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1.
Nat Rev Drug Discov ; 19(3): 149-150, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127666
2.
Chem Biodivers ; 17(2): e1900512, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31900973

RESUMO

Velvet antler (VA) is crucial and precious nourishment in China and some countries in Southeast Asia and has excellent anti-fatigue effect. The incidence of fatigue syndrome has increased gradually. VA can be a potential source of anti-fatigue products. Therefore, we investigated the anti-fatigue activity of different sections (upper, middle, and basal section) of VA from different species (red deer and sika deer) via loading swimming test in mice. Furthermore, nucleosides are one kind of active components in VA which could considerably reduce fatigue in mice. In order to explore whether the nucleosides are correlated with anti-fatigue effect, the contents of eight nucleosides (uracil, cytidine, hypoxanthine, xanthine, thymine, inosine, guanosine, and adenosine) were determined simultaneously using high-performance liquid chromatography. The results indicated that the swimming time in mice was increased from basal to upper section, which was consistent with the change trend of the total contents of eight nucleosides of VA. Therefore, we speculated that the contents of nucleosides in VA may affect its anti-fatigue effect. Furthermore, the contents of nucleosides were also used as a reference for evaluating the quality of different parts of VA obtained from red and sika deer.


Assuntos
Chifres de Veado/metabolismo , Fadiga/tratamento farmacológico , Nucleosídeos/uso terapêutico , Animais , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cervos , Masculino , Camundongos , Nucleosídeos/análise , Nucleosídeos/farmacologia , Condicionamento Físico Animal
3.
Biosci Trends ; 14(1): 69-71, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-31996494

RESUMO

As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the 2019-nCoV outbreak. Three general methods, which include existing broad-spectrum antiviral drugs using standard assays, screening of a chemical library containing many existing compounds or databases, and the redevelopment of new specific drugs based on the genome and biophysical understanding of individual coronaviruses, are used to discover the potential antiviral treatment of human pathogen coronavirus. Lopinavir /Ritonavir, Nucleoside analogues, Neuraminidase inhibitors, Remdesivir, peptide (EK1), abidol, RNA synthesis inhibitors (such as TDF, 3TC), anti-inflammatory drugs (such as hormones and other molecules), Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be the drug treatment options for 2019-nCoV. However, the efficacy and safety of these drugs for 2019- nCoV still need to be further confirmed by clinical experiments.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Alanina/análogos & derivados , Alanina/uso terapêutico , Combinação de Medicamentos , Descoberta de Drogas , Humanos , Lopinavir/uso terapêutico , Neuraminidase/antagonistas & inibidores , Nucleosídeos/uso terapêutico , Ribonucleotídeos/uso terapêutico , Ritonavir/uso terapêutico
4.
Zhonghua Gan Zang Bing Za Zhi ; 27(8): 577-581, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594074

RESUMO

The World Health Organization (WHO) has put forward the strategic goal of eliminating viral hepatitis as a major public health threat by 2030, and the research and development of new treatment for chronic hepatitis B (CHB) patients is an important part of this. In recent years, functional or clinical cure marked by HBsAg clearance and continuous undetectable HBV DNA has gradually become an ideal treatment endpoint recommended by clinical guidelines at home and abroad. Studies have shown that CHB patients who achieved long-term viral suppression after nucleoside analogues (NAs), adding or switching to interferons may have the potential to improve the clearance rate of HBsAg. However, the HBsAg conversion rate of patients in each treatment group in these studies was still low, and a reasonable combined therapy strategy and suitable patient population need to be further explored. In addition, some new drugs are being developed in pursuit of a CHB cure, though many clinical trials of new drugs are still based from a long-term treatment of NAs. Therefore, NAs antiviral therapy remains the cornerstone at this stage for CHB.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/análogos & derivados , Nucleosídeos/uso terapêutico , DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B , Humanos
5.
Medicine (Baltimore) ; 98(36): e17022, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490387

RESUMO

Pegylated interferon alpha (PEG-IFN-α) is a first-line treatment for patients with chronic hepatitis B (CHB), but its efficacy varies from individual to individual. Early discrimination between responder and non-responder patients is important for optimal clinical management. In addition, low therapeutic efficacy is still a major issue; thus, treatment timing should be optimized.We reviewed our experience with hepatitis B e-antigen (HBeAg)-positive patients treated with PEG-IFN-α, alone or in combination with nucleoside analogues (NAs), from 2009 through 2014. Collected data included both general characteristics of 113 patients and laboratory data at baseline and at treatment weeks 12, 24, 52, and 76. The endpoint was HBeAg seroconversion at week 76.A total of 113 patients with changed to or start of NAs therapy were included in this study. At the end of treatment, 44 (38.9%) patients exhibited HBeAg seroconversion. Patients with HBeAg seroconversion had lower baseline HBeAg (475.5 vs 751.7; P = .007). The incidence of HBeAg seroconversion was significantly higher among patients with HBeAg ≤ 500 signal-to-cutoff ratio (S/CO) (OR = 2.60, 95% CI: 1.16-5.83, P = .02) at baseline, HBeAg S/CO ≤ 20 (OR = 3.37, 95% CI: 1.47-7.73, P = .003), or a higher than 10-fold HBeAg drop (OR = 3.55, 95% CI: 1.50-8.37, P = .003) at week 12 or HBeAg ≤ 15 S/CO (OR = 10.35, 95% CI: 4.09-26.20, P < .001) at week 24. Subgroup analyses demonstrated that in patients with HBeAg >20 S/CO at 24 weeks, the addition of NAs treatment may increase HBeAg seroconversion (23.3% vs 0%, P = .03).HBeAg levels had an impact on the rate of serological conversion in CHB patients receiving PEG-IFN-based treatment. Combination therapy with NAs should be considered in CHB patients maintaining a high HBeAg level after 24 weeks of PEG-IFN monotherapy.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Nucleosídeos/uso terapêutico , Adolescente , Adulto , Quimioterapia Combinada , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/imunologia , Humanos , Masculino , Estudos Retrospectivos , Soroconversão , Adulto Jovem
6.
Int J Infect Dis ; 86: 201-207, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31394205

RESUMO

OBJECTIVES: The aim of this study was to identify the predictors of relapse after the withdrawal of nucleos(t)ide analog (NA) therapy in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). METHODS: The PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched through January 2019. A random-effects model meta-analysis was performed, with hazard ratios (HR) and 95% confidence intervals (CI) used as summary statistics. RESULTS: Seventeen studies were included in the meta-analysis. Age (HR=1.022 per year), baseline hepatitis B surface antigen (HBsAg) (HR=1.509 per log IU/l), end of treatment (EOT) HBsAg level (HR=1.896 per log IU/l), EOT HBsAg level ≥1000 IU/ml (HR=1.749), and HBsAg decline from baseline to EOT (HR=0.748 per log IU/l) were associated with virological relapse. The predictors of clinical relapse were baseline HBsAg level (HR=1.312 per log IU/l), EOT HBsAg level (HR=1.458 per log IU/l), EOT HBsAg level ≥100IU/ml (HR=3.199) or ≥1000 IU/ml (HR=1.810), and duration of consolidation therapy (HR=0.991 per month). CONCLUSIONS: This meta-analysis indicates that age, the duration of consolidation therapy, and levels of baseline and EOT HBsAg were factors predictive of relapse in HBeAg-negative CHB patients who discontinued NA treatment.


Assuntos
Antivirais/administração & dosagem , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/administração & dosagem , Suspensão de Tratamento , Adulto , Antivirais/uso terapêutico , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Masculino , Nucleosídeos/uso terapêutico , Modelos de Riscos Proporcionais , Recidiva
7.
Gut ; 68(12): 2206-2213, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31462554

RESUMO

OBJECTIVE: Although most patients with chronic hepatitis B (CHB) reach effective virological suppression with long-term nucleos(t)ide analogues (NA) therapy, some might not need to continue treatment for life. In this randomised, controlled, phase IV trial, we evaluated off-therapy outcomes in patients after discontinuing long-term NA therapy. DESIGN: Patients who had received NA therapy for ≥1 year and achieved virological suppression (hepatitis B e antigen (HBeAg) seroconversion combined with undetectable hepatitis B virus (HBV) DNA ≥12 months in HBeAg-positive patients or undetectable HBV DNA ≥36 months in HBeAg-negative patients) were randomised 2:1 to stop or continue NA therapy for 72 weeks. Sustained disease remission (HBeAg negative, HBV DNA <2000 IU/mL and normal alanine aminotransferase (ALT)) was evaluated at 72 weeks after stopping NA therapy. RESULTS: Among 67 enrolled patients, sustained disease remission was observed in 13/45 (29%) stop versus 18/22 (82%) continue patients. Hepatitis B surface antigen (HBsAg) loss occurred in two patients (one in each group). The median HBsAg decline from randomisation to week 72 was similar in both groups (0.2 (0.0-0.4) vs 0.1 (0.0-0.2) log IU/mL in stop vs continue patients). Among patients who stopped, 15/45 (33%) had virological or biochemical relapse and 17/45 (38%) were retreated according to predefined criteria. A total of 11/18 (61%) pretreatment HBeAg-positive versus 6/27 (22%) HBeAg-negative patients required retreatment (p=0.01). Fourteen (31%) patients developed ALT >10× upper limit of normal (ULN) and another 7 (16%) had ALT >5× ULN. No patients experienced liver decompensation or died. CONCLUSION: The findings of this prospective study suggest limited benefit of stopping NA therapy in chronic hepatitis B. TRIAL REGISTRATION NUMBER: NCT01911156.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/análogos & derivados , DNA Viral/análise , Feminino , Seguimentos , 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 , Masculino , Pessoa de Meia-Idade , Nucleosídeos/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento
8.
Zhonghua Gan Zang Bing Za Zhi ; 27(5): 343-346, 2019 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-31177657

RESUMO

Oral nucleos(t)ide analogues (NAs) is one of the main and efficient way for the treatment of chronic hepatitis B (CHB). Considering the antiviral potency and drug resistance of domestic and foreign guidelines, NAs are divided into first-line and non-first-line drugs. "An Expert Consensus for the Adjustment of Treatment Strategies in Patients with Chronic Hepatitis B Treated with Non-first-line Nucleos(t)ide Analogues," is mainly aimed at those patients who are currently using non-first-line NAs drugs. In addition, how to standardize the adjustment to first-line NAs drugs of choice, which can strengthen the effectiveness of initial antiviral treatment to obtain better antiviral efficacy, and improve patient compliance, coinciding with the avoidance of occurrence of serious drug adverse reactions in patients with CHB is presented.


Assuntos
Antivirais/uso terapêutico , Guias como Assunto/normas , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/uso terapêutico , Guias de Prática Clínica como Assunto , Consenso , Vírus da Hepatite B , Humanos , Resultado do Tratamento
9.
Dtsch Med Wochenschr ; 144(8): 528-534, 2019 04.
Artigo em Alemão | MEDLINE | ID: mdl-30986860

RESUMO

With approximately 240 million chronically infected people, hepatitis B virus (HBV) infection is a leading cause of cirrhosis and hepatocellular carcinoma in the world. Chronic HBV infection should be treated with antivirals, if either liver cirrhosis with detectable HBV DNA or relevant viral load (HBV DNA > 2000 IU/ml) and signs of liver damage (transaminase elevation, fibrosis, risk of liver cancer or similar) are present. The current standard therapy is a long-term treatment with nucleoside or nucleotide analogues such as entecavir, tenofovir disoproxil fumarate or tenofovir alafenamide, while in selected cases interferon treatment (for 48 weeks) may be useful. Entecavir and the new drug tenofovir alafenamide (TAF) are to be preferred over tenofovir disoproxil fumarate in patients with concomitant renal insufficiency or osteoporosis. Pregnant women with high viral load (> 200 000 IU/ml) should be treated with tenofovir in the third trimester to minimize the risk of neonatal transmission (in addition to immediate active-passive immunization). In conditions of immunosuppression (e. g. chemotherapy, rituximab, anti-TNF), even a "healed" HBV infection may reactivate in a life-threatening manner, requiring prophylactic antiviral therapy in addition to testing for HBV in high-risk situations. The current therapies primarily achieve virus suppression, but rarely the loss of HBs antigen, which is considered a functional cure. New strategies such as discontinuation of long-term antiviral therapy with provoked reactivation and also completely new drugs are currently in clinical trials. The most serious form of viral hepatitis is the co-/superinfection of HBV with the delta virus (HDV). Standard therapy for delta hepatitis is pegylated interferon-alfa, but the approval of new drugs such as the HBV entry inhibitor Myrcludex is expected in the near future.


Assuntos
Hepatite B Crônica/terapia , Hepatite D/terapia , Antivirais/uso terapêutico , Feminino , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Hepatite D/diagnóstico , Hepatite D/epidemiologia , Humanos , Interferons/uso terapêutico , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/terapia , Fatores de Risco
10.
Zhonghua Gan Zang Bing Za Zhi ; 27(2): 85-87, 2019 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-30818909

RESUMO

The main transmission route of chronic hepatitis B virus infection is mother-to-child transmission of hepatitis B virus and the main cause of combined immune prophylaxis failure in neonates at the end of pregnancy is high viral load. Moreover, oral administration of nucleos(t)ide analogues (NAs) during the second and third trimesters of pregnancy can significantly reduce or even completely block mother-to-child transmission of HBV. This article focuses on the necessity and feasibility of oral NAs antiviral therapy for HBV carrier pregnant woman with high viral load, and the issues commences at the time of medication and viral load thresholds.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/transmissão , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Antivirais/administração & dosagem , DNA Viral , Feminino , Hepatite B Crônica/prevenção & controle , Humanos , Recém-Nascido , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/virologia , Carga Viral
11.
Dig Dis Sci ; 64(4): 1041-1049, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30874985

RESUMO

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the most important underlying causes for the development of hepatocellular carcinoma (HCC) worldwide. Determining the optimal approach for management of the viral infection and the HCC depends on the virus and the stage of the cancer. In patients with HCV-associated HCC, there are multiple reasons to first treat the HCC. Firstly, in case of a curable HCC, the urgency for HCC treatment is important to avoid progression during HCV treatment. Secondly, the presence of HCC itself appears to reduce the rates of sustained virological response (SVR) achieved with direct-acting antivirals (DAAs). And finally, the evidence does not support the concept of an increase in HCC recurrence due to DAAs, so a patient can safely be treated after HCC cure. For patients with very advanced HCC, the benefits of HCV therapy are questionable. In contrast, those who develop HCC in the setting of chronic HBV infection, treatment with nucleoside analogues (NAs) is recommended prior to treating HCC, to prevent further liver injury and reduce the risk for HCC recurrence. Ultimately, earlier diagnosis and treatment of HBV and HCV will hopefully reduce the incidence of HCC worldwide.


Assuntos
Antivirais/efeitos adversos , Carcinoma Hepatocelular/terapia , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia/induzido quimicamente , Carcinoma Hepatocelular/virologia , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Humanos , Neoplasias Hepáticas/virologia , Nucleosídeos/uso terapêutico , Vigilância da População , Resposta Viral Sustentada
12.
Dig Dis Sci ; 64(8): 2187-2198, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30815819

RESUMO

BACKGROUND: The role of nucleos(t)ide analogs (NAs) therapy in intermediate and advanced hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear. AIMS: The aim was to evaluate the effect of NAs therapy on survival of intermediate- and advanced-stage HBV-related HCC patients initially treated with chemoembolization. METHODS: A total of 1016 Barcelona Clinic Liver Cancer (BCLC) stage B/C HBV-related HCC patients initially treated with chemoembolization were included. Propensity score matching (PSM) was performed to decrease heterogeneity between the antiviral and non-antiviral groups. Kaplan-Meier and Cox regression analysis were performed to evaluate the effects of NAs therapy on overall survival (OS). RESULTS: Antiviral group (n = 394) significantly prolonged OS compared with non-antiviral group (n = 622) (p = 0.003). NAs therapy (p < 0.001) along with tumor size (p = 0.002), tumor number (p = 0.001), gross vascular invasion (p < 0.001), metastasis (p < 0.001), α-fetoprotein (p < 0.001), Child-Pugh score (p = 0.008), aspartate aminotransferase (p < 0.001), and HBV DNA (p = 0.018) were identified as independent prognostic factors for OS. After PSM processing, deducting the influence of subsequent treatments for HCC, NAs therapy was still identified as an independent protective factor (p = 0.009) for OS in patients who survived ≥ 7 months, regardless of BCLC stage B or C HCC. CONCLUSION: NAs therapy prolongs OS in intermediate- and advanced-stage HBV-related HCC patients initially treated with chemoembolization. After PSM processing, patients who survived ≥ 7 months still benefited from NAs therapy.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/virologia , Quimioembolização Terapêutica , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/virologia , Nucleosídeos/análogos & derivados , Biomarcadores Tumorais/sangue , Terapia Combinada , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nucleosídeos/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida
13.
Expert Opin Pharmacother ; 20(7): 873-885, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30857443

RESUMO

INTRODUCTION: Hepatitis B virus (HBV) infection remains a global challenge with several hundred million infected individuals. Disease activity can be controlled, and adverse outcomes prevented when treatment can be provided. Frequently life-long therapy is required instead of defined treatment periods such as with the case of Hepatitis C Virus (HCV) infection. AREAS COVERED: In this review, the authors provide an overview of current start of the art therapy for HBV and indicate where variation from the current guidelines could be considered. Certain patients may be eligible for treatment with suboptimal therapies when their baseline viral load is low. Identifying ideal candidates for interferon therapy will result in good sustained responses for some patients. EXPERT OPINION: The biggest challenge remains linking patients to care and therapy. Patients can nowadays be sufficiently treated before the disease advances to a more progressed phase. However, future therapies must be extremely safe and ideally limit the required treatment period. Given Hepatitis D Virus's dependence on HBV and being a disease with an unmet clinical need, HDV may be the best target group for the development of a functional cure for hepatitis B.


Assuntos
Antivirais/uso terapêutico , Hepatite B/tratamento farmacológico , Farmacorresistência Viral , Antígenos E da Hepatite B/sangue , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Nucleosídeos/análogos & derivados , Nucleosídeos/uso terapêutico , Resposta Viral Sustentada , Carga Viral
14.
Medicine (Baltimore) ; 98(6): e14386, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30732177

RESUMO

Numerous studies suggested that antiviral therapy could reduce the recurrence in hepatocellular carcinoma (HCC) patients after hepatectomy. The impact of nucleotide and nucleoside analogues on prognosis of chronic hepatitis B (CHB) related HCC remains to be explored. We aimed to investigate the role of the telbivudine and adefovir dipivoxil on the prognosis of CHB-related HCC patients after hepatectomy.One hundred eighty-eight CHB-related patients who received hepatectomy from February 2010 to February 2017 were divided into telbivudine (LdT) and adefovir dipivoxil (ADV) groups. The characteristics and survival information of both groups were retrospectively compared and analyzed.One hundred eleven and 77 patients received telbivudine and adefovir dipivoxil monotherapy, respectively. Alanine aminotransferase (ALT), total bilirubin level, status of hepatitis B e antigen (HBeAg), serum HBV-DNA level were compared between groups. OS and DFS in ADV-treatment group were significantly better than it in LdT-treatment group (P < .05). In the subgroups analysis, we found that ADV treatment was significantly associated with better DFS and OS among patients with cirrhosis, HBeAg-negative patients, or those with detectable HBV-DNA.CHB-related HCC patients receiving long-term ADV-treatment had a better OS and DFS than patients receiving LdT-treatment after hepatectomy.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Organofosfonatos/uso terapêutico , Telbivudina/uso terapêutico , Adenina/administração & dosagem , Adenina/uso terapêutico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/cirurgia , DNA Viral , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/complicações , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/cirurgia , Masculino , Recidiva Local de Neoplasia , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Organofosfonatos/administração & dosagem , Prognóstico , Estudos Retrospectivos , Telbivudina/administração & dosagem
15.
Zhonghua Gan Zang Bing Za Zhi ; 27(1): 27-32, 2019 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-30685920

RESUMO

Objective: To investigate the molecular mechanism of poor response of nucleoside and interferon therapy in some patients with chronic hepatitis B (CHB) and the negative regulatory factor of suppressor of cytokine signaling 3 (SOCS3) expression in the interferon-signaling pathway. Also, study the clinical relationship between SOCS3 and antiviral efficacy of nucleoside and interferon. Methods: Peripheral blood and matched liver tissue samples from 54 CHB patients who participated in the OSST study were selected. HBsAg was measured at different time points (baseline and weeks 12, 24, 36, and 48) to observe the antiviral efficacy. Meanwhile, quantitative real-time PCR, and immunohistochemistry were used to detect the expression levels of SOCS3 mRNA in peripheral blood mononuclear cells (PBMCs) and matched liver tissues (baseline and 48 weeks). At the end of the 48-week treatment, patients with HBsAg negative or HBeAg seroconversion were defined as response group, and vice versa. Paired t-tests were used to compare normal distribution variables and the Mann-Whitney U test was used to compare the median differences between groups of non-normally distributed variables. Results: After 48 weeks of treatment, serum HBsAg levels in the Peg-IFN group continued to decline (average decrease of 1.14 log(10) IU / ml at week 48; P = 0.001 compared with baseline), while the entecavir group remained almost unchanged during treatment (average decrease was 0.05 log(10) IU / ml at week 48; compared with baseline P = 0.12). The expression of SOCS3 mRNA (Messenger RNA, mRNA) in peripheral blood and liver tissues of non-responder group was significantly higher than the response group in the course of Peg-IFNα2a treatment. The immunohistochemical results of liver tissue showed that the expression of SOCS3 in the non-responder group was significantly higher than that in the response group at baseline (P = 0.027). After 48 weeks of treatment with Peg-IFNα2a, the expression of SOCS3 in the non-responder group was significantly higher than that in the baseline and response groups (P = 0.003, P = 0.012, respectively). Conclusion: The expression of SOCS3 in peripheral blood mononuclear cells and liver tissues of non-responding CHB patients was significantly higher than that of responding CHB patients during interferon and nucleoside antiviral therapy. We speculated that SOCS3 might affect the antiviral efficacy through negative regulation of JAK-STAT signaling pathway, and partly expose the mechanism of interferon resistance.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Leucócitos Mononucleares , Nucleosídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Proteína 3 Supressora da Sinalização de Citocinas/genética , DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Humanos , Interferon-alfa/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Resultado do Tratamento
16.
PLoS One ; 14(1): e0209605, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30650082

RESUMO

The prevalence of transmitted drug resistance (TDR) in antiretroviral therapy (ART)-naïve individuals remains stable in most developed countries despite a decrease in the prevalence of acquired drug resistance. This suggests that persistence and further transmission of HIV-1 that encodes transmitted drug resistance mutations (TDRMs) is occurring in ART-naïve individuals. In this study, we analysed the prevalence and persistence of TDRMs in the protease and reverse transcriptase-sequences of ART-naïve patients within the German HIV-1 Seroconverter Study Cohort who were infected between 1996 and 2017. The prevalence of TDRMs and baseline susceptibility to antiretroviral drugs were assessed using the Stanford HIVdb list and algorithm. Mean survival times of TDRMs were calculated by Kaplan-Meier analysis. The overall prevalence of TDR was 17.2% (95% CI 15.7-18.6, N = 466/2715). Transmitted NNRTI resistance was observed most frequently with 7.8% (95% CI 6.8-8.8), followed by NRTI resistance (5.0%, 95% CI 4.2-5.9) and PI resistance (2.8%, 95% CI 2.2-3.4). Total TDR (OR = 0.89, p = 0.034) and transmitted NRTI resistance (OR = 0.65, p = 0.000) decreased between 1996 and 2017 but has remained stable during the last decade. Viral susceptibility to NNRTIs (6.5%-6.9% for individual drugs) was mainly reduced, while <3% of the recommended NRTIs and PIs were affected. The longest mean survival times were calculated for the NNRTI mutations K103N (5.3 years, 95% CI 4.2-5.6) and E138A/G/K (8.0 years, 95% CI 5.8-10.2 / 7.9 years, 95% CI 5.4-10.3 / 6.7 years, 95% CI 6.7-6.7) and for the NRTI mutation M41L (6.4 years, 95% CI 6.0-6.7).The long persistence of single TDRMs indicates that onward transmission from ART-naïve individuals is the main cause for TDR in Germany. Transmitted NNRTI resistance was the most frequent TDR, showing simultaneously the highest impact on baseline ART susceptibility and on TDRMs with prolonged persistence. These results give cause for concern regarding the use of NNRTI in first-line regimens.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Soropositividade para HIV/tratamento farmacológico , HIV-1/genética , HIV-1/imunologia , Adulto , Antirretrovirais/uso terapêutico , Estudos de Coortes , Farmacorresistência Viral/genética , Farmacorresistência Viral/imunologia , Feminino , Alemanha , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Soropositividade para HIV/virologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Nucleosídeos/uso terapêutico , Prevalência , Inibidores da Transcriptase Reversa/uso terapêutico , Soroconversão
17.
Medicine (Baltimore) ; 98(3): e13929, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30653099

RESUMO

The prognositc value of dynamic liver stiffness (LS) variation on hepatocellular carcinoma (HCC) incidence in patients with chronic hepatitis B (CHB) remains to be explored. We aim to compare HCC incidence in patients with compensated CHB-related cirrhosis with increased and decreased LS after nucleos(t)ide analog (NA) regimens.A total of 168 patients with CHB-related compensated cirrhosis were divided into groups according to LS variation post to NA treatment. The laboratory results of 2 groups were reviewed and investigated. The probability of HCC development among each group was analyzed and compared.A total of 168 patients with CHB with compensated cirrhosis received NA treatment and Fibroscan. Child-Pugh score, alanine aminotransferase, total bilirubin level, status of hepatitis B e antigen, and serum hepatitis B virus DNA level were compared between groups. The cumulative probability of HCC development in patients with decreased LS was significantly lower than in patients with increased LS (P < .05). Multi-variant analysis indicated that decreased LS was significantly associated with lower probability of HCC development (hazard ratio, 0.65; 95% confidence interval range, 0.33-0.84, P < .05).Decreased LS after NA treatment indicates a lower HCC incidence in patients with CHB with compensated cirrhosis.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/patologia , Fígado/diagnóstico por imagem , Adulto , Idoso , Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Humanos , Incidência , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Nucleosídeos/uso terapêutico , Estudos Retrospectivos
18.
Environ Mol Mutagen ; 60(5): 404-409, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-29206312

RESUMO

All nucleoside analogues for treating HIV infection, due to their capacity to integrate into and alter human DNA, are experimentally genotoxic to some extent. The long-term oncogenic risk after in utero exposure remains to be determined. Cancer incidence in uninfected children exposed to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) was evaluated, by cross-checking against the National Cancer Registry, in the French perinatal study of children born to HIV+ mothers. Twenty-one cancers were identified in 15,163 children (median age: 9.9 years [interquartile range (IQR): 5.8-14.2]) exposed to at least one NRTI in utero between 1990 and 2014. Five of these children were exposed to zidovudine monotherapy, and 15 to various combinations, seven of which included didanosine. Overall, the total number of cases was not significantly different from that expected for the general population (SIR = 0.8[0.47-1.24]), but the number of cases after didanosine exposure was twice that expected (SIR = 2.5 [1.01-5.19]). Didanosine accounted for only 10% of prescriptions but was associated with one-third of cancers. In multivariate analysis, didanosine exposure was significantly associated with higher risk (HR = 3.0 [0.9-9.8]). This risk was specifically linked to first-trimester exposure (HR = 5.5 [2.1-14.4]). Three cases of pineoblastoma, a very rare cancer, were observed, whereas 0.03 were expected. Two were associated with didanosine exposure. Despite reassuring data overall, there is strong evidence to suggest that didanosine displays transplacental oncogenicity. These findings cannot be extrapolated to other NRTIs, but they highlight the need for comprehensive evaluations of the transplacental genotoxicity of this antiretroviral class. Environ. Mol. Mutagen., 60:404-409, 2019. © 2017 Wiley Periodicals, Inc.


Assuntos
Fármacos Anti-HIV/toxicidade , Exposição Materna , Troca Materno-Fetal/fisiologia , Neoplasias/epidemiologia , Nucleosídeos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/patologia , Adolescente , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Didanosina/uso terapêutico , Didanosina/toxicidade , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Neoplasias/genética , Nucleosídeos/uso terapêutico , Gravidez , Estudos Prospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Inibidores da Transcriptase Reversa/toxicidade , Risco , Inquéritos e Questionários , Zidovudina/uso terapêutico , Zidovudina/toxicidade
19.
Clin Res Hepatol Gastroenterol ; 43(1): 67-76, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30219693

RESUMO

BACKGROUND: Nucleoside and nucleotide analogues (NAs) have a risk of mitochondrial toxicity and then inducing the increase of lactate. We aim to evaluate the impact of lactate on the effects of NAs therapy in hepatitis B virus-related hepatocellular carcinoma (HCC) patients after curative liver resection. MATERIALS AND METHODS: Five hundred and fifty-seven HBV-related HCC patients were divided into the treatment and control group according to whether they received NAs therapy or not. Perioperative and prognosis data were retrospectively reviewed. RESULTS: The treatment group had a better overall survival rate (OS) than the control group (P = 0.017). The recurrence-free survival rate (RFS) did not significantly differ between the two groups (P = 0.174). NAs could improve the OS of early stage HCC patients (P = 0.028), as well as the OS of advanced stage HCC patients with low level of lactate in subgroup analysis stratified against the level of lactate (P = 0.037). Advanced stage HCC patients in the treatment group had a higher value of lactate than those in the control group (P = 0.024). Besides, advanced stage HCC patients had a higher value of lactate than early stage HCC patients in the treatment group (P < 0.001), as well as in the control group (P < 0.001). CONCLUSIONS: NAs could improve the long-term outcomes of HBV-related HCC patients after curative liver resection. However, the improvement effect of NAs therapy is counteracted by the adverse effect of elevated lactate in advanced stage HBV-related HCC patients.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Lactatos/sangue , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Feminino , Hepatite B Crônica/complicações , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Nucleosídeos/análogos & derivados , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
20.
Clin Immunol ; 198: 31-38, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30503407

RESUMO

In this study, we investigated whether plasma cytokine/chemokine levels could predict HBsAg loss or clinical relapse (CR) after stopping nucleos(t)ides analogue (NA) treatment. Theplasma cytokines/chemokines levels were measured at 0, 4, 8, 12, 24 and 48 weeks after NA discontinuation by using the enzyme-linked immunoassay (ELISA) kit. Cox regression analysis revealed that CXCL13 level at the end of treatment (EOT) was an independent predictor for CR (HR 0.26, p < 0.001) and HBsAg loss (HR 3.01, p = 0.008) after treatment cessation. Among the patients with EOT CXCL13 level < 80 pg/ml, the cumulative incidences of CR and HBsAg loss were 65% and 0% at 4 years, respectively. As for the patients with EOT CXCL13 level ≥ 1000 pg/ml, 47.5% cases had HBsAg loss. Our study showed that EOT CXCL13 level was associated with off-treatment response, which may be used to guide cessation of NA treatment in clinical practice.


Assuntos
Antivirais/uso terapêutico , Quimiocina CXCL13/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Adulto , Citocinas/sangue , Feminino , Hepatite B Crônica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Nucleosídeos/uso terapêutico , Estudos Prospectivos , Recidiva
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