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1.
World J Gastroenterol ; 27(31): 5181-5188, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34497443

RESUMO

Hepatitis C virus (HCV) reactivation occurs in 23% of HCV-infected cancer patients receiving chemotherapy. Forty-three percent of the patients with reactivation of HCV during chemotherapy develop a hepatitis flare. Most of the cancer patients with HCV reactivation have an unremarkable clinical course following an HCV-related hepatitis flare during chemotherapy. However, 26%-57% of the cancer patients developing an acute flare of chronic hepatitis C during chemotherapy require unanticipated discontinuation or dose reduction of chemotherapy, which results in deleterious changes in the cancer treatment plan. Although an optimal strategy for HCV screening in cancer patients receiving chemotherapy has not been established, universal pre-chemotherapy HCV testing for patients with hematological malignancies is recommended by current guidelines. All the currently approved direct-acting antivirals (DAAs) can be used in cancer patients, but the use of DAAs during chemotherapy should avoid drug-drug interactions between chemotherapy and antiviral agents. If there are no contraindications or anticipated drug-drug interactions, DAAs treatment can be administered before, during, or after chemotherapy. In conclusion, HCV reactivation occurs in approximately one-fourth of HCV-infected cancer patients receiving chemotherapy. An HCV-related hepatitis flare during chemotherapy may lead to the discontinuation of potentially life-saving chemotherapy. Currently, universal HCV screening is recommended in hematological malignancy patients before chemotherapy, but there is no evidence-based guideline for other cancer patients. DAAs treatment can cure HCV infection and prevent HCV reactivation during chemotherapy.


Assuntos
Hepatite B Crônica , Hepatite C Crônica , Hepatite C , Antivirais/efeitos adversos , Hepacivirus , Hepatite B Crônica/tratamento farmacológico , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Exacerbação dos Sintomas , Ativação Viral
2.
Medicine (Baltimore) ; 100(33): e26917, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414947

RESUMO

BACKGROUND: Hepatitis B Virus (HBV) infection is a global public health problem. After infection, patients experience a natural course from chronic hepatitis to cirrhosis and even Hepatitis B associated Hepatocellular Carcinoma (HBV-HCC). With the multi-omics research, many differentially expressed genes from chronic hepatitis to HCC stages have been discovered. All these provide important clues for new biomarkers and therapeutic targets. The purpose of this study is to explore the differential gene expression of HBV and HBV-related liver cancer, and analyze their enrichments and significance of related pathways. METHODS: In this study, we downloaded four microarray datasets GSE121248, GSE67764, GSE55092, GSE55092 and GSE83148 from the Gene Expression Omnibus (GEO) database. Using these four datasets, patients with chronic hepatitis B (CHB) differentially expressed genes (CHB DEGs) and patients with HBV-related HCC differentially expressed genes (HBV-HCC DEGs) were identified. Then Protein-protein Interaction (PPI) network analysis, Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to excavate the functional interaction of these two groups of DEGs and the common DEGs. Finally, the Kaplan website was used to analyze the role of these genes in HCC prognostic. RESULTS: A total of 241 CHB DEGs, 276 HBV-HCC DEGs, and 4 common DEGs (cytochrome P450 family 26 subfamily A member 1 (CYP26A1), family with sequence similarity 110 member C(FAM110C), SET and MYND domain containing 3(SMYD3) and zymogen granule protein 16(ZG16)) were identified. CYP26A1, FAM110C, SMYD3 and ZG16 exist in 4 models and interact with 33 genes in the PPI network of CHB and HBV-HCC DEGs,. GO function analysis showed that: CYP26A1, FAM110C, SMYD3, ZG16, and the 33 genes in their models mainly affect the regulation of synaptic vesicle transport, tangential migration from the subventricular zone to the olfactory bulb, cellular response to manganese ion, protein localization to mitochondrion, cellular response to dopamine, negative regulation of neuron death in the biological process of CHB. In the biological process of HBV-HCC, they mainly affect tryptophan catabolic process, ethanol oxidation, drug metabolic process, tryptophan catabolic process to kynurenine, xenobiotic metabolic process, retinoic acid metabolic process, steroid metabolic process, retinoid metabolic process, steroid catabolic process, retinal metabolic process, and rogen metabolic process. The analysis of the 4 common DEGs related to the prognosis of liver cancer showed that: CYP26A1, FAM110C, SMYD3 and ZG16 are closely related to the development of liver cancer and patient survival. Besides, further investigation of the research status of the four genes showed that CYP26A1 and SMYD3 could also affect HBV replication and the prognosis of liver cancer. CONCLUSION: CYP26A1, FAM110C, SMYD3 and ZG16 are unique genes to differentiate HBV infection and HBV-related HCC, and expected to be novel targets for HBV-related HCC occurrence and prognostic judgement.


Assuntos
Carcinoma Hepatocelular/virologia , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Neoplasias Hepáticas/virologia , Carcinoma Hepatocelular/tratamento farmacológico , Biologia Computacional , Hepatite B Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico
3.
BMC Health Serv Res ; 21(1): 846, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419018

RESUMO

BACKGROUND: The PAGE-B score (Platelet Age GEnder-HBV) selects chronic hepatitis B (cHB) patients showing no relevant 5-year risk for hepatocellular carcinoma (HCC). We, therefore, explored potential cost reduction following the introduction of a PAGE-B tailored ultrasound screening in a single center cohort of cHB patients receiving stable antiviral therapy. METHODS: cHB patients attending throughout the year 2018 were documented. Patients eligible for PAGE-B score were classified into high (≥18 points), intermediate (10-17 points) and low (≤9 points) HCC risk groups. Patients of the low HCC risk group could postpone HCC screening to reduce HCC screening expenses. Full costs for hepatic ultrasound were assessed. RESULTS: Throughout the year cHB patients (n = 607) attended our clinic, which included PAGE-B eligible patients (n = 227, 37.4%) of whom n = 94 (15.8%) were allocated to the low HCC risk group. Sonographic HCC screening during a median exam time of 12.4 min (IQR 9.2-17.2) resulted in total costs of 22.82 Euro/exam. Additional opportunistic expenses caused by patient's lost earnings or productivity were 15.6-17.5 €/exam and 26.7 €/exam, respectively. Following a PAGE-B tailored HCC screening at our institution annual full costs for cHB patients could be reduced by 15.51%, which equals a cost reduction by 1.91% for our total sonography unit. In comparison, 1.35% up to 7.65% of HBV-infected patients of Caucasian descent could postpone HCC screening according to population-based estimates from Germany. CONCLUSIONS: PAGE-B risk score adapted screening for HCC is an efficient and cost neutral tool to reduce costs for sonography in Caucasian patients with chronic hepatitis B receiving antiviral treatment.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Fatores de Risco , Ultrassonografia
4.
Medicina (Kaunas) ; 57(8)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34440963

RESUMO

Background and Objectives: Hepatitis B virus infection remains a major public health concern. The interaction between hepatitis B virus (HBV) hepatitis B virus and the host inflammatory response is an important contributing factor driving liver damage and diseases outcomes. The management of chronic hepatitis B virus infection is an area of massive unmet clinical need worldwide. Our primary aim for this study was to evaluate biological response rates and sustained virological response in patients with chronic hepatitis B treated with Peg-IFN α-2a/b. The second aim of the study was the identification of metabolic changes and insulin resistance. Materials and Methods: We enrolled in this study 166 patients who fulfilled all inclusion and exclusion criteria. These treatment-naive patients with chronic HBV were treated with Pegylated Interferon α-2a/b. HBV infection was defined by the presence of HBV serological markers (HBsAg, anti-HBsAb, anti-HBcAb, HBeAg, anti HBeAb) by Enzyme-Linked Immuno Sorbent Assay (ELISA) and serum HBV-DNA levels were estimated by a commercially available quantitative polymerase chain reaction (PCR) assay. Results: Patients' recovery progress has been evaluated by determining the following: age, gender; biochemical tests; alanine aminotransferase, aspartate aminotransferase; serological assays for HBV serological markers (HBsAg, anti-HBsAc/Ab, anti-HBcAc/Ab, HBeAg, anti HBeAc/Ab); molecular tests to detect viral particles, testing for HBV DNA (PCR) to confirm the diagnosis and quantify the number of viral copies in the blood (viremia); liver ultrasound-performed through epigastric and intercostal approach (transversal and longitudinal sections). Conclusions: Our results indicated that only HOMA index values, that of fasting insulin, together with baseline HBV DNA, alanine aminotransferase values, mean blood glucose at the beginning of treatment may be predictive of the early viral response in chronic hepatitis B.


Assuntos
Hepatite B Crônica , Antivirais/uso terapêutico , DNA Viral , Antígenos de Superfície da Hepatite B/uso terapêutico , Antígenos E da Hepatite B/uso terapêutico , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Polietilenoglicóis/uso terapêutico , Resultado do Tratamento
5.
World J Gastroenterol ; 27(29): 4831-4845, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34447229

RESUMO

Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts. Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients. The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments. Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence, the number of new infections. Antiviral treatments have decreased the rates of liver decompensation and as a result, lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection. The quality of life of chronically infected patients has also been improved significantly by modern treatment. Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis. Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation. This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Qualidade de Vida
8.
Zhonghua Gan Zang Bing Za Zhi ; 29(7): 666-672, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34371537

RESUMO

Objective: To observe the dynamic changes of serum RANTES during the treatment with nucleos(t)ide analogues combined with pegylated interferon alpha (peginterferon-α), and further analyze the predictive effect of RANTES on HBsAg clearance in patients with chronic hepatitis B. Methods: 98 cases of chronic hepatitis B with quantitative HBsAg < 3 000 IU/ml and HBV DNA < 20 IU/ml after≥1 year NAs treatment were enrolled. Among them, 26 cases continued to receive NAs monotherapy, 72 cases received NAs combined with pegylated interferon alpha therapy. The changes in RANTES during treatment were observed. The receiver operating characteristic curve was used to analyze the early changes of RANTES to predict the HBsAg clearance during 48 weeks. Results: During 48 weeks, 15 cases (20.83%) had achieved HBsAg clearance in combination group, while no patient had achieved HBsAg clearance in NAs group. The overall serum RANTES level had decreased from baseline in NAs and combination group. At week 48, in the combination group, the serum RANTES level was decreased more significantly in patients with HBsAg clearance than patients without. Further analysis showed that, in combination group, HBsAg clearance rate of patients with serum RANTES decreased at week 12 and 24 was higher than patients with elevated (29.17% vs. 4.17%, P = 0.014; 28.00% vs. 4.55%, P = 0.052), and quantitative HBsAg reduction was larger significantly [(1.49 ± 1.26) log(10)IU/ml vs. (0.73 ± 0.81) log(10)IU/ml, P = 0.017; (1.54 ± 1.27) log(10)IU/ml vs. (0.57 ± 0.56) log(10)IU/ml, P = 0.004]. Receiver operating characteristic curve analysis showed that the baseline quantitative HBsAg and the reduction in quantitative HBsAg and serum RANTES during the early period were predictors of HBsAg clearance after 48-week combination therapy. Furthermore, the combination of baseline quantitative HBsAg and 12 - or 24-week reduction of serum RANTES were better predictors of HBsAg clearance than that of baseline quantitative HBsAg combined with HBsAg decrease at week 12 or 24. The area under the receiver operating characteristic curve of the former was 0.925 and 0.939, while that of the latter was 0.909 and 0.929, respectively. Conclusion: Early reduction of serum RANTES at week 12 and 24 can predict HBsAg loss in CHB patients receiving addition of peginterferon-α to ongoing NAs Therapy, so serum RANTES could be one of the key immunological markers for predicting HBsAg clearance.


Assuntos
Antígenos de Superfície da Hepatite B , Hepatite B Crônica , Antivirais/uso terapêutico , Quimiocina CCL5/uso terapêutico , DNA Viral , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Resultado do Tratamento
9.
Zhonghua Gan Zang Bing Za Zhi ; 29(7): 673-678, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34371538

RESUMO

Objective: To explore the possibility of hepatitis B core antibody (anti-HBc) in predicting hepatitis B virus surface antigen (HBsAg) clearance. Methods: Sixty cases with chronic hepatitis B who were previously treated with peginterferon α-2a combined with nucleos(t)ide analogues (NAs) antiviral therapy were divided according to the HBsAg clearance or non-clearance; 41 cases in the clearance group and 19 cases in the non-clearance group. Double antigen sandwich method was used to detect patients anti-HBc quantitative levels during the course of treatment and at baseline, 24, 48, 72 and 96 weeks. Logistic regression analysis and receiver operating characteristic curve (ROC) were used to evaluate the predictive ability of related influencing factors for HBsAg clearance. Results: With antiviral treatment prolongation, anti-HBC quantitative levels in the overall population showed a progressive downward trend in the clearance group and the non-clearance group, but the anti-HBC level in the clearance group was significantly higher than non-clearance group at the baseline and successive detection time points during the antiviral treatment (P < 0.05). Multivariate logistic regression showed that baseline quantitative anti-HBC level, HBsAg decline at week 24 (log10 IU / ml), and alanine aminotransferase (ALT) > 1.5 times the upper limit of normal value (ULN) were all influencing factors for HBsAg clearance during the treatment (OR = 0.156, P = 0.026; OR = 0.134, P = 0.023; OR = 0.239, P = 0.028). Among them, the baseline quantitative anti-HBc level was the best independent predictor for HBsAg clearance (OR = 0.235; P = 0.004), and the sensitivity and specificity for predicting HBsAg clearance at > 3.40 log10 IU/ mL were 56.1% and 89.5%, respectively. Logistic regression model was used as a reference to construct combined predictors in order to improve the prediction accuracy. Among them, the combined factor 3 had the highest predictive value (the area under the ROC curve had reached up to 0.870; 95%CI was 0.781 ~ 0.960; P < 0.001). The cut-off value of combined factor 3 was > 0.386, and the sensitivity and specificity were 80.5% and 78.9%, respectively. In addition, the combined index had further improved the predictive value, which is the combination of any two or more indexes based on the baseline quantitative anti-HBC level, and HBsAg clearance predictive rate had reached 94.12% ~ 100%. Conclusion: The baseline quantitative anti-HBC level has the highest predictive value for HBsAg clearance. The combination of ALT > 1.5×ULN and HBsAg decline at 24 weeks during the treatment can more precisely predict HBsAg clearance. Therefore, it is a reliable non-invasive biomarker.


Assuntos
Antígenos de Superfície da Hepatite B , Hepatite B Crônica , Alanina Transaminase , Antivirais/uso terapêutico , DNA Viral , Anticorpos Anti-Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Resultado do Tratamento
10.
Zhonghua Gan Zang Bing Za Zhi ; 29(7): 685-689, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34371540

RESUMO

Objective: To investigate the effect of anti-liver fibrosis treatment on the occurrence of liver cancer in patients with hepatitis B-related liver cirrhosis within three years. Methods: 1,049 cases with hepatitis B-related liver cirrhosis who were hospitalized in Beijing Ditan Hospital affiliated to Capital Medical University from October 2008 to August 2016 were enrolled. Clinical data were collected, and COX regression analysis was used to find the independent influencing factors for the occurrence of liver cancer in patients with hepatitis B-related liver cirrhosis within three years. According to whether the patients had received anti-liver fibrosis treatment for ≥ 6 months, they were divided into combination and antiviral group. There were 388 cases in combination group and 661 cases in antiviral group. In addition, the combination group received anti-liver fibrosis therapy with Chinese patent medicine on the basis of antivirus, and the antiviral group received antiviral treatment. The incidence of liver cancer within three years were compared between the two groups, and the incidence of liver cancer in patients with different Child-Pugh grades and mPAGE-B risks was further analyzed. The independent samples t-test, Mann Whitney U test, χ2 test or Fisher's exact probability method were used for data comparison. Results: Anti-liver fibrosis treatment was an independent protective factor to prevent liver cancer in patients with hepatitis B-related liver cirrhosis within 3 years (P < 0.05). The incidence of liver cancer in the combination group was lower than antiviral group within 3 years (10.3% vs. 15.4%, χ (2) = 5.480, P < 0.05). Child-Pugh stratified analysis showed that the risk of liver cancer was significantly reduced in Child-Pugh grade A patients (6.7% vs. 12.6%, χ (2) = 2.857, P = 0.040). Among high-risk patients with mPAGE-B, the incidence of liver cancer was significantly lower in combination group than control group (13.7% vs. 19.9%, χ (2) = 6.671, P = 0.031). Conclusion: Compared to antiviral therapy alone, combined anti-liver fibrosis and antiviral therapy can reduce the liver cancer occurrence risk in patients with hepatitis B-related liver cirrhosis for 3 years. Patients with Child-Pugh grade A and high-risk group by mPAGE-B scores are the dominant population to receive treatment.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Estudos Retrospectivos
11.
Aliment Pharmacol Ther ; 54(5): 709-714, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34275138

RESUMO

BACKGROUND: Nucleos(t)ide analogue (NA) discontinuation may be attempted in carefully selected patients with chronic hepatitis B (CHB) infection. AIM: To investigate whether a novel serum marker of quantitative hepatitis B virus (HBV) RNA levels could predict biochemical relapse after NA discontinuation. METHODS: We prospepctively followed non-cirrhotic Asian patients with CHB who stopped NA according to pre-specified stopping criteria. The primary endpoint was biochemical relapse (HBV DNA >2000 IU/mL and alanine transaminase >2x upper limit of normal), which were also the re-treatment criteria. RESULTS: Biochemical relapse occurred in 50 patients (48.3% at year 6). Multivariable analysis showed that higher HBV RNA levels (HR 1.34; P < 0.001) at the time of NA discontinuation were associated with increased biochemical relapse risk. The area under the curve of HBV RNA at the time of NA discontinuation for the incidence of biochemical relapse was 0.760 at 6 years. Six years after treatment discontinuation, all patients with HBV RNA levels ≥20 000 copies/mL at the end of treatment developed a biochemical relapse compared with 23.8% of patients with HBV RNA levels<1000 copies/mL (P < 0.001). More patients with HBV RNA levels <1000 copies/mL at end of treatment achieved loss of hepatitis B surface antigen than patients with higher levels (30.9% vs 1.6%; P = 0.027). CONCLUSIONS: The HBV RNA level at end of treatment predicted biochemical relapse after treatment discontinuation and may be used to guide decisions on treatment discontinuation.


Assuntos
Vírus da Hepatite B , Hepatite B Crônica , Antivirais/uso terapêutico , DNA Viral , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , RNA/uso terapêutico , Recidiva , Resultado do Tratamento
12.
Lancet Gastroenterol Hepatol ; 6(9): 723-732, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34237271

RESUMO

BACKGROUND: RO7049389, a hepatitis B virus (HBV) core protein allosteric modulator being developed for the treatment of chronic HBV infection, was found to be safe and well tolerated in healthy participants (part 1 of this study). The objective of this proof-of-mechanism study (part 2) was to evaluate the safety, pharmacokinetics, and antiviral activity of RO7049389 in patients with chronic HBV infection. METHODS: This was a multicentre, randomised, placebo-controlled, phase 1 study. Patients with chronic HBV infection who were not currently on anti-HBV therapy were enrolled at 11 liver disease centres in Hong Kong, New Zealand, Singapore, Taiwan, and Thailand. Seven patients per dose cohort were randomly assigned (6:1) to receive oral administration of RO7049389 at 200 mg or 400 mg twice a day, or 200 mg, 600 mg, or 1000 mg once a day, for 4 weeks, or matching placebo. Randomisation was via interactive voice web response system-generated numbers, with study participants, investigators, and site personnel masked to treatment allocation. The primary endpoint of the study was safety of RO7049389 and its antiviral effect on HBV DNA concentration at the end of treatment, assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02952924. FINDINGS: Between May 21, 2017, and April 3, 2019, 62 patients were screened for eligibility, and 37 eligible patients were enrolled in five dose cohorts sequentially. All adverse events were of mild or moderate intensity. Among the 31 patients who received RO7049389, the most common adverse events were headache (in five [16%] of 31 patients), increased alanine aminotransferase (ALT; five [16%]), increased aspartate aminotransferase (AST; four [13%]), upper respiratory tract infection (four [13%]), and diarrhoea (three [10%]). The most common moderate adverse events were ALT increase (three [10%]) and AST increase (two [6%]), and there were no serious adverse events. At the end of 4 weeks treatment, mean HBV DNA declines from baseline in RO7049389-treated patients were 2·44 log10 IU/mL (SD 0·98) in the 200 mg twice a day group, 3·33 log10 IU/mL (1·14) in the 400 mg twice a day group, 3·00 log10 IU/mL (0·54) in the 200 mg once a day group, 2·86 log10 IU/mL (0·79) in the 600 mg once a day group, and 3·19 log10 IU/mL (0·33) in the 1000 mg once a day group versus 0·34 log10 IU/mL (0·54) in the pooled placebo patients. INTERPRETATION: RO7049389 was safe and well tolerated and demonstrated antiviral activity over 4 weeks of treatment in patients with chronic HBV infection. These findings support further clinical development of RO7049389 as a component of novel combination treatment regimens for patients with chronic HBV infection. FUNDING: F Hoffmann-La Roche.


Assuntos
Antivirais/farmacocinética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Sítio Alostérico , Antivirais/administração & dosagem , DNA Viral/análise , Relação Dose-Resposta a Droga , Feminino , Vírus da Hepatite B/genética , Hepatite B Crônica/metabolismo , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
World J Gastroenterol ; 27(26): 4004-4017, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34326610

RESUMO

Chronic viral hepatitis is a significant health problem throughout the world, which already represents high annual mortality. By 2040, chronic viral hepatitis due to virus B and virus C and their complications cirrhosis and hepatocellular carcinoma will be more deadly than malaria, vitellogenesis-inhibiting hormone, and tuberculosis altogether. In this review, we analyze the global impact of chronic viral hepatitis with a focus on the most vulnerable groups, the goals set by the World Health Organization for the year 2030, and the key points to achieve them, such as timely access to antiviral treatment of direct-acting antiviral, which represents the key to achieving hepatitis C virus elimination. Likewise, we review the strategies to prevent transmission and achieve control of hepatitis B virus. Finally, we address the impact that the coronavirus disease 2019 pandemic has had on implementing elimination strategies and the advantages of implementing telemedicine programs.


Assuntos
COVID-19 , Hepatite B Crônica , Hepatite C Crônica , Hepatite Viral Humana , Neoplasias Hepáticas , Antivirais/uso terapêutico , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/tratamento farmacológico , Hepatite Viral Humana/epidemiologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle
14.
West Afr J Med ; 38(7): 629-633, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34330611

RESUMO

INTRODUCTION: Chronic hepatitis B (CHB) is an international public health problem. Treatment reduces its morbidity, mortality and infectivity. The aim of this study was to determine adherence among CHB infected patients on Tenofovir and the reasons for non-adherence. METHODOLOGY: It was a cross-sectional study of patients on tenofovir for at least 6 months. Information was obtained on bio- data, adherence to tenofovir, duration and reasons for nonadherence using an interviewer administered questionnaire. Non- adherence was defined as patient reporting missing medication at all. Chi square or Fisher exact test and Student's t-test were used to determine associations. P value less than 0.05 was considered significant. RESULTS: A total of 150 participants comprising of 76 (50.7%) females and 74 (49.3%) males with mean age of 39.2 ± 11.4 years, participated in the study. Non adherence rate was 65%. There was no significant association between non-adherence and tribe (p=0.7), level of education (p=0.8), religion (p=0.2), sex (p=0.9), clinical state (p=0.8), treatment experience (p=0.8) and months on Tenofovir (0.1) while a significant association existed with age (0.01), the presence of comorbidity (p=0.02) and taking another medication apart from tenfovir (0.00). The reasons for non-adherence included out of station 22 (14.7%), financial constraint 19(12.5%), unavailability of the drug 19 (12.5%), forgetfulness 15 (10%), perceived side effects 12 (8%), undetectable serum DNA quantification 11 (7.3%), ignorance of continuous use of Tenofovir 10 (6.7%), and pregnancy 9 (6%) among others. CONCLUSION: Adherence to Tenofovir is poor among CHB patients attending University College Hospital, Ibadan.


Assuntos
Hepatite B Crônica , Adesão à Medicação , Adulto , Estudos Transversais , Feminino , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Centros de Atenção Terciária
15.
World J Gastroenterol ; 27(24): 3466-3482, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34239263

RESUMO

Primary liver cancers carry significant morbidity and mortality. Hepatocellular carcinoma (HCC) develops within the hepatic parenchyma and is the most common malignancy originating from the liver. Although 80% of HCCs develop within background cirrhosis, 20% may arise in a non-cirrhotic milieu and are referred to non-cirrhotic-HCC (NCHCC). NCHCC is often diagnosed late due to lack of surveillance. In addition, the rising prevalence of non-alcoholic fatty liver disease and diabetes mellitus have increased the risk of developing HCC on non-cirrhotic patients. Viral infections such as chronic Hepatitis B and less often chronic hepatitis C with advance fibrosis are associated with NCHCC. NCHCC individuals may have Hepatitis B core antibodies and occult HBV infection, signifying the role of Hepatitis B infection in NCHCC. Given the effectiveness of current antiviral therapies, surgical techniques and locoregional treatment options, nowadays such patients have more options and potential for cure. However, these lesions need early identification with diagnostic models and multiple surveillance strategies to improve overall outcomes. Better understanding of the NCHCC risk factors, tumorigenesis, diagnostic tools and treatment options are critical to improving prognosis and overall outcomes on these patients. In this review, we aim to discuss NCHCC epidemiology, risk factors, and pathogenesis, and elaborate on NCHCC diagnosis and treatment strategies.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/terapia , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/terapia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia
16.
Biomed Environ Sci ; 34(6): 443-453, 2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284852

RESUMO

Objective: To investigate the changes in the cytokine profiles of chronic hepatitis B (CHB) patients undergoing antiviral treatment. Methods: Hepatitis B e antigen (HBeAg)-positive patients were treated with Pegylated interferon (PEG-IFN) and entecavir (ETV). Clinical biochemistry and cytokines were detected at baseline and every 3 months. Results: In all, 200 patients completed 48 weeks of treatment, 100 in the PEG-IFN group and 100 in the ETV group. During 3-6 months of treatment, compared with baseline, the PEG-IFN group showed a significant decrease in interferon-gamma (IFN-γ), interleukin-17A (IL-17A), interleukin-6(IL-6), interleukin-10(IL-10), and transforming growth factor beta (TGF-ß) ( P < 0.001) and a significant increase in interferon-alpha 2(IFN-α2) ( P < 0.001). In the ETV group, IL-10 and TGF-ß1 decreased significantly ( P < 0.001). After 3 months, the levels of IFN-α2, IL-17A, and tumor necrosis factor-alpha(TNF-α) in the PEG-IFN group were significantly higher than those in the ETV group ( P < 0.01). The levels of IL-6 and TGF-ß3 were significantly lower than those in the ETV group ( P < 0.01). After 6 months, the levels of IFN-α2, IFN-γ, and TNF-α in the PEG-IFN group were significantly higher than those in the ETV group ( P < 0.01), while the levels of IL-6 and TGF-ß3 were significantly lower than those in the ETV group ( P < 0.01). Compared with ETV, PEG-IFN had higher HBeAg and HBsAg disappearance rates. Conclusion: During antiviral therapy, a change in the cytokine profile occurred; in the aspect of immune control and functional cure, PEG-IFN was significantly better than ETV.


Assuntos
Antivirais/uso terapêutico , Citocinas/sangue , Guanina/análogos & derivados , Hepatite B Crônica/sangue , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Antivirais/farmacologia , Feminino , Guanina/farmacologia , Guanina/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Humanos , Interferon-alfa/farmacologia , Masculino , Polietilenoglicóis/farmacologia , Estudos Prospectivos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico
18.
J Gen Virol ; 102(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34292864

RESUMO

Hepatitis B virus surface antigen (HBsAg) encoded by the S gene is highly expressed during the replication cycle of hepatitis B virus (HBV). However, the frequent usage of tryptophan in HBsAg, which leads to a high cost of biosynthesis, is inconsistent with the high expression level of this protein. Tryptophan-truncated mutation of HBsAg, that is, a tryptophan to stop codon mutation resulting in truncated HBsAg, might help to maintain its high expression with lower biosynthetic cost. We aimed to investigate the prevalence of tryptophan-truncated S quasispecies in treatment-naïve patients with chronic hepatitis B (CHB) by applying CirSeq as well as a site-by-site algorithm developed by us to identify variants at extremely low frequencies in the carboxyl terminus of HBsAg. A total of 730 mutations were identified in 27 patients with CHB, varying from seven to 56 mutations per sample. The number of synonymous mutations was much higher than that of nonsynonymous mutations in the reverse transcriptase (RT) coding region and vice versa in the S coding region, implying that the evolutionary constraints on the RT and S genes might be different. We showed that 25 (92.6 %) of 27 patients had at least one S-truncated mutation, most of which were derived from tryptophan, indicating a high prevalence of tryptophan-truncated S mutations in treatment-naïve patients with CHB. In terms of the RT gene, 21 (77.8 %) patients had pre-existing drug-resistant mutations, while no truncated mutations were detected. Our findings that tryptophan-truncated S quasispecies and drug-resistant RT mutants were highly prevalent in treatment-naïve patients with CHB provide new insights into the composition of the HBV population, which might help optimize the treatment and management of patients with CHB.


Assuntos
Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Mutação , Triptofano/genética , Adolescente , Adulto , Algoritmos , Motivos de Aminoácidos , Antivirais/farmacologia , Antivirais/uso terapêutico , Códon , Farmacorresistência Viral , Evolução Molecular , Feminino , Genes Virais , Antígenos de Superfície da Hepatite B/química , Vírus da Hepatite B/química , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Quase-Espécies , DNA Polimerase Dirigida por RNA/genética , Análise de Sequência de DNA , Adulto Jovem
20.
Adv Exp Med Biol ; 1322: 115-138, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34258739

RESUMO

Currently, there are two safe and effective therapeutic strategies for chronic hepatitis B treatment, namely, nucleoside analogs and interferon alpha (pegylated or non-pegylated). These treatments can control viral replication and improve survival; however, they do not eliminate the virus and therefore require long-term continued therapy. In addition, there are significant concerns about virus rebound on discontinuation of therapy and the development of fibrosis and hepatocellular carcinoma despite therapy. Therefore, the search for new, more effective, and safer antiviral agents that can cure hepatitis B virus (HBV) continues. Anti-HBV drug discovery and development is fundamentally impacted by our current understanding of HBV replication, disease physiopathology, and persistence of HBV covalently closed circular DNA (cccDNA). Several HBV replication targets are the basis for novel anti-HBV drug development strategies. Many of them are already in clinical trial phase 1 or 2, while others with promising results are still in preclinical stages. As research intensifies, potential HBV curative therapies and modalities in the pipeline are now on the horizon.


Assuntos
Hepatite B Crônica , Hepatite B , Antivirais/farmacologia , Antivirais/uso terapêutico , DNA Circular/genética , DNA Circular/farmacologia , DNA Circular/uso terapêutico , DNA Viral/genética , Hepatite B/tratamento farmacológico , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Replicação Viral
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