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Evaluate the real-world effectiveness and safety of different treatment regimens for treatment-naïve high viral load chronic hepatitis B (CHB) patients. Between January 2021 and August 2022, CHB patients with HBV DNA ≥ 107 IU/mL were collected from four medical centers in Shenzhen. Patients treated with mono or combine antiviral therapy. The primary endpoint was the cumulative incidence of virological response at 48 weeks, and other endpoints included changes in HBsAg, HBeAg, ALT, and eGFR at 48 weeks. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the bias. Weighted logistics regression was used to estimate the factors affecting virological response. A total of 391 patients were included in the study, with 296 patients undergoing statistical analysis after IPTW. The patients were distributed into four groups: ETV (n = 62), TDF (n = 89), TAF (n = 36), TDF + LdT/ETV (n = 109). The 48-week cumulative incidence of virological response was significantly lower in ETV group (52.3%) compared to TDF (71.7%), TAF (74.2%), and TDF + LdT/ETV groups (77.9%) (P < 0.05). There were no significant differences in HBsAg loss among the four groups, but the HBeAg seroconversion rate was significantly higher in the TAF group. The ALT normalization rate was significantly higher in the TAF group (72.2%) compared to the others at 48 weeks (P < 0.05). In treatment-naïve CHB patients with high viral load, combination therapy was not superior to TDF or TAF monotherapy in virological response. Patients treated with TDF or TAF showed superior virological response compared to those treated with ETV. The TAF group demonstrated superiority in terms of ALT normalization and HBeAg seroconversion.
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Antivirais , Vírus da Hepatite B , Hepatite B Crônica , Carga Viral , Humanos , Feminino , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Masculino , Carga Viral/efeitos dos fármacos , Antivirais/uso terapêutico , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , Vírus da Hepatite B/genética , DNA Viral/sangue , Quimioterapia Combinada , Antígenos E da Hepatite B/sangue , Tenofovir/uso terapêutico , Estudos RetrospectivosRESUMO
Despite antiviral treatment, some patients with chronic hepatitis B (CHB) progress to cirrhosis. Enhancement of autophagy was implicated in the proliferation of hepatitis B in hepatocytes. This study aimed to evaluate the potential role of autophagy in the progression of liver fibrosis in patients receiving antiviral treatments and having completely inhibited viral replication. This descriptive-analytical study was designed and conducted in 2020 at Mottahhari Hepatitis Clinic affiliated with Shiraz University of Medical Science (Shiraz, Iran). Patients who were on anti-hepatitis B nucleotide treatments for at least two years, and those who were not cirrhotic at baseline but later progressed to cirrhosis were identified to be included in the case group. Besides, for the control group, patients on the nucleotide regimens who did not have cirrhosis at baseline or during follow-up were randomly selected. Ultimately, 16 cases and 14 controls were included in the study. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant. Serum Beclin-1 and LC3 levels were compared between the two groups using enzyme-linked immunosorbent assays. The t test was used to assess the statistical differences between the case and control groups. Beclin-1 level was significantly higher in cirrhosis patients than the control group (1283±244 vs. 1063±257, P=0.024). However, there was no statistical difference between the level of LC3 in the cirrhotic group (168±31) and the control group (150±16) (P=0.065). Autophagy may have a role in the progression of cirrhosis in patients with CHB. Future larger prospective studies are required to determine the effect of blocking on the progression of liver disease in this population A preprint of this study was published at https://www.researchsquare.com/article/rs-1435490/v1.pdf.
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Hepatite B Crônica , Humanos , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , Proteína Beclina-1 , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Nucleotídeos/uso terapêutico , AutofagiaRESUMO
BACKGROUND: The timing of antiviral therapy for chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) or aged < 30 years is still undetermined. We aimed to elucidate the correlation between liver histology, age, and ALT level in CHB patients and analyze the histological characteristics of the liver among patients with persistently normal ALT or aged < 30 years. METHODS: A retrospective analysis was conducted on 697 treatment-naive CHB patients. Liver biopsies were performed, and significant histological damage was defined as the grade of liver inflammation ≥ G2 and/or fibrosis ≥ S2 based on the Scheuer scoring system. RESULTS: The liver inflammation grades and fibrosis stages correlated positively with age, ALT, AST, GGT levels and negatively with the counts of PLT (all p < 0.050) in HBeAg-positive patients. Higher ALT levels and lower PLT counts were independently associated with significant liver inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients. Furthermore, among those with persistently normal ALT levels, the incidence of significant liver inflammation and fibrosis were 66.1% and 53.7% in HBeAg-positive groups, and 63.0% and 55.5% in HBeAg-negative groups. Moreover, there was no significant difference in the prevalence of significant liver damage between patients aged < 30 years and those aged ≥ 30 years, in both HBeAg-positive (≥ G2 or ≥ S2: 63.8% vs. 75.8%, p = 0.276) and HBeAg-negative (≥ G2 or ≥ S2: 65.9% vs. 72.5%, p = 0.504) groups, among patients with persistently normal ALT levels. CONCLUSIONS: A considerable proportion of CHB patients with persistently normal ALT, including those below the age of 30 years, exhibited significant histological damage. This highlights the importance of initiating early antiviral therapy for HBV-infected individuals, even in the absence of elevated ALT levels.
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Hepatite B Crônica , Humanos , Hepatite B Crônica/tratamento farmacológico , Alanina Transaminase , Antígenos E da Hepatite B , Estudos Retrospectivos , Fibrose , Cirrose Hepática/tratamento farmacológico , Antivirais/uso terapêutico , Inflamação/tratamento farmacológico , Vírus da Hepatite B/genética , DNA ViralRESUMO
Background/Aims: : Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB). However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB. Methods: : We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes. Results: : A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (-0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15. Conclusions: : BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB.
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Carcinoma Hepatocelular , Guanina/análogos & derivados , Hepatite B Crônica , Neoplasias Hepáticas , Organofosfonatos , Humanos , Tenofovir/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Antivirais/uso terapêutico , Adenina , Neoplasias Hepáticas/tratamento farmacológico , AlaninaRESUMO
INTRODUCTION: Recent studies have found that lipid levels in patients with chronic hepatitis B (CHB) may change during antiviral therapy. OBJECTIVE: To assess the effects of first-line nucleot(s)ide analogues (NAs) on lipid profiles in patients with CHB using network meta-analysis. METHODS: Seven electronic databases (PubMed, Embase, Cochrane Library, and four Chinese databases) were searched for cohort studies on the effect of NA on lipids in patients with CHB up to August 1, 2023. The changes of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were taken as outcomes. The mean difference (MD) of continuous variables and 95% confidence intervals (CI) were calculated using RevMan 5.4 and Stata 16.0 software, and network meta-analysis was based on a frequentist framework. RESULTS: A total of 4194 patients were included in the study, including patients with CHB treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), as well as patients not receiving antiviral therapy [patients with inactive CHB who were not receiving antiviral therapy (referred as inactive CHB patients) and non-HBV-infected patients]. TDF reduced TC levels compared to the non-antiviral group (TDF vs. inactive CHB patients: MD = - 17.27, 95% CI (- 30.03, - 4.47); TDF vs. non-HBV-infected individuals: MD = - 17.10, 95% CI (- 20.13, - 14.07)). TC changes in the TAF and ETV groups were not statistically different from the non-antiviral group (TAF vs. inactive CHB patients: MD = - 2.69, 95% CI (- 14.42, 9.04); TAF vs. non-HBV-infected individuals: MD = - 2.52, 95% CI (- 8.47, 3.43); ETV vs. inactive CHB patients: MD = - 4.24, 95% CI (- 17.12, 8.64); ETV vs. non-HBV-infected individuals: MD = - 4.07, 95% CI (- 9.90, 1.75)). The ranking of the effects for lowering TC is as follows: CHB patients treated with nucleotide analogues [with varying efficacy: TDF (SUCRA = 99.9) > ETV (SUCRA = 59.3) > TAF (SUCRA = 43.6)] > inactive CHB patients (SUCRA = 27.3) > non-HBV-infected individuals (SUCRA = 19.9). As for secondary outcomes, among the three antiviral drugs, TDF had the most significant effect on lowering TG, LDL-C, and HDL-C, but none of the three drugs was statistically different from the non-antiviral group. Subgroup analysis showed that the lipid-lowering effect of TDF was more pronounced in the elderly (≥ 50 years). CONCLUSION: TDF was effective in lipid reduction, particularly pronounced in the older population. TAF and ETV had a neutral effect to TC, TG, LDL-C, and HDL-C. Despite a relative increase in lipids observed in patients transitioning from TDF to TAF or ETV, these changes remained within acceptable limits.
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Antivirais , Hepatite B Crônica , Humanos , Antivirais/uso terapêutico , LDL-Colesterol , Hepatite B Crônica/tratamento farmacológico , Metanálise em Rede , Tenofovir/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the effects of Zhenggan Huayu decoction (, ZGHY) combined with entecavir (ETV) on the gut microbiota in patients with chronic hepatitis B (CHB) fibrosis. METHODS: A total of 59 CHB-related fibrosis patients were enrolled and treated with ZGHY combined with ETV (ZGHY + ETV) and ETV alone. Fecal samples were collected from patients at weeks 0, 12, and 24 after treatment and gut microbiota were analyzed by 16S rRNA gene sequencing. RESULTS: Compared to the ETV group, microbiota diversity in the ZGHY + ETV group was increased after 24 weeks. Some potentially pathogenic bacteria, including spp., spp., and spp. were reduced in the ZGHY + ETV group, while spp., spp., and several other beneficial bacteria were increased. CONCLUSION: Decreases in pathogenic bacteria and increases in probiotics were not always observed in the Traditional Chinese Medicine (TCM) group (e.g., was abundant). As an adjuvant TCM formulation for ETV, ZGHY had a positive role in the treatment of CHB patients.
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Microbioma Gastrointestinal , Hepatite B Crônica , Humanos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Antivirais/uso terapêutico , RNA Ribossômico 16S , Cirrose Hepática/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). METHODS: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. RESULTS: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65-0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61-0.68; untreated models: 0.51-0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. CONCLUSION: The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Antivirais/uso terapêutico , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Vírus da Hepatite BAssuntos
Hepatite B Crônica , Humanos , Hepatite B Crônica/patologia , Fígado/patologia , Prognóstico , BiópsiaRESUMO
Objectives: An estimated 887 000 deaths were due to chronic hepatitis B (CHB) related complications in 2015 worldwide. Most of these deaths were related to decompensated liver cirrhosis and hepatocellular carcinoma (HCC). Oman is a country with an intermediate prevalence of CHB. The Hepatitis B vaccine was introduced in Oman in 1990, with a vaccine coverage rate of > 95% reported in 2005. Despite the association between CHB and liver cirrhosis and HCC, no available data from Oman demonstrates CHB-related liver cirrhosis. We sought to estimate the prevalence of CHB among patients with liver cirrhosis from Oman. Methods: We conducted a retrospective chart review of patients diagnosed with liver cirrhosis at Sultan Qaboos University Hospital and Armed Forces Hospital between January 2006 and April 2013. All pediatric and adult patients with liver cirrhosis were included. We collected demographic data and liver cirrhosis investigations. Results: A total of 419 patients were included. Two-thirds of the patients were males. The median age was 59 years. Omani patients represented the majority (97.1%) of patients with cirrhosis. Diabetes mellitus was present in almost half of the patients, and 22.2% indicated alcohol consumption. Evidence of previous or current hepatitis B virus (HBV) infection was found in about half of the cohort (51.3%). Only 3.3% of CHB patients were positive for hepatitis B e-Antigen. HBV DNA was detected in 47 patients (21.9%), of which 20 patients had a high viral load > 2000 IU/ml. More than a third (36.7%) had positive hepatitis B surface antibody (anti-HBs), indicating immunity to HBV, and 27.1% was due to previous HBV infection, 5.2% was immune due to vaccination, and 3.7% had positive anti-HBs and unknown anti-HBc status. Negative anti-HBs was found in 34.1% of the cohort and 29.9% had unknown immunity status. HBV coinfection with HCV was found in 24.7% of HBV patients with cirrhosis. Conclusions: Serological markers of CHB are common among liver cirrhosis patients in Oman. CHB related cirrhosis was more common in old age males than females (70.7% vs. 29.3%, respectively; p < 0.010). Evidence of past or present HBV infection was found in > 50% of the patients.
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This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.
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Hepatite B Crônica , Antivirais/efeitos adversos , China , DNA Viral , Genótipo , Guanina/análogos & derivados , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Humanos , Maleatos , Resultado do TratamentoRESUMO
Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mechanisms promoting hepatocarcinogenesis. The molecular profile of HBV-HCC is extensively and continuously under study, and it is the result of altered molecular pathways, which modify the microenvironment and lead to DNA damage. HBV produces the protein HBx, which has a central role in the oncogenetic process. Furthermore, the molecular profile of HBV-HCC was recently discerned from that of HDV-HCC, despite the obligatory dependence of HDV on HBV. Proper management of the underlying HBV-related liver disease is fundamental, including HCC surveillance, viral suppression, and application of adequate predictive models. When HBV-HCC occurs, liver function and HCC characteristics guide the physician among treatment strategies but always considering the viral etiology in the treatment choice.
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Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Hepatite B/complicações , Vírus da Hepatite B/genética , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/genética , Microambiente TumoralRESUMO
Changes in the prevalence of disease over time provide valuable information from a public health perspective. We used data from Korea Military Manpower Administration medical examinations for conscription between 2003 and 2019 (n = 5,355,941), which involved young men aged 19 years, to observe changes in liver disease over time at a population level. Trends in the prevalence of hepatitis B surface antigen (HBsAg), elevated alanine aminotransferase (ALT) levels, the fibrosis-4 (FIB-4) index, obesity, and hypertension were assessed. The prevalence of HBsAg steadily decreased from 3.19% for men born in 1984 to 0.18% for men born in 2000. Among HBsAg-negative subjects, the prevalence of elevated ALT levels increased from 13.15% for men born in 1986 to 16.48% for men born in 2000. The prevalence of obesity, hypertension and the proportion with high FIB-4 scores (≥ 1.45) also increased. This population-based nationwide analysis showed a decreasing trend of HBsAg and increasing trends of possible non-alcoholic fatty liver disease.
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Hepatite B Crônica , Hepatite B , Hipertensão , Hepatopatia Gordurosa não Alcoólica , Adulto , Alanina Transaminase , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade , PrevalênciaRESUMO
With the wide use of potent and safe nucloes(t-)ide analogues (NAs) treatment, patient-centered care is getting important. Intensive care for comorbidity has gain utmost importance in care of aging chronic hepatitis B (CHB) patients with life-long antiviral treatment. Linkage to care of patients with CHB is essential for the goal of hepatitis B virus (HBV) eradication. As long-term suppression of HBV DNA replication does not prevent hepatocellular carcinoma (HCC), prevention of HCC is another challenge for NAs treatment. There is a possibility of hepatocarcinogenesis in the immune-tolerant phase and risk of loss of patients during active monitoring seeking the time point for antiviral treatment initiation. Initiation of NAs treatment from the immune-tolerant phase would improve the linkage to care. However, universal recommendation is premature and evidence for cost-effectiveness needs to be accumulated. Early initiation of NAs in the evidence of significant disease progression, either HBV associated or comorbidity associated, would be a better strategy to reduce the risk of HCC in patients located in the gray zone.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Medicina de PrecisãoRESUMO
In the natural course of chronic hepatitis B, the immune tolerance phase is characterized by HBeAg positivity, very high levels of HBV DNA, and persistent normal alanine aminotransferase. The international guideline recommendation for patients in this phase is observation without antiviral treatment because of the low risk of disease progression and the lack of effective antiviral agents. However, recent retrospective studies have shown that progression to hepatic fibrosis and hepatocellular carcinoma may occur in patients who are in the immune tolerance phase. Despite the conceptual definition and clinical diagnostic criteria for this phase, it is difficult to accurately diagnose the true immune tolerance phase. Therefore, we should pay attention to the clinical evaluation and interpretation of the immune tolerance phase and understand the clinical situations in which antiviral treatments should be considered.
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Hepatite B Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Tolerância Imunológica , Cirrose Hepática/diagnóstico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
BACKGROUND: Tenofovir disoproxil fumarate (TDF, Viread®) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. METHODS: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. RESULTS: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was -5.13 ± 1.40 in the DA-2802 group and -4.97 ± 1.40 log10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. CONCLUSION: DA-2802 is considered an effective and safe treatment for patients with CHB. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02967939.
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Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Ácido Orótico/uso terapêutico , Tenofovir/uso terapêutico , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Resultado do TratamentoRESUMO
PURPOSE: Studies have found that both FibroScan (FS) and Gd-EOB-DTPA-enhanced T1 mapping magnetic resonance imaging (Gd-MRI) could assess liver fibrosis (LF) with high effectiveness. The aim of this study is to compare their accuracy in the quantitative evaluation of LF in patients with chronic hepatitis B (CHB), and to explore the diagnostic accuracy of their combination. METHODS: 160 patients with CHB were included in this study. FS and Gd-MRI were performed within 3 months before the pathological LF staging, which was classified according to the Scheuer-Ludwig scale. The liver stiffness measurement (LSM) was obtained by FS. T1 mapping images of the liver before and 20 min after enhancement were obtained by Look-Locker Gd-MRI. RESULTS: There were 45, 35, 31 and 49 patients with stage S1, S2, S3 and S4 LF, respectively. LSM increased and the reduction rate of T1 relaxation time of 20 min (rrT120min%) decreased with the severity of LF. The area under curve (AUC) of LSM, rrT120min% and LSM + rrT120min% for the diagnosis of ≥ S2 LF were 0.892, 0.811 and 0.900, respectively. The AUC for ≥ S3 LF was 0.883, 0.838 and 0.899, respectively. The AUC for S4 LF was 0.882, 0.894 and 0.928, respectively. CONCLUSION: The diagnostic accuracy of FS is better than that of Gd-MRI in the evaluation of ≥ S2 stage LF. The combination of these two methods significantly improved the diagnostic efficiency in the evaluation of S4 stage LF.
Assuntos
Hepatite B Crônica , Meios de Contraste , Gadolínio DTPA , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico por imagem , Hepatite B Crônica/patologia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
Introducción: En Cuba se produce la vacuna HeberNasvac® para el tratamiento de la hepatitis B crónica. Su relevancia radica en lograr resultados de control virológico sostenido en una mayor proporción de pacientes. Objetivo: Evaluar seguridad y efectividad de la vacuna terapéutica HeberNasvac® en el tratamiento de la hepatitis B crónica, en la provincia Camagüey en el periodo comprendido de enero de 2019 a diciembre de 2020. Métodos: Se realizó un estudio cuasi experimental de intervención terapéutica, en pacientes atendidos en la Consulta Provincial de hepatitis virales crónicas. El universo estuvo constituido por 24 pacientes adultos, con carga viral detectable al inicio del estudio. La fuente primaria de la investigación estuvo dada por la historia clínica. Resultados: En el primer ciclo fueron más frecuentes la cefalea y los estornudos; y en el segundo ciclo la fiebre y el malestar general. Al concluir el tratamiento la mayoría mostraron mejoría de resultados de las pruebas de función hepática. Antes del tratamiento el mayor número de pacientes presentó una carga viral detectable por encima de 250 copias/mL y después de haber recibido tratamiento varios de los casos resultaron carga no detectable. El tratamiento se consideró con mediana seguridad en el mayor número de pacientes y la efectividad fue alta. Conclusiones: Se presentaron más eventos adversos en el segundo ciclo del tratamiento. Las pruebas de función hepática mostraron mejoría al concluir tratamiento. La carga viral después del tratamiento presentó un descenso. El tratamiento mostró mediana seguridad y efectividad alta.
Introduction: Cuba produces the HeberNasvac® vaccine for the treatment of chronic hepatitis B. Its relevance lies in achieving sustained virological control results in a greater proportion of patients. Objective: To evaluate the safety and effectiveness of the therapeutic vaccine HeberNasvac® in the treatment of chronic hepatitis B, in the province of Camagüey in the period from January 2019 to December 2020. Methods: A quasi-experimental study of therapeutic intervention was carried out in patients treated at the Provincial Consultation of Chronic Viral Hepatitis. The universe consisted of 24 adult patients, with detectable viral load at the beginning of the study. The primary source of the investigation was given by the medical history. Results: In the first cycle, headache and sneezing were more prevalent; and in the second cycle, fever and general malaise were more prevalent. At the end of the treatment, the majority showed improvement in the results of liver function tests. Before treatment, the largest number of patients had a detectable viral load above 250 copies / mL and after receiving treatment, several of the cases resulted in an undetectable load. The treatment was considered to be of medium safety in the largest number of patients and the effectiveness was high. Conclusions: There were more adverse events in the second cycle of treatment. Liver function tests showed improvement at the end of treatment. The viral load after treatment showed a decrease. The treatment showed medium safety and high effectiveness.
RESUMO
RESUMEN Introducción: Las hepatitis virales son un problema de salud a nivel mundial, provocan elevada mortalidad y morbilidad. A pesar de los avances en la prevención, diagnóstico y tratamiento de la hepatitis B, esta enfermedad es todavía preocupación de las autoridades sanitarias. Objetivo: Realizar una actualización acerca del comportamiento y manejo actual de la infección por el virus de la hepatitis B. Métodos: Se realizó una revisión bibliográfica durante abril y mayo de 2021, se consultaron 211 artículos en idioma inglés y español en las bases de datos como SciELO, PubMed, Lilacs y Medigraphic, de ellos se utilizaron 30 citas. Se empleó la combinación de términos y operadores booleanos y métodos teóricos como: análisis-síntesis, inducción-deducción e histórico-lógico. Resultados: Se abordó el comportamiento de la infección causada por el virus de la hepatitis B, se hizo hincapié en su epidemiología, características morfológicas y funcionales que permiten su infectividad, evolución y manifestaciones clínicas, complicaciones, tratamiento y perspectivas actuales. Conclusiones: La historia natural de la infección es dinámica y las manifestaciones clínicas dependen de diversos factores. La infección por el virus de la hepatitis B puede causar complicaciones como: la cirrosis hepática y el carcinoma hepatocelular y su principal vía de transmisión es la parenteral. El diagnóstico se realiza a través de técnicas serológicas. Es imprescindible la atención diferenciada a los grupos con riesgo y, aunque se cuenta con una vacuna eficaz, aún existen casos y se han desarrollado tratamientos con resultados positivos.
ABSTRACT Introduction: Viral hepatitis is a global health problem, causing high mortality and morbidity. Despite advances in the prevention, diagnosis and treatment of hepatitis B, this disease is still a concern of health authorities. Objective: Toupdate on current behavior and management of hepatitis B virus infection. Methods: A bibliographic review was carried out during April and May 2021, consulting 211 articles in English and Spanish from databases such as SciELO, PubMed, Lilacs and Medigraphic, of which 30 citations were used. The combination of Boolean terms and operators and theoretical methods such as: analysis-synthesis, induction-deduction and historical-logical were used. Results: The behavior of the infection caused by the hepatitis B virus was addressed, emphasizing its epidemiology, morphological and functional characteristics that allow its infectivity, evolution and clinical manifestations, complications, treatment and current perspectives. Conclusions: The natural history of infection is dynamic, and clinical manifestations depend on various factors. Hepatitis B virus infection can cause complications such as liver cirrhosis and hepatocellular carcinoma, and its main route of transmission is parenterally. The diagnosis is made mainly through serological techniques. Differentiated care for groups at risk is essential and, although there is an effective vaccine, there are still cases and treatments have been developed with positive results.