Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Effect of entecavir on IL-6/STAT3/SOCS3 pathway in patients with chronic hepatitis B-induced liver fibrosis

Shuqiao Wang, Ziqi Sui, Kaili Peng, Hefei Cheng

Department of Gastroenterology, The First People's Hospital of Linping District, Hangzhou, China;

For correspondence:- Shuqiao Wang Email:

Accepted: 30 August 2023 Published: 30 September 2023

Citation: Wang S, Sui Z, Peng K, Cheng H. Effect of entecavir on IL-6/STAT3/SOCS3 pathway in patients with chronic hepatitis B-induced liver fibrosis. Trop J Pharm Res 2023; 22(9):1929-1935 doi: 10.4314/tjpr.v22i9.22

© 2023 The authors.
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Abstract

Purpose: To evaluate the impact of entecavir (ENT) on patients with liver fibrosis resulting from chronic hepatitis B (CHB) and its association with the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3)/suppressor of cytokine signaling 3 (SOCS3) pathway.

Methods: Thirty-one patients with liver fibrosis received ENT at a dose of 0.5 mg/day for 48 weeks. Relevant protein levels in patient’s serum before and after treatment were assayed using enzyme-linked immunosorbent assay (ELISA). Furthermore, human hepatic stellate cells (HSCs) were cultured in vitro and divided into three groups: control, transforming growth factor beta 1 (TGF-β1) induction (TGF-β1 group), and ENT treatment (TGF-β1 + ENT group). Protein levels in the supernatant were assayed using ELISA, while the expression levels of related genes were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). expression of α-SMA was visualized using immunofluorescence assay and the relevant protein levels were determined by Western blotting.

Results: Treatment with ENT significantly decreased (p < 0.01) IL-6 and STAT3 expression, increased SOCS3 expression and significantly reduced (p < 0.01) the concentrations of hyaluronic acid (HA), type IV collagen (IVC), laminin (LN) and pro-collagen type III (PCIII) in patients with liver fibrosis. TGF-β1 significantly (p < 0.01) elevated IL-6, STAT3 and Col-I expressions and a tissue inhibitor of metalloproteinases-1 (TIMP-1) suppressed the expression of SOCS3 in human HSCs and induced fibrosis. Entecavir mitigated TGF-β1-induced fibrogenesis in HSCs (p < 0.01).

Conclusion: Entecavir has a positive effect on liver fibrosis resulting from CHB by regulating IL-6/STAT3/SOCS3 pathway. Future research will focus on conducting larger clinical trials to further validate these findings and explore the long-term effects of ENT on liver fibrosis progression and patient outcomes.

Keywords: Entecavir, Chronic hepatitis B (CHB), Liver fibrosis, IL-6/STAT3/SOCS3 pathway