The burden of pancreatitis continues to rise and is projected to increase substantially by 2050 1. Addressing this trend will require a fundamental shift in clinical practice toward a holistic prevention framework that harmoniously integrates primary, secondary, and tertiary prevention 2. This stands in contrast to the traditional disproportionate focus on in-hospital outcomes of pancreatitis (i.e., secondary prevention). Primary prevention has been established in routine gastroenterology practice only for one type of pancreatitis—post–endoscopic retrograde cholangiopancreatography pancreatitis 2. Recurrent acute pancreatitis represents a potentially more consequential yet markedly understudied type. Historically, it was considered important mainly because of its association with an increased risk of chronic pancreatitis 3. However, more recent evidence indicates that it is also linked to a higher risk of pancreatic cancer and post-pancreatitis diabetes mellitus, regardless of whether chronic pancreatitis ultimately develops 4, 5. Efforts at primary prevention of recurrent acute pancreatitis have traditionally been led by surgeons, with cholecystectomy remaining the standard intervention to prevent recurrent biliary events 2. Gastroenterologists have also sought to contribute to the primary prevention of recurrent acute pancreatitis, for example through repurposing older drug classes such as statins; however, a 2026 randomised controlled trial demonstrated that this approach effectively represents a dead end 6. Professor Loomba and colleagues are to be applauded for renewing optimism in this issue of the Journal by highlighting the potential for gastroenterologists to play a meaningful role in the primary prevention of recurrent acute pancreatitis 7. This includes the exploration of RNA interference therapy—a form of gene silencing in which synthetic RNA molecules are engineered to selectively bind to a target messenger RNA and block its translation into protein. The protein central to their research programme—apolipoprotein C-III—is small (approximately 9 kilodaltons) yet plays a major role in impeding the clearance of triglyceride-rich lipoproteins by restricting lipoprotein lipase access to its substrates, while also exerting a range of lipoprotein lipase–independent effects 8. The drug that silences the messenger RNA encoding apolipoprotein C-III was trialled in patients with familial chylomicronaemia syndrome (median plasma triglyceride concentration of 22 mmol/L at baseline) and its use resulted in an 82% absolute risk reduction in recurrent episodes of acute pancreatitis 7. Although the sample size was limited—67 patients recruited from 58 participating centres across 21 countries—the study provides an important proof of principle. As the inclusion criteria were not constrained to genetically confirmed familial chylomicronaemia syndrome, the findings are likely generalisable beyond this rare genetic disorder. Further, the substantial reduction in plasma triglyceride concentration observed just one month after the initial administration (given once quarterly) suggests that the utility of this novel drug may extend beyond patients with very severe hypertriglyceridaemia. Gene silencing therapy has made considerable advances and should be evaluated in clinical trials with pancreatitis as the primary endpoint. Whether these studies succeed will likely depend on how well cutting-edge mechanistic insights into disease pathogenesis inform their design 9, 10. A new era of pancreatitis prevention may be closer than commonly anticipated. Maxim S. Petrov: conceptualization, writing – original draft. The author has nothing to report. This article is linked to Loomba et al. paper. To view this article, visit https://doi.org/10.1111/apt.70623. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Maxim S. Petrov (Thu,) studied this question.