Pub Date : 2024-09-01Epub Date: 2024-09-13DOI: 10.3390/livers4030033
Forkan Ahamed, Natalie Eppler, Elizabeth Jones, Yuxia Zhang
Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), with MASH posing a risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The global prevalence of MASLD is estimated at approximately a quarter of the population, with significant healthcare costs and implications for liver transplantation. The pathogenesis of MASLD involves intrahepatic liver cells, extrahepatic components, and immunological aspects, particularly the involvement of macrophages. Hepatic macrophages are a crucial cellular component of the liver and play important roles in liver function, contributing significantly to tissue homeostasis and swift responses during pathophysiological conditions. Recent advancements in technology have revealed the remarkable heterogeneity and plasticity of hepatic macrophage populations and their activation states in MASLD, challenging traditional classification methods like the M1/M2 paradigm and highlighting the coexistence of harmful and beneficial macrophage phenotypes that are dynamically regulated during MASLD progression. This complexity underscores the importance of considering macrophage heterogeneity in therapeutic targeting strategies, including their distinct ontogeny and functional phenotypes. This review provides an overview of macrophage involvement in MASLD progression, combining traditional paradigms with recent insights from single-cell analysis and spatial dynamics. It also addresses unresolved questions and challenges in this area.
{"title":"Understanding Macrophage Complexity in Metabolic Dysfunction-Associated Steatotic Liver Disease: Transitioning from the M1/M2 Paradigm to Spatial Dynamics.","authors":"Forkan Ahamed, Natalie Eppler, Elizabeth Jones, Yuxia Zhang","doi":"10.3390/livers4030033","DOIUrl":"https://doi.org/10.3390/livers4030033","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), with MASH posing a risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The global prevalence of MASLD is estimated at approximately a quarter of the population, with significant healthcare costs and implications for liver transplantation. The pathogenesis of MASLD involves intrahepatic liver cells, extrahepatic components, and immunological aspects, particularly the involvement of macrophages. Hepatic macrophages are a crucial cellular component of the liver and play important roles in liver function, contributing significantly to tissue homeostasis and swift responses during pathophysiological conditions. Recent advancements in technology have revealed the remarkable heterogeneity and plasticity of hepatic macrophage populations and their activation states in MASLD, challenging traditional classification methods like the M1/M2 paradigm and highlighting the coexistence of harmful and beneficial macrophage phenotypes that are dynamically regulated during MASLD progression. This complexity underscores the importance of considering macrophage heterogeneity in therapeutic targeting strategies, including their distinct ontogeny and functional phenotypes. This review provides an overview of macrophage involvement in MASLD progression, combining traditional paradigms with recent insights from single-cell analysis and spatial dynamics. It also addresses unresolved questions and challenges in this area.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333915","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}
Acetaminophen (APAP) overdose can induce hepatocyte necrosis and acute liver failure in experimental rodents and humans. APAP is mainly metabolized via hepatic cytochrome P450 enzymes to generate the highly reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI), which forms acetaminophen protein adducts (APAP-adducts) and damages mitochondria, triggering necrosis. APAP-adducts and damaged mitochondria can be selectively removed by autophagy. Increasing evidence implies that the activation of autophagy may be beneficial for APAP-induced liver injury (AILI). In this minireview, we briefly summarize recent progress on autophagy, in particular, the pharmacological targeting of SQSTM1/p62 and TFEB in AILI.
{"title":"Targeting Autophagy for Acetaminophen-Induced Liver Injury: An Update.","authors":"Kaitlyn Hinz, Mengwei Niu, Hong-Min Ni, Wen-Xing Ding","doi":"10.3390/livers4030027","DOIUrl":"https://doi.org/10.3390/livers4030027","url":null,"abstract":"<p><p>Acetaminophen (APAP) overdose can induce hepatocyte necrosis and acute liver failure in experimental rodents and humans. APAP is mainly metabolized via hepatic cytochrome P450 enzymes to generate the highly reactive metabolite <i>N</i>-acetyl-<i>p</i>-benzoquinone imine (NAPQI), which forms acetaminophen protein adducts (APAP-adducts) and damages mitochondria, triggering necrosis. APAP-adducts and damaged mitochondria can be selectively removed by autophagy. Increasing evidence implies that the activation of autophagy may be beneficial for APAP-induced liver injury (AILI). In this minireview, we briefly summarize recent progress on autophagy, in particular, the pharmacological targeting of SQSTM1/p62 and TFEB in AILI.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302760","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}
Federica Ferraina, Alessandro Fogliati, M. Scotti, Fabrizio Romano, M. Garancini, C. Ciulli
Segmental or lobar liver atrophy is a common but not well-understood clinical condition. Hepatic atrophy can be classified into hepatic atrophy secondary to other pathologies and primary segmental hepatic atrophy, which is a benign intrahepatic lesion (pseudotumor) not associated with any other pathology. The pathophysiological mechanisms underlying atrophy can be divided into three main situations: obstruction of biliary outflow, obstruction of the systemic venous outflow, and obstruction of incoming portal venous flow. For what may concern secondary hepatic atrophy, there are many pathologies that could underlie this condition, ranging from benign to intrahepatic malignancies, with particular reference to particularly hepatocellular carcinoma and biliary duct carcinoma. An accurate and prompt differential diagnosis between the various forms and causes of atrophy is important for early identification and adequate treatment of underlying pathologies. A comprehensive review of the literature on the etiology and the radiological and histological characteristics of different types of hepatic atrophy is currently unavailable. Therefore, the aim of this review is to summarize the primary and secondary causes of segmental or lobar liver atrophy (excluding forms involving the entire liver parenchyma) and to provide practical tools for clinical and radiological differential diagnosis.
{"title":"Lobar and Segmental Atrophy of the Liver: Differential Diagnoses and Treatments","authors":"Federica Ferraina, Alessandro Fogliati, M. Scotti, Fabrizio Romano, M. Garancini, C. Ciulli","doi":"10.3390/livers4030023","DOIUrl":"https://doi.org/10.3390/livers4030023","url":null,"abstract":"Segmental or lobar liver atrophy is a common but not well-understood clinical condition. Hepatic atrophy can be classified into hepatic atrophy secondary to other pathologies and primary segmental hepatic atrophy, which is a benign intrahepatic lesion (pseudotumor) not associated with any other pathology. The pathophysiological mechanisms underlying atrophy can be divided into three main situations: obstruction of biliary outflow, obstruction of the systemic venous outflow, and obstruction of incoming portal venous flow. For what may concern secondary hepatic atrophy, there are many pathologies that could underlie this condition, ranging from benign to intrahepatic malignancies, with particular reference to particularly hepatocellular carcinoma and biliary duct carcinoma. An accurate and prompt differential diagnosis between the various forms and causes of atrophy is important for early identification and adequate treatment of underlying pathologies. A comprehensive review of the literature on the etiology and the radiological and histological characteristics of different types of hepatic atrophy is currently unavailable. Therefore, the aim of this review is to summarize the primary and secondary causes of segmental or lobar liver atrophy (excluding forms involving the entire liver parenchyma) and to provide practical tools for clinical and radiological differential diagnosis.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141645473","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}
Nathaniel S. Ash, Thomas D. Schiano, J. Safer, M. Fiel, Aren H. Skolnick, Nancy Bach
Background: As transgender people initiate gender-affirming hormone therapy (GAHT), they are exposed to exogenous sex hormones that have effects that have not yet been fully studied. While exogenous estrogen is associated with a risk of venous thrombosis, the full impact of estrogen on the liver is unknown. Conversely, the erroneous attribution of risks from GAHT presents a barrier to treatment for some patients. We present a case of obliterative portal venopathy (OPV) and possible DILI occurring after the initiation of estrogen in a transgender woman. Case presentation: A 28-year-old transgender woman on GAHT was referred to hepatology for liver enzyme elevations. She did not have any notable comorbid conditions, family history, or psychosocial history. Lab and imaging workup were unremarkable, and the patient underwent liver biopsy. The patient’s biopsy results showed OPV. The patient continued GAHT at a lower dose and liver enzyme elevations resolved. Conclusions: OPV is a vascular disease that falls under the category of porto-sinusoidal vascular disorder. Patients with this condition can present with or without overt clinical signs of portal hypertension. Porto-sinusoidal vascular disorder is rare and given the timing and possible dose dependence, it might be reasonable to consider that the observed OPV was influenced by the exogenous estrogen administered in an association not previously reported. Alternatively, the patient’s continued estrogen treatment without ill effect could suggest that the events were not connected and that the fear of harm could have served as a barrier to the patient receiving indicated care.
{"title":"Obliterative Portal Venopathy during Estrogen Therapy in a Transgender Woman: A Case Report","authors":"Nathaniel S. Ash, Thomas D. Schiano, J. Safer, M. Fiel, Aren H. Skolnick, Nancy Bach","doi":"10.3390/livers4030022","DOIUrl":"https://doi.org/10.3390/livers4030022","url":null,"abstract":"Background: As transgender people initiate gender-affirming hormone therapy (GAHT), they are exposed to exogenous sex hormones that have effects that have not yet been fully studied. While exogenous estrogen is associated with a risk of venous thrombosis, the full impact of estrogen on the liver is unknown. Conversely, the erroneous attribution of risks from GAHT presents a barrier to treatment for some patients. We present a case of obliterative portal venopathy (OPV) and possible DILI occurring after the initiation of estrogen in a transgender woman. Case presentation: A 28-year-old transgender woman on GAHT was referred to hepatology for liver enzyme elevations. She did not have any notable comorbid conditions, family history, or psychosocial history. Lab and imaging workup were unremarkable, and the patient underwent liver biopsy. The patient’s biopsy results showed OPV. The patient continued GAHT at a lower dose and liver enzyme elevations resolved. Conclusions: OPV is a vascular disease that falls under the category of porto-sinusoidal vascular disorder. Patients with this condition can present with or without overt clinical signs of portal hypertension. Porto-sinusoidal vascular disorder is rare and given the timing and possible dose dependence, it might be reasonable to consider that the observed OPV was influenced by the exogenous estrogen administered in an association not previously reported. Alternatively, the patient’s continued estrogen treatment without ill effect could suggest that the events were not connected and that the fear of harm could have served as a barrier to the patient receiving indicated care.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141657909","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}
Glen P. Lockwood, Nicholas J. Hunt, M. Kockx, Sun Woo Sophie Kang, D. L. Le Couteur, V. Cogger
The clearance of peripheral beta amyloid (Aβ) is a potential target for the treatment of Alzheimer’s disease (AD). The liver has been implicated in the elimination of Aβ from the peripheral circulation. Here, the single-pass uptake of Aβ40 in perfused livers from young and old rats (6 to 10 rats per group) was investigated with the multiple indicator dilution technique. Aβ40 had volumes of distribution between those of the vascular marker Evans Blue and the extracellular marker sucrose. The hepatic extraction of Aβ40 was negligible, explained in part by the small permeability surface area products consistent with a high endothelial barrier to liver uptake. There were no substantial effects of age on any of these results. In vitro experiments with isolated hepatocytes and liver sinusoidal endothelial cells showed only very small amounts of Aβ uptake consistent with low intrinsic clearance. These results indicate that the hepatic clearance of Aβ is capacity-limited, explained by the low-permeability surface area products and hepatocyte uptake. However, this does not preclude an effect of aging in longer-term in vivo studies where age-related changes in liver blood flow and protein binding influence liver clearance.
{"title":"Understanding the Liver’s Role in the Clearance of Aβ40","authors":"Glen P. Lockwood, Nicholas J. Hunt, M. Kockx, Sun Woo Sophie Kang, D. L. Le Couteur, V. Cogger","doi":"10.3390/livers4020018","DOIUrl":"https://doi.org/10.3390/livers4020018","url":null,"abstract":"The clearance of peripheral beta amyloid (Aβ) is a potential target for the treatment of Alzheimer’s disease (AD). The liver has been implicated in the elimination of Aβ from the peripheral circulation. Here, the single-pass uptake of Aβ40 in perfused livers from young and old rats (6 to 10 rats per group) was investigated with the multiple indicator dilution technique. Aβ40 had volumes of distribution between those of the vascular marker Evans Blue and the extracellular marker sucrose. The hepatic extraction of Aβ40 was negligible, explained in part by the small permeability surface area products consistent with a high endothelial barrier to liver uptake. There were no substantial effects of age on any of these results. In vitro experiments with isolated hepatocytes and liver sinusoidal endothelial cells showed only very small amounts of Aβ uptake consistent with low intrinsic clearance. These results indicate that the hepatic clearance of Aβ is capacity-limited, explained by the low-permeability surface area products and hepatocyte uptake. However, this does not preclude an effect of aging in longer-term in vivo studies where age-related changes in liver blood flow and protein binding influence liver clearance.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141103493","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}
Rebeca Sierra, Ana Marenco-Flores, Marwan Alsaqa, R. Barba, Marcela Cuellar-Lobo, Carla Barberan, Leandro Sierra
Autoimmune hepatitis (AIH) is a varied inflammatory chronic liver disease. AIH’s prevalence varies and has increased recently. Diagnosis involves the discovery of histologic features following liver biopsy and serologic testing. Clinical features vary, and up to 40% of patients may be asymptomatic. Evaluating thiopurine methyltransferase (TMPM) activity before treatment is crucial for an optimal response. The primary treatment goal is biochemical remission, normalized serum IgG, and liver enzymes. Induction therapy typically involves azathioprine and corticosteroids. Close monitoring of liver function tests and serum immunoglobulin levels is essential. Medications can be tapered after achieving biochemical remission. Liver transplantation may be required for refractory disease or cirrhosis. Further therapeutic approaches are needed, particularly for non-responders to first-line treatments.
{"title":"Autoimmune Hepatitis Management: Recent Advances and Future Prospects","authors":"Rebeca Sierra, Ana Marenco-Flores, Marwan Alsaqa, R. Barba, Marcela Cuellar-Lobo, Carla Barberan, Leandro Sierra","doi":"10.3390/livers4020017","DOIUrl":"https://doi.org/10.3390/livers4020017","url":null,"abstract":"Autoimmune hepatitis (AIH) is a varied inflammatory chronic liver disease. AIH’s prevalence varies and has increased recently. Diagnosis involves the discovery of histologic features following liver biopsy and serologic testing. Clinical features vary, and up to 40% of patients may be asymptomatic. Evaluating thiopurine methyltransferase (TMPM) activity before treatment is crucial for an optimal response. The primary treatment goal is biochemical remission, normalized serum IgG, and liver enzymes. Induction therapy typically involves azathioprine and corticosteroids. Close monitoring of liver function tests and serum immunoglobulin levels is essential. Medications can be tapered after achieving biochemical remission. Liver transplantation may be required for refractory disease or cirrhosis. Further therapeutic approaches are needed, particularly for non-responders to first-line treatments.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140977550","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}
Rajiv Kurup, E. Kalo, S. Read, Wai-See Ma, Jacob George, G. Ahlenstiel
(Non-invasive tests (NITs) are a potential alternative to screening oesophagogastroduodenoscopy OGD) for ruling out high-risk varices (HRVs) in patients with compensated advanced chronic liver disease (cACLD). This retrospective study aimed to externally validate and compare various NITs in a multi-centre Australian cohort. Patients with cACLD were enrolled between January 2013 and December 2022. Liver stiffness measurements (LSMs), clinicopathological data, and OGD results were collected. A total of 210 patients were included. The median age was 57 years and 65.7% were male. The main aetiology of cACLD was hepatitis C (41.9%), and 91.9% of patients were Child–Pugh A. HRV prevalence was 12.4%. The Baveno VI criteria (B6C) was the only NIT that could safely reduce the need for OGDs across all aetiologies of cACLD, with a negative predictive value of 98.6 and spared OGD in 33.8%. The FIB-4 would have avoided the most OGDs (71%); however, the HRV miss rate was 6%. The results suggest that the B6C is the best performing NIT in our cohort and reliably excludes HRVs in cACLD patients, regardless of aetiology. This study confirms that the Baveno VI criteria can be applied in an Australian, mixed aetiology cohort to avoid unnecessary screening OGD.
{"title":"Validation and Comparison of Non-Invasive Tests for the Exclusion of High-Risk Varices in Compensated Advanced Chronic Liver Disease","authors":"Rajiv Kurup, E. Kalo, S. Read, Wai-See Ma, Jacob George, G. Ahlenstiel","doi":"10.3390/livers4020014","DOIUrl":"https://doi.org/10.3390/livers4020014","url":null,"abstract":"(Non-invasive tests (NITs) are a potential alternative to screening oesophagogastroduodenoscopy OGD) for ruling out high-risk varices (HRVs) in patients with compensated advanced chronic liver disease (cACLD). This retrospective study aimed to externally validate and compare various NITs in a multi-centre Australian cohort. Patients with cACLD were enrolled between January 2013 and December 2022. Liver stiffness measurements (LSMs), clinicopathological data, and OGD results were collected. A total of 210 patients were included. The median age was 57 years and 65.7% were male. The main aetiology of cACLD was hepatitis C (41.9%), and 91.9% of patients were Child–Pugh A. HRV prevalence was 12.4%. The Baveno VI criteria (B6C) was the only NIT that could safely reduce the need for OGDs across all aetiologies of cACLD, with a negative predictive value of 98.6 and spared OGD in 33.8%. The FIB-4 would have avoided the most OGDs (71%); however, the HRV miss rate was 6%. The results suggest that the B6C is the best performing NIT in our cohort and reliably excludes HRVs in cACLD patients, regardless of aetiology. This study confirms that the Baveno VI criteria can be applied in an Australian, mixed aetiology cohort to avoid unnecessary screening OGD.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140709880","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}
Stephen D. H. Malnick, Ali Abdullah, Fadi Ghanem, Sheral Ohayon Michael, Manuela G. Neuman
Making a diagnosis of alcoholic liver disease is not always easy. There are problems in obtaining an accurate and reliable history of alcohol consumption. Laboratory findings and hepatic imaging studies are neither sensitive or specific, and newer test are being considered. Recently, a patient was admitted with possible alcoholic hepatitis. The first-year resident who admitted the patient mistakenly ordered a blood test for serum IgE. The result was a markedly elevated −6440 IU/mL. There was no evidence of parasitic infections, atopy or autoimmune disease nor was there any eosinophilia. A literature search showed that elevated IgE levels are associated with alcohol abuse. This association has been forgotten and does not appear in standard reference sources such as UptoDate or Harrison’s Principles of Internal Medicine. This judicious use of examining serum IgE levels may aid in the diagnosis of alcoholic hepatitis.
{"title":"Serendipity in Medicine-Elevated Immunoglobulin E Levels Associated with Excess Alcohol Consumption","authors":"Stephen D. H. Malnick, Ali Abdullah, Fadi Ghanem, Sheral Ohayon Michael, Manuela G. Neuman","doi":"10.3390/livers4020012","DOIUrl":"https://doi.org/10.3390/livers4020012","url":null,"abstract":"Making a diagnosis of alcoholic liver disease is not always easy. There are problems in obtaining an accurate and reliable history of alcohol consumption. Laboratory findings and hepatic imaging studies are neither sensitive or specific, and newer test are being considered. Recently, a patient was admitted with possible alcoholic hepatitis. The first-year resident who admitted the patient mistakenly ordered a blood test for serum IgE. The result was a markedly elevated −6440 IU/mL. There was no evidence of parasitic infections, atopy or autoimmune disease nor was there any eosinophilia. A literature search showed that elevated IgE levels are associated with alcohol abuse. This association has been forgotten and does not appear in standard reference sources such as UptoDate or Harrison’s Principles of Internal Medicine. This judicious use of examining serum IgE levels may aid in the diagnosis of alcoholic hepatitis.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140380932","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}
Ramakrushna Paul, Smriti Shreya, Shweta Pandey, Srishti Shriya, Aya Abou Hammoud, Christophe F Grosset, Buddhi Prakash Jain
Heat shock proteins are intracellular proteins expressed in prokaryotes and eukaryotes that help protect the cell from stress. They play an important role in regulating cell cycle and cell death, work as molecular chaperons during the folding of newly synthesized proteins, and also in the degradation of misfolded proteins. They are not only produced under stress conditions like acidosis, energy depletion, and oxidative stress but are also continuously synthesized as a result of their housekeeping functions. There are different heat shock protein families based on their molecular weight, like HSP70, HSP90, HSP60, HSP27, HSP40, etc. Heat shock proteins are involved in many cancers, particularly hepatocellular carcinoma, the main primary tumor of the liver in adults. Their deregulations in hepatocellular carcinoma are associated with metastasis, angiogenesis, cell invasion, and cell proliferation and upregulated heat shock proteins can be used as either diagnostic or prognostic markers. Targeting heat shock proteins is a relevant strategy for the treatment of patients with liver cancer. In this review, we provide insights into heat shock proteins and heat shock protein-like proteins (clusterin) in the progression of hepatocellular carcinoma and their use as therapeutic targets.
{"title":"Functions and Therapeutic Use of Heat Shock Proteins in Hepatocellular Carcinoma","authors":"Ramakrushna Paul, Smriti Shreya, Shweta Pandey, Srishti Shriya, Aya Abou Hammoud, Christophe F Grosset, Buddhi Prakash Jain","doi":"10.3390/livers4010011","DOIUrl":"https://doi.org/10.3390/livers4010011","url":null,"abstract":"Heat shock proteins are intracellular proteins expressed in prokaryotes and eukaryotes that help protect the cell from stress. They play an important role in regulating cell cycle and cell death, work as molecular chaperons during the folding of newly synthesized proteins, and also in the degradation of misfolded proteins. They are not only produced under stress conditions like acidosis, energy depletion, and oxidative stress but are also continuously synthesized as a result of their housekeeping functions. There are different heat shock protein families based on their molecular weight, like HSP70, HSP90, HSP60, HSP27, HSP40, etc. Heat shock proteins are involved in many cancers, particularly hepatocellular carcinoma, the main primary tumor of the liver in adults. Their deregulations in hepatocellular carcinoma are associated with metastasis, angiogenesis, cell invasion, and cell proliferation and upregulated heat shock proteins can be used as either diagnostic or prognostic markers. Targeting heat shock proteins is a relevant strategy for the treatment of patients with liver cancer. In this review, we provide insights into heat shock proteins and heat shock protein-like proteins (clusterin) in the progression of hepatocellular carcinoma and their use as therapeutic targets.","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140265783","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}
Pub Date : 2024-03-01Epub Date: 2023-12-26DOI: 10.3390/livers4010002
Giselle Sanchez-Guerrero, David S Umbaugh, Abhay A Ramachandran, Antonio Artigues, Hartmut Jaeschke, Anup Ramachandran
The adenosine A2B receptor (A2BAR) is a member of a family of G-protein coupled receptors (GPCRs), which has a low affinity for adenosine and is now implicated in several pathophysiological conditions. We have demonstrated the beneficial effects of A2BAR activation in enhancing recovery after acute liver injury induced by an acetaminophen (APAP) overdose. While receptor trafficking within the cell is recognized to play a role in GPCR signaling, its role in the mediation of A2BAR effects in the context of APAP-induced liver injury is not well understood. This was investigated here, where C57BL/6J mice were subjected to an APAP overdose (300 mg/kg), and the temporal course of A2BAR intracellular localization was examined. The impact of A2BAR activation or inhibition on trafficking was examined by utilizing the A2BAR agonist BAY 60-6583 or antagonist PSB 603. The modulation of A2BAR trafficking via APAP-induced cell signaling was explored by using 4-methylpyrazole (4MP), an inhibitor of Cyp2E1 and JNK activation. Our results indicate that APAP overdose induced the translocation of A2BAR to mitochondria, which was prevented via 4MP treatment. Furthermore, we demonstrated that A2BAR is localized on the mitochondrial outer membrane and interacts with progesterone receptor membrane component 1 (PGRMC1). While the activation of A2BAR enhanced mitochondrial localization, its inhibition decreased PGRMC1 mitochondria levels and blunted mitochondrial Cyp2E1 activity. Thus, our data reveal a hitherto unrecognized consequence of A2BAR trafficking to mitochondria and its interaction with PGRMC1, which regulates mitochondrial Cyp2E1 activity and modulates APAP-induced liver injury.
{"title":"Translocation of Adenosine A2B Receptor to Mitochondria Influences Cytochrome P450 2E1 Activity after Acetaminophen Overdose.","authors":"Giselle Sanchez-Guerrero, David S Umbaugh, Abhay A Ramachandran, Antonio Artigues, Hartmut Jaeschke, Anup Ramachandran","doi":"10.3390/livers4010002","DOIUrl":"10.3390/livers4010002","url":null,"abstract":"<p><p>The adenosine A2B receptor (A2BAR) is a member of a family of G-protein coupled receptors (GPCRs), which has a low affinity for adenosine and is now implicated in several pathophysiological conditions. We have demonstrated the beneficial effects of A2BAR activation in enhancing recovery after acute liver injury induced by an acetaminophen (APAP) overdose. While receptor trafficking within the cell is recognized to play a role in GPCR signaling, its role in the mediation of A2BAR effects in the context of APAP-induced liver injury is not well understood. This was investigated here, where C57BL/6J mice were subjected to an APAP overdose (300 mg/kg), and the temporal course of A2BAR intracellular localization was examined. The impact of A2BAR activation or inhibition on trafficking was examined by utilizing the A2BAR agonist BAY 60-6583 or antagonist PSB 603. The modulation of A2BAR trafficking via APAP-induced cell signaling was explored by using 4-methylpyrazole (4MP), an inhibitor of Cyp2E1 and JNK activation. Our results indicate that APAP overdose induced the translocation of A2BAR to mitochondria, which was prevented via 4MP treatment. Furthermore, we demonstrated that A2BAR is localized on the mitochondrial outer membrane and interacts with progesterone receptor membrane component 1 (PGRMC1). While the activation of A2BAR enhanced mitochondrial localization, its inhibition decreased PGRMC1 mitochondria levels and blunted mitochondrial Cyp2E1 activity. Thus, our data reveal a hitherto unrecognized consequence of A2BAR trafficking to mitochondria and its interaction with PGRMC1, which regulates mitochondrial Cyp2E1 activity and modulates APAP-induced liver injury.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617768","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号