver, lungs and kidneys was also alleviated, as indicated by decreased ALT, AST, BUN, and Cr levels as well as improved histopathology. Moreover, Se@SiO2 nanospheres reduced oxidative stress, and ultimately inhibited TLR4/ MyD88/p-p65 pathway and increased the protein expressions of NQO1, Nrf2, and HO-1. CONCLUSION: Se@SiO2 nanospheres may alleviate AP by relieving oxidative stress and targeting the TLR4/Myd88/p-p65 and NQO1/Nrf2/HO-1 pathways.


Assuntos
Ceruletídeo , Nanosferas , Pancreatite , Selênio , Doença Aguda , Animais , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Estresse Oxidativo , Porosidade
3.
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
4.
J Dig Dis ; 22(2): 72-82, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33385317

RESUMO

Nonalcoholic steatohepatitis (NASH) is an inflammatory type of nonalcoholic fatty liver disease and is associated with the development and progression of cirrhosis. Lifestyle intervention is still the predominant treatment for NASH. So far, no drugs have been approved to treat NASH by the U.S. Food and Drug Administration (FDA). Vitamin E has been recommended for patients with NASH without type 2 diabetes mellitus (T2DM), whereas a combination of pioglitazone and vitamin E is recommended for patients with both NASH and T2DM. Encouragingly, drugs are currently being developed for different NASH mechanisms. Some of the drugs are at phase III clinical trials, including obeticholic acid (OCA), Elafibranor, Cenicriviroc, Selonsertib, Resmetirom, Emricasan and Aramchol. Due to its positive interim effect in attenuating the degree of hepatic fibrosis OCA was filing in FDA. However, it has been rejected by the U.S FDA and has been advised to conduct long-term studies. Therefore, in this article, we reviewed the efficacy and safety of drugs currently under clinical trials for NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Diabetes Mellitus Tipo 2 , Humanos , Cirrose Hepática , Preparações Farmacêuticas , Pioglitazona
5.
J Clin Transl Hepatol ; 8(3): 304-312, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33083254

RESUMO

Liver fibrosis is not an independent disease. It refers to the abnormal proliferation of connective tissues in the liver caused by various pathogenic factors. Thus far, liver fibrosis has been considered to be associated with a set of factors, such as viral infection, alcohol abuse, non-alcoholic fatty liver disease, and autoimmune hepatitis, as well as genetic diseases. To date, clinical therapeutics for liver fibrosis still face challenges, as elimination of potential causes and conventional antifibrotic drugs cannot alleviate fibrosis in most patients. Recently, potential therapeutic targets of liver fibrosis, such as metabolism, inflammation, cell death and the extracellular matrix, have been explored through basic and clinical research. Therefore, it is extremely urgent to review the antihepatic fibrosis therapeutics for treatment of liver fibrosis in current clinical trials.

6.
J Dig Dis ; 21(5): 293-300, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32279460

RESUMO

OBJECTIVE: To evaluate whether patients with malignant biliary obstruction (MBO) benefit from balloon dilation before the placement of a self-expanding metal stent (SEMS) for palliative biliary drainage. METHODS: Consecutive patients who underwent endoscopic retrograde cholangiopancreatography with SEMS placement for palliative management of MBO were retrospectively included. Comparative analyses of serum bilirubin levels, post-procedural adverse events, stent patency time, stent dysfunction, and patient survival were performed between the dilation and non-dilation groups. RESULTS: A total of 221 patients underwent palliative endoscopic SEMS implantation for MBO from January 2014 to June 2018. Dilation significantly improved the percentage of serum bilirubin improvement (37.0% vs 14.3%, P = 0.001), with a decreasing trend in the incidence of post-procedural cholangitis (2.5% vs 7.8%, P = 0.075), while the rates of other complications such as pancreatitis and bleeding were not increased. The patency time of SEMS and patient survival did not significantly differ between patients with and without dilation. Patients had endoscopic nasobiliary drainage (ENBD) but not dilation showed similar short-term outcomes as patients underwent dilation but without ENBD. CONCLUSIONS: Dilation with a small-caliber balloon catheter before the placement of SEMS is a safe and effective approach for MBO. Balloon dilation may improve the short-term efficacy of SEMS placement, while long-term outcomes are not obviously affected. The short-term effect of stricture dilation may be achieved by ENBD. Further studies are needed to confirm our results.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Cateterismo/instrumentação , Colangiopancreatografia Retrógrada Endoscópica , Colestase/cirurgia , Dilatação/métodos , Cuidados Pré-Operatórios/métodos , Idoso , Neoplasias dos Ductos Biliares/complicações , Cateterismo/métodos , Colestase/etiologia , Dilatação/instrumentação , Drenagem/instrumentação , Drenagem/métodos , Feminino , Humanos , Masculino , Cuidados Paliativos/métodos , Estudos Retrospectivos , Stents Metálicos Autoexpansíveis , Resultado do Tratamento
7.
FASEB J ; 33(2): 2105-2115, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30226813

RESUMO

The biologic roles of long noncoding RNAs (lncRNAs) in liver fibrosis remained unknown. Through microarray analysis, linc-SCRG1 (a lncRNA with transcript length 3118 bp) was found up-regulated 13.62-fold in human cirrhotic tissues. Quantitative PCR verified that linc-SCRG1 increased along with liver fibrosis progression in human tissues and in activated LX2 cells induced by TGF-ß1. Knockdown of linc-SCRG1 significantly reversed the effects of TGF-ß1 on LX2, including inhibiting activation, promoting apoptosis, reducing proliferation, lessening invasion, and down-regulating genes [fibrosis-related mRNA: α-smooth muscle actin ( α-SMA), type I collagen, and B-cell lymphoma-2; invasion-related mRNA: matrix metallopeptidase-2 ( MMP-2), MMP-9, and MMP-13; inflammation-related mRNA: TNF-α, IL-6, and IL-10]. linc-SCRG1 had binding sites with tristetraprolin (TTP), a kind of RNA-binding protein, and specifically combined to TTP proteins. Overexpression of linc-SCRG1 would cause TTP mRNA unstably and proteins decreasing. TTP mRNA was proved having negative relevance with linc-SCRG1 and was gradually reduced during human liver fibrosis progression. Overexpressing TTP resulted in knockdown of lincSCRG1 and degraded downstream target genes ( MMP-2 and TNF-α) in activated LX2. Overexpressing TTP had the same effects as small interfering RNA-lincSCRG1 (si- lincSCRG1), whereas knockdown of TTP had reversal effects on si- lincSCRG1 in activated LX2. In summary, linc-SCRG1 reduced TTP and restricted its degradation of target genes TNF-α and MMP-2. Therefore, linc-SCRG1 had a repressing TTP-elicited inactivation effect on hepatic stellate cell (HSC) phenotypes. Inhibition of linc-SCRG1 may be a novel therapeutic approach to inactivate HSCs and extenuate human liver fibrosis.-Wu, J.-C., Luo, S.-Z., Liu, T., Lu, L.-G., Xu, M.-Y. linc-SCRG1 accelerates liver fibrosis by decreasing RNA-binding protein tristetraprolin.


Assuntos
Regulação da Expressão Gênica , Células Estreladas do Fígado/citologia , Cirrose Hepática/patologia , Proteínas do Tecido Nervoso/genética , RNA Longo não Codificante/genética , Tristetraprolina/metabolismo , Proliferação de Células , Células Cultivadas , Regulação para Baixo , Células Estreladas do Fígado/metabolismo , Humanos , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Tristetraprolina/genética
8.
Oncol Rep ; 40(3): 1684-1694, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015944

RESUMO

An early diagnosis of colitis­associated colorectal cancer (CAC) is important for its clinical management. However, it is currently difficult to distinguish the different stages of CAC development. MicroRNA dysregulation is common in human colorectal disorders, however little is known regarding whether miRNA affects tumor progression by regulating inflammation. In the present study, we identified a novel miRNA (miR­449a), the expression of which was significantly reduced in CAC tissues than in paired adjacent non­cancerous tissues (ANTs). Notably, the level of miR­449a was in a markedly decreased pattern during the neoplastic transformation of ulcerative colitis (UC)­to­CAC, as demonstrated by both clinical investigations and the experimental mouse model induced by AOM/DSS treatment. In addition, we observed that decreased miR­449a expression was associated with advanced T or N status, later clinical stage and poor histological differentiation of CAC. Mechanistic studies revealed that miR­449a inhibited the growth and metastasis of human colon cancer cells by directly binding to the 3'­UTR of Notch­1 and thereby, suppressed the activation of the Notch signaling pathway. Therefore, these findings provide strong evidence for the translational potential of miR­449a in the discrimination of patients with UC that is likely to progress into CAC, from those unlikely to progress, as well as in the prognosis and diagnosis of CAC.


Assuntos
Biomarcadores Tumorais/metabolismo , Colite/complicações , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Animais , Apoptose , Azoximetano/toxicidade , Biomarcadores Tumorais/genética , Carcinógenos/toxicidade , Estudos de Casos e Controles , Proliferação de Células , Colite/induzido quimicamente , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Sulfato de Dextrana/toxicidade , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Receptor Notch1/genética , Receptor Notch1/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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.
Biomed Pharmacother ; 98: 214-221, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29268242

RESUMO

Signal transducer and activator of transcription 3 (STAT3) has been shown to affect epithelial-to-mesenchymal transition (EMT) in cancers. We investigated the underlying molecular mechanisms of STAT3 crosstalk with Snail-Smad3/transforming growth factor (TGF)-ß1 signaling pathways during the EMT in hepatocellular carcinoma (HCC). STAT3 and TGF-ß1 expressions are examined in liver tissues of HCC patients and rats. The effect of IL-6/ STAT3 crosstalk with Snail-Smad3/TGF-ß1 on EMT, carcinogenesis, migration and invasion are tested in vitro and in vivo. Phosphorylation of STAT3 and TGF-ß1 proteins are universally high and positively co-expressed in HCC tissues from human and rats. Hepatic lower p-STAT3 proteins are related to earlier tumor stages in HCC patients. AG490 (a JAK2-specific inhibitor) treatment could reduce tumor numbers and sizes depending on suppression of STAT3 signaling in HCC rats. TGF-ß1 could induce EMT along with an E-cadherin decrease, while vimentin, Snail, p-Smad2/3, and p-STAT3/STAT3 increase in HepG2. SIS3 (a specific inhibitor of Smad3) could markedly inhibit Snail, Vim and p-STAT3 along with blocking phosphorylation of Smad3, but E-cadherin could be activated in HepG2. IL-6 activates STAT3 signaling and then has cascading consequences for activating Snail-Smad3/TGF-ß1 and vimentin as well as migration and invasion in liver cancer cells. In contrast, AG490 has an effect that inhibits phosphorylation of STAT3, lowers Snail-p-Smad3 protein levels, decreases TGF-ß1-related PAI-1 promoter activation and then reduces migration or invasion of liver cancer cells. STAT3 functions as a positive regulator to activate TGF-ß1-induced EMT and metastasis of HCC. STAT3 and the Snail-Smad3/TGF-ß1 signaling pathways synergistically augment EMT and migration in HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Movimento Celular/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Hepáticas/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Células Hep G2 , Humanos , Masculino , Ratos , Ratos Wistar , Fator de Transcrição STAT3/farmacologia , Fator de Crescimento Transformador beta1/antagonistas & inibidores
11.
J Clin Transl Hepatol ; 6(4): 425-430, 2018 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-30637221

RESUMO

Bile acids (BAs) are the major metabolic product of cholesterol, having detergent-like activities and being responsible for absorption of lipid and lipid-soluble vitamins. In addition, it has been increasingly recognized that BAs are important signaling molecules, regulating energy metabolism and immunity. Under physiological circumstances, synthesis and transport of BAs are precisely regulated to maintain bile acid homeostasis. Disruption of bile acid homeostasis results in pathological cholestasis and metabolic liver diseases. During the last decades, BAs have been gradually recognized as an important therapeutic target for novel treatment in chronic liver diseases. This review will provide an update on the current understanding of synthesis, transport and regulation of BAs, with a focus on the therapeutic roles of bile acid signaling in chronic liver diseases.

12.
J Dig Dis ; 18(6): 349-358, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28544403

RESUMO

OBJECTIVE: To investigate serine protease inhibitor Kazal type 1 (SPINK1) expression and its influence on the prognosis of human hepatocellular carcinoma (HCC) and to explore the underlying molecular mechanisms involved. METHODS: Altogether 80 patients with HCC who underwent curative resection were followed up for a median of 58.6 months. SPINK1 expression was detected in the primary HCC samples by immunohistochemistry. Its role in tumor invasion and metastasis was evaluated in vitro by gene silencing using a small interfering RNA-mediated approach, recombinant SPINK1 and U0126 (an inhibitor of MEK/ERK). The proteins in the MEK/ERK signaling pathway were detected by Western blot. RESULTS: Patients with high SPINK1 expression showed poor overall survival (P = 0.0001) and recurrence-free survival (P = 0.001) compared with those with low SPINK1 expression. The suppression of SPINK1 resulted in reduced cell migration and invasion. SPINK1 overexpression was significantly associated with increased cell migration and invasion in vitro. Furthermore, SPINK1 promoted cancer cells motility and epithelial-mesenchymal transition (EMT) via the mitogen-activated protein kinase kinase (MAPK) and extracellular regulated kinase (ERK) pathway, resulting in increased vimentin expression and decreased E-cadherin expression. CONCLUSION: SPINK1 may be an oncogene that induces EMT via the MEK/ERK pathway and is a potential target for HCC therapy.


Assuntos
Caderinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Inibidor da Tripsina Pancreática de Kazal/fisiologia , Adulto , Idoso , Antígenos CD , Carcinoma Hepatocelular/patologia , Regulação para Baixo , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica
13.
Hepatol Int ; 11(3): 221-241, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28405790

RESUMO

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Colestase/induzido quimicamente , Suplementos Nutricionais/efeitos adversos , Hepatopatias/epidemiologia , Antibacterianos/efeitos adversos , Antibacterianos/toxicidade , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , China/epidemiologia , Colestase/complicações , Colestase/patologia , Diagnóstico Diferencial , Suplementos Nutricionais/toxicidade , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Guias como Assunto , Humanos , Incidência , Hepatopatias/patologia , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Masculino , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
14.
J Dig Dis ; 18(2): 115-124, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28127890

RESUMO

OBJECTIVE: We aimed to identify the features of microRNA (miRNA) at different fibrotic stages in patients with hepatitis B virus (HBV)-related liver fibrosis. METHODS: Liver tissues were collected from 40 chronic hepatitis B (CHB) patients at fibrotic stages S0-4. Microarrays of miRNAs and genomic informatics analysis were performed. RESULTS: In total, 105 miRNAs were differentially expressed in fibrotic tissues (S1-4 groups) compared with no fibrotic tissues (S0 group; P < 0.05). Combined with three classifications, 17 differential miRNAs were found to be closely related to fibrotic stages (over twofold change and P < 0.05). Five miRNAs had a signature that correlated with serum biochemical parameters and liver inflammatory grades. The receiver operating characteristic (ROC) curve showed that six miRNAs performed excellently in the diagnosis of liver fibrosis, with the area under the ROC curve (AUROC) over 0.8; among them hsa-miR-214-3p had the highest AUROC (0.867). Gene ontology functions of differential miRNAs mainly involved in the cellular and developmental processes, localization, biological regulation, binding, transcriptional regulator and organelle. We also found that 23 novel signaling pathways were dysregulated in the liver fibrosis. CONCLUSIONS: MiRNA profile signature, including 17 differential miRNAs and 23 dysregulated signaling pathways, was associated with liver fibrosis. Hepatic inflammatory grades were correlated with the differential miRNA. Some miRNAs can be used for the diagnosis of liver fibrosis.


Assuntos
Hepatite B Crônica/complicações , Cirrose Hepática/genética , Cirrose Hepática/patologia , MicroRNAs/genética , Transdução de Sinais/genética , Adulto , Área Sob a Curva , Feminino , Genômica , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Masculino , MicroRNAs/análise , Análise de Sequência com Séries de Oligonucleotídeos , Curva ROC
15.
Clin Invest Med ; 39(5): E150-E160, 2016 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-27805898

RESUMO

PURPOSE: Staging liver cirrhosis is essential for the management of chronic hepatitis C (CHC). The current meta-analysis evaluated the accuracy of transient elastography for detecting liver cirrhosis in patients with CHC. METHODS: Either prospective or retrospective studies, including cohort and cross sectional studies, in patients diagnosed with chronic hepatitis C, as assessed by transient elastography, were searched from Medline, Cochrane, EMBASE, and Google Scholar databases until March 3, 2015, using the terms "transient elastography, chronic hepatitis C and liver cirrhosis". The primary outcome analyzed was the diagnostic performance, which included sensitivity, specificity, diagnostic odds ratio and area under the receiver-operating characteristic (ROC) curve. RESULTS: Data from 24 articles included in the meta-analysis demonstrated high sensitivity (84%) and specificity (90%) of transient elastography (TE) for assessing liver cirrhosis patients with HCV. Subgroup analysis of patients by underlying diseases revealed a sensitivity and specificity of 91% and 92% (HCV alone), 100% and 75% (HCV-liver transplant), 83.6% and 89.7% (HIV/HCV co-infection) and 97.1% and 90.7% (recurrent CHC after liver transplantation). The pooled diagnostic odds ratio was 61.57 (95% CI, 39.5 - 96.00) and the area under the summary ROC curves was 0.952 ± 0.008, suggesting high diagnostic accuracy of TE. CONCLUSION: Transient elastography can accurately predict liver cirrhosis in patients with hepatitis C, with a sensitivity and specificity of 84% and 90%, respectively. The present results further validate the utility of TE in staging liver cirrhosis in chronic HCV infections.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatite C Crônica/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença
16.
J Dig Dis ; 17(9): 565-571, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27429213

RESUMO

The prevalence of nonalcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases worldwide, has been increasing. In terms of pathological changes, NAFLD can be divided into simple steatosis, nonalcoholic steatohepatitis (NASH) and liver cirrhosis. Hepatocyte damage and inflammatory activity are the main characteristics for evaluating the progress of liver disease. Early and effective diagnosis of the disease is quite important. Pathological findings based on liver biopsy or resected specimens are considered the gold standard for diagnosing and staging steatosis, fibrosis and cirrhosis; however, it is invasive and may lead to related complications. Non-imaging methods such as clinical features and biochemical tests, and imaging methods such as ultrasonography, FibroScan, computed tomography and magnetic resonance imaging are the commonly used noninvasive alternatives, being relatively novel, safe and reliable. In this review, we summarized the benefits and shortcomings of these non-invasive methods for the evaluation of NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica/diagnóstico , Biomarcadores/sangue , Humanos , Imageamento por Ressonância Magnética/métodos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia/métodos
17.
Protein Cell ; 7(9): 662-72, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27342773

RESUMO

Matrine (MT), the effective component of Sophora flavescens Ait, has been shown to have anti-inflammation, immune-suppressive, anti-tumor, and anti-hepatic fibrosis activities. However, the pharmacological effects of MT still need to be strengthened due to its relatively low efficacy and short half-life. In the present study, we report a more effective thio derivative of MT, MD-1, and its inhibitory effects on the activation of hepatic stellate cells (HSCs) in both cell culture and animal models. Cytological experiments showed that MD-1 can inhibit the proliferation of HSC-T6 cells with a half-maximal inhibitory concentration (IC50) of 62 µmol/L. In addition, MD-1 more strongly inhibits the migration of HSC-T6 cells compared to MT and can more effectively induce G0/G1 arrest and apoptosis. Investigating the biological mechanisms underlying anti-hepatic fibrosis in the presence of MD-1, we found that MD-1 can bind the epidermal growth factor receptor (EGFR) on the surface of HSC-T6 cells, which can further inhibit the phosphorylation of EGFR and its downstream protein kinase B (Akt), resulting in decreased expression of cyclin D1 and eventual inhibition of the activation of HSC-T6 cells. Furthermore, in rats with dimethylnitrosamine (DMN)-induced hepatic fibrosis, MD-1 slowed the development and progression of hepatic fibrosis, protecting hepatic parenchymal cells and improving hepatic functions. Therefore, MD-1 is a potential drug for anti-hepatic fibrosis.


Assuntos
Alcaloides/farmacologia , Receptores ErbB/metabolismo , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/prevenção & controle , Quinolizinas/farmacologia , Animais , Linhagem Celular , Ciclina D1/metabolismo , Dimetilnitrosamina/toxicidade , Ativação Enzimática/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Células Estreladas do Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
18.
PLoS One ; 11(6): e0155934, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27276081

RESUMO

BACKGROUND: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. METHODS: A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. RESULTS: Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China. CONCLUSION: Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.


Assuntos
Benzimidazóis/economia , Fluorenos/economia , Hepacivirus , Hepatite C/economia , Modelos Econômicos , Sofosbuvir/economia , Grupo com Ancestrais do Continente Asiático , Benzimidazóis/administração & dosagem , China/epidemiologia , Custos e Análise de Custo , Feminino , Fluorenos/administração & dosagem , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos , Masculino , Cadeias de Markov , Sofosbuvir/administração & dosagem
19.
Cancer Lett ; 374(2): 241-9, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-26902423

RESUMO

Zinc-α2-glycoprotein 1 (AZGP1) has been found to play important roles in TGF-ß1 induced epithelial-to-mesenchymal transition (EMT). However, the mechanisms of AZGP1 inhibiting EMT and its therapeutic potential remain unknown in hepatocellular carcinoma (HCC). AZGP1, TGF-ß1 or ERK2 expressions were examined in liver tissues of HCC patients and rat model. The effect of AZGP1 on EMT and crosstalking of TGFß1-ERK2 signaling in human hepatic cancer cell was tested in vitro and in vivo. Hepatic expression of AZGP1 was nearly deficient in HCC patients and rats. It was proved that AZGP1 has the ability of down-regulating mesenchymal markers, up-regulating epithelial marker, inhibiting cell invasion and suppressing EMT in human HCC cells. The results clarified that AZGP1 has the effect on blocking TGF-ß1 mediated ERK2 phosphorylation leading to depressing EMT and invasive potential in vitro. Local injection of AZGP1 mimic in vivo could significantly withhold lung metastasis in HCC. In conclusion, loss of AZGP1 could trigger EMT induced by TGFß1-ERK2 signaling, confuse in energy metabolism, reduce cell proliferation and apoptosis, activate survival signals and promote invasion. Up-regulation of AZGP1 should be proposed to reverse EMT and might be a new promising therapy for HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas de Plasma Seminal/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adipocinas , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Materiais Biomiméticos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/biossíntese , Proteínas de Transporte/genética , Regulação para Baixo , Transição Epitelial-Mesenquimal , Glicoproteínas/biossíntese , Glicoproteínas/genética , Células Hep G2 , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/genética , Hepatite B Crônica/metabolismo , Hepatite B Crônica/patologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Proteínas de Plasma Seminal/biossíntese , Proteínas de Plasma Seminal/genética
20.
Front Biosci (Landmark Ed) ; 21: 479-86, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26709788

RESUMO

Clinical factors and liver biopsy cannot accurately predict the risk of developing cirrhosis in chronic hepatitis B (CHB).This study was to develop a predictive gene signature for cirrhosis in CHB patients. A total of 183 untreated CHB patients were enrolled. GeneChip, significant analysis of microarray (SAM) and prediction analysis of microarray (PAM) were used to select predictor genes (PGs) in liver tissues. The Cirrhosis Risk Score (CRS) was calculated based on 6 PG variables and the predictive value of CRS was evaluated. Firstly differentially expressed genes were filtered from a genome scan and SAM, and 87 significant genes were selected for the signature building. Secondly a signature consisting of 6 PGs (CD24, CXCL6, EHF, ITGBL1, LUM and SOX9) most predictive for cirrhosis risk in CHB patients was developed in the selection set (n=40) by use of PAM and PCR approach. Finally the CRS was calculated to estimate the risk of developing cirrhosis and then tested in validation cohort (n=143). The area under the ROC curves (AUROC) of the CRS was 0.944 and exceeded to 6 PGs and clinical factors. A low CRS cutoff of 6.43 to identify low-risk patients would misclassify only 8.16% of high-risk patients, while a high cutoff of 8.32 to identify high-risk patients would misclassify 0% of low-risk patients. So CRS is a better predictor than clinical factors in differentiating high-risk versus low-risk for cirrhosis and application of CRS in clinical practice could help to reduce the rate of liver biopsy in patients with CHB.


Assuntos
Predisposição Genética para Doença , Hepatite B Crônica/genética , Cirrose Hepática/genética , Algoritmos , Perfilação da Expressão Gênica , Humanos , Fatores de Risco
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