Livers最新文献

{"title":"Decoding the Complexity of Hepatocellular Carcinoma: Clinical Challenges and Targeting HuR as a Novel Therapeutic Strategy.","authors":"Elizabeth Jones, Natalie Eppler, Forkan Ahamed, Yuxia Zhang","doi":"10.3390/livers6040074","DOIUrl":"10.3390/livers6040074","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and remains a major therapeutic challenge due to its marked inter- and intratumoral heterogeneity, diverse etiologies, and high propensity for therapeutic resistance. This review summarizes the biological complexity of HCC and current therapeutic challenges, with a particular focus on the RNA-binding protein human antigen R (HuR) as an emerging therapeutic target.</p><p><strong>Methods: </strong>A comprehensive narrative review of peer-reviewed literature was conducted, focusing on HCC pathogenesis, molecular heterogeneity, tumor microenvironment, mechanisms of therapeutic resistance, and recent advances in treatment. Emphasis was placed on studies investigating the biological functions of HuR and its therapeutic potential in HCC.</p><p><strong>Results: </strong>HCC progression is driven by complex interactions among genetic, epigenetic, metabolic, and environmental factors, resulting in substantial tumor heterogeneity and variable therapeutic responses. Dysregulated oncogenic signaling and immunosuppressive tumor microenvironment collectively contribute to resistance against current therapies, including multikinase inhibitors and immune checkpoint inhibitors. Although emerging strategies, such as combination immunotherapy, metabolic targeting, epigenetic modulation, and precision medicine, have shown encouraging preclinical and clinical results, their efficacy remains limited by tumor complexity and adaptive resistance. HuR functions as a master post-transcriptional regulator that stabilizes and promotes the translation of numerous mRNAs encoding oncogenic, inflammatory, and pro-survival factors. Accumulating preclinical evidence demonstrates that pharmacological inhibition of HuR suppresses multiple tumor-promoting pathways and enhances therapeutic sensitivity, supporting its potential as a novel therapeutic strategy for HCC.</p><p><strong>Conclusions: </strong>The biological complexity of HCC necessitates multifaceted, precision-based therapeutic approaches. Although additional HCC-specific mechanistic and translational studies are needed, targeting HuR represents a promising strategy to overcome tumor heterogeneity, therapeutic resistance, and disease progression. Continued integration of molecular profiling, advanced omics technologies, and rational combination therapies will be essential for translating these advances into improved clinical outcomes for patients with HCC.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":"6 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714904","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":"The Hepatic Crown-like Structure: A Focal Point for Macrophage Evolution and Disease Response in Steatotic Liver Disease.","authors":"Kyle Yuquimpo, Ayobami Dare, Isabel Aranzazu Pulido Ruiz, Steven A Weinman","doi":"10.3390/livers6040072","DOIUrl":"10.3390/livers6040072","url":null,"abstract":"<p><p>The hepatic crown-like structure (hCLS) is a shell-like aggregate of macrophages surrounding a large lipid-laden dying hepatocyte. This feature was initially assumed to simply be a response to increased inflammatory stress during steatotic liver disease, but recent studies have shown that the hCLS is a critical site for lipid processing, inflammation regulation, fibrosis modulation and macrophage development. Furthermore, advances in lineage tracing and transcriptomic analysis have provided information on the nature of the macrophage subtypes present in the hCLS. The hCLS consists of a heterogeneous mixture of macrophages that arise largely from bone marrow-derived infiltrating macrophages (IMs) but also have some of the properties of Kupffer cells (KCs). Most of the cells are variations of Lipid-Associated Macrophages (LAMs) expressing surface proteins such as GPNMB, TREM2, CD9, CD36, CD63 and CD11c. In addition, a class of LAM-like KCs is also present and these typically express many of the LAM proteins along with KC lineage proteins such as VSIG4 and CLEC4F. The hCLS plays an important role in lipid disposition and inflammation but conflicting evidence appears to support roles in fibrogenesis, extracellular matrix remodeling, and matrix degradation. This review aims to describe the critical findings and discoveries made regarding hCLSs and their role in macrophage development and function in steatotic liver diseases.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":"6 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714962","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":"Are CD4⁺ T-Cell Counts Associated with <i>Pneumocystis jirovecii</i> Detection in Hospitalized Patients with Liver Disease? A Retrospective Exploratory Pilot Analysis.","authors":"Antonios Katsounas, Amer Nashtar, Jasmin Weninger, Michael Steckstor, Despoina Koulenti, Joshua D Nosanchuk, Mustafa Özcürümez, Ali Canbay, Peter M Rath","doi":"10.3390/livers6030040","DOIUrl":"10.3390/livers6030040","url":null,"abstract":"<p><strong>Background: </strong>Advanced cirrhosis induces profound CD4⁺ T-cell depletion through splenic sequestration and immune dysregulation. <i>Pneumocystis jirovecii</i> pneumonia risk thresholds remain undefined in non-HIV immunocompromised populations, necessitating investigation in cirrhotic patients.</p><p><strong>Objectives: </strong>To investigate the potential association between peripheral CD4⁺ T-cell counts and opportunistic infections (OI)-specifically <i>Pneumocystis jirovecii</i> (PJ)-in hospitalized patients with liver disease, and to characterize clinical outcomes across immunological risk strata.</p><p><strong>Methods: </strong>We retrospectively analyzed 455 adults hospitalized in a single institution with hepatic disorders. CD4⁺ T-cell counts were available in 227/455 patients. Among these, 22 patients met predefined immunological risk criteria (CD4⁺ < 500/μL and/or HIV positivity) and were classified into three immunological risk clusters (IRCs): IRC-A (HIV-, CD4⁺ < 200/μL; n = 9), IRC-B (HIV+, CD4⁺ < 200/μL; n = 7), and IRC-C (HIV-, CD4⁺ 200-499/μL; n = 6). PJ PCR testing was evaluated when available.</p><p><strong>Results: </strong>Among 455 patients, in-hospital mortality was 103/455 (22.6%). Of the 22 immunologically at risk patients, 15/22 had cirrhosis. PJ PCR was performed in 8/22 patients (IRC-A: 2; IRC-B: 4; IRC-C: 2), with 3/8 positive (37.5%): IRC-A (1/2), IRC-B (1/4), IRC-C (1/2). Ct values ranged from 27.0 to 31.7. Two PJ-PCR-positive cirrhotic patients (IRC-A: n = 1; IRC-C: n = 1) survived without specific anti-PJ therapy; one HIV-positive patient (IRC-B) received trimethoprim-sulfamethoxazole and survived. In-hospital mortality was 5/9 (55.6%) in IRC-A, 2/7 (28.6%) in IRC-B, and 3/6 (50.0%) in IRC-C; none of the deaths were attributable to PJ pneumonia.</p><p><strong>Conclusions: </strong>Severe CD4⁺ T-cell depletion (<200/μL) was common among cirrhotic patients and associated with PJ detection (3/8 tested), but not with PJ-related mortality (0/3). Mortality was primarily driven by hepatic decompensation and bacterial infections. CD4⁺ assessment may improve risk stratification in cirrhosis; however, prospective, multicenter studies are warranted to validate these findings and to evaluate CD4-guided strategies for the prevention of opportunistic infections.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":"6 3","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148152396","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":"Special Issue \"Mechanistic and Prognostic Biomarkers in Liver Diseases\".","authors":"Hartmut Jaeschke, Mitchell R McGill","doi":"10.3390/livers5040060","DOIUrl":"10.3390/livers5040060","url":null,"abstract":"","PeriodicalId":74083,"journal":{"name":"Livers","volume":"5 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12795593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967812","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":"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":"Effects of Chronic Elevation in Plasma Membrane Cholesterol on the Function of Human Na⁺/Taurocholate Cotransporting Polypeptide (NTCP) and Organic Cation Transporter 1 (OCT1).","authors":"Jessica Y Idowu, Caylie McKimens, Bruno Hagenbuch","doi":"10.3390/livers5030045","DOIUrl":"10.3390/livers5030045","url":null,"abstract":"<p><strong>Background: </strong>We have previously demonstrated that the function and expression of the Na⁺/taurocholate cotransporting polypeptide (NTCP) and the organic cation transporter 1 (OCT1) are affected by increasing free or unesterified cholesterol in the plasma membrane by an acute incubation with cholesterol for 30 min. In the current study we wanted to extend these findings to a more chronic condition to mimic what would be seen in obese patients.</p><p><strong>Methods: </strong>We incubated HEK293 cells that stably express NTCP or OCT1 for 24 h with 0.05 mM cholesterol and determined their function by measuring uptake of radio-active taurocholate or MPP⁺. Expression at the plasma membrane was quantified with a biotinylation assay combined with Western blots.</p><p><strong>Results: </strong>Incubation with cholesterol increased the cholesterol content of the cells by about 2-fold. Transport mediated by NTCP and OCT1 was decreased. Membrane expression for both transporters showed a slight decrease, and when kinetics were normalized for the membrane expression, the V_max for NTCP-mediated taurocholate uptake slightly decreased, but the V_max and the capacity (V_max/K_m) for OCT1-mediated MPP⁺ uptake increased by 2.5-fold and 3-fold, respectively. Acyl-Coenzyme A acyltransferase inhibitors enhanced the decrease in transport function, potentially due to retention of more free cholesterol in the plasma membrane.</p><p><strong>Conclusions: </strong>Chronic increases in free cholesterol in the plasma membrane can result in increased or decreased transporter function and expression. In the case of OCT1, which is involved in the uptake of the anti-diabetic drug metformin into hepatocytes, the 3-fold increase in transport capacity might affect drug therapy.</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/PMC12687901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727771","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}