Unveiling the Deregulated Pathophysiology for Precision Diagnostics and Personalized Clinical Management of Acute on Chronic Pancreatitis: A Narrative Review

Acute on chronic pancreatitis (ACP) is a transitional condition between acute and chronic pancreatitis, which often gets missed due to overlapping clinical features with other pancreatitis states. The low sensitivity of standard tests like serum amylase and lipase, leading to underreported epidemiological data. This review examines the current knowledge on ACP’s pathophysiology, risk factors, and molecular diagnostic markers differentiating it as a separate entity. ACP clinically presents as ductal obstruction, premature enzyme activation, acinar cell injury, oxidative stress, or / and inflammation. Over the time, it can lead to complications like formation of pseudocyst(s) and type 3 pancreatogenic diabetes mellitus (T3cDM) which could be life threatening, if not treated properly. Sometimes, ACP might also progress to CP, thereby affecting the patients’ quality of life. Literature survey from 2007 to 2025, identifies sphincter of Oddi dysfunction, chronic alcohol consumption, smoking, and medications like hydrochlorothiazide and ACE inhibitors, as accountable factors. Limited studies available highlight a handful of molecular markers, like oxidative stress indicators and inflammatory cytokines as predictors of ACP events, having a potential for improving diagnostic accuracy, but more laboratory studies are needed to validate their utility for addressing the critical gaps. In context to the above scenario, a holistic approach needs to be adopted to deal with ACP inclusive of novel molecular markers for precision diagnosis of ACP events and risk prediction, followed by personalized therapeutic interventions to target inflammation, and other co-morbidities to improve outcomes in ACP patients.