Publication Name	World Journal of Hepatology
Manuscript ID	107705
Country	China

Category	Gastroenterology & Hepatology
Manuscript Type	Review
Article Title	Pathogenesis and clinical management of liver damage in porphyrias: Mechanisms and therapeutic approaches
Manuscript Source	Invited Manuscript
All Author List	Tao Zeng, Shu-Ying Huang, Jian-Ning Chen, Jia-Hui Pang, Yu-Tian Chong and Xin-Hua Li
Funding Agency and Grant Number
Corresponding Author	Xin-Hua Li, Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China, Guangzhou 510630, Guangdong Province, China. lixinh8@mail.sysu.edu.cn
Key Words	Porphyria; Porphyria-related liver injury; Pathophysiology; Hepatic cutaneous porphyrias; Protoporphyria; Acute hepatic porphyrias
Core Tip	Porphyria-related liver injury, driven by toxic accumulation of heme biosynthesis intermediates, presents diagnostic challenges due to nonspecific symptoms and insidious progression. The "Two-Hit Model" (porphyrin-protein aggregation and oxidative stress) underpins hepatotoxicity, while protoporphyria-associated cholestasis, liver failure, and acute hepatic porphyria-linked hepatocellular carcinoma (HCC) further increase morbidity. Diagnosis follows a multistep process integrating biochemical profiling, histopathological examination, and genetic testing. Current therapies are palliative, whereas emerging approaches—such as RNA interference (givosiran), melanocortin agonists (afamelanotide), and gene-editing technologies—provide mechanistic targeting. Early surveillance for HCC and multidisciplinary management are essential to mitigate life-threatening complications in these rare metabolic disorders.
Citation	Zeng T, Huang SY, Chen JN, Pang JH, Chong YT, Li XH. Pathogenesis and clinical management of liver damage in porphyrias: Mechanisms and therapeutic approaches. World J Hepatol 2025; In press

Received	2025-04-01 13:36
Peer-Review Started	2025-04-01 13:37
To Make the First Decision
Return for Revision	2025-05-03 16:04
Revised	2025-05-16 12:34
Second Decision	2025-08-07 02:44
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-08-08 09:47
Articles in Press	2025-08-08 09:47
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-5182 (online)
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