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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.
Dis Markers ; 2019: 2585409, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885733

RESUMO

Background and Aim: Little information is available about the assessment and optimal use of the gamma-glutamyl transpeptidase-to-platelet ratio (GPR) and transient elastography (TE) in predicting liver cirrhosis in patients with chronic hepatitis B (CHB) and concurrent nonalcoholic fatty liver disease (NAFLD). This study is aimed at comparing their diagnostic performances and developing an optimal approach for predicting liver cirrhosis in CHB patients with NAFLD. Methods: Consecutive CHB patients with NAFLD were enrolled. The GPR was calculated, and TE was performed using liver biopsy as a reference standard. The accuracy of predicting liver cirrhosis using GPR and TE was assessed and compared, and an optimal approach was developed. Results: Both TE and GPR correlated significantly with the histological fibrosis stage. TE and GPR had excellent performance in predicting liver cirrhosis, and the comparison of areas under the receiver operating characteristic curves revealed that TE was superior to GPR (0.95 vs. 0.85, P = 0.039). Moreover, the dual cutoffs established by the likelihood ratio showed that GPR had a similar misclassification but higher indeterminate rate than TE (54.5% vs. 11.7%, P < 0.001). Additionally, a 2-step approach using GPR followed by TE had comparable performance to that of both GPR and TE tests for all patients (misclassification: 8.9% vs. 8.3%, P = 0.866; indeterminate rate: 15.2% vs. 17.2%, P = 0.750) but could reduce TE scans by approximately one-third. Conclusions: Both TE and GPR show excellent performance in predicting liver cirrhosis in CHB patients with NAFLD. The 2-step approach using GPR followed by TE may be optimal for the assessment of cirrhosis in CHB patients with NAFLD.

3.
Medicine (Baltimore) ; 98(33): e16778, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415381

RESUMO

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been widely recommended as a first-line antiviral agent to treat chronic hepatitis B (CHB). Qingzhong and Viread, formulations of TDF commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd and GlaxoSmithKline, respectively, have both been approved by the State Food and Drug Administration, China. This study analyzed the efficacy and safety of these 2 TDF agents in Chinese patients with CHB. METHODS: In this multicenter, randomized, double-blind, double-dummy, noninferiority phase 3 clinical trial (ClinicalTrials.gov identifier: NCT02287857), 330 Chinese patients with CHB [hepatitis B envelope antigen-positive (HBeAg) (+): 232] were randomly assigned to receive Qingzhong (group A: 161 patients) or Viread (group B: 169 patients) 300 mg once daily for 48 weeks. Subsequently, all patients were administered Qingzhong 300 mg once daily from week 49 to week 240. The primary end point was the degree of decline of plasma hepatitis B virus (HBV) DNA levels at week 48 and the secondary endpoints were viral suppression, normalization of alanine aminotransferase (ALT) levels, hepatitis B surface antigen (HBsAg)/HBeAg loss or seroconversion, and virological breakthrough. RESULTS: Among patients with CHB who were HBeAg (+), the mean HBV DNA titer decreased similarly between the groups at week 48. The percentages of patients who achieved undetectable HBV DNA were similar between the groups (85.11% and 82.35% in groups A and B, respectively) and similar losses of HBeAg and HBeAg seroconversion rates were achieved. Moreover, for patients with CHB who were HBeAg (-), reductions in HBV DNA were similar. Among all patients with CHB, the rates of normalization of ALT and the loss of HBsAg were similar. The overall incidence of adverse events was comparable between the groups. CONCLUSION: In conclusion, the 48-week administration of Qingzhong showed noninferior efficacy and safety profiles compared to Viread in Chinese patients with CHB.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , China , Método Duplo-Cego , Esquema de Medicação , Composição de Medicamentos , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir/administração & dosagem , Resultado do Tratamento , Adulto Jovem
4.
J Immunol Res ; 2019: 1538439, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31198792

RESUMO

Background and Aims: Serum immunoglobulins are frequently increased in patients with chronic liver disease, but little is known about the role of serum immunoglobulins and their correlations with interleukin-27 (IL-27) in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). This study was aimed at determining the role of serum immunoglobulin (IgG, IgA, and IgM) levels and their associations with IL-27 in noncirrhotic patients with HBV-ACLF. Methods: Samples were assessed from thirty patients with HBV-ACLF, twenty-four chronic hepatitis B (CHB) subjects, and eighteen normal controls. Disease severity of HBV-ACLF was evaluated. Serum IL-27 levels were examined by enzyme-linked immunosorbent assay. Immunoglobulin levels were assessed using immunoturbidimetric assay. Correlations between immunoglobulin levels and IL-27 were analyzed. Receiver operating characteristic (ROC) curves were used to predict the 3-month mortality. Results: 25 (83.3%) HBV-ACLF patients had elevated serum IgG levels (>1 ULN), 14 (46.7%) patients had elevated IgA, and 15 (50%) had raised IgM. IgG, IgA, and IgM levels were higher in HBV-ACLF patients than in CHB patients and normal controls. Moreover, IgG, IgA, and IgM levels were positively correlated with Tbil levels but negatively correlated with prothrombin time activity (PTA) levels. Additionally, IgG levels were significantly increased in nonsurviving patients than in surviving HBV-ACLF patients (P = 0.007) and positively correlated with MELD score (r = 0.401, P = 0.028). Also, IgG levels were positively correlated with IL-27 levels in HBV-ACLF patients (r = 0.398, P = 0.029). Furthermore, ROC curve showed that IgG levels could predict the 3-month mortality in HBV-ACLF patients (the area under the ROC curve: 0.752, P = 0.005). Conclusions: Our findings demonstrated that serum immunoglobulins were preferentially elevated in HBV-ACLF patients. IgG levels were positively correlated with IL-27 and may predict prognosis in HBV-ACLF patients.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Vírus da Hepatite B/fisiologia , Hepatite B/diagnóstico , Imunoglobulina G/sangue , Fígado/patologia , Doença Aguda , Insuficiência Hepática Crônica Agudizada/mortalidade , Adulto , Feminino , Hepatite B/imunologia , Hepatite B/mortalidade , Humanos , Interleucina-27/sangue , Masculino , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Regulação para Cima
5.
J Viral Hepat ; 26(10): 1146-1155, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31087479

RESUMO

Hepatitis B virus (HBV) infection continues to be a major public health issue worldwide. HBsAg loss is associated with functional remission and improved long-term outcome, and is considered to be a 'functional cure' (also referred to as clinical or immunologic cure) for chronic hepatitis B. This ideal goal of therapy can be achieved using optimized combination regimens with direct-acting antivirals [eg nucleos(t)ide analogues (NAs)] and immunomodulators [eg pegylated interferon alpha2a (Peg-IFN)] in selected patients with chronic hepatitis B. Among different combination therapies currently available, those with NA lead-in followed by Peg-IFN in virally suppressed patients has been demonstrated to be effective. This review provides an updated overview of the evidence supporting the use of combination therapies and summarizes expert consensus on the roadmap to attain functional cure for chronic hepatitis B patients.

6.
Stem Cells Int ; 2019: 4130757, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863450

RESUMO

Background: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a common type of liver failure with a high mortality. This study aimed at investigating the safety and efficacy of the combination treatment of plasma exchange (PE) and umbilical cord-derived mesenchymal stem cell (UC-MSCs) transplantation for HBV-ACLF patients. Methods: A total of 110 HBV-ACLF patients treated in our hospital from January 2012 to September 2017 were enrolled into this trial and divided into the control group (n = 30), UC-MSC group (n = 30), PE group (n = 30), and UC-MSC + PE group (n = 20) based on their treatments. The hepatic function, coagulation, and virological and immunological markers were assessed at baseline and 30, 60, 90, 180, and 360 days. The endpoint outcomes were death and unfavorable outcome (need for liver transplantation or death). Results: The UC-MSC + PE group had the lowest rates of death and unfavorable outcome at 30 days, 60 days, and 90 days posttreatment among the four groups, but the difference did not reach significances. The multivariate logistic regression analysis demonstrated that hemoglobin, prothrombin activity, and MELD (model for end-stage liver disease) score were the independent factors associated with the unfavorable outcome (all P < 0.05). The levels of total bilirubin, alanine aminotransferase, aspartate transaminase, and MELD score were significantly decreased during treatments (all P < 0.05). Conclusion: UC-MSCs combined with PE treatment had good safety but cannot significantly improve the short-term prognosis of HBV-ACLF patients with as compared with the single treatment. The long-term efficacy should be further evaluated. This trial is registered with registration no. NCT01724398.

7.
Biomed Res Int ; 2019: 3951574, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809540

RESUMO

Background and Aims: Concordance between transient elastography (TE) and ultrasonography (US) in assessing liver fibrosis in patients with chronic hepatitis B (CHB) and concurrent nonalcoholic fatty liver disease (NAFLD) has been rarely studied. This study aimed to evaluate the individual and combined performances of TE and US in assessing liver fibrosis and cirrhosis. Patients and Methods: Consecutive CHB patients with NAFLD were prospectively enrolled. TE and US examinations were performed, with liver biopsy as a reference standard. Receiver operating characteristic (ROC) curves were obtained to evaluate the diagnostic performance. Differences between the areas under the ROC curves (AUCs) were compared using DeLong's test. Results: TE and US scores correlated significantly with the histological fibrosis staging scores. TE was significantly superior to US in the diagnosis of significant fibrosis (AUC, 0.84 vs 0.73; P=0.02), advanced fibrosis (AUC, 0.95 vs 0.76; P<0.001), and cirrhosis (AUC, 0.96 vs 0.71; P<0.001). Combining TE with US did not increase the accuracy of detecting significant fibrosis, advanced cirrhosis, or cirrhosis (P=0.62, P=0.69, and P=0.38, respectively) compared to TE alone. However, TE combined with US significantly increased the positive predictive value for significant fibrosis when compared to TE alone. The optimal cut-off values of TE for predicting advanced fibrosis and cirrhosis were 8.7 kPa and 10.9 kPa, with negative predictive values of 92.4% and 98.7%, respectively. Conclusions: TE is useful for predicting hepatic fibrosis and excluding cirrhosis in CHB patients with NAFLD. A combination of TE and US does not improve the accuracy in assessing liver fibrosis or cirrhosis.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatite B Crônica/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Ultrassonografia , Adulto , Área Sob a Curva , Biópsia , Índice de Massa Corporal , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/virologia , Curva ROC
8.
Lancet Gastroenterol Hepatol ; 4(2): 127-134, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30555048

RESUMO

BACKGROUND: Treatment with combined sofosbuvir and velpatasvir has resulted in high sustained virological response rates in patients chronically infected with hepatitis C virus (HCV) with genotypes 1-6 in clinical trials and real-world settings, but its efficacy and safety has not been assessed in Asia, a region with diverse HCV genotypes. METHODS: In this single-arm, open-label, phase 3 trial, we recruited patients from 38 sites across China, Thailand, Vietnam, Singapore, and Malaysia, who were chronically infected with HCV genotypes 1-6, and were HCV treatment-naive or treatment-experienced, either without cirrhosis or with compensated cirrhosis. Patients self-administered a combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks. The primary efficacy endpoint was sustained virological response, defined as HCV RNA less than 15 IU/mL at 12 weeks after completion of treatment (SVR12), assessed in all patients who received at least one dose of study drug. The primary safety endpoint was the proportion of adverse events leading to premature discontinuation of study drug. This trial is registered with ClinicalTrials.gov, number NCT02671500, and is completed. FINDINGS: Between April 14, 2016, and June 30, 2017, 375 patients were enrolled in the study, of whom 374 completed the full treatment course and one discontinued treatment. Overall, 362 (97% [95% CI 94-98]) of 375 patients achieved SVR12. Among 42 patients with HCV genotype 3b, all of whom had baseline resistance-associated substitutions in NS5A, 25 (89% [95% CI 72-98]) of 28 patients without cirrhosis and seven (50% [23-77]) of 14 patients with cirrhosis achieved SVR12. The most common adverse events were upper respiratory tract infection (36 [10%] patients) and headache (18 [5%] patients). There were no discontinuations due to adverse events. Serious adverse events were reported in three (1%) patients, none of which was judged to be related to sofosbuvir-velpatasvir treatment. INTERPRETATION: Consistent with data from other phase 3 studies, single-tablet sofosbuvir-velpatasvir for 12 weeks is an efficacious and safe treatment for Asian patients with chronic HCV infection, but might have lower efficacy in those infected with HCV genotype 3b and with cirrhosis. FUNDING: Gilead Sciences.

9.
Can J Gastroenterol Hepatol ; 2018: 1020925, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402448

RESUMO

T follicular helper cells (Tfh cells) affect essential immune pathogenesis in chronic hepatitis B virus (HBV) infection. The CCR7loPD-1hi Tfh subset has a partial Tfh effector phenotype and is associated with active Tfh differentiation, whereas the CCR7hiPD-1lo Tfh subset is a resting phenotype. We recruited 20 healthy volunteers and 77 patients with chronic HBV infection, including those in the immune tolerant (IT) phase (n=19), immune clearance (IC) phase (n=20), low replicative (LR) phase (n=18), and reactivation (RA) phase (n=20). The expression of CD4, CXCR5, PD-1, and CCR7 was detected in T cells from peripheral blood by flow cytometry. The frequency of the CCR7loPD-1hi T subset was significantly higher in the patients than in the healthy controls (14.92±4.87% vs 12.23±2.95%, p=0.018). The frequency of this Tfh subset in the IC group (18.42%±3.08) was increased compared with the IT group (11.94±2.87%, p=0.001) and LR group (13.65±4.93%, p=0.031) and was higher in the RA group than in the IT group (16.03±5.37% vs 11.94±2.87%, p=0.030). We observed a weak positive correlation between the CCR7loPD-1hi Tfh subset population and the alanine transaminase (ALT) level (r=0.370, p=0.001). The CCR7loPD-1h Tfh subset in the chronic HBV-infected patients was elevated to various degrees among the different immune phases. CCR7loPD-1hiCXCR5+CD4+ T cells are correlated with the immune status of chronic HBV infection patients and may be developed as a potential indicator for antiviral treatment.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Hepatite B Crônica/imunologia , Receptor de Morte Celular Programada 1/imunologia , Receptores CCR7/imunologia , Receptores CXCR5/imunologia , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Citometria de Fluxo , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Imunidade Ativa/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Ther Clin Risk Manag ; 14: 2127-2136, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464485

RESUMO

Background: IL-17-producing CD8+ T (Tc17) cells promote inflammation and have been identified in chronic hepatitis. However, the role of Tc17 cells in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF) remains unclear. Methods: The frequency of Tc17 cells in blood samples from 66 patients with HBV-ACLF was determined by flow cytometry. The levels of Tc17 cell-related cytokines were measured by FlowCytomix assays. The prognostic prediction accuracy was evaluated by the receiver operating characteristic (ROC) curve analysis. Survival was analyzed using Kaplan-Meier curves. Mortality predictors were determined by the Cox regression analysis. Results: The frequency of Tc17 cells was markedly higher in patients with HBV-ACLF than in those with chronic hepatitis B and normal control subjects. Increased frequencies of Tc17 cells may indicate liver injury and were positively correlated with disease severity. The Tc17 cell frequency was significantly higher in non-surviving patients with HBV-ACLF than in surviving patients. The ROC curve analysis showed that Tc17 cell frequency accurately predicted 90-day survival in patients with HBV-ACLF, with an accuracy equivalent to those of the Model for End-Stage Liver Disease (MELD), MELD-Na, and Chronic Liver Failure Consortium ACLF scores. Kaplan-Meier analysis showed an association between the increase in circulating Tc17 cells and poor overall survival in patients with HBV-ACLF. Moreover, the multivariate Cox regression analysis showed that Tc17 cell frequency was an independent predictor of overall survival in patients with HBV-ACLF. Conclusion: Tc17 cells may play a proinflammatory role in HBV-ACLF pathogenesis. Furthermore, the increased frequency of circulating Tc17 cells could be an independent prognostic biomarker in patients with HBV-ACLF.

11.
Medicine (Baltimore) ; 97(40): e12656, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30290645

RESUMO

Our previous study demonstrated that Th17 cells increased significantly in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). However, their prognostic role in HBV-ACLF patients remains unknown.Sixty-eight consecutive HBV-ACLF patients were enrolled in this cohort study. Th17 cells were examined using flow cytometry. Disease severity scores were assessed. ROC curves were used to evaluate the value in predicting prognosis. Survival was analyzed using Kaplan-Meier curves. Predictors of mortality were determined by regression analysis.Th17 cells were significantly higher in HBV-ACLF patients compared to patients with chronic hepatitis B and normal controls (both P < .001). Also, Th17 cells were higher in nonsurviving HBV-ACLF patients than in surviving patients (P = .014). Th17 cells were positively correlated with CLIF-Consortium ACLF (CLIF-C ACLF) score (r = 0.240, P = .048). ROC curves showed that the frequency of Th17 cells had accuracy in predicting 90-day prognosis equivalent to MELD, MELD-Na and CLIF-C ACLF scores in HBV-ACLF (P = .34, P = .26, and P = .15, respectively). More importantly, the area under the ROC curve (AUROC) increased when Th17 cells were combined with MELD, MELD-Na or CLIF-C ACLF score than using Th17 cells alone (P = .021, P = .006, and P = .023, respectively). Kaplan-Meier analysis revealed that higher Th17 cells (≥5.9%) were closely associated with poor overall survival in HBV-ACLF (P = .0086). Additionally, multivariate regression analysis showed that the frequency of Th17 cells over 5.9% was an independent predictor of mortality (OR = 0.154, P = .025).Circulating Th17 cells positively correlated with disease severity in HBV-ACLF. The frequency of Th17 cells over 5.9% could serve as a prognostic biomarker for HBV-ACLF patients.


Assuntos
Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/etiologia , Hepatite B Crônica/complicações , Células Th17/citologia , Insuficiência Hepática Crônica Agudizada/mortalidade , Adolescente , Adulto , Idoso , Comorbidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
12.
Cell Physiol Biochem ; 49(3): 1007-1018, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30196292

RESUMO

BACKGROUND/AIMS: Zinc finger antiviral protein (ZAP) has been reported to be expressed in hepatocellular carcinoma (HCC), and ZAP expression is associated with apoptotic signaling in cancer cells. This study aimed at investigating the expression of ZAP in HCC cells and its significance in clinical pathology. METHODS: Real-time quantitative PCR and western blot assays were employed to detect ZAP RNA and protein expression in normal human hepatocytes, HCC cells, and five primary HCC cell lines. Immunohistochemistry was performed to detect ZAP expression in 147 paraffin-embedded HCC tissues and adjacent normal tissues. The clinical significance of ZAP expression was analyzed in tissue samples from patients with or without infection by hepatitis B virus (HBV). RESULTS: ZAP expression in HCC cells and human primary HCC cell lines was significantly lower than that of normal human hepatocytes. Among 147 HCC samples, ZAP expression was lower in HCC tissues than in adjacent normal tissues for 107 (77.0%) samples. In patients with HCC and HBV infection, ZAP expression was related to pathological grade (P < 0.05); in HBV-negative patients with HCC, ZAP expression was associated with tumor size (P < 0.05) and clinical stage (P < 0.05). The overall survival time in patients with low ZAP expression was significantly shorter than survival times of those with high ZAP expression (P < 0.05), especially for patients with moderately to well-differentiated HCC (Grade 1-2) and HCC at stage T1 and T2 (P < 0.05). Cox multivariate analysis showed that ZAP expression was an independent predictor of survival of patients with HCC (P < 0.01). CONCLUSION: Low ZAP expression is closely associated with disease progression and poor prognosis for patients with HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas de Ligação a RNA/metabolismo , Adulto , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Hepatite B/complicações , Antígenos de Superfície da Hepatite B/sangue , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/complicações , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais
13.
Can J Gastroenterol Hepatol ; 2018: 1817680, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29862225

RESUMO

Background and Aims: We aimed to ascertain the feasibility and safety of NA cessation, the status of patients after cessation, and the predictive factors for relapse and subsequent retreatment. Methods: A total of 92 patients were enrolled in this prospective study. Patients were monitored every month for the first 3 months after cessation and every 3 months thereafter. Results: Sixty-two patients finished 48 weeks of follow-up. None died or developed liver failure, cirrhosis, or HCC. The 62 patients could be divided into 4 categories according to the 48-week clinical development of relapse. Virologic relapses occurred in 39 (62.9%) patients, with 72.7% occurring in the first 24 weeks in origin HBeAg positive patients and 82.4% in the first 12 weeks in origin HBeAg negative patients. Age (OR = 1.06, 95% CI = 1.02-1.10; p = 0.003), the HBsAg level (OR = 2.21, 95% CI = 1.47-3.32; p < 0.001), and positive origin HBeAg status (OR = 0.32, 95% CI = 0.14-0.74; p = 0.008) were predictive factors to virologic relapse. HBV DNA level (OR = 1.34, 95% CI = 1.13-1.58; p < 0.001) was predictive factor to retreatment. Conclusions: NA cessation is safe under supervision. Age, HBsAg level, and origin HBeAg status can be predictive factors for virologic relapse. The study was submitted to ClinicalTrials.gov Protocol Registration and Results System with the assigned NCT ID NCT02883647.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/uso terapêutico , Suspensão de Tratamento , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Feminino , Seguimentos , Guanina/análogos & derivados , Guanina/uso terapêutico , Antígenos de Superfície da Hepatite B/análise , Antígenos E da Hepatite B/análise , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/virologia , Humanos , Lamivudina/uso terapêutico , Masculino , Organofosfonatos/uso terapêutico , Pacientes Ambulatoriais , Prognóstico , Estudos Prospectivos , RNA Viral/análise , Recidiva , Fatores de Risco , Telbivudina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
14.
Eur Radiol ; 28(10): 4465-4474, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29696433

RESUMO

OBJECTIVES: To evaluate accuracy of two-dimensional shear wave elastography (2D SWE) and develop and validate a new prognostic score in predicting prognosis of acute-on-chronic liver failure (ACLF) patients. METHODS: From 1 October 2013 to 30 September 2015, we consecutively enrolled 290 patients, sequentially collected data (including 2D SWE, ultrasound parameters, laboratory data and prognostic scores) and recorded patients' outcome (recovering/steady or worsening) during a 90-day follow-up period. We evaluated ability of 2D SWE to predict outcomes of acute-on-chronic hepatitis B liver failure (ACLF-HBV) patients. We developed a new score (MELD-SWE, combining MELD and SWE values) for predicting mortality risk of ACLF-HBV in 179 patients in a derivation group, and validated in 111 patients. RESULTS: 2D SWE values were higher in worsening patients than recovering/steady ones (p < 0.001). Accuracy of 2D SWE in predicting outcomes of ACLF-HBV was comparable to that of the MELD score (p = 0.441). MELD-SWE showed a significantly higher prognostic value than MELD in both derivation (AUROC, 0.80 vs. 0.76, p = 0.040) and validation (AUROC, 0.87 vs. 0.82, p = 0.018) group. CONCLUSIONS: The MELD-SWE score, combining MELD and SWE values, was superior to MELD alone for outcoming prediction in patients with ACLF-HBV. KEY POINTS: • 2D SWE is a simple prognostic evaluation tool in patients with ACLF-HBV. • MELD-SWE was created in this study: 1.3×MELD + 0.3×2D SWE (kPa). • MELD-SWE score was superior to MELD alone for outcoming prediction in ACLF-HBV. • In this study, 46.8 was the optimal cut-off value of MELD-SWE score.


Assuntos
Insuficiência Hepática Crônica Agudizada/complicações , Insuficiência Hepática Crônica Agudizada/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Doença Hepática Terminal/complicações , Doença Hepática Terminal/diagnóstico por imagem , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
J Gastroenterol Hepatol ; 33(6): 1168-1176, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29380415

RESUMO

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


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China , Esquema de Medicação , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento , Adulto Jovem
16.
Sci Rep ; 7(1): 9214, 2017 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-28835676

RESUMO

SLC10A1 codes for the sodium-taurocholate cotransporting polypeptide (NTCP), which is a hepatocellular transporter for bile acids (BAs) and the receptor for hepatitis B and D viruses. NTCP is also a target of multiple drugs. We aimed to evaluate the medical consequences of the loss of function mutation p.Ser267Phe in SLC10A1. We identified eight individuals with homozygous p.Ser267Phe mutation in SLC10A1 and followed up for 8-90 months. We compared their total serum BAs and 6 species of BAs with 170 wild-type and 107 heterozygous healthy individuals. We performed in-depth medical examinations and exome sequencing in the homozygous individuals. All homozygous individuals had persistent hypercholanemia (P = 5.8 × 10-29). Exome sequencing excluded the involvement of other BA metabolism-associated genes in the hypercholanemia. Although asymptomatic, all individuals had low vitamin D levels. Of six adults that were subjected to bone mineral density analysis, three presented with osteoporosis/osteopenia. Sex hormones and blood lipids were deviated in all subjects. Homozygosity of p.Ser267Phe in SLC10A1 is associated with asymptomatic hypercholanemia. Individuals with homozygous p.Ser267Phe in SLC10A1 are prone to vitamin D deficiency, deviated sex hormones and blood lipids. Surveillance of these parameters may also be needed in patients treated with drugs targeting NTCP.


Assuntos
Alelos , Substituição de Aminoácidos , Homozigoto , Hipercolesterolemia/sangue , Hipercolesterolemia/genética , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Medicina de Precisão , Simportadores/genética , Adolescente , Adulto , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/metabolismo , Densidade Óssea , Criança , Feminino , Seguimentos , Humanos , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Sequenciamento Completo do Exoma , Adulto Jovem
17.
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
18.
Biomed Res Int ; 2017: 8061091, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28232944

RESUMO

Few studies have conducted follow-up investigations of the clinical course in HCV-related cirrhotic patients who achieved a sustained virological response (SVR) with pegylated interferon plus ribavirin treatment (PegIFN + RBV). We investigated the clinical course and laboratory data in a prospective cohort study enrolling HCV-related cirrhotic patients who received PegIFN + RBV between August 2008 and July 2013 in China. Complete blood counts, liver function tests, and HCV-RNA were serially examined. Liver-related complications were recorded. To detect hepatocellular carcinoma (HCC), alpha-fetoprotein assays, and ultrasound scans were repeated at 6-month intervals. Twenty-five patients were enrolled, including 8 patients with decompensation events before treatment. Eighteen patients achieved SVR with a mean follow-up period of 25.78 months. During the follow-up period, only one patient exhibited HCV-RNA positivity and no decompensation events were detected, but 4 patients developed HCC after SVR. APRI decreased more in patients with SVR than in patients with non-SVR (median, -1.33 versus 0.86, P < 0.001). The albumin levels and platelet counts significantly increased during the follow-up period after SVR (44.27 ± 4.09 versus 42.63 ± 4.37, P = 0.037 and 173.89 ± 87.36 versus 160.11 ± 77.97, P = 0.047). These data indicated that HCV-related cirrhotic patients with SVR after PegIFN + RBV may have a favorable clinical course and improvements in laboratory data. Moreover, HCC should be monitored.


Assuntos
Grupo com Ancestrais do Continente Asiático , Hepacivirus/fisiologia , Interferon-alfa/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Polietilenoglicóis/química , Ribavirina/uso terapêutico , Adulto , Idoso , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Aspartato Aminotransferases/sangue , Quimioterapia Combinada , Feminino , Seguimentos , Hepacivirus/efeitos dos fármacos , Humanos , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Albumina Sérica/metabolismo , Resultado do Tratamento
19.
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
20.
Am J Ther ; 24(3): e250-e258, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-25923228

RESUMO

The aim of this study was to evaluate the efficacy and safety of entecavir (ETV) combined treatment with adefovir (ADV) on chronic hepatitic B (CHB) patients who failed to respond to nucleotide (acid) analog (NA) treatment. On this basis, the possible factors in the combined treatment of these patients will be analyzed. The safety, biochemical index, and the possible factors that might affect the ETV and ADV combined treatment at different points in time were retrospectively analyzed. The biochemical index included the following: virological response, hepatitis B virus (HBV) DNA decline, primary nonresponse, biochemical response, and the hepatitis B virus E antigen/hepatitis B virus E antibody seroconversion rate. There were 94 CHB patients and compensated liver cirrhosis patients who received ETV plus ADV treatment for over 12 weeks after failure of treatment with NAs. The authors have also investigated 76 CHB patients (80.9%) and 18 hepatitis B cirrhosis patients (19.1%) in this study. The HBV DNA baseline was 4.4 ± 1.4 log10 IU/mL, and the positive rate of HBeAg before salvage treatment was 78.7% (74/94). The sample sizes were 94, 78, 42, 10, 6, and 1 for follow-up of 24, 48, 96, 144, 192, and 240 weeks, respectively. The virological responses (HBV DNA < 2 log10 IU/mL) and biochemical responses were 52.1%, 74.3%, and 90.4% and 63.1%, 61.6%, and 81.1%, respectively, at 24, 48, and 96 weeks, which showed significant differences (P < 0.001 and P < 0.005, respectively). The HBV DNA decline was presented as mean ± SEM, which were 1.53 ± 1.23, 1.75 ± 1.37, 2.07 ± 1.54, and 2.39 ± 1.77 log10 IU/mL at 12, 24, 48, and 96 weeks, respectively. They showed significant differences compared with the baseline (χ = 8.084, P < 0.05). The rate of primary nonresponse was 30.9% (29/94), and the primary treatment failure rates were 26.6% (25/94), 24.4% (19/78), and 4.8% (2/42) at 24, 48, and 96 weeks, respectively. They all have statistical difference (P = 0.011 < 0.05). There were 23 patients who experienced virological breakthrough after the HBV DNA levels were undetectable, whereas after follow-up for 12-24 weeks, the HBV DNA levels were back to undetectable again. ETV plus ADV treatment is an efficient and safe treatment for CHB and compensated liver cirrhosis patients who experienced NA treatment failure. The high quantity of baseline HBV DNA level is a risk factor for poor efficacy of salvage treatment.


Assuntos
Adenina/análogos & derivados , Antivirais/administração & dosagem , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/administração & dosagem , Adenina/administração & dosagem , Adenina/efeitos adversos , Adulto , Antivirais/efeitos adversos , DNA Viral/sangue , Quimioterapia Combinada , Feminino , Seguimentos , Guanina/administração & dosagem , Guanina/efeitos adversos , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Organofosfonatos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
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