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1.
Hepatology ; 66(1): 209-219, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28370357

RESUMO

Mortality from hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is high due to limited treatment options. Preclinical and clinical investigations have proved that treatment with mesenchymal stromal cells (MSCs) is beneficial for recovery from liver injury. We hypothesized that the outcome of HBV-related ACLF would be improved by MSC treatment. From 2010 to 2013, 110 patients with HBV-related ACLF were enrolled in this open-label, nonblinded randomized controlled study. The control group (n = 54) was treated with standard medical therapy (SMT) only. The experimental group (n = 56) was infused weekly for 4 weeks with 1.0 to 10 × 105 cells/kg allogeneic bone marrow-derived MSCs and then followed for 24 weeks. The cumulated survival rate of the MSC group was 73.2% (95% confidence interval 61.6%-84.8%) versus 55.6% (95% confidence interval 42.3%-68.9%) for the SMT group (P = 0.03). There were no infusion-related side effects, but fever was more frequent in MSC compared to SMT patients during weeks 5-24 of follow-up. No carcinoma occurred in any trial patient in either group. Compared with the control group, allogeneic bone marrow-derived MSC treatment markedly improved clinical laboratory measurements, including serum total bilirubin and Model for End-Stage Liver Disease scores. The incidence of severe infection in the MSC group was much lower than that in the SMT group (16.1% versus 33.3%, P = 0.04). Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group (37.0% versus 17.9%, P = 0.02). CONCLUSION: Peripheral infusion of allogeneic bone marrow-derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209-219).


Assuntos
Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/terapia , Vírus da Hepatite B/isolamento & purificação , Hepatite B/complicações , Transplante de Células-Tronco Mesenquimais/métodos , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/fisiopatologia , Adulto , Causas de Morte , China , Feminino , Hepatite B/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento
2.
J Gastroenterol Hepatol ; 29(4): 800-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24224656

RESUMO

BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) caused by hepatitis B virus (HBV) is a severe disease with high mortality. Immune injury plays an important role during the early stage of the disease. Our research aimed to investigate the safety and efficacy of dexamethasone therapy for patients with HBV-related ACLF. METHODS: A total of 134 inpatients with HBV-induced ACLF were enrolled from January 2009 to December 2012. All the patients received the standard medicine treatment (SMT), among whom 31 cases underwent additional dexamethasone injection for three times (dexamethasone treatment [DMT] Group). A total of 35 patients (SMT Group) matched for baseline characters served as controls. Both the groups were followed up for 12 weeks. The survival rates, liver functions, and complications were recorded. RESULTS: The 12-week cumulative survival rates were 45.7% (16/35)and 48.4% (15/31) for SMT Group and DMT Group, respectively, and no significant differences were found (P = 0.959). There were no dramatic differences in liver function and model for end-stage liver disease (MELD) score at 1, 2, 4, 8, and 12 weeks between two groups. There were no significant differences in the incidence of complications (i.e. infection, gastrointestinal bleeding, encephalopathy, hepatorenal syndrome, and ascites) from 1 to 12 weeks between Group SMT and Group DMT. More than 40 ages, MELD score more than 28 and encephalopathy were independent risk factors for the mortality of patients. CONCLUSIONS: Dexamethasone cannot improve liver functions and 12-week survival rates of patients with HBV-related ACLF. Age, MELD score, and encephalopathy are independent risk factors.


Assuntos
Dexametasona/uso terapêutico , Doença Hepática Terminal/tratamento farmacológico , Doença Hepática Terminal/etiologia , Glucocorticoides/uso terapêutico , Hepatite B/complicações , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/etiologia , Adulto , Fatores Etários , Encefalopatias , Dexametasona/administração & dosagem , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/fisiopatologia , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/fisiopatologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
3.
Zhonghua Gan Zang Bing Za Zhi ; 20(12): 892-5, 2012 Dec.
Artigo em Zh | MEDLINE | ID: mdl-23522248

RESUMO

OBJECTIVE: To explore the relationship between polymorphism in the interleukin (IL)-28B gene and sustained virologic response (SVR) in chronic hepatitis C (CHC) patients. METHODS: A total of 220 patients with CHC were prospectively treated with pegylated-interferon (peg-IFN) in combination with ribavirin (RBV) for 48 weeks, and followed-up for an additional 24 weeks. All patients were genotyped for the rs8099917 polymorphism and correlations with antiviral efficacy were determined by statistical analysis. RESULTS: One-hundred-and-eighty-two (82.7%) of the patients achieved end-of-treatment virological response (ETVR). Significantly more patients in the ETVR group carried the rs8099917 genotypes of TT (93.5%) and GT+GG (68.8%), compared to the patients who did not achieve ETVR (X2=23.287, P less than 0.01). In addition, the patients who achieved SVR also represented significantly higher rates of both genotypes (TT: 86.2% and GT+GG: 60.6%; X2=15.531, P less than 0.01). In the SVR group: TT vs. GT+GG: odds ratio (OR)=4.063, 95% confidence interval (CI): 1.972-8.369; X2=15.531, P less than 0.01. In the RP group: TT vs. GT+GG: OR=0.246, 95% CI: 0.119-0.507; X2=15.531, P less than 0.01). CONCLUSION: The IL-28B rs8099917 genotype is closely related to antiviral response of patients with chronic hepatitis C. Compared to carriers of the GT and GG genotypes, carriers of the TT genotype have higher SVR rates and lower RP rates. The TT genotype may be an important predictor of antiviral efficacy.


Assuntos
Hepatite C Crônica/genética , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Antivirais/uso terapêutico , Feminino , Genótipo , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Carga Viral
4.
Zhonghua Gan Zang Bing Za Zhi ; 19(6): 445-9, 2011 Jun.
Artigo em Zh | MEDLINE | ID: mdl-22053376

RESUMO

OBJECTIVE: To get mesenchymal stem cells (MSCs) from hepatitis B patient and to valuate the safety and quality after long-term culture in vitro. METHODS: The cells obtained directly from bone marrow and cultured in Mesen Pro medium supplemented with FGF, and the morphology of MSCs was observed. Surface antigens of the MSCs were analyzed by flow-cytometry. The bacteria, virus, endotoxin and residual serum of cell suspension were detected. The MSCs and perpheral blood T lymphocytes were co-cultured in 48 well plates for 72 h and the T lymphocyte proliferation was measured by using MTT reduction method and the effect of MSCs on T lymphocyte transformation stimulated by PHA was also observed. The oncogenicity of MSCs was verified by the tumorigenesis test in sofo agar. The genetic stability of MSCs was examined by karyotype analysis. RESULT: The MSCs from hepatitis B patient could be passaged to many generations and had strong abilities of proliferation. They expressed stem cell-surface antigens and maintained normal karyotype, prevented the pollution of bacteria and viruses, inhibited the immune response of allogenic T lymphocytes and no oncogenicity found. CONCLUSION: The MSCs have proliferative potentials, can be passaged in long-term cultures in Mesen Pro medium without oncogenicity, can maintain normal karyotype, can inhibit the immune response of T lymphocytes and can alleviate the grafe-versus diseases. The MSCs can be served as a new type of cells in cell and gene therapy.


Assuntos
Células da Medula Óssea/citologia , Hepatite B , Células-Tronco Mesenquimais/citologia , Técnicas de Cultura de Células , Proliferação de Células , Células Cultivadas , Citometria de Fluxo , Humanos , Controle de Qualidade , Linfócitos T/citologia
5.
Zhonghua Gan Zang Bing Za Zhi ; 19(3): 186-90, 2011 Mar.
Artigo em Zh | MEDLINE | ID: mdl-21586236

RESUMO

OBJECTIVE: To investigate the effect of HBV antigens and pathological mechanism of chronic HBV infection by analyzing the cellular immune function of peripheral blood mononuclear cells (PBMCs) from HBsAg carriers. METHODS: PBMCs were prepared from individuals with chronic asymptomatic HBV infection and cultured in the presence of different antigens and/ or cytokines. The levels of cytokines in culture supernatants were detected by ELISA method. The phenotype of the cells was detected by FACS. RESULTS: The levels of IFN y secreted by PBMCs from HBsAg carriers were (48.3+/-19.8) pg/ml, significantly lower than that from healthy controls (t = 3.023, P less than 0.05); The IFN y produced by PBMCs from HBeAg positive patients due to HBsAg and HBcAg stimulation were (50.4+/-51.6) pg/ml and (63.2+/-36.9) pg/ml, significantly lower than that of HBeAg negative patients (t = 2.468 and 3.184, P less than 0.05, respectively). The IL-12p70 secreted by PBMCs from HBeAg positive patients was also significantly lower than that of HBeAg negative patients (P less than 0.05); Exogenous IL-12 promoted significantly PBMCs to secrete IFN y (P less than 0.01) and IL-12 combined with HBV antigens activated CD8+CD45RA+CCR7+ and CD8+CD45RA-CD62L+ cells. IL-12 secreted by PBMCs decreased in HBeAg positive patients, which may be the crucial reason of viral persistence in chronic HBV carriers. Exogenous IL-12 combined with specific HBV antigen could promote the central memory CD8+ T cells to produce IFN y.


Assuntos
Portador Sadio/imunologia , Antígenos da Hepatite B/sangue , Hepatite B/imunologia , Interleucina-12/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Portador Sadio/sangue , Portador Sadio/virologia , Estudos de Casos e Controles , Hepatite B/sangue , Vírus da Hepatite B/imunologia , Humanos , Interferon gama/sangue , Interleucina-12/sangue , Leucócitos Mononucleares/imunologia , Adulto Jovem
6.
Artigo em Zh | MEDLINE | ID: mdl-23189850

RESUMO

OBJECTIVE: To explore the effect of IL-28B variation on the response of patients with chronic hepatitis C virus (HCV) infection to therapy. METHODS: A total of 220 patients with chronic hepatitis C (CHC) were prospectively treated with pegilated interferon (peg-IFN) in combination with ribavirin (RBV) for 48 weeks. After completing the therapy, the patients were followed-up for 24 weeks and the therapeutic effectiveness was evaluated. The rs8099917 was identified from each cohort. The IL28B genotype was compared in hepatitis C patients to assess the effect of single nucleotide polymorphism (SNP) on different treatment response. RESULT: The proportion of the rs8099917 TT, TG, and GG genotypes was 71.4%, 25.0%, and 3.6% in sustained viral response (SVR) group; 15.8%, 60.5%, 23.7% in null response (NR) group; 38.1%, 52.3%, 9.6% in relapse (RP) group. There was a statistically significant difference in the genotype among SVR, NR and RP groups (P < 0.001, Chi-square test). NR vs. SVR (TG vs. TT: OR = 7.67, 95% CI: 2.91-20.56, P < 0.001). RP vs. SVR (TG vs. TT: OR = 3.10, 95% CI: 1.14-6.36, P < 0.01). CONCLUSIONS: The genotypes of IL-28 B (rs8099917) is closely related to the effectiveness of peg-IFN-alpha/RBV therapy, and it is an important predictive factor before treatment in patients with chronic hepatitis C.


Assuntos
Antivirais/uso terapêutico , Variação Genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Interleucinas/genética , Adulto , Idoso , Quimioterapia Combinada , Feminino , Seguimentos , Hepacivirus/efeitos dos fármacos , Hepacivirus/fisiologia , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/uso terapêutico , Interferons , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Ribavirina/uso terapêutico , Resultado do Tratamento
7.
Chin Med J (Engl) ; 125(13): 2334-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22882858

RESUMO

BACKGROUND: Genetic variations at the interleukin 28B (IL-28B) locus are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. The aim of this research was to evaluate the role of IL-28B single nucleotide polymorphism (SNP) variations in Chinese patients undergoing pegylated interferon-α plus ribavirin (PEG-IFN-α/RBV) treatment. METHODS: To determine the effect of IL-28B variation on the response to HCV therapy, these variants were genotyped in a cohort of 220 patients who were chronically infected with HCV and received combined PEG-IFN-α/RBV therapy. RESULTS: The proportions of rs12979860 CC, CT, and TT genotypes were 71.4%, 25.0%, and 3.6% respectively, in the sustained virological response (SVR) group; 15.8%, 60.5%, and 23.7% respectively, in the null virological response (NVR) group; and 38.1%, 52.4%, and 9.5% respectively, in the relapse (Rel) group (P < 0.05). Logistic regression analysis showed that, compared to those having the CC genotype, CT heterozygotes had an increased risk of NVR and Rel (OR = 10.95, 95%CI = 4.12-29.11, P = 1.5×10(-7) and OR = 3.93, 95%CI = 1.86-8.32, P = 2.1×10(-4) respectively). The RNA quantification assay showed that patients with genotype CC exhibited much higher levels of IL-28 expression than those with genotype CT or TT (P < 0.001). CONCLUSIONS: The IL-28B SNP rs12979860 genotype was related to the effectiveness of HCV therapy: patients with the CC rs12979860 genotype had higher rates of SVR than those with the CT or TT genotype, and the CC genotype revealed a significantly higher level of IL-28 mRNA expression.


Assuntos
Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Interleucinas/genética , Adulto , Antivirais/uso terapêutico , Genótipo , Humanos , Interferon-alfa/uso terapêutico , Interferons , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genética , Ribavirina/uso terapêutico
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