Cause-specific mortality in patients with chronic pancreatitis: a nationwide population-based cohort study

BACKGROUND: Chronic pancreatitis is associated with high mortality, but evidence on the causes of death is limited. We investigated cause-specific mortality, including cancer-related deaths, over a 20-year period following chronic pancreatitis diagnosis. METHODS: Using Danish national health registries, we conducted a nationwide cohort study of incident adult (>18 years) chronic pancreatitis cases from 2002 to 2022. Patients were followed from diagnosis until death or the end of follow-up. Cause-specific mortality was estimated using cumulative incidence functions accounting for competing risks. FINDINGS: Among 14,565 patients (mean age 59 years; 64% male) followed for a median of 10.2 years, 7001 (48%) died. In the first 5 years after chronic pancreatitis diagnosis, the leading causes of death were pancreatitis-related, pancreatic cancer, and liver disease, with corresponding 5-year cumulative incidences of 4.5%, 3.4%, and 4.4%, respectively. Beyond 5 years, deaths from extra-pancreatic cancers, respiratory, and cardiovascular disease became more common with corresponding 20-year cumulative risk incidences of 13.4%, 6.1% and 7.0%, respectively. Among cancer deaths, pancreatic cancer predominated early, whereas lung cancer became the leading cause of cancer-related deaths after 5 years. In sensitivity analyses with a 2-year lag between chronic pancreatitis and pancreatic cancer diagnosis, the 5-year cumulative pancreatic cancer incidence decreased from 3.4% to 0.5%, indicating misclassification of early pancreatic cancers. INTERPRETATION: Cause-specific mortality in chronic pancreatitis changes over time. Early deaths are driven by pancreatitis-related deaths and liver disease, whereas extra-pancreatic cancers, respiratory, and cardiovascular deaths become more prominent later. FUNDING: This study was not funded.