Researchers have found that a pair of existing drugs is far more effective when used together than when either is taken alone. The findings point to a practical and potentially fast route toward a long-awaited treatment for liver fibrosis.

Liver fibrosis is a common but often overlooked condition that affects hundreds of millions of people worldwide. Over time, it can worsen into cirrhosis or liver cancer. Even after decades of scientific effort, there are still no antifibrotic drugs approved for clinical use.

The disease develops when repeated or long-term liver damage -- caused by viral hepatitis, excessive alcohol use, metabolic disorders, toxins, or autoimmune disease -- triggers an overactive healing response. A major driver of this process is the activation of hepatic stellate cells (HSCs). Under normal conditions, these cells remain inactive. When injury occurs, they switch into collagen-producing cells that build up scar tissue in the liver.

This harmful transformation is controlled by several overlapping signaling systems, including TGF-β, PDGF, and Wnt/β-catenin pathways. Because fibrosis involves many biological routes at once, drugs that target only one pathway often have limited success. This complexity has fueled growing interest in combination treatments that can block multiple drivers of disease at the same time.

A New Use for Two Familiar Drugs

A study published in Targetome on December 15, 2025 by Hong Wang's & Haiping Hao's team, China Pharmaceutical University, reports that a fixed-dose combination of silybin and carvedilol can strongly suppress hepatic stellate cell activation. By targeting Wnt4/β-catenin signaling, the drug pair was able to reverse liver fibrosis in experimental models, offering a promising strategy for a disease that currently lacks approved therapies.

To better understand silybin's potential and its limitations, the researchers combined laboratory experiments, animal studies, phenotype-based drug screening, and molecular analysis. Early tests focused on liver cell injury models triggered by ActD/TNFα, tBHP, and TNFα. These experiments showed that silybin effectively protected liver cells by restoring viability, lowering harmful reactive oxygen species, and reducing inflammatory gene activity. It also showed strong antiapoptotic, antioxidative, and anti-inflammatory effects without detectable toxicity.

However, when researchers examined whether silybin could directly stop fibrosis, the results were less impressive. In human LX-2 and rat HSC-T6 stellate cells stimulated with TGFβ1, silybin only slightly lowered key fibrosis-related markers such as COL1A1, COL1A2, ACTA2, and TGFB. Similar patterns appeared in mice with liver fibrosis caused by carbon tetrachloride exposure. While silybin led to modest improvements in liver enzymes, collagen buildup, and fibrotic gene expression, its benefits appeared to come mainly from protecting liver cells rather than directly blocking stellate cell activation.