Hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection are among the leading causes of chronic liver diseases worldwide. Through the same transmission routes, HBV/HCV coinfection is widespread and aggravates liver damage. In this study, we aimed to assess the safety and efficacy of sofosbuvir/velpatasvir (SOF/VEL) and the pre-treatment of tenofovir alafenamide fumarate (TAF) on HBV reactivation in HBV/HCV coinfected patients.

A multicenter, prospective, single-arm, open-label 12-week trial, followed by a 12/48-week observational clinical trial, was conducted. Ninety-six adults with chronic HBV/HCV coinfection were enrolled from May 2021 to December 2024 in thirteen centers in China. Seventy-seven non-cirrhotic patients were included in Group 1 and nineteen compensated cirrhotic patients in Group 2. All subjects were enrolled to receive SOF/VEL once daily for 12 weeks. Non-cirrhotic subjects received TAF once daily for 28 weeks, and compensated cirrhotic subjects received TAF once daily for 64 weeks simultaneously. Statistical significance was set at P < 0.05.

At the end of SOF/VEL treatment, the overall sustained virologic response was 97.9%, of which 100% was achieved in Group 2. HCV RNA, HBV DNA, and HBV RNA levels were substantially decreased in all patients. Alanine aminotransferase (ALT) (61.5 vs. 21.9, P < 0.001) and aspartate aminotransferase (AST) (50.8 vs. 25.7, P < 0.001) levels decreased, and albumin (ALB) (42.4 vs. 45.1, P < 0.001) level increased compared to pre-treatment in Group 1 at 12 weeks post-treatment. ALT (64.1 vs. 25.2, P < 0.001), AST (65.7 vs. 29.7, P < 0.001), alkaline phosphatase (ALP) (111.6 vs. 88.2, P < 0.05), and alpha-fetoprotein (AFP) (17.9 vs. 4.7, P < 0.05) levels decreased, and ALB (41.3 vs. 42.5, P = 0.051) and platelet count (PLT) (114.0 vs. 127.2, P = 0.052) levels showed a trend toward increase compared to pre-treatment in Group 2 at 48 weeks post-treatment. Liver stiffness measurement (LSM) (22.6 vs. 12.7, P < 0.01), aspartate aminotransferase to platelet ratio index (APRI) (1.6 vs. 0.6, P < 0.001), and fibrosis-4 index (FIB-4) (4.7 vs. 2.6, P < 0.05) significantly decreased after treatment in Group 2. Two patients in Group 1 with genotype 3 showed HBV reactivation and HCV relapse, respectively. No drug-related adverse events were observed in the study.

SOF/VEL effectively achieves a sustained virologic response and improves liver function, with an acceptable safety profile in chronic HBV/HCV coinfected patients, including those with compensated cirrhosis, who achieved modest improvement in non-invasive fibrosis indices. Pre-administration of TAF may mitigates the risk of HBV reactivation in this population.

Studies suggest that Yiguanjian (YGJ) may exert a therapeutic effect on liver fibrosis. However, the active components and molecular targets responsible for its action remain unclear. This study aimed to systematically evaluate the active ingredients and potential targets of YGJ in the treatment of liver fibrosis.

Active compounds and corresponding targets of YGJ were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Liver fibrosis-related datasets were obtained from the Gene Expression Omnibus (GEO) database and divided into training and validation sets. Differentially expressed genes (DEGs) from the training set were subsequently analyzed using network pharmacology, molecular dynamics simulations, and immune infiltration analysis. Three machine learning models were employed to screen for core targets, followed by Gene Set Enrichment Analysis (GSEA) and Mendelian randomization (MR) analysis. The validation set was used to assess the expression levels and diagnostic potential of core targets.

A total of 2,887 liver fibrosis-related targets and 1,198 YGJ-related targets were identified. Three hundred and three putative targets for YGJ in the treatment of liver fibrosis were identified. Three machine learning methods further narrowed these down to five core targets. Immune infiltration analysis revealed an increase in effector B cells, resting CD4+ memory T cells, γδ T cells, and M1 macrophages during liver fibrosis progression. MR analysis showed that all five core targets (FABP4, MDM2, AKR1B1, PDGFRB, and NR1H4) had odds ratios greater than 1, indicating that they function as risk factors. Expression analyses in both the training and validation sets consistently validated the MR results, demonstrating strong diagnostic potential. GSEA revealed that the core targets were enriched in key signaling pathways, including Wnt, PPAR, and MAPK. Molecular docking and molecular dynamics simulations showed that the active compounds of YGJ exhibited strong binding affinity and stability with the core targets.

YGJ exerts its potential antifibrotic effects by downregulating or antagonizing the risk-associated targets (FABP4, MDM2, AKR1B1, PDGFRB, and NR1H4). These findings provide new insights into the potential of YGJ for treating liver fibrosis, while offering a scientific reference for the prevention and treatment of chronic liver diseases.

Luteolin is a dietary flavonoid widely distributed in fruits and vegetables. It has attracted substantial preclinical interest due to its pleiotropic hepatoprotective effects against hepatic steatosis, inflammation, fibrosis, and hepatocellular carcinoma. By reviewing data from in vitro and in vivo studies, this review comprehensively synthesizes the full spectrum of liver-directed pharmacology of luteolin, covering metabolic and toxic liver injury, fibrosis, cancer, and viral hepatitis, while critically mapping each mechanism to specific disease contexts and systematically identifying the key challenges limiting its clinical translation. The underlying mechanisms of luteolin action involve activation of Nrf2-mediated antioxidant defense, suppression of NF-κB- and NLRP3-driven inflammatory responses, inhibition of hepatic stellate cell activation via the TGF-β/Smad and STAT3 pathways, and regulation of metabolic homeostasis through liver X receptor (LXR)/SREBP-1c and AMPK signaling. Despite well-characterized mechanisms in preclinical models, several critical gaps hinder its clinical translation: (1) Rigorous randomized controlled trials in well-defined patient populations are scarce, with only one combination supplement study reported. (2) The relative contribution of luteolin metabolites to its overall bioactivity remains poorly understood, even though derivatives such as luteolin-7-diglucuronide exhibit distinct pharmacological properties. Cell-type-specific delivery systems, which show promise in preclinical fibrosis and cancer models, have not been evaluated clinically. (3) Systematic studies on the synergistic effects of luteolin with standard-of-care drugs remain largely exploratory. Overall, luteolin is a promising multi-target nutraceutical for liver diseases, and its clinical translation requires optimized delivery strategies, investigation of metabolite activity, and well-designed human clinical trials.