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1.
J Med Virol ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31609007

RESUMO

AIMS: The aim of this retrospective study was to compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) monotherapy and TDF + entecavir (ETV) combination therapy for chronic hepatitis B (CHB) patients with the partial virological response (PVR) to ETV. METHODS: CHB patients with PVR to ETV were switched to TDF monotherapy or TDF + ETV combination therapy. The primary efficacy outcome was a virological response (VR), and the secondary efficacy outcomes were hepatitis B e antigen (HBeAg) seroconversion and alanine aminotransferase (ALT) normalization. The primary safety outcomes were changes in serum creatinine and serum phosphorus levels. RESULTS: A total of 143 patients were investigated, including 63 patients in the TDF monotherapy group and 80 patients in the TDF + ETV combination therapy group. Baseline demographics and clinical characteristics were comparable between groups. The median age of patients was 44.5 years, and 76.2% of them were male. The VR rate in TDF + ETV group was higher than that of the TDF group at 48 weeks (88.8% vs 71.4%; P = .009). At 48 weeks, the HBeAg seroconversion rate of TDF + ETV group was higher than that of the TDF group (30% vs 15.9%; P = .049). There was no significant difference in the proportion of patients with elevated ALT in the TDF group and TDF + ETV group at 48 weeks (9.5% vs 7.5%; P = .665). After adjusting the treatment regimen, serum creatinine levels increased slightly and serum phosphorus level decreased slightly in both groups. CONCLUSIONS: TDF + ETV combination therapy for 48 weeks had a higher VR rate than TDF monotherapy in CHB patients with PVR to ETV.

2.
J Transl Med ; 17(1): 151, 2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077206

RESUMO

BACKGROUND: Fulminant liver failure (FHF) is a serious clinical problem and liver transplantation is the major intervention. But the overall survival rate of FHF is low owing to the donated organ shortage. Apolipoprotein A-V (ApoA5) is a regulator of triglyceride metabolism and has been reported to act as a predictor for remnant liver growth after preoperative portal vein embolization and liver surgery. This study aimed to investigate the therapeutic effect of ApoA5 on lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced fulminant liver failure in mice. METHODS: FHF mouse model was established using LPS/D-GalN and ApoA5 plasmid was injected by tail vein prior to LPS/D-GalN treatment. The expressions of ApoA5, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B p65 (NF-κBp65) were assessed by real-time PCR and western blotting. Serum alanine aminotransferase (ALT) and tumor necrosis factor-α (TNF-α) levels were measured using automatic biochemical analyzer. Histological assessment and immunohistochemical (IHC) staining were conducted. Survival rate after LPS/D-GalN administration was also determined with Kaplan-Meier curve. Meanwhile, the expression of ApoA5 in injured huh7 cells was tested. Cell apoptosis analysis was performed after huh7 cells were transfected with ApoA5 plasmid and stimulated with LPS. RESULTS: The expressions of ApoA5 decreased both in injured huh7 cells and FHF mice. ApoA5 overexpression reduced cell death rate using flow cytometry. ApoA5 not only decreased the serum ALT and TNF-α levels but also attenuated hepatic damage in hematoxylin-eosin (HE)-stained liver section. The protein expressions of TLR4, MyD88 and NF-κBp65 were inhibited when ApoA5 overexpressed. But the inhibitory effect would weaken with the increasing concentration of LPS in spite of ApoA5 overexpression. Besides, ApoA5 improved liver injury in a dose-dependent manner and the survival rate in FHF mice increased with increasing concentration of ApoA5. CONCLUSION: ApoA5 had a protective effect against LPS/D-GalN-induced fulminant liver failure in mice within a certain range by inhibiting TLR4-mediated NF-κB pathway.

4.
J Viral Hepat ; 26(5): 586-595, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30632235

RESUMO

The correlation between serum HBcrAg and HBV RNA is unclear, and correlations of intrahepatic cccDNA with HBcrAg, HBV RNA and HBsAg are rarely reported in the same cohort. This study aimed to assess the correlation of HBcrAg with HBV RNA and HBsAg, and investigate whether serum HBcrAg is superior to serum HBV RNA and HBsAg in reflecting intrahepatic HBV cccDNA in HBeAg-positive and HBeAg-negative CHB patients. In this study, 85 HBeAg-positive and 25 HBeAg-negative patients who have never received antiviral therapy were included. Among HBeAg-positive patients, HBcrAg was correlated positively with HBsAg (r = 0.564, P < 0.001) and HBV RNA (r = 0.445, P < 0.001), and HBV RNA was also correlated positively with HBsAg (r = 0.323, P = 0.003). Among HBeAg-negative patients, no significant correlation was observed between HBcrAg, HBsAg and HBV RNA. By multivariable linear regression, HBcrAg (ß = -0.563, P < 0.001), HBsAg (ß = -0.328, P < 0.001) and HBV RNA (ß = 0.180, P = 0.003) were all associated with cccDNA levels among HBeAg-positive patients, but only serum HBcrAg was associated with cccDNA level (ß = 0.774, P = 0.000) among HBeAg-negative patients. HBcrAg was better correlated with cccDNA as compared to HBsAg and HBV RNA, irrespective of HBeAg status. Among HBeAg-positive patients, though HBcrAg level was influenced by hepatic inflammatory activity and HBV DNA levels, the good correlations of HBcrAg with cccDNA persisted after stratification by inflammatory activity and HBV DNA levels. In conclusion, correlations of serum HBcrAg, HBV RNA and HBsAg levels differ significantly between HBeAg-positive and HBeAg-negative patients, but serum HbcrAg correlates with cccDNA levels better than HBV RNA and HBsAg, irrespective of HBeAg status.

5.
Artigo em Inglês | MEDLINE | ID: mdl-30497844

RESUMO

AIM: This study aimed to investigate long-term kinetics of serum hepatitis B core-related antigen (HBcrAg) and its correlation with serum hepatitis B surface antigen (HBsAg) in a real-world cohort of patients who had received over 8 years of nucleos(t)ide analogs(NAs) therapy. METHODS: This was a retrospective study. All patients were recruited from our previous published study, who started therapy with NAs between 2007 and 2008. Serum HBcrAg and HBsAg levels were quantitatively measured at baseline, the sixth month and each year of follow-up, using the stored serum samples. RESULTS: Among the 94 patients, serum HBcrAg presented a gradually decreasing trend from baseline to year 8, either in HBeAg-negative or HBeAg-positive patients. After 8 years of NAs treatment, 21.3% of patients achieved serum HBcrAg < 3 log 10 U/mL, and only baseline HBcrAg was an independent predictor. Additionally, good correlation of HBcrAg and HBsAg was observed at baseline, but this correlation weakened remarkably during treatment. CONCLUSION: Serum HBcrAg is decreasing gradually with the duration of antiviral therapy, and baseline HBcrAg level is an independent predictor of long-term HBcrAg below the limit of detection.

6.
J Viral Hepat ; 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30380166

RESUMO

Optional treatments for patients with chronic hepatitis C virus (HCV) genotype (GT) 6 infection have not been extensively studied. This study aimed to evaluate the safety and efficacy of sofosbuvir (SOF)-based direct-acting antiviral agents (DAAs) for HCV GT6. We performed a retrospective study at the West China Hospital of Sichuan University in Southwest China from January 2016 to May 2017. Our study screened 130 treatment-naïve patients with chronic HCV GT6 and without liver cirrhosis. A total of 60 HCV GT6 patients were ultimately enrolled. All patients received SOF-based DAAs therapy, including SOF 400 mg plus daclatasvir (DCV) 60 mg daily or SOF 400 mg plus velpatasvir (VEL) 100 mg daily for 12 weeks. The sustained virological response 12 weeks after treatment (SVR12) was 100% (60/60) in treatment-naïve patients with HCV GT6, including 100% (37/37) of patients receiving SOF plus DCV therapy and 100% (23/23) of patients receiving SOF plus VEL therapy. Measurements of liver stiffness were significantly decreased in patients at week 12 (P = 0.014) and week 24 (P < 0.001) of DAAs treatment compared to baseline values. The serum biomarker aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 score were also significantly reduced at week 12 and week 24 compared to before treatment (both P < 0.001). SOF-based therapy was well-tolerated, and no serious adverse events were reported. In conclusion, SOF plus DCV and SOF plus VEL were safe and achieved a high SVR12 rate for treatment-naïve patients with HCV GT6 without liver cirrhosis.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30383554

RESUMO

BACKGROUND: A combination of sofosbuvir (SOF)+NS5A inhibitor therapies is the main treatment for patients with hepatitis C virus (HCV) genotype-2 (GT-2) chronic infection, but the data are rarely reported in China. This study aimed to investigate the virological response and liver fibrosis improvement among GT-2 patients receiving SOF+NS5A inhibitors. PATIENTS AND METHODS: In this retrospective study, patients who received SOF+NS5A inhibitors between March 2016 and July 2017 were recruited. The treatment duration was 12 weeks and the treatment strategies included SOF+daclatasvir, SOF/ledipasvir, and SOF/velpatasvir. The primary endpoint was a sustained virologic response (serum HCV RNA undetectable) at week 12 after the end of therapy and the secondary endpoint was the improvement in liver stiffness and scores of apartate aminotransferase to platelet ratio index and fibrosis-4. RESULTS: A total of 30 GT-2 patients were enrolled, with 13 (43.3%) patients in SOF+daclatasvir, 13 (43.3%) patients in SOF/ledipasvir, and four (13.3%) patients in SOF/velpatasvir. All patients [30/30 (100%)] achieved SVR, irrespective of treatment regimens and degree of liver fibrosis. After the treatment, liver fibrosis scores of apartate aminotransferase to platelet ratio index (2.27±2.14 vs. 0.89±0.77, P=0.003) and fibrosis-4 (1.17±1.22 vs. 0.42±0.25, P=0.013) were both significantly lower than those before treatment. CONCLUSION: SOF+NS5A inhibitor therapies may induce an excellent virological response and fibrosis improvement in HCV GT-2-infected patients.

8.
Virol J ; 15(1): 150, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30285800

RESUMO

BACKGROUND: Chronic hepatitis C virus (HCV) genotype (GT) 3 infection with advanced liver disease has emerged as a challenging to treat by direct-acting antivirals (DAAs), but the efficacy of DAAs in Chinese HCV-GT3 patients is rarely reported. This study aimed to analyze the efficacy of sofosbuvir (SOF)-based regimens in Chinese patients with HCV-GT3 and compensated liver disease. METHODS: This was a registered retrospective study. All patients had completed at least 12 weeks SOF-based regimens therapy (with or without RBV), and were followed up for at least 24 weeks after therapy discontinuation. The primary endpoint was sustained virological response 24 weeks after end of therapy (SVR24). RESULTS: A total of 102 patients who completed at least 12 weeks therapy were finally included, with 57 in SOF + Daclatasvir (SOF + DCV), 24 in SOF + DCV + ribavirin (RBV) and 21 in SOF/Velpatasvir (SOF/VEL). The total SVR24 rate was achieved in 90.20% (92/102), with 85.96% (49/57) in SOF + DCV, 91.67% (22/24) in SOF + DCV + RBV and 100.00% (21/21) in SOF/VEL. Among 10 relapsed patients (8 in SOF + DCV and 2 in SOF + DCV + RBV), the short course (12 weeks) of therapy and no RBV addition may be the leading cause. In this cohort, the SVR24 rate was not statistically different between patients with and without cirrhosis (81.82% [27/33] vs. 94.20% [65/69], P = 0.073). Additionally, both FIB-4 (4.03 vs. 2.08, P < 0.001) and APRI (2.15 vs. 0.68, P < 0.001) scores were significant improved from baseline to week 24 after completion of therapy, regardless of the presence of cirrhosis. CONCLUSION: SOF-based regimens are highly effective in viral clearance and fibrosis remission for Chinese patients with HCV-GT3 infection. If available, SOF/VEL should be first considered.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/classificação , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/patologia , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Adulto , Grupo com Ancestrais do Continente Asiático , Carbamatos/uso terapêutico , Feminino , Seguimentos , Genótipo , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resultado do Tratamento
9.
Dig Liver Dis ; 2018 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-30274791

RESUMO

AIMS: To analyze the role of serum miR-125b-5p in reflecting liver damage and predicting outcomes in chronic hepatitis B (CHB) patients with acute-on-chronic liver failure (ACLF). METHODS: CHB patients with normal hepatic function (n = 100), moderate-to-severe liver damage (n = 90), and ACLF (n = 136) were included. Among hepatitis B virus (HBV)-ACLF patients, 86 and 50 were in the training and validation cohorts, respectively. Serum miR-125b-5p level was measured by quantitative real-time PCR. RESULTS: Serum miR-125b-5p level increased with disease progression, and serum miR-125b-5p level was lower in surviving than in dead HBV-ACLF patients. Among HBV-ACLF patients, miR-125b-5p positively correlated with total bilirubin (TBil; r = 0.214, p < 0.05) and model for end-stage liver disease (MELD) score (r = 0.382, p < 0.001) and negatively correlated with prothrombin activity(PTA; r = -0.215, p < 0.05). MiR-122 showed a contrasting performance compared with miR-125b-5p. Cox regression analysis showed that miR-125b-5p, miR-122, and PTA were independent survival predictors for HBV-ACLF, and low miR-125b-5p and high miR-122 levels may predict a longer survival in HBV-ACLF. MiR-125b-5p (AUC = 0.814) had a higher performance for survival prediction in HBV-ACLF compared with miR-122 (AUC = 0.804), PTA (AUC = 0.762), MELD score (AUC = 0.799), and TBil (AUC = 0.670) alone; predictive effectiveness of miR-125b-5p was increased by combination with miR-122 (AUC = 0.898). MiR-125b-5p was an effective predictor of HBV-ACLF outcomes in the validation cohort. CONCLUSIONS: MiR-125b-5p increase is associated with severity of liver damage; high serum miR-125b-5p may serve as a predictor for poor outcomes in HBV-ACLF cases.

10.
Virol J ; 15(1): 61, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29609638

RESUMO

BACKGROUND: It has been reported that the emergence of HBV rtA181T/sW172* mutant could result in a dominant secretion defect of HBsAg and increase the risk of HCC development. This study was designed to reveal the role and possible pathogenic mechanism of truncated mutant HBsAg in tumorigenesis of HBV rtA181T/sW172* mutant. RESULTS: As compared to wide type or substituted mutant HBsAg, the ratio of cell clones was significant higher in L02 cells stable expressing truncated mutant HBsAg. Injection of L02 cells stable expressing truncated mutant HBsAg into the dorsal skin fold of nude mice resulted in increased primary tumor growth compared to L02 cells stable expressing wide-type and substituted mutant HBsAg. In HBV replication L02 cell lines, the key molecular involved in TGF-ß/Smad pathway was also investigated. We found that the mRNA and protein levels of Smad3/2, CREB and CyclinD1 were significantly higher and TGFBI level was significantly lower in cells stably expressing truncated mutant HBsAg as compared to cells stably expressing wide-type and substituted mutant HBsAg. Additionally, after administration of TGF-ß1 (increasing TGFBI level), the volume of tumor is obviously reduced in nude mice with injection of L02 cells stable expressing truncated HBsAg. CONCLUSIONS: The emergence of sW172* mutant may increase the tumorigenesis of HBV, and its mechanism may be associated with down-regulated expression of TGFBI in TGF-ß/Smad signaling pathway.


Assuntos
Transformação Celular Neoplásica , Expressão Gênica , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B/metabolismo , Hepatite B/virologia , Mutação , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Linhagem Celular , Transformação Celular Viral , Modelos Animais de Doenças , Feminino , Hepatite B/complicações , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Camundongos , Camundongos Nus , Transdução de Sinais
11.
Infect Dis (Lond) ; 50(7): 522-530, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29463147

RESUMO

AIM: Recent studies revealed that both quantitative hepatitis B surface antigen (qHBsAg) and hepatitis B core-related antigen (qHBcrAg) could serve as a good marker for predicting treatment response and indirectly reflecting intrahepatic cccDNA levels. This study aimed to compare the value of qHBsAg and qHBcrAg in predicting HBeAg seroconversion among patients undergoing PEG-IFN therapy. METHODS: A total of 31 HBeAg-positive patients, who underwent PEG-IFN therapy for 12 months and follow-up for six months were retrospectively included in this study. The serum qHBsAg level was measured using Elecsys® HBsAg II Quant Assay and serum qHBcrAg level was measured using chemiluminescence enzyme immunoassay. RESULTS: During the 12-month treatment, the absolute levels of serum qHBsAg and qHBcrAg were both lower in patients with HBeAg seroconversion as compared to patients without HBeAg seroconversion, but only the difference in qHBcrAg was significant. During the 6-month follow-up period, both qHBsAg and qHBcrAg levels were rebounded significantly among patients without HBeAg seroconversion. Among patients with HBeAg seroconversion, no sustained significant decline of qHBsAg was observed, but serum qHBcrAg levels continued to decline significantly. The ROC curves analysis showed that both absolute qHBcrAg level and the extent of qHBcrAg decline at month 1 had better performance for the prediction of HBeAg seroconversion at month 6 after treatment, as compared to that of qHBsAg. CONCLUSION: Early on-treatment qHBcrAg may be a good biomarker for predicting off-treatment HBeAg seroconversion in patients receiving PEG-IFN therapy.


Assuntos
Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/imunologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Antivirais/uso terapêutico , Biomarcadores/sangue , DNA Viral/sangue , Feminino , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/química , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Curva ROC , Estudos Retrospectivos , Soroconversão , Adulto Jovem
12.
Curr Stem Cell Res Ther ; 13(3): 193-201, 2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-29303079

RESUMO

BACKGROUND: Liver failure is a life-threatening liver disease encompassing severe acute deterioration of liver function. Emergency liver transplantation is the only curative treatment for liver failure, but is restricted by the severe shortage of organ donors. Stem cell, including embroyonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells and hepatic progenitor cells, have capacity to proliferate and differentiate and could be used in a variety of liver diseases including hereditary liver diseases, cirrhosis and liver failure. OBJECTIVE: We summarized the basic experimental and clinical advances of stem cell transplantation in liver failure treatment, and also discussed the advantages and disadvantage of different stem cells subtype in this field, aiming to provide a perspective on the stem cell-based therapy for liver failure. RESULTS: Stem cells, especially mesenchymal stem cells (mainly low immunogenicity and paracrine characteristics) and induced pluripotent stem cells (generation of desired cell type from somatic cell), are feasible candidates for cell therapy in the treatment of liver failure, but there are some drawbacks remaining to be resolved, such as low engraftment, cryotpreservation methods and tumorigenesis. CONCLUSION: Stem cell transplantation is a promising but challenging strategy and paves a new way for curing liver failure. But more efforts need to be made to overcome problems before this new strategy could be safely and effectively applied to humans.


Assuntos
Cirrose Hepática/terapia , Falência Hepática/terapia , Transplante de Células-Tronco , Animais , Humanos , Medicina Regenerativa
13.
Expert Rev Gastroenterol Hepatol ; 12(3): 287-294, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29140126

RESUMO

INTRODUCTION: In addition to being crucial for host immune defense, vitamin D is involved in cell proliferation, apoptosis, differentiation, inflammation, invasion and metastasis, angiogenesis and micro-RNA modulation. To date, clinical studies have demonstrated that vitamin D deficiency is common not only in patients with chronic liver diseases but also in those with hepatocellular carcinoma (HCC). Experimental studies have also demonstrated that vitamin D and its receptors are related to the occurrence of HCC and the prognoses of patients with HCC. Areas covered: In this review, we discuss the potential anti-tumor role of vitamin D in HCC based on current findings from epidemiological studies, basic science, and clinical studies and provide new insights into the pathogenesis and treatment of HCC. Expert commentary: Recent studies have revealed the anti-tumor effects of vitamin D to a certain degree. Vitamin D and its analogs may provide new treatment targets and prognostic factors for HCC that might be essential for the primary or secondary prevention of HCC and the monitoring of its progression.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Vitamina D/metabolismo , Animais , Carcinogênese , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Receptores de Calcitriol/metabolismo , Vitamina D/análogos & derivados , Vitamina D/biossíntese , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações
14.
Scand J Gastroenterol ; 52(12): 1420-1426, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28880694

RESUMO

AIMS: This study aims to investigate the kinetics of serum HBsAg levels in chronic hepatitis B patients with long-term nucleos(t)ide analogs (NAs) therapy. METHODS: This was a retrospective clinical study. Serum HBsAg in serial samples of 94 patients, who received at least 8 years of NAs therapy, were measured using Elecsys® HBsAg II Quant Assay. RESULTS: In this cohort, serum HBsAg levels reduced from 3.80 log10 IU/mL at baseline to 2.72 log10 IU/mL at year 8 (p < .001), and the percentage of patients with HBsAg <1000 IU/mL increased from 14.9% at baseline to 55.3% at year 8 (p < .001). The reduction of serum HBsAg did not differ significantly between patients stratified by baseline virological parameters and type of antiviral agents. But as compared to patients without HBeAg seroconversion, HBsAg levels were significant lower in patients with HBeAg seroconversion (3.19 vs. 2.47 log10 IU/mL at year 8, p = .001). As compared to patients with slow (0-1 log10 IU/mL) or steady HBsAg(≤0 log10 IU/mL) decline at year 1, patients with a rapid HBsAg (≥1 log10 IU/mL) decline had a significantly lower HBsAg levels from year 2 to 8. However, Cox regression analysis showed that only absolute HBsAg levels at year 1 was an independent predictor of subsequent HBsAg <1000 IU/mL at year 8 of antiviral therapy(HR 0.242, p = .004). CONCLUSION: Pronounced HBsAg declines could be achieved in patients after long-term effective therapy with NAs, and on-treatment low serum HBsAg level at year 1 might be a predictor of serum HBsAg <1000 IU/mL at year 8.


Assuntos
Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/uso terapêutico , Adulto , DNA Viral/sangue , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
15.
Hepatobiliary Pancreat Dis Int ; 16(4): 370-374, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28823366

RESUMO

BACKGROUND: Controlled attenuation parameter (CAP) is a non-invasive method for diagnosing hepatic steatosis based on vibration-controlled transient elastography. The objective of this study was to investigate the effect of high value of CAP on antiviral therapy in patients with chronic hepatitis B (CHB). METHODS: Patients with CHB receiving enticavir for initial antiviral therapy were studied; they were divided into the high CAP group and normal CAP group at baseline according to the CAP values. The effect of the antiviral therapy between the two groups were compared at week 12, 24 and 48. Patients with high CAP value at baseline were divided into three subgroups, mild, moderate and severe elevation; the therapeutic response were compared among patients with normal CAP and subgroups of patients with elevated CAP. RESULTS: A total of 153 patients were enrolled. Among them, 63 were in the high CAP group and 90 in the normal CAP group. Patients with high CAP had lower rates of ALT normalization and HBV DNA clearance in response to antiviral therapy compared with those with normal CAP at week 12, 24 and 48. Further analysis showed that the rate of ALT normalization in patients with mildly and moderately elevated CAP were significant lower than those with normal CAP at week 12 and 24; while the difference was not significant between the patients with normal CAP and those with severely elevated CAP. The rate of HBV DNA clearance was significantly lower in patients with severely elevated CAP compared with those with normal CAP at week 12, 24 and 48. CONCLUSION: CHB patients with high CAP had poor response to antiviral therapy.


Assuntos
Antivirais/uso terapêutico , Técnicas de Imagem por Elasticidade , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Adulto , Antivirais/efeitos adversos , DNA Viral/genética , Feminino , Guanina/efeitos adversos , Guanina/uso terapêutico , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/virologia , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Carga Viral
16.
Sci Rep ; 7: 45576, 2017 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-28358016

RESUMO

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition, and the lipid metabolism disorder is common in the development of this disease. This prospective observational study aimed to define the characteristics of plasma apolipoprotein A-V (apoA-V) in long-term outcome prediction of HBV-ACLF, and a total of 330 HBV-ACLF patients were included and followed for more than 12 months. In this cohort, the 4-week, 12-week, 24-week and 48-week cumulative mortality of HBV-ACLF was 18.2%(60/330), 50.9%(168/330), 59.7%(197/330) and 63.3%(209/330), respectively. As compared to survivors, the non-survivors had significantly lower concentrations of plasma apoA-V on admission. Plasma apoA-V concentrations were positively correlated with prothrombin time activity (PTA), and negatively correlated with interleukin-10, tumor necrosis factor-α, and iMELD scores. Though plasma apoA-V, PTA, total bilirubin(TBil) and blood urea nitrogen(BUN) were all independent factors to predict one-year outcomes of HBV-ACLF, plasma apoA-V had the highest prediction accuracy. And its optimal cutoff value for one-year survival prediction was 480.00 ng/mL, which had a positive predictive value of 84.68% and a negative predictive value of 92.23%. In summary, plasma apoA-V decreases significantly in non-survivors of HBV-ACLF, and it may be regarded as a new predictive marker for the prognosis of patients with HBV-ACLF.

17.
Sci Rep ; 7(1): 173, 2017 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-28282964

RESUMO

Recently, hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. This study aimed to investigate whether serum quantitative HBcrAg (qHBcrAg) was a satisfactory surrogate marker of intrahepatic covalently closed circular DNA (cccDNA). A total of 139 patients with liver biopsy were enrolled, consisting of 59 patients in immune tolerance (IT) phase, 52 patients in immune clearance (IC) phase, 18 patients in low-replication (LR) phase, and 10 patients in reactivation phase. All patients in IC phase have received entecavir (ETV) therapy, and 32 of them undergone a second liver biopsy at 24 months. Among those patients, qHBcrAg was strongly correlated with intrahepatic cccDNA, which is superior to that of qHBsAg and HBV DNA. And similar findings were also observed in patients in IT, IC, LR and reactivation phases. Among the 32 ETV-treated patients with a second liver biopsy in IC phase, the decline of intrahepatic cccDNA was accompanied by changes in both qHBcrAg and qHBsAg. However, as compared to qHBsAg, the change of qHBcrAg was more strongly associated with intrahepatic cccDNA-decline. In summary, serum qHBcrAg should be a satisfactory surrogate of intrahepatic HBV cccDNA in CHB patients.


Assuntos
DNA Circular/genética , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/imunologia , Fígado/virologia , Adulto , Antivirais/uso terapêutico , DNA Viral/genética , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Vírus da Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/genética , Hepatite B Crônica/virologia , Humanos , Fígado/química , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
18.
Hepatobiliary Pancreat Dis Int ; 15(6): 579-586, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27919846

RESUMO

BACKGROUND: The long-term use of nucleos(t)ide analogues causes drug resistance and mutations in the HBV reverse transcriptase (RT) region of the polymerase gene. The RT region overlaps the HBV surface gene (S gene) and therefore, the mutations in the RT region simultaneously modify S gene sequence. Certain mutations in the RT region bring about truncated S proteins because the corresponding changed S gene encodes a stop codon which results in the loss of a large portion of the C-terminal hydrophobic region of HBV surface protein. The rtA181T/sW172*, rtM204I/sW196* and rtV191I/sW182* are the most frequently reported drug-resistant mutations with C-terminal truncation, these mutations have oncogenic potential. DATA SOURCES: PubMed and Web of Science were searched using terms: "hepatitis B virus", "HBV drug resistance mutation", "HBV surface protein", "HBV truncation", "hepatocellular carcinoma", "rtA181T/sW172*", "rtM204I/sW196*", "rtV191I/sW182*", and relevant articles published in English in the past decades were reviewed. RESULTS: The rtA181T/sW172* and rtV191I/sW182* mutants occurred more frequently than the rtM204I/sW196* mutant both in chronic hepatitis B patients and the HBV-related hepatocellular carcinoma tissues. Although these mutations occur naturally, nucleos(t)ide analogues therapy is the main driving force. These mutations may exist alone or coexist with other HBV mutations. All these three mutants impair the virion secretion and result in HBV surface protein retention and serum HBV DNA level reduction. These mutations possess potential carcinogenic properties. The three mutations are resistant to more than one nucleos(t)ide analogue and therefore, it is difficult to treat the patients with the truncated mutations. CONCLUSIONS: Nucleos(t)ide analogues induce drug resistance and HBV S gene truncated mutations. These mutations have potential carcinogenesis.


Assuntos
Antivirais/efeitos adversos , Carcinoma Hepatocelular/virologia , Transformação Celular Viral/genética , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/virologia , Mutação , Nucleosídeos/efeitos adversos , Nucleotídeos/efeitos adversos , Animais , Carcinoma Hepatocelular/patologia , Farmacorresistência Viral/genética , Genótipo , Vírus da Hepatite B/genética , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/patologia , Fatores de Risco
19.
Sci Rep ; 6: 39260, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27976732

RESUMO

The hepatitis B virus(HBV) polymerase rtA181T mutation is selected during long-term antiviral therapy. As the polymerase gene completely overlaps with the envelope (S) gene, HBV rtA181T mutation also carries sW172 mutations. In this study, we investigated whether there were biological differences between rtA181T/sW172* (coding truncated HBsAg) and rtA181T/sW172L (coding substituted HBsAg) mutants. In cell experiments, a slight decline of viral replication was observed in both two mutants as compared to wild-type strains, but the levels of supernatant HBsAg and HBV DNA in rtA181T/sW172* were significantly lower than those in rtA181T/sW172L transfected cells. In animal experiments, we were amazed to find that viral replication in rtA181T/sW172* mutant increased and maintained significantly longer than that in rtA181T/sW172L mutant, while no significant difference was observed between rtA181T/sW172L and wild-type strains. Compared with wild-type strains, there were intracellular accumulations of HBsAg and HBcAg in rtA181/sW172* but none in rtA181/sW172L mutant strains. Importantly, we also found that truncated HBsAg could increase the activity of HBV core promoter, but substituted HBsAg could not. In summary, the characteristics of above two rtA181T mutants mentioned above were significantly different, and it is necessary and important for us to distinguish sW172* truncated mutation from sW172L substituted mutation.


Assuntos
Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/enzimologia , DNA Polimerase Dirigida por RNA/genética , Animais , DNA Viral/sangue , DNA Viral/metabolismo , Células Hep G2 , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/genética , Humanos , Fígado/metabolismo , Camundongos , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas , DNA Polimerase Dirigida por RNA/metabolismo , Transfecção , Replicação Viral
20.
Viral Immunol ; 29(6): 332-42, 2016 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27104358

RESUMO

Changes of Treg/Th17 cells ratio and their associated cytokines have some correlations with an immune modulatory effect of Telbivudine treatment. The aim of our study was to investigate the role of the dynamic ratio of Treg/Th17 cells in the mechanism of LdT therapy and their relationships with the clinical responses. We detected the frequency and cytokines production of Treg and Th17 cells in 28 hepatitis B envelope antigen (HBeAg)-positive CHB patients at 0, 12, 24, 36, 48, and 96 weeks after initial LdT therapy. LdT could upregulate the frequency of Th17 cells and Th17 cells associated cytokines, downregulated the frequency of Treg cells and level of TGF-ß, which leads to the decrease of Treg/Th17 ratio in HBeAg-positive CHB patients. Treg/Th17 ratio at treatment week 36 could independently predict HBeAg seroconversion in the first 2 years of Telbivudine treatment. Telbivudine therapy can decrease Treg/Th17 ratio, which may predict HBeAg seroconversion during treatment.


Assuntos
Antivirais/uso terapêutico , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Soroconversão , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Timidina/análogos & derivados , Adolescente , Adulto , Feminino , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/patologia , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Telbivudina , Timidina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
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