FYB2 (also known as C1orf168 or ARAP) is an adaptor protein involved in T-cell receptor (TCR)-mediated T-cell activation and adhesion. However, the correlation of FYB2 with prognosis and cancer needs further investigation. In this study, we analyzed the expression levels of FYB2 in hepatocellular carcinoma (LIHC) tumor tissues and correlated it with the pathological stages, survival outcomes, and tumor grades. We found that the expression of FYB2 was significantly downregulated in LIHC. Low FYB2 level leading to weak survival outcomes is linked with advanced tumor grades and elevated pathological stages. Cox regression analysis showed that FYB2 and AJCC-M stages can be used as independent prognostic factors for LIHC. GSEA analysis revealed that FYB2 would be notably correlated with the cellular metabolism-related pathways and particularly involved in the regulation of cancer-related pathways. Single-cell transcriptome analysis revealed that FYB2-positive cells were mainly distributed in hepatocytes, and compared with other cells, the upregulated genes of these cells were mainly enriched in metabolism-related functions. The results of the spatial transcriptome revealed that the expression of FYB2 in the adjacent area was higher than in the tumor area. These results showed that FYB2 is likely to be a new prognostic biomarker in LIHC and would help provide individual treatment decisions for LIHC patients.
{"title":"FYB2 Is a Potential Prognostic Biomarker for Hepatocellular Carcinoma","authors":"Yifang Qu, X. Shen, Xinpei Yuan, Bing Lu","doi":"10.3390/livers2040027","DOIUrl":"https://doi.org/10.3390/livers2040027","url":null,"abstract":"FYB2 (also known as C1orf168 or ARAP) is an adaptor protein involved in T-cell receptor (TCR)-mediated T-cell activation and adhesion. However, the correlation of FYB2 with prognosis and cancer needs further investigation. In this study, we analyzed the expression levels of FYB2 in hepatocellular carcinoma (LIHC) tumor tissues and correlated it with the pathological stages, survival outcomes, and tumor grades. We found that the expression of FYB2 was significantly downregulated in LIHC. Low FYB2 level leading to weak survival outcomes is linked with advanced tumor grades and elevated pathological stages. Cox regression analysis showed that FYB2 and AJCC-M stages can be used as independent prognostic factors for LIHC. GSEA analysis revealed that FYB2 would be notably correlated with the cellular metabolism-related pathways and particularly involved in the regulation of cancer-related pathways. Single-cell transcriptome analysis revealed that FYB2-positive cells were mainly distributed in hepatocytes, and compared with other cells, the upregulated genes of these cells were mainly enriched in metabolism-related functions. The results of the spatial transcriptome revealed that the expression of FYB2 in the adjacent area was higher than in the tumor area. These results showed that FYB2 is likely to be a new prognostic biomarker in LIHC and would help provide individual treatment decisions for LIHC patients.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44767772","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}
Chronic liver diseases (CLDs) that lead to hepatic fibrosis, cirrhosis, and/or hepatocellular carcinoma (HCC) have become a major cause of illness and death worldwide. The main causative factors for CLDs are chronic viral infections, excessive alcohol consumption, non-alcoholic fatty liver disease (NAFLD), and cholestatic diseases. The primary approach to managing cirrhosis should be removing the causative agent, and the secondary approach should address fibrogenesis. Liver cancer is also a leading cause of death worldwide, and many therapeutic approaches exist to treat the disease. However, liver transplantation remains the last treatment option for cirrhosis and liver cancer. Thus, this review discusses the pathophysiology of liver fibrosis, its progression to cirrhosis and HCC, and current therapeutic options available to treat the diseases with potential therapeutic options that will be available in the near future.
{"title":"Liver Fibrosis, Liver Cancer, and Advances in Therapeutic Approaches","authors":"Indu G. Rajapaksha","doi":"10.3390/livers2040028","DOIUrl":"https://doi.org/10.3390/livers2040028","url":null,"abstract":"Chronic liver diseases (CLDs) that lead to hepatic fibrosis, cirrhosis, and/or hepatocellular carcinoma (HCC) have become a major cause of illness and death worldwide. The main causative factors for CLDs are chronic viral infections, excessive alcohol consumption, non-alcoholic fatty liver disease (NAFLD), and cholestatic diseases. The primary approach to managing cirrhosis should be removing the causative agent, and the secondary approach should address fibrogenesis. Liver cancer is also a leading cause of death worldwide, and many therapeutic approaches exist to treat the disease. However, liver transplantation remains the last treatment option for cirrhosis and liver cancer. Thus, this review discusses the pathophysiology of liver fibrosis, its progression to cirrhosis and HCC, and current therapeutic options available to treat the diseases with potential therapeutic options that will be available in the near future.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47757217","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}
Ragini Singh, Shu-Li Cheng, Qinghua Zeng, Santosh Kumar, Carlos Marques
Hepatocellular carcinoma (HCC) is the third major cause of cancer-related death worldwide and responds positively to tyrosine kinase inhibitors (TKIs). Dasatinib (Das) is an Src/Abl family kinase and has been successfully utilized in the treatment of various cancers. Cancer cells are known to limit their oxidative phosphorylation to minimize oxidative stress. Palmitoylcarnitine (Pcar) incubation triggers mitochondria-mediated apoptosis in cancer cells by increasing the mitochondrial respiration rate. It stimulates the H2O2 production in cancer cells and thus induces oxidative stress. Thus, considering the above observations, the combined effect of Pcar and Das on HepG2, liver cancer cells has been evaluated in the present study. Results demonstrated that combined exposure to Pcar and dasatinib inhibited cell growth, proliferation, and invasion efficiency of cancerous cells more than single-drug treatment. Further, cells undergo membrane depolarization and caspase-dependent apoptosis upon exposure to combined treatment. In addition, in vivo study showed that Pcar and dasatinib treatment reduced the tumor size in mice more significantly than single-drug treatment. Thus, considering the above remarks, combined therapy of Pcar and dasatinib may serve as a potential candidate in the treatment of liver cancer in human and animal tissues.
{"title":"Synergistic Anti-tumor Effect of Palmitoylcarnitine and Dasatinib in Liver Cancer","authors":"Ragini Singh, Shu-Li Cheng, Qinghua Zeng, Santosh Kumar, Carlos Marques","doi":"10.3390/livers2040026","DOIUrl":"https://doi.org/10.3390/livers2040026","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the third major cause of cancer-related death worldwide and responds positively to tyrosine kinase inhibitors (TKIs). Dasatinib (Das) is an Src/Abl family kinase and has been successfully utilized in the treatment of various cancers. Cancer cells are known to limit their oxidative phosphorylation to minimize oxidative stress. Palmitoylcarnitine (Pcar) incubation triggers mitochondria-mediated apoptosis in cancer cells by increasing the mitochondrial respiration rate. It stimulates the H2O2 production in cancer cells and thus induces oxidative stress. Thus, considering the above observations, the combined effect of Pcar and Das on HepG2, liver cancer cells has been evaluated in the present study. Results demonstrated that combined exposure to Pcar and dasatinib inhibited cell growth, proliferation, and invasion efficiency of cancerous cells more than single-drug treatment. Further, cells undergo membrane depolarization and caspase-dependent apoptosis upon exposure to combined treatment. In addition, in vivo study showed that Pcar and dasatinib treatment reduced the tumor size in mice more significantly than single-drug treatment. Thus, considering the above remarks, combined therapy of Pcar and dasatinib may serve as a potential candidate in the treatment of liver cancer in human and animal tissues.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47434927","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}
Patients with advanced hepatocellular carcinoma (HCC) have a very limited survival rate even after the recent inclusion of kinase inhibitors or immune checkpoint inhibitors in the therapeutic armamentarium. A significant problem with the current proposed therapies is the considerable cost of treatment that may be a serious obstacle in low- and middle-income countries. Implementation of somatostatin analogues (SSAs) has the potential to overcome this obstacle, but due to some negative studies their extensive evaluation came to a halt. However, experimental evidence, both in vitro and in vivo, has revealed various mechanisms of the anti-tumor effects of these analogues, including inhibition of cancer cell proliferation and angiogenesis and induction of apoptosis. Favorable indirect effects such as inhibition of liver inflammation and fibrosis and influence on macrophage-mediated innate immunity have also been noted and are presented in this review. Furthermore, the clinical application of SSAs is both presented and compared with clinical trials of kinase and immune checkpoint inhibitors (ICIs). No direct trials have been performed to compare survival in the same cohort of patients, but the cost of treatment with SSAs is a fraction compared to the other modalities and with significantly less serious side effects. As in immunotherapy, patients with viral HCC (excluding alcoholics), as well as Barcelona stage B or C and Child A patients, are the best candidates, since they usually have a survival prospect of at least 6 months, necessary for optimum results. Reasons for treatment failures are also discussed and further research is proposed.
{"title":"Is There a Place for Somatostatin Analogues for the Systemic Treatment of Hepatocellular Carcinoma in the Immunotherapy Era?","authors":"E. Kouroumalis, Ioannis Tsomidis, A. Voumvouraki","doi":"10.3390/livers2040024","DOIUrl":"https://doi.org/10.3390/livers2040024","url":null,"abstract":"Patients with advanced hepatocellular carcinoma (HCC) have a very limited survival rate even after the recent inclusion of kinase inhibitors or immune checkpoint inhibitors in the therapeutic armamentarium. A significant problem with the current proposed therapies is the considerable cost of treatment that may be a serious obstacle in low- and middle-income countries. Implementation of somatostatin analogues (SSAs) has the potential to overcome this obstacle, but due to some negative studies their extensive evaluation came to a halt. However, experimental evidence, both in vitro and in vivo, has revealed various mechanisms of the anti-tumor effects of these analogues, including inhibition of cancer cell proliferation and angiogenesis and induction of apoptosis. Favorable indirect effects such as inhibition of liver inflammation and fibrosis and influence on macrophage-mediated innate immunity have also been noted and are presented in this review. Furthermore, the clinical application of SSAs is both presented and compared with clinical trials of kinase and immune checkpoint inhibitors (ICIs). No direct trials have been performed to compare survival in the same cohort of patients, but the cost of treatment with SSAs is a fraction compared to the other modalities and with significantly less serious side effects. As in immunotherapy, patients with viral HCC (excluding alcoholics), as well as Barcelona stage B or C and Child A patients, are the best candidates, since they usually have a survival prospect of at least 6 months, necessary for optimum results. Reasons for treatment failures are also discussed and further research is proposed.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45566965","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}
L. Conde de la Rosa, Leire Goicoechea, S. Torres, C. Garcia-Ruiz, J. Fernandez-Checa
Oxygen is vital for life as it is required for many different enzymatic reactions involved in intermediate metabolism and xenobiotic biotransformation. Moreover, oxygen consumption in the electron transport chain of mitochondria is used to drive the synthesis of ATP to meet the energetic demands of cells. However, toxic free radicals are generated as byproducts of molecular oxygen consumption. Oxidative stress ensues not only when the production of reactive oxygen species (ROS) exceeds the endogenous antioxidant defense mechanism of cells, but it can also occur as a consequence of an unbalance between antioxidant strategies. Given the important role of hepatocytes in the biotransformation and metabolism of xenobiotics, ROS production represents a critical event in liver physiology, and increasing evidence suggests that oxidative stress contributes to the development of many liver diseases. The present review, which is part of the special issue “Oxidant stress in Liver Diseases”, aims to provide an overview of the sources and targets of ROS in different liver diseases and highlights the pivotal role of oxidative stress in cell death. In addition, current antioxidant therapies as treatment options for such disorders and their limitations for future trial design are discussed.
{"title":"Role of Oxidative Stress in Liver Disorders","authors":"L. Conde de la Rosa, Leire Goicoechea, S. Torres, C. Garcia-Ruiz, J. Fernandez-Checa","doi":"10.3390/livers2040023","DOIUrl":"https://doi.org/10.3390/livers2040023","url":null,"abstract":"Oxygen is vital for life as it is required for many different enzymatic reactions involved in intermediate metabolism and xenobiotic biotransformation. Moreover, oxygen consumption in the electron transport chain of mitochondria is used to drive the synthesis of ATP to meet the energetic demands of cells. However, toxic free radicals are generated as byproducts of molecular oxygen consumption. Oxidative stress ensues not only when the production of reactive oxygen species (ROS) exceeds the endogenous antioxidant defense mechanism of cells, but it can also occur as a consequence of an unbalance between antioxidant strategies. Given the important role of hepatocytes in the biotransformation and metabolism of xenobiotics, ROS production represents a critical event in liver physiology, and increasing evidence suggests that oxidative stress contributes to the development of many liver diseases. The present review, which is part of the special issue “Oxidant stress in Liver Diseases”, aims to provide an overview of the sources and targets of ROS in different liver diseases and highlights the pivotal role of oxidative stress in cell death. In addition, current antioxidant therapies as treatment options for such disorders and their limitations for future trial design are discussed.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44904998","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}
Adnan Khan, H. M. Ross, N. Parra, Sarah L. Chen, Kashyap Chauhan, Makala Wang, Binghai Yan, John Magagna, Jake Beiriger, Y. Shah, Taha Shahzad, D. Halegoua-DeMarzio
Non-alcoholic fatty liver disease (NAFLD) is a serious clinicopathological condition that is recognized as the most frequent chronic liver disease, affecting 14%-30% of the world’s population. The prevalence of NAFLD has rapidly grown and is correlated with the growth in obesity and type 2 diabetes, among other factors. NAFLD often results in long-term complications including cardiovascular disease, liver cirrhosis, and liver fibrosis. This paper provides an updated overview of NAFLD with a focus on epidemiology, etiology, pathophysiology, screening, complications, and pharmacological therapies to identify effective risk prevention and health promotion.
{"title":"Risk Prevention and Health Promotion for Non-Alcoholic Fatty Liver Diseases (NAFLD)","authors":"Adnan Khan, H. M. Ross, N. Parra, Sarah L. Chen, Kashyap Chauhan, Makala Wang, Binghai Yan, John Magagna, Jake Beiriger, Y. Shah, Taha Shahzad, D. Halegoua-DeMarzio","doi":"10.3390/livers2040022","DOIUrl":"https://doi.org/10.3390/livers2040022","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD) is a serious clinicopathological condition that is recognized as the most frequent chronic liver disease, affecting 14%-30% of the world’s population. The prevalence of NAFLD has rapidly grown and is correlated with the growth in obesity and type 2 diabetes, among other factors. NAFLD often results in long-term complications including cardiovascular disease, liver cirrhosis, and liver fibrosis. This paper provides an updated overview of NAFLD with a focus on epidemiology, etiology, pathophysiology, screening, complications, and pharmacological therapies to identify effective risk prevention and health promotion.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41671162","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}
L. Abenavoli, L. Boccuto, A. Corea, M. Gambardella, R. Spagnuolo, F. Luzza
Alagille syndrome (ALGS) is a genetic-driven condition of chronic cholestasis, involving the intrahepatic bile ducts, heart, vessels, kidneys, skeletal tissues, eyes, and nervous system. Pathological mechanisms are still not defined. JAG1 and NOTCH2 gene mutations are responsible for most cases (96–97%). Diagnosis is based on clinical and laboratory findings—especially the presence of chronic cholestasis—and on genetic assessment. Bone abnormalities, deficiency of liposoluble vitamins, heart issues, and pruritus are the most prominent features of ALGS. Diagnostic imaging, such as ultrasonography, magnetic resonance imaging, and bone mass density assessment, is useful to study hepatic disease progression, estimate the risk of bone fracture, and rule out malignities. Therapy is based on ursodeoxycholic acid, rifampicin, cholestyramine, and supplementation of liposoluble vitamins. New therapeutic approaches are under investigation. Here, we describe a case of an individual with ALGS presenting with congenital chronic cholestasis and a long clinical history, in which pruritus is the main symptom.
{"title":"Alagille Syndrome and Its Clinical and Laboratory Features: A Case Report","authors":"L. Abenavoli, L. Boccuto, A. Corea, M. Gambardella, R. Spagnuolo, F. Luzza","doi":"10.3390/livers2040021","DOIUrl":"https://doi.org/10.3390/livers2040021","url":null,"abstract":"Alagille syndrome (ALGS) is a genetic-driven condition of chronic cholestasis, involving the intrahepatic bile ducts, heart, vessels, kidneys, skeletal tissues, eyes, and nervous system. Pathological mechanisms are still not defined. JAG1 and NOTCH2 gene mutations are responsible for most cases (96–97%). Diagnosis is based on clinical and laboratory findings—especially the presence of chronic cholestasis—and on genetic assessment. Bone abnormalities, deficiency of liposoluble vitamins, heart issues, and pruritus are the most prominent features of ALGS. Diagnostic imaging, such as ultrasonography, magnetic resonance imaging, and bone mass density assessment, is useful to study hepatic disease progression, estimate the risk of bone fracture, and rule out malignities. Therapy is based on ursodeoxycholic acid, rifampicin, cholestyramine, and supplementation of liposoluble vitamins. New therapeutic approaches are under investigation. Here, we describe a case of an individual with ALGS presenting with congenital chronic cholestasis and a long clinical history, in which pruritus is the main symptom.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46479466","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}
Amaar A. Akbaraliev, L. Akhvlediani, Ana Kavazashvili, E. Diasamidze, Omar Surmanidze, N. Gassen, E. Anderzhanova
Polyamines (PAs), endogenous metabolites with a wide range of biological activities, are synthesized at a high rate in liver supporting hepatocyte proliferation and survival. The liver appears as an important regulator of plasma PAs; however, the perspective to exploit plasma PA measurements as indicators for liver function was not explored. This study aimed to evaluate the value of the plasma levels of PAs as a biomarker of pathological changes in the liver in patients with obstructive cholecystitis. The levels of polyamines and their acetylated forms were measured using HPLC/UV in the plasma of patients with obstructive cholecystitis and in healthy subjects. PA turnover was assessed by the ratio between an acetylated form of PA and PA. An effect of diet preference of cheese or meat, the major exogenous sources of PAs, smoking, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in anamnesis was also evaluated in healthy subjects. We found that the plasma levels of spermine and acetylated spermidine decreased in patients with obstructive cholecystitis without a concurring increase in the total plasma bilirubin and amylase levels. The turnover of spermine and spermidine was also changed, suggesting a decrease in the rate of PA degradation in the liver. In healthy subjects, the PA levels tended to mirror chronic smoking and recent SARS-CoV-2 infection but were not relevant to diet factors. A number of observations indicated the role of physical exercise in the regulation of the plasma pool of PA. The decrease in plasma PA levels and index of PA turnover in the cholestasis syndrome indicate the liver’s metabolic function reduction. A conceivable effect of lung-related conditions on plasma PA, while indicating low specificity, nonetheless, speaks favorably about the high sensitivity of plasma PA measurement as an early diagnostic test in the clinic.
{"title":"Plasma Polyamines Decrease in Patients with Obstructive Cholecystitis","authors":"Amaar A. Akbaraliev, L. Akhvlediani, Ana Kavazashvili, E. Diasamidze, Omar Surmanidze, N. Gassen, E. Anderzhanova","doi":"10.3390/livers2030019","DOIUrl":"https://doi.org/10.3390/livers2030019","url":null,"abstract":"Polyamines (PAs), endogenous metabolites with a wide range of biological activities, are synthesized at a high rate in liver supporting hepatocyte proliferation and survival. The liver appears as an important regulator of plasma PAs; however, the perspective to exploit plasma PA measurements as indicators for liver function was not explored. This study aimed to evaluate the value of the plasma levels of PAs as a biomarker of pathological changes in the liver in patients with obstructive cholecystitis. The levels of polyamines and their acetylated forms were measured using HPLC/UV in the plasma of patients with obstructive cholecystitis and in healthy subjects. PA turnover was assessed by the ratio between an acetylated form of PA and PA. An effect of diet preference of cheese or meat, the major exogenous sources of PAs, smoking, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in anamnesis was also evaluated in healthy subjects. We found that the plasma levels of spermine and acetylated spermidine decreased in patients with obstructive cholecystitis without a concurring increase in the total plasma bilirubin and amylase levels. The turnover of spermine and spermidine was also changed, suggesting a decrease in the rate of PA degradation in the liver. In healthy subjects, the PA levels tended to mirror chronic smoking and recent SARS-CoV-2 infection but were not relevant to diet factors. A number of observations indicated the role of physical exercise in the regulation of the plasma pool of PA. The decrease in plasma PA levels and index of PA turnover in the cholestasis syndrome indicate the liver’s metabolic function reduction. A conceivable effect of lung-related conditions on plasma PA, while indicating low specificity, nonetheless, speaks favorably about the high sensitivity of plasma PA measurement as an early diagnostic test in the clinic.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41570429","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}
Background: Spontaneous bacterial peritonitis (SBP) is defined as a bacterial infection of the ascitic fluid without a surgically treatable intra-abdominal infection source. SBP is a common, severe complication in cirrhosis patients with ascites, and if left untreated, in-hospital mortality may exceed 90%. However, the incidence of SBP has been lowered to approx. 20% through early diagnosis and antibiotic therapy. Clinical awareness, prompt diagnosis, and immediate treatment are advised when caring for these patients to reduce mortality and morbidity. Aim: To discuss important issues comprising types of SBP, pathogenesis, bacteriology, including the emergence of multidrug-resistant (MDR) microorganisms, prompt diagnosis, risk factors, prognosis, treatment strategies, as well as recurrence prevention through antibiotic prophylaxis until liver transplantation and future trends in treating and preventing SBP in detail. Methods: This article is a literature review and appraisal of guidelines, randomized controlled trials, meta-analyses, and other review articles found on PubMed from between 1977 and 2022. Results: There are three types of SBP. Bacterial translocation from GI tract is the most common source of SBP. Therefore, two thirds of SBP cases were caused by Gram-negative bacilli, of which Escherichia coli is the most frequently isolated pathogen. However, a trend of Gram-positive cocci associated SBP has been demonstrated in recent years, possibly related to more invasive procedures and long-term quinolone prophylaxis. A diagnostic paracentesis should be performed in all patients with cirrhosis and ascites who require emergency room care or hospitalization, who demonstrate or report consistent signs/symptoms in order to confirm evidence of SBP. Distinguishing SBP from secondary bacterial peritonitis is essential because the conditions require different therapeutic strategies. The standard treatment for SBP is prompt broad-spectrum antibiotic administration and should be tailored according to community-acquired SBP, healthcare-associated or nosocomial SBP infections and local resistance profile. Albumin supplementation, especially in patients with renal impairment, is also beneficial. Selective intestinal decontamination is associated with a reduced risk of bacterial infection and mortality in high-risk group. Conclusions: The standard treatment for SBP is prompt broad-spectrum antibiotic administration and should be tailored according to community-acquired SBP, healthcare-associated or nosocomial SBP infections and local resistance profile. Since the one-year overall mortality rates for SBP range from 53.9 to 78%, liver transplantation should be seriously considered for SBP survivors who are good candidates for transplantation. Further development of non-antibiotic strategies based on pathogenic mechanisms are also urgently needed.
{"title":"Spontaneous Bacterial Peritonitis in Decompensated Liver Cirrhosis—A Literature Review","authors":"Chien‐Hao Huang, Chen-Hung Lee, Chin-Cheng Chang","doi":"10.3390/livers2030018","DOIUrl":"https://doi.org/10.3390/livers2030018","url":null,"abstract":"Background: Spontaneous bacterial peritonitis (SBP) is defined as a bacterial infection of the ascitic fluid without a surgically treatable intra-abdominal infection source. SBP is a common, severe complication in cirrhosis patients with ascites, and if left untreated, in-hospital mortality may exceed 90%. However, the incidence of SBP has been lowered to approx. 20% through early diagnosis and antibiotic therapy. Clinical awareness, prompt diagnosis, and immediate treatment are advised when caring for these patients to reduce mortality and morbidity. Aim: To discuss important issues comprising types of SBP, pathogenesis, bacteriology, including the emergence of multidrug-resistant (MDR) microorganisms, prompt diagnosis, risk factors, prognosis, treatment strategies, as well as recurrence prevention through antibiotic prophylaxis until liver transplantation and future trends in treating and preventing SBP in detail. Methods: This article is a literature review and appraisal of guidelines, randomized controlled trials, meta-analyses, and other review articles found on PubMed from between 1977 and 2022. Results: There are three types of SBP. Bacterial translocation from GI tract is the most common source of SBP. Therefore, two thirds of SBP cases were caused by Gram-negative bacilli, of which Escherichia coli is the most frequently isolated pathogen. However, a trend of Gram-positive cocci associated SBP has been demonstrated in recent years, possibly related to more invasive procedures and long-term quinolone prophylaxis. A diagnostic paracentesis should be performed in all patients with cirrhosis and ascites who require emergency room care or hospitalization, who demonstrate or report consistent signs/symptoms in order to confirm evidence of SBP. Distinguishing SBP from secondary bacterial peritonitis is essential because the conditions require different therapeutic strategies. The standard treatment for SBP is prompt broad-spectrum antibiotic administration and should be tailored according to community-acquired SBP, healthcare-associated or nosocomial SBP infections and local resistance profile. Albumin supplementation, especially in patients with renal impairment, is also beneficial. Selective intestinal decontamination is associated with a reduced risk of bacterial infection and mortality in high-risk group. Conclusions: The standard treatment for SBP is prompt broad-spectrum antibiotic administration and should be tailored according to community-acquired SBP, healthcare-associated or nosocomial SBP infections and local resistance profile. Since the one-year overall mortality rates for SBP range from 53.9 to 78%, liver transplantation should be seriously considered for SBP survivors who are good candidates for transplantation. Further development of non-antibiotic strategies based on pathogenic mechanisms are also urgently needed.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42991707","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}
Mascha Korsch, A. Margetts, C. Wahlestedt, I. Lohse
Liver cancer ranks as the fourth leading cause of cancer-related deaths. Despite extensive research efforts aiming to evaluate the biological mechanisms underlying hepatocellular carcinoma (HCC) development, little has been translated towards new diagnostic and treatment options for HCC patients. Historically, the focus has been centered on coding RNAs and their respective proteins. However, significant advances in sequencing and RNA detection technologies have shifted the research focus towards non-coding RNAs (ncRNA), as well as their impact on HCC development and progression. A number of studies reported complex post-transcriptional interactions between various ncRNA and coding RNA molecules. These interactions offer insights into the role of ncRNAs in both the known pathways leading to oncogenesis, such as dysregulation of p53, and lesser-known mechanisms, such as small nucleolar RNA methylation. Studies investigating these mechanisms have identified prevalent ncRNA changes in microRNAs, snoRNAs, and long non-coding RNAs that can both pre- and post-translationally regulate key factors in HCC progression. In this review, we present relevant publications describing ncRNAs to summarize the impact of different ncRNA species on liver cancer development and progression and to evaluate recent attempts at clinical translation.
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