Natural History of Chronic Pancreatitis: A Systematic Review

Purpose: Chronic pancreatitis (CP) is characterised by pain, functional deficits, nutritional and mechanical complications. Despite advances in defining aetiology , diagnostics and therapeutic interventions, the clinical course is unpredictable. Moreover, the natural history of the disease as well as the timing of onset of important complications is not well described and there remains substantial variation in management. Factors that influence progression or the onset of important complications in CP are poorly understood, and this limits prognostication and benchmarking of potentially effective interventions. We conducted a systematic review to characterise the natural history of CP, and specifically the progression, complications, and mortality in this condition. Methods: A systematic search was developed with a medical librarian using the Embase, Medline and Cochrane databases. Original articles and conference abstracts describing natural history or prognosis in CP and reporting pre-specified clinical outcomes including pain, endocrine or exocrine dysfunction, mechanical complication and cancer incidence were included. Studies reporting on outcomes from a specific intervention only were excluded. The search was restricted to studies published between 01/01/2000 and 14/09/2020. Results: Following screening of 2,149 titles and 144 full papers, 27 original observational studies reporting on 11,507 patients were included in the systematic review. Number of participants ranged from 23 to 1415. Follow-up ranged from 12 months to 41 years. The most commonly patient-reported complication was pain. Functional pancreatic complications frequently reported include exocrine dysfunction, endocrine insufficiency and in more recently published studies, bone health and sarcopenia. Malignancy outcomes were reported in some studies with a low incidence. There was sparse reporting of progression of major complications, and the use and timing of surgical and endoscopic interventions. Conclusions: This review highlights that the natural history of CP is insufficiently described. More consistent reporting of progression and outcomes would allow for improved monitoring of patients, compare effectiveness of interventions and identify areas of unmet need for research.