Chronic liver disease (CLD) is a major global health concern, affecting approximately 1.5 billion people. This life-threatening disease often progresses silently, eventually leading to worsened conditions like liver cirrhosis or liver cancer. There is currently no treatment for CLD other than liver transplantation.
Vitamin D is commonly consumed for enhanced bone health. This study opens exciting possibilities for repurposing an inexpensive supplement as a complementary therapy for liver diseases. Prof. Hyo-Jung Kwon from the College of Veterinary Medicine, Chungnam National University in Daejeon, Republic of Korea, and his colleagues have studied the underlying mechanisms and therapeutic implications of Vitamin D in liver disease. "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," comments Prof. Kwon. Their study was published online on 13 May 2025, in Nature Communications .
Ductular reaction refers to the proliferation of ductular cells (primarily cholangiocytes) in response to liver injury. While initially protective, excessive or prolonged ductular reaction contributes to inflammation and fibrosis. In this study, researchers observed that lower plasma levels of vitamin D were associated with more severe ductular reaction in patients with CLD.
Vitamin D upregulates the expression of TXNIP (Thioredoxin-interacting protein). This was confirmed in a mouse study where Txnip deletion in cholangiocytes promoted ductular reaction and even exacerbated liver inflammation and fibrosis. In vitro analysis revealed the Vitamin D/TXNIP molecular axis. "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," adds Prof. Kwon.
Research that supports early diagnosis and better treatment for CLD is not only warranted but essential. "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," comments Prof. Kwon. Further research is needed to validate the clinical application of vitamin D supplementation as a standard supportive therapy for patients with chronic liver disease.
Ultimately, this work could improve outcomes for millions worldwide by offering safer and more personalized liver disease therapies.
