Livers Pub Date : 2023-03-01 DOI: 10.3390/livers3010003

Karima Begriche, Clémence Penhoat, Pénélope Bernabeu-Gentey, Julie Massart, Bernard Fromenty

{"title":"Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review.","authors":"Karima Begriche, Clémence Penhoat, Pénélope Bernabeu-Gentey, Julie Massart, Bernard Fromenty","doi":"10.3390/livers3010003","DOIUrl":"https://doi.org/10.3390/livers3010003","url":null,"abstract":"The epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk of adverse events including liver injury. For more than 30 years, a series of experimental and clinical investigations reported or suggested that the common pain reliever acetaminophen (APAP) could be more hepatotoxic in obesity and related metabolic diseases, at least after an overdose. Nonetheless, several investigations did not reproduce these data. This discrepancy might come from the extent of obesity and steatosis, accumulation of specific lipid species, mitochondrial dysfunction and diabetes-related parameters such as ketonemia and hyperglycemia. Among these factors, some of them seem pivotal for the induction of cytochrome P450 2E1 (CYP2E1), which favors the conversion of APAP to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). In contrast, other factors might explain why obesity and NAFLD are not always associated with more frequent or more severe APAP-induced acute hepatotoxicity, such as increased volume of distribution in the body, higher hepatic glucuronidation and reduced CYP3A4 activity. Accordingly, the occurrence and outcome of APAP-induced liver injury in an obese individual with NAFLD would depend on a delicate balance between metabolic factors that augment the generation of NAPQI and others that can mitigate hepatotoxicity.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"3 1","pages":"33-53"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10816740","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}

引用次数: 3

Role of Genetic and Epigenetic Modifications in the Progression of Hepatocellular Carcinoma in Chronic HCV Patients 遗传和表观遗传修饰在慢性HCV患者肝细胞癌进展中的作用

Livers Pub Date : 2023-02-20 DOI: 10.3390/livers3010008

Anum Syyam, Hira Raheem Akbar, Z. Jílková, S. Afzal

{"title":"Role of Genetic and Epigenetic Modifications in the Progression of Hepatocellular Carcinoma in Chronic HCV Patients","authors":"Anum Syyam, Hira Raheem Akbar, Z. Jílková, S. Afzal","doi":"10.3390/livers3010008","DOIUrl":"https://doi.org/10.3390/livers3010008","url":null,"abstract":"Globally, hepatocellular carcinoma (HCC) is a significant cause of mortality and morbidity among chronically infected HCV patients. It is established that HCV is a primary risk factor for HCC progression. The treatment of HCV infection has been transformed by the introduction of DAAs with high rates of virological clearance. The reduction in cirrhosis-related consequences, particularly HCC, is the long-term objective of DAAs therapy for HCV. Although the risk of developing HCC is decreased in HCV patients who achieve a disease-sustaining virological response, these patients are nevertheless at risk, especially those with severe fibrosis and cirrhosis. Previous studies have shown that HCV induce several mechanisms of hepatocarcinogenesis in the host’s hepatic micro- and macro-environment, which leads to HCC progression. In an HCV-altered environment, compensatory liver regeneration favors chromosomal instability and irreversible alterations, which encourage hepatocyte neoplastic transformation and the development of malignant clones. These mechanisms involve a series of genetic and epigenetic modifications including host genetic factors, dysregulation of several signaling pathways, histone, and DNA modifications including methylation and acetylation. This review highlights the genetic and epigenetic factors that lead to the development of HCC in chronic HCV-infected individuals and can be targeted for earlier HCC diagnosis and prevention.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41533962","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}

引用次数: 0

Liver Transplantation and dd-cfDNA: A Small Solution for a Big Problem 肝移植和dd-cfDNA:大问题的小解决方案

Livers Pub Date : 2023-02-20 DOI: 10.3390/livers3010007

E. Avramidou, S. Vasileiadou, N. Antoniadis, G. Katsanos, Athanasios Kofinas, K. Karakasi, G. Tsoulfas

引用次数: 0

Bio-Artificial Liver Support System: A Prospective Future Therapy 生物人工肝支持系统：一种前瞻性的未来治疗方法

Livers Pub Date : 2023-02-09 DOI: 10.3390/livers3010006

C. Jasirwan, A. Muradi, R. Antarianto

{"title":"Bio-Artificial Liver Support System: A Prospective Future Therapy","authors":"C. Jasirwan, A. Muradi, R. Antarianto","doi":"10.3390/livers3010006","DOIUrl":"https://doi.org/10.3390/livers3010006","url":null,"abstract":"Whether acute or chronic, liver failure is a state of liver dysfunction that can progress to multiorgan failure. Mortality in liver failure patients is approximately 80–90% and is caused by detoxification failure, which triggers other immediate complications, such as encephalopathy, coagulopathy, jaundice, cholestasis, and acute kidney failure. The ideal treatment for liver failure is liver transplantation, but the long waiting period for the right donor match causes unavoidable deaths in most patients. Therefore, new therapies, such as tissue engineering, hepatocyte transplantation, and stem cells, are now being studied to anticipate the patient’s condition while waiting for liver transplantation. This literature review investigated the effectiveness of some bio-artificial liver support systems using review methods systematically from international publication sites, including PubMed, using keywords, such as bio-artificial liver, acute and chronic liver failure, extracorporeal liver support system (ECLS), MARS, single-pass albumin dialysis (SPAD). Artificial and bioartificial liver systems can show specific detoxification abilities and pathophysiological improvements in liver failure patients but cannot reach the ideal criteria for actual liver function. The liver support system must provide the metabolic and synthetic function as in the actual liver while reducing the pathophysiological changes in liver failure. Aspects of safety, cost efficiency, and practicality are also considered. Identifying the technology to produce high-quality hepatocytes on a big scale is essential as a medium to replace failing liver cells. An increase in detoxification capacity and therapeutic effectiveness must also focus on patient survival and the ability to perform liver transplantation.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49607034","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}

引用次数: 1

Acknowledgment to the Reviewers of Livers in 2022 对2022年《肝脏》评审者的感谢

Livers Pub Date : 2023-01-19 DOI: 10.3390/livers3010005

引用次数: 0

Lights and Shadows of Paracentesis: Is an Ultrasound Guided Approach Enough to Prevent Bleeding Complications? 穿刺的光影：超声引导的方法足以预防出血并发症吗？

Livers Pub Date : 2023-01-16 DOI: 10.3390/livers3010004

M. Patturelli, L. Pignata, P. Venetucci, M. Guarino

引用次数: 0

Metabolic Associated Fatty Liver Disease as a Risk Factor for the Development of Central Nervous System Disorders 代谢相关脂肪肝是中枢神经系统疾病发展的危险因素

Livers Pub Date : 2023-01-05 DOI: 10.3390/livers3010002

Sayuri Yoshikawa, Kurumi Taniguchi, Haruka Sawamura, Yuka Ikeda, Tomoko Asai, Ai Tsuji, Satoru Matsuda

引用次数: 2

Support Needs and Coping Strategies in Non-Alcoholic Fatty Liver Disease (NAFLD): A Multidisciplinary Approach to Potential Unmet Challenges beyond Pharmacological Treatment 非酒精性脂肪性肝病(NAFLD)的支持需求和应对策略:药物治疗之外潜在未满足挑战的多学科方法

Livers Pub Date : 2022-12-23 DOI: 10.3390/livers3010001

S. Shea, C. Lionis, L. Atkinson, C. Kite, Lukasz Lagojda, Surinderjeet S. Chaggar, I. Kyrou, H. Randeva

{"title":"Support Needs and Coping Strategies in Non-Alcoholic Fatty Liver Disease (NAFLD): A Multidisciplinary Approach to Potential Unmet Challenges beyond Pharmacological Treatment","authors":"S. Shea, C. Lionis, L. Atkinson, C. Kite, Lukasz Lagojda, Surinderjeet S. Chaggar, I. Kyrou, H. Randeva","doi":"10.3390/livers3010001","DOIUrl":"https://doi.org/10.3390/livers3010001","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD) is the most frequently occurring chronic liver disease, affecting approximately 25–30% of the adult general population worldwide. NAFLD reflects excess hepatic accumulation of fat in the absence of increased alcohol intake, and, due to its close association with obesity, is frequently referred to as the ‘hepatic manifestation’ of metabolic syndrome. Indeed, a high percentage of individuals with NAFLD present with a combination of the cardio-metabolic comorbidities that are associated with the metabolic syndrome. In addition to its well-established link with the metabolic syndrome and increased risk for cardiovascular disease, NAFLD has also been associated with certain mental health issues (e.g., depression and stress). Although this link is now being increasingly recognized, there are still unmet needs regarding the holistic management of patients with NAFLD, which could further contribute to feelings of social isolation and loneliness. The latter conditions are also increasingly reported to pose a substantial risk to overall health and quality of life. To date, there is limited research that has explored these issues among patients with NAFLD, despite existing data which indicate that perceived loneliness and isolation may pose an additional health risk. Notably, many features associated with NAFLD have been related to these concepts, such as perceived stigma, fatigue, stress, and confusion regarding this diagnosis. As such, this review aimed to assess such potential problems faced by patients with NAFLD, and to explore the possibility of unmet support needs which could lead to perceived social isolation. Moreover, the importance of a compassionate approach towards such patients is discussed, together with potential coping strategies. Future research directions and the need for a multidisciplinary approach are also highlighted.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43905477","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}

引用次数: 2

A Simple Algorithm for Semiquantitative Analysis of Scored Histology Data in the R Environment, on the Example of Murine Non-Alcoholic Steatohepatitis Pharmacotherapy 一种在R环境中对评分组织学数据进行半定量分析的简单算法，以小鼠非酒精性脂肪性肝炎药物治疗为例

Livers Pub Date : 2022-12-09 DOI: 10.3390/livers2040031

V. Prikhodko, V. Karev, Yuriy I. Sysoev, D. Ivkin, S. Okovityi

{"title":"A Simple Algorithm for Semiquantitative Analysis of Scored Histology Data in the R Environment, on the Example of Murine Non-Alcoholic Steatohepatitis Pharmacotherapy","authors":"V. Prikhodko, V. Karev, Yuriy I. Sysoev, D. Ivkin, S. Okovityi","doi":"10.3390/livers2040031","DOIUrl":"https://doi.org/10.3390/livers2040031","url":null,"abstract":"Despite the high medical and socioeconomic burden of non-alcoholic fatty liver disease (NAFLD), treatments that could effectively reduce histological liver damage in this condition are lacking. As providing only qualitative data is a major limitation of most histological scoring systems, we aimed to develop a simple and straightforward algorithm for semiquantitative analysis of scored histology data using the extended Fisher’s exact test in the R environment. As an illustrative example, we used the effects of L-ornithine L-aspartate (LOLA) and empagliflozin (EMPA) in a 3-month chemical/dietary murine model of NAFLD. 100 C57Bl/6 mice were randomized into 4 groups: Intact (n = 10), Control (NAFLD; n = 30), LOLA (NAFLD + 1.5 g·kg−1 b.w./d LOLA orally; n = 30), and EMPA (NAFLD + 10 mg·kg−1 b.w./d EMPA orally; n = 30). LOLA reduced hepatitis activity (p < 0.05), cholestasis, necrosis, and fibrosis severity (p < 0.01), and EMPA prevented necrosis (p < 0.05) and reduced fibrosis severity (p < 0.01). The statistical approach we suggest can be used as a simple complementary tool for exploratory analysis of scored histology data.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42242241","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}

引用次数: 0

One Carbon Metabolism and S-Adenosylmethionine in Non-Alcoholic Fatty Liver Disease Pathogenesis and Subtypes. 1碳代谢和s -腺苷蛋氨酸在非酒精性脂肪肝发病机制和亚型中的作用。

Livers Pub Date : 2022-12-01 DOI: 10.3390/livers2040020

David Fernández-Ramos, Fernando Lopitz-Otsoa, Oscar Millet, Cristina Alonso, Shelly C Lu, José M Mato

{"title":"One Carbon Metabolism and S-Adenosylmethionine in Non-Alcoholic Fatty Liver Disease Pathogenesis and Subtypes.","authors":"David Fernández-Ramos, Fernando Lopitz-Otsoa, Oscar Millet, Cristina Alonso, Shelly C Lu, José M Mato","doi":"10.3390/livers2040020","DOIUrl":"https://doi.org/10.3390/livers2040020","url":null,"abstract":"One carbon metabolism (1CM) can be defined as the transfer of a carbon unit from one metabolite to another and its replenishment by different sources of labile methyl-group nutrients: primarily choline, methionine, betaine, and serine. This flow of carbon units allows the biosynthesis of nucleotides, amino acids, formylated methionyl-tRNA, polyamines, glutathione, phospholipids, detoxification reactions, maintenance of the redox status and the concentration of NAD, and methylation reactions including epigenetic modifications. That is, 1CM functions as a nutrient sensor and integrator of cellular metabolism. A critical process in 1CM is the synthesis of S-adenosylmethionine (SAMe), the source of essentially all the hundreds of millions of daily methyl transfer reactions in a cell. This versatility of SAMe imposes a tight control in its synthesis and catabolism. Much of our knowledge concerning 1CM has been gained from studies in the production and prevention of nonalcoholic fatty liver disease (NAFLD). Here, we discuss in detail the function of the most important enzymes for their quantitative contribution to maintaining the flux of carbon units through 1CM in the liver and discuss how alterations in their enzymatic activity contribute to the development of NAFLD. Next, we discuss NAFLD subtypes based on serum lipidomic profiles with different risk of cardiovascular disease. Among the latter, we highlight the so-called subtype A for its serum lipidomic profile phenocopying that of mice deficient in SAMe synthesis and because its high frequency (about 50% of the NAFLD patients).","PeriodicalId":74083,"journal":{"name":"Livers","volume":"2 4","pages":"243-257"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9751790","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}

引用次数: 2

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