Groover S, Addison S, Nicks S, Mwangi M, Brooks A, Kaul A, Kaul R. Sex based relative expression of estrogen receptors and tumor necrosis factor-alpha in liver affects hepatitis C virus viral pathogenesis. World J Gastroenterol 2025; 31(32): 104277 [PMID: 40900774 DOI: 10.3748/wjg.v31.i32.104277]
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05533197
Submitted on:
September 02, 2025, 10:12
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Reader Comments:
This timely basic study by Groover et al. (WJG 2025; 31: 104277) investigates sex‑based differences in liver expression of estrogen receptors (ERα/ERβ) and tumor necrosis factor-alpha (TNF‑α), elucidating their roles in hepatitis C virus (HCV) pathogenesis. Leveraging human explant tissues from HCV-related cirrhosis and hepatocellular carcinoma (HCC) alongside normal controls, the authors perform RT‑qPCR and Western blot analyses to reveal differential expression patterns by sex and disease state. These findings advance our understanding of why HCV disease progression may diverge between males and females.
The study is commendable for its focus on human tissue specimens and its dual molecular and protein-level methodology, enhancing translational relevance. Additionally, exploring both ER subtypes and TNF-α offers a multifaceted view of hormonal and inflammatory interplay in HCV-mediated liver pathology. The observations pave the way for sex-informed therapeutic strategies and risk stratification.
Nonetheless, the commentary could be strengthened by more detailed insights into downstream signaling pathways, such as NF-κB or apoptosis pathways, which are alluded to but not fully dissected. Moreover, whether the observed ER and TNF-α alterations are causative or reactive remains open. Future investigations integrating functional assays, prospective cohorts, and multi-omics profiling would significantly bolster mechanistic clarity and clinical translation.
In summary, Groover et al. deliver a valuable contribution linking sex-specific molecular expression to HCV pathogenesis, highlighting promising directions for future research.
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