New study shows how the vitamin D/TXNIP axis modulates ductular reaction in chronic liver disease, opening potential for affordable adjunct therapy

A team from Chungnam National University in Korea has uncovered a new mechanism by which vitamin D may help reduce liver inflammation and fibrosis in patients with chronic liver disease (CLD). The study, published in Nature Communications, suggests that vitamin D activates the TXNIP gene in cholangiocytes — the ductular cells of the liver — thereby reducing damaging inflammatory processes that drive liver disease progression.

Chronic liver disease affects an estimated 1.5 billion people globally and remains difficult to treat, with liver transplantation as the only curative option in advanced stages. While vitamin D is widely recognised for its role in maintaining bone health, its effects on liver disease have remained underexplored.

“Here, we explored the effects of vitamin D on ductular reaction and CLDs, and investigated underlying mechanisms. Our data reveal that vitamin D supplementation ameliorates ductular reaction and reduces liver inflammation and fibrosis largely through TXNIP,” said Prof Hyo-Jung Kwon, who led the study from the College of Veterinary Medicine at Chungnam National University.

The study found that patients with CLD and low plasma vitamin D levels showed more severe ductular reactions — a response to liver injury characterised by the proliferation of cholangiocytes. While this reaction is initially protective, sustained activation leads to inflammation, fibrosis and long-term damage.

Using a mouse model, the researchers showed that deletion of the Txnip gene in cholangiocytes worsened ductular reaction and liver fibrosis. In vitro experiments further revealed that loss of TXNIP led to increased TNF-α and TGF-β secretion by cholangiocytes, which then activated Kupffer cells and hepatic stellate cells — key drivers of inflammation and collagen deposition.

“Furthermore, Txnip deficiency increases TNF-α and TGF-β secretion by cholangiocytes to stimulate Kupffer cells and hepatic stellate cells, consequently leading to inflammation and collagen deposition,” added Prof Kwon.

The findings offer a possible explanation for how vitamin D could act as a regulatory signal in liver homeostasis and fibrosis — and point to the vitamin D/TXNIP axis as a potential therapeutic target for slowing or preventing CLD progression.

“Our preclinical data reveal a new mechanism by which vitamin D supplementation ameliorates CLDs and support the idea that the vitamin D/TXNIP axis could be a promising therapeutic target in clinically addressing the ductular reaction and CLDs,” said Prof Kwon.

While clinical studies are still needed to confirm efficacy in patients, the study opens the door to more personalised, safer, and affordable interventions — and highlights the growing interest in repurposing well-known agents like vitamin D for complex chronic diseases.