Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
1.
J Dig Dis ; 21(9): 519-525, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32700794

RESUMO

OBJECTIVES: To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS: In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to < 0.0001). Optimal LSM cut-off values for diagnosing fibrosis stage ≥ F1, ≥ F2, ≥ F3, and F4 were 5.5 kPa, 7.85 kPa, 10.0 kPa, and 12.7 kPa, respectively. CONCLUSION: FibroTouch has a high success rate and good reliability in staging liver fibrosis in patients with CHB.

2.
Medicine (Baltimore) ; 98(44): e17867, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31689880

RESUMO

AIMS: Interleukin(IL)-22 plays an important role in promoting liver regeneration and repair, but its role in chronic HBV-related liver diseasesis not clear. The goal of this study was to evaluate associations between eight IL22 single nucleotide polymorphisms (SNPs) and the development of chronic HBV cirrhosis and HBV-related HCC within a Chinese Han population. METHODS: We investigated associations between single nucleotide polymorphisms (SNPs) in the IL22 gene (rs1026788, rs2227472, rs2227491, rs2227485, rs1179249, rs2046068,rs2227473, and rs7314777) and the risk of HBV-related chronic liver diseases within a Han population in Northeast China. A total of 649 participants were included in the study, including 103 patients with CHB, 264 patients with LC, and 282 patients with HCC. The odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated using chi-square test. Haplotype analysis was conducted by haploview software. RESULTS: Genotype and allele distributions of SNPs rs1179249 and rs2227472 differed between LC and CHB groups (both P < 0.05).The G alleles of SNP rs2227491 and rs1026788 were more frequent in the LC group than in the CHB group (P = 0.046, P = 0.041 respectively). A IL22 haplotype consisting of the minor alleles of SNP rs1179249 and the major alleles of seven other SNPs occurred less frequently in the LC and HCC groups than in the CHB group (28.2%, 33.94%, and 37.86%, respectively, P < 0.05). Moreover, there were no significant associations between smoking or drinking and IL22 SNPs on the risk of HCC (P > 0.05). CONCLUSION: IL22 genetic variations were associated with chronic HBV infection progression, especially in the HBV-LC group. The IL22 genetic variations may help clinicians initiate the correct treatment strategy at the CHB stage.


Assuntos
Carcinoma Hepatocelular/virologia , Hepatite B Crônica/genética , Interleucinas/genética , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Polimorfismo de Nucleotídeo Único , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Progressão da Doença , Feminino , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Estudos Retrospectivos , Fumar/efeitos adversos
3.
Theranostics ; 9(24): 7345-7358, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695772

RESUMO

Rationale: Hepatitis B virus (HBV) is a leading cause of liver diseases. HBV covalently closed circular DNA (cccDNA) is a critical obstacle of complete elimination by anti-HBV therapy. HBV cccDNA accumulates in nucleus as a chromatin-like cccDNA minichromosome assembled by histones and non-histones. However, the underlying mechanism of modulation of cccDNA minichromosome in hepatocytes is poorly understood. Methods: A human liver-chimeric mouse model was established. The cccDNA-ChIP, Southern blot analysis, confocal assays, RIP assays and RNA pull-down assays, et al. were performed to assess the mechanism of assembly and epigenetic regulation of cccDNA minichromosome in human liver-chimeric mouse model, human primary hepatocytes (PHH), dHepaRG, HepG2-NTCP cell lines and clinical liver tissues. Results: Importantly, the expression levels of HAT1, CAF-1 and lncRNA HULC were significantly elevated in the liver from HBV-infected human liver-chimeric mice. Strikingly, the depletion of HAT1 reduced HBV replication and cccDNA accumulation, and impaired the assembly of histone H3/H4 and the deposition of HBx and p300 onto cccDNA to form cccDNA minichromosome in the cells. Mechanically, chromatin assembly factor-1 (CAF-1) was involved in the events. Interestingly, HAT1 modified the acetylation of histone H3K27/H4K5/H4K12 on cccDNA minichromosome. Moreover, lncRNA HULC-scaffold HAT1/HULC/HBc complex was responsible for the modification on cccDNA minichromosome. Additionally, HBV activated HAT1 through HBx-co-activated transcriptional factor Sp1 in a positive feedback manner. Conclusion: HAT1 signaling contributes to assembly and epigenetic regulation of HBV cccDNA minichromosome.


Assuntos
DNA Circular/genética , DNA Viral/genética , Vírus da Hepatite B/genética , Hepatite B/enzimologia , Hepatite B/genética , Histona Acetiltransferases/metabolismo , Animais , DNA Circular/metabolismo , DNA Viral/metabolismo , Epigênese Genética , Feminino , Hepatite B/metabolismo , Hepatite B/virologia , Vírus da Hepatite B/fisiologia , Histona Acetiltransferases/genética , Histonas/metabolismo , Humanos , Masculino , Camundongos , Camundongos SCID , Replicação Viral
4.
Medicine (Baltimore) ; 98(46): e17775, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725618

RESUMO

INTRODUCTION: Glycogen storage disease (GSD) type IX, characterized by liver enlargement and elevated aminotransferase levels, is the most frequent type of GSD. The global incidence of GSD type IXa is only about 1/100,000 individuals. Case reports of GSD type IX are rare in China. We present the first case report of GSD type IXa in Northeast China caused by mutation of PHKA2. PATIENT CONCERNS: An 11-year-old boy was referred to our hospital because of liver enlargement with consistently elevated transaminase levels over 6 months. DIAGNOSIS: Histopathological results following an ultrasound-guided liver biopsy confirmed a diagnosis of GSD. Further genetic testing showed that the patient had GSD type IXa caused by the c.133C>T mutation in PHAK2. INTERVENTIONS: We placed the patient on a high-protein and high-starch diet and provided hepatoprotective and supportive therapy. OUTCOMES: The patient's transaminase levels decreased significantly and were nearly normal at 10-month follow-up. CONCLUSION: This is the first reported case of GSD type IXa in Northeast China. We hope that the detailed and complete report of this case will provide a reference for the diagnosis of liver enlargement of unknown etiology in future clinical practice.


Assuntos
Doença de Depósito de Glicogênio/genética , Fosforilase Quinase/genética , Biópsia , Criança , Doença de Depósito de Glicogênio/patologia , Humanos , Fígado/patologia , Masculino , Mutação
5.
World J Clin Cases ; 7(13): 1717-1725, 2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31367632

RESUMO

BACKGROUND: Benzbromarone is a uricosuric agent that reduces proximal tubular reabsorption of uric acid. Because of hepatotoxicity, it has been withdrawn from the market in Europe. Recently, some benefit-risk assessments of benzbromarone suggest that benzbromarone has greater benefits than risks, and the application of benzbromarone in the treatment of gout and hyperuricemia is still under debate. CASE SUMMARY: A 39-year-old man was admitted to the hospital for icterus and nausea, and he was treated with benzbromarone (100 mg/d) for 4 mo because of hyperuricemia. He had a 10-year history of beer drinking (alcohol: about 28 g/d). Laboratory data showed severe liver injury and serious coagulation dysfunction; tests for autoimmune antibodies, viral hepatitis, and human immunodeficiency virus were negative. Despite administration of liver function-protecting drugs and efficient supportive treatment, the patient deteriorated quickly after hospitalization and developed grade II encephalopathy within a few days. The patient accepted continuous plasma exchange six times; however, his condition did not improve. Based on suggestions from multidisciplinary consultation, the patient underwent liver transplantation 26 d after admission. Liver specimen pathology results showed massive necrosis consistent with drug-induced liver injury, supporting the diagnosis of acute liver failure associated with benzbromarone. The patient recovered quickly thereafter. CONCLUSION: This case highlights that clinicians should be on the alert for the severe hepatotoxicity of benzbromarone. Before prescribing benzbromarone, physicians should evaluate the high-risk factors that may lead to liver injury and provide suggestions for monitoring benzbromarone's hepatotoxicity during treatment.

6.
Nat Commun ; 10(1): 1507, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944315

RESUMO

Exhaustion of cytotoxic effector natural killer (NK) and CD8+ T cells have important functions in the establishment of persistent viral infections, but how exhaustion is induced during chronic hepatitis C virus (HCV) infection remains poorly defined. Here we show, using the humanized C/OTg mice permissive for persistent HCV infection, that NK and CD8+ T cells become sequentially exhausted shortly after their transient hepatic infiltration and activation in acute HCV infection. HCV infection upregulates Qa-1 expression in hepatocytes, which ligates NKG2A to induce NK cell exhaustion. Antibodies targeting NKG2A or Qa-1 prevents NK exhaustion and promotes NK-dependent HCV clearance. Moreover, reactivated NK cells provide sufficient IFN-γ that helps rejuvenate polyclonal HCV CD8+ T cell response and clearance of HCV. Our data thus show that NKG2A serves as a critical checkpoint for HCV-induced NK exhaustion, and that NKG2A blockade sequentially boosts interdependent NK and CD8+ T cell functions to prevent persistent HCV infection.


Assuntos
Hepacivirus/imunologia , Hepatite C Crônica/imunologia , Células Matadoras Naturais/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Citocinas/imunologia , Modelos Animais de Doenças , Hepatite C Crônica/virologia , Hepatócitos/virologia , Antígenos de Histocompatibilidade Classe I/imunologia , Interferon gama/imunologia , Ativação Linfocitária/fisiologia , Proteínas de Membrana/imunologia , Camundongos , Distribuição Aleatória
7.
World J Gastroenterol ; 25(12): 1445-1456, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30948908

RESUMO

Explosive economic growth and increasing social openness in China over the last 30 years have significantly boosted alcohol consumption, and consequently, the incidence of alcoholic liver disease (ALD) in China has increased. Because the epidemiologic and clinical features of ALD in the Chinese population may differ from those of the Caucasian population, this review describes the epidemiology, pathogenesis, genetic polymorphisms, diagnosis, and treatment of ALD in the Chinese population. This updated knowledge of ALD in China provides information needed for a global understanding of ALD and may help in the development of useful strategies for reducing the global ALD burden.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Efeitos Psicossociais da Doença , Hepatopatias Alcoólicas/epidemiologia , Fatores Socioeconômicos , Consumo de Bebidas Alcoólicas/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , China/epidemiologia , Predisposição Genética para Doença , Humanos , Incidência , Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/terapia , Polimorfismo Genético , Fatores de Risco
8.
World J Clin Cases ; 7(24): 4414-4419, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31911926

RESUMO

BACKGROUND: Macro-aspartate aminotransferase (AST), a macroenzyme, is a high-molecular mass complex formed by self-polymerization or association with other serum components that are difficult for the kidney to clear, leading to the isolated elevation of serum AST activity. Cases of macro-AST formation are rare, with only 3 published in the English language literature up to September 2019 in China. In this paper, we present a case in which an asymptomatic woman with persistent isolated elevated AST was confirmed as having macro-AST by the polyethylene glycol precipitation method. CASE SUMMARY: A 34-year-old woman was referred to our clinic for elevated AST levels with normal levels of other liver-associated enzymes on November 12, 2018. Her AST level of liver function test had been abnormal for 7 mo before she came to the clinic. The patient was asymptomatic with a normal physical examination. There was no relevant family history and no alcohol consumption or smoking. She had a several-month history of traditional Chinese medical taking and had stopped it 1 year prior. The laboratory tests in our clinic showed only the elevation of AST (89.5 U/L) with no other significant abnormalities. We performed the precipitation technique with polyethylene glycol to confirm the presence of macro-AST. Then for almost a year, her AST level still fluctuated in the abnormal range. CONCLUSION: This case highlights that clinical physicians should be familiar with this rare condition of persistent isolated AST elevation due to the presence of macro-AST to avoid unnecessary investigation and patient anxiety.

9.
J Gastroenterol Hepatol ; 34(1): 12-21, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30311701

RESUMO

BACKGROUND AND AIM: Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). METHODS: C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group. RESULTS: A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). CONCLUSIONS: Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.


Assuntos
Antivirais/uso terapêutico , Benzofuranos/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Adulto , Alanina Transaminase/sangue , Antivirais/efeitos adversos , Aspartato Aminotransferases/sangue , Austrália , Benzofuranos/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Farmacorresistência Viral/genética , Extremo Oriente , Feminino , Genótipo , Hepacivirus/enzimologia , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Quinoxalinas/efeitos adversos , Federação Russa , Resposta Viral Sustentada , Tailândia , Vietnã , Proteínas não Estruturais Virais/metabolismo , Adulto Jovem
10.
World J Clin Cases ; 6(13): 600-610, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30430115

RESUMO

AIM: To investigate the relationship between levels of iron metabolism markers and hepatitis B virus (HBV)-related chronic liver diseases. METHODS: This case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed. Child-Pugh grade and Barcelona Clinic Liver Cancer stage were determined for each hepatocellular carcinoma patient. Perls' staining was performed on liver sections. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05. RESULTS: Significantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. Correlation analysis indicated that serum hepcidin was negatively correlated with HBV-DNA load (P < 0.01). Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores (P < 0.05). The decreased serum iron and transferrin saturation levels were significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. Liver histology showed a clearly increasing trend in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3 (severe liver fibrosis) and 4 (cirrhosis). CONCLUSION: Iron metabolism disorders occur in patients with HBV-related liver diseases. The serum markers of iron metabolism disorders vary in different stages of HBV-related liver diseases.

11.
Mol Med Rep ; 18(3): 3211-3218, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30085342

RESUMO

Chitosan is a linear polysaccharide that is made by treating the chitin shells of shrimp and crustaceans with an alkaline substance, for example sodium hydroxide. Due to its unique physical and chemical properties, chitosan has a wide range of applications in the medical field. Currently, there are no effective treatments for liver fibrosis; therefore, the aim of the present study was to investigate the therapeutic effect of chitosan in a CCl4­induced hepatic fibrosis (HF) rat model. The serum levels of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were measured by ELISA. Collagen (COL) 3 and α­smooth muscle actin (SMA) expression levels in the rat liver were detected by reverse transcription­semiquantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that treatment with chitosan significantly improved HF, by decreasing the serum levels of AST, ALT, and ALP; improving liver histology; and decreasing the expression levels of COL3 and α­SMA. Chitosan may offer an alternative approach for the clinical treatment of HF.


Assuntos
Antioxidantes/uso terapêutico , Quitosana/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Actinas/genética , Actinas/metabolismo , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antioxidantes/química , Aspartato Aminotransferases/sangue , Tetracloreto de Carbono , Quitosana/química , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Expressão Gênica/efeitos dos fármacos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Sprague-Dawley
12.
BMC Infect Dis ; 18(1): 274, 2018 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-29898681

RESUMO

BACKGROUND: Infants born to hepatitis B surface antigen (HBsAg) positive mothers are at a higher risk for Hepatitis B virus (HBV) infection. Host genetic background plays an important role in determining the strength of immune response to vaccination. We conducted this study to investigate the association between Tumor necrosis factor (TNF) and Mitogen-activated protein kinase eight (MAPK8) polymorphisms and low response to hepatitis B vaccines. METHODS: A total of 753 infants of HBsAg positive and hepatitis Be antigen (HBeAg) negative mothers from the prevention of mother-to-infant transmission of HBV cohort were included. Five tag single nucleotide polymorphism (SNPs) (rs1799964, rs1800629, rs3093671, rs769177 and rs769178) in TNF and two tag SNPs (rs17780725 and rs3827680) in MAPK8 were genotyped using the MassARRAY platform. RESULTS: A higher percentage of breastfeeding (P = 0.013) and a higher level of Ab titers were observed in high responders (P < 0.001). The MAPK8 rs17780725 AA genotype increased the risk of low response to hepatitis B vaccines (OR = 3.176, 95% CI: 1.137-8.869). Additionally, subjects with the AA genotype may have a lower Ab titer than subjects with GA or GG genotypes (P = 0.051). Compared to infants who were breastfed, infants who were not breastfed had an increased risk of low response to hepatitis B vaccine (OR = 2.901, 95% CI:1.306-6.441). CONCLUSIONS: MAPK8 polymorphisms are associated with immune response to HBV vaccinations in infants of HBsAg(+)/HBeAg(-) mothers.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Antígenos E da Hepatite B/sangue , Hepatite B/prevenção & controle , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Proteína Quinase 8 Ativada por Mitógeno/genética , Adulto , Alelos , Feminino , Genótipo , Haplótipos , Hepatite B/imunologia , Humanos , Imunidade Inata , Lactente , Recém-Nascido , Masculino , Mães , Polimorfismo de Nucleotídeo Único , Gravidez , Fator de Necrose Tumoral alfa/genética
13.
Rev Assoc Med Bras (1992) ; 64(3): 253-263, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29641778

RESUMO

OBJECTIVE: The aim of this study was to assess the efficacy and safety of ceftazidime-avibactam in the treatment of complicated intra-abdominal infections (CIAIs) and complicated urinary tract infections (CUTIs) with meta-analysis method. METHOD: We included six randomized clinical trials identified from Medline, Embase, Cochrane Library, "ISRCTN Register" and "ClinicalTrials.gov" which compared ceftazidime-avibactam with comparison group. The meta-analysis was performed using Review Manager software version 5.3. RESULTS: Ceftazidime-avibactam versus active comparisons demonstrated a statistically significant higher rate of microbiological response success on microbiological evaluable populations at the test-of-cure visit (95CI 1.10-2.38, p=0.02) and late-follow-up visit (95CI 1.09-2.23, p=0.02) for the treatment of CUTIs. Ceftazidime-avibactam versus active comparisons demonstrated a statistically significant higher rate of microbiological response success on EME populations at the test-of-cure visit (95CI 1.08-4.27, p=0.03) and late-follow-up visit (OR=1.75, 95CI 1.33-2.29, p<0.0001) for the treatment of CUTIs. Similar results were obtained at the late-follow-up visit (OR = 1.58, 95CI 1.26-1.97, p<0.0001) on microbiologically modified intent-to-treat (mMITT) populations for the treatment of CUTIs. We can find better eradication rates for E. coli and Klebsiella pneumoniae based on mMITT populations. In terms of AEs, SAEs and mortality, ceftazidime-avibactam had a safety and tolerability profile broadly similar to the comparison group. CONCLUSION: This meta-analysis provides evidence of the efficacy of ceftazidime-avibactam as a potential alternative for the treatment of patients with CUTIs, and CIAIs.


Assuntos
Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Ceftazidima/uso terapêutico , Infecções Intra-Abdominais/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Combinação de Medicamentos , Humanos , Infecções Intra-Abdominais/microbiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento , Infecções Urinárias/microbiologia
14.
World J Gastroenterol ; 24(12): 1361-1372, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29599611

RESUMO

AIM: To assess daclatasvir plus asunaprevir (DUAL) in treatment-naïve patients from mainland China, Russia and South Korea with hepatitis C virus (HCV) genotype 1b infection. METHODS: Patients were randomly assigned (3:1) to receive 24 wk of treatment with DUAL (daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period (immediate treatment arm) or following 12 wk of matching placebo (placebo-deferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12 (SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin (70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in DUAL-treated patients compared with placebo patients during the first 12 wk (double-blind phase), and during 24 wk of DUAL in both arms combined. RESULTS: In total, 207 patients were randomly assigned to immediate (n = 155) or placebo-deferred (n = 52) treatment. Most patients were Asian (86%), female (59%) and aged < 65 years (90%). Among them, 13% had cirrhosis, 32% had IL28B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/mL. Among patients in the immediate treatment arm, SVR12 was achieved by 92% (95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate (70%). SVR12 was largely unaffected by cirrhosis (89%), age ≥ 65 years (92%), male sex (90%), baseline HCV RNA ≥ 6 million (89%) or IL28B non-CC genotypes (96%), although SVR12 was higher among patients without (96%) than among those with (53%) baseline NS5A resistance-associated polymorphisms (at L31 or Y93H). During the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving DUAL. During 24 wk of DUAL therapy (combined arms), the most common adverse events (≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities (alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued DUAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths. CONCLUSION: DUAL was well-tolerated during this phase 3 study, and SVR12 with DUAL treatment (92%) exceeded the historical SVR rate for peg-interferon plus ribavirin of 70%.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , China , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Imidazóis/uso terapêutico , Isoquinolinas/uso terapêutico , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Placebos , República da Coreia , Federação Russa , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , Falha de Tratamento , Adulto Jovem
15.
Rev. Assoc. Med. Bras. (1992) ; 64(3): 253-263, Mar. 2018. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-896448

RESUMO

Summary Objective: The aim of this study was to assess the efficacy and safety of ceftazidime-avibactam in the treatment of complicated intra-abdominal infections (CIAIs) and complicated urinary tract infections (CUTIs) with meta-analysis method. Method: We included six randomized clinical trials identified from Medline, Embase, Cochrane Library, "ISRCTN Register" and "ClinicalTrials.gov" which compared ceftazidime-avibactam with comparison group. The meta-analysis was performed using Review Manager software version 5.3. Results: Ceftazidime-avibactam versus active comparisons demonstrated a statistically significant higher rate of microbiological response success on microbiological evaluable populations at the test-of-cure visit (95CI 1.10-2.38, p=0.02) and late-follow-up visit (95CI 1.09-2.23, p=0.02) for the treatment of CUTIs. Ceftazidime-avibactam versus active comparisons demonstrated a statistically significant higher rate of microbiological response success on EME populations at the test-of-cure visit (95CI 1.08-4.27, p=0.03) and late-follow-up visit (OR=1.75, 95CI 1.33-2.29, p<0.0001) for the treatment of CUTIs. Similar results were obtained at the late-follow-up visit (OR = 1.58, 95CI 1.26-1.97, p<0.0001) on microbiologically modified intent-to-treat (mMITT) populations for the treatment of CUTIs. We can find better eradication rates for E. coli and Klebsiella pneumoniae based on mMITT populations. In terms of AEs, SAEs and mortality, ceftazidime-avibactam had a safety and tolerability profile broadly similar to the comparison group. Conclusion: This meta-analysis provides evidence of the efficacy of ceftazidime-avibactam as a potential alternative for the treatment of patients with CUTIs, and CIAIs.

16.
J Dig Dis ; 19(3): 144-154, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29389068

RESUMO

OBJECTIVE: To evaluate tolvaptan as a novel therapeutic option for Chinese patients with liver cirrhosis-associated ascites in a phase 2 clinical trial. METHODS: This randomized, double-blind, placebo-controlled, multicenter trial was conducted in patients with insufficient responses to combination therapies of an oral loop diuretic and an aldosterone antagonist. Reduction in body weight and abdominal circumference, increase in 24-h cumulative urine volume and improvement in serum sodium level from baseline to the end of treatment in the tolvaptan groups (15 mg/day or 30 mg/day orally) were compared with those in the placebo group. Drug safety was also assessed. RESULTS: Sixty-two patients were allocated to the placebo group, 56 to the tolvaptan 15-mg group and 63 to the tolvaptan 30-mg group. Their mean changes in body weight were -0.5 ± 1.6 kg, -2.1 ± 2.0 kg and -1.9 ± 2.0 kg, respectively. Body weight reductions in both tolvaptan groups were significantly greater than that in the placebo group (difference -1.6, 95% confidence interval [CI] -2.5 to -0.8, and difference -1.4, 95% CI, -2.2 to -0.7, both P < 0.0001). The administration of tolvaptan also significantly reduced the abdominal circumference, increased 24-h cumulative urine volume and serum sodium level compared with placebo. The most common adverse events in the tolvaptan groups were constipation, diarrhea, dry mouth and thirst, with no severe adverse events observed. CONCLUSION: Tolvaptan at 15 mg/day significantly reduced the body weight and abdominal circumference in patients with liver cirrhosis-associated ascites, which needs to be confirmed in a phase 3 trial.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/administração & dosagem , Ascite/tratamento farmacológico , Benzazepinas/administração & dosagem , Cirrose Hepática/tratamento farmacológico , Abdome/patologia , Adolescente , Adulto , Idoso , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Antagonistas dos Receptores de Hormônios Antidiuréticos/farmacologia , Ascite/patologia , Ascite/fisiopatologia , Benzazepinas/efeitos adversos , Benzazepinas/farmacologia , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sódio/sangue , Tolvaptan , Urina , Adulto Jovem
17.
J Gastroenterol Hepatol ; 33(6): 1168-1176, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29380415

RESUMO

BACKGROUND AND AIM: Sofosbuvir is a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA polymerase with pangenotypic potency. This phase 3b study evaluated the safety and efficacy of sofosbuvir + ribavirin ± peginterferon in Chinese patients infected with HCV genotype 1, 2, 3, or 6. METHODS: Patients with genotype 1 or 6 received sofosbuvir + peginterferon/ribavirin for 12 weeks or sofosbuvir + ribavirin for 24 weeks, depending on prior treatment and interferon eligibility. Patients with genotype 2 or 3 received sofosbuvir + ribavirin for 12 or 24 weeks, respectively. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR12). RESULTS: Of 389 patients, 42% had genotype 1, 16% genotype 2, 32% genotype 3, and 9% genotype 6. Half were male, 58% were treatment-naïve, and 15% had cirrhosis. SVR12 rates for patients receiving 12 weeks of sofosbuvir + peginterferon/ribavirin were 94% (95% confidence interval [CI], 87-98%) for HCV genotype 1 and 97% (95% CI, 84-100%) for genotype 6. SVR12 rates for those receiving sofosbuvir + ribavirin for 24 weeks were 95% (95% CI, 87-99%) for genotype 1, 100% (95% CI, 40-100%) for genotype 6, and 95% (95% CI, 90-98%) for genotype 3. For genotype 2 patients receiving sofosbuvir + ribavirin for 12 weeks, the SVR12 rate was 92% (95% CI, 83-97%). Twenty patients (5%) relapsed. Ten (3%) experienced serious adverse events. Three (< 1%) discontinued treatment because of adverse events, of whom one died because of treatment-unrelated adverse events. CONCLUSIONS: Sofosbuvir-based regimens were highly effective and safe in Chinese patients with HCV genotype 1, 2, 3, or 6, suggesting sofosbuvir could serve as the backbone for HCV treatment in China irrespective of genotype.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China , Esquema de Medicação , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento , Adulto Jovem
18.
Acta Pharmacol Sin ; 38(8): 1161-1170, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28603285

RESUMO

Aberrant expression of miR-511 is involved in the development of cancer, but the role of miR-511 in hepatocellular carcinoma (HCC) is not well documented. In this study, we explored the molecular mechanisms of miR-511 in hepatocarcinogenesis. Our results of bioinformatics analysis suggested that B cell translocation gene 1 (BTG1), a member of anti-proliferative gene family, was one of the putative targets of miR-511. The expression levels of miR-511 were significantly higher in 30 clinical HCC tissues than in corresponding peritumor tissues, and were negatively correlated with those of BTG1 in the HCC tissues (r=-0.6105, P<0.01). In human hepatoma cell lines HepG2 and H7402, overexpression of miR-511 dose-dependently inhibited the expression of BTG1, whereas knockdown of miR-511 dose-dependently increased the expression of BTG1. Luciferase reporter gene assays verified that miR-511 targeted the 3'UTR of BTG1 mRNA. In the hepatoma cells, overexpression of miR-511 significantly decreased BTG1-induced G1 phase arrest, which was rescued by overexpression of BTG1. Furthermore, overexpression of miR-511 promoted the proliferation of the hepatoma cells, which was rescued by overexpression of BTG1. Conversely, knockdown of miR-511 inhibited cell proliferation, which was reversed by knockdown of BTG1. In conclusion, miR-511 promotes the proliferation of human hepatoma cells in vitro by targeting the 3'UTR of BTG1 mRNA.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Regiões 3' não Traduzidas , Western Blotting , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Citometria de Fluxo , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Environ Toxicol Pharmacol ; 51: 16-22, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28262508

RESUMO

Dioscorea bulbifera L. (DB) is a traditional Chinese herb used in thyroid disease and cancer. However, the clinical use of DB remains a challenge due to its hepatotoxicity, which is caused, in part, by the presence of Diosbulbin B (DIOB), a toxin commonly found in DB extracts. As abnormal expression of hepatobiliary transporters plays an important role in drug-induced liver injury, we assessed the hepatotoxicity induced by DB and DIOB, and explored their impacts on hepatobiliary transporter expression levels. Following liquid chromatography-tandem mass analysis of the DIOB content of DB extract, male ICR mice were randomly orally administered DB or DIOB for 14days. Liver injury was assessed by histopathological and biochemical analysis of liver fuction. The levels of transporter protein and mRNA were determined by western blotting and real-time PCR. Liver function and histopathological analysis indicated that both DB and DIOB could induce liver injury in mice, and that DIOB might be the primary toxic compound in DB. Moreover, down-regulation of Mrp2 blocked the excretion of bilirubin, glutathione disulfide, and bile acids, leading to the accumulation of toxic substrates in the liver and a redox imbalance. We identified down-regulated expression of Mrp2 as potential factors linked to increased serum bilirubin levels and decreased levels of glutathione in the liver and increased liver injury severity. In summary, our study indicates that down-regulation of Mrp2 represents the primary mechanism of DB- and DIOB-induced hepatotoxicity, and provides insight into novel therapies that could be used to prevent DB- and DIOB-mediated liver injury.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dioscorea/química , Medicamentos de Ervas Chinesas/toxicidade , Compostos Heterocíclicos de 4 ou mais Anéis/toxicidade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Simportadores/metabolismo , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos ICR , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Simportadores/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA