Livers最新文献

{"title":"The Pivotal Role of the Membrane-Bound O-Acyltransferase Domain Containing 7 in Non-Alcoholic Fatty Liver Disease","authors":"Preethi Chandrasekaran, Ralf Weiskirchen","doi":"10.3390/livers4010001","DOIUrl":"https://doi.org/10.3390/livers4010001","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD) is a common and prevalent disorder affecting 25 percent of the adults in the United States and 32 percent of adults globally. It is one of the common causes of chronic liver disease characterized by steatosis, which can lead to inflammation, fibrosis, and cirrhosis. NAFLD is strongly associated with obesity and insulin resistance. Multiple genetic variants have been consistently found to be associated with NAFLD; one of them is found in the TMC4-MBOAT7 loci. One variant (rs641738 C>T) within MBOAT7 encoding lysophosphatidyl inositol acyltransferase increases the risk for NAFLD development and triggers hepatic inflammation by regulating arachidonic acid levels. This review provides an overview of the MBOAT7 gene, pathogenesis of NAFLD, understanding the regulation of MBOAT7 and mechanistic link between MBOAT7 and NAFLD. It further summarizes pathophysiologically relevant in vivo and in vitro studies on MBOAT7 and challenges in treating complex NAFLD with recent progress made in the treatment of NAFLD. As such, this review provides useful information on MBOAT7 and NAFLD interrelation, which has the potential of deciphering novel therapeutic targets rather than well-known genetic variants such as PNPLA3 and TM6SF2.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"11 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138955467","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":"The Role of Normothermic Machine Perfusion in Extended Criteria Donor Grafts: A New Direction in Liver Graft Assessment and Preservation","authors":"D. Malkawi, Kush Savsani, Anjelica Alfonso, Seung Duk Lee, Nicholas James, Devanand Sarkar, D. Imai, Aamir A Khan, Amit Sharma, Vinay Kumaran, David A Bruno, A. Cotterell, Marlon Levy","doi":"10.3390/livers3040046","DOIUrl":"https://doi.org/10.3390/livers3040046","url":null,"abstract":"Despite improvements in short-term and long-term outcomes of liver transplant patients, the discrepancy between the number of available livers and transplant candidates continues to increase. The use of expanded criteria donors is one strategy that can be used to address donor shortages. In recent years, preservation strategies such as normothermic machine perfusion (NMP) have been explored to improve the preservation of organs and test their viability before transplantation. We reviewed the recent literature and trials assessing the use of NMP in the setting of liver transplantation. Multiple feasibility trials have demonstrated the clinical prospect of NMP and proved its numerous advantages compared to conventional static cold storage. These advantages include preservation and viability assessment of high-risk donor allografts and grafts that would have otherwise been discarded. This review aims to address the topic of liver NMP in the setting of current and future applications in the setting of extended criteria donor grafts.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"102 45","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138608041","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":"Crosstalk between Lipids and Non-Alcoholic Fatty Liver Disease","authors":"Divyavani Gowda, Chandra Shekar, S. G. B. Gowda, Yifan Chen, Shu-Ping Hui","doi":"10.3390/livers3040045","DOIUrl":"https://doi.org/10.3390/livers3040045","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD), a complex liver disorder that can result in non-alcoholic steatohepatitis, cirrhosis, and liver cancer, is the accumulation of fat in the liver seen in people due to metabolic dysfunction. The pathophysiology of NAFLD is influenced by several variables, such as metabolic dysregulation, oxidative stress, inflammation, and genetic susceptibility. This illness seriously threatens global health because of its link to obesity, insulin resistance, type 2 diabetes, and other metabolic disorders. In recent years, lipid–NAFLD crosstalk has drawn a lot of interest. Through numerous methods, lipids have been connected to the onset and advancement of the illness. The connection between lipids and NAFLD is the main topic of the current review, along with the various therapeutic targets and currently available drugs. The importance of hepatic lipid metabolism in the progression of NAFLD is summarized with the latest results in the field.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"6 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139244966","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":"Posterosuperior Segments of the Liver: Comparison of Short-Term Outcomes between Open and Minimally Invasive Surgery Performed by a Single Surgeon","authors":"M. Giuffrida, M. Iaria, R. Dalla Valle","doi":"10.3390/livers3040044","DOIUrl":"https://doi.org/10.3390/livers3040044","url":null,"abstract":"Laparoscopic posterosuperior liver segment resection is considered technically challenging. This is a retrospective single-center single-surgeon study. The aim of the present study is to investigate the short-term outcomes in a single institution between laparoscopic (LLR) and open (OLR) posterosuperior liver segments (PSSs) resections performed by a single surgeon at Parma University Hospital. The patients were divided into Group 1 (OLR) and Group 2 (LLR) and stratified in two different time settings according to the experience of the surgeon (2010–2015 and 2016–2021). A total 112 patients were included in the study. The 75.3% of OLR were performed in the first period, while 70.2% of LLR were carried out during the second period (2016–2021). The Iwate score was significantly (p < 0.001) higher in OLR group compared to the LLR group. Most of the advanced (77%) and expert (100%) LLRs were performed during the second period. LOS was shorter in LLR group comparing to OLR group (p < 0.001). The postoperative morbidity rate was similar in both groups (p > 0.05). The presence of liver cirrhosis and multiple lesions were identified as risk factors for severe postoperative complications. PSS-LLR has become much safer and more effective due to increasing surgeon’s expertise along with the implementation of cutting-edge technology and innovative surgical techniques.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139270100","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":"The Computed Sinusoid","authors":"Matteo Boninsegna, Peter A. G. McCourt, Christopher Florian Holte","doi":"10.3390/livers3040043","DOIUrl":"https://doi.org/10.3390/livers3040043","url":null,"abstract":"Hepatic sinusoids are lined with thin endothelial cells with transcellular pores, termed fenestrations. These fenestrations are open channels that connect the sinusoidal lumen to the underlying Space of Disse (SoD) and the hepatocytes of the liver parenchyma. Fenestrations range from 0.05 to 0.35 µm in diameter and cover 5–15% of the sinusoidal endothelial surface area, depending on their location along the sinusoids. The direct measurement of hemodynamic parameters, such as pressure and flow velocity, remains challenging within the narrow sinusoids. Such knowledge would increase our understanding of the physiology of the hepatic niche and possible implications in aging or diseases in which fenestrations are reduced or lost. Few simulations of liver blood flow focus on the level of the individual sinusoid, and fewer still include the transcellular pores (fenestrations) of the sinusoidal endothelium. Furthermore, none have included (i) a porosity gradient along the sinusoid wall, modeled using through-all pores rather than a porous medium, (ii) the presence of the SoD, or (iii) lymphatic drainage. Herein, computed fluid dynamics (CFD) simulations were performed using a numerical model with relevant anatomical characteristics (length, diameter, porosity, inlet/outlet pressure, and lymphatic outflow from the portal region of the SoD). The greatest contribution to luminal velocity magnitude and pressure was the overall shape of the vessel. Divergent-radius models yielded velocity magnitudes 1.5–2 times higher than constant-radius models, and pressures were 5–8% lower in the divergent-radius models compared to the constant-radius models. Porosity only modestly contributed to luminal pressure. The luminal velocity magnitude was largely unaffected by the presence or absence of lymphatic drainage. Velocity magnitudes through fenestrations were lower in higher-porosity models (20%) vs. lower-porosity models (5%) across all models (0.4–0.55-fold lower). Velocity magnitudes through the space of Disse were increased 3–4 times via the addition of lymphatic drainage to the models, while pressures were decreased by 6–12%. The flow velocity in the SoD was modified via differences in porosity, while the flow velocity in the lumens of the sinusoids was largely unaffected. The overall shape of the vessel is the single most important factor in the pressure flow behavior of the sinusoidal lumen. The flow rate over hepatocytes and the SoD is modestly affected by the distribution of porosity along the sinusoid and greatly affected by the lymphatic drainage, parameters that would be of interest for modeling the exchange of blood with the hepatic parenchyma.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"39 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135086867","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":"Advancements in Understanding and Treating NAFLD: A Comprehensive Review of Metabolic-Associated Fatty Liver Disease and Emerging Therapies","authors":"Jacob Beiriger, Kashyap Chauhan, Adnan Khan, Taha Shahzad, Natalia Salinas Parra, Peter Zhang, Sarah Chen, Anh Nguyen, Brian Yan, John Bruckbauer, Dina Halegoua-DeMarzio","doi":"10.3390/livers3040042","DOIUrl":"https://doi.org/10.3390/livers3040042","url":null,"abstract":"This paper provides a comprehensive review of the current understanding of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH), focusing on key factors influencing its pathogenesis and emerging therapeutic strategies. This review highlights the growing prevalence of NAFLD and NASH, emphasizing their multifactorial nature. The manuscript identifies various contributors to NAFLD development, including genetic, dietary, and environmental factors, while examining the intricate interplay between these factors and their impact on hepatic lipid metabolism, inflammation, and insulin resistance. Genetic predisposition, dietary fat intake, and excessive fructose consumption are discussed as significant contributors to NAFLD progression. The article emphasizes the lack of a single therapeutic approach and underscores the need for combination strategies. Lifestyle interventions, particularly weight loss through diet and exercise, remain crucial, while pharmacological options like GLP-1 receptor agonists, obeticholic acid, lanifibranor, and resmetirom show promise but require further validation. Bariatric surgery and emerging endoscopic procedures offer potential in eligible patients. In sum, this article underscores the complexity of NAFLD and NASH, addresses key factors influencing pathogenesis, and discusses emerging therapies advocating for a multifaceted approach to this increasingly prevalent and clinically relevant condition.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"56 11","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135539720","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":"Hidden Dangers: Herbal and Dietary Supplement Induced Hepatotoxicity","authors":"Shannan Tujios","doi":"10.3390/livers3040041","DOIUrl":"https://doi.org/10.3390/livers3040041","url":null,"abstract":"Herbal and dietary supplements represent a multi-billion-dollar industry reportedly used by over half of American adults. However, these products are not regulated by the Federal Drug Agency and contain a wide range of contaminants, leading to over 50,000 adverse events each year. This review aims to highlight the widespread use and current regulatory status of herbal and dietary supplements, identify the presentation and diagnostic dilemmas faced with liver injury, and discuss the most common agents implicated in herbal and dietary supplement hepatotoxicity.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"24 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135765825","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":"Therapeutics for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)","authors":"Kamlesh K. Bhopale, Mukund P. Srinivasan","doi":"10.3390/livers3040040","DOIUrl":"https://doi.org/10.3390/livers3040040","url":null,"abstract":"Metabolic dysfunction associated fatty liver disease (MAFLD) has been recently recognized as a new global chronic liver disease entity with non-alcoholic fatty liver disease (NAFLD) associated with overweight/obesity or type 2 diabetes mellitus (T2DM) and evidence of metabolic dysregulation. Due to the rising rates of obesity and diabetes, MAFLD is considered a rapidly emerging chronic liver disease globally. Nearly 25–30% of the global population poses health issues due to MAFLD with a substantial economic burden to societies. Disease progression depends on the persistence of risk factors and etiological agents, from simple steatosis, hepatitis, fibrosis, to cirrhosis, and if untreated, leads to hepatocellular carcinoma. In this review article we summarize various risk and etiological factors, diagnostic techniques, and therapeutic evaluation of pharmacological agents developed for MAFLD. Effective pharmaceutical agents for the treatment of MAFLD (and NAFLD) are lacking, and research is ongoing to search for effective medications in this direction. Currently, pioglitazone is advised for MAFLD patients, whereas Vitamin E is advised for non-diabetic MAFLD patients with ≥F2 non-cirrhosis. Current approaches to disease management emphasize diet control, lifestyle changes, and weight loss. In this review, we summarized the pharmacological agents currently being developed and their current status to treat patients with MAFLD.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"10 17","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136232693","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":"The Evolution of Circulating Biomarkers for Use in Acetaminophen/Paracetamol-Induced Liver Injury in Humans: A Scoping Review","authors":"Mitchell R. McGill, Steven C. Curry","doi":"10.3390/livers3040039","DOIUrl":"https://doi.org/10.3390/livers3040039","url":null,"abstract":"Acetaminophen (APAP) is a widely used drug, but overdose can cause severe acute liver injury. The first reports of APAP hepatotoxicity in humans were published in 1966, shortly after the development of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as the first biomarkers of liver injury as opposed to liver function. Thus, the field of liver injury biomarkers has evolved alongside the growth in APAP hepatotoxicity incidence. Numerous biomarkers have been proposed for use in the management of APAP overdose patients in the intervening years. Here, we comprehensively review the development of these markers from the 1960s to the present day and briefly discuss possible future directions.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"9 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136234795","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":"Pemafibrate Improves Alanine Aminotransferase Levels Independently of Its Lipid-Lowering Effect","authors":"Azuma Watanabe, Ryoko Horigome, Yumiko Nakatsuka, Shuji Terai","doi":"10.3390/livers3040038","DOIUrl":"https://doi.org/10.3390/livers3040038","url":null,"abstract":"Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Pemafibrate, a selective peroxisome-proliferator-activated receptor α modulator (SPPARMα), has been reported to ameliorate liver function among patients with dyslipidemia. However, there are not many reports of the clinical effects of pemafibrate. This study aims to summarize the experience of using pemafibrate and analyze the effects on liver function in patients with dyslipidemia. Methods: One hundred twelve cases of hyperlipidemia receiving pemafibrate 0.2 mg/day were retrospectively enrolled in this study. Age, gender, BMI, complications, concomitant medications, serum parameters (TG, HDL-C, LDL-C, AST, ALT, γGTP, ALP, platelets, M2BPGi, Cre, eGFR, HbA1c, blood glucose level at any time) were investigated and evaluated. Results: Pemafibrate administration significantly improved serum TG and HDL-C, but not in LDL-C. Serum AST, ALT, γGTP, and ALP were also significantly improved. The fib-4 index, a liver fibrosis score, did not significantly change, but M2-BPGi, an index of fibrosis, significantly decreased. No correlation was observed between each lipid parameter and ALT, and ALT decreased independently of the lipid parameters. Conclusions: As we expected, pemafibrate demonstrated a lipid-improving effect without adversely affecting hepatic and renal functions. An unexpected finding was the decrease in ALT that was independent of lipid parameters.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"SE-12 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135405195","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}