Qiu-Ju Liang, Qin-Qin Long, Feng-Qin Tian, Qun-Ying Su, Xiao-Ying Zhu, Xi-Dai Long
Background: The dysregulation of tissue inhibitor of metalloproteinase-3 (TIMP3) was positively correlated with the progression of hepatocellular carcinoma (HCC). However, it is not clear whether TIMP3 expression is associated with the clinicopathological features and prognosis of aflatoxin B1 (AFB1)-related HCC (AHCC).
Aim: To assess the effects of TIMP3 expression on the clinicopathological features and prognosis of AHCC.
Methods: A retrospective study, including 182 patients with AHCC, was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinicopathological characteristics and prognosis of AHCC. TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis. Odds ratio, hazard ratio (HR), median overall survival time (MST), median tumor recurrence-free survival time (MRT), and corresponding 95% confidential interval (CI) was calculated to evaluate the potential of TIMP3 expression in predicting AHCC prognosis.
Results: Kaplan-Meier survival analysis showed that compared with high TIMP3 expression, low TIMP3 expression in tumor tissues significantly decreased the MST (36.00 mo vs 18.00 mo) and MRT (32.00 mo vs 16 mo) of patients with AHCC. Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death (HR = 2.85, 95%CI: 2.04-4.00) and tumor recurrence (HR = 2.26, 95%CI: 1.57-3.26). Furthermore, decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopathological features, such as tumor size, tumor grade and stage, tumor microvessel density, and tumor blood invasion. Additionally, TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.
Conclusion: These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome, suggesting that TIMP3 may act as a prognostic biomarker for AHCC.
背景：组织金属蛋白酶抑制剂-3（TIMP3）的失调与肝细胞癌（HCC）的进展呈正相关。目的：评估 TIMP3 表达对 AHCC 临床病理特征和预后的影响：方法：对182例AHCC患者进行回顾性研究，探讨TIMP3在癌组织中的表达与AHCC临床病理特征和预后之间的联系。采用免疫组化方法检测 TIMP3 的表达，并通过 Kaplan-Meier 生存分析和 Cox 回归生存分析评估其对 AHCC 临床病理特征和预后的影响。计算胜数比、危险比（HR）、中位总生存时间（MST）、中位无肿瘤复发生存时间（MRT）及相应的95%保密区间（CI），以评估TIMP3表达在预测AHCC预后方面的潜力：Kaplan-Meier生存分析显示，与TIMP3高表达相比，肿瘤组织中TIMP3低表达会显著降低AHCC患者的MST（36.00 mo vs 18.00 mo）和MRT（32.00 mo vs 16 mo）。多变量 Cox 回归生存分析进一步证明，TIMP3 表达降低会增加死亡风险（HR = 2.85，95%CI：2.04-4.00）和肿瘤复发风险（HR = 2.26，95%CI：1.57-3.26）。此外，AHCC 组织中 TIMP3 蛋白表达的减少与肿瘤的临床病理特征（如肿瘤大小、肿瘤分级和分期、肿瘤微血管密度和肿瘤血侵）显著相关。此外，TIMP3 蛋白表达还与肿瘤组织中 AFB1-DNA 加合物的量呈负相关：这些研究结果表明，TIMP3表达失调与AHCC的生物学行为有关，并影响肿瘤的预后，提示TIMP3可作为AHCC的预后生物标志物。
{"title":"Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma.","authors":"Qiu-Ju Liang, Qin-Qin Long, Feng-Qin Tian, Qun-Ying Su, Xiao-Ying Zhu, Xi-Dai Long","doi":"10.4254/wjh.v16.i8.1131","DOIUrl":"10.4254/wjh.v16.i8.1131","url":null,"abstract":"<p><strong>Background: </strong>The dysregulation of tissue inhibitor of metalloproteinase-3 (TIMP3) was positively correlated with the progression of hepatocellular carcinoma (HCC). However, it is not clear whether TIMP3 expression is associated with the clinicopathological features and prognosis of aflatoxin B1 (AFB1)-related HCC (AHCC).</p><p><strong>Aim: </strong>To assess the effects of TIMP3 expression on the clinicopathological features and prognosis of AHCC.</p><p><strong>Methods: </strong>A retrospective study, including 182 patients with AHCC, was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinicopathological characteristics and prognosis of AHCC. TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis. Odds ratio, hazard ratio (HR), median overall survival time (MST), median tumor recurrence-free survival time (MRT), and corresponding 95% confidential interval (CI) was calculated to evaluate the potential of TIMP3 expression in predicting AHCC prognosis.</p><p><strong>Results: </strong>Kaplan-Meier survival analysis showed that compared with high TIMP3 expression, low <i>TIMP3</i> expression in tumor tissues significantly decreased the MST (36.00 mo <i>vs</i> 18.00 mo) and MRT (32.00 mo <i>vs</i> 16 mo) of patients with AHCC. Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death (HR = 2.85, 95%CI: 2.04-4.00) and tumor recurrence (HR = 2.26, 95%CI: 1.57-3.26). Furthermore, decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopathological features, such as tumor size, tumor grade and stage, tumor microvessel density, and tumor blood invasion. Additionally, TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.</p><p><strong>Conclusion: </strong>These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome, suggesting that TIMP3 may act as a prognostic biomarker for AHCC.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112529","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}
In this editorial, we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology (2024; 30: 1346-1357). The study highlights a noteworthy association between persistently elevated, yet high-normal levels of alanine transaminase (ALT) and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD has emerged as a globally prevalent chronic liver condition, whose incidence is steadily rising in parallel with improvements in living standards. Left unchecked, MAFLD can progress from hepatic steatosis to liver fibrosis, cirrhosis, and even hepatocellular carcinoma, underscoring the importance of early screening and diagnosis. ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage. While ALT levels demonstrate a significant correlation with the severity of fatty liver disease, they lack specificity. The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels. Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD, emphasizing the need for closer monitoring and potential intervention in such cases.
在这篇社论中，我们对 Chen 等人发表在最近一期《世界胃肠病学杂志》（2024; 30: 1346-1357）上的文章进行了评论。该研究强调了丙氨酸转氨酶（ALT）持续升高但仍处于正常水平与患代谢功能障碍相关性脂肪肝（MAFLD）的累积风险上升之间存在值得注意的关联。代谢功能障碍相关性脂肪肝已成为一种全球流行的慢性肝病，其发病率随着生活水平的提高而稳步上升。如果不加以控制，MAFLD 可从肝脂肪变性发展为肝纤维化、肝硬化，甚至肝细胞癌，这凸显了早期筛查和诊断的重要性。ALT 被公认为是评估肝细胞损伤程度的可靠生物标志物。虽然 ALT 水平与脂肪肝的严重程度有显著相关性，但缺乏特异性。Chen 等人的文章通过研究高正常 ALT 水平的长期影响，有助于我们了解 MAFLD 的发展。他们的研究结果表明，正常范围内的持续升高与罹患 MAFLD 的可能性增加有关，强调了对此类病例进行更密切监测和潜在干预的必要性。
{"title":"Predictive value of serum alanine aminotransferase for fatty liver associated with metabolic dysfunction","authors":"Wen-Xiu Liu, Lei Liu","doi":"10.4254/wjh.v16.i7.990","DOIUrl":"https://doi.org/10.4254/wjh.v16.i7.990","url":null,"abstract":"In this editorial, we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology (2024; 30: 1346-1357). The study highlights a noteworthy association between persistently elevated, yet high-normal levels of alanine transaminase (ALT) and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD has emerged as a globally prevalent chronic liver condition, whose incidence is steadily rising in parallel with improvements in living standards. Left unchecked, MAFLD can progress from hepatic steatosis to liver fibrosis, cirrhosis, and even hepatocellular carcinoma, underscoring the importance of early screening and diagnosis. ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage. While ALT levels demonstrate a significant correlation with the severity of fatty liver disease, they lack specificity. The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels. Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD, emphasizing the need for closer monitoring and potential intervention in such cases.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797797","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}
In this editorial we expand the discussion on the article by Zhang et al published in the recent issue of the World Journal of Hepatology . We focus on the diagnostic and therapeutic targets identified on the basis of the current understanding of the molecular mechanisms of liver disease. Transforming growth factor-β (TGF-β) belongs to a structurally related cytokine super family. The family members display different time- and tissue-specific expression patterns associated with autoimmunity, inflammation, fibrosis, and tumorigenesis; and, they participate in the pathogenesis of many diseases. TGF-β and its related signaling pathways have been shown to participate in the progression of liver diseases, such as injury, inflammation, fibrosis, cirrhosis, and cancer. The often studied TGF-β/Smad signaling pathway has been shown to promote or inhibit liver fibrosis under different circumstances. Similarly, the early immature TGF-β molecule functions as a tumor suppressor, inducing apoptosis; but, its interaction with the mitogenic molecule epidermal growth factor alters this effect, activating anti-apoptotic signals that promote liver cancer development. Overall, TGF-β signaling displays contradictory effects in different liver disease stages. Therefore, the use of TGF-β and related signaling pathway molecules for diagnosis and treatment of liver diseases remains a challenge and needs further study. In this editorial, we aim to review the evidence for the use of TGF-β signaling pathway molecules as diagnostic or therapeutic targets for different liver disease stages.
{"title":"Roles of transforming growth factor-β signaling in liver disease","authors":"Xiaoling Wang, Meng Yang, Ying Wang","doi":"10.4254/wjh.v16.i7.973","DOIUrl":"https://doi.org/10.4254/wjh.v16.i7.973","url":null,"abstract":"In this editorial we expand the discussion on the article by Zhang et al published in the recent issue of the World Journal of Hepatology . We focus on the diagnostic and therapeutic targets identified on the basis of the current understanding of the molecular mechanisms of liver disease. Transforming growth factor-β (TGF-β) belongs to a structurally related cytokine super family. The family members display different time- and tissue-specific expression patterns associated with autoimmunity, inflammation, fibrosis, and tumorigenesis; and, they participate in the pathogenesis of many diseases. TGF-β and its related signaling pathways have been shown to participate in the progression of liver diseases, such as injury, inflammation, fibrosis, cirrhosis, and cancer. The often studied TGF-β/Smad signaling pathway has been shown to promote or inhibit liver fibrosis under different circumstances. Similarly, the early immature TGF-β molecule functions as a tumor suppressor, inducing apoptosis; but, its interaction with the mitogenic molecule epidermal growth factor alters this effect, activating anti-apoptotic signals that promote liver cancer development. Overall, TGF-β signaling displays contradictory effects in different liver disease stages. Therefore, the use of TGF-β and related signaling pathway molecules for diagnosis and treatment of liver diseases remains a challenge and needs further study. In this editorial, we aim to review the evidence for the use of TGF-β signaling pathway molecules as diagnostic or therapeutic targets for different liver disease stages.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797288","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}
A. Wakil, Yasameen E Muzahim, Mina Awadallah, Vikash Kumar, Natale Mazzaferro, Patricia Greenberg, Nikolaos T. Pyrsopoulos
BACKGROUND Autoimmune liver diseases (AiLD) encompass a variety of disorders that target either the liver cells (autoimmune hepatitis, AIH) or the bile ducts [(primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC)]. These conditions can progress to chronic liver disease (CLD), which is characterized by fibrosis, cirrhosis, and hepatocellular carcinoma. Recent studies have indicated a rise in hospitalizations and associated costs for CLD in the US, but information regarding inpatient admissions specifically for AiLD remains limited. AIM To examine the trends and mortality of inpatient hospitalization of AiLD from 2011 to 2017. METHODS This study is a retrospective analysis utilizing the National Inpatient Sample (NIS) databases. All subjects admitted between 2011 and 2017 with a diagnosis of AiLD (AIH, PBC, PSC) were identified using the International Classification of Diseases (ICD-9) and ICD-10 codes. primary AiLD admission was defined if the first admission code was one of the AiLD codes. secondary AiLD admission was defined as having the AiLD diagnosis anywhere in the admission diagnosis (25 diagnoses). Subjects aged 21 years and older were included. The national estimates of hospitalization were derived using sample weights provided by NIS. χ 2 tests for categorical data were used. The primary trend characteristics were in-hospital mortality, hospital charges, and length of stay. RESULTS From 2011 to 2017, hospitalization rates witnessed a significant decline, dropping from 83263 admissions to 74850 admissions (P < 0.05). The patients hospitalized were predominantly elderly (median 53% for age > 65), mostly female (median 59%) (P < 0.05), and primarily Caucasians (median 68%) (P < 0.05). Medicare was the major insurance (median 56%), followed by private payer (median 27%) (P < 0.05). The South was the top geographical distribution for these admissions (median 33%) (P < 0.05), with most admissions taking place in big teaching institutions (median 63%) (P < 0.05). Total charges for admissions rose from 66031 in 2011 to 78987 in 2017 (P < 0.05), while the inpatient mortality rate had a median of 4.9% (P < 0.05), rising from 4.67% in 2011 to 5.43% in 2017. The median length of stay remained relatively stable, changing from 6.94 days (SD = 0.07) in 2011 to 6.51 days (SD = 0.06) in 2017 (P < 0.05). Acute renal failure emerged as the most common risk factor associated with an increased death rate, affecting nearly 68% of patients (P < 0.05). CONCLUSION AiLD-inpatient hospitalization showed a decrease in overall trends over the studied years, however there is a significant increase in financial burden on healthcare with increasing in-hospital costs along with increase in mortality of hospitalized patient with AiLD.
{"title":"Trends of autoimmune liver disease inpatient hospitalization and mortality from 2011 to 2017: A United States nationwide analysis","authors":"A. Wakil, Yasameen E Muzahim, Mina Awadallah, Vikash Kumar, Natale Mazzaferro, Patricia Greenberg, Nikolaos T. Pyrsopoulos","doi":"10.4254/wjh.v16.i7.1029","DOIUrl":"https://doi.org/10.4254/wjh.v16.i7.1029","url":null,"abstract":"BACKGROUND\u0000 Autoimmune liver diseases (AiLD) encompass a variety of disorders that target either the liver cells (autoimmune hepatitis, AIH) or the bile ducts [(primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC)]. These conditions can progress to chronic liver disease (CLD), which is characterized by fibrosis, cirrhosis, and hepatocellular carcinoma. Recent studies have indicated a rise in hospitalizations and associated costs for CLD in the US, but information regarding inpatient admissions specifically for AiLD remains limited.\u0000 AIM\u0000 To examine the trends and mortality of inpatient hospitalization of AiLD from 2011 to 2017.\u0000 METHODS\u0000 This study is a retrospective analysis utilizing the National Inpatient Sample (NIS) databases. All subjects admitted between 2011 and 2017 with a diagnosis of AiLD (AIH, PBC, PSC) were identified using the International Classification of Diseases (ICD-9) and ICD-10 codes. primary AiLD admission was defined if the first admission code was one of the AiLD codes. secondary AiLD admission was defined as having the AiLD diagnosis anywhere in the admission diagnosis (25 diagnoses). Subjects aged 21 years and older were included. The national estimates of hospitalization were derived using sample weights provided by NIS. χ 2 tests for categorical data were used. The primary trend characteristics were in-hospital mortality, hospital charges, and length of stay.\u0000 RESULTS\u0000 From 2011 to 2017, hospitalization rates witnessed a significant decline, dropping from 83263 admissions to 74850 admissions (P < 0.05). The patients hospitalized were predominantly elderly (median 53% for age > 65), mostly female (median 59%) (P < 0.05), and primarily Caucasians (median 68%) (P < 0.05). Medicare was the major insurance (median 56%), followed by private payer (median 27%) (P < 0.05). The South was the top geographical distribution for these admissions (median 33%) (P < 0.05), with most admissions taking place in big teaching institutions (median 63%) (P < 0.05). Total charges for admissions rose from 66031 in 2011 to 78987 in 2017 (P < 0.05), while the inpatient mortality rate had a median of 4.9% (P < 0.05), rising from 4.67% in 2011 to 5.43% in 2017. The median length of stay remained relatively stable, changing from 6.94 days (SD = 0.07) in 2011 to 6.51 days (SD = 0.06) in 2017 (P < 0.05). Acute renal failure emerged as the most common risk factor associated with an increased death rate, affecting nearly 68% of patients (P < 0.05).\u0000 CONCLUSION\u0000 AiLD-inpatient hospitalization showed a decrease in overall trends over the studied years, however there is a significant increase in financial burden on healthcare with increasing in-hospital costs along with increase in mortality of hospitalized patient with AiLD.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797861","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}
Cytokines like interleukins (ILs) play important roles in inflammation and innate immune. Yang and Zhang carried out an interesting study related to ILs and hepatic diseases. They described the role of ILs in the pathogenesis and resolution of hepatic disorders. The authors summarized alcohol-related liver disease and virus-induced hepatitis, as far as clinical studies a fortiori carried out on IL-mediated treatments pertaining to these dysfunctions. This editorial contributes to the review by Yang and Zhang titled, "Interleukins in liver disease treatment", and focuses on therapies mediated by ILs in comorbid liver diseases. The documentary search was conducted on recent pertinent literature, primarily using the Google Scholar and PubMed databases.
白细胞介素（ILs）等细胞因子在炎症和先天性免疫中发挥着重要作用。杨和张进行了一项有关 ILs 和肝病的有趣研究。他们描述了 ILs 在肝脏疾病的发病和缓解过程中的作用。作者总结了与酒精相关的肝病和病毒引起的肝炎，以及与这些功能障碍相关的IL介导治疗的临床研究。这篇社论是对杨和张题为 "白细胞介素在肝病治疗中的应用 "的综述的补充，重点是白细胞介素介导的治疗合并肝病的方法。文献检索主要通过谷歌学术和PubMed数据库对近期相关文献进行了检索。
{"title":"Interleukin-mediated therapies in liver diseases and comorbidity effects","authors":"Nouhoum Bouare, Jean Delwaide","doi":"10.4254/wjh.v16.i7.980","DOIUrl":"https://doi.org/10.4254/wjh.v16.i7.980","url":null,"abstract":"Cytokines like interleukins (ILs) play important roles in inflammation and innate immune. Yang and Zhang carried out an interesting study related to ILs and hepatic diseases. They described the role of ILs in the pathogenesis and resolution of hepatic disorders. The authors summarized alcohol-related liver disease and virus-induced hepatitis, as far as clinical studies a fortiori carried out on IL-mediated treatments pertaining to these dysfunctions. This editorial contributes to the review by Yang and Zhang titled, \"Interleukins in liver disease treatment\", and focuses on therapies mediated by ILs in comorbid liver diseases. The documentary search was conducted on recent pertinent literature, primarily using the Google Scholar and PubMed databases.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141798068","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}
Acute liver failure presents as a clinical syndrome characterized by swift deterioration and significant mortality rates. Its underlying mechanisms are intricate, involving intricate interplays between various cells. Given the current scarcity of treatment options, there's a pressing need to diligently uncover the disease's core mechanisms and administer targeted therapies accordingly.
{"title":"Acute liver failure: A clinically severe syndrome characterized by intricate mechanisms","authors":"Ran An, Jing-Lin Wang","doi":"10.4254/wjh.v16.i7.1067","DOIUrl":"https://doi.org/10.4254/wjh.v16.i7.1067","url":null,"abstract":"Acute liver failure presents as a clinical syndrome characterized by swift deterioration and significant mortality rates. Its underlying mechanisms are intricate, involving intricate interplays between various cells. Given the current scarcity of treatment options, there's a pressing need to diligently uncover the disease's core mechanisms and administer targeted therapies accordingly.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797269","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}
Sahal Darar Dirir, Ambroise D. Ahouidi, Aboubacry Dramé, Warsama Osman Abdi, Guelleh Youssouf Kayad, Mohamed Houmed Aboubakar, M. Camara, Coumba Kane Toure, Halimatou Diop Ndiaye
BACKGROUND In endemic areas, vertical transmission of hepatitis B virus (HBV) remains a major source of the global reservoir of infected people. Eliminating mother-to-child transmission (MTCT) of HBV is at the heart of World Health Organization’s goal of reducing the incidence of HBV in children to less than 0.1% by 2030. Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures. AIM To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen (HBsAg)-positive mothers in Djibouti city. METHODS We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants. The study ran from January 2021 to May 2022, and infants were followed up to 7 mo of age. HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay (Biomérieux, Paris, France) and the automated Amplix platform (Biosynex, Strasbourg, France). All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth. These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis. Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response. All statistical analyses were performed with version 4.0.1 of the R software. RESULTS Of the 50 pregnant women recruited, the median age was 31 years, ranging from 18 years to 41 years. The MTCT rate in this cohort was 4% (2/50) in HBsAg-positive women and 67% (2/3) in hepatitis B e antigen-positive women with a viral load > 200000 IU/mL. Of the 48 infants who did not fail immunoprophylaxis, 8 (16%) became poor responders (anti-HB < 100 mIU/mL) after HBV vaccination and hepatitis B immunoglobulin, while 40 (84%) infants achieved a good level of seroprotection (anti-HB > 100 mIU/mL). Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels (> 200000 IU/mL) and hepatitis B e antigen-positive status (odds ratio = 158, 95% confidence interval: 5.05-4958, P < 0.01). Birth weight < 2500 g was associated with a poor immune response to vaccination (odds ratio = 34, 95% confidence interval: 3.01-383.86, P < 0.01). CONCLUSION Despite a failure rate of immunoprophylaxis higher than the World Health Organization target, this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV. Therefore, further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.
{"title":"Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti","authors":"Sahal Darar Dirir, Ambroise D. Ahouidi, Aboubacry Dramé, Warsama Osman Abdi, Guelleh Youssouf Kayad, Mohamed Houmed Aboubakar, M. Camara, Coumba Kane Toure, Halimatou Diop Ndiaye","doi":"10.4254/wjh.v16.i7.1039","DOIUrl":"https://doi.org/10.4254/wjh.v16.i7.1039","url":null,"abstract":"BACKGROUND\u0000 In endemic areas, vertical transmission of hepatitis B virus (HBV) remains a major source of the global reservoir of infected people. Eliminating mother-to-child transmission (MTCT) of HBV is at the heart of World Health Organization’s goal of reducing the incidence of HBV in children to less than 0.1% by 2030. Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures.\u0000 AIM\u0000 To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen (HBsAg)-positive mothers in Djibouti city.\u0000 METHODS\u0000 We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants. The study ran from January 2021 to May 2022, and infants were followed up to 7 mo of age. HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay (Biomérieux, Paris, France) and the automated Amplix platform (Biosynex, Strasbourg, France). All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth. These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis. Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response. All statistical analyses were performed with version 4.0.1 of the R software.\u0000 RESULTS\u0000 Of the 50 pregnant women recruited, the median age was 31 years, ranging from 18 years to 41 years. The MTCT rate in this cohort was 4% (2/50) in HBsAg-positive women and 67% (2/3) in hepatitis B e antigen-positive women with a viral load > 200000 IU/mL. Of the 48 infants who did not fail immunoprophylaxis, 8 (16%) became poor responders (anti-HB < 100 mIU/mL) after HBV vaccination and hepatitis B immunoglobulin, while 40 (84%) infants achieved a good level of seroprotection (anti-HB > 100 mIU/mL). Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels (> 200000 IU/mL) and hepatitis B e antigen-positive status (odds ratio = 158, 95% confidence interval: 5.05-4958, P < 0.01). Birth weight < 2500 g was associated with a poor immune response to vaccination (odds ratio = 34, 95% confidence interval: 3.01-383.86, P < 0.01).\u0000 CONCLUSION\u0000 Despite a failure rate of immunoprophylaxis higher than the World Health Organization target, this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV. Therefore, further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797617","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}
Jia-Yao Huang, Jian-Yun Peng, Hai-Yi Long, Xian Zhong, Yuhua Xie, Lu Yao, Xiao-Yan Xie, Man-Xia Lin
BACKGROUND Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma (HCC), but a convenient and comprehensive method to assess liver condition is lacking. Liver stiffness (LS) measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition. Chronic hepatitis B (CHB) is an important risk factor for HCC progression, but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication. We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition. AIM To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB. METHODS A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus (HBV)-DNA levels [HBV-DNA ≥ 100.00 IU/mL as Pos group (n = 200) and < 100.00 IU/mL as Neg group (n = 84)]. Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition. RESULTS A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition (P < 0.05). When alanine aminotransferase (ALT) concentrations were normal (≤ 40 U/L), LS was correlated with liver condition indices (P < 0.05), but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group (9.30 kPa) than the Pos group (7.40 kPa). When ALT levels were elevated (> 40 U/L), the correlations between LS and liver condition indices were not significant (P > 0.05). CONCLUSION LS was significantly correlated with most liver condition indices in patients with CHB and HCC. However, these correlations varied according to differences in HBV-DNA and transaminase concentrations.
背景 肝脏状况是肝细胞癌（HCC）患者的一个重要预后因素，但目前还缺乏一种方便、全面的方法来评估肝脏状况。通过二维剪切波弹性成像测量肝脏硬度（LS）有助于评估肝纤维化和肝脏状况。慢性乙型肝炎（CHB）是导致 HCC 进展的一个重要风险因素，但研究发现 LS 在评估肝炎病毒根除后的肝纤维化方面不太可靠。我们假设肝炎病毒感染状况会影响 LS 评估肝脏状况的准确性。目的 检验使用LS评估HCC和CHB患者肝脏状况的可行性和影响因素。方法 回顾性招募 284 例患者，并根据血清 CHB 病毒乙型肝炎病毒（HBV）-DNA 水平分为两组[HBV-DNA ≥ 100.00 IU/mL 为 Pos 组（n = 200），< 100.00 IU/mL 为 Neg 组（n = 84）]。进行相关性分析和接收器操作特征分析，以评估 LS 与肝脏状况之间的关系。结果 发现 LS 与大多数被认为能够评估肝脏状况的参数之间存在明显相关性（P < 0.05）。当丙氨酸氨基转移酶（ALT）浓度正常（≤ 40 U/L）时，LS 与肝脏状况指数相关（P < 0.05），但 Neg 组（9.30 kPa）比 Pos 组（7.40 kPa）确定 Child-Pugh 评分 5 分的最佳 LS 临界值更高。当 ALT 水平升高（> 40 U/L）时，LS 与肝脏状况指数之间的相关性不显著（P > 0.05）。结论 LS 与 CHB 和 HCC 患者的大多数肝脏状况指数有明显相关性。然而，这些相关性因 HBV DNA 和转氨酶浓度的不同而异。
{"title":"Liver stiffness in hepatocellular carcinoma and chronic hepatitis patients: Hepatitis B virus infection and transaminases should be considered","authors":"Jia-Yao Huang, Jian-Yun Peng, Hai-Yi Long, Xian Zhong, Yuhua Xie, Lu Yao, Xiao-Yan Xie, Man-Xia Lin","doi":"10.4254/wjh.v16.i7.1018","DOIUrl":"https://doi.org/10.4254/wjh.v16.i7.1018","url":null,"abstract":"BACKGROUND\u0000 Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma (HCC), but a convenient and comprehensive method to assess liver condition is lacking. Liver stiffness (LS) measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition. Chronic hepatitis B (CHB) is an important risk factor for HCC progression, but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication. We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition.\u0000 AIM\u0000 To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB.\u0000 METHODS\u0000 A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus (HBV)-DNA levels [HBV-DNA ≥ 100.00 IU/mL as Pos group (n = 200) and < 100.00 IU/mL as Neg group (n = 84)]. Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition.\u0000 RESULTS\u0000 A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition (P < 0.05). When alanine aminotransferase (ALT) concentrations were normal (≤ 40 U/L), LS was correlated with liver condition indices (P < 0.05), but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group (9.30 kPa) than the Pos group (7.40 kPa). When ALT levels were elevated (> 40 U/L), the correlations between LS and liver condition indices were not significant (P > 0.05).\u0000 CONCLUSION\u0000 LS was significantly correlated with most liver condition indices in patients with CHB and HCC. However, these correlations varied according to differences in HBV-DNA and transaminase concentrations.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797493","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 The modified Xiaoyao San (MXS) formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer, which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival. However, the molecular mechanisms underlying that remain unclear. AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury, steatosis and inflammation. METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis (NASH) model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes. Liver tissues were collected for western blotting and immunohistochemistry (IHC) assays. Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining. The serum samples were collected for biochemical assays and NMR-based metabonomics analysis. The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH. RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress. The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation, inflammation and hepatic fibrosis in the pathogenesis of NASH. The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis. Mechanistically, we found that MXS protected against NASH by attenuating the sex hormone-related metabolism, especially the metabolism of male hormones. CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones. Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.
{"title":"Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism","authors":"Xiao-Li Mei, Shu-Yi Wu, Si-Lan Wu, Xiao-Lin Luo, Si-Xing Huang, Rui Liu, Zhe Qiang","doi":"10.4254/wjh.v16.i7.1051","DOIUrl":"https://doi.org/10.4254/wjh.v16.i7.1051","url":null,"abstract":"BACKGROUND\u0000 The modified Xiaoyao San (MXS) formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer, which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival. However, the molecular mechanisms underlying that remain unclear.\u0000 AIM\u0000 To investigate the role and mechanisms of MXS in ameliorating hepatic injury, steatosis and inflammation.\u0000 METHODS\u0000 A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis (NASH) model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes. Liver tissues were collected for western blotting and immunohistochemistry (IHC) assays. Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining. The serum samples were collected for biochemical assays and NMR-based metabonomics analysis. The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.\u0000 RESULTS\u0000 MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress. The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation, inflammation and hepatic fibrosis in the pathogenesis of NASH. The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis. Mechanistically, we found that MXS protected against NASH by attenuating the sex hormone-related metabolism, especially the metabolism of male hormones.\u0000 CONCLUSION\u0000 MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones. Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797670","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}
N. Y. Ismael, S. A. Usmael, N. B. Belay, Hailemichael Desalegn Mekonen, A. Johannessen, Stian Orlien
BACKGROUND Chronic hepatitis B (CHB) virus infection is a major cause of liver-associated morbidity and mortality, particularly in low-income countries. A better understanding of the epidemiological, clinical, and virological characteristics of CHB will guide appropriate treatment strategies and improve the control and management of CHB in Ethiopia. AIM To investigate the characteristics of CHB in Eastern Ethiopia and assess the efficacy and safety of antiviral treatment. METHODS This cohort study included 193 adults who were human immunodeficiency virus-negative with CHB between June 2016 and December 2019. Baseline assessments included chemistry, serologic, and viral markers. χ 2 tests, Mann-Whitney U tests, and logistic regression analyses were used to identify the determinants of cirrhosis. Tenofovir disoproxil fumarate (TDF) was initiated using treatment criteria from the Ethiopian CHB pilot program. RESULTS A total of 132 patients (68.4%) were men, with a median age of 30 years [interquartile range (IQR): 24-38]. At enrollment, 60 (31.1%) patients had cirrhosis, of whom 35 (58.3%) had decompensated cirrhosis. Khat use, hepatitis B envelope antigen positivity, and a high viral load were independently associated with cirrhosis. Additionally, 66 patients (33.4%) fulfilled the treatment criteria and 59 (30.6%) started TDF. Among 29 patients who completed 24 months of treatment, the median aspartate aminotransferase to platelet ratio index declined from 1.54 (IQR: 0.66-2.91) to 1.10 (IQR: 0.75-2.53) (P = 0.002), and viral suppression was achieved in 80.9% and 100% of patients after 12 months and 24 months of treatment, respectively. Among the treated patients, 12 (20.3%) died within the first 6 months of treatment, of whom 8 had decompensated cirrhosis. CONCLUSION This study highlights the high prevalence of cirrhosis, initial mortality, and the efficacy of TDF treatment. Scaling up measures to prevent and control CHB infections in Ethiopia is crucial.
{"title":"Chronic hepatitis B virus infection in Eastern Ethiopia: Clinical characteristics and determinants of cirrhosis","authors":"N. Y. Ismael, S. A. Usmael, N. B. Belay, Hailemichael Desalegn Mekonen, A. Johannessen, Stian Orlien","doi":"10.4254/wjh.v16.i7.995","DOIUrl":"https://doi.org/10.4254/wjh.v16.i7.995","url":null,"abstract":"BACKGROUND\u0000 Chronic hepatitis B (CHB) virus infection is a major cause of liver-associated morbidity and mortality, particularly in low-income countries. A better understanding of the epidemiological, clinical, and virological characteristics of CHB will guide appropriate treatment strategies and improve the control and management of CHB in Ethiopia.\u0000 AIM\u0000 To investigate the characteristics of CHB in Eastern Ethiopia and assess the efficacy and safety of antiviral treatment.\u0000 METHODS\u0000 This cohort study included 193 adults who were human immunodeficiency virus-negative with CHB between June 2016 and December 2019. Baseline assessments included chemistry, serologic, and viral markers. χ 2 tests, Mann-Whitney U tests, and logistic regression analyses were used to identify the determinants of cirrhosis. Tenofovir disoproxil fumarate (TDF) was initiated using treatment criteria from the Ethiopian CHB pilot program.\u0000 RESULTS\u0000 A total of 132 patients (68.4%) were men, with a median age of 30 years [interquartile range (IQR): 24-38]. At enrollment, 60 (31.1%) patients had cirrhosis, of whom 35 (58.3%) had decompensated cirrhosis. Khat use, hepatitis B envelope antigen positivity, and a high viral load were independently associated with cirrhosis. Additionally, 66 patients (33.4%) fulfilled the treatment criteria and 59 (30.6%) started TDF. Among 29 patients who completed 24 months of treatment, the median aspartate aminotransferase to platelet ratio index declined from 1.54 (IQR: 0.66-2.91) to 1.10 (IQR: 0.75-2.53) (P = 0.002), and viral suppression was achieved in 80.9% and 100% of patients after 12 months and 24 months of treatment, respectively. Among the treated patients, 12 (20.3%) died within the first 6 months of treatment, of whom 8 had decompensated cirrhosis.\u0000 CONCLUSION\u0000 This study highlights the high prevalence of cirrhosis, initial mortality, and the efficacy of TDF treatment. Scaling up measures to prevent and control CHB infections in Ethiopia is crucial.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797596","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}
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