Liver Research最新文献

{"title":"Prolonged existence of SARS-CoV-2 RNAs in the extracellular vesicles of respiratory specimens from patients with negative reverse transcription-polymerase chain reaction","authors":"P. Debishree Subudhi ,&nbsp;Sheetalnath Rooge ,&nbsp;Chhagan Bihari ,&nbsp;Swati Thangariyal ,&nbsp;Sivang Goswami ,&nbsp;Reshu Agarwal ,&nbsp;Savneet Kaur ,&nbsp;Ekta Gupta ,&nbsp;Sukriti Baweja","doi":"10.1016/j.livres.2023.09.004","DOIUrl":"https://doi.org/10.1016/j.livres.2023.09.004","url":null,"abstract":"<div><h3>Background and aim</h3><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily in the respiratory tract, particularly in patients with underlying comorbidities. This study aimed to investigate the presence of the virus inside the extracellular vesicles (EVs) in patients with and without chronic liver disease (CLD).</p></div><div><h3>Methods</h3><p>Eighty patients with positive SARS-CoV-2, including twenty-four patients with CLD and fifty-six patients without CLD, and five healthy controls with negative SARS-CoV-2 were enrolled. Nasal swab specimens were tested for the detection of SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR). Patients with coronavirus disease 2019 (COVID-19) were followed up on days 7 and 14. Nasal swab, collected in viral transport media (VTM), and plasma samples were investigated at each time point. EVs were isolated from the nasal swabs (collected in VTM) and plasma using differential ultracentrifugation and estimated at each time point. The transmission or replication by the EVs was assessed in Vero E6 cells.</p></div><div><h3>Results</h3><p>In patients with baseline RT-PCR positive, SARS-CoV-2 RNAs inside the EVs were found in 68/80 (85%) patients with higher viral load in the nasal swabs than in the EVs (cycle threshold (Ct) value, 23.4 ± 5.7 <em>vs</em>. 30.3 ± 5.0, <em>P</em> &lt; 0.001). On follow-up at day 7, of the 32 patients negative for COVID-19, 15 (46.9%) had virus persistence in the EVs (Ct value, 30.7 ± 2.7), and on day 14, of the 56 patients with negative SARS-CoV-2, 16 patients (28.6%) had positive SARS-CoV-2 RNAs in the EVs (Ct value, 31.4 ± 3.0). The mean viral load decreased on days 7 and 14 compared to baseline in the nasal swabs (<em>P</em> &lt; 0.001) but not in the EVs. Additionally, SARS-CoV-2 RNAs were undetectable in the plasma, but 12.5% of patients were positive in the plasma EVs. Significantly prolonged and high viral load was found in the EVs on day 14 in COVID-19 patients combined with CLD compared with COVID-19 patients (<em>P</em> = 0.0004). We found significant higher levels of EV-associated with endothelial cells and hepatocytes in the COVID-19 + CLD group than COVID-19 group (<em>P</em> = 0.032 and <em>P</em> = 0.002, respectively), suggesting more endothelial cells and hepatocytes cellular injury in liver disease patients with COVID-19. Interestingly, we also found EVs could transmit SARS-CoV-2 RNAs into Vero E6 cells at 24 h post-infection.</p></div><div><h3>Conclusions</h3><p>The identification of SARS-CoV-2 RNAs in the EVs in patients with negative RT-PCR indicates the persistence of infection and likely recurrence of the infection. It is suggestive of another route of transmission as EVs harbor SARS-CoV-2 RNAs. EV-associated RNAs may determine the ongoing inflammation and clinical course of subjects with undetectable SARS-CoV-2 virus and this may have relevance to better management of patients with CLD.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 228-236"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50203026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 associated liver injury: An updated review on the mechanisms and management of risk groups","authors":"Yue Shi ,&nbsp;Mina Wang ,&nbsp;Liqun Wu ,&nbsp;Xuexin Li ,&nbsp;Zehuan Liao","doi":"10.1016/j.livres.2023.07.001","DOIUrl":"10.1016/j.livres.2023.07.001","url":null,"abstract":"<div><p>Coronavirus disease 2019 (COVID-19) has been associated with various liver injury cases worldwide. To date, the prevalence, mechanism, clinical manifestations, diagnosis, and outcomes of COVID-19-induced liver injury in various at-risk groups are not well defined. Liver injury may arise in the prevention and treatment of COVID-19 from direct causes such as viral infection and indirect causes such as systemic inflammation, hypoxic changes, and drugs that exacerbate any pre-existing liver disease. Studies have found that patients with underlying liver disease are at higher risk of COVID-19-induced liver injury. Certain condition of cardiopulmonary and metabolic diseases and vulnerable stages in lifespan may also involve in the development of COVID-19-induced liver injury. This review summarized studies of COVID-19-induced liver injury in different at-risk groups regarding their clinical characteristics, parameters, and correlations of the severity with these indicators and signs as well as potential treatment suggestions, to increase attention to physiological and pathological conditions and continue liver function monitoring as they can help in strengthening early supportive treatment and reducing the incidence of adverse outcomes.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 207-215"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44789961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-molecule chemical probes for the potential therapeutic targets in alcoholic liver diseases","authors":"Ashish Dogra ,&nbsp;Feng Li","doi":"10.1016/j.livres.2023.09.001","DOIUrl":"https://doi.org/10.1016/j.livres.2023.09.001","url":null,"abstract":"<div><p>Alcoholic liver disease (ALD) encompasses a range of conditions resulting from prolonged and excessive alcohol consumption, causing liver damage such as alcoholic fatty liver, inflammation, fibrosis, and cirrhosis. Alcohol consumption contributes to millions of deaths each year. So far, the effective treatments for ALD are limited. To date, the most effective treatment for ALD is still prevention by avoiding excessive alcohol consumption, and only few specialized medicines are in the market for the treatment of patients suffering from ALD. Small molecules targeting various pathways implicated in ALD pathogenesis can potentially be used for effective therapeutics development. In this review, we provide a concise overview of the latest research findings on potential therapeutic targets, specifically emphasizing small-molecule interventions for the treatment and prevention of ALD.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 177-188"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50202257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum regarding missing declaration of competing interest statements in previously published articles","authors":"","doi":"10.1016/j.livres.2023.08.002","DOIUrl":"https://doi.org/10.1016/j.livres.2023.08.002","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 272-273"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50203028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal use of red cell volume distribution width-to-platelet ratio to exclude cirrhosis in patients with chronic hepatitis B","authors":"Hongsheng Yu ,&nbsp;Chao Li ,&nbsp;Mingkai Li ,&nbsp;Zixi Liang ,&nbsp;Abdukyamu Smayi ,&nbsp;Bilan Yang ,&nbsp;Kodjo-Kunale Abassa ,&nbsp;Jianning Chen ,&nbsp;Bin Wu ,&nbsp;Yidong Yang","doi":"10.1016/j.livres.2023.08.006","DOIUrl":"10.1016/j.livres.2023.08.006","url":null,"abstract":"<div><h3>Background and aims</h3><p>Hepatitis B virus (HBV) infection is a major public health issue worldwide as it may cause serious liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Ruling out cirrhosis is important when treating chronic hepatitis B (CHB). The aim of this study was to compare the performance of the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis score based on four factors (FIB-4), and red cell volume distribution width-to-platelet ratio (RPR) in diagnosing liver fibrosis stages and to identify new cut-off values to rule out cirrhosis.</p></div><div><h3>Methods</h3><p>Between 2005 and 2020, 2182 eligible individuals who underwent liver biopsy were randomly assigned to derivation and validation cohorts in a 6:4 ratio. A grid search was applied to identify optimal cut-off values with a sensitivity of &gt;90% and a negative predictive value (NPV) of at least 95%.</p></div><div><h3>Results</h3><p>Overall, 1309 individuals (175 patients with cirrhosis) were included in the derivation dataset, and 873 (117 patients with cirrhosis) were included in the validation cohort. The area under the receiver operating characteristic curve of RPR for diagnosing cirrhosis was 0.821, which was comparable to that of APRI (0.818, <em>P</em> = 0.7905) and FIB-4 (0.803, <em>P</em> = 0.2395). When applying an RPR of 0.06, cirrhosis was correctly identified with a sensitivity of 93.1% and an NPV of 97.1%, while it misclassified 12 of 175 (6.9%) patients in the derivation cohort. In the validation cohort, RPR had a sensitivity and NPV of 97.4% and 99.0%, respectively, and only misclassified 3 of 117 (2.6%) patients. Subgroup analysis indicated that the new RPR cut-off value performed more consistently than that of APRI and FIB-4 in all subgroups.</p></div><div><h3>Conclusion</h3><p>A recently established cut-off value for RPR (≤0.06) was validated and was more effective than APRI and FIB-4 in excluding patients with cirrhosis due to a higher sensitivity and NPV and a lower misclassification rate. This simple and dependable test could have significant clinical implications in identifying patients who require monitoring for portal hypertension-associated complications and screening for HCC, particularly in middle and primary healthcare settings.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 244-251"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48337729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinoic acid signaling in fatty liver disease","authors":"Fathima N. Cassim Bawa,&nbsp;Yanqiao Zhang","doi":"10.1016/j.livres.2023.07.002","DOIUrl":"10.1016/j.livres.2023.07.002","url":null,"abstract":"<div><p>Retinoic acid (RA) is a metabolite of vitamin A and is essential for development and growth as well as cellular metabolism. Through genomic and nongenomic actions, RA regulates a variety of physiological functions. Dysregulation of RA signaling is associated with many diseases. Targeting RA signaling has been proven valuable to human health. All-trans<em>-</em>RA (AtRA) and anthracycline-based chemotherapy are the standard treatment of acute promyelocytic leukemia (APL). Both human and animal studies have shown a significant relationship between RA signaling and the development and progression of non-alcoholic fatty liver disease (NAFLD). In this review article, we will first summarize vitamin A metabolism and then focus on the role of RA signaling in NAFLD. AtRA inhibits the development and progression of NAFLD by regulating lipid metabolism, inflammation, thermogenesis, etc.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 189-195"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44839164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian rhythms and inflammatory diseases of the liver and gut","authors":"Jessica M. Ferrell","doi":"10.1016/j.livres.2023.08.004","DOIUrl":"10.1016/j.livres.2023.08.004","url":null,"abstract":"<div><p>Circadian rhythms play a central role in maintaining metabolic homeostasis and orchestrating inter-organ crosstalk. Research evidence indicates that disruption to rhythms, which occurs through shift work, chronic sleep disruption, molecular clock polymorphisms, or the consumption of alcohol or high-fat diets, can influence inflammatory status and disrupt timing between the brain and periphery or between the body and the external environment. Within the liver and gut, circadian rhythms direct the timing of glucose and lipid homeostasis, bile acid and xenobiotic metabolism, and nutrient absorption, making these systems particularly susceptible to the effects of disrupted rhythms. In this review, the impacts of circadian disruption will be discussed with emphasis on inflammatory conditions affecting the liver and gut, and the potential for chronotherapy for these conditions will be explored.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 196-206"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46272795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-alcoholic fatty liver disease: Dietary and nutraceutical approaches","authors":"Ludovica Cogorno ,&nbsp;Elena Formisano ,&nbsp;Andrea Vignati ,&nbsp;Amalia Prigione ,&nbsp;Antonio Tramacere ,&nbsp;Consuelo Borgarelli ,&nbsp;Samir Giuseppe Sukkar ,&nbsp;Livia Pisciotta","doi":"10.1016/j.livres.2023.08.005","DOIUrl":"https://doi.org/10.1016/j.livres.2023.08.005","url":null,"abstract":"<div><p>Non-alcoholic fatty liver disease (NAFLD), defined as the presence of fat accumulation in imaging or histology in more than 5% of hepatocytes and exclusion of other causes for secondary hepatic fat accumulation, is one of the major causes of chronic liver disease worldwide. Metabolic syndrome is associated with an increased risk of progression from NAFLD to non-alcoholic steatohepatitis (NASH), fibrosis, and forthcoming liver failure. Also, genetic predisposition contributes to the risk of NAFLD development. This review explores the role of diets and nutraceuticals in delaying the development and the evolution of NAFLD to chronic liver disease. The Mediterranean diet, high-protein diet, low-carbohydrate/high-fat diet, high-carbohydrate/low-fat diet, and intermittent fasting are the dietary approaches investigated given the presence of relevant literature data. Moreover, this review focused on nutraceuticals with proven efficacy in ameliorating NAFLD and grouped them into four different categories: plant-based nutraceuticals (<em>Ascophyllum nodosum</em> and <em>Fucus vesiculosus</em>, <em>Silymarin</em>, Berberine, Curcumin, Resveratrol, <em>Nigella sativa</em>, Quercetin), vitamin-like substances (vitamin E, vitamin D, vitamin C, coenzyme Q10, inositol), fatty acids (omega-3), and microbiota-management tools (probiotics).</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 216-227"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50203024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial transformations of bile acids and their receptors in the regulation of metabolic dysfunction-associated steatotic liver disease","authors":"Yuhua Gao ,&nbsp;Jun Lin ,&nbsp;Chuan Ye ,&nbsp;Siqi Guo ,&nbsp;Changtao Jiang","doi":"10.1016/j.livres.2023.09.002","DOIUrl":"https://doi.org/10.1016/j.livres.2023.09.002","url":null,"abstract":"<div><p>Bile acids (BAs) play important roles in the digestion of dietary fats and molecular signal transduction, and modulation of the BA composition usually affects the progression of metabolic diseases. While the liver produces primary BAs, the gut microbiota modifies these products into various forms that greatly increase their diversity and biological functions. Mechanistically, BAs can regulate their own metabolism and transport as well as other key aspects of metabolic processes via dedicated BA receptors. Disruption of BA transport and homeostasis leads to the progression of liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). Here, we summarize the microbial transformations of BAs and their downstream signaling in the development of metabolic diseases and present new insights into novel therapeutic strategies targeting BA pathways that may contribute to these diseases.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 165-176"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50203025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of high throughput spectral flow cytometry for immune cell profiling in mouse liver","authors":"Grayson W. Way ,&nbsp;Hongkun Lu ,&nbsp;Xuan Wang ,&nbsp;Derrick Zhao ,&nbsp;Carmen Camarena ,&nbsp;Devanand Sarkar ,&nbsp;Rebecca K. Martin ,&nbsp;Huiping Zhou","doi":"10.1016/j.livres.2023.08.001","DOIUrl":"10.1016/j.livres.2023.08.001","url":null,"abstract":"<div><p>The liver plays an important role in both metabolism and immunity. Disruption of the hepatic immune microenvironment is closely associated with various liver diseases. To gain a better understanding of how different types of immune cells contribute to the progression of liver diseases, it is crucial to thoroughly characterize hepatic immune cells. Although direct digestion of liver tissue is a relatively simple method for isolating immune cells, it often induces excessive hepatocyte death, which causes a release of intracellular components that leads to the activation of stress responses and injury in the surrounding cells. This injury can lead to excessive death in the hepatic immune cells, making isolation and accurate characterization of the immune profile challenging, especially in diseased livers. The method described here addresses these challenges by utilizing Phosphate buffered saline (PBS) and digestion buffer perfusions to eliminate contaminating blood cells, ensure a pure hepatic immune population, and minimize hepatic immune cell death. Further <em>ex vivo</em> digestion of the liver enables the isolation of the immune cells from the hepatic tissues and the generation of a single-cell suspension that can be stained for spectral flow cytometry. To enhance intracellular cytokine detection and maintain signaling under different physiological and pathological conditions, this protocol uses an <em>in vivo</em> administration of Brefeldin A, a less toxic inhibitor of cytokine secretion. This <em>in vivo</em> administration of Brefeldin A allows for a more accurate representation of the immune cell function and cytokine expression compared to the traditionally used <em>ex vivo</em> Brefeldin A administration. A comprehensive spectral flow cytometry panel, comprising extracellular and intracellular staining, is used for deep immunophenotyping and immune cell effector function profiling. While this protocol is specifically designed for liver digestion of <em>Mdr2</em> knockout mice (a model for primary sclerosing cholangitis) and flow cytometry staining, it can also be applied to other liver diseases and sensitive tissues.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"7 3","pages":"Pages 263-271"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46914746","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}