New precision therapies reshape the future of pancreatitis treatment

Pancreatitis remains a major global health burden, encompassing acute pancreatitis (AP), chronic pancreatitis (CP), and autoimmune pancreatitis (AIP). AP affects 13-49 people per 100,000 annually, with up to 20% developing severe complications such as organ failure. CP, although less common, causes persistent pain, malabsorption, and metabolic disorders that severely impair quality of life. AIP, an immune-mediated subtype, is characterized by systemic inflammation and fibrosis. Despite advances in clinical care, available therapies often fail to halt disease progression or prevent recurrence. Due to these persistent challenges, there is an urgent need to develop novel, mechanism-based, and personalized therapeutic strategies for pancreatitis.

Hepatobiliary & Pancreatic Diseases International has launched a special issue on "Novel Treatment Strategies for Pancreatitis" in August 2025. Professor Zhao-Shen Li and Professor Wen-Bin Zou from the Department of Gastroenterology at Changhai Hospital, Naval Medical University are invited as the Guest Editors. The editorial (DOI: 10.1016/j.hbpd.2025.06.005) summarizes emerging therapies that are transforming pancreatitis care—from optimized fluid resuscitation and anticoagulant therapy to stem-cell transplantation, endoscopic innovations, and gene-targeted treatments—laying the groundwork for more effective, individualized, and minimally invasive management of pancreatic diseases.

This editorial outlines how treatment strategies for AP are evolving from supportive care to mechanism-driven interventions. Controlled trials show that moderate rather than aggressive fluid resuscitation improves outcomes, while low-molecular-weight heparin reduces necrosis and inflammation. Hypoxia-preconditioned mesenchymal stem cells can deliver functional mitochondria, restore cellular energy metabolism, and repair acinar injury. Molecular studies targeting calcium signaling—such as ORAI1 channel inhibitors—represent promising early-stage drug candidates.

For CP, innovative local treatments like "chemical pancreatectomy" can ablate diseased tissue while preserving endocrine function, and AAV8-mediated SPINK1 gene therapy reverses fibrosis in animal models. Endoscopic retrograde cholangiopancreatography (ERCP) combined with extracorporeal shock wave lithotripsy (ESWL) remains key for removing pancreatic stones, with preoperative indomethacin effectively preventing post-procedure pancreatitis. In AIP, corticosteroids remain the first-line therapy, while immunosuppressants, biologics such as rituximab, and TNF inhibitors are used in refractory cases. Single-cell transcriptomic studies have revealed fibrosis-related targets like the HIF-1α-VISFATIN axis, providing potential pathways for immunomodulatory therapy. Together, these findings signal a shift toward precision and mechanism-guided management.

Pancreatitis research is entering a transformative stage. Integrating molecular mechanisms with clinical innovation is redefining our understanding of this disease. From mitochondria-based cell therapies to gene modulation strategies, every discovery moves us closer to precise and durable treatment. The next challenge is to translate these promising approaches into large-scale clinical practice that can truly improve patient survival and quality of life."

Professor Zhao-Shen Li, senior gastroenterologist at Changhai Hospital

The editorial underscores that the future of pancreatitis management lies in precision, integration, and innovation. By combining molecular targeting, regenerative medicine, and immune modulation, upcoming therapies could revolutionize care for millions of patients worldwide. The translation of stem cell and gene therapies may not only relieve pain and organ dysfunction but also prevent disease progression from acute to chronic stages. As multidisciplinary collaboration strengthens among gastroenterologists, surgeons, geneticists and immunologists, precision gastroenterology is poised to become the cornerstone of pancreatitis treatment, offering renewed hope for better long-term outcomes.