Annals of hepatology最新文献

{"title":"Alcohol-related liver disease: A global perspective","authors":"","doi":"10.1016/j.aohep.2024.101499","DOIUrl":"10.1016/j.aohep.2024.101499","url":null,"abstract":"<div><p>Alcohol-associated liver disease (ALD) represents one of the deadliest yet preventable consequences of excessive alcohol use. It represents 5.1 % of the global burden of disease, mainly involving the productive-age population (15-44 years) and leading to an increased mortality risk from traffic road injuries, suicide, violence, cardiovascular disease, neoplasms, and liver disease, among others, accounting for 5.3 % of global deaths. Daily alcohol consumption, binge drinking (BD), and heavy episodic drinking (HED) are the patterns associated with a higher risk of developing ALD. The escalating global burden of ALD, even exceeding what was predicted, is the result of a complex interaction between the lack of public policies that regulate alcohol consumption, low awareness of the scope of the disease, late referral to specialists, underuse of available medications, insufficient funds allocated to ALD research, and non-predictable events such as the COVID-19 pandemic, where increases of up to 477 % in online alcohol sales were registered in the United States. Early diagnosis, referral, and treatment are pivotal to achieving the therapeutic goal in patients with alcohol use disorder (AUD) and ALD, where complete alcohol abstinence and prevention of alcohol relapse are expected to enhance overall survival. This can be achieved through a combination of cognitive behavioral, motivational enhancement and pharmacological therapy. Furthermore, the appropriate use of available pharmacological therapy and implementation of public policies that comprehensively address this disease will make a real difference.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S166526812400293X/pdfft?md5=b887279b30a598b1047389f31be78895&pid=1-s2.0-S166526812400293X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140616839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatitis B virus X protein differentially regulates the angiogenesis of Hepatocellular Carcinoma through p53-VEGF axis according to glucose levels","authors":"","doi":"10.1016/j.aohep.2024.101543","DOIUrl":"10.1016/j.aohep.2024.101543","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>Blood glucose fluctuates severely in the diabetes (DM) and tumor microenvironment. Our previous works have found Hepatitis B virus X protein (HBx) differentially regulated metastasis and apoptosis of hepatoma cells depending on glucose concentration. We here aimed to explore whether HBx played dual roles in the angiogenesis of hepatocellular carcinoma varying on different glucose levels.</p></div><div><h3>Materials and Methods</h3><p>We collected conditioned medium from HBx-overexpressing cells cultured with two solubilities of glucose, and then applied to EA.hy926 cells. Alternatively, a co-culture cell system was established with hepatoma cells and EA.hy926 cells. We analyzed the angiogenesis of EA.hy926 cells with CCK8, wound-healing, transwell-migartion and tube formation experiment. ELISA was conducted to detect the secretion levels of angiogenesis-related factors. siRNAs were used to detect the P53-VEGF axis.</p></div><div><h3>Results</h3><p>HBx expressed in hepatoma cells suppressed VEGF secretion, and subsequently inhibited the proliferation, migration and tube formation of EA.hy926 cells in a high glucose condition, while attenuating these in the lower glucose condition. Furthermore, the p53-VEGF axis was required for the dual role of HBx in angiogenesis. Additionally, HBx mainly regulated the nuclear p53.</p></div><div><h3>Conclusions</h3><p>These data suggest that the dual roles of HBx confer hepatoma cells to remain in a glucose-rich environment and escape from the glucose-low milieu through tumor vessels, promoting liver tumor progression overall. We exclusively revealed the dual role of HBx on the angiogenesis of liver tumors, which may shed new light on the mechanism and management strategy of HBV- and DM-related hepatocellular carcinoma.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268124003375/pdfft?md5=e5108f85d7a786e2689d8e7855c5a7eb&pid=1-s2.0-S1665268124003375-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between sarcopenia and metabolic dysfunction-associated steatotic liver disease (MASLD): A systematic review and meta-analysis","authors":"","doi":"10.1016/j.aohep.2024.101544","DOIUrl":"10.1016/j.aohep.2024.101544","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) formerly known as Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease. Identifying MASLD risk factors could help early intervention and reduce the burden of the disease. Previous studies investigated the association between sarcopenia and NAFLD. Several trials were published after the last meta-analysis with indecisive results. This is an updated meta-analysis which aims to assess the association between sarcopenia, MASLD, and MASLD-related fibrosis.</p></div><div><h3>Materials and Methods</h3><p>Relevant trials published on PubMed, Web of Science, Scopus, and Cochrane Library databases until October 2022 were included. We included studies in which skeletal mass index (SMI) or sarcopenia was compared between patients with and without NAFLD now MASLD. Also, studies comparing fibrosis between MASLD patients with and without sarcopenia were included. Data were pooled as odds ratios (ORs) and 95 % confidence intervals (CIs) using Review Manager Software.</p></div><div><h3>Results</h3><p>A total of 25 studies were included. The incidence of sarcopenia was significantly higher in MASLD than controls (OR, 1.25; 95 % CI, 1.08-1.44; P = 0.003). SMI odds showed no significant difference between MASLD patients and controls (OR, 1.02; 95 % CI, 0.91-1.15; P = 0.7). MASLD patients with sarcopenia had higher odds of fibrosis than MASLD patients without sarcopenia (OR, 1.49; 95 % CI, 1.03-2.14; P = 0.03).</p></div><div><h3>Conclusions</h3><p>Sarcopenia increased MASLD's probability and was associated with a higher probability of liver fibrosis in MASLD patients. However, SMI had no predictive value of MASLD occurrence.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268124003387/pdfft?md5=840ab2b9fd6c63babd4fff6b502d77d2&pid=1-s2.0-S1665268124003387-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helicobacter pylori cagA/vacAs1-m1 strain is associated with high risk of fibrosis in metabolic-dysfunction-associated steatotic liver disease","authors":"","doi":"10.1016/j.aohep.2024.101541","DOIUrl":"10.1016/j.aohep.2024.101541","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>Recent studies have suggested an association between <em>H. pylori</em> and metabolic dysfunction associated steatotic liver disease (MASLD). We aim to evaluate the association of <em>H. pylori</em> virulence genes with non-invasive markers of liver injury and fibrosis in MASLD subjects.</p></div><div><h3>Patients and Methods</h3><p>A total of 362 dyspeptic patients who underwent gastroscopy were selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), gastric biopsies, and <em>H. pylori</em> virulence genes (cagA, vacA) were evaluated.</p></div><div><h3>Results</h3><p>A cohort comprised of 61 % women and 39 % men with a median age of 52 (40–60) years. MASLD was observed in 42 %, and <em>H. pylori</em>-positive in 45 %. No differences were observed regarding <em>H. pylori</em> status at co-morbid metabolic conditions. In MASLD cohort, <em>H. pylori</em>-positive was associated with higher AST, ALT, FIB-4 and LSM. Indeed, carriers of cagA/vacA-s1/m1-positive allelic combination were associated with higher AST, ALT, FIB-4 and LSM but not cagA/vacA-s1/m1-negative. The OR for high-risk of significant/advanced- fibrosis by VCTE (≥8 kPa) with <em>H. pylori</em>-positive was 2.56 (95 % CI, 1.2–5.75) and for cagA/vacA-s1/-m1-positive allelic carriers was 4.01 (95 % CI, 1.38–11.56), but non-significant association in cagA/vacA-s1/-m1-negative. After adjusting for age, gender, diabetes, BMI and hypertension the OR for VCTE ≥8 kPa with <em>H. pylori</em>-positive was 2.43 (95 % CI, 1.88–12.44), and cagA/vacA-s1/m1-positive allelic carriers was 4.06 (95 % CI, 1.22–14.49).</p></div><div><h3>Conclusions</h3><p>In our cohort of functional dyspepsia (FD) patients with MASLD, <em>H. pylori</em> was associated with non-invasive markers of liver injury and fibrosis. Carriers of cagA/vacA-s1/m1-positive allelic combination showed an independent risk of significant/advanced fibrosis by VCTE.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268124003351/pdfft?md5=04c9bcbd2115e0c3d900a09fc780b896&pid=1-s2.0-S1665268124003351-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic factors influencing outcomes in hepatocellular carcinoma patients undergoing selective internal radiation therapy","authors":"","doi":"10.1016/j.aohep.2024.101539","DOIUrl":"10.1016/j.aohep.2024.101539","url":null,"abstract":"<div><p>Selective internal radiation therapy (SIRT) has emerged as a viable endovascular treatment strategy for hepatocellular carcinoma (HCC). According to the Barcelona Clinic Liver Cancer (BCLC) classification, SIRT is currently recommended for early- and intermediate-stage HCC that is unsuitable for alternative locoregional therapies. Additionally, SIRT remains a recommended treatment for patients with advanced-stage HCC and portal vein thrombosis (PVT) without extrahepatic metastasis. Several studies have shown that SIRT is a versatile and promising treatment with a wide range of applications. Consequently, given its favourable characteristics in various scenarios, SIRT could be an encouraging treatment option for patients with HCC across different BCLC stages. Over the past decade, an increasing number of studies have focused on better understanding the prognostic factors associated with SIRT to identify patients who derive the most benefit from this treatment or to refine the optimal technical procedures of SIRT. Several variables can influence treatment decisions, with a growing emphasis on a personalised approach. This review, based on the literature, will focus on the prognostic factors associated with the effectiveness of radioembolization and related complications. By comprehensively analysing these factors, we aimed to provide a clearer understanding of how to optimise the use of SIRT in managing HCC patients, thereby enhancing outcomes across various clinical scenarios.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268124003338/pdfft?md5=69a179c75b056d162814acdfcaaddbc1&pid=1-s2.0-S1665268124003338-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of machine learning-based personalized predictive models for risk evaluation of hepatocellular carcinoma in hepatitis B virus-related cirrhosis patients with low levels of serum alpha-fetoprotein","authors":"","doi":"10.1016/j.aohep.2024.101540","DOIUrl":"10.1016/j.aohep.2024.101540","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>The increasing incidence of hepatocellular carcinoma (HCC) in China is an urgent issue, necessitating early diagnosis and treatment. This study aimed to develop personalized predictive models by combining machine learning (ML) technology with a demographic, medical history, and noninvasive biomarker data. These models can enhance the decision-making capabilities of physicians for HCC in hepatitis B virus (HBV)-related cirrhosis patients with low serum alpha-fetoprotein (AFP) levels.</p></div><div><h3>Patients and Methods</h3><p>A total of 6,980 patients treated between January 2012 and December 2018 were included. Pre-treatment laboratory tests and clinical data were obtained. The significant risk factors for HCC were identified, and the relative risk of each variable affecting its diagnosis was calculated using ML and univariate regression analysis. The data set was then randomly partitioned into validation (20 %) and training sets (80 %) to develop the ML models.</p></div><div><h3>Results</h3><p>Twelve independent risk factors for HCC were identified using Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random forest, and least absolute shrinkage and selection operation regression models. Multivariate analysis revealed that male sex, age &gt;60 years, alkaline phosphate &gt;150 U/L, AFP &gt;25 ng/mL, carcinoembryonic antigen &gt;5 ng/mL, and fibrinogen &gt;4 g/L were the risk factors, whereas hypertension, calcium &lt;2.25 mmol/L, potassium ≤3.5 mmol/L, direct bilirubin &gt;6.8 μmol/L, hemoglobin &lt;110 g/L, and glutamic-pyruvic transaminase &gt;40 U/L were the protective factors in HCC patients. Based on these factors, a nomogram was constructed, showing an area under the curve (AUC) of 0.746 (sensitivity = 0.710, specificity=0.646), which was significantly higher than AFP AUC of 0.658 (sensitivity = 0.462, specificity=0.766). Compared with several ML algorithms, the XGBoost model had an AUC of 0.832 (sensitivity = 0.745, specificity=0.766) and an independent validation AUC of 0.829 (sensitivity = 0.766, specificity = 0.737), making it the top-performing model in both sets. The external validation results have proven the accuracy of the XGBoost model.</p></div><div><h3>Conclusions</h3><p>The proposed XGBoost demonstrated a promising ability for individualized prediction of HCC in HBV-related cirrhosis patients with low-level AFP.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S166526812400334X/pdfft?md5=82d35e2d0a0e066c7691927642b98ea4&pid=1-s2.0-S166526812400334X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic instabilities in hepatocellular carcinoma: biomarkers and application in immunotherapies","authors":"","doi":"10.1016/j.aohep.2024.101546","DOIUrl":"10.1016/j.aohep.2024.101546","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is one of the deadliest cancers. For patients with advanced HCC, liver function decompensation often occurs, which leads to poor tolerance to chemotherapies and other aggressive treatments. Therefore, it remains critical to develop effective therapeutic strategies for HCC. Etiological factors for HCC are complex and multifaceted, including hepatitis virus infection, alcohol, drug abuse, chronic metabolic abnormalities, and others. Thus, HCC has been categorized as a “genomically unstable” cancer due to the typical manifestation of chromosome breakage and aneuploidy, and oxidative DNA damage. In recent years, immunotherapy has provided a new option for cancer treatments, and the degree of genomic instability positively correlates with immunotherapy efficacies. This article reviews the endogenous and exogenous causes that affect the genomic stability of liver cells; it also updates the current biomarkers and their detection methods for genomic instabilities and relevant applications in cancer immunotherapies. Including genomic instability biomarkers in consideration of cancer treatment options shall increase the patients’ well-being.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268124003405/pdfft?md5=743982fdcb7f7d0d5fb3cc57442ec238&pid=1-s2.0-S1665268124003405-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircROBO1 knockdown improves the radiosensitivity of hepatocellular carcinoma by regulating RAD21.","authors":"Kai Yang, Yanpeng Ding, Jun Han, Rui He","doi":"10.1016/j.aohep.2024.101536","DOIUrl":"10.1016/j.aohep.2024.101536","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Radioresistance is a common problem in the treatment of many cancers, including hepatocellular carcinoma (HCC). Previous studies have shown that circROBO1 is highly expressed in HCC tissues and acts as a cancer promoter to accelerate the malignant progression of HCC. However, the role and mechanism of circROBO1 in HCC radioresistance remain unclear.</p><p><strong>Materials and methods: </strong>CircROBO1, microRNA (miR)-136-5p and RAD21 expression levels were analyzed by quantitative real-time PCR. Cell function and radioresistance were evaluated by colony formation assay, cell counting kit 8 assay, EdU assay and flow cytometry. Protein expression was determined using western blot analysis. RNA interaction was analyzed by dual-luciferase reporter assay and RNA pull-down assay. In vivo experiments were performed by constructing mice xenograft models.</p><p><strong>Results: </strong>CircROBO1 was highly expressed in HCC, and its knockdown inhibited HCC cell proliferation and promoted apoptosis to enhance cell radiosensitivity. On the mechanism, circROBO1 could serve as miR-136-5p sponge to positively regulate RAD21. MiR-136-5p inhibitor or RAD21 overexpression reversed the regulation of circROBO1 knockdown on the radiosensitivity of HCC cells. Also, circROBO1 interference improved the radiosensitivity of HCC tumors in vivo.</p><p><strong>Conclusions: </strong>CircROBO1 might be a promising target for treating HCC radioresistance.</p>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-6/STAT3 signaling pathway induces prostate apoptosis response protein-4(PAR-4) to stimulate malignant behaviors of hepatocellular carcinoma cells","authors":"","doi":"10.1016/j.aohep.2024.101538","DOIUrl":"10.1016/j.aohep.2024.101538","url":null,"abstract":"<div><h3>Introduction and Objectives</h3><p>Prostate apoptosis response protein-4 (PAR-4) is considered a tumor suppressor. However, the role of PAR-4 in hepatocellular carcinoma (HCC) has rarely been reported. The study explores the role of PAR-4 in the malignant behaviors of HCC cells.</p></div><div><h3>Materials and Methods</h3><p>TCGA database was applied to analyze the expression of PAR-4 in HCC. Evaluated PAR-4 relationship with clinical parameters and prognosis by tissue microarray; expression of STAT3, p-STAT3, Src and Ras was detected by Western blotting or laser confocal microscopy. Cell scratch and flow cytometry assays were used to observe IL-6 regulation of the malignant behaviors of HCC cells. The tumorigenic potential of HCC cells in vivo was evaluated in a nude mouse tumor model.</p></div><div><h3>Results</h3><p>Analysis indicated that the expression of PAR-4 in HCC tissues was significantly higher than that in normal liver tissues; and PAR-4 interacted with STAT3. KEGG analysis showed that PAR-4 plays a role in the Janus kinase (JAK)/STAT signaling pathway. The positive expression rate of PAR-4 in HCC tissues was significantly higher than that in adjacent tissues. Positive correlation between IL-6 and PAR-4 expression in the HCC tissues. Exogenous IL-6 significantly promoted the proliferation and migration of HCC cells and up-regulated the expression of PAR-4 and p-STAT3 in HCC cells. Interference of the expression of PAR-4 could reduce the malignant behaviors of HCC cells and inhibit tumorigenesis in a nude mouse tumor model.</p></div><div><h3>Conclusions</h3><p>PAR-4 expression is positively correlated with HCC; PAR-4 promotes malignant behavior of HCC cells mediated by the IL-6/STAT3 signaling pathway.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268124003326/pdfft?md5=37afd3d4a443acbf80cb11fd14ebfd92&pid=1-s2.0-S1665268124003326-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cccDNA epigenetic regulator as target for therapeutical vaccine development against hepatitis B","authors":"","doi":"10.1016/j.aohep.2024.101533","DOIUrl":"10.1016/j.aohep.2024.101533","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":7979,"journal":{"name":"Annals of hepatology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1665268124003272/pdfft?md5=25de653ac295e8ff5358063ede9c3136&pid=1-s2.0-S1665268124003272-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}