As the body's core metabolic hub, the liver carries out key functions including nutrient processing, toxin filtration, bile production, and immune regulation. The complex structure of the liver, however, makes it vulnerable damages from sepsis, surgery, drugs, viruses, and chronic disease. In a review published in Hepatobiliary Communications , a team of researchers from China highlights a promising protective agent: ulinastatin (UTI).
UTI, a protein naturally present in human urine, is a broad-spectrum serine protease inhibitor that blocks a range of enzymes whose overactivation causes serious tissue damage. Notably, its protective effects go well beyond just stopping these enzymes —it works through multiple pathways to deliver therapeutic effects.
“Accumulating evidence from both preclinical and clinical studies has revealed that UTI exerts significant hepatoprotective effects,” says co-lead author Jia Li from Tianjin Medical University General Hospital. “The pharmacological effects of ulinastatin and current advances in UTI research for liver diseases highlight its potential as a supportive treatment.”
“UTI inhibits cytokines and other inflammatory mediators, reduces cell death and oxidative stress, and helps regulate immune function,” explains corresponding author Chao Sun from the First Affiliated Hospital of Xi'an Medical University. “It also adjusts the activity of enzymes involved in the blood clotting and fibrinolysis system.”
The researchers also summarized UTI’s protective effects across seven liver conditions. “In sepsis induced liver injury, UTI reduces oxidative stress, apoptosis, and inflammatory cell infiltration, thereby lowering liver enzyme levels,” shares Sun. “For hepatic ischemia reperfusion injury, it inhibits neutrophil elastase and chemokine production to mitigate the damage that occurs when blood flow returns to the liver after surgery or transplantation.”
Meanwhile, in liver failure, studies have shown that UTI exerts antioxidant and anti inflammatory actions in multiple models, including drug induced injury and in hepatitis, plasma UTI levels correlate with disease severity and normalise during recovery, suggesting its potential as a biomarker.
“In liver fibrosis, UTI suppresses TGF β activation, a key driver of scar tissue formation,” adds Sun. “For hepatocellular carcinoma, it may enhance chemotherapy sensitivity by inhibiting Wnt/β catenin signalling.”
As for hepatic encephalopathy, preclinical evidence indicates that UTI protects the blood brain barrier and maintains brain water balance.
Nonetheless, while UTI is already approved for conditions including acute pancreatitis and sepsis China in Japan, the researchers cautioned that high-quality randomized controlled trials are needed to establish optimal dosing and confirm benefits on hard outcomes like mortality. “Side effects are generally mild, including dizziness, rash, or gastrointestinal discomfort, but drug interactions and dose-related risks require further investigation,” says Li.
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Contact the author : Jia Li, Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China. Email: JiaLi1299@tmu.edu.cn.
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Literature review
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The medicinal effect of ulinastatin in various liver diseases
The authors declare that they have no competing interests.