V. Prikhodko, T. M. Matuzok, Vadim E. Karev, A. V. Karavaeva, O. M. Spasenkova, Nadezhda V. Kirillova, D. Ivkin, S. V. Okovityi
Non-alcoholic metabolic-associated steatohepatitis (MASH) is a condition characterized by increasingly high prevalence and incidence, and also represents an important unmet medical need when it comes to effective pharmacotherapy. In this work, we aimed to explore the therapeutic possibilities of the synergistic combined use of glycyrrhizinic acid (GA) and phosphatidylcholine (PC) to prevent experimental MASH. Adult C57Bl/6 mice were used to model dietary/toxic MASH and treated orally by either GA (34.3 mg/kg/d) or a GA + PC combination (34.3 + 158.1 mg/kg/d) for 3 months. Animal locomotion, behaviour, short-term memory, physical performance, neuromuscular joint function, blood biochemistry, and oxidative stress marker levels were evaluated, followed by histological examination of the liver, skeletal muscle and sciatic nerve with tissue ammonia and lipid content determination. Real-time polymerase chain reaction was used to measure the relative expression of several pathogenetic transcript markers. GA and PC showed moderate additive synergism in their anti-inflammatory, antioxidant, hypoammonaemic, hypoglycaemic, and pro-cognitive activities. Differential effects of the agents were seen in regard to anxiety- and depression-like behaviour as well as gene expression. Our results indicate partial pharmacological synergism between GA and PC and validate further research of its potential clinical applications.
非酒精性代谢相关性脂肪性肝炎（MASH）是一种发病率和患病率越来越高的疾病，同时也是一种尚未得到有效药物治疗的重要医疗需求。在这项工作中，我们旨在探索联合使用甘草酸（GA）和磷脂酰胆碱（PC）协同预防实验性 MASH 的治疗可能性。成年 C57Bl/6 小鼠被用来建立饮食/毒性 MASH 模型，并接受 GA（34.3 毫克/千克/天）或 GA + PC 组合（34.3 + 158.1 毫克/千克/天）口服治疗 3 个月。对动物的运动、行为、短期记忆、体能、神经肌肉关节功能、血液生化和氧化应激标记物水平进行评估，然后对肝脏、骨骼肌和坐骨神经进行组织学检查，并测定组织氨和脂质含量。采用实时聚合酶链反应测量了几种致病转录标记物的相对表达。GA 和 PC 在抗炎、抗氧化、低血氨、降血糖和促进认知等方面显示出适度的相加协同作用。在焦虑和抑郁样行为以及基因表达方面，这些药物的作用存在差异。我们的研究结果表明了 GA 和 PC 之间的部分药理协同作用，并验证了对其潜在临床应用的进一步研究。
{"title":"Glycyrrhizinic Acid and Phosphatidylcholine Combination as a Preventive Therapy for Experimental Murine Non-Alcoholic Steatohepatitis","authors":"V. Prikhodko, T. M. Matuzok, Vadim E. Karev, A. V. Karavaeva, O. M. Spasenkova, Nadezhda V. Kirillova, D. Ivkin, S. V. Okovityi","doi":"10.3390/livers4010006","DOIUrl":"https://doi.org/10.3390/livers4010006","url":null,"abstract":"Non-alcoholic metabolic-associated steatohepatitis (MASH) is a condition characterized by increasingly high prevalence and incidence, and also represents an important unmet medical need when it comes to effective pharmacotherapy. In this work, we aimed to explore the therapeutic possibilities of the synergistic combined use of glycyrrhizinic acid (GA) and phosphatidylcholine (PC) to prevent experimental MASH. Adult C57Bl/6 mice were used to model dietary/toxic MASH and treated orally by either GA (34.3 mg/kg/d) or a GA + PC combination (34.3 + 158.1 mg/kg/d) for 3 months. Animal locomotion, behaviour, short-term memory, physical performance, neuromuscular joint function, blood biochemistry, and oxidative stress marker levels were evaluated, followed by histological examination of the liver, skeletal muscle and sciatic nerve with tissue ammonia and lipid content determination. Real-time polymerase chain reaction was used to measure the relative expression of several pathogenetic transcript markers. GA and PC showed moderate additive synergism in their anti-inflammatory, antioxidant, hypoammonaemic, hypoglycaemic, and pro-cognitive activities. Differential effects of the agents were seen in regard to anxiety- and depression-like behaviour as well as gene expression. Our results indicate partial pharmacological synergism between GA and PC and validate further research of its potential clinical applications.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140488632","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}
Buket Engin, S. Willis, Sundus Malaikah, J. Sargeant, D. Stensel, C. Jelleyman, G. Ennequin, G. Aithal, Thomas Yates, James A. King
The hepatokine leukocyte cell-derived chemotaxin-2 (LECT2) promotes insulin resistance and hepatic fibrogenesis. In rodents, acute exercise suppresses circulating LECT2; however, human data are lacking. This study compared circulating LECT2 across populations and explored whether acute exercise impacts circulating LECT2. In Part A (n = 43), data were pooled from three experimental studies, regarding the following groups: healthy individuals, individuals with impaired glycaemic regulation (IGR), and individuals with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (T2DM-MASLD). Generalised linear models assessed differences in circulating LECT2 among groups. Part B (n = 20) involved exercise (30 min, 65% peak oxygen uptake) and control (resting) trials in the healthy and IGR groups. Circulating LECT2 was measured before and at 0, 1, 2 and 3 h post-exercise. Generalised estimating equations assessed differences in LECT2 responses to the trials among groups. In Part A, circulating LECT2 levels were 28.7% and 37.3% higher in the IGR and T2DM-MASLD groups, vs. healthy individuals (p ≤ 0.038), with BMI identified as the main predictor (p = 0.008). In Part B, average circulating LECT2 levels were 6.3% higher after exercise vs. in the control (p < 0.001), with similar responses between groups (p = 0.829). In the combined cohort, circulating LECT2 levels were elevated 1–3 h after exercise vs. control (p ≤ 0.009). LECT2 is elevated in people with dysglycaemia, with BMI as a leading predictor. Contrary to previous rodent work, acute exercise augments, rather than suppresses, circulating LECT2 in humans.
{"title":"The Hepatokine Leukocyte Cell-Derived Chemotaxin-2 Is Elevated in People with Impaired Glycaemic Regulation and Augmented by Acute Exercise","authors":"Buket Engin, S. Willis, Sundus Malaikah, J. Sargeant, D. Stensel, C. Jelleyman, G. Ennequin, G. Aithal, Thomas Yates, James A. King","doi":"10.3390/livers4010005","DOIUrl":"https://doi.org/10.3390/livers4010005","url":null,"abstract":"The hepatokine leukocyte cell-derived chemotaxin-2 (LECT2) promotes insulin resistance and hepatic fibrogenesis. In rodents, acute exercise suppresses circulating LECT2; however, human data are lacking. This study compared circulating LECT2 across populations and explored whether acute exercise impacts circulating LECT2. In Part A (n = 43), data were pooled from three experimental studies, regarding the following groups: healthy individuals, individuals with impaired glycaemic regulation (IGR), and individuals with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (T2DM-MASLD). Generalised linear models assessed differences in circulating LECT2 among groups. Part B (n = 20) involved exercise (30 min, 65% peak oxygen uptake) and control (resting) trials in the healthy and IGR groups. Circulating LECT2 was measured before and at 0, 1, 2 and 3 h post-exercise. Generalised estimating equations assessed differences in LECT2 responses to the trials among groups. In Part A, circulating LECT2 levels were 28.7% and 37.3% higher in the IGR and T2DM-MASLD groups, vs. healthy individuals (p ≤ 0.038), with BMI identified as the main predictor (p = 0.008). In Part B, average circulating LECT2 levels were 6.3% higher after exercise vs. in the control (p < 0.001), with similar responses between groups (p = 0.829). In the combined cohort, circulating LECT2 levels were elevated 1–3 h after exercise vs. control (p ≤ 0.009). LECT2 is elevated in people with dysglycaemia, with BMI as a leading predictor. Contrary to previous rodent work, acute exercise augments, rather than suppresses, circulating LECT2 in humans.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139616758","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}
Carolina Larrain, Alejandro Torres-Hernandez, Daniel Brock Hewitt
Artificial Intelligence (AI) can be a useful tool in the management of disease processes such as hepatocellular carcinoma (HCC) as treatment decisions are often complex and multifaceted. AI applications in medicine are expanding with the ongoing advances in AI including more sophisticated machine learning and deep learning processes. In preliminary studies, AI algorithms have demonstrated superiority in predicting the development of HCC compared with standard models. Radiomics, a quantitative method used to extract features from medical imaging, has been applied to numerous liver imaging modalities to aid in the diagnosis and prognostication of HCC. Deep learning methodologies can help us to identify patients at higher likelihood of disease progression and improve risk stratification. AI applications have expanded into the field of surgery as models not only help us to predict surgical outcomes but AI methodologies are also used intra-operatively, in real time, to help us to define anatomic structures and aid in the resection of complex lesions. In this review, we discuss promising applications of AI in the management of HCC. While further clinical validation is warranted to improve generalizability through the inclusion of larger and more diverse populations, AI is expected to play a central role in assisting clinicians with the management of complex disease processes such as HCC.
{"title":"Artificial Intelligence, Machine Learning, and Deep Learning in the Diagnosis and Management of Hepatocellular Carcinoma","authors":"Carolina Larrain, Alejandro Torres-Hernandez, Daniel Brock Hewitt","doi":"10.3390/livers4010004","DOIUrl":"https://doi.org/10.3390/livers4010004","url":null,"abstract":"Artificial Intelligence (AI) can be a useful tool in the management of disease processes such as hepatocellular carcinoma (HCC) as treatment decisions are often complex and multifaceted. AI applications in medicine are expanding with the ongoing advances in AI including more sophisticated machine learning and deep learning processes. In preliminary studies, AI algorithms have demonstrated superiority in predicting the development of HCC compared with standard models. Radiomics, a quantitative method used to extract features from medical imaging, has been applied to numerous liver imaging modalities to aid in the diagnosis and prognostication of HCC. Deep learning methodologies can help us to identify patients at higher likelihood of disease progression and improve risk stratification. AI applications have expanded into the field of surgery as models not only help us to predict surgical outcomes but AI methodologies are also used intra-operatively, in real time, to help us to define anatomic structures and aid in the resection of complex lesions. In this review, we discuss promising applications of AI in the management of HCC. While further clinical validation is warranted to improve generalizability through the inclusion of larger and more diverse populations, AI is expected to play a central role in assisting clinicians with the management of complex disease processes such as HCC.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"57 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139441944","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}
Nicholas Noverati, Jay W. Jun, Vivian Yan, D. Halegoua-DeMarzio, Hie-Won Hann
Chronic hepatitis B is still a disease process that affects millions around the world. Serologies used to diagnose and follow the progression (or resolution) of the disease can be confusing for clinicians. Further, throughout years of treatment, there may be nuances in presentation that complicate management even further. In this short communication, we highlight six themes in response to treatment and outcomes, including complications. We have the unique perspective of following many patients over extended periods of time at our institution, which has brought these themes to life in order that they can be shared with other clinicians who may encounter similar situations.
{"title":"Chronic Hepatitis B: A Summarized Anecdote of Complexities in Natural History, Treatment, and Complications","authors":"Nicholas Noverati, Jay W. Jun, Vivian Yan, D. Halegoua-DeMarzio, Hie-Won Hann","doi":"10.3390/livers4010003","DOIUrl":"https://doi.org/10.3390/livers4010003","url":null,"abstract":"Chronic hepatitis B is still a disease process that affects millions around the world. Serologies used to diagnose and follow the progression (or resolution) of the disease can be confusing for clinicians. Further, throughout years of treatment, there may be nuances in presentation that complicate management even further. In this short communication, we highlight six themes in response to treatment and outcomes, including complications. We have the unique perspective of following many patients over extended periods of time at our institution, which has brought these themes to life in order that they can be shared with other clinicians who may encounter similar situations.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" 29","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139142690","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}
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.
{"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}
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
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.
{"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}
Divyavani Gowda, Chandra Shekar, S. G. B. Gowda, Yifan Chen, Shu-Ping Hui
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.
{"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}
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.
腹腔镜肝后段切除术在技术上具有挑战性。这是一项单中心、单外科医生的回顾性研究。本研究旨在调查帕尔马大学医院（Parma University Hospital）由一名外科医生实施的腹腔镜肝后段切除术（LLR）和开腹肝后段切除术（OLR）的短期疗效。患者被分为第1组（OLR）和第2组（LLR），并根据外科医生的经验在两个不同的时间段（2010-2015年和2016-2021年）进行分层。研究共纳入了 112 名患者。75.3%的OLR在第一阶段进行，而70.2%的LLR在第二阶段（2016-2021年）进行。与 LLR 组相比，OLR 组的岩手评分明显更高（P < 0.001）。大多数高级 LLR（77%）和专家 LLR（100%）是在第二阶段进行的。LLR 组的 LOS 比 OLR 组短（P 0.05）。肝硬化和多发性病变是导致严重术后并发症的危险因素。随着外科医生专业知识的不断提高，以及尖端技术和创新手术技巧的应用，PSS-LLR 已经变得更加安全和有效。
{"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}
Matteo Boninsegna, Peter A. G. McCourt, Christopher Florian Holte
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.
{"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}
Jacob Beiriger, Kashyap Chauhan, Adnan Khan, Taha Shahzad, Natalia Salinas Parra, Peter Zhang, Sarah Chen, Anh Nguyen, Brian Yan, John Bruckbauer, Dina Halegoua-DeMarzio
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.
{"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}
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