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1.
Int Immunol ; 35(8): 387-400, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37202206

RESUMO

The roles of tumor-infiltrating CD4+Foxp3- T cells are not well characterized due to their plasticity of differentiation, and varying levels of activation or exhaustion. To further clarify this issue, we used a model featuring subcutaneous murine colon cancer and analyzed the dynamic changes of phenotype and function of the tumor-associated CD4+ T-cell response. We found that, even at a late stage of tumor growth, the tumor-infiltrating CD4+Foxp3- T cells still expressed effector molecules, inflammatory cytokines and molecules that are expressed at reduced levels in exhausted cells. We used microarrays to examine the gene-expression profiles of different subsets of CD4+ T cells and revealed that the tumor-infiltrating CD4+Foxp3- T cells expressed not only type 1 helper (Th1) cytokines, but also cytolytic granules such as those encoded by Gzmb and Prf1. In contrast to CD4+ regulatory T cells, these cells exclusively co-expressed natural killer receptor markers and cytolytic molecules as shown by flow-cytometry studies. We used an ex vivo killing assay and proved that they could directly suppress CT26 tumor cells through granzyme B and perforin. Finally, we used pathway analysis and ex vivo stimulation to confirm that the CD4+Foxp3- T cells expressed higher levels of IL12rb1 genes and were activated by the IL-12/IL-27 pathway. In conclusion, this work finds that, in late-stage tumors, the tumor-infiltrating lymphocyte population of CD4+ cells harbored a sustained, hyper-maturated Th1 status with cytotoxic function supported by IL-12.


Assuntos
Linfócitos T CD4-Positivos , Interleucina-12 , Neoplasias Experimentais , Microambiente Tumoral , Animais , Camundongos , Linfócitos T CD4-Positivos/imunologia , Interleucina-12/imunologia , Exaustão das Células T , Linfócitos do Interstício Tumoral/imunologia , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/imunologia , Células T de Memória/imunologia , Granzimas , Perforina
2.
Nanotechnology ; 35(44)2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39094606

RESUMO

Cesium lead bromide (CsPbBr3) perovskite nanocrystals are becoming a popular alternative to chalcogenide quantum dots because of their bright green fluorescence and high color purity. However, owing to the poor stability caused by their highly ionic nature and the dynamic binding of long-chain capping ligands, their practical applications are limited. Although (3-aminopropyl)triethoxysilane (APTES) is a frequently used insulating material for wrapping CsPbBr3nanocrystals, it often causes surface etching. To address this issue, we introduced oleic acid into the anti-solvent toluene to inhibit the etching effect of APTES using a modified room-temperature ligand-assisted reprecipitation process. We utilized in situ time-dependent photoluminescence measurements to study the formation kinetics of CsPbBr3nanocrystals and determine the optimal ligands ratio. This innovative approach enables precise control over CsPbBr3@SiO2nanoparticles synthesis, yielding uniformly shaped nanocrystals with a silica shell, a consistent size around 10.17 ± 1.6 nm, and enhanced photoluminescence quantum yields ranging from 90% and 100%. The photoluminescence lifetimes of our CsPbBr3@SiO2nanoparticles were significantly prolonged owing to a reduction in non-radiative recombination. This boosts their stability in thermal and polar solvent environments, making them superior candidates for use in photonic devices.

3.
Int J Mol Sci ; 25(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38542062

RESUMO

Hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC) presents a substantial mortality and hepatocellular carcinoma (HCC) risk. While antiviral therapy (AVT) is the standard, complete HBV clearance remains elusive and may not reduce the risk of death in patients with decompensated cirrhosis. Silymarin, a centuries-old herbal remedy, has shown promise against HBV infection and as an antifibrosis therapy. This study explores the potential of silymarin combined with AVT to reduce mortality and HCC incidence in patients with HBV-LC. This research, spanning from 2001 to 2019, entailed a multi-institutional retrospective cohort study which included 8447 HBV-LC patients all undergoing AVT. After applying inclusion and exclusion criteria, the study comprised two cohorts: a case cohort receiving silymarin alongside AVT for at least 30 days, and a control cohort on AVT alone. Propensity score matching, based on baseline parameters including HBV-DNA levels, comorbidity, and an important LC medication, namely, non-selective ß-blockers, was employed to ensure balanced groups, resulting in 319 patients in each cohort for subsequent analyses. Overall mortality was the primary outcome, with HCC occurrence as a secondary outcome. Among 319 patients in both cohorts, the case cohort exhibited significant improvements in the international normalized ratio (INR), model for end-stage liver disease (MELD) score and the Charlson comorbidity index (CCI) one year after the index date. A competing risk survival analysis demonstrated superior one-year and two-year mortality outcomes in the case cohort. However, no significant impact on one-year and two-year HCC occurrence was observed in either cohort. The combination of silymarin and AVT in HBV-LC patients demonstrated a synergistic effect, leading to decreased overall mortality and an improved comorbidity index. While the incidence of HCC remained unchanged, our results suggested promising potential for further clinical trials investigating the synergistic role of silymarin in the treatment of HBV-LC.


Assuntos
Carcinoma Hepatocelular , Doença Hepática Terminal , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Humanos , Vírus da Hepatite B/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Hepatite B Crônica/complicações , Estudos Retrospectivos , Pontuação de Propensão , Doença Hepática Terminal/complicações , Fatores de Risco , Índice de Gravidade de Doença , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Antivirais/uso terapêutico
4.
Hepatology ; 76(3): 803-818, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35060158

RESUMO

BACKGROUND AND AIMS: HCV-specific T cells are few and exhausted in patients with chronic hepatitis C (CHC). Whether these T cells are responsible for the liver damage and fibrosis is still debated. However, cluster of differentiation 38-positive (CD38+ ) human leukocyte antigen DR-positive (HLA-DR+ ) CD8+ T cells are regarded as bystander CD8+ T cells that cause liver injury in acute hepatitis. We propose that these innate CD8+ T cells play a pathogenic role in CHC. METHODS: Lymphocytes from peripheral blood were obtained from 108 patients with CHC and 43 healthy subjects. Immunophenotyping, functional assays, T-cell receptor (TCR) repertoire, and cytotoxic assay of CD38+ HLA-DR+ CD8+ T cells were studied. RESULTS: The percentage of CD38+ HLA-DR+ CD8+ T cells increased significantly in patients with CHC. These cells expressed higher levels of effector memory and proinflammatory chemokine molecules and showed higher interferon-γ production than CD38- HLA-DR- CD8 T cells. They were largely composed of non-HCV-specific CD8+ T cells as assessed by HLA-A2-restricted pentamers and next-generation sequencing analysis of the TCR repertoire. In addition, these CD38+ HLA-DR+ CD8+ T cells had strong cytotoxicity, which could be inhibited by anti-DNAX accessory molecule 1, anti-NKG2 family member D, and anti-natural killer NKp30 antibodies. Lastly, the percentage of CD38+ HLA-DR+ CD8+ T cells was significantly associated with liver injury and fibrosis and decreased significantly along with serum alanine aminotransferase normalization after successful direct-acting antiviral treatment. CONCLUSIONS: The TCR-independent, cytokine-responsive bystander CD38+ HLA-DR+ CD8+ T cells are strongly cytotoxic and play a pathogenic role in patients with CHC.


Assuntos
Linfócitos T CD8-Positivos , Hepatite C Crônica , ADP-Ribosil Ciclase 1/imunologia , Antivirais , Antígenos HLA-DR , Humanos , Glicoproteínas de Membrana/imunologia , Receptores de Antígenos de Linfócitos T
5.
Europace ; 25(5)2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-37000581

RESUMO

AIMS: Limited data compared antiarrhythmic drugs (AADs) with concomitant non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients, hence the aim of the study. METHODS AND RESULTS: National health insurance database were retrieved during 2012-17 for study. We excluded patients not taking AADs, bradycardia, heart block, heart failure admission, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up <3 months. Outcomes were compared in Protocol 1, dronedarone vs. non-dronedarone; Protocol 2, dronedarone vs. amiodarone; and Protocol 3, dronedarone vs. propafenone. Outcomes were acute myocardial infarction (AMI), ischaemic stroke/systemic embolism, intracranial haemorrhage (ICH), major bleeding, cardiovascular death, all-cause mortality, and major adverse cardiovascular event (MACE) (including AMI, ischaemic stroke, and cardiovascular death). In Protocol 1, 2298 dronedarone users and 6984 non-dronedarone users (amiodarone = 4844; propafenone = 1914; flecainide = 75; sotalol = 61) were analysed. Dronedarone was associated with lower ICH (HR = 0.61, 95% CI = 0.38-0.99, P = 0.0436), cardiovascular death (HR = 0.24, 95% CI = 0.16-0.37, P < 0.0001), all-cause mortality (HR = 0.33, 95% CI = 0.27-0.42, P < 0.0001), and MACE (HR = 0.56, 95% CI = 0.45-0.70, P < 0.0001). In Protocol 2, 2231 dronedarone users and 6693 amiodarone users were analysed. Dronedarone was associated with significantly lower ICH (HR = 0.53, 95%=CI 0.33-0.84, P = 0.0078), cardiovascular death (HR = 0.20, 95% CI = 0.13-0.31, P < 0.0001), all-cause mortality (HR 0.27, 95% CI 0.22-0.34, P < 0.0001), and MACE (HR = 0.53, 95% CI = 0.43-0.66, P < 0.0001), compared with amiodarone. In Protocol 3, 812 dronedarone users and 2436 propafenone users were analysed. There were no differences between two drugs for primary and secondary outcomes. CONCLUSION: The use of dronedarone with NOACs was associated with cardiovascular benefits in an Asian population, compared with non-dronedarone AADs and amiodarone.


Assuntos
Amiodarona , Fibrilação Atrial , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Propafenona/uso terapêutico , Administração Oral , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Amiodarona/efeitos adversos , Dronedarona/efeitos adversos
6.
Dig Dis Sci ; 68(6): 2747-2756, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37071242

RESUMO

BACKGROUND: The prognostic effects of liver fibrosis and steatosis in patients with chronic hepatitis B or C are unclear. We investigated the prognostic effects of liver fibrosis and steatosis determined through transient elastography (TE) in patients with chronic hepatitis B or C. METHODS: This retrospective cohort study enrolled 5528 patients with chronic hepatitis B or C who received TE. Multivariate Cox regression was used to evaluate the associations between fibrosis and steatosis grades and the occurrence of hepatic-related events, cardiovascular events, and mortality. Liver stiffness measurements of ≥ 7.1, ≥ 9.5, and ≥ 12.5 kPa were considered to indicate significant fibrosis (≥ F2), advanced fibrosis (≥ F3), and cirrhosis (≥ F4), and controlled attenuation parameters of ≥ 230 and ≥ 264 dB/m were considered to indicate mild (S1) and moderate-to-severe (S2-S3) steatosis, respectively. RESULTS: During a median follow-up of 3.1 years, 489 patients died, 814 had hepatic-related events, and 209 had cardiovascular events. The incidences of these outcomes were lowest among individuals with no- or mild-fibrosis (F0-F1), and increased with fibrosis severity. The incidence of adverse outcomes was highest among patients without steatosis (S0) and lowest among those with moderate-to-severe steatosis. Adjusted models indicated that F2, F3, and F4 were independent risk factors and that moderate-to-severe steatosis was a favorable marker for hepatic-related events. Cirrhosis was an independent factor for mortality. CONCLUSIONS: According to TE, increasing fibrosis grades and absence of steatosis were associated with higher risks of hepatic-related events, whereas cirrhosis was a risk factor for mortality in patients with chronic hepatitis B or C.


Assuntos
Doenças Cardiovasculares , Técnicas de Imagem por Elasticidade , Hepatite B Crônica , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prognóstico , Estudos Retrospectivos , Cirrose Hepática/complicações , Fígado/diagnóstico por imagem , Fígado/patologia , Biópsia/efeitos adversos , Doenças Cardiovasculares/complicações
7.
Clin Exp Dermatol ; 47(7): 1366-1368, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35267209

RESUMO

It is extremely rare for males with incontinentia pigmenti to survive. We summarize a diagnostic evaluation protocol for such individuals to provide an explanation for male survival.


Assuntos
Incontinência Pigmentar , Algoritmos , Humanos , Incontinência Pigmentar/diagnóstico , Lactente , Masculino
9.
J Formos Med Assoc ; 119(2): 635-643, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31495543

RESUMO

BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC) patients. Variceal bleeding is a life-threatening complication and may alter the initial treatment plan. This study was aimed to elucidate the risk factors for variceal bleeding in HCC patients receiving TACE treatment. METHODS: From 2005 to 2016, a total of 1233 treatment-naive HCC patients receiving first time TACE treatment in Chang Gung Memorial Hospital, Linkou medical center were recruited. Pre-TACE status including baseline characteristics, prior history of ascites, and parameters for liver function evaluation were analyzed. All the variables were compared between patients with and without variceal bleeding. RESULTS: Among the 1233 patients, the median age was 63.7 (range 25.8-91.5) years old, and 73.5% were male. Variceal bleeding events were documented in 19 patients (1.5%) within 3 months post TACE treatment. Patients with younger age, cirrhosis, pre-treatment ascites and advanced fibrosis status (higher MELD score, CTP score, ALBI grade, FIB-4 and APRI score) were more likely to encounter post-treatment variceal bleeding. Multivariate Cox regression analysis revealed existence of ascites (adjusted HR: 4.859 (1.947-12.124), p = 0.001), and higher FIB-4 score (adjusted HR: 4.481 (1.796-11.179), p = 0.001) were the independent predictive factors for variceal bleeding. Patients with post-TACE variceal bleeding are more likely to encounter tumor progression (42.1% vs. 20.3%, p = 0.039) and mortality owing to GI bleeding (15.8% vs. 3%, p = 0.032). CONCLUSION: The incidence of post-TACE variceal bleeding was 1.5%. Patients with post-TACE variceal bleeding have poorer TACE treatment response. The pre-treatment ascites and FIB-4 score are the independent predictors for post-TACE variceal bleeding.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Varizes Esofágicas e Gástricas/etiologia , Hemorragia Gastrointestinal/etiologia , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Feminino , Hemorragia Gastrointestinal/mortalidade , Humanos , Incidência , Cirrose Hepática/complicações , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Análise de Sobrevida , Taiwan/epidemiologia , Resultado do Tratamento
12.
J Formos Med Assoc ; 118(8): 1239-1246, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30581103

RESUMO

BACKGROUND: Secondary prevention of hepatocellular carcinoma (HCC) among patients with chronic hepatitis C (CHC) who achieve sustained virologic response (SVR) with interferon-based therapy has been proved effective. However, tertiary prevention with PegIFN/RBV therapy of HCC recurrence seems limited effect in CHC-HCC patients post curative therapies. This study aims to investigate the timing and impact of PegIFN/RBV treatment on prevention of HCC recurrence in patients after RFA treatment. METHODS: From 2013 to 2016, a total of 137 CHC-HCC patients from a 508 patient based cohort receiving complete RFA treatment in Chang Gung Memorial Hospital, Linkou Medical Center were retrospectively recruited. Pre-RFA patient demographics were analyzed by cox regression analysis for prediction on tumor recurrence. Statistics analysis was performed with SPSS V.20 (IBM, USA). RESULTS: The mean age of the 137 patients were 69.6 year-old and 71.5% of patients were cirrhotic. After propensity score matching, one hundred and two patients were enrolled into the analysis. Fifty-one patients (50%) received PegIFN/RBV therapy and twenty-seven patients (52.9%) achieved SVR. Patients who could achieve SVR had lower tumor recurrence rate than non-SVR and untreated groups (29.6% vs. 66.7% vs. 49.0%, P = 0.030). The effect is more prominent in those achieve SVR prior to compared with after RFA despite not reach statistically significant (26.1% vs. 50.0%, P = 0.334). CONCLUSION: Timely treatment with SVR achievement has the lowest tumor recurrence rate in CHC-HCC patients. Secondary prevention might be even more important than tertiary prevention in CHC patients, especially regarding prevention of post RFA HCC recurrence.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Neoplasias Hepáticas/virologia , Ribavirina/uso terapêutico , Idoso , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Quimioterapia Combinada , Feminino , Hepatite C Crônica/complicações , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Polietilenoglicóis , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Prevenção Secundária , Resposta Viral Sustentada , Taiwan , Prevenção Terciária , Carga Viral , Viremia/tratamento farmacológico
13.
Nutr Cancer ; 70(1): 116-124, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29111778

RESUMO

Carotenoids have been shown to exhibit antiangiogenic activities. Several studies have indicated that carotenoids used in combination were more effective on antioxidation and anticancer actions than carotenoids used singly. However, it is unclear whether multi-carotenoids have antiangiogenic effects. We investigated the effects of multi-carotenoids at physiological plasma levels of Taiwanese (abbreviated as MCT, with a total of 1.4 µM) and Americans (abbreviated as MCA, with a total of 1.8 µM), and of post-supplemental plasma levels (abbreviated as HMC with a total of 3.55 µM) on vascular endothelial growth factor (VEGF)-induced tube formation in human umbilical vein endothelial cells (HUVECs) and rat aortic rings. MCT, MCA, and HMC inhibited VEGF-induced migration, invasion, and tube formation of HUVECs as well as new vessels formation in rat aortic rings. MCT, MCA, and HMC inhibited activities o\f matrix metalloproteinase (MMP)-2, urokinase plasminogen activator, and phosphorylation of VEGF receptor 2 induced by VEGF. Moreover, MCT, MCA, and HMC significantly upregulated protein expression of tissue inhibitors of MMP-2 and plasminogen activator inhibitor-1. These results demonstrate the antiangiogenic effect of multi-carotenoids both in vitro and ex vivo with possible mechanistic actions involving attenuation of VEGF receptor 2 phosphorylation and extracellular matrix degradation.


Assuntos
Inibidores da Angiogênese/farmacologia , Aorta/efeitos dos fármacos , Carotenoides/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Animais , Carotenoides/sangue , Movimento Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Fosforilação/efeitos dos fármacos , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
14.
BMC Gastroenterol ; 17(1): 169, 2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29284412

RESUMO

BACKGROUND: Chemokines/cytokines play important roles in the pathogenesis of chronic hepatitis C (CHC). However, their clinical characteristics and implications in treatment responses to pegylated interferon plus ribavirin treatment (PegIFN/RBV) have not been fully illustrated yet. In this study, we intended to investigate the possible predictability of serum chemokines/cytokines on the treatment response in Taiwanese of CHC, genotype-1 (GT-1). METHODS: 60 Patients with GT-1 CHC infection who had been treated with PegIFN/RBV were enrolled, including 27 (45%) with sustained virological response (SVR), 11 (18%) with relapse after 48 weeks of treatment and 22 (37%) non-response (NR). Clinical parameters, seven chemokines/cytokines, CCL3, CCL4, CXCL9, CXCL10, CXCL11, IL-10 and IFN-γ, and genotypes of rs12979860, the single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) were analyzed for their relationship to treatment response. RESULTS: Baseline serum levels of CXCL10, CXCL11, CCL3 and CCL4 were significantly higher in NR group while comparing with non-NR group. (CXCL10: p = 0.001; CXCL11: p < 0.001; CCL3: p = 0.006; CCL4: p = 0.005). However, only rs12979860 CC genotype was the independent factors for NR in GT-1 CHC infection (OR, 8.985; p = 0.008). In addition, baseline serum level of CCL4 was found to be the only independent factor for NR in GT-1 CHC patients with favorable IL28B genotype (OR, 1.134; p = 0.039). CONCLUSIONS: IL28B genotype is the predictor for NR in GT-1 CHC patients treated with PegIFN/RBV, while baseline serum level of CCL4 is the only predictor for NR in GT-1 CHC patients with favorable IL28B genotype.


Assuntos
Antivirais/uso terapêutico , Quimiocinas/sangue , Citocinas/sangue , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/genética , Humanos , Interferon alfa-2 , Interferons , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
15.
J Gastroenterol Hepatol ; 30(4): 775-83, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25250558

RESUMO

BACKGROUND AND AIM: Patients with liver cirrhosis (LC) were regarded as immunocompromised status with high incidence of bacterial infection. Regulatory T cell (Treg cell) is known as an immune suppressor and also plays an important role in patients with sepsis. This paper aims to study the role of Treg cells in patients with liver cirrhosis and their correlations to bacterial complications. METHODS: Thirty-three normal controls (NC) and 82 cirrhotic patients were enrolled for the case-control study. The Treg cells, defined as CD4+ CD25+ Foxp3+ T cells, in peripheral blood of these patients were evaluated. RESULTS: The percentage of Treg cells increased significantly in patients with liver cirrhosis when compared with normal volunteers. Furthermore, this increase of Treg cells was mainly memory phenotype defined as CD45RO+ Treg cells and was significantly correlated with serum bilirubin levels as evaluated by multiple linear regression analysis. In addition, the tumor necrosis factor (TNF)-α receptor II (TNFRII) expression also significantly increased on Treg cells in these patients. Interestingly, these membranous TNFRII would be shed and released into supernatant. Lastly, this increased percentage of Treg cells in cirrhotic patients correlate well with and predict subsequent bacterial complications. CONCLUSION: The Treg cells, mainly with memory phenotype and with high TNFRII expression, increased significantly in patients with liver cirrhosis and significantly correlated with the serum bilirubin levels. Furthermore, this increased Treg cells correlate with and predict subsequent bacterial complications in cirrhotic patients.


Assuntos
Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/imunologia , Hiperbilirrubinemia/complicações , Hiperbilirrubinemia/imunologia , Cirrose Hepática/complicações , Cirrose Hepática/imunologia , Contagem de Linfócitos , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Bilirrubina , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Previsões , Humanos , Hospedeiro Imunocomprometido/imunologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/sangue
16.
J Ultrasound Med ; 34(5): 813-21, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25911714

RESUMO

OBJECTIVES: The purpose of this study was to evaluate liver fibrosis by acoustic radiation force impulse (ARFI) measurements at 2 locations in patients with chronic hepatitis B and C. METHODS: A total of 204 consecutive patients (146 male and 58 female) with chronic hepatitis B (n = 121) and C (n = 83) who underwent liver biopsy were enrolled. All patients received ARFI measurements at 2 locations in the right intercostal space on the same day as biopsy. RESULTS: There was no difference in median ARFI values between detection locations. However, a significant difference was found for low and high values between locations (median ± SD, 1.38 ± 0.43 versus 1.56 ± 0.55 m/s; P < .001). By receiver operating characteristic (ROC) curve analysis for a METAVIR fibrosis score of F4 (cirrhosis), the lower value of 2 measurements had the highest area under the ROC curve (0.750), followed by the mean value (0.744) and the higher value (0.730). Patients with hepatitis C had a higher area under the ROC curve than patients with hepatitis B (0.824 versus 0.707) for predicting liver cirrhosis. By logistic regression analysis, ARFI was the best modality for predicting liver cirrhosis in hepatitis C, and conventional sonography was the best modality in hepatitis B (P < .001). The ARFI value in patients with hepatitis B was significantly influenced by liver inflammation (P = .019). CONCLUSIONS: Acoustic radiation force impulse imaging is the modality of choice for predicting liver cirrhosis in chronic hepatitis C, whereas conventional sonography is still the modality of choice in chronic hepatitis B.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite B Crônica/diagnóstico por imagem , Hepatite C Crônica/diagnóstico por imagem , Aumento da Imagem/métodos , Cirrose Hepática/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
World J Hepatol ; 16(2): 115-119, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38495281

RESUMO

Hepatic encephalopathy (HE) is a formidable complication in patients with decompensated cirrhosis, often necessitating the administration of rifaximin (RFX) for effective management. RFX, is a gut-restricted, poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE. It has shown notable reductions in infection, hospital readmission, duration of hospital stay, and mortality. However, limited data exist about the concurrent use of RFX with broad-spectrum antibiotics, because the patients are typically excluded from studies assessing RFX efficacy in HE. A pharmacist-driven quasi-experimental pilot study was done to address this gap. They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment, particularly in critically ill patients in intensive care unit (ICU). The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered. The findings also indicate that RFX discontinuation during broad-spectrum antibiotic therapy was not associated with higher rates of delirium or coma, and this result remained robust after adjustment in multivariate analysis. Furthermore, rates of other secondary clinical and safety outcomes, including ICU mortality and 48-hour changes in vasopressor requirements, were comparable. However, since the activity of RFX is mainly confined to the modulation of gut microbiota, its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable, given the overlapping antibiotic activity. Further, this suggests that the action of RFX on HE is class-specific (related to its activity on gut microbiota), rather than drug-specific. A recent double-blind randomized controlled (ARiE) trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics. Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections. Despite these compelling results, both studies have limitations. A prospective, multi-center evaluation of a larger sample, with placebo control, and comprehensive neurologic evaluation of HE is warranted. It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.

18.
Intern Emerg Med ; 19(3): 721-730, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38386096

RESUMO

Acute-on-chronic liver failure (ACLF) implies high short-term mortality rates and usually requires intensive care unit (ICU) admission. Proper prognosis for these patients is crucial for early referral for liver transplantation. The superiority of CLIF-C ACLF score in Asian patients with ACLF admitted to an ICU remains inconclusive when compared to other scoring systems. The purpose of the study is (i) to compare the predictive performance of original MELD, MELD-Lactate, CLIF-C ACLF, CLIF-C ACLF-Lactate, and APACHE-II scores for short-term mortality assessment. (ii) to build and validate a novel scoring system and to compare its predictive performance to that of the original five scores. Two hundred sixty-five consecutive cirrhotic patients with ACLF who were admitted to our ICU were enrolled. The prognostic values for mortality were assessed by ROC analysis. A novel model was developed and internally validated using fivefold cross-validation. Alcohol abuse was identified as the primary etiology of cirrhosis. The AUROC of the five prognostic scores were not significantly superior to each other in predicting 1-month and 3-month mortality. The newly developed prognostic model, incorporating age, alveolar-arterial gradient (A-a gradient), BUN, total bilirubin level, INR, and HE grades, exhibited significantly improved performance in predicting 1-month and 3-month mortality with AUROC of 0.863 and 0.829, respectively, as compared to the original five prognostic scores. The novel ACLF model seems to be superior to the original five scores in predicting short-term mortality in ACLF patients admitted to an ICU. Further rigorous validation is required.


Assuntos
Insuficiência Hepática Crônica Agudizada , Unidades de Terapia Intensiva , Humanos , Insuficiência Hepática Crônica Agudizada/mortalidade , Masculino , Feminino , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Curva ROC , Índice de Gravidade de Doença , Valor Preditivo dos Testes , APACHE
19.
J Clin Gastroenterol ; 47(9): 794-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23842218

RESUMO

BACKGROUND: Age is one of the sustained virologic response (SVR) predictors for genotype-1 chronic hepatitis C patients treated with pegylated interferon-α/ribavirin. However, variation of SVR predictors in different age groups was not explored before. We therefore conducted this study for investigating this issue. METHODS: We retrospectively analyzed 265 genotype-1 chronic hepatitis C patients who received pegylated interferon-α/ribavirin treatment. These patients were divided into 3 age groups. Clinical parameters including the genotype of rs12979860 were analyzed. RESULTS: SVR rate was highest in patients younger than 45 years and lowest in patients older than 65 years even through propensity score matching analysis. As for rapid virologic response (RVR) predictors, genotype of rs12979860 was the predictor for the patients younger than 45 years and patients aged between 45 and 65 years, but no RVR predictor was found for patients older than 65 years. As for the SVR predictors, HbA1c, baseline viral load, and RVR but not genotype of rs12979860 were the predictors in patients younger than 45 years. For patients between 45 and 65 years, the predictors for SVR were liver fibrosis, genotype of rs12979860, and RVR. For patients older than 65 years, RVR was the only predictor for SVR. CONCLUSIONS: SVR predictors are various in different age groups. RVR is the SVR predictor for all age groups, but the genotype of rs12979860 is the SVR predictor only for patients with age between 45 and 65 years but not younger or older patients.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Antivirais/administração & dosagem , Estudos de Coortes , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Resultado do Tratamento
20.
Ann Hepatol ; 12(1): 62-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23293195

RESUMO

BACKGROUND AND RATIONALE: Age is one of the predictors for sustained virological response (SVR) when treating chronic hepatitis C (CHC) patients with pegylated-interferon/ribavirin (PegIFN/RBV). However, the treatment responses of the young patients had not been analyzed before. Therefore, we conducted this study to investigate the treatment responses of CHC patients younger than 40 years old (y/o). MATERIAL AND METHODS: We retrospectively analyzed our prospective cohort of genotype 1 (GT1)- and genotype 2 (GT2)-CHC patients who received 24-week PegIFN/RBV treatment. We divided these patients into two groups according to their age younger or older than 40 y/o. Clinical parameters including viral responses and single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) had been analyzed. RESULTS: In GT1- CHC patients, the rapid, complete early viral response rates and the SVR rate were significantly higher in patients younger than 40 y/o. In GT-1 CHC patients younger than 40 y/o, the SVR rate was similar to the GT2-CHC patients, either with high or low baseline viral load. As for the SVR predictors, in CHC patients younger than 40 y/o, only BMI but not the genotype of HCV, not baseline viral load, and not IL28B SNP was the predictor. CONCLUSIONS: GT1-CHC patients younger than 40 y/o had SVR rate similar to GT2-CHC patients. The IL28B polymorphism had no impact on the SVR rate in these young GT1-CHC patients.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interleucinas/genética , Adulto , Fatores Etários , Biópsia com Agulha de Grande Calibre , Índice de Massa Corporal , Estudos de Coortes , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Interferons , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
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