Milena Peruhova, Sonya Banova-Chakarova, Dimitrina Miteva, T. Velikova
Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal role in the development and progression of liver cancer. This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer. We discuss the genetic underpinnings of liver cancer, emphasizing the critical role of risk-associated genetic variants, somatic mutations, and epigenetic alterations. We also explore the intricate interplay between environmental factors and genetics, highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy, and advancements in high-throughput sequencing technologies. By synthesizing the latest research findings, we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer, shedding light on their potential to revolutionize early detection, risk assessment, and targeted therapies in the fight against this devastating disease.
{"title":"Genetic screening of liver cancer: State of the art","authors":"Milena Peruhova, Sonya Banova-Chakarova, Dimitrina Miteva, T. Velikova","doi":"10.4254/wjh.v16.i5.716","DOIUrl":"https://doi.org/10.4254/wjh.v16.i5.716","url":null,"abstract":"Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal role in the development and progression of liver cancer. This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer. We discuss the genetic underpinnings of liver cancer, emphasizing the critical role of risk-associated genetic variants, somatic mutations, and epigenetic alterations. We also explore the intricate interplay between environmental factors and genetics, highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy, and advancements in high-throughput sequencing technologies. By synthesizing the latest research findings, we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer, shedding light on their potential to revolutionize early detection, risk assessment, and targeted therapies in the fight against this devastating disease.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141098119","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}
T. Daniel-Robin, Pradeep Kumar, Bernard Benichou, J. Combal
BACKGROUND Wilson disease (WD) is a progressive, potentially fatal degenerative disease affecting the liver and central nervous system. Given its low prevalence, collecting data on large cohorts of patients with WD is challenging. Comprehensive insurance claims databases provide powerful tools to collect retrospective data on large numbers of patients with rare diseases. AIM To describe patients with WD in the United States, their treatment and clinical outcome, using a large insurance claims database. METHODS This retrospective, longitudinal study was performed in the Clarivate Real-World Data Product database. All patients with ≥ 2 claims associated with an International Classification of Diseases 10 (ICD-10) diagnostic code for WD (E83.01) between 2016 and 2021 were included and followed until death or study end. Patients were divided into two groups by whether or not they were documented to have received a specific treatment for WD. Clinical manifestations, hospitalisations, liver transplantation and death were documented. RESULTS Overall, 5376 patients with an ICD-10 diagnostic code for WD were identified. The mean age at inclusion was 41.2 years and 52.0% were men. A specific WD treatment was documented for 885 patients (15.1%), although the number of patients taking zinc salts may be underestimated due to over the counter purchase. At inclusion, the mean age of patients with a documented treatment was 36.6 ± 17.8 years vs 42.2 ± 19.6 years in those without a documented treatment. During follow-up, 273 patients (5.1%) died. Compared with the American general population, the standardised mortality ratio was 2.19. The proportion of patients with a documented WD-specific treatment who died during follow-up was 4.0% and the mean age at death 52.7 years. CONCLUSION Patients treated for WD in the United States had an excess early mortality compared with the American population. These findings indicate that there is a significant unmet need for effective treatment for WD in the United States.
{"title":"Characteristics of patients with Wilson disease in the United States: An insurance claims database study","authors":"T. Daniel-Robin, Pradeep Kumar, Bernard Benichou, J. Combal","doi":"10.4254/wjh.v16.i5.791","DOIUrl":"https://doi.org/10.4254/wjh.v16.i5.791","url":null,"abstract":"BACKGROUND\u0000 Wilson disease (WD) is a progressive, potentially fatal degenerative disease affecting the liver and central nervous system. Given its low prevalence, collecting data on large cohorts of patients with WD is challenging. Comprehensive insurance claims databases provide powerful tools to collect retrospective data on large numbers of patients with rare diseases.\u0000 AIM\u0000 To describe patients with WD in the United States, their treatment and clinical outcome, using a large insurance claims database.\u0000 METHODS\u0000 This retrospective, longitudinal study was performed in the Clarivate Real-World Data Product database. All patients with ≥ 2 claims associated with an International Classification of Diseases 10 (ICD-10) diagnostic code for WD (E83.01) between 2016 and 2021 were included and followed until death or study end. Patients were divided into two groups by whether or not they were documented to have received a specific treatment for WD. Clinical manifestations, hospitalisations, liver transplantation and death were documented.\u0000 RESULTS\u0000 Overall, 5376 patients with an ICD-10 diagnostic code for WD were identified. The mean age at inclusion was 41.2 years and 52.0% were men. A specific WD treatment was documented for 885 patients (15.1%), although the number of patients taking zinc salts may be underestimated due to over the counter purchase. At inclusion, the mean age of patients with a documented treatment was 36.6 ± 17.8 years vs 42.2 ± 19.6 years in those without a documented treatment. During follow-up, 273 patients (5.1%) died. Compared with the American general population, the standardised mortality ratio was 2.19. The proportion of patients with a documented WD-specific treatment who died during follow-up was 4.0% and the mean age at death 52.7 years.\u0000 CONCLUSION\u0000 Patients treated for WD in the United States had an excess early mortality compared with the American population. These findings indicate that there is a significant unmet need for effective treatment for WD in the United States.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141098260","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}
Due to its complex pathogenesis, treatment of hepatic encephalopathy (HE) continues to be a therapeutic challenge. Of late, gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use. New evidence suggests that gut microbiota plays a significant role in cerebral homeostasis. Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies. Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics, prebiotics and the latest fecal microbiota transplantation (FMT). Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE. However, questions over the appropriate dose, duration and route of administration for best treatment outcome remains unsettled.
由于肝性脑病（HE）的发病机制复杂，其治疗仍然是一项挑战。近来，肠道微生物群因其在各种胃肠道和肝脏疾病发病机制中的作用及其潜在的治疗用途而备受关注。新的证据表明，肠道微生物群在大脑稳态中发挥着重要作用。许多临床和实验研究都记录了 HE 患者肠道微生物群的改变。对高血压患者肠道菌群失调的研究为益生菌、益生元和最新的粪便微生物群移植（FMT）开辟了新的治疗途径。最近的研究表明，FMT 是安全的，而且可以有效改善晚期肝病患者的预后。然而，如何使用适当的剂量、疗程和给药途径才能达到最佳治疗效果，目前仍是一个悬而未决的问题。
{"title":"Fecal microbiota transplantation in the treatment of hepatic encephalopathy: A perspective","authors":"A. Samanta, Moinak Sen Sarma","doi":"10.4254/wjh.v16.i5.678","DOIUrl":"https://doi.org/10.4254/wjh.v16.i5.678","url":null,"abstract":"Due to its complex pathogenesis, treatment of hepatic encephalopathy (HE) continues to be a therapeutic challenge. Of late, gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use. New evidence suggests that gut microbiota plays a significant role in cerebral homeostasis. Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies. Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics, prebiotics and the latest fecal microbiota transplantation (FMT). Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE. However, questions over the appropriate dose, duration and route of administration for best treatment outcome remains unsettled.","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141098423","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}
S. Iacob, Liana Gheorghe, M. Onica, L. Huiban, C. Pop, C. Brisc, Roxana Sirli, C. Ester, C. Brisc, S. Diaconu, Ion Rogoveanu, Larisa Sandulescu, D. Vuletici, A. Trifan
BACKGROUND The global burden of hepatitis D virus (HDV) infection represents a major medical challenge and a public health crisis worldwide. However, there is a lack of accurate data on the epidemiology and risk factors for HDV. Hepatitis B virus (HBV) and HDV coinfection causes the most severe form of viral hepatitis, leading to a higher cumulative incidence of liver-related events compared with HBV monoinfection, including the need for liver transplantation and death. AIM To investigate the epidemiology, natural history, risk factors and clinical management of HBV and HDV coinfection in Romanian patients. METHODS This prospective study was conducted between January and July 2022 in six tertiary gastroenterology and hepatology referral centres in Romania. All consecutive adults admitted for any gastroenterology diagnosis who were HBV-positive were enrolled. Patients with acute hepatitis or incomplete data were excluded. Of the 25390 individuals who presented with any type of gastroenterology diagnosis during the study period, 963 met the inclusion criteria. Testing for anti-HDV antibodies and HDV RNA was performed for all participants. Demographic and risk factor data were collected by investigators using medical charts and patient questionnaires. All data were stored in an anonymized online database during the study. RESULTS The prevalence of HBV was 3.8%; among these patients, the prevalence of HBV/HDV coinfection was 33.1%. The median age of the study population was 54.0 years, and it consisted of 55.1% men. A higher prevalence of HBV/HDV coinfection was observed in patients 50–69 years old. Patients with HBV/HDV coinfection were significantly older than those with HBV monoinfection (P = 0.03). Multivariate multiple regression analysis identified female gender (P = 0.0006), imprisonment (P < 0.0001), older age at diagnosis (P = 0.01) and sexual contact with persons with known viral hepatitis (P = 0.0003) as significant risk factors for HDV. CONCLUSION This study shows that HDV infection among those with HBV remains endemic in Romania and updates our understanding of HDV epidemiology and associated risk factors. It emphasizes the need for systematic screening for HDV infection and collaborative initiatives for controlling and preventing HBV and HDV infection.
{"title":"Prospective study of hepatitis B and D epidemiology and risk factors in Romania: A 10-year update","authors":"S. Iacob, Liana Gheorghe, M. Onica, L. Huiban, C. Pop, C. Brisc, Roxana Sirli, C. Ester, C. Brisc, S. Diaconu, Ion Rogoveanu, Larisa Sandulescu, D. Vuletici, A. Trifan","doi":"10.4254/wjh.v16.i4.640","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.640","url":null,"abstract":"BACKGROUND\u0000 The global burden of hepatitis D virus (HDV) infection represents a major medical challenge and a public health crisis worldwide. However, there is a lack of accurate data on the epidemiology and risk factors for HDV. Hepatitis B virus (HBV) and HDV coinfection causes the most severe form of viral hepatitis, leading to a higher cumulative incidence of liver-related events compared with HBV monoinfection, including the need for liver transplantation and death.\u0000 AIM\u0000 To investigate the epidemiology, natural history, risk factors and clinical management of HBV and HDV coinfection in Romanian patients.\u0000 METHODS\u0000 This prospective study was conducted between January and July 2022 in six tertiary gastroenterology and hepatology referral centres in Romania. All consecutive adults admitted for any gastroenterology diagnosis who were HBV-positive were enrolled. Patients with acute hepatitis or incomplete data were excluded. Of the 25390 individuals who presented with any type of gastroenterology diagnosis during the study period, 963 met the inclusion criteria. Testing for anti-HDV antibodies and HDV RNA was performed for all participants. Demographic and risk factor data were collected by investigators using medical charts and patient questionnaires. All data were stored in an anonymized online database during the study.\u0000 RESULTS\u0000 The prevalence of HBV was 3.8%; among these patients, the prevalence of HBV/HDV coinfection was 33.1%. The median age of the study population was 54.0 years, and it consisted of 55.1% men. A higher prevalence of HBV/HDV coinfection was observed in patients 50–69 years old. Patients with HBV/HDV coinfection were significantly older than those with HBV monoinfection (P = 0.03). Multivariate multiple regression analysis identified female gender (P = 0.0006), imprisonment (P < 0.0001), older age at diagnosis (P = 0.01) and sexual contact with persons with known viral hepatitis (P = 0.0003) as significant risk factors for HDV.\u0000 CONCLUSION\u0000 This study shows that HDV infection among those with HBV remains endemic in Romania and updates our understanding of HDV epidemiology and associated risk factors. It emphasizes the need for systematic screening for HDV infection and collaborative initiatives for controlling and preventing HBV and HDV infection.","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":"140651942","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}
Sanjib Kumar Das, Koushik Sen, Biswatosh Ghosh, Nabanita Ghosh, Krishnendu Sinha, P. Sil
The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications, spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics. Consequently, humans encounter nanomaterials through diverse exposure routes, giving rise to potential health considerations. Noteworthy among these materials are silica and specific metallic nanoparticles, extensively utilized in consumer products, which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver. This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity, drawing insights from both in vitro and in vivo studies. Primarily, the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation. Additionally, we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials, emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.
{"title":"Molecular mechanism of nanomaterials induced liver injury: A review","authors":"Sanjib Kumar Das, Koushik Sen, Biswatosh Ghosh, Nabanita Ghosh, Krishnendu Sinha, P. Sil","doi":"10.4254/wjh.v16.i4.566","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.566","url":null,"abstract":"The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications, spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics. Consequently, humans encounter nanomaterials through diverse exposure routes, giving rise to potential health considerations. Noteworthy among these materials are silica and specific metallic nanoparticles, extensively utilized in consumer products, which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver. This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity, drawing insights from both in vitro and in vivo studies. Primarily, the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation. Additionally, we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials, emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.","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":"140651950","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}
Yang Zheng, Yi-Hui Zheng, Jiahui Wang, Tie-Jian Zhao, Lei Wang, Tianjian Liang
The endoplasmic reticulum (ER) is connected to mitochondria through mitochondria-associated ER membranes (MAMs). MAMs provide a framework for crosstalk between the ER and mitochondria, playing a crucial role in regulating cellular calcium balance, lipid metabolism, and cell death. Dysregulation of MAMs is involved in the development of chronic liver disease (CLD). In CLD, changes in MAMs structure and function occur due to factors such as cellular stress, inflammation, and oxidative stress, leading to abnormal interactions between mitochondria and the ER, resulting in liver cell injury, fibrosis, and impaired liver function. Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD. This paper reviews the literature on the association between mitochondria and the ER, as well as the intervention of traditional Chinese medicine in regulating CLD.
{"title":"Progress of mitochondrial and endoplasmic reticulum-associated signaling and its regulation of chronic liver disease by Chinese medicine","authors":"Yang Zheng, Yi-Hui Zheng, Jiahui Wang, Tie-Jian Zhao, Lei Wang, Tianjian Liang","doi":"10.4254/wjh.v16.i4.494","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.494","url":null,"abstract":"The endoplasmic reticulum (ER) is connected to mitochondria through mitochondria-associated ER membranes (MAMs). MAMs provide a framework for crosstalk between the ER and mitochondria, playing a crucial role in regulating cellular calcium balance, lipid metabolism, and cell death. Dysregulation of MAMs is involved in the development of chronic liver disease (CLD). In CLD, changes in MAMs structure and function occur due to factors such as cellular stress, inflammation, and oxidative stress, leading to abnormal interactions between mitochondria and the ER, resulting in liver cell injury, fibrosis, and impaired liver function. Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD. This paper reviews the literature on the association between mitochondria and the ER, as well as the intervention of traditional Chinese medicine in regulating CLD.","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":"140652038","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 worldwide epidemiology of non-alcoholic fatty liver disease (NAFLD) is showing an upward trend, parallel to the rising trend of metabolic syndrome, owing to lifestyle changes. The pathogenesis of NAFLD has not been fully understood yet. Therefore, NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide. Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication. Lifestyle changes are the main treatment modality. Recently, clinical trial using drugs that target ‘insulin resistance’ which is the driving force behind NAFLD, have shown promising results. Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets. The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively. Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.
{"title":"Metabolic dysfunction-associated steatotic liver disease: A silent pandemic","authors":"A. Samanta, Moinak Sen Sarma","doi":"10.4254/wjh.v16.i4.511","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.511","url":null,"abstract":"The worldwide epidemiology of non-alcoholic fatty liver disease (NAFLD) is showing an upward trend, parallel to the rising trend of metabolic syndrome, owing to lifestyle changes. The pathogenesis of NAFLD has not been fully understood yet. Therefore, NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide. Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication. Lifestyle changes are the main treatment modality. Recently, clinical trial using drugs that target ‘insulin resistance’ which is the driving force behind NAFLD, have shown promising results. Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets. The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively. Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.","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":"140652179","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}
Hepatitis E virus (HEV) is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden. There are eight genotypes of HEV. Among them, the four common ones known to infect humans, genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world. Asymptomatic HEV viremia in the general population, especially among blood donors, has been reported in the literature worldwide. The clinical implications related to this asymptomatic viremia are unclear and need further exploration. Detection of viremia due to HEV genotype 1 infection, apparently among healthy blood donors is also reported without much knowledge about its infection rate. Similarly, while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations, instances of transmission have also been documented albeit without significant clinical consequences. Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern. Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen. In absence of known animal reservoir, where HEV exists in between outbreak is a mystery that needs further exploration. However, occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir. Since HEV genotype 1 infection cannot cause chronicity, subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period. This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it. In view of existing evidence, we propose the concept of “Dynamic Human Reservoir.” Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community. The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature. This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.
戊型肝炎病毒（HEV）在南亚和非洲流行严重，占全球 HEV 总负担的一半。戊型肝炎病毒有八种基因型。其中，已知可感染人类的四种常见基因型中，基因型 1 和基因型 2 盛行于发展中国家，而基因型 3 和基因型 4 则给工业化国家带来了挑战。世界各地都有文献报道普通人群，尤其是献血者中存在无症状 HEV 病毒血症。这种无症状病毒血症的临床影响尚不明确，需要进一步探讨。健康献血者中显然也有因 HEV 基因型 1 感染而检测到病毒血症的报道，但对其感染率却知之甚少。同样，虽然已知 HEV 基因型 3 可通过输血在人体内传播，并已在许多欧洲国家进行了筛查，但也有记录显示存在传播情况，尽管未造成重大临床后果。HEV 基因型 1 在流行地区的流行病学通常呈现消长模式。偶尔发生的零星 HEV 感染常被疫情爆发打断。由于没有已知的动物贮藏库，疫情爆发间歇期 HEV 存在于何处仍是一个谜，需要进一步探索。然而，在流行病学静止期，HEV 基因型 1 导致无症状 HEV 病毒血症的发生，可能说明这种现象可能是一种动态贮藏库。由于 HEV 基因 1 型感染不会导致慢性化，亚临床一过性感染和病毒传播可能是它在流行病间歇期持续存在的原因。这可能与 SARS COVID-19 日冕病毒感染的现象相似，尽管注射了疫苗，但该病毒在全球范围内的流行仍有明显的阶段性高峰和低谷。鉴于现有证据，我们提出了 "动态人类储库 "的概念。静止的亚临床感染 HEV 但没有任何临床后果，随后的传播可能会导致病毒在社区中的存在。无症状 HEV 感染者通过粪便脱落病毒传播 HEV 感染的可能性尚未见文献报道。这一缺失的环节可能是潘多拉盒子的关键，有助于了解基因 1 型占主导地位地区 HEV 感染的流行病学。
{"title":"Subclinical hepatitis E virus genotype 1 infection: The concept of “dynamic human reservoir”","authors":"Ananta Shrestha, Suresh Basnet, Sudhamshu Kc","doi":"10.4254/wjh.v16.i4.506","DOIUrl":"https://doi.org/10.4254/wjh.v16.i4.506","url":null,"abstract":"Hepatitis E virus (HEV) is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden. There are eight genotypes of HEV. Among them, the four common ones known to infect humans, genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world. Asymptomatic HEV viremia in the general population, especially among blood donors, has been reported in the literature worldwide. The clinical implications related to this asymptomatic viremia are unclear and need further exploration. Detection of viremia due to HEV genotype 1 infection, apparently among healthy blood donors is also reported without much knowledge about its infection rate. Similarly, while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations, instances of transmission have also been documented albeit without significant clinical consequences. Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern. Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen. In absence of known animal reservoir, where HEV exists in between outbreak is a mystery that needs further exploration. However, occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir. Since HEV genotype 1 infection cannot cause chronicity, subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period. This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it. In view of existing evidence, we propose the concept of “Dynamic Human Reservoir.” Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community. The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature. This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.","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":"140651946","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}
Dorothy Liu, Mark M Youssef, Josephine A Grace, Marie Sinclair
BACKGROUND 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. AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation. METHODS 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. RESULTS 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. CONCLUSION 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.
{"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
Background: Liver cirrhosis patients admitted to intensive care unit (ICU) have a high mortality rate.
Aim: To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis.
Methods: 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.
Results: 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.
Conclusion: The nomogram has high accuracy in predicting in-hospital mortality. Improving the included predictors may help improve the prognosis of patients.
{"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}
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