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1.
Chin Med J (Engl) ; 133(3): 253-261, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31934936

RESUMO

BACKGROUND: Hepatitis C virus (HCV) genotype 3, particularly subtype 3b, is increasing in prevalence and distribution in China. This study evaluated the prevalence, regional distribution, clinical characteristics, host factors, treatment outcomes, and disease progression of patients with HCV genotype 3 in China. METHODS: A 5-year follow-up was preceded by a cross-sectional study. Treatment choices were at the discretion of treating physicians. Estimated infection time to overall-disease-progression (defined by ≥1 of: newly diagnosed cirrhosis; cirrhosis at baseline, Child-Turcotte-Pugh score increased 2 points or more; progression from compensated cirrhosis to decompensated cirrhosis; hepatocellular carcinoma; liver transplantation; or death) was calculated using the Kaplan-Meier method. Cox regression analyses were conducted to evaluate the risk factors for disease progression. RESULTS: The cross-sectional study enrolled 997 patients, including 91 with HCV genotype 3 infection. Among them, subtype 3b (57.1%) was more dominant than subtype 3a (38.5%). Five hundred and twelve patients were included into the follow-up phase. Among patients analyzed for estimated infection time to overall-disease-progression, 52/304 (17.1%) patients with HCV genotype 1 and 4/41 (9.8%) with HCV genotype 3 (4/26 with genotype 3b, 0/13 with genotype 3a, and 0/2 with undefined subtype of genotype 3) experienced overall-disease-progression. Patients with HCV genotype 3 were younger than those with genotype 1 (mean age: 39.5 ±â€Š8.7 vs. 46.9 ±â€Š13.6 years) and demonstrated more rapid disease progression (mean estimated infection time to overall-disease-progression 27.1 vs. 35.6 years). CONCLUSIONS: HCV genotype 3, specifically subtype 3b, is associated with more rapid progression of liver disease. Further analysis to compare HCV subtype 3a and 3b is needed in high prevalence regions. TRIAL REGISTRATION: NCT01293279, https://clinicaltrials.gov/ct2/show/NCT01293279; NCT01594554, https://clinicaltrials.gov/ct2/show/NCT01594554.

2.
Hepatology ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600834

RESUMO

Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. Clinical trials use the NASH Clinical Research Network (CRN) system for semiquantitative histological assessment of disease severity. Interobserver variability may hamper histological assessment, and diagnostic consensus is not always achieved. We evaluate a novel second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) imaging-based tool to provide an automated quantitative assessment of histological features pertinent to NASH. Images were acquired by SHG/TPEF from 219 nonalcoholic fatty liver disease (NAFLD)/NASH liver biopsy samples from seven centers in Asia and Europe. These were used to develop and validate qFIBS, a computational algorithm that quantifies key histological features of NASH. qFIBS was developed based on in silico analysis of selected signature parameters for four cardinal histopathological features, that is, fibrosis (qFibrosis), inflammation (qInflammation), hepatocyte ballooning (qBallooning), and steatosis (qSteatosis), treating each as a continuous rather than categorical variable. Automated qFIBS analysis outputs showed strong correlation with each respective component of the NASH CRN scoring (P < 0.001) (qFibrosis [r = 0.776], qInflammation [r = 0.557], qBallooning [r = 0.533], and qSteatosis [r = 0.802]) and high area under the receiver operating characteristic curve (AUROC) values (qFibrosis [0.870-0.951; 95% confidence interval (CI), 0.787-1.000; P < 0.001], qInflammation [0.820-0.838; 95% CI, 0.726-0.933; P < 0.001 ), qBallooning [0.813-0.844; 95% CI, 0.708-0.957; P < 0.001], and qSteatosis [0.939-0.986; 95% CI, 0.867-1.000; P < 0.001]) and was able to distinguish differing grades/stages of histological disease. Performance of qFIBS was best when assessing degree of steatosis and fibrosis but performed less well when distinguishing severe inflammation and higher ballooning grades. Conclusion: qFIBS is an automated tool that accurately quantifies the critical components of NASH histological assessment. It offers a tool that could potentially aid reproducibility and standardization of liver biopsy assessments required for NASH therapeutic clinical trials.

3.
BMC Public Health ; 18(1): 708, 2018 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-29879949

RESUMO

BACKGROUND: Hepatitis C is a curable disease, but reinfection from household contact may occur in patients who have achieved sustained viral response (SVR). METHODS: A total of 997 ethnic Han HCV treatment-naïve adult patients were enrolled in a cross-sectional study with stratified sampling based on the populations of five geographic regions across China to examine the genetic and physiological parameters associated with the phenomenon of HCV familial clustering. RESULTS: Of the total 997 patients, there were 59 patients who had at least one family member with HCV infection according to patient self-report. Comparison between patients with and without HCV familial clustering by univariate regression analysis showed that genotype 2, sexual transmission, long-term exposure to HCV patients, monthly family income per person less than 2000 yuan, farming occupation, and the southern and northern regions were associated with HCV familial clustering. Blood transfusion was negatively associated with HCV familial clustering. Multivariate logistic regression analysis suggested that long-term exposure to HCV patients and low family income were correlated with HCV familial clustering, whereas blood transfusion was negatively associated, which meant that blood transfusion was not the main transmission route in HCV familial clustering. CONCLUSION: Long-term exposure to HCV patients and low family income were correlated with HCV familial clustering, whereas blood transfusion was not the main transmission route in HCV familial clustering. To reduce reinfection from household contacts, education and awareness of HCV transmission routes and familial clustering should be strengthened, especially among HCV patients' family members, low-income families and non-blood transmission hepatitis C patients.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Família/etnologia , Hepatite C/etnologia , Adulto , China/epidemiologia , Análise por Conglomerados , Estudos Transversais , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Feminino , Hepatite C/genética , Hepatite C/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Pobreza/estatística & dados numéricos , Fatores de Risco
5.
Am J Clin Pathol ; 148(6): 502-512, 2017 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-29165568

RESUMO

Objectives: Investigate subtle fibrosis similarities and differences in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using second harmonic generation (SHG). Methods: SHG/two-photon excitation fluorescence imaging quantified 100 collagen parameters and determined qFibrosis values by using the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) scoring system in 62 adult and 36 pediatric NAFLD liver specimens. Results: Six distinct parameters identified differences among the NASH CRN stages with high accuracy (area under the curve, 0835-0.982 vs 0.885-0.981, adult and pediatric). All portal region parameters showed similar changes across early stages 0, 1C, and 2, in both groups. Parameter values decreased in adults with progression from stage 1A/B to 2 in the central vein region. In children, aggregated collagen parameters decreased, but nearly all distributed collagen parameters increased from stage 1A/B to 2. Conclusions: SHG analysis accurately reproduces NASH CRN staging in NAFLD, as well as reveals differences and similarities between adult and pediatric collagen deposition not captured by currently available quantitative methods.


Assuntos
Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Adolescente , Adulto , Fatores Etários , Biópsia/métodos , Criança , Progressão da Doença , Feminino , Fibrose , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto Jovem
6.
J Gastroenterol Hepatol ; 32(1): 244-252, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27289083

RESUMO

BACKGROUND AND AIM: In China, chronic hepatitis C virus (HCV) infection represents a considerable healthcare burden. Although interferon-based therapy has been the standard-of-care for many years, few long-term, real-life studies have assessed interferon-based treatment in China. The objective of CCgenos follow-up study was to analyze long-term treatment patterns and outcomes in a cohort of treatment-naïve, Han ethnic, patients with chronic HCV infection. METHODS: Patients who had participated in the CCgenos cross-sectional study were invited to enter this 5-year follow up. Clinical information and centralized HCV-RNA measures were collected at scheduled study visits every 6 months for untreated patients and every 3 months for treated patients. RESULTS: Among 512 patients enrolled, 334 (65.2%) received interferon-based treatment and 178 (34.8%) remained untreated over a median of 4.1 (1.2-4.3) years. A total of 82.8% (424/512) of patients had an IL28B CC genotype (GT); 60.7% (311/512) had HCV GT1b infection, including 121 (38.9%) untreated. Most patients with baseline cirrhosis were untreated (26/46, 56.5%). Among patients who completed treatment and 24 weeks of post-treatment follow up, the duration of interferon-based therapy was frequently longer than recommended (52.9% [92/174] of GT1b-infected were treated for > 1 year). Rates of sustained virologic response (SVR24) were 71.1% (226/318) overall; 62.4% (111/178) among patients with HCV GT1b infection; and 42.9% (15/35) among patients with cirrhosis. CONCLUSIONS: There remains a high unmet need for effective HCV treatment in China, evidenced by a high proportion of patients remaining untreated by the current standard-of-care and relatively low SVR24 rates for patients with both GT1b infection and cirrhosis.


Assuntos
Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Fatores de Tempo , Resultado do Tratamento
7.
Lab Invest ; 97(1): 84-92, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27918557

RESUMO

Animal models provide a useful platform for developing and testing new drugs to treat liver fibrosis. Accordingly, we developed a novel automated system to evaluate liver fibrosis in rodent models. This system uses second-harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy to assess a total of four mouse and rat models, using chemical treatment with either thioacetamide (TAA) or carbon tetrachloride (CCl4), and a surgical method, bile duct ligation (BDL). The results obtained by the new technique were compared with that using Ishak fibrosis scores and two currently used quantitative methods for determining liver fibrosis: the collagen proportionate area (CPA) and measurement of hydroxyproline (HYP) content. We show that 11 shared morphological parameters faithfully recapitulate Ishak fibrosis scores in the models, with high area under the receiver operating characteristic (ROC) curve (AUC) performance. The AUC values of 11 shared parameters were greater than that of the CPA (TAA: 0.758-0.922 vs 0.752-0.908; BDL: 0.874-0.989 vs 0.678-0.966) in the TAA mice and BDL rat models and similar to that of the CPA in the TAA rat and CCl4 mouse models. Similarly, based on the trends in these parameters at different time points, 9, 10, 7, and 2 model-specific parameters were selected for the TAA rats, TAA mice, CCl4 mice, and BDL rats, respectively. These parameters identified differences among the time points in the four models, with high AUC accuracy, and the corresponding AUC values of these parameters were greater compared with those of the CPA in the TAA rat and mouse models (rats: 0.769-0.894 vs 0.64-0.799; mice: 0.87-0.93 vs 0.739-0.836) and similar to those of the CPA in the CCl4 mouse and BDL rat models. Similarly, the AUC values of 11 shared parameters and model-specific parameters were greater than those of HYP in the TAA rats, TAA mice, and CCl4 mouse models and were similar to those of HYP in the BDL rat models. The automated evaluation system, combined with 11 shared parameters and model-specific parameters, could specifically, accurately, and quantitatively stage liver fibrosis in animal models.


Assuntos
Automação Laboratorial/métodos , Cirrose Hepática/diagnóstico , Fígado/patologia , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Animais , Ductos Biliares/cirurgia , Tetracloreto de Carbono , Modelos Animais de Doenças , Hidroxiprolina/metabolismo , Ligadura/efeitos adversos , Fígado/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ratos Sprague-Dawley , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Especificidade da Espécie , Tioacetamida
8.
BMJ Open ; 6(10): e012016, 2016 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-27733412

RESUMO

OBJECTIVES: Little is known about hepatitis B virus (HBV) infection in patients with hepatitis C virus (HCV) infection in China. This study aimed to evaluate the prevalence, clinical characteristics, viral interactions and host genotypes of HBV/HCV dual infection compared with HCV monoinfection. STUDY DESIGN: A cross-sectional study. SETTING: China. PARTICIPANTS AND METHODS: 997 patients with HCV from 28 university-affiliated hospitals in China were enrolled in this research. Patients were divided into two subgroups. RESULTS: The prevalence of HBV infection in patients with HCV was 4.11% (41/997). The age-specific prevalence of HBsAg was 0.70%, 3.97% and 5.85% in groups aged 18-30, 30-50 and >50 years old (p=0.057), respectively. Patients with HBV/HCV dual infection and patients with HCV monoinfection had similar HCV viral loads (5.80±0.89 vs 5.83±1.00 log10 IU/mL, p=0.904). The dominant HCV genotype was 1b in both groups (53.65% vs 56.90%, p=0.493). The protective C allele in IL-28B (rs12979860) was also the dominant allele type in both patient groups (85.36% vs 83.99%, p=0.814). Patients with HBV/HCV dual infection had a higher ratio of liver cirrhosis and hepatic decompensation than patients with HCV monoinfection (39.02% vs 17.69%, p=0.001; 31.70% vs 12.13%, p=0.001). CONCLUSIONS: The HBV burden was moderate in HCV-infected patients in China. Liver cirrhosis was more common in patients with HBV/HCV dual infection, suggesting the need for closer monitoring of dual-infected individuals. TRIAL REGISTRATION NUMBER: NCT01293279; Post-results.


Assuntos
Coinfecção/epidemiologia , Hepacivirus/patogenicidade , Vírus da Hepatite B/patogenicidade , Hepatite B , Hepatite C , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Coinfecção/genética , Coinfecção/virologia , Estudos Transversais , Feminino , Genótipo , Hepacivirus/genética , Hepatite B/epidemiologia , Hepatite B/genética , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Hepatite C/epidemiologia , Hepatite C/genética , Hepatite C/patologia , Hepatite C/virologia , Humanos , Interferons , Interleucinas/metabolismo , Cirrose Hepática/epidemiologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
9.
Hepatobiliary Pancreat Dis Int ; 15(1): 55-64, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26818544

RESUMO

BACKGROUND: Chronic hepatitis C virus (HCV) infection causes the skewing and activation of B cell subsets, but the characteristics of IgG+ B cells in patients with chronic hepatitis C (CHC) infection have not been thoroughly elucidated. CD4+CXCR5+ follicular helper T (Tfh) cells, via interleukin (IL)-21 secretion, activate B cells. However, the role of CD4+CXCR5+ T cells in the activation of IgG+ B cells in CHC patients is not clear. METHODS: The frequency of IgG+ B cells, including CD27-IgG+ B and CD27+IgG+ B cells, the expression of the activation markers (CD86 and CD95) in IgG+ B cells, and the percentage of circulating CD4+CXCR5+ T cells were detected by flow cytometry in CHC patients (n=70) and healthy controls (n=25). The concentrations of serum IL-21 were analyzed using ELISA. The role of CD4+CXCR5+ T cells in the activation of IgG+ B cells was investigated using a co-culture system. RESULTS: A significantly lower proportion of CD27+IgG+ B cells with increased expression of CD86 and CD95 was observed in CHC patients. The expression of CD95 was negatively correlated with the percentage of CD27+IgG+ B cells, and it contributed to CD27+IgG+ B cell apoptosis. Circulating CD4+CXCR5+ T cells and serum IL-21 were significantly increased in CHC patients. Moreover, circulating CD4+CXCR5+ T cells from CHC patients induced higher expressions of CD86 and CD95 in CD27+IgG+ B cells in a co-culture system; the blockade of the IL-21 decreased the expression levels of CD86 and CD95 in CD27+IgG+ B cells. CONCLUSIONS: HCV infection increased the frequency of CD4+CXCR5+ T cells and decreased the frequency of CD27+IgG+ B cells. CD4+CXCR5+ T cells activated CD27+IgG+ B cells via the secretion of IL-21.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Comunicação Celular , Hepatite C Crônica/imunologia , Imunoglobulina G/imunologia , Interleucinas/imunologia , Ativação Linfocitária , Receptores CXCR5/imunologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Adulto , Apoptose , Linfócitos B/metabolismo , Antígeno B7-2/sangue , Antígeno B7-2/imunologia , Biomarcadores/sangue , Relação CD4-CD8 , Linfócitos T CD4-Positivos/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Feminino , Citometria de Fluxo , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Humanos , Imunoglobulina G/sangue , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Receptores CXCR5/sangue , Transdução de Sinais , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue , Receptor fas/sangue , Receptor fas/imunologia
10.
Chin Med J (Engl) ; 128(19): 2625-31, 2015 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-26415801

RESUMO

BACKGROUND: It has been reported that several baseline polymorphisms of direct-acting antivirals (DAAs) agents resistance-associated variants (RAVs) would affect the treatment outcomes of patients chronically infected with hepatitis C virus (CHC). The aim of this study is to investigate the prevalence of DAAs RAVs in treatment-naÏve GT1b CHC patients. METHODS: Direct sequencing and ultra-deep sequencing of the HCV NS3, NS5A, and NS5B gene were performed in baseline serum samples of treatment-naÏve patients infected with genotype 1b hepatitis C virus (HCVs). RESULTS: One hundred and sixty CHC patients were studied. Complete sequence information was obtained for 145 patients (NS3), 148 patients (NS5A), and 137 patients (NS5B). Treatment-failure associated variants of DAAs were detected: 56.6% (82/145) of the patients presented S122G for simeprevir (NS3 protease inhibitor); 10.1% (14/148) of the patients presented Y93H for daclatasvir and ledipasvir (NS5A protein inhibitors); 94.2% (129/137) of the patients presented C316N for sofosbuvir (NS5B polymerase inhibitor). Nearly, all of the DAAs RAVs detected by ultra-deep sequencing could be detected by direct sequencing. CONCLUSIONS: The majority of genotype 1b CHC patients in China present a virus population carrying HCV DAAs RAVs. Pretreatment sequencing of HCV genome might need to be performed when patients infected with GT1b HCV receiving DAAs-containing regimens in China. Population sequencing would be quite quantified for the work.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepacivirus/patogenicidade , Polimorfismo Genético/genética , Adulto , Idoso , Benzimidazóis/uso terapêutico , China , Farmacorresistência Viral/genética , Feminino , Fluorenos/uso terapêutico , Genótipo , Hepatite C/tratamento farmacológico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Simeprevir/uso terapêutico
11.
Braz. j. infect. dis ; 19(4): 390-398, July-Aug. 2015. tab, ilus
Artigo em Inglês | LILACS | ID: lil-759273

RESUMO

Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expen- sive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen) had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%), and hepatitis C virus core antigen decrease greater than 1 log10 IU/mL (early virological response based on hepatitis C virus core antigen) had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.Z%). Analysis on the validation group demonstrated a positive predictivevalue of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to hepatitis C virus RNA in predicting sustained virologic response of chronic genotype 1 hepatitis C virus infected patients, and can be used to guide anti-hepatitis C virus treatment, especially in resource-limited areas.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Hepacivirus/imunologia , Antígenos da Hepatite C/imunologia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Genótipo , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Valor Preditivo dos Testes , Curva ROC , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Proteínas do Core Viral/imunologia
12.
Braz J Infect Dis ; 19(4): 390-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26100438

RESUMO

Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expensive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen) had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%), and hepatitis C virus core antigen decrease greater than 1log10IU/mL (early virological response based on hepatitis C virus core antigen) had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.2%). Analysis on the validation group demonstrated a positive predictive value of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to hepatitis C virus RNA in predicting sustained virologic response of chronic genotype 1 hepatitis C virus infected patients, and can be used to guide anti-hepatitis C virus treatment, especially in resource-limited areas.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/imunologia , Antígenos da Hepatite C/imunologia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Feminino , Genótipo , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Proteínas do Core Viral/imunologia
13.
BMC Public Health ; 15: 460, 2015 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-25933922

RESUMO

BACKGROUND: The epidemiologies of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in specific populations in certain areas of China are poorly understood. A pilot survey of HCV/HBV infections was carried out in villages in Kuancheng County, Heben Province, where injection of sodium benzoate or amphetamines using shared needles has been a common practice. The aims of this study were to analyze the endemicity and characterize HCV/HBV infections in this population. METHODS: Data on demographic characteristics and drug abuse were collected from individuals who signed informed consent forms. Serum HCV antibody (anti-HCV), hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (anti-HBc) were measured in all participants. HCV RNA was measured in samples positive for anti-HCV using real-time polymerase chain reaction. RESULTS: Among 852 participants from 11 villages, 49.9% had used sodium benzoate or amphetamine at least once, by intravenous injection. The overall prevalence of anti-HCV, HCV RNA, anti-HBc, HBsAg, and HCV/HBV co-infection was 37.1%, 26.6%, 67.7%, 10.7%, and 30.0%, respectively. Two-hundred-twenty-three of 227 (98.2%) participants positive for HCV RNA were aged >40 years. Co-infection was related to sex, age, number of injections, and time from first injection. The rate of spontaneous HCV RNA clearance was 28.2% (89/316), and was related to the number of injections, time from first injection, and HBsAg positivity. However, HBsAg was related to the anti-HBc signal/cut-off ratio rather than to the above parameters. Trend tests demonstrated that the prevalence of anti-HCV, HCV RNA, and anti-HBc was related to the number of injections (P < 0.001), while HBsAg prevalence was not (P = 0.347). CONCLUSIONS: The prevalence of HCV and HBV infection is likely to be high among individuals older than 40 years in areas of needle sharing, and one-time screening for HCV infection should be offered to these populations.


Assuntos
Hepatite B/epidemiologia , Hepatite C/epidemiologia , Uso Comum de Agulhas e Seringas/estatística & dados numéricos , Adulto , Idoso , China/epidemiologia , Coinfecção , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Transtornos Relacionados ao Uso de Substâncias , Adulto Jovem
14.
BMC Gastroenterol ; 14: 47, 2014 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-24625322

RESUMO

BACKGROUND: Earlier kinetics of serum HCV core antigen (HCVcAg) and its predictive value on sustained virological response (SVR) were investigated in patients with genotype 1 HCV infection during antiviral treatment. METHODS: In a multi-centered, randomized and positive drug-controlled phase IIb clinical trial on type Y peginterferon α-2b ( NCT01140997), forty-eight CHC patients who participated in pharmacokinetics were randomly divided into 4 cohorts and treated with PegIFNα (type Y peginterferon α-2b 90 µg, 135 µg, 180 µg and PegIFNα-2a 180 µg, respectively, once a week) and ribavirin (< 75 kg, 1000 mg daily and ≥ 75 kg, 1200 mg daily) for 48 weeks, and then followed up for 24 weeks. 32 patients infected with genotype 1 HCV and completed the whole process were included in this study. HCV RNAs were detected at baseline, and weeks 4, 12, 24, 48 and 72 using Cobas TaqMan. ARCHITECT HCVcAg was performed at 24, 48, 72, 96, 120 and 144 h in addition to the above time points. The receiver operating curves (ROCs) were performed to study the predictive values of HCVcAg decline on SVR. RESULTS: Following antiviral treatment, serum HCVcAg levels rapidly declined within the first week and correlated well with corresponding HCV RNA at baseline, weeks 4, 12, 24, 48 and 72 (rs = 0.969, 0.928, 0.999, 0.983, 0.985 and 0.946, respectively, P < 0.001). All of the areas under the receiver operating curves (AUROCs) were more than 0.80 and showed good predictive power on SVR at 24, 48, 72, 96, 120 and 144 h. The144 h was the best predictive time point of HCVcAg decline on SVR because of its largest AUROC (more than 0.90). CONCLUSIONS: Early kinetics of serum HCVcAg predicts SVR very well in genotype 1 CHC patients during antiviral treatment, and its reduction value at 144 h is an earlier and stronger predictor on SVR than rapid virological response and early virological response. (TRN: NCT01140997).


Assuntos
Antivirais/uso terapêutico , Hepacivirus/imunologia , Antígenos da Hepatite C/sangue , Hepatite C Crônica/tratamento farmacológico , RNA Viral/sangue , Proteínas do Core Viral/imunologia , Adulto , Área Sob a Curva , Biomarcadores/sangue , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/sangue , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Valor Preditivo dos Testes , Curva ROC , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Fatores de Tempo
15.
Zhonghua Gan Zang Bing Za Zhi ; 21(6): 438-41, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-24034845

RESUMO

OBJECTIVE: To conduct a meta-analysis to study the effect of antiviral therapy on the prognosis of patients with chronic hepatitis B (CHB)-related cirrhosis. METHODS: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese Biomedical Database, Chinese Journals Full-text Database, and Wan Fang Digital Journal Full-text Database were searched for studies on nucleoside analogues antiviral treatment outcome of patients with CHB-related cirrhosis (vs. controls without antiviral therapy) published between January 1998 and March 2012. Data extraction and quality assessment was performed by two independent investigators. Heterogeneity was assessed by the I2 index. In the case of homogeneity the random-effects model was applied, and in the case of heterogeneity the fixed-effects model was applied. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Seven studies were included in the meta-analysis: one high-quality randomized-controlled trial (RCT) study, four prospective cohort studies, and two case-control studies. Compared to the control group, the group treated with antiviral therapy showed a significantly lower incidence of hepatocellular carcinoma (11.2%, 76/680 vs. 6.7%, 75/1116; OR = 0.56, 95% CI: 0.40 to 0.79, P = 0.001) and lower mortality (23.6%, 78/331 vs. 10.8%, 43/398; OR = 0.36, 95% CI: 0.23 to 0.55, P = 0.000). CONCLUSION: Antiviral therapy with nucleoside analogues significantly reduces the incidence of hepatocellular carcinoma and mortality in patients with CHB-related cirrhosis.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Nucleotídeos/uso terapêutico , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Prognóstico
16.
Chin Med J (Engl) ; 126(13): 2430-4, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23823813

RESUMO

BACKGROUND: The etiological spectrum of cirrhosis has changed over the years, but our knowledge of it is limited. The present study aimed to investigate the etiological features of cirrhosis inpatients and their variation in the past 18 years in Beijing. METHODS: A retrospective analysis was performed on all patients with cirrhosis diagnosed for the first time in Peking University People's Hospital from January 1, 1993, to October 25, 2010. Data were analyzed using SPSS 20.0. RESULTS: A total of 2119 cirrhosis inpatients were included in this study: 1412 (66.6%) male and 707 (33.4%) female. Chronic hepatitis B accounted for 58.7%; chronic hepatitis C for 7.6%; chronic hepatitis B and hepatitis C virus co-infection for 0.8% (16 cases); alcoholic liver disease for 9.4% (200 cases); and autoimmune diseases for 9.4% (199 cases). In the past 18 years, the percentage of chronic hepatitis B has decreased from 75.2% to 48.7%; alcoholic liver disease has increased from 5.1% to 10.6%; and autoimmune disease has increased from 2.2% to 12.9%. The percentages of chronic hepatitis B and alcoholic liver disease were higher among men, whereas the percentages of chronic hepatitis C, autoimmune diseases and cryptogenic cirrhosis were higher among women. CONCLUSIONS: Chronic hepatitis B was still the most common etiology of cirrhosis in China, but the percentage has been decreasing. The percentages of alcoholic liver disease and autoimmune diseases have been increasing. The etiological spectrum of cirrhosis inpatients differed significantly according to sex.


Assuntos
Cirrose Hepática/etiologia , Adulto , Idoso , Feminino , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Hepatopatias Alcoólicas/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Caracteres Sexuais
17.
J Gastroenterol Hepatol ; 28(7): 1114-21, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23611115

RESUMO

BACKGROUND AND AIM: Recent studies suggested that interleukin 28B (IL28B) polymorphisms may affect spontaneous clearance (SC) of hepatitis C virus (HCV) infection. Our purpose was to update the meta-analysis to reevaluate the impact of IL28B rs12979860 and rs8099917 polymorphisms on SC in patients infected with HCV. METHODS: We searched PubMed, Web of Science, and Embase up to February 2013. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated by fixed- or random-effects models. Heterogeneity, sensitivity analysis, and publication bias were also assessed. RESULTS: Seventeen eligible papers were involved in this study. The SC rate was higher in patients with the rs12979860 CC (vs CT/TT OR = 2.98, 95% CI 2.53-3.50) and rs8099917 TT (vs GT/GG OR = 2.80, 95% CI 2.23-3.51) in the IL28B polymorphisms. Ethnicity stratification revealed that rs12979860 CC was associated with SC for Caucasians (vs CT/TT OR = 3.05, 95% CI 2.67-3.49), Asians (vs CT/TT OR = 1.88, 95% CI 1.33-2.66), and Africans (vs CT/TT OR = 3.15, 95% CI 2.39-4.15); rs8099917 TT was associated with SC for Caucasians (vs GT/GG OR = 2.48, 95% CI 1.96-3.15). CONCLUSIONS: IL28B rs12979860 and rs8099917 single nucleotide polymorphisms are significantly associated with SC of HCV infection. The predictive value of rs12979860 CC was stronger in Caucasians and Africans than in Asians.


Assuntos
Hepatite C/genética , Interleucinas/genética , Polimorfismo Genético , Grupos de Populações Continentais , Genótipo , Hepatite C/tratamento farmacológico , Hepatite C/etnologia , Hepatite C/virologia , Humanos , Interferons , Remissão Espontânea
18.
PLoS One ; 7(6): e39272, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22768067

RESUMO

BACKGROUND: There is a significant association between effects of interferon-alpha treatment and the risk of developing hyperglycemia in patients with chronic hepatitis C virus (HCV) infection. The objective of this systematic review and meta-analysis on the basis of published observational studies was to estimate risk of hyperglycemia in chronic HCV patients who had acquired sustained virological responses (SVR) compared to those without SVR. METHODOLOGY: We identified eligible studies by searching the relevant databases, including PubMed, Embase, and Google, for papers published between January 1990 and April 2011. The selection of eligible papers was carried out using a scoring system based on guidelines and inclusion criteria that were established before the articles were identified. Heterogeneity across studies was determined and the meta-analysis was performed following standard guidelines. CONCLUSIONS: Eleven eligible studies provided data of the incidence of hyperglycemia in chronic hepatitis C patients with SVR in comparison with patients without these conditions. The results demonstrated that SVR was associated with a lower risk of hyperglycemia (odds ratio = 0.497, 95% confidence interval 0.421-0.587, p<0.001), and there was no evidence of any substantial between-study heterogeneity (I(2) = 24.4%, p>0.1). Results of meta-regression showed patients with different baseline glucose (normal vs. abnormal) and patients with co-infected HIV (presence vs. absence) as the sources of low heterogeneity (p<0.15).The lowest risk of hyperglycemia was described in patients with normal glucose baseline (OR = 0.402, 95%CI 0.297-0.543, p<0.001). This is the first systematic review and meta-analysis performed to examine the association between SVR and risk of hyperglycemia in patients with HCV infection. Our meta-analysis suggests that SVR reduce the risk of developing glucose abnormalities, especially in patients with normal glucose baseline.


Assuntos
Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hiperglicemia/induzido quimicamente , Hiperglicemia/epidemiologia , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Intervalos de Confiança , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Hiperglicemia/complicações , Incidência , Razão de Chances , Viés de Publicação
19.
Nephrol Dial Transplant ; 27(2): 640-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21558431

RESUMO

BACKGROUND: Hepatitis C virus (HCV) is associated with various glomerulopathies, in which HCV is responsible not only for the onset of glomerulopathy but also for its progressive loss of kidney function. The effect of antiviral treatment on the glomerular lesions and subsequent course of kidney disease remains controversial. Therefore, we performed a systematic analysis of the available evidence on the effect of interferon (IFN)-α-based therapy on HCV-associated chronic kidney disease. METHODS: A meta-analysis was performed of controlled and uncontrolled clinical studies related to IFNα-based antiviral therapy and its impact on kidney function in HCV-associated glomerulonephritis. Improvement of proteinuria and serum creatinine levels after antiviral therapy was taken as the end points of interest. Data from eligible studies selected according to protocols were analysed using Review Manager 5.0. RESULTS: Eleven clinical trials involving 225 patients were included in our meta-analysis. At the end of antiviral therapy, the summary estimate of the mean decrease in proteinuria was 2.71 g/24 h [95% confidence interval (CI) 1.38-4.04, P < 0.0001], P-value for heterogeneity 0.05 (I(2) = 53%). The pooled decrease in mean serum creatinine levels was 0.23 mg/dL (95% CI 0.02-0.44, P = 0.03), P-value for heterogeneity 0.30 (I(2) = 17%). Comparison of non-sustained virological response (SVR) to SVR groups demonstrated a mean difference of proteinuria decrease in the SVR group of 1.04 g/24 h (95% CI 0.20-1.89, P = 0.02), P-value for heterogeneity 0.21 (I(2) = 36%) and of serum creatinine decrease of 0.05 mg/dL (95% CI -0.33 to 0.43, P = 0.80), P-value for heterogeneity 0.70 (I(2) = 0%). CONCLUSION: Antiviral therapy based on IFNα can significantly decrease proteinuria and stabilize serum creatitine, and therefore, should be undertaken in patients with HCV-associated glomerulonephritis. The improvement in protein excretion is greater in those who achieve HCV RNA clearance, a finding in line with a causal role for HCV in glomerulonephritis.


Assuntos
Antivirais/uso terapêutico , Glomerulonefrite/epidemiologia , Glomerulonefrite/virologia , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Interferon-alfa/uso terapêutico , Comorbidade , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Medicina Baseada em Evidências , Feminino , Seguimentos , Taxa de Filtração Glomerular , Hepacivirus/efeitos dos fármacos , Hepatite C/diagnóstico , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
20.
J Gastroenterol Hepatol ; 27(3): 526-32, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21871021

RESUMO

BACKGROUND AND AIMS: Commercial plasma donation was introduced in China in the 1970s. Cases of non-A, non-B hepatitis (hepatitis C) continued to occur, with multiple outbreaks among plasma donors in Guan county, Hebei province between 1972 and 1990. The outcomes of hepatitis C virus (HCV) infection in these paid plasma donors from six villages of Guan county were followed up for 12-19 years. METHODS: A total of 402 plasma donors with HCV infection were enrolled since anti-HCV-positive in 1991 or 1998. Follow up was maintained until death or the end of the observation period. No antiviral treatment was applied during the period of infection. RESULTS: Follow up was lost in 23 cases. After a 12-19-year follow up, 31 donors died, with the cause of death directly related to liver disease in 15 cases, and an overall mortality of 8.18% (31/379). The incidence of liver cirrhosis was 10.03%, and hepatocellular carcinoma (HCC) was 2.90%. The rate of viral spontaneous clearing was 20.32% (77/379), and 13.69% (23/168) in males and 25.59% (54/211) in females. In May 2010, detections were performed in 348 cases. Abnormality of liver function was related to HCV viremia. Sex and alcohol intake impacted the outcome of HCV infection. There was no correlation between the viral spontaneous clearance with age of infection and genotype. CONCLUSIONS: This area has a high rate of chronicity in HCV infection due to plasma donation. Twenty-five years after virus infection, liver cirrhosis or HCC developed in one-tenth of patients, with an overall mortality of 8.18%.


Assuntos
Anticorpos Antivirais/sangue , Doadores de Sangue , Carcinoma Hepatocelular/complicações , Hepacivirus/imunologia , Hepatite C Crônica/complicações , Neoplasias Hepáticas/complicações , RNA Viral/sangue , Adulto , Fatores Etários , Idoso , Alanina Transaminase/sangue , Consumo de Bebidas Alcoólicas , Aspartato Aminotransferases/sangue , Carcinoma Hepatocelular/mortalidade , Distribuição de Qui-Quadrado , China , Elasticidade , Feminino , Seguimentos , Genótipo , Hepacivirus/genética , Hepatite C Crônica/diagnóstico por imagem , Hepatite C Crônica/mortalidade , Hepatite C Crônica/virologia , Humanos , Fígado/diagnóstico por imagem , Fígado/fisiopatologia , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Razão de Chances , Remissão Espontânea , Fatores Sexuais , Ultrassonografia , Adulto Jovem
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