Background: 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.
Aim: 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.
Methods: 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.
Results: 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, P = 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).
Conclusion: 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.
{"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
BACKGROUND 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. AIM To assess KPI incidence, timing, distribution, drug resistance, and risk factors following LT and its association with outcomes. METHODS 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. RESULTS 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. CONCLUSION 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.
{"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}
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.
{"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
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.
{"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}
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.
{"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}
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.
{"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}
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.
{"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}
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.
慢性乙型肝炎病毒（HBV）感染影响着全球超过 2.95 亿人，在美国估计有 160 万人。慢性乙型肝炎病毒感染与肝硬化、肝功能衰竭和肝癌等重大疾病的发病率和死亡率密切相关。使用口服核苷（t）ide 类似物进行抗病毒治疗的病毒抑制率很高，这反过来又与肝脏并发症风险的降低有关。然而，目前的抗病毒治疗方案受到不良反应、依从性、耐药性、长期治疗和持续肝脏事件风险等问题的限制。目前正在开发的新型研究药物旨在通过持续的乙肝表面抗原（HBsAg）丢失和 HBV DNA 抑制实现功能性治愈。在此，我们回顾了 II 期和 III 期试验的关键证据，这些试验确定了用于慢性乙型肝炎功能性治愈的主要研究药物的疗效和安全性，包括核心/外壳抑制剂、入口抑制剂、RNA 干扰（siRNA/ASO）、HBsAg 抑制剂、Toll 样受体激动剂、检查点抑制剂和治疗性疫苗。
{"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}
Sarah Khan, Hanna Hong, Stephanie Bass, Yifan Wang, Xiao-Feng Wang, Omar T Sims, Christine E Koval, Aanchal Kapoor, Christina C Lindenmeyer
Background: Due to development of an immune-dysregulated phenotype, advanced liver disease in all forms predisposes patients to sepsis acquisition, including by opportunistic pathogens such as fungi. Little data exists on fungal infection within a medical intensive liver unit (MILU), particularly in relation to acute on chronic liver failure.
Aim: To investigate the impact of fungal infections among critically ill patients with advanced liver disease, and compare outcomes to those of patients with bacterial infections.
Methods: From our prospective registry of MILU patients from 2018-2022, we included 27 patients with culture-positive fungal infections and 183 with bacterial infections. We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts. Data was extracted through chart review.
Results: All fungal infections were due to Candida species, and were most frequently blood isolates. Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort (93% vs 52%, P < 0.001). The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure (ACLF) (90% vs 64%, P = 0.02). Patients in the fungal cohort had increased use of vasopressors (96% vs 70%, P = 0.04), mechanical ventilation (96% vs 65%, P < 0.001), and dialysis due to acute kidney injury (78% vs 52%, P = 0.014). On MILU admission, the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation (108 vs 91, P = 0.003), Acute Physiology Score (86 vs 65, P = 0.003), and Model for End-Stage Liver Disease-Sodium scores (86 vs 65, P = 0.041). There was no significant difference in the rate of central line use preceding culture (52% vs 40%, P = 0.2). Patients with fungal infection had higher rate of transplant hold placement, and lower rates of transplant; however, differences did not achieve statistical significance.
Conclusion: Mortality was worse among patients with fungal infections, likely attributable to severe ACLF development. Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.
背景：由于出现免疫失调表型，各种形式的晚期肝病患者容易感染败血症，包括真菌等机会性病原体。目的：调查真菌感染对晚期肝病重症患者的影响，并将结果与细菌感染患者的结果进行比较：从我们 2018-2022 年对 MILU 患者的前瞻性登记中，我们纳入了 27 名培养阳性真菌感染患者和 183 名细菌感染患者。我们比较了入住 MILU 的真菌感染患者与细菌感染患者的治疗效果。通过病历审查提取数据：结果：所有真菌感染都是由念珠菌引起的，最常见的是血液分离菌。真菌感染患者的死亡率明显低于细菌感染患者（93% vs 52%，P < 0.001）。大多数真菌感染者都出现了 2 级或 3 级急性慢性肝功能衰竭 (ACLF)（90% 对 64%，P = 0.02）。真菌组患者使用血管加压药（96% vs 70%，P = 0.04）、机械通气（96% vs 65%，P < 0.001）和急性肾损伤透析（78% vs 52%，P = 0.014）的比例增加。在 MILU 入院时，真菌队列的急性生理学和慢性健康评估（108 vs 91，P = 0.003）、急性生理学评分（86 vs 65，P = 0.003）和终末期肝病模型-钠评分（86 vs 65，P = 0.041）均显著高于真菌队列。培养前使用中心管的比例无明显差异（52% 对 40%，P = 0.2）。真菌感染患者的移植支架置入率较高，移植率较低；但差异未达到统计学意义：结论：真菌感染患者的死亡率较高，这可能与严重的前交叉韧带纤维化有关。对严重 ACLF 的经验性抗真菌药物以及真菌感染与移植结果之间的关系进行前瞻性研究至关重要。
{"title":"Comparison of fungal <i>vs</i> bacterial infections in the medical intensive liver unit: Cause or corollary for high mortality?","authors":"Sarah Khan, Hanna Hong, Stephanie Bass, Yifan Wang, Xiao-Feng Wang, Omar T Sims, Christine E Koval, Aanchal Kapoor, Christina C Lindenmeyer","doi":"10.4254/wjh.v16.i3.379","DOIUrl":"https://doi.org/10.4254/wjh.v16.i3.379","url":null,"abstract":"<p><strong>Background: </strong>Due to development of an immune-dysregulated phenotype, advanced liver disease in all forms predisposes patients to sepsis acquisition, including by opportunistic pathogens such as fungi. Little data exists on fungal infection within a medical intensive liver unit (MILU), particularly in relation to acute on chronic liver failure.</p><p><strong>Aim: </strong>To investigate the impact of fungal infections among critically ill patients with advanced liver disease, and compare outcomes to those of patients with bacterial infections.</p><p><strong>Methods: </strong>From our prospective registry of MILU patients from 2018-2022, we included 27 patients with culture-positive fungal infections and 183 with bacterial infections. We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts. Data was extracted through chart review.</p><p><strong>Results: </strong>All fungal infections were due to <i>Candida</i> species, and were most frequently blood isolates. Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort (93% <i>vs</i> 52%, <i>P</i> < 0.001). The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure (ACLF) (90% <i>vs</i> 64%, <i>P</i> = 0.02). Patients in the fungal cohort had increased use of vasopressors (96% <i>vs</i> 70%, <i>P</i> = 0.04), mechanical ventilation (96% <i>vs</i> 65%, <i>P</i> < 0.001), and dialysis due to acute kidney injury (78% <i>vs</i> 52%, <i>P</i> = 0.014). On MILU admission, the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation (108 <i>vs</i> 91, <i>P</i> = 0.003), Acute Physiology Score (86 <i>vs</i> 65, <i>P</i> = 0.003), and Model for End-Stage Liver Disease-Sodium scores (86 <i>vs</i> 65, <i>P</i> = 0.041). There was no significant difference in the rate of central line use preceding culture (52% <i>vs</i> 40%, <i>P</i> = 0.2). Patients with fungal infection had higher rate of transplant hold placement, and lower rates of transplant; however, differences did not achieve statistical significance.</p><p><strong>Conclusion: </strong>Mortality was worse among patients with fungal infections, likely attributable to severe ACLF development. Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.</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/PMC10989308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864839","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}
Background: The prevalence of metabolic-associated fatty liver disease (MAFLD) is a growing public health issue in people living with human immunodeficiency virus (PLWH). However, the pathophysiology of MAFLD is still unknown, and the role of genetic variables is only now becoming evident.
Aim: To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.
Methods: The study employed transient elastography with a controlled attenuation parameter ≥ 248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand. Candidate single-nucleotide polymorphisms (SNPs) were genotyped using TaqMan® MGB probe 5' nuclease assays for seven MAFLD-related genes. Statistical analyses included SNP frequency analysis, Fisher's Exact and Chi-square tests, odds ratio calculations, and multivariable logistic regression.
Results: The G-allele carriers of PNPLA3 (rs738409) exhibited a two-fold rise in MAFLD, increasing by 2.5 times in MAFLD with human immunodeficiency virus infection. The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times (P = 0.001) more significant chance of developing aberrant triglyceride among PLWH.
Conclusion: The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.
{"title":"Associations of <i>PNPLA3</i> and <i>LEP</i> genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus.","authors":"Kanuengnit Choochuay, Punna Kunhapan, Apichaya Puangpetch, Sissades Tongsima, Pornpen Srisawasdi, Abhasnee Sobhonslidsuk, Somnuek Sungkanuparph, Mohitosh Biswas, Chonlaphat Sukasem","doi":"10.4254/wjh.v16.i3.366","DOIUrl":"https://doi.org/10.4254/wjh.v16.i3.366","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of metabolic-associated fatty liver disease (MAFLD) is a growing public health issue in people living with human immunodeficiency virus (PLWH). However, the pathophysiology of MAFLD is still unknown, and the role of genetic variables is only now becoming evident.</p><p><strong>Aim: </strong>To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.</p><p><strong>Methods: </strong>The study employed transient elastography with a controlled attenuation parameter ≥ 248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand. Candidate single-nucleotide polymorphisms (SNPs) were genotyped using TaqMan<sup>®</sup> MGB probe 5' nuclease assays for seven MAFLD-related genes. Statistical analyses included SNP frequency analysis, Fisher's Exact and Chi-square tests, odds ratio calculations, and multivariable logistic regression.</p><p><strong>Results: </strong>The G-allele carriers of <i>PNPLA3</i> (rs738409) exhibited a two-fold rise in MAFLD, increasing by 2.5 times in MAFLD with human immunodeficiency virus infection. The clinical features and genetic patterns imply that <i>LEP</i> rs7799039 A-allele carriers had a nine times (<i>P</i> = 0.001) more significant chance of developing aberrant triglyceride among PLWH.</p><p><strong>Conclusion: </strong>The current study shows an association between <i>PNPLA3</i> rs738409 and <i>LEP</i> rs7799039 with MAFLD in PLWH.</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/PMC10989307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872124","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}
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