Treat-to-target in pancreatic exocrine insufficiency: moving from symptom control to nutrition outcomes

Pancreatic exocrine insufficiency (PEI) is a high-prevalence, high-impact syndrome that remains disproportionately under-recognized in routine care. Contemporary guidance from the American Gastroenterological Association (AGA) and the 2025 European multidisciplinary guideline (including the Pancreatology recommendations summary) converges on three practical principles: (I) identify PEI early in at-risk populations (chronic pancreatitis, pancreatic cancer, pancreatic surgery, and other causes of pancreatic damage); (II) use fecal elastase-1 (FE-1) as an accessible first-line test; and (III) treat with pancreatic enzyme replacement therapy (PERT) at adequate doses with structured titration (1-3). Yet, implementation lags: FE-1 is not ordered systematically, PERT is often under-dosed, and follow-up frequently focuses on symptom relief rather than nutritional recovery. Recent Hepatobiliary Surgery and Nutrition (HBSN) editorials/commentaries have emphasized persistent diagnostic and dosing compromises in PEI care (4) and the importance of nutrition-focused, outcome-driven management (5). HBSN reviews also highlight the clinical relevance of muscle-wasting endpoints in pancreatic disease (6), while methodological work in pancreatic surgery underscores the need for standardized nutrition outcome reporting (7).

A pragmatic outpatient laboratory audit underscores the scale of the problem. In 64 stool samples submitted for FE-1 testing in routine pancreatology practice, 26.6% met the biochemical threshold for PEI (FE-1 ≤200 µg/g) and 15.6% met criteria for severe PEI (FE-1 ≤100 µg/g) (Table 1). These data are aggregated and de-identified; clinical metadata (diagnosis, stool consistency, body mass index, laboratory nutrition markers, and PERT use) were not linked. Even with these limitations, the “one-in-four” signal is clinically instructive: a substantial fraction of clinic patients may harbor treatable maldigestion that is unlikely to be corrected by sporadic testing or low-dose empiricism.

Why does this matter? PEI is not merely a symptom generator; it is a driver of downstream morbidity through chronic energy and micronutrient deficits. In chronic pancreatitis cohorts, sarcopenia associates with higher hospitalization rates and reduced survival, and recent meta-analytic data suggest sarcopenia affects a large minority of patients (8,9). Bone disease is similarly common and frequently missed, with observational studies demonstrating a high burden of osteoporosis/osteopenia and insufficient detection in usual care (10,11). Micronutrient deficiencies (fat-soluble vitamins and trace elements) are prevalent and warrant routine biochemical assessment and targeted supplementation (12).

These outcomes expose a central weakness in symptom-first PERT practice: diarrhea or bloating may improve at doses that remain inadequate for nutritional repletion. A recent systematic review of real-world PERT dosing and effectiveness highlights variable adherence to guideline-recommended doses and inconsistent measurement of nutritional outcomes (13). If clinicians do not measure nutrition endpoints, they cannot reliably know whether digestion has been restored.

We propose operationalizing PEI management as a treat-to-target pathway (Figure 1), consistent with recent guideline and nutrition-focused recommendations (1-3,14). The target is not only symptom reduction, but objective stabilization or improvement in nutritional status. A minimal panel is feasible in most clinics: baseline weight and recent weight change; FE-1 with attention to pre-analytics (particularly watery stools, which may artifactually lower FE-1); and a focused nutrition set (albumin as a coarse marker, 25-hydroxyvitamin D and calcium, and selected trace elements where available) (1-3,12). For body composition, a pragmatic approach is to use existing cross-sectional imaging (when present) to screen for low muscle mass, and to arrange DXA in patients with chronic pancreatitis, longstanding PEI, or other fracture risks, consistent with guideline-recommended bone and nutrition monitoring (1,2).

Figure 1 Treat-to-target clinic pathway for PEI. Key elements include: (I) systematic identification of at-risk phenotypes; (II) baseline FE-1 and a minimal nutrition panel; (III) prompt initiation of adequately dosed PERT; (IV) reassessment at 4–8 weeks with explicit dose escalation when targets are not met; and (V) longer-term monitoring of micronutrients, sarcopenia and bone health. FE-1 values may be falsely low in watery stools. DXA, dual energy x-ray absorptiometry; FE-1, fecal elastase-1; PEI, pancreatic exocrine insufficiency; PERT, pancreatic enzyme replacement therapy.

Once PEI is diagnosed or strongly suspected, PERT should be started at an evidence-based dose (typically 40,000–50,000 lipase units with main meals and 20,000–25,000 units with snacks) and titrated using a structured algorithm (1-3). At 4–8 weeks, reassess stool form and frequency, abdominal symptoms, weight trajectory, and selected nutrition markers; if targets are not met, escalate dose, optimize timing with meals, consider acid suppression, and evaluate common confounders (e.g., small intestinal bacterial overgrowth, bile acid diarrhea, or ongoing alcohol/tobacco exposure) (1-3,13). Longer-term, repeat clinical and biochemical monitoring (symptoms, weight trajectory, and selected nutrition markers) approximately every 6 months (2,3). Bone and body composition assessment by DXA is typically performed less frequently (e.g., every 1–2 years) in guideline-based pathways (1,2).

Patient experience must remain central. Narrative syntheses describe substantial symptom burden, quality-of-life impairment, and unmet needs among individuals living with PEI; “adequate dosing” is not only a biochemical goal but a patient-centered intervention (15).

In summary, our outpatient audit reinforces that PEI is common among patients presenting to a pancreatology clinic, even when only laboratory data are considered. Closing the implementation gap requires a shift in mindset: test systematically, start adequate PERT, and treat to objective nutrition outcomes. A practical clinic pathway with explicit reassessment intervals and dose-escalation rules can convert guideline knowledge into measurable patient benefit.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Funding: The research was funded by the National Key Research and Development Program of China (No. 2024YFA0918504), the National Natural Science Foundation of China (No. 82460135), the Beijing Natural Science Foundation (No. L248074), and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2024-RW320-01).

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2026-0177/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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