Comparison of the efficacy and action mechanism of Chinese patent medicines for liver fibrosis and cirrhosis

Background

Liver fibrosis is a critical stage in liver disease progression and can advance to cirrhosis without appropriate treatment. Hepatitis B virus infection is the primary cause of liver fibrosis. Antiviral drugs, e.g., entecavir, are widely used to treat liver fibrosis and cirrhosis. Additionally, Chinese patent medicines, such as Biejiajian Pill (BJP), Liuwei Wuling Tablet (LWT), Fufang Biejia Ruangan Tablet (FFT), Fuzheng Huayu Capsule (FZC), and Anluo Huaxian Pill (AHP), demonstrate therapeutic effects. However, there is still insufficient evidence-based agreement on the most effective therapies and how they work.

Objective

This study aims to identify the most effective Chinese patent medicines for treating liver fibrosis and cirrhosis by combining network meta-analysis and network pharmacology. It also summarises and evaluates the potential mechanisms of effective treatment methods based on published clinical research data. The aim is to provide scientific evidence for clinical decision-making. Finally, these results were verified through experiments. The aim is to provide a scientific basis for clinical decision-making.

Methods

We conducted a comprehensive search of eight databases (PubMed, Web of Science, Excerpta Medica Database (EMBASE), Cochrane Library, China National Knowledge Infrastructure (CNKI), Weipu Database (VIP), and Wanfang) for studies published up to April 2025. After applying inclusion and exclusion criteria, clinical outcomes such as Hyaluronic Acid (HA), Laminin (LN), Type IV Collagen (IV-C), Type III Procollagen (PC-III), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Total Bilirubin (TBIL) were analyzed. A protein-protein interaction (PPI) network was constructed using network pharmacology, with core genes identified via CytoHubba in CytoScape 3.10.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to explore the underlying mechanisms. Next, we validated these predictions using in vivo experiments, observing pathological changes through HE Staining, Masson’s Trichrome Staining, Picro Sirius Red Staining, and Immunohistochemistry, and performing protein expression analysis using Western blotting.

Results

A total of 380 studies involving 37,380 patients, were included. Surface Under the Cumulative Ranking Curve (SUCRA) and Rank 1 probability were used to assess the therapeutic efficacy of each prescription. For liver fibrosis, AHP was the most effective, followed by LWT, FZC, BJP, and FFT. In cirrhosis treatment, LWT was the most effective, followed by AHP, FZC, BJP, and FFT. Combined with network pharmacology analyses revealed that AHP and LWT might play a role in liver fibrosis and cirrhosis by regulating targets such as Signal Transducer and Activator of Transcription 3 (STAT3), Matrix Metallopeptidase 9 (MMP9), Protein kinase B (AKT1), etc. Animal experiments have shown that Chinese patent medicines such as LWT and AHP can significantly improve liver damage in mice and reduce the levels of Alpha-Smooth Muscle Actin (α-SMA), Transforming Growth Factor Beta (TGF-β), Fibronectin (FN), STAT3, and MMP9 in the CCL₄ group, while increasing the expression and content of AKT1.

Conclusion

AHP and LWT are the most effective treatments for liver fibrosis and cirrhosis, respectively according to current network meta-analysis. LWT and AHP may play a role in liver fibrosis and cirrhosis by regulating targets such as STAT3, MMP9, and AKT1, providing a solid foundation for clinical treatment strategies.