Livers最新文献

{"title":"Multifaceted Human Antigen R (HuR): A Key Player in Liver Metabolism and MASLD.","authors":"Natalie Eppler, Elizabeth Jones, Forkan Ahamed, Yuxia Zhang","doi":"10.3390/livers5030033","DOIUrl":"10.3390/livers5030033","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the leading cause of chronic liver disease worldwide, affecting approximately 25-30% of the global adult population and highlighting the urgent need for effective therapeutics and prevention strategies. MASLD is characterized by excessive hepatic lipid accumulation and can progress, in a subset of patients, to metabolic dysfunction-associated steatohepatitis (MASH), a pro-inflammatory and pro-fibrotic condition associated with increased risk of liver cirrhosis and hepatocellular carcinoma. Although the molecular drivers of MASLD progression remain incompletely understood, several key metabolic pathways-such as triglyceride handling, cholesterol catabolism, bile acid metabolism, mitochondrial function, and autophagy-are consistently dysregulated in MASLD livers. This narrative review summarizes primary literature and highlights insights from recent reviews on the multifaceted role of the mRNA-binding protein Human antigen R (HuR) in the post-transcriptional regulation of critical cellular processes, including nutrient metabolism, cell survival, and stress responses. Emerging evidence underscores HuR's essential role in maintaining liver homeostasis, particularly under metabolic stress conditions characteristic of MASLD, with hepatocyte-specific <i>HuR</i> depletion associated with exacerbated disease severity. Moreover, comorbid conditions such as obesity, type 2 diabetes mellitus, and cardiovascular disease not only exacerbate MASLD progression but also involve HuR dysregulation in extrahepatic tissues, further contributing to liver dysfunction. A deeper understanding of HuR-regulated post-transcriptional networks across metabolic organs may enable the development of targeted therapies aimed at halting or reversing MASLD progression.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":"5 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849976","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}

{"title":"Serological Status of Vaccine and Hepatitis B Virus Exposure Among Children Under 5 and Aged 15-17 Years in Kampala, Uganda.","authors":"Fahad Muwanda, Edward Kiyonga, Joan Nambafu, Agnes Turyamubona, Hussein Mukasa Kafeero, Edgar Kigozi, Harriet Mupere Babikako, Enock Wekiya, Gerald Mboowa, David Patrick Kateete, Hakim Sendagire, Paul J Norman, Bernard Ssentalo Bagaya","doi":"10.3390/livers4040039","DOIUrl":"https://doi.org/10.3390/livers4040039","url":null,"abstract":"<p><strong>Background: </strong>Pediatric hepatitis B virus (HBV) serostatus remains variably characterized, hardly determined at times, or documented as part of national monitoring of the Extended Programs for Immunization (EPI).</p><p><strong>Methods: </strong>We cross-sectionally characterized the seroprevalence of HBV vaccine and/or infection status among 501 and 288 children <5 and 15-17 years old, respectively, in Kawempe Division, Kampala, Uganda, between May and August 2023. These children received HBV vaccination under the Uganda National Extended Program on Immunizations (UNEPI). Samples were qualitatively screened for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb or anti-HBs), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb or anti-HBe), and for hepatitis B core antibody (HBcAb or anti-HBc) using three different HBV Combo test rapid immunochromatographic diagnostic tests: Nova, Fastep, and Beright.</p><p><strong>Results: </strong>The seroprevalence of HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc was 1.52%, 27.75%, 0.88%, 0.63%, and 0.76%, respectively, for the combined study age groups. The HBsAg seroprevalence of 2.78% was almost 3.5-fold higher among adolescents when compared to the 0.8% observed in the under-5-year-olds. The qualitative seroprevalence of anti-HBs was 33.1% and 18.4% in the under-5 and among the 15-17-year-old study groups, respectively.</p><p><strong>Conclusions: </strong>The proportion of qualitatively detectable anti-HBs in both groups of vaccinated children is low and probably indicates reduced seroprotection. Consequently, a large proportion of children who received the hepatitis B vaccine under UNEPI may be at risk of HBV infection, especially adolescents. A booster dose of the Hepatitis B Vaccine may be required for adolescents.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":"4 4","pages":"550-561"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981356","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}

{"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":"4 3","pages":"455-478"},"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}

{"title":"Role of Mitochondrial Iron Uptake in Acetaminophen Hepatotoxicity.","authors":"Jiangting Hu, Anna-Liisa Nieminen, Zhi Zhong, John J Lemasters","doi":"10.3390/livers4030024","DOIUrl":"10.3390/livers4030024","url":null,"abstract":"<p><p>Overdose of acetaminophen (APAP) produces fulminant hepatic necrosis. The underlying mechanism of APAP hepatotoxicity involves mitochondrial dysfunction, including mitochondrial oxidant stress and the onset of mitochondrial permeability transition (MPT). Reactive oxygen species (ROS) play an important role in APAP-induced hepatotoxicity, and iron is a critical catalyst for ROS formation. This review summarizes the role of mitochondrial ROS formation in APAP hepatotoxicity and further focuses on the role of iron. Normally, hepatocytes take up Fe³⁺-transferrin bound to transferrin receptors via endocytosis. Concentrated into lysosomes, the controlled release of iron is required for the mitochondrial biosynthesis of heme and non-heme iron-sulfur clusters. After APAP overdose, the toxic metabolite, NAPQI, damages lysosomes, causing excess iron release and the mitochondrial uptake of Fe²⁺ by the mitochondrial calcium uniporter (MCU). NAPQI also inhibits mitochondrial respiration to promote ROS formation, including H₂O₂, with which Fe²⁺ reacts to form highly reactive •OH through the Fenton reaction. •OH, in turn, causes lipid peroxidation, the formation of toxic aldehydes, induction of the MPT, and ultimately, cell death. Fe²⁺ also facilitates protein nitration. Targeting pathways of mitochondrial iron movement and consequent iron-dependent mitochondrial ROS formation is a promising strategy to intervene against APAP hepatotoxicity in a clinical setting.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":"4 3","pages":"333-351"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649864","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}

{"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":"4 3","pages":"377-387"},"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}

{"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":"29 41","pages":""},"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}

{"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":"86 11","pages":""},"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}

{"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":"45 10","pages":""},"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}

{"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":"123 4","pages":""},"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}

{"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":"68 12","pages":""},"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}