RESUMO
BACKGROUND: Hepatic steatosis (HS) can cause substantial problems for both donors and recipients in living donor liver transplantation. The controlled attenuation parameter (CAP) is a noninvasive method of measuring HS using a process based on transient elastography. AIM: To evaluate the accuracy of CAP in quantifying HS during living donor liver transplantation. METHODS: A total of 54 liver donors who received CAP and intraoperative liver biopsy (LB) were enrolled in this study. The performance of CAP compared with LB for diagnosing HS was assessed using areas under receiver operating characteristic curves. HS was defined by the presence of steatosis in >5% of hepatocytes. RESULTS: No HS was found in 47 donors, while the remaining 7 donors showed HS ranging from 10% to 30%. Using CAP, the area under receiver operating characteristic curve was 0.96 (95% CI, 0.91-1; P < .001) for HS; the optimal cutoff value for HS was 257 dB/m (sensitivity: 100%, specificity: 89.4%, positive predictive value: 58.3%, negative predictive value: 100%). Among the 42 candidates with CAP <257 dB/m, none had HS, while of the 12 candidates with CAP ≥257 dB/m, 7 had HS. In a multivariate linear regression analyses, body mass index (ß = 0.71, P < .001) was found to be independently associated with CAP in those without HS. CONCLUSIONS: CAP might be a promising tool to exclude HS in East Asian living liver donors. Body mass index was found to be independently associated with CAP values in those without HS.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Fígado Gorduroso/diagnóstico por imagem , Transplante de Fígado , Doadores Vivos , Transplantes/patologia , Adulto , Área Sob a Curva , Povo Asiático , Biópsia , Índice de Massa Corporal , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Curva ROC , Índice de Gravidade de Doença , Transplantes/diagnóstico por imagemRESUMO
OBJECTIVES: To realize the automated bone age assessment by applying deep learning to digital radiography ï¼DRï¼ image recognition of left wrist joint in Uyghur teenagers, and explore its practical application value in forensic medicine bone age assessment. METHODS: The X-ray films of left wrist joint after pretreatment, which were taken from 245 male and 227 female Uyghur nationality teenagers in Uygur Autonomous Region aged from 13.0 to 19.0 years old, were chosen as subjects. And AlexNet was as a regression model of image recognition. From the total samples above, 60ï¼ of male and female DR images of left wrist joint were selected as net train set, and 10ï¼ of samples were selected as validation set. As test set, the rest 30ï¼ were used to obtain the image recognition accuracy with an error range in ±1.0 and ±0.7 age respectively, compared to the real age. RESULTS: The modelling results of deep learning algorithm showed that when the error range was in ±1.0 and ±0.7 age respectively, the accuracy of the net train set was 81.4% and 75.6% in male, and 80.5% and 74.8% in female, respectively. When the error range was in ±1.0 and ±0.7 age respectively, the accuracy of the test set was 79.5% and 71.2% in male, and 79.4% and 66.2% in female, respectively. CONCLUSIONS: The combination of bone age research on teenagers' left wrist joint and deep learning, which has high accuracy and good feasibility, can be the research basis of bone age automatic assessment system for the rest joints of body.
Assuntos
Determinação da Idade pelo Esqueleto/métodos , Medicina Legal , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Articulação do Punho/diagnóstico por imagem , Adolescente , Algoritmos , Inteligência Artificial , Povo Asiático/etnologia , China , Feminino , Humanos , Masculino , Redes Neurais de Computação , Articulação do Punho/patologia , Filme para Raios XRESUMO
This study investigates the incidences and predictors of hepatitis B virus (HBV) relapse after tenofovir disoproxil fumarate (TDF) therapy in hepatitis B e antigen (HBeAg)-positive and -negative patients. We retrospectively recruited 143 chronic hepatitis B (CHB) patients without cirrhosis (39 HBeAg-positive and 104 HBeAg-negative patients) who were previously treated with TDF and had post-treatment follow-up for at least 6 months (median: 55, IQR 36-85 weeks). All the patients fulfilled the stopping criteria of APASL 2012. The virological and clinical relapse rates at 104 weeks in HBeAg-positive patients were 66.6% and 59.1%, while they were 72.3% and 55.9%, respectively, in HBeAg-negative patients. Cox regression analysis revealed that the higher end-of-treatment HBsAg levels were an independent factor of virological relapse in HBeAg-positive and HBeAg-negative patients. The end-of-treatment HBsAg levels of 200 (area under the receiver operating characteristic (AUROC): 0.624) and 80 IU/mL (AUROC: 0.959) were the optimal values for predicting HBV relapse in HBeAg-positive and HBeAg-negative patients, respectively. The virological relapse rate at 78 weeks was 14.3% and 19.6% in HBeAg-positive and HBeAg-negative patients who achieved HBsAg ≤200 IU/mL and HBsAg ≤80 IU/mL, respectively. Two patients experienced hepatic decompensation upon hepatitis flares, and no patient died after timely retreatment. Seven patients experienced off-therapy HBsAg loss. The cumulative rates of HBsAg loss at 104 weeks were 45.5% and 59.3% in patients with end-of-treatment HBsAg ≤80 IU/mL and ≤50 IU/mL, respectively. In conclusions, the end-of-treatment HBsAg levels were a useful marker for predicting HBV relapse in HBeAg-positive and HBeAg-negative CHB patients.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Tenofovir/uso terapêutico , Adulto , Idoso , Feminino , Seguimentos , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Medição de RiscoRESUMO
OBJECTIVE: To investigate the long-term incidence and predictors for hepatitis B surface antigen (HBsAg) loss after nucleoside analogue therapy. METHODS: The study included 411 noncirrhotic chronic hepatitis B patients (148 hepatitis B e antigen (HBeAg)-positive and 263 HBeAg-negative patients) who were treated with lamivudine (n = 110) or entecavir (n = 301) with posttreatment follow-up of at least 12 months. RESULTS: In HBeAg-positive patients, the 8-year cumulative rates of virologic relapse, clinical relapse and HBsAg loss were 55.6%, 47.7% and 19.6%, respectively. In HBeAg-negative patients, the rates were 69.3%, 58.9% and 33.1%, respectively. Cox regression analysis showed that hepatitis B virus genotype C and lower end-of-treatment HBsAg levels were independent predictors of HBsAg loss in HBeAg-positive and -negative patients. The 5-year HBsAg loss rate was 47.3% in HBeAg-positive patients with end-of-treatment HBsAg levels <300 IU/mL, while the 8-year HBsAg loss rate was 69.3% in HBeAg-negative patients with end-of-treatment HBsAg levels <200 IU/mL. Five patients experienced hepatitis flares with decompensation after stopping nucleoside analogue therapy, and one died after retreatment. Of the 48 patients who developed off-therapy HBsAg loss, two developed hepatocellular carcinoma. CONCLUSIONS: The rate of HBsAg loss was relatively high and the rate of hepatic events was low in noncirrhotic patients who discontinued nucleoside analogue therapy.
Assuntos
Antivirais/administração & dosagem , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Adulto , Antivirais/farmacologia , Feminino , Genótipo , Guanina/administração & dosagem , Guanina/análogos & derivados , Guanina/farmacologia , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/genética , Antígenos E da Hepatite B/metabolismo , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Humanos , Incidência , Lamivudina/administração & dosagem , Lamivudina/farmacologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVES: The aims of this study are to compare the long-term efficacy and safety of entecavir and tenofovir in nucleos(t)ide analogue (NA)-naive patients with chronic hepatitis B (CHB) with high hepatitis B virus (HBV) DNA (> 6 log10 IU/mL). METHODS: We recruited 419 NA-naive patients for analysis (313 entecavir, 106 tenofovir). We used propensity-score matching to match 106 patients in the tenofovir group with 212 patients in the entecavir group by age, baseline HBV DNA levels and cirrhosis after subgrouping by hepatitis B e antigen (HBeAg) status. RESULTS: There was no significant difference in 3-year cumulative rates of virological response (VR) (96.4% versus 92.1%, p 0.26 in HBeAg-positive or 98.2% versus 98.6%, p 0.64 in HBeAg-negative patients), HBeAg loss (53.8% versus 47.4%, p 0.89) or seroconversion (40.2% versus 41.3%, p 0.77), and hepatocellular carcinoma (HCC) development (4% versus 2.7%, p 0.55) between the tenofovir and entecavir groups in either cohort or propensity-score matching patients. In subgroup analysis of patients with HBV DNA >108 IU/mL, entecavir and tenofovir showed similar effectiveness in achieving VR (90.9% versus 87.7% at 3 years; p 0.13). Tenofovir and diabetes mellitus were independent factors for acute kidney injury during treatment. Multivariate analysis showed that HBeAg-negative status, and lower baseline HBV DNA and HBV surface antigen levels were independent factors for achieving VR. Older age, lower baseline HBV DNA levels, cirrhosis and α-fetoprotein ≥8 ng/mL at 12 months of treatment were independently associated with HCC development. CONCLUSIONS: Tenofovir and entecavir have similar effectiveness in NA-naive CHB patients with high viraemia. Tenofovir might have a higher incidence of acute kidney injury compared with entecavir during treatment.
Assuntos
Antivirais/efeitos adversos , Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Adulto , Idoso , DNA Viral/sangue , Feminino , Guanina/efeitos adversos , Guanina/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Carga ViralRESUMO
We investigated the incidence and predictors of post-treatment hepatitis B virus (HBV) relapse and hepatitis B surface antigen (HBsAg) loss. After cessation of nucleoside analogue (NA) treatment in hepatitis B e antigen (HBeAg)-negative patients with cirrhosis. The rates of HBsAg loss and hepatocellular carcinoma (HCC) development in HBeAg-negative patients with cirrhosis who continued NA treatment were compared with those who discontinued treatment. Patients with compensated cirrhosis who had discontinued NA treatment for at least 12 months (discontinuing group; n=73) and patients who continued entecavir treatment for at least 4 years (continuing group; n=158) were recruited. Serum HBsAg levels were analysed at the end of treatment (discontinuing group) or at 2.5-3 years of treatment (continuing group). In the discontinuing group, the 6-year cumulative incidence of post-treatment virological relapse and HBsAg loss were 56.3% and 46.7%, respectively. The end-of-treatment HBsAg level of 300 IU/mL was a cut-off value for subsequent post-treatment HBsAg loss and sustained response. In the continuing group, HBsAg loss occurred in five of 158 patients. Cox regression analysis showed that HBsAg levels in the discontinuing group were independent predictors for HBsAg loss in all patients and 104 propensity score (PS)-matched patients. There was no significant difference in HCC development between the groups in all patients and 104 PS-matched patients. Two patients experienced post-treatment alanine aminotransferase flare with hepatic decompensation, and neither of them died after retreatment. In conclusion, HBeAg-negative patients with cirrhosis who discontinued NA treatment might have a higher rate of HBsAg loss and their risk of developing HCC did not increase compared with those who continued entecavir treatment.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Guanina/análogos & derivados , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Feminino , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Deep learning and neural network models have been new research directions and hot issues in the fields of machine learning and artificial intelligence in recent years. Deep learning has made a breakthrough in the applications of image and speech recognitions, and also has been extensively used in the fields of face recognition and information retrieval because of its special superiority. Bone X-ray images express different variations in black-white-gray gradations, which have image features of black and white contrasts and level differences. Based on these advantages of deep learning in image recognition, we combine it with the research of bone age assessment to provide basic datum for constructing a forensic automatic system of bone age assessment. This paper reviews the basic concept and network architectures of deep learning, and describes its recent research progress on image recognition in different research fields at home and abroad, and explores its advantages and application prospects in bone age assessment.
Assuntos
Osso e Ossos/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Algoritmos , Inteligência Artificial , Osso e Ossos/patologia , Humanos , Redes Neurais de ComputaçãoAssuntos
Carcinoma Hepatocelular/patologia , Fator VII/metabolismo , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/metabolismo , Fator VII/antagonistas & inibidores , Fator VII/genética , Humanos , Neoplasias Hepáticas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptor PAR-2/antagonistas & inibidores , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Transdução de Sinais , Tromboplastina/metabolismoRESUMO
This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients with chronic hepatitis B treated with tenofovir (n = 170), telbivudine (n = 184) and entecavir (n = 233) for at least 1 year. Renal function and efficacy were assessed. The estimated glomerular filtration rate (eGFR) decreased significantly in the tenofovir group after a mean of 17 months treatment (from 92.2 to 85.6 mL/min/1.73 m(2), p < 0.001), but increased in the telbivudine group after a mean of 32 months of treatment (from 86.1 to 95 mL/min/1.73 m(2), p < 0.001). There was no significant change in eGFR in the entecavir group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), tenofovir (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virological breakthrough was 0% in tenofovir after 2 years, 3.4% in entecavir after 7 years and 22.9% in telbivudine after 5 years. Liver cirrhosis (p = 0.008) and virological breakthrough (p = 0.040) were independently associated with increased risk of hepatocellular carcinoma development. Tenofovir may lead to deterioration in renal function as assessed by serial eGFR measurements. Although telbivudine appeared to be associated with an improvement in eGFR, it was associated with high rates of virological breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, entecavir could be the best choice among these three agents.
Assuntos
Antivirais/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Nefropatias/induzido quimicamente , Tenofovir/administração & dosagem , Timidina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Guanina/administração & dosagem , Guanina/efeitos adversos , Humanos , Nefropatias/epidemiologia , Nefropatias/patologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Telbivudina , Tenofovir/efeitos adversos , Timidina/administração & dosagem , Timidina/efeitos adversos , Resultado do TratamentoRESUMO
We previously demonstrated PAR2 starts upstreamed with tissue factor (TF) and factor VII (FVII), inhibited autophagy via mTOR signaling in HCC. However, the mechanism underlying for merging functions of PAR2 with the coagulation system in HCC progression remained unclear. The present study aimed to investigate the role of TF, FVII and PAR2 in tumor progression of HCC. The expressions of TF, FVII and PAR2 from HCC specimens were evaluated by immunohistochemical stains and western blotting. We found that the expression of FVII, but not TF and PAR2, directly related to the vascular invasion and the clinical staging. Importantly, a lower level of FVII expression was significantly associated with the longer disease-free survival. The addition of FVII but not TF induced the expression of PAR2 and phosphorylation of ERK1/2, whereas knockdown of FVII decreased PAR2 expression and ERK1/2 phosphorylation in HCC cell lines. Furthermore, levels of phosphor-TSC2 (Ser664) were increased after treatment with FVII and PAR2 agonist whereas these were significantly abolished in the presence of a potent and specific MEK/ERK inhibitor U0126. Moreover, mTOR knockdown highly reduced Hep3B migration, which could be reverted by FVII but not TF and PAR2. These results indicated that FVII/PAR2 signaling through MEK/ERK and TSC2 axis for mTOR activation has potent effects on the migration of HCC cells. In addition, FVII/PAR2 signaling elicits an mTOR-independent signaling, which promotes hepatoma cell migration in consistent with the clinical observations. Our study indicates that levels of FVII, but not TF, are associated with tumor migration and invasiveness in HCC, and provides clues that evaluation of FVII expression in HCC may be useful as a prognostic indicator in patients with HCC and may form an alternative target for further therapy.
RESUMO
Autophagy has an important role in tumor biology of hepatocellular carcinoma (HCC). Recent studies demonstrated that tissue factor (TF) combined with coagulation factor VII (FVII) has a pathological role by activating a G-protein-coupled receptor called protease-activated receptor 2 (PAR2) for tumor growth. The present study aimed to investigate the interactions of autophagy and the coagulation cascade in HCC. Seventy HCC patients who underwent curative liver resection were recruited. Immunohistochemical staining and western blotting were performed to determine TF, FVII, PAR2 and light chain 3 (LC3A/B) expressions in tumors and their contiguous normal regions. We found that the levels of autophagic marker LC3A/B-II and coagulation proteins (TF, FVII and PAR2) were inversely correlated in human HCC tissues. Treatments with TF, FVII or PAR2 agonist downregulated LC3A/B-II with an increased level of mTOR in Hep3B cells; in contrast, knockdown of TF, FVII or PAR2 increased LC3A/B. Furthermore, mTOR silencing restored the impaired expression of LC3A/B-II in TF-, FVII- or PAR2-treated Hep3B cells and activated autophagy. Last, as an in vivo correlate, we administered TF, FVII or PAR2 agonist in a NOD/severe combined immunodeficiency xenograft model and showed decreased LC3A/B protein levels in HepG2 tumors with treatments. Overall, our present study demonstrated that TF, FVII and PAR2 regulated autophagy mainly via mTOR signaling. The interaction of coagulation and autophagic pathways may provide potential targets for further therapeutic application in HCC.
Assuntos
Autofagia , Coagulação Sanguínea , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Animais , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Proliferação de Células , Fator VII/administração & dosagem , Fator VII/genética , Fator VII/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Oligopeptídeos/farmacologia , Interferência de RNA , Receptor PAR-2/agonistas , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Tromboplastina/administração & dosagem , Tromboplastina/genética , Tromboplastina/metabolismo , Fatores de Tempo , Transfecção , Carga Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
There are limited data comparing the clinical outcomes between telbivudine and entecavir. We consecutively enrolled 115 telbivudine-naive and 115 entecavir-naive chronic hepatitis B patients, who were matched for age, sex, hepatitis B e antigen (HBeAg) status and cirrhosis, and treated for at least 2 years or less than 2 years but had developed resistance. Except for the rate of HBeAg seroconversion, which was similar, patients in the entecavir group had better clinical outcomes than those in the telbivudine group for alanine aminotransferase normalization (85.2% vs 78.4%, p <0.048), undetectable HBV DNA (96.5% vs 74.8%, p <0.001), and viral resistance (0.9% vs 21.7%, p <0.001) after 2 years of treatment, After applying roadmap or super-responders concepts, entecavir still had better outcomes than telbivudine in undetectable HBV DNA and viral resistance. The cumulative incidence of hepatocellular carcinoma development was similar between telbivudine-naive and entecavir-naive patients (p 0.565). In renal function analysis, there were significantly more patients with estimated glomerular filtration rate (eGFR) category improvement in both the telbivudine and entecavir groups at year 1 (p 0.006 and p 0.047, respectively). The rate of virological improvement was significantly higher with entecavir than with telbivudine after 2 years of treatment, whether applying the concepts of roadmap or super-responders. The incidence of hepatocellular carcinoma was similar between telbivudine and entecavir. Both telbivudine and entecavir were associated with eGFR improvement, especially in patients with renal insufficiency.
Assuntos
Antivirais/administração & dosagem , Antivirais/efeitos adversos , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Timidina/análogos & derivados , Adulto , Idoso , Alanina Transaminase/sangue , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , DNA Viral/sangue , Farmacorresistência Viral , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Taxa de Filtração Glomerular , Guanina/administração & dosagem , Guanina/efeitos adversos , Hepatite B Crônica/complicações , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Telbivudina , Timidina/administração & dosagem , Timidina/efeitos adversos , Resultado do TratamentoRESUMO
Recent studies have indicated that amino acid (aa) substitutions in the core region and NS5A interferon sensitivity-determining region (ISDR) of hepatitis C virus (HCV) as well as genetic polymorphisms in the interleukin-28B (IL-28B) locus affect the outcome of interferon (IFN)-based therapies. We aimed to investigate the role of these factors on response to peginterferon plus ribavirin in a prospective study of response-guided therapy. The aa sequences in core region and ISDR and rs12979860 genotypes were analysed in 115 HCV-1 patients. The treatment was 24 weeks for patients achieving a rapid virological response (RVR), 48 weeks for those with an early virological response (EVR) and early terminated in those without an EVR. A sustained virological response (SVR) was achieved in 82% of 34 RVR patients, 45% of 74 EVR patients and 0% of seven non-EVR patients. Logistic regression analysis showed that ISDR mutation (≥2) [odds ratio(OR): 6.024], double core 70/91 mutations (OR: 0.136), and platelet counts≥15×10(4) /µL (OR: 3.119) were independent pretreatment factors associated with SVR. Apart from rs12979860 CC genotype, low viral load and ISDR mutation (≥2) were significant factors predictive of RVR. Combination of rs12979860 genotype and baseline viral characteristics (viral load and core/ISDR mutations) could predict RVR and SVR with positive predictive value of 100% and 91%, and negative predictive value of 80% and 54%, respectively. In conclusion, pretreatment screening rs12979860 genotype and aa substitutions in the core region and ISDR could help identifying patients who are good candidates for peginterferon plus ribavirin therapy.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Interleucinas/genética , Polimorfismo Genético , Ribavirina/uso terapêutico , Proteínas não Estruturais Virais/genética , Idoso , Quimioterapia Combinada/métodos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND: Interferon (IFN)-based therapies could eradicate hepatitis C (HCV) and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still happen after sustained virological response (SVR). We aimed to develop a simple scoring system to predict the risk of HCC development among HCV patients after antiviral therapies. METHODS: From 1999 to 2009, 1879 patients with biopsy-proven HCV infection treated with IFN-based therapies were analyzed. RESULTS: Multivariable analysis showed old age (adjusted HR (aHR)=1.73, 95% CI=1.13-2.65 for aged 60-69 and aHR=2.20, 95% CI=1.43-3.37 for aged ≥ 70), Male gender (aHR=1.74, 95% CI=1.26-2.41), platelet count <150 × 10(9)/l (HR=1.91, 95% CI=1.27-2.86), α-fetoprotein ≥ 20 ng ml(-1) (HR=2.23, 95% CI=1.58-3.14), high fibrotic stage (HR=3.32, 95% CI=2.10-5.22), HCV genotype 1b (HR=1.53, 95% CI=1.10-2.14), and non SVR (HR=2.40, 95% CI=1.70-3.38) were independent risk factors for HCC. Regression coefficients were used to build up a risk score and the accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC). Three groups as low-, intermediate-, and high-risk are classified based on the risk scores. One hundred sixty patients (12.78%) in the derivation and 82 patients (13.08%) in the validation cohort developed HCC with AUC of 79.4%, sensitivity of 84.38%, and specificity of 60.66%. In the validation cohort, the 5-year HCC incidence was 1.81%, 12.92%, and 29.95% in low-, intermediate-, and high-risk groups, with hazard ratios 4.49 in intermediate- and 16.14 in high-risk group respectively. The risk reduction of HCC is greatest in patients with SVR, with a 5-year and 10-year risk reduction of 28.91% and 27.99% respectively. CONCLUSION: The risk scoring system is accurate in predicting HCC development for HCV patients after antiviral therapies.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Interferons/uso terapêutico , Neoplasias Hepáticas/virologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite C Crônica/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Risco , Fatores de Risco , Taiwan/epidemiologiaRESUMO
BACKGROUND/AIMS: The independent and interactive effects of hepatitis B virus (HBV) and hepatitis C virus (HCV) factors on the development of hepatocellular carcinoma (HCC) in chronic HBV/HCV dually-infected patients remain unclear. METHODS: In a cross-sectional and case-controlled study, the HBV and HCV loads and genotypes and the sequences of pre-S and precore/core promoter regions were determined in 146 HCC patients and 167 chronic carriers with HBV/HCV dual infection. RESULTS: Age (odds ratio (OR) 1.1), male sex (OR 2.3), pre-S deletion (OR 5.0), A1762T/G1764A mutant (OR 2.5), HCV genotype-1 (OR 2.4) and platelet count <15 × 10(4)/µl (OR 1.9) were independently associated with HCC by stepwise logistic regression analysis. Patients with combined HBV mutations (pre-S deletion and A1762T/G1764A mutant) and HCV genotype-1 had a 39-fold increased risk of developing HCC compared to those with A1762T/G1764A and pre-S wild-type strains and HCV genotype non-1. In the nested case-control study, patients with HCC had a higher HBV DNA level (p < 0.001), a higher frequency of pre-S deletion (p < 0.001) and A1762T/G1764A mutant (p = 0.005), a lower HCV RNA level (p = 0.012) and a higher prevalence of HCV genotype-1 (p = 0.002) than those without. CONCLUSIONS: Pre-S deletion, A1762T/G1764A mutation and HCV genotype-1 are important in hepatocarcinogenesis in chronic HBV/HCV dual infection.
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Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Coinfecção/virologia , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Hepatite C Crônica/virologia , Adulto , Idoso , Estudos de Casos e Controles , Coinfecção/complicações , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/classificação , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Fatores de Risco , Deleção de Sequência , Carga ViralRESUMO
Despite a dramatic reduction in incidence and mortality rates, gastric cancer still remains one of the most common malignant tumors worldwide, especially in China. We sought to identify a set of discriminating genes that could be used for characterization and prediction of response to gastric cancer. Using bioinformatics analysis, two gastric cancer datasets, GSE19826 and GSE2685, were merged to find novel target genes and domains to explain pathogenesis; we selected differentially expressed genes in these two datasets and analyzed their correlation in order to construct a network. This network was examined to find graph clusters and related significant pathways. We found that ALDH2 and CCNB1 were associated with gastric cancer. We also mined for the underlying molecular mechanisms involving these differently expressed genes. We found that ECM-receptor interaction, focal adhesion, and cell cycle were among the significantly associated pathways. We were able to detect genes and pathways that were not considered in previous research on gastric cancer, indicating that this approach could be an improvement on the investigative mechanisms for finding genetic associations with disease.
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Biologia Computacional/métodos , Redes Reguladoras de Genes/genética , Redes e Vias Metabólicas/genética , Neoplasias Gástricas/genética , Análise por Conglomerados , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , HumanosRESUMO
Background and Aims: Patients suffering from peptic ulcer (PU) bleeding who have end-stage renal disease (ESRD) may encounter more adverse outcomes. The primary objective is to investigate the risk factors that influence the outcomes of ESRD and chronic kidney disease (CKD) patients with PU bleeding after successful initial endoscopic haemostasis. Methods: A total of 540 patients with PU bleeding after initial endoscopic haemostasis in a tertiary hospital were investigated retrospectively. They were sorted into three groups after randomised age-matched adjustment: ESRD group (n = 90), CKD group (n = 90) and control group (n = 360). Main outcome measurements were rebleeding, requirement for blood transfusion and surgery, length of hospital stay and mortality. Results: The rebleeding rates were 43% for the ESRD group vs. 21% for the CKD group vs. 12% for the control group (overall p = < 0.001). Multivariate analysis showed the predictors of rebleeding were ESRD, time to endoscope, and non-high-dose proton-pump inhibitors (PPI) users. The risk factors for bleeding-related mortality were presence of moderate degree of CKD and ESRD group, time to endoscope, and Rockall score. All-cause mortality was related to presence of moderate degree of CKD and ESRD group, platelet count, time to endoscope, Rockall score and length of hospital stay. Conclusions: ESRD patients who suffered from PU bleeding were at risk of excessive rebleeding and mortality with frequent occurrence of delayed rebleeding. This study suggests that early endoscopy for initial haemostasis and high-dose intravenous PPI are associated with the reduction of rebleeding risk especially in patients with high Rockall scores.
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This study evaluated TMAH biodegradation under methanogenic conditions. Under methanogenic conditions, a sludge from a full-scale UASB treating TFT-LCD wastewater was able to degrade 2,000 mg/L of TMAH within 10 h and attained a specific degradation rate of 19.2 mgTMAH/gVSS-h. Furthermore, several chemicals including some surfactants, DMSO, and sulfate were examined for their potential inhibitory effects on TMAH biodegradation under methanogenic conditions. The results indicated that surfactant S1 (up to 2%) and DMSO (up to 1,000 mg/L) presented negligible inhibitory effects on TMAH degradation, while surfactant S2 (0.2-1%) might inhibit methanogenic reaction without any TMAH degradation for 3-5 h. At sulfate concentrations higher than 300 mg/L, a complete inhibition of methanogenic reaction and TMAH biodegradation was observed. Results from cloning and sequencing of archaeal 16S rRNA gene fragments showed that Methanosarcina barkeri and Methanosarcina mazei were the dominant methanogens in the UASB treating TMAH-containing TFT-LCD wastewater.
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Metano/química , Metano/metabolismo , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/metabolismo , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Methanosarcina/classificação , Methanosarcina/genética , Methanosarcina/metabolismo , FilogeniaRESUMO
OBJECTIVE: Ano-perianal tuberculosis (TB) is a rare extrapulmonary form of the disease. Most publications are in case report form. We report our cohort retrospective study on ano-perianal TB, which is one of the very few original reports in the literature. METHOD: Over a period of 15 years (January 1992-December 2006), file records revealed cases with confirmed diagnosis of ano-perianal TB after screening from a total of 1251 patients with the diagnosis of TB from Chang Gung Memorial Hospital-Kaohsiung, Taiwan. RESULTS: This study recruited 17 patients (14 male patients and 3 female patients). The age ranged from 18 to 81 years with a mean age of 44.8 +/- 18.2 years. Thirteen patients had coexistent pulmonary TB (76.5%). Eight patients had at least one concomitant co-morbid illness (47.1%). The most common clinical manifestations were anal fistulae (n = 16). All patients who completed a full course of anti-mycobacterial treatment for at least 6 months after surgical intervention were cured without recurrence except for one patient who was lost to follow-up after 2 months of treatment. Seven of the nine patients with complicated fistulae needed longer anti-mycobacterium treatment duration (9-18 months). CONCLUSION: Ano-perianal TB should be kept in mind for all patients with prolonged or repeatedly recurrent ano-perianal symptoms and signs such as complicated fistulae in an endemic TB area like Taiwan. Management strategy is with conventional anti-mycobacterium therapy for at least 6 months after surgery. An extension of the anti-mycobacterium treatment course to 9-18 months is mandatory for patients with complicated disease presentations.
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Canal Anal/microbiologia , Doenças do Ânus/epidemiologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Gastrointestinal/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal/patologia , Doenças do Ânus/diagnóstico , Doenças do Ânus/microbiologia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan/epidemiologia , Fatores de Tempo , Tuberculose Gastrointestinal/diagnóstico , Tuberculose Gastrointestinal/microbiologia , Adulto JovemRESUMO
BACKGROUND: Combinations of Child-Pugh classification and Liver Cancer Study Group of Japan/Tumor-Node-Metastasis (LCSGJ/TNM) have been reported as Japan Integrated Staging (JIS). We previously modified the 6th AJCC/TNM to serve as a better staging system than the 5th and 6th AJCC/TNM. AIMS: To develop a modified TNM-based JIS to predict the survival of hepatocellular carcinoma (HCC) patients more accurately. METHODS: 3764 HCC patients were enrolled from 1986 to 2002 (2882 patients from 1986 to 2000 and 882 patients from 2001 to 2002). We compared the performance of original JIS, modified TNM-based JIS, modified TNM-based JIS combined alpha-fetoprotein (AFP), BCLC, and CLIP. Lower Akaike information criteria (AIC) values indicated better discriminatory abilities. RESULTS: AIC value was lowest in CLIP during all periods. However, during 2001-2002, when early-stage HCC patients were predominant, AIC value was lowest when modified TNM-based JIS combined AFP was used. CONCLUSION: The CLIP system provided the best prognostic stratification in the present cohort of HCC patients who were mainly at late stages. However, early detection of HCCs has become more common in Taiwan in recent years, which has led to the predominance of early-stage HCC patients. Therefore, modified TNM-based JIS combined AFP may now be the most applicable system in recent years.