Dorothy Liu, Mark M Youssef, Josephine A Grace, Marie Sinclair
{"title":"Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care","authors":"Dorothy Liu, Mark M Youssef, Josephine A Grace, Marie Sinclair","doi":"10.4254/wjh.v16.i4.650","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.650","url":null,"abstract":"BACKGROUND\u0000 De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients. Cumulative immunosuppression has been shown to contribute to post-transplant malignancy (PTM) risk. There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs, independent of the net effect of immunosuppression. Calcineurin inhibitors such as tacrolimus may promote tumourigenesis, whereas mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, may limit tumour progression. Liver transplantation (LT) is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable, which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort. However, there is limited clinical data on this subject in both LT and other solid organ transplant recipients.\u0000 AIM\u0000 To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.\u0000 METHODS\u0000 A literature search was conducted using MEDLINE and Embase databases using the key terms “solid organ transplantation”, “tacrolimus”, “mycophenolic acid”, and “carcinogenicity”, in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022. Related terms, synonyms and explosion of MeSH terms, Boolean operators and truncations were also utilised in the search. Reference lists of retrieved articles were also reviewed to identify any additional articles. Excluding duplicates, abstracts from 1230 records were screened by a single reviewer, whereby 31 records were reviewed in detail. Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.\u0000 RESULTS\u0000 A total of 6 studies were included in this review. All studies were large population registries or cohort studies, which varied in transplant era, type of organ transplanted and immunosuppression protocol used. Overall, there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation. Furthermore, no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.\u0000 CONCLUSION\u0000 The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies, and its application in solid organ transplantation, is yet to be confirmed in clinical studies. Thus, the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao-Wei Tang, Wen-Sen Ren, Shu Huang, Kang Zou, Huan Xu, Xiao-Min Shi, Wei Zhang, Lei Shi, Mu-Han Lü
{"title":"Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis.","authors":"Xiao-Wei Tang, Wen-Sen Ren, Shu Huang, Kang Zou, Huan Xu, Xiao-Min Shi, Wei Zhang, Lei Shi, Mu-Han Lü","doi":"10.4254/wjh.v16.i4.625","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.625","url":null,"abstract":"<p><strong>Background: </strong>Liver cirrhosis patients admitted to intensive care unit (ICU) have a high mortality rate.</p><p><strong>Aim: </strong>To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis.</p><p><strong>Methods: </strong>We extracted demographic, etiological, vital sign, laboratory test, comorbidity, complication, treatment, and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and electronic ICU (eICU) collaborative research database (eICU-CRD). Predictor selection and model building were based on the MIMIC-IV dataset. The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors. The final predictors were included in the multivariate logistic regression model, which was used to construct a nomogram. Finally, we conducted external validation using the eICU-CRD. The area under the receiver operating characteristic curve (AUC), decision curve, and calibration curve were used to assess the efficacy of the models.</p><p><strong>Results: </strong>Risk factors, including the mean respiratory rate, mean systolic blood pressure, mean heart rate, white blood cells, international normalized ratio, total bilirubin, age, invasive ventilation, vasopressor use, maximum stage of acute kidney injury, and sequential organ failure assessment score, were included in the multivariate logistic regression. The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases, respectively. The calibration curve also confirmed the predictive ability of the model, while the decision curve confirmed its clinical value.</p><p><strong>Conclusion: </strong>The nomogram has high accuracy in predicting in-hospital mortality. Improving the included predictors may help improve the prognosis of patients.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11056901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy.","authors":"Shuai-Jun Ren, Jia-Ting Feng, Ting Xiang, Cai-Lian Liao, Yu-Ping Zhou, Rong-Rong Xuan","doi":"10.4254/wjh.v16.i4.601","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.601","url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy. Short-chain fatty acids (SCFAs), prominent metabolites of the gut microbiota, have significant connections with various pregnancy complications, and some SCFAs hold potential for treating such complications. However, the metabolic profile of SCFAs in patients with ICP remains unclear.</p><p><strong>Aim: </strong>To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.</p><p><strong>Methods: </strong>Maternal serum and cord blood samples were collected from both patients with ICP (ICP group) and normal pregnant women (NP group). Targeted metabolomics was used to assess the SCFA levels in these samples.</p><p><strong>Results: </strong>Significant differences in maternal SCFAs were observed between the ICP and NP groups. Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group, mirroring the pattern seen in maternal serum. Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs [r (Pearson) = 0.88, <i>P</i> = 7.93e-95]. In both maternal serum and cord blood, acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups (variable importance for the projection > 1). Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP, with caproic acid exhibiting the highest diagnostic efficacy (area under the curve = 0.97).</p><p><strong>Conclusion: </strong>Compared with the NP group, significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group, although they displayed distinct patterns of change. Furthermore, the SCFA levels in maternal serum and cord blood were significantly positively correlated. Notably, certain maternal serum SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11056904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guo Long, Peng Peng, Wei-Ting Peng, Jie Zhao, Qi-Quan Wan
{"title":"Klebsiella pneumoniae infections after liver transplantation: Drug resistance and distribution of pathogens, risk factors, and influence on outcomes","authors":"Guo Long, Peng Peng, Wei-Ting Peng, Jie Zhao, Qi-Quan Wan","doi":"10.4254/wjh.v16.i4.612","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.612","url":null,"abstract":"BACKGROUND\u0000 Liver transplantation (LT) is the only curative treatment for end-stage liver disease. However, LT recipients are susceptible to infection, which is the leading cause of early mortality after LT. Klebsiella pneumoniae infections (KPIs) in the bloodstream are common in LT recipients. We hypothesized that KPIs and carbapenem-resistant Klebsiella pneumoniae (CRKP) infections may affect the outcomes of LT recipients.\u0000 AIM\u0000 To assess KPI incidence, timing, distribution, drug resistance, and risk factors following LT and its association with outcomes.\u0000 METHODS\u0000 This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University, a tertiary hospital, from January 2015 to January 2023. We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.\u0000 RESULTS\u0000 KPI incidence was 7.9% (n = 32), with lung/thoracic cavity the most frequent site of infection; the median time from LT to KPI onset was 7.5 d. Of 44 Klebsiella pneumoniae isolates, 43 (97.7%) and 34 (77.3%) were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline, respectively; > 70% were resistant to piperacillin/ tazobactam, ceftazidime, cefepime, aztreonam, meropenem, and levofloxacin. Female sex [odds ratio (OR) = 2.827, 95% confidence interval (CI): 1.256-6.364; P = 0.012], pre-LT diabetes (OR = 2.794, 95%CI: 1.070-7.294; P = 0.036), day 1 post-LT alanine aminotransferase (ALT) levels ≥ 1500 U/L (OR = 3.645, 95%CI: 1.671-7.950; P = 0.001), and post-LT urethral catheter duration over 4 d (OR = 2.266, 95%CI: 1.016-5.054; P = 0.046) were risk factors for KPI. CRKP infections, but not KPIs, were risk factors for 6-month all-cause mortality post-LT.\u0000 CONCLUSION\u0000 KPIs occur frequently and rapidly after LT. Risk factors include female sex, pre-LT diabetes, increased post-LT ALT levels, and urethral catheter duration. CRKP infections, and not KPIs, affect mortality.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen: Novel viral biomarkers for chronic hepatitis B management","authors":"Wattana Leowattana, Pathomthep Leowattana, Tawithep Leowattana","doi":"10.4254/wjh.v16.i4.550","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.550","url":null,"abstract":"The management of hepatitis B virus (HBV) infection now involves regular and appropriate monitoring of viral activity, disease progression, and treatment response. Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness. Quantitation of HBV core antibodies (qAnti-HBc) is a novel non-invasive biomarker that may help with a variety of diagnostic issues. It was shown to correlate strongly with infection stages, hepatic inflammation and fibrosis, chronic infection exacerbations, and the presence of occult infection. Furthermore, qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance, relapse after medication termination, re-infection following liver transplantation, and viral reactivation in the presence of immunosuppression. qAnti-HBc, on the other hand, cannot be relied on as a single diagnostic test to address all problems, and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg. Commercial qAnti-HBc diagnostic kits are currently not widely available. Because many methodologies are only semi-quantitative, comparing data from various studies and defining universal cut-off values remains difficult. This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing-Jing Li, Jiaxi Mao, Han-Xiang Zhong, Yuan-Yu Zhao, Fei Teng, Xin-Yi Lu, Li-Ye Zhu, Yang Gao, Hong Fu, Wen-yuan Guo
{"title":"Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma: A comprehensive review","authors":"Jing-Jing Li, Jiaxi Mao, Han-Xiang Zhong, Yuan-Yu Zhao, Fei Teng, Xin-Yi Lu, Li-Ye Zhu, Yang Gao, Hong Fu, Wen-yuan Guo","doi":"10.4254/wjh.v16.i4.537","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.537","url":null,"abstract":"The tumor microenvironment is a complex network of cells, extracellular matrix, and signaling molecules that plays a critical role in tumor progression and metastasis. Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits. However, recent studies have shown that lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) also play multifaceted roles in the tumor microenvironment beyond their structural functions, particularly in hepatocellular carcinoma (HCC). This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC, including their involvement in angiogenesis, immune modulation, lymphangiogenesis, and metastasis. By providing a detailed account of the complex interplay between LECs, BECs, and tumor cells, this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erdafitinib and checkpoint inhibitors for first-line and second-line immunotherapy of hepatic, gastrointestinal, and urinary bladder carcinomas: Recent concept","authors":"Mohamed Wishahi","doi":"10.4254/wjh.v16.i4.490","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.490","url":null,"abstract":"Cancer immunotherapy is administered for first-line, second-line, neoadjuvant, or adjuvant treatment of advanced, metastatic, and recurrent cancer in the liver, gastrointestinal tract, and genitourinary tract, and other solid tumors. Erdafitinib is a fibroblast growth factor receptor (FGFR) inhibitor, and it is an adenosine triphosphate competitive inhibitor of FGFR1, FGFR2, FGFR3, and FGFR4. Immune checkpoint inhibitors are monoclonal antibodies that block programmed cell death protein 1 (PD-1) and its ligand that exert intrinsic antitumor mechanisms. The promising results of first-line treatment of advanced and metastatic urothelial carcinoma with PD-1 blockades with single or combined agents, indicate a new concept in the treatment of advanced, metastatic, and recurrent hepatic and gastrointestinal carcinomas. Cancer immunotherapy as first-line treatment will improve overall survival and provide better quality of life. Debate is arising as to whether to apply the cancer immunotherapy as first-line treatment in invasive carcinomas, or as second-line treatment in recurrent or metastatic carcinoma following the standard chemotherapy. The literature in the field is not definite, and so far, there has been no consensus on the best approach in this situation. At present, as it is described in this editorial, the decision is applied on a case-by-case basis.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spectrum of COVID-19 induced liver injury: A review report","authors":"Lokjan Singh, Anil Kumar, Maya Rai, Bibek Basnet, Nishant Rai, Pukar Khanal, Kok-Song Lai, Wan-Hee Cheng, A. Asaad, Shamshul Ansari","doi":"10.4254/wjh.v16.i4.517","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.517","url":null,"abstract":"The coronavirus disease 2019 (COVID-19) pandemic has caused changes in the global health system, causing significant setbacks in healthcare systems worldwide. This pandemic has also shown resilience, flexibility, and creativity in reacting to the tragedy. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection targets most of the respiratory tract, resulting in a severe sickness called acute respiratory distress syndrome that may be fatal in some individuals. Although the lung is the primary organ targeted by COVID-19 viruses, the clinical aspect of the disease is varied and ranges from asymptomatic to respiratory failure. However, due to an unorganized immune response and several affected mechanisms, the liver may also experience liver cell injury, ischemic liver dysfunction, and drug-induced liver injury, which can result in respiratory failure because of the immune system’s disordered response and other compromised processes that can end in multisystem organ failure. Patients with liver cirrhosis or those who have impaired immune systems may be more likely than other groups to experience worse results from the SARS-CoV-2 infection. We thus intend to examine the pathogenesis, current therapy, and consequences of liver damage concerning COVID-19.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B: A meta-analysis","authors":"Shiyi Liu, Dian Wang, Jing Liu, Lu-Ping Yang, Gongying Chen","doi":"10.4254/wjh.v16.i3.465","DOIUrl":"https://doi.org/10.4254/wjh.v16.i3.465","url":null,"abstract":"BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally, nonalcoholic fatty liver disease (NAFLD) is gradually gaining attention as another major chronic liver disease. The number of patients having chronic hepatitis B (CHB) with concomitant hepatic steatosis has increased. AIM To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB. METHODS Relevant English studies were systematically searched across PubMed, EMBASE, Web of Science, and Cochrane Library until October 2023. Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included. RESULTS Of the 2502 retrieved studies, 11 articles were finally included. Biochemical response until 48 wk (OR = 0.87, 95%CI: 0.50–1.53, P = 0.000) and 96 wk (OR = 0.35, 95%CI: 0.24–0.53, P = 0.24) and virological response until 96 wk (OR = 0.80, 95%CI: 0.43–1.49, P = 0.097) were lower in patients with hepatic steatosis than in patients with CHB alone. CONCLUSION Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140376522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in discovery of novel investigational agents for functional cure of chronic hepatitis B: A comprehensive review of phases II and III therapeutic agents.","authors":"Robert Lam, Joseph K Lim","doi":"10.4254/wjh.v16.i3.331","DOIUrl":"https://doi.org/10.4254/wjh.v16.i3.331","url":null,"abstract":"<p><p>Chronic hepatitis B virus (HBV) infection affects over 295 million people globally and an estimated 1.6 million people in the United States. It is associated with significant morbidity and mortality due to cirrhosis, liver failure, and liver cancer. Antiviral therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression, which in turn has been associated with a decreased risk of liver complications. However, current antiviral regimens are limited by concerns with adverse effects, adherence, resistance, long-term treatment, and ongoing risk for liver events. Novel investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen (HBsAg) loss and suppression of HBV DNA. Herein we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B, including core/capsid inhibitors, entry inhibitors, RNA interference (siRNA/ASO), HBsAg inhibitors, Toll-like receptor agonists, checkpoint inhibitors, and therapeutic vaccines.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10989302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}