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Chronic hepatitis B virus infection (CHB) remains a global health concern, with currently available antiviral therapies demonstrating limited effectiveness in preventing hepatocellular carcinoma (HCC) development. Two primary challenges in CHB treatment include the persistence of the minichromosome, covalently closed circular DNA (cccDNA) of the hepatitis B virus (HBV), and the failure of the host immune response to eliminate cccDNA. Recent findings indicate several host and HBV proteins involved in the epigenetic regulation of cccDNA, including HBV core protein (HBc) and HBV x protein (HBx). Both proteins might contribute to the stability of the cccDNA minichromosome and interact with viral and host proteins to support transcription. One potential avenue for CHB treatment involves the utilization of therapeutic vaccines. This paper explores HBV antigens suitable for epigenetic manipulation of cccDNA, elucidates their mechanisms of action, and evaluates their potential as key components of epigenetically-driven vaccines for CHB therapy. Molecular targeted agents with therapeutic vaccines offer a promising strategy for addressing CHB by targeting the virus and enhancing the host's immunological response. Despite challenges, the development of these vaccines provides new hope for CHB patients by emphasizing the need for HBV antigens that induce effective immune responses without causing T cell exhaustion.

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PURPOSE: There is an unmet clinical need for non-invasive imaging biomarkers that could replace liver biopsy in the management of patients with autoimmune hepatitis (AIH). In this study, we sought to evaluate the diagnostic accuracy of a simple uncorrected, non-contrast T1 mapping for detecting fibrosis and inflammation in AIH patients using histopathology as a reference standard. MATERIAL AND METHODS: Over 3 years, 33 patients with AIH were prospectively studied using a multiparametric liver MRI protocol which included T1 mapping. Biopsies were performed up to 3 months before imaging, and a standardized histopathological score for fibrosis (F0-F4) and inflammatory activity (PPA0-4) was used as a reference. Statistical analysis included independent t test, Mann-Whitney U-test, and ROC (receiver operating characteristic) analysis. RESULTS: T1 mapping values were significantly higher in patients with advanced fibrosis (F0-2 vs. F3-4; p < 0.015), significant fibrosis (F0-1 vs. F2-4; p < 0.005), and significant inflammatory activity (PPA 0-1 vs. PPA 2-4 p = 0.048). Moreover, the technique demonstrated a good diagnostic performance in detecting significant (AUC 0.856) and advanced fibrosis (AUC 0.835), as well as significant inflammatory activity (AUC 0.763). CONCLUSION: A rapid, simple, uncorrected, non-contrast T1 mapping sequence showed satisfactory diagnostic performance in comparison with histopathology for detecting significant tissue inflammation and fibrosis in AIH patients, being a potential non-invasive imaging biomarker for monitoring disease activity in such individuals.

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This study aims to evaluate the impact of liver fibrosis stages of chronic infection with hepatitis C virus (HCV) on the in vivo activity of organic cation transporters (hepatic OCT1 and renal OCT2) using metformin (MET) as a probe drug. Participants allocated in Group 1 (n = 15, mild to moderate liver fibrosis) or 2 (n = 13, advanced liver fibrosis and cirrhosis) received a single MET 50 mg oral dose before direct-acting antiviral (DAA) drug treatment (Phase 1) and 30 days after achieving sustained virologic response (Phase 2). OCT1/2 activity (MET AUC0-24) was found to be reduced by 25% when comparing the two groups in Phase 2 (ratio 0.75 (0.61-0.93), p < 0.05) but not in Phase 1 (ratio 0.81 (0.66-0.98), p > 0.05). When Phases 1 and 2 were compared, no changes were detected in both Groups 1 (ratio 1.10 (0.97-1.24), p > 0.05) and 2 (ratio 1.03 (0.94-1.12), p > 0.05). So, this study shows a reduction of approximately 25% in the in vivo activity of OCT1/2 in participants with advanced liver fibrosis and cirrhosis after achieving sustained virologic response and highlights that OCT1/2 in vivo activity depends on the liver fibrosis stage of chronic HCV infection.

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Objective: The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after directacting antivirals (DAA) therapy. Materials and methods: Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/ type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control. Results: The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range [IQR] 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years. Conclusion: Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.

Assuntos

Antivirais , Glicemia , Hemoglobinas Glicadas , Hepatite C Crônica , Resposta Viral Sustentada , Humanos , Feminino , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/sangue , Masculino , Pessoa de Meia-Idade , Hemoglobinas Glicadas/análise , Glicemia/análise , Glicemia/efeitos dos fármacos , Idoso , Estudos Prospectivos , Resultado do Tratamento , Hepacivirus/genética , Hepacivirus/efeitos dos fármacos , Brasil , Adulto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue

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INTRODUCTION AND OBJECTIVES: Chronic hepatitis B (CHB) may progress to more serious liver diseases and it is often accompanied by non-alcoholic fatty liver disease (NAFLD). NAFLD and CHB share risk factors for liver fibrosis and cirrhosis, but the influence of NAFLD on fibrosis progression is controversial. This retrospective study evaluated the prevalence of NAFLD in patients with CHB and investigated associations between NAFLD and liver fibrosis in a large multi-center cohort of hepatitis B patients submitted to liver biopsy. PATIENTS AND METHODS: Treatment-naïve patients with CHB who underwent liver biopsy were analyzed. Propensity score matching (PSM) was performed to adjust the confounders between patients with and without NAFLD. RESULTS: A total of 1496 CHB patients were included. Two hundred and ninety (19.4%) patients were diagnosed with NAFLD by liver biopsy. The proportions of significant liver fibrosis (52.8% vs. 63.9%, P<0.001), advanced liver fibrosis (27.2% vs. 36.5%, P=0.003), and cirrhosis (13.4% vs. 19.7%, P=0.013) was considerably lower in CHB patients with NAFLD compared to those without NAFLD. 273 patients were included in each group after PSM adjusted for age, sex, hepatitis B envelope antigen status, and hepatitis B virus DNA. Liver fibrosis remained less severe in CHB patients with NAFLD than those without NAFLD (P<0.05) after PSM. The presence of NAFLD was considered an independent negative factor of significant liver fibrosis (odds ratio (OR) 0.692, P=0.013) and advanced liver fibrosis (OR 0.533, P = 0.002) in CHB patients. CONCLUSIONS: NAFLD is not uncommon in CHB patients with the prevalence of 19.4%. The presence of NAFLD is associated with less severe liver fibrosis in CHB patients. OF THE STUDY/TRIAL: NCT03097952.

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Hepatite B Crônica , Hepatite B , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatite B/complicações , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos Retrospectivos

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INTRODUCTION AND OBJECTIVES: Seroclearance of hepatitis B e antigen (HBeAg) is an important treatment goal for patients with chronic hepatitis B (CHB). This study developed a nomogram for predicting HBeAg seroclearance in CHB patients treated with nucleos(t)ide analogues (NAs). PATIENTS AND METHODS: Five hundred and sixty-nine CHB patients treated with NAs from two institutions between July 2016 to November 2021 were retrospectively included. One institution served as the training set (n = 374) and the other as the external validation set (n = 195). A predictive nomogram was established based on cox regression analysis. RESULTS: The overall HBeAg seroclearance rates were 27.3 and 21.5 % after the median follow-up of 100.2 weeks and 65.1 weeks in the training set and validation set, respectively. In the training set, baseline aspartate aminotransferase, gamma-glutamyl transpeptidase, HBeAg, and hepatitis B core antibody levels were independently associated with HBeAg seroclearance and were used to establish the HBEAg SeroClearance (ESC)-nomogram. The calibration curve revealed that the ESC-nomogram had a good agreement with actual observation. The ESC-nomogram showed relatively high accuracy for predicting 48 weeks, 96 weeks, and 144 weeks of HBeAg seroclearance in the training set (AUCs: 0.782, 0.734 and 0.671) and validation set (AUCs: 0.699, 0.718 and 0.689). The patients with high ESC-nomogram scores (≥ 79.51) had significantly higher cumulative incidence of HBeAg seroclearance and seroconversion than patients with low scores (< 79.51) in both sets (P < 0.01). CONCLUSIONS: The novel ESC-nomogram showed good performance for predicting antiviral efficacy in HBeAg-positive CHB patients with NAs treatment.

Assuntos

Hepatite B Crônica , Humanos , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/complicações , Antígenos E da Hepatite B , Antivirais/uso terapêutico , Estudos Retrospectivos , Nomogramas , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Resultado do Tratamento , DNA Viral

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ABSTRACT Objective: The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after direct-acting antivirals (DAA) therapy. Materials and methods: Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control. Results: The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range [IQR] 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3­%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years. Conclusion: Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.

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ABSTRACT Despite good hepatitis B virus (HBV) inhibition by nucleoside analogs (NAs), cases of hepatocellular carcinoma (HCC) still occur. This study proposed a non-invasive predictive model to assess HCC risk in patients with chronic hepatitis B (CHB) receiving NAs treatment. Data were obtained from a hospital-based retrospective cohort registered on the Platform of Medical Data Science Academy of Chongqing Medical University, from 2013 to 2019. A total of 501 patients under NAs treatment had their FIB-4 index updated semiannually by recalculation based on laboratory values. Patients were divided into three groups based on FIB-4 index values: < 1.45, 1.45-3.25, and ≥ 3.25. Subsequently, HCC incidence was reassessed every six months using Kaplan-Meier curves based on the updated FIB-4 index. The median follow-up time of CHB patients after receiving NAs treatment was 2.5 years. HCC incidences with FIB-4 index < 1.45, 1.45-3.25, and ≥ 3.25 were 1.18%, 1.32%, and 9.09%, respectively. Dynamic assessment showed that the percentage of patients with FIB-4 index < 1.45 significantly increased semiannually (P < 0.001), and of patients with FIB-4 index ≥ 3.25 significantly decreased (P < 0.001). HCC incidence was the highest among patients with FIB-4 index ≥ 3.25. The FIB-4 index effectively predicted HCC incidence, and its dynamic assessment could be used for regular surveillance to implement early intervention and reduce HCC risk.

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In the management of the growing population of hepatitis C virus-infected patients, a significant clinical challenge exists in determining the most effective methods for assessing liver impairment. The prognosis and treatment of chronic hepatitis C depend, in part, on the evaluation of histological activity, specifically cell necrosis and inflammation, and the extent of liver fibrosis. These parameters are traditionally obtained through a liver biopsy. However, liver biopsy presents both invasiveness and potential sampling errors, primarily due to inadequate biopsy size. To circumvent these issues, several non-invasive markers have been proposed as alternatives for diagnosing liver damage. Different imaging techniques and blood parameters as single markers or combined with clinical information are included. This Editorial discusses the identification of a set of six distinctive lipid metabolites in every fibrosis grade that appear to show a pronounced propensity to create clusters among patients who share the same fibrosis grade, thereby demonstrating enhanced efficacy in distinguishing between the different grades.

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BACKGROUND: Chronic Hepatitis C (CHC) affects 71 million people globally and leads to liver issues such as fibrosis, cirrhosis, cancer, and death. A better understanding and prognosis of liver involvement are vital to reduce morbidity and mortality. The accurate identification of the fibrosis stage is crucial for making treatment decisions and predicting outcomes. Tests used to grade fibrosis include histological analysis and imaging but have limitations. Blood markers such as molecular biomarkers can offer valuable insights into fibrosis. AIM: To identify potential biomarkers that might stratify these lesions and add information about the molecular mechanisms involved in the disease. METHODS: Plasma samples were collected from 46 patients with hepatitis C and classified into fibrosis grades F1 (n = 13), F2 (n = 12), F3 (n = 6), and F4 (n = 15). To ensure that the identified biomarkers were exclusive to liver lesions (CHC fibrosis), healthy volunteer participants (n = 50) were also included. An untargeted metabolomic technique was used to analyze the plasma metabolites using mass spectrometry and database verification. Statistical analyses were performed to identify differential biomarkers among groups. RESULTS: Six differential metabolites were identified in each grade of fibrosis. This six-metabolite profile was able to establish a clustering tendency in patients with the same grade of fibrosis; thus, they showed greater efficiency in discriminating grades. CONCLUSION: This study suggests that some of the observed biomarkers, once validated, have the potential to be applied as prognostic biomarkers. Furthermore, it suggests that liquid biopsy analyses of plasma metabolites are a good source of molecular biomarkers capable of stratifying patients with CHC according to fibrosis grade.