66 As the body’s core metabolic hub, the liver carries out key functions including nutrient processing, toxin filtration, bile production, and immune regulation. Its complex structure, however, makes it vulnerable to damage 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. Its protective effects extend beyond enzyme inhibition, working through multiple pathways to deliver therapeutic benefits. “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 summarised 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. For hepatic ischaemia-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. In liver failure, studies have shown that UTI exerts antioxidant and anti-inflammatory actions across multiple models, including drug-induced injury. 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. 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. Ulinastatin is already approved for conditions including acute pancreatitis and sepsis in China and Japan. The researchers cautioned that high-quality randomised 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. Experts note that ulinastatin’s multi-pathway action makes it particularly interesting for complex liver injuries where inflammation and oxidative stress play major roles. While much of the evidence comes from preclinical models and smaller clinical studies, larger trials could clarify its place in routine care for patients facing liver damage from critical illness or surgery. Liver disease remains a significant global health challenge, with conditions such as sepsis-related injury and ischaemia-reperfusion damage contributing to high rates of complications following transplantation and major abdominal procedures. Supportive therapies like ulinastatin that target underlying mechanisms without replacing standard care could offer clinicians additional tools to improve outcomes. The review underscores the need for further research to translate these promising findings into clinical practice, particularly in Western healthcare settings where ulinastatin is not yet widely available. Future studies should focus on standardised dosing regimens and long-term patient outcomes to fully evaluate its potential.