Published online Jun 21, 2024. doi: 10.3748/wjg.v30.i23.2931
Revised: April 30, 2024
Accepted: May 24, 2024
Published online: June 21, 2024
Processing time: 117 Days and 4.4 Hours
In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a critical condition characterized by rapid hepatocellular injury and organ dysfunction, and it often nece
Core Tip: Understanding the interplay between ferroptosis and pyroptosis is crucial for delineating the complex pathophysiology of acute liver failure (ALF). Targeting key regulators of these cell death pathways, particularly silent information regulator sirtuin 1, holds promise for the development of novel therapeutic strategies for mitigating hepatocyte injury and improving clinical outcomes in patients with ALF. Multidisciplinary collaborations that integrate basic science, translational research, and clinical trials should be conducted to accelerate the translation of the experimental findings into effective treatments for this life-threatening condition.
- Citation: Cheng CY, Hao WR, Cheng TH. Understanding the molecular crossroads in acute liver failure: A pathway to new therapies. World J Gastroenterol 2024; 30(23): 2931-2933
- URL: https://www.wjgnet.com/1007-9327/full/v30/i23/2931.htm
- DOI: https://dx.doi.org/10.3748/wjg.v30.i23.2931
Acute liver failure (ALF) poses a major clinical challenge because of its rapid onset and high mortality rate. Characterized by extensive hepatocellular injury leading to organ dysfunction, ALF has various etiologies, including drug toxicity, viral hepatitis, and metabolic disorders. Despite advancements in medical care, liver transplant remains the primary the
ALF is a severe manifestation of liver injury, often resulting from factors such as drug toxicity, viral infections, or metabolic disorders. The hallmark of ALF is the rapid and heavy loss of hepatocytes, leading to impaired liver function and systemic complications. For example, Chen et al[2] demonstrated the mitigative effects of boswellic acid on acetaminophen-induced hepatic injury, suggesting the potential of natural compounds in ameliorating liver damage[2]. Despite advancements in medical care, the mortality rate associated with ALF remains unacceptably high[3]. As mentioned, the study by Zhou et al[1] explored the molecular intricacies of ALF and focused on two pathways of cell death, namely ferroptosis and pyroptosis. Ferroptosis is characterized by iron-dependent lipid peroxidation and mitochondrial dysfunction, whereas pyroptosis is a proinflammatory form of cell death; both pathways have gained attention for their roles in various pathological conditions, including liver diseases[4,5].
Zhou et al[1] investigated the involvement of ferroptosis and pyroptosis in ALF by using clinical samples and animal models. They observed the dysregulation of key proteins involved in these pathways — such as GPX4, SLC7A11, p53, and GSDMD — in liver tissues from patients with ALF. Furthermore, in mouse models where ALF was induced by lipo
In summary, the intricate interplay between ferroptosis and pyroptosis underscores the multifaceted nature of cell death pathways in ALF. Targeting the key regulators of these pathways, particularly SIRT1, holds promise for the development of novel therapeutic strategies for mitigating hepatocyte injury and improving clinical outcomes in patients with ALF. Further research is warranted to clarify the mechanistic complexities of cell death pathways and confirm their therapeutic potential in clinical settings. Collaboration across multiple disciplines is essential for translating experimental insights into effective treatments for this life-threatening condition.
1. | Zhou XN, Zhang Q, Peng H, Qin YJ, Liu YH, Wang L, Cheng ML, Luo XH, Li H. Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis. World J Gastroenterol. 2024;30:1588-1608. [PubMed] [DOI] [Cited in This Article: ] [Reference Citation Analysis (0)] |
2. | Chen LC, Hu LH, Yin MC. Alleviative effects from boswellic acid on acetaminophen-induced hepatic injury - Corrected and republished from: Biomedicine (Taipei). 2016 Jun; 6 (2): 9. doi: 10.7603/s40681-016-0009-1PMCID: PMC4864770. Biomedicine (Taipei). 2017;7:13. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2] [Cited by in F6Publishing: 3] [Article Influence: 0.4] [Reference Citation Analysis (0)] |
3. | Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology. 2012;55:965-967. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 330] [Cited by in F6Publishing: 329] [Article Influence: 27.4] [Reference Citation Analysis (0)] |
4. | Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060-1072. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 4711] [Cited by in F6Publishing: 9022] [Article Influence: 751.8] [Reference Citation Analysis (1)] |
5. | Vande Walle L, Lamkanfi M. Pyroptosis. Curr Biol. 2016;26:R568-R572. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 282] [Cited by in F6Publishing: 425] [Article Influence: 60.7] [Reference Citation Analysis (0)] |