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Eurasian Journal of
Medicine and Oncology Progress in the research of pathology and therapy in liver fibrosis

Figure 2. Clinical assessment of liver fibrosis. Diagnostic methods for suspected liver fibrosis include liver biopsy and non-invasive approaches. The
hepatic injury and inflammation burden of the liver can be precisely assessed by different fibrosis histological staging systems. However, biomarker- and
imaging-based non-invasive methods have emerged as reliable alternatives, showing strong concordance with liver biopsy and reducing its necessity in
routine surveillance.
Abbreviations: MRI: Magnetic resonance imaging; TGF-β: Transforming growth factor beta; PLT: Platelet count; AST: Aspartate aminotransferase;
ALT: Alanine aminotransferase; PDGFR-β: Platelet-derived growth factor receptor beta.

randomized Phase II trial (NCT01357486) has provided TGF-β-stimulated HSC activation, reducing TNF-α-
initial evidence suggesting that sorafenib may benefit a induced hepatocyte apoptosis, and increasing the number
subgroup of cirrhotic patients with HCC, specifically those of M2 macrophages. 72-75 Glutaredoxin-1 has been identified
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with Child-Pugh B7 or albumin-bilirubin grade 1/2. A as the drug target of PFD and plays a role in hepatic
previous study proposed that a low dose and short period fibrosis by curbing Smad3 phosphorylation and reversing
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of sorafenib treatment triggered autophagy rather than oxidative stress-related protein S-glutathionylation. A
apoptosis in HSCs by activating the JNK/c-Jun pathway pilot clinical study of PFD therapy showed that different
and suppressing the Akt/mTOR/p70S6K signaling degrees of improvements in liver histology were observed
pathway. However, in vitro and in vivo studies have proven in 15 patients with HCV-infection-induced cirrhosis
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that sorafenib and its derivative SC-1 can ameliorate liver who had not previously received antiviral therapy after
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fibrosis by decreasing HSC activation and ECM synthesis, 12 months of PFD treatment. The results of a 2-year
as well as by promoting HSC apoptosis through three key PFD treatment in an HCV-liver fibrosis patient cohort
signaling pathways: the signal transducer and activator (NCT02161952) also confirmed the efficacy and safety of
of transcription 3 (STAT3) pathway, the TGF-β1/Smad PFD, which attenuated fibrosis, inflammation, and steatosis
signaling pathway, and PDGFR-β/Akt signaling pathway. stage in liver histology, decreased relative serum cytokines
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In addition, another study reported that sorafenib (TGF-β1 and IL-6) levels, and concurrently enhanced
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reduced liver fibrosis by inducing hypoxia‐inducible anti-fibrogenic cannabinoid receptor 2 gene expression.
factor 1α-mediated ferroptosis in HSCs, which offers a In addition, prolonged-release PFD (PR-PFD), as an
new perspective on its anti-fibrotic effect. In addition, agonist of peroxisome proliferator-activated receptor
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in CCl4-treated rats, sorafenib treatment was correlated alpha (PPAR-α), protected a mouse model of NASH from
to increased lysine crotonylation protein synthesis and inflammation and fibrosis and mitigated hepatic steatosis
decreased expression of related enzymes, which correlated through the activation of the sirtuin 1/liver kinase B1/
with improved liver fibrosis. However, the underlying phospho‐5’ adenosine monophosphate-activated protein
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mechanisms remain to be elucidated. 71 kinase (pAMPK) pathway. Recently, additional data
from a clinical trial (NCT04099407) aimed to assess a
Pirfenidone (PFD) is an orally bioavailable pyridone 12-month treatment of PR-PFD has been reported. A total
derivative that was first approved for the treatment of of 122 advanced liver fibrosis patients with different
idiopathic pulmonary fibrosis. PFD has been reported to etiologic factors were enrolled in the study and received
alleviate fibrosis associated with cystic echinococcosis, PR-PFD plus standard of care. In the PR-PFD group, 35%
CCl4-induced liver injury, and NASH in mice by inhibiting of participants showed significant liver fibrosis regression

Volume 9 Issue 3 (2025) 8 doi: 10.36922/ejmo.8125