Joseph Delo, D. Forton, E. Triantafyllou, A. Singanayagam
The peritoneum represents a confined microenvironment that has an emerging role as a distinct immunological compartment. In health, this niche is mainly populated by a heterogenous group of macrophages and T lymphocytes but also Natural Killer cells and B lymphocytes. Together they are crucial for immunological surveillance, clearance of infection and resolution of inflammation. Development of ascites is a defining feature of decompensated liver cirrhosis, and spontaneous bacterial peritonitis is the most frequent bacterial infection occurring in this patient group. Recent studies of ascitic fluid have revealed quantitative, phenotypic and functional differences in both innate and adaptive immune cells compared to the healthy state. This review summarises current knowledge of these alterations and explores how the peritoneum in chronic liver disease is simultaneously an immunologically compromised site and yet capable of provoking an intense inflammatory response. A better understanding of this might enable identification of new therapeutic targets aimed to rebalance the peritoneal immunity and reduce the reliance on antimicrobials in an era of increasing antimicrobial resistance.
{"title":"Peritoneal Immunity in Liver Disease","authors":"Joseph Delo, D. Forton, E. Triantafyllou, A. Singanayagam","doi":"10.3390/livers3020016","DOIUrl":"https://doi.org/10.3390/livers3020016","url":null,"abstract":"The peritoneum represents a confined microenvironment that has an emerging role as a distinct immunological compartment. In health, this niche is mainly populated by a heterogenous group of macrophages and T lymphocytes but also Natural Killer cells and B lymphocytes. Together they are crucial for immunological surveillance, clearance of infection and resolution of inflammation. Development of ascites is a defining feature of decompensated liver cirrhosis, and spontaneous bacterial peritonitis is the most frequent bacterial infection occurring in this patient group. Recent studies of ascitic fluid have revealed quantitative, phenotypic and functional differences in both innate and adaptive immune cells compared to the healthy state. This review summarises current knowledge of these alterations and explores how the peritoneum in chronic liver disease is simultaneously an immunologically compromised site and yet capable of provoking an intense inflammatory response. A better understanding of this might enable identification of new therapeutic targets aimed to rebalance the peritoneal immunity and reduce the reliance on antimicrobials in an era of increasing antimicrobial resistance.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46379313","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 hepatitis B remains a major public health concern and a leading cause of morbidity and mortality worldwide, specifically through its causative role in chronic liver disease and hepatocellular carcinoma. Worldwide, it affects up to 292 million people. In this paper, we review the historic discovery of the hepatitis B virus and chronicle the significant advances in our understanding of the virus and its interactions with the human host to cause disease. We also overview advancements in therapies for hepatitis B virus and the current absence of curative therapies and highlight on-going therapeutic efforts in search of curative therapies to control transmission and eradicate hepatitis B virus.
{"title":"Chronicles of HBV and the Road to HBV Cure","authors":"Rukaiya Bashir Hamidu, Richard R. Hann, H. Hann","doi":"10.3390/livers3020015","DOIUrl":"https://doi.org/10.3390/livers3020015","url":null,"abstract":"Chronic hepatitis B remains a major public health concern and a leading cause of morbidity and mortality worldwide, specifically through its causative role in chronic liver disease and hepatocellular carcinoma. Worldwide, it affects up to 292 million people. In this paper, we review the historic discovery of the hepatitis B virus and chronicle the significant advances in our understanding of the virus and its interactions with the human host to cause disease. We also overview advancements in therapies for hepatitis B virus and the current absence of curative therapies and highlight on-going therapeutic efforts in search of curative therapies to control transmission and eradicate hepatitis B virus.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49260847","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}
E. M. Elsebaie, Alyaa Nasr Abdel-Fattah, Nagwa Awad Bakr, Kadry Mohamed Attalah, Abdel-Hady Ahmed Aweas
According to studies, the liver’s ability to perform its physiological functions in the body determines the diet of patients with liver diseases. Malnutrition results from the liver’s inability to metabolize nutrients as a result of chronic liver dysfunctions. Objectives: Reviewing the data about diets and dietary supplements that manage liver dysfunctions nutritionally. Results: Malnutrition is particularly prevalent in cirrhosis patients, according to clinical studies. Because malnutrition has a significant negative impact on morbidity, mortality, and quality of life, it is crucial to evaluate all cirrhosis patients, regardless of etiology or severity. A term of supplemental enteral nutrition may be suggested for patients who do not achieve their nutritional objectives. A detailed nutritional and exercise assessment will enable the development of an individualized treatment plan that includes dietary and exercise plans. The dietary treatment should outline daily calorie targets with a focus on high-quality protein and address any vitamin and micronutrient deficiencies, with a diet high in those nutrients or supplements. Conclusions: While there is evidence to support the use of particular restricted dietary plans and dietary supplements to manage liver diseases, these findings should be regarded as preliminary until they are confirmed in larger randomized controlled clinical trials.
{"title":"Principles of Nutritional Management in Patients with Liver Dysfunction—A Narrative Review","authors":"E. M. Elsebaie, Alyaa Nasr Abdel-Fattah, Nagwa Awad Bakr, Kadry Mohamed Attalah, Abdel-Hady Ahmed Aweas","doi":"10.3390/livers3020013","DOIUrl":"https://doi.org/10.3390/livers3020013","url":null,"abstract":"According to studies, the liver’s ability to perform its physiological functions in the body determines the diet of patients with liver diseases. Malnutrition results from the liver’s inability to metabolize nutrients as a result of chronic liver dysfunctions. Objectives: Reviewing the data about diets and dietary supplements that manage liver dysfunctions nutritionally. Results: Malnutrition is particularly prevalent in cirrhosis patients, according to clinical studies. Because malnutrition has a significant negative impact on morbidity, mortality, and quality of life, it is crucial to evaluate all cirrhosis patients, regardless of etiology or severity. A term of supplemental enteral nutrition may be suggested for patients who do not achieve their nutritional objectives. A detailed nutritional and exercise assessment will enable the development of an individualized treatment plan that includes dietary and exercise plans. The dietary treatment should outline daily calorie targets with a focus on high-quality protein and address any vitamin and micronutrient deficiencies, with a diet high in those nutrients or supplements. Conclusions: While there is evidence to support the use of particular restricted dietary plans and dietary supplements to manage liver diseases, these findings should be regarded as preliminary until they are confirmed in larger randomized controlled clinical trials.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42927288","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}
Bahareh Farasati Far, Ali Attaripour Isfahani, Elnaz Nasiriyan, Ali Pourmolaei, Golnaz Mahmoudvand, A. Karimi Rouzbahani, Mohammed Namiq Amin, M. Naimi-Jamal
More than 90% of all liver malignancies are hepatocellular carcinomas (HCCs), for which chemotherapy and immunotherapy are the ideal therapeutic choices. Hepatocellular carcinoma is descended from other liver diseases, such as viral hepatitis, alcoholism, and metabolic syndrome. Normal cells and tissues may suffer damage from common forms of chemotherapy. In contrast to systemic chemotherapy, localized chemotherapy can reduce side effects by delivering a steady stream of chemotherapeutic drugs directly to the tumor site. This highlights the significance of controlled-release biodegradable hydrogels as drug delivery methods for chemotherapeutics. This review discusses using hydrogels as drug delivery systems for HCC and covers thermosensitive, pH-sensitive, photosensitive, dual-sensitive, and glutathione-responsive hydrogels. Compared to conventional systemic chemotherapy, hydrogel-based drug delivery methods are more effective in treating cancer.
{"title":"An Updated Review on Advances in Hydrogel-Based Nanoparticles for Liver Cancer Treatment","authors":"Bahareh Farasati Far, Ali Attaripour Isfahani, Elnaz Nasiriyan, Ali Pourmolaei, Golnaz Mahmoudvand, A. Karimi Rouzbahani, Mohammed Namiq Amin, M. Naimi-Jamal","doi":"10.3390/livers3020012","DOIUrl":"https://doi.org/10.3390/livers3020012","url":null,"abstract":"More than 90% of all liver malignancies are hepatocellular carcinomas (HCCs), for which chemotherapy and immunotherapy are the ideal therapeutic choices. Hepatocellular carcinoma is descended from other liver diseases, such as viral hepatitis, alcoholism, and metabolic syndrome. Normal cells and tissues may suffer damage from common forms of chemotherapy. In contrast to systemic chemotherapy, localized chemotherapy can reduce side effects by delivering a steady stream of chemotherapeutic drugs directly to the tumor site. This highlights the significance of controlled-release biodegradable hydrogels as drug delivery methods for chemotherapeutics. This review discusses using hydrogels as drug delivery systems for HCC and covers thermosensitive, pH-sensitive, photosensitive, dual-sensitive, and glutathione-responsive hydrogels. Compared to conventional systemic chemotherapy, hydrogel-based drug delivery methods are more effective in treating cancer.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46090815","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}
Bahareh Farasati Far, Dorsa Rabie, P. Hemati, Parastoo Fooladpanjeh, Neda Faal Hamedanchi, Nima Broomand Lomer, A. Karimi Rouzbahani, M. Naimi-Jamal
With an expected incidence of more than 1 million cases by 2025, liver cancer remains a problem for world health. With over 90% of cases, hepatocellular carcinoma (HCC) is the most prevalent kind of liver cancer. In this review, we presented the range of experimental therapeutics for patients with advanced HCC, the successes and failures of new treatments, areas for future development, the evaluation of dose-limiting toxicity in different drugs, and the safety profile in patients with liver dysfunction related to the underlying chronic liver disease. In addition to the unmet demand for biomarkers to guide treatment decisions and the burgeoning fields of immunotherapy and systemic therapy in hepatocellular carcinoma, the development of old and new drugs, including their failures and current advancements, has been reviewed. This review aims to evaluate the updated optimal clinical treatment of unresectable hepatocellular carcinomas in clinical practice, mainly through targeted therapy. Although surgical treatment can significantly enhance the survival probability of early and intermediate-stage patients, it is unsuitable for most HCC patients due to a lack of donors. Due to their severe toxicity, the few first-line anti-HCC drugs, such as sorafenib, are often reserved for advanced HCC patients for whom other therapies have failed. The second-line drugs are usually alternatives for patients with intolerance or resistance. Consequently, the ongoing growth of possible preclinical drugs and studies on miRNAs, lncRNAs, and numerous other signaling pathway targets for developing novel drugs may introduce additional treatment prospects for HCC.
{"title":"Unresectable Hepatocellular Carcinoma: A Review of New Advances with Focus on Targeted Therapy and Immunotherapy","authors":"Bahareh Farasati Far, Dorsa Rabie, P. Hemati, Parastoo Fooladpanjeh, Neda Faal Hamedanchi, Nima Broomand Lomer, A. Karimi Rouzbahani, M. Naimi-Jamal","doi":"10.3390/livers3010011","DOIUrl":"https://doi.org/10.3390/livers3010011","url":null,"abstract":"With an expected incidence of more than 1 million cases by 2025, liver cancer remains a problem for world health. With over 90% of cases, hepatocellular carcinoma (HCC) is the most prevalent kind of liver cancer. In this review, we presented the range of experimental therapeutics for patients with advanced HCC, the successes and failures of new treatments, areas for future development, the evaluation of dose-limiting toxicity in different drugs, and the safety profile in patients with liver dysfunction related to the underlying chronic liver disease. In addition to the unmet demand for biomarkers to guide treatment decisions and the burgeoning fields of immunotherapy and systemic therapy in hepatocellular carcinoma, the development of old and new drugs, including their failures and current advancements, has been reviewed. This review aims to evaluate the updated optimal clinical treatment of unresectable hepatocellular carcinomas in clinical practice, mainly through targeted therapy. Although surgical treatment can significantly enhance the survival probability of early and intermediate-stage patients, it is unsuitable for most HCC patients due to a lack of donors. Due to their severe toxicity, the few first-line anti-HCC drugs, such as sorafenib, are often reserved for advanced HCC patients for whom other therapies have failed. The second-line drugs are usually alternatives for patients with intolerance or resistance. Consequently, the ongoing growth of possible preclinical drugs and studies on miRNAs, lncRNAs, and numerous other signaling pathway targets for developing novel drugs may introduce additional treatment prospects for HCC.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49103422","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}
Ishrat Jahan, Md. Didarul Islam, Sumaia Sarif, Israt Jahan Amena, Asif Ul Haque Shuvo, N. Akter, F. I. Chowdhury, R. Akter, Iqbal Ahmed, Ferdous Khan, Nusrat Subhan, Md. Ashraful Alam
The purpose of this study was to determine the effect of the superoxide dismutase mimic compound “tempol” on liver and renal damage in Long Evans male rats administered with carbon tetrachloride (CCl4). Methods: The antioxidant enzyme activity and oxidative stress parameters were investigated in the liver, kidney, and plasma tissues. Histological examination of the liver and kidney sections affirmed inflammatory cell infiltration, collagen deposition, and iron deposition. RT-PCR was also employed to evaluate the expression of oxidative stress and inflammatory genes. Results: The CCl4-administered rats exhibited increased plasma activities of ALT, AST, and ALP compared to the control rats. The tempol treatment in the CCl4-administered rats significantly lowered ALT, AST, and ALP enzyme activities compared to the CCl4 group. Oxidative stress parameters, such as the MDA, NO, and APOP levels in various tissues of the CCl4-administered rats, showed increased concentrations, whereas tempol significantly lowered the level of oxidative stress. Moreover, CCl4 administration decreased the antioxidant enzyme activities, which were further significantly restored by the tempol treatment. The control rats that underwent treatment with tempol did not present with any abnormality or toxicity. Furthermore, the tempol treatment in the CCl4-administered rats increased Nrf-2-HO-1-mediated gene expression and enhanced related antioxidant enzyme gene expressions. The tempol treatment in the CCl4-administered rats also decreased anti-inflammatory gene expressions in the liver. In histological sections of the liver, CCl4 increased inflammatory cell infiltration, collagen deposition, and iron deposition, which were reduced significantly due to the tempol treatment. Conclusion: The results of this investigation revealed that tempol could protect against liver and kidney damage in CCl4-administered rats by modulating antioxidant gene expressions and restoring antioxidant defense mechanisms.
{"title":"Tempol Alters Antioxidant Enzyme Function, Modulates Multiple Genes Expression, and Ameliorates Hepatic and Renal Impairment in Carbon Tetrachloride (CCl4)-Intoxicated Rats","authors":"Ishrat Jahan, Md. Didarul Islam, Sumaia Sarif, Israt Jahan Amena, Asif Ul Haque Shuvo, N. Akter, F. I. Chowdhury, R. Akter, Iqbal Ahmed, Ferdous Khan, Nusrat Subhan, Md. Ashraful Alam","doi":"10.3390/livers3010010","DOIUrl":"https://doi.org/10.3390/livers3010010","url":null,"abstract":"The purpose of this study was to determine the effect of the superoxide dismutase mimic compound “tempol” on liver and renal damage in Long Evans male rats administered with carbon tetrachloride (CCl4). Methods: The antioxidant enzyme activity and oxidative stress parameters were investigated in the liver, kidney, and plasma tissues. Histological examination of the liver and kidney sections affirmed inflammatory cell infiltration, collagen deposition, and iron deposition. RT-PCR was also employed to evaluate the expression of oxidative stress and inflammatory genes. Results: The CCl4-administered rats exhibited increased plasma activities of ALT, AST, and ALP compared to the control rats. The tempol treatment in the CCl4-administered rats significantly lowered ALT, AST, and ALP enzyme activities compared to the CCl4 group. Oxidative stress parameters, such as the MDA, NO, and APOP levels in various tissues of the CCl4-administered rats, showed increased concentrations, whereas tempol significantly lowered the level of oxidative stress. Moreover, CCl4 administration decreased the antioxidant enzyme activities, which were further significantly restored by the tempol treatment. The control rats that underwent treatment with tempol did not present with any abnormality or toxicity. Furthermore, the tempol treatment in the CCl4-administered rats increased Nrf-2-HO-1-mediated gene expression and enhanced related antioxidant enzyme gene expressions. The tempol treatment in the CCl4-administered rats also decreased anti-inflammatory gene expressions in the liver. In histological sections of the liver, CCl4 increased inflammatory cell infiltration, collagen deposition, and iron deposition, which were reduced significantly due to the tempol treatment. Conclusion: The results of this investigation revealed that tempol could protect against liver and kidney damage in CCl4-administered rats by modulating antioxidant gene expressions and restoring antioxidant defense mechanisms.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46523955","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}
Amala J. Alenchery, Sophia Patel, L. Mahajan, J. Kurowski, S. Worley, V. Hupertz, Kaddakal Radhakrishnan, M. Kabbany
There is no single proven therapy that prolongs hepatic transplant-free survival in patients with primary sclerosing cholangitis (PSC). Oral vancomycin (OV) has shown some benefit in small pediatric and adult series. We describe the effect of OV on pediatric onset PSC at our tertiary hospital. This is a single-center, retrospective, descriptive case series involving patients (<21 years at diagnosis) with PSC on OV from 2001 till 2021. The therapy effect was assessed based on symptoms, biochemical labs, imaging and liver biopsy at six and twelve months, and then annually until therapy was discontinued. The inclusion criteria identified 17 patients. Baseline GGT (n = 17) was elevated among 88.2% which then normalized among 53.8% (n = 13) at six months and 55.6% (n = 9) at one year post-OV. Baseline ALT normalized in 58.8% (n = 17) at six months and 42.8% (n = 14) at one year. Imaging findings within one year of OV revealed improved/stable biliary findings among 66.7% (n = 8/12). No adverse events were reported. OV was associated with an improvement in bile duct injury marker (GGT) after at least six months of therapy, with no disease progression on imaging within one year of therapy.
{"title":"Single Center Experience of Oral Vancomycin Therapy in Young Patients with Primary Sclerosing Cholangitis: A Case Series","authors":"Amala J. Alenchery, Sophia Patel, L. Mahajan, J. Kurowski, S. Worley, V. Hupertz, Kaddakal Radhakrishnan, M. Kabbany","doi":"10.3390/livers3010009","DOIUrl":"https://doi.org/10.3390/livers3010009","url":null,"abstract":"There is no single proven therapy that prolongs hepatic transplant-free survival in patients with primary sclerosing cholangitis (PSC). Oral vancomycin (OV) has shown some benefit in small pediatric and adult series. We describe the effect of OV on pediatric onset PSC at our tertiary hospital. This is a single-center, retrospective, descriptive case series involving patients (<21 years at diagnosis) with PSC on OV from 2001 till 2021. The therapy effect was assessed based on symptoms, biochemical labs, imaging and liver biopsy at six and twelve months, and then annually until therapy was discontinued. The inclusion criteria identified 17 patients. Baseline GGT (n = 17) was elevated among 88.2% which then normalized among 53.8% (n = 13) at six months and 55.6% (n = 9) at one year post-OV. Baseline ALT normalized in 58.8% (n = 17) at six months and 42.8% (n = 14) at one year. Imaging findings within one year of OV revealed improved/stable biliary findings among 66.7% (n = 8/12). No adverse events were reported. OV was associated with an improvement in bile duct injury marker (GGT) after at least six months of therapy, with no disease progression on imaging within one year of therapy.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44783226","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}
Karima Begriche, Clémence Penhoat, Pénélope Bernabeu-Gentey, Julie Massart, Bernard Fromenty
The epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk of adverse events including liver injury. For more than 30 years, a series of experimental and clinical investigations reported or suggested that the common pain reliever acetaminophen (APAP) could be more hepatotoxic in obesity and related metabolic diseases, at least after an overdose. Nonetheless, several investigations did not reproduce these data. This discrepancy might come from the extent of obesity and steatosis, accumulation of specific lipid species, mitochondrial dysfunction and diabetes-related parameters such as ketonemia and hyperglycemia. Among these factors, some of them seem pivotal for the induction of cytochrome P450 2E1 (CYP2E1), which favors the conversion of APAP to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). In contrast, other factors might explain why obesity and NAFLD are not always associated with more frequent or more severe APAP-induced acute hepatotoxicity, such as increased volume of distribution in the body, higher hepatic glucuronidation and reduced CYP3A4 activity. Accordingly, the occurrence and outcome of APAP-induced liver injury in an obese individual with NAFLD would depend on a delicate balance between metabolic factors that augment the generation of NAPQI and others that can mitigate hepatotoxicity.
{"title":"Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review.","authors":"Karima Begriche, Clémence Penhoat, Pénélope Bernabeu-Gentey, Julie Massart, Bernard Fromenty","doi":"10.3390/livers3010003","DOIUrl":"https://doi.org/10.3390/livers3010003","url":null,"abstract":"<p><p>The epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk of adverse events including liver injury. For more than 30 years, a series of experimental and clinical investigations reported or suggested that the common pain reliever acetaminophen (APAP) could be more hepatotoxic in obesity and related metabolic diseases, at least after an overdose. Nonetheless, several investigations did not reproduce these data. This discrepancy might come from the extent of obesity and steatosis, accumulation of specific lipid species, mitochondrial dysfunction and diabetes-related parameters such as ketonemia and hyperglycemia. Among these factors, some of them seem pivotal for the induction of cytochrome P450 2E1 (CYP2E1), which favors the conversion of APAP to the toxic metabolite N-acetyl-<i>p</i>-benzoquinone imine (NAPQI). In contrast, other factors might explain why obesity and NAFLD are not always associated with more frequent or more severe APAP-induced acute hepatotoxicity, such as increased volume of distribution in the body, higher hepatic glucuronidation and reduced CYP3A4 activity. Accordingly, the occurrence and outcome of APAP-induced liver injury in an obese individual with NAFLD would depend on a delicate balance between metabolic factors that augment the generation of NAPQI and others that can mitigate hepatotoxicity.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10816740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anum Syyam, Hira Raheem Akbar, Z. Jílková, S. Afzal
Globally, hepatocellular carcinoma (HCC) is a significant cause of mortality and morbidity among chronically infected HCV patients. It is established that HCV is a primary risk factor for HCC progression. The treatment of HCV infection has been transformed by the introduction of DAAs with high rates of virological clearance. The reduction in cirrhosis-related consequences, particularly HCC, is the long-term objective of DAAs therapy for HCV. Although the risk of developing HCC is decreased in HCV patients who achieve a disease-sustaining virological response, these patients are nevertheless at risk, especially those with severe fibrosis and cirrhosis. Previous studies have shown that HCV induce several mechanisms of hepatocarcinogenesis in the host’s hepatic micro- and macro-environment, which leads to HCC progression. In an HCV-altered environment, compensatory liver regeneration favors chromosomal instability and irreversible alterations, which encourage hepatocyte neoplastic transformation and the development of malignant clones. These mechanisms involve a series of genetic and epigenetic modifications including host genetic factors, dysregulation of several signaling pathways, histone, and DNA modifications including methylation and acetylation. This review highlights the genetic and epigenetic factors that lead to the development of HCC in chronic HCV-infected individuals and can be targeted for earlier HCC diagnosis and prevention.
{"title":"Role of Genetic and Epigenetic Modifications in the Progression of Hepatocellular Carcinoma in Chronic HCV Patients","authors":"Anum Syyam, Hira Raheem Akbar, Z. Jílková, S. Afzal","doi":"10.3390/livers3010008","DOIUrl":"https://doi.org/10.3390/livers3010008","url":null,"abstract":"Globally, hepatocellular carcinoma (HCC) is a significant cause of mortality and morbidity among chronically infected HCV patients. It is established that HCV is a primary risk factor for HCC progression. The treatment of HCV infection has been transformed by the introduction of DAAs with high rates of virological clearance. The reduction in cirrhosis-related consequences, particularly HCC, is the long-term objective of DAAs therapy for HCV. Although the risk of developing HCC is decreased in HCV patients who achieve a disease-sustaining virological response, these patients are nevertheless at risk, especially those with severe fibrosis and cirrhosis. Previous studies have shown that HCV induce several mechanisms of hepatocarcinogenesis in the host’s hepatic micro- and macro-environment, which leads to HCC progression. In an HCV-altered environment, compensatory liver regeneration favors chromosomal instability and irreversible alterations, which encourage hepatocyte neoplastic transformation and the development of malignant clones. These mechanisms involve a series of genetic and epigenetic modifications including host genetic factors, dysregulation of several signaling pathways, histone, and DNA modifications including methylation and acetylation. This review highlights the genetic and epigenetic factors that lead to the development of HCC in chronic HCV-infected individuals and can be targeted for earlier HCC diagnosis and prevention.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41533962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Avramidou, S. Vasileiadou, N. Antoniadis, G. Katsanos, Athanasios Kofinas, K. Karakasi, G. Tsoulfas
Dd-cfDNA is a novel biomarker with many diagnostic applications in various areas of medicine. In this review of the literature, we investigate its role in the diagnosis of many complications that occur in liver transplantations. In our review, we retrieved data from the medical databases PubMed and Scopus. In our bibliography, many areas concerning the contributions of dd-cfDNA to the field of liver transplantation, such as in the diagnosis of complications that include signsof rejection or graft injury, are mentioned. Dd-cfDNA, which are correlated with other biomarkers such as liver enzymes, can have a high diagnostic value. Measurements of Dd-cfDNA also depend on the graft’s size and origin; therefore, these data should be taken into account for the estimation and explanation of dd-cfDNA values. Despite the utility of this novel diagnostic technique, it comes with some limitations and applicational exclusions, such as cases where there is a blood relation between the donor and recipient.
{"title":"Liver Transplantation and dd-cfDNA: A Small Solution for a Big Problem","authors":"E. Avramidou, S. Vasileiadou, N. Antoniadis, G. Katsanos, Athanasios Kofinas, K. Karakasi, G. Tsoulfas","doi":"10.3390/livers3010007","DOIUrl":"https://doi.org/10.3390/livers3010007","url":null,"abstract":"Dd-cfDNA is a novel biomarker with many diagnostic applications in various areas of medicine. In this review of the literature, we investigate its role in the diagnosis of many complications that occur in liver transplantations. In our review, we retrieved data from the medical databases PubMed and Scopus. In our bibliography, many areas concerning the contributions of dd-cfDNA to the field of liver transplantation, such as in the diagnosis of complications that include signsof rejection or graft injury, are mentioned. Dd-cfDNA, which are correlated with other biomarkers such as liver enzymes, can have a high diagnostic value. Measurements of Dd-cfDNA also depend on the graft’s size and origin; therefore, these data should be taken into account for the estimation and explanation of dd-cfDNA values. Despite the utility of this novel diagnostic technique, it comes with some limitations and applicational exclusions, such as cases where there is a blood relation between the donor and recipient.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48346558","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：