Exocrine Pancreatic Insufficiency Estimated in 40% of Chronic Pancreatitis

About 40% of patients with chronic pancreatitis (CP) have exocrine pancreatic insufficiency (EPI), according to a systematic review and meta-analysis published in the Journal of Pancreatology.¹ ² The analysis also found smoking was associated with increased odds of EPI. Prevalence estimates varied substantially depending on which diagnostic test was used.²

EPI occurs when the pancreas can no longer produce enough digestive enzymes. It leads to fat malabsorption, weight loss, malnutrition, and deficiencies in fat-soluble vitamins A, D, E, and K.² Left untreated, EPI has been linked to increased morbidity, reduced physical function, and greater health care use.²

"This meta-analysis provides critical benchmarks for clinical practice," wrote Xinying Tang, of the Department of Gastroenterology at Eastern Hepatobiliary Surgery Hospital, Naval Medical University, in Shanghai, China, and colleagues. "These findings underscore the need for standardized EPI screening protocols and targeted interventions (eg, smoking cessation) to mitigate complications."²

Why EPI Prevalence Estimates in Chronic Pancreatitis Have Varied

Previous research has reported EPI rates in CP ranging from 14% to 66%. The authors attributed this spread to differences in diagnostic methods, patient populations, and definitions of CP.² Prior studies also focused mainly on prevalence and did not extensively evaluate risk factors.²

To address this gap in research, the investigators searched PubMed, Embase, Cochrane Library, and Web of Science. They looked for English language studies published between November 2004 and November 2024.² The review was registered with PROSPERO and followed PRISMA guidelines.²

After applying the eligibility criteria, the team included 14 studies encompassing 7663 patients with CP, of whom 2947 had EPI.² Seven studies were from Europe, 4 from Asia, and 3 from North America. Exclusion criteria included prior diabetes, previous acute pancreatitis, cystic fibrosis, hereditary pancreatic disorders, and prior pancreatic surgery. The team analyzed data using a random effects model, with subgroup analyses by geographic region, diagnostic method, and study design.²

Fecal Elastase-1 Testing Yielded Greatest EPI Prevalence Estimate

The pooled EPI prevalence was 40.0% (95% Confidence Interval [CI], 33.5% to 46.7%), with high heterogeneity (I² = 96.7%; P < .001).² The authors noted that a high I² in a pooled prevalence analysis does not by itself indicate inconsistency, since some variability is inherent in prevalence data.²

According to investigators, diagnostic method was the most influential factor. Studies using the fecal elastase-1 (FE-1) test reported a prevalence of 52.1% (95% CI, 44.2% to 59.9%). The rate was 31.6% with the ¹³C-mixed triglyceride breath test and 21.1% with steatorrhea/fecal fat testing.²

The authors attributed the gap to FE-1's sensitivity for mild to moderate exocrine dysfunction, whereas fecal fat testing captures overt malabsorption. They also noted that FE-1 can produce false positive results in patients with watery diarrhea. FE-1 cutoffs varied across studies, at 100 μg/g vs 200 μg/g.²

"A lack of standardized diagnostic protocols for EPI in current CP studies substantially compromises the consistency and comparability of findings across cohorts," wrote Tang and colleagues.²

Two Chinese cohorts (n = 946) showed a pooled prevalence of 21.1%. The authors linked this lower rate to reliance on fecal fat testing. Regional estimates were 31.3% in Asia, 44.5% in Europe, and 39.8% in North America, but these differences were not statistically significant.²

Smoking Associated With 51% Greater Odds of EPI in Chronic Pancreatitis

Pooled data from 4 studies showed a significant association between smoking and EPI (OR, 1.51; 95% CI, 1.25 to 1.76).² The small number of studies limited the ability to detect publication bias for this analysis.

Individual studies, rather than the pooled analysis, reported additional factors associated with EPI in multivariate analyses. These included low body mass index and male sex (HR, 1.84).² A single cross-sectional cohort also reported associations with diabetes (OR, 2.45), pancreatic or common bile duct stenting (OR, 1.44), pancreatic resection (OR, 1.54), and bile duct stenosis (OR, 1.48). Main pancreatic duct dilation and gland atrophy were correlated with EPI in univariate analysis.²

Using data from a prior meta-analysis and 2 subsequent studies, the team estimated EPI prevalence in painless CP at 47.6%. A comparison with painful CP could not be performed.²

Heterogeneity and Observational Data Limit Conclusions on EPI Risk Factors

Heterogeneity persisted despite sensitivity and subgroup analyses. Disease duration, a likely confounder, was inconsistently reported across studies.² Limited and partially adjusted risk factor data precluded causal inference.

The authors called for routine EPI screening in patients with CP, particularly those with a smoking history, malnutrition, or advanced pancreatic damage. They recommended FE-1 as a first-line test.² They also noted that pancreatic enzyme replacement therapy remains underused and inadequately monitored. They identified harmonized FE-1 cutoffs, longitudinal natural history studies, and research on smoking cessation as priorities.¹ ²

References

1. Chinese Medical Journals Publishing House Co., Ltd. Exocrine pancreatic insufficiency affects 40% of chronic pancreatitis patients. EurekAlert! Published September 28, 2026. Accessed September 29, 2026. https://www.eurekalert.org/news-releases/1145667

2. Tang X, Guan H, Wu H, et al. Prevalence and risk factors of exocrine pancreatic insufficiency in patients with chronic pancreatitis: a systematic review and meta-analysis. J Pancreatol. 2026;9(3):173-181. doi:10.1097/JP9.0000000000000263