A new study by researchers in Korea uncovers how Vitamin D reduces inflammation and fibrosis in chronic liver disease by activating the TXNIP gene in ductular cells.
Chronic Liver Disease
Chronic Liver Disease (CLD) affects millions of people worldwide and lacks a universal cure. Vitamin D is widely recognized for its role in bone health. Yet it remains underexplored in the regions of its effect on liver disease. Recent research in Korea has shown that Vitamin D supplements activate the TXNIP gene in ductular cells, which can reduce liver inflammation and fibrosis. Moreover, these suggest that Vitamin D can be a favorable, low-cost complementary medication for treating CLD.
Affecting approximately 1.5 billion people, CLD has become a major global health concern. This life-threatening disease, often progressing silently, can lead to worse cases like liver cirrhosis or liver cancer. As of now, there is no treatment found for CLD apart from liver transplantation.
Vitamin D is commonly consumed to enhance bone health. A recent study has opened a possibility which shows that Vitamin D can act as a supplement, and in turn, a complementary therapy for liver diseases. The research team, comprising of Prof. Hyo-Jung Kwon, the College of Veterinary Medicine, Chungnam National University in Daejeon, Republic of Korea, and his colleagues, has studied the underlying mechanisms and therapeutic implications of Vitamin D in liver disease.
Prof. Kwon comments: “Here, we explored the effects of vitamin D on ductular reaction, CLDs, and investigated underlying mechanisms. Our data reveal that vitamin D supplementation ameliorates ductular reaction, reduces liver inflammation, and fibrosis largely through TXNIP.”
Their study was published on May 13, 2025, in Nature Communications.
What is Ductular Reaction?
Ductular reaction refers to the proliferation of ductular cells (primarily cholangiocytes) in response to liver injury. Though it is initially protective, an excessive or prolonged ductular reaction can lead to inflammation and fibrosis. The researchers have observed, in this study, that lower plasma levels of vitamin D were associated with more severe ductular reaction in patients suffering from CLD.
More About the Findings
Vitamin D upregulates the expression of TXNIP (Thioredoxin-interacting protein). This was confirmed by a mouse study where TXNIP deletion, in cholangiocytes, promoted ductular reaction. Further, it also worsened liver inflammation and fibrosis. In vitro, analysis revealed the Vitamin D / TXNIP molecular axis.
Prof. Kwon added, “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.”
It is extremely essential for research that supports early diagnosis and better treatment for CLD. “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,” says Prof. Kwon.
There is also a need for further research to validate the clinical application of Vitamin D supplementation as a standard supportive therapy for patients with chronic liver disease (CLD).
Ultimately, this research can improve the lives of millions worldwide by offering safer, low-cost, and more personalized liver disease therapies.
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