Steatohepatitis and Pancreatic Insufficiency Are Associated with Increased Risk of Peptic Ulcer Disease in the Cystic Fibrosis Population: A National Database Study

Introduction: The prevalence of cystic fibrosis (CF)-specific gastrointestinal symptoms and disease has continued to rise. Prior literature indicates that CF patients suffer from pancreatic insufficiency and steatohepatitis secondary to CF. However, peptic ulcer disease (PUD) has not been well-studied among adults with CF-related disorders and may be a common cause of abdominal symptoms. In CF patients, impaired bicarbonate secretion and unbuffered gastric acid production have been attributed to the development of ulcers. The objective of this study is to evaluate the prevalence of PUD in adult CF patients (Table 1). Methods: This study utilized the National Inpatient Sample (NIS) database, the largest inpatient database in the United States. All patients 18 years or older with CF were identified from 2014 to 2019. Relevant patient characteristics and procedures were identified using ICD-9 codes. Bivariate analyses were conducted using chi-square tests for categorical variables and t-tests for continuous measures and trend analysis. The outcomes of interest were PUD, pancreatic insufficiency, and NASH. All analyses accounted for the complex sampling scheme of the NIS. P-values less than 0.05 were considered statistically significant. Results: The total number of CF patients in the database was stable year to year from 2014 to 2019. During this time, 34690 adults carried a diagnosis of CF. Of those, 414 had peptic ulcers. 51.9% of patients were male, the majority (74%) were white, and 35.3% had private insurance. Hispanic patients were more likely to be diagnosed with PUD than other races (P = 0.005). Comorbid conditions associated with PUD in Cystic Fibrosis include NASH (P = 0.0139) and pancreatic insufficiency (P < 0.0001). All outcomes were adjusted for the use of proton pump inhibitors, H2 blockers, and NSAIDs. Conclusion: Although cystic fibrosis has been historically known as a disease of childhood, advancements in therapy have led to prolonged life expectancy and higher prevalence for CF-related digestive diseases. As lifespan extends, we anticipate a higher prevalence of gastrointestinal sequelae and complications of CF. This study revealed a significant difference in the prevalence of PUD in Hispanics with CF. CF patients who had pancreatic insufficiency, obesity, or NASH were also more likely to develop peptic ulcers. Although peptic ulcers are uncommon in CF, we believe that CF in association with NASH, obesity, or pancreatic insufficiency may lead to a higher risk of peptic ulcers. Table 1. - Demographic and clinical characteristics of adult patients with cystic fibrosis No Ulcer Ulcer All CF Diagnosed N 34276 414 34690 Weighted N 171380 2070 173450 % % % P value Age at hospitalization, years < .0001 0 - 18 27.2 (25.6,28.8) 13.8 (10.4,17.2) 27.0 (25.5,28.6) 19 - 35 50.8 (49.5,52.1) 48.6 (43.5,53.6) 50.8 (49.5,52.1) 36 - 45 9.4 (8.9,9.9) 11.8 (8.7,15.0) 9.4 (9.0,9.9) 46 - 64 7.4 (7.0,7.8) 16.4 (12.8,20.1) 7.5 (7.1,7.9) ≥65 2.4 (2.2,2.6) 6.8 (4.2,9.3) 2.5 (2.3,2.7) Unknown 2.8 (2.5,3.0) 2.7 (0.7,4.6) 2.8 (2.5,3.0) Sex 0.0145 Male 45.8 (45.2,46.4) 51.9 (47.0,56.8) 45.9 (45.3,46.5) Female 54.2 (53.6,54.8) 48.1 (43.2,53.0) 54.1 (53.5,54.7) Race 0.0268 White 78.6 (77.3,79.9) 74.4 (69.9,78.8) 78.5 (77.3,79.8) Black 4.5 (4.2,4.8) 5.8 (3.5,8.1) 4.5 (4.2,4.8) Hispanic 8.7 (8.1,9.4) 12.6 (9.2,15.9) 8.8 (8.1,9.5) Other/mixed/unknown 8.2 (7.0,9.3) 7.2 (4.6,9.9) 8.1 (7.0,9.3) Primary payer < .0001 Medicare 18.9 (18.1,19.6) 27.8 (23.3,32.2) 19.0 (18.2,19.7) Medicaid 33.5 (32.6,34.5) 30.2 (25.7,34.7) 33.5 (32.5,34.5) Private 41.7 (40.9,42.5) 35.3 (30.5,40.1) 41.6 (40.8,42.4) Self-pay or other 5.9 (5.4,6.4) 6.8 (4.4,9.1) 5.9 (5.4,6.4) Median household income for patient's ZIP Code 0.1801 Q1 24.3 (23.4,25.2) 24.5 (20.1,28.9) 24.3 (23.4,25.2) Q2 26.8 (26.1,27.6) 30.6 (26.0,35.3) 26.9 (26.2,27.6) Q3 26.6 (25.9,27.3) 22.1 (17.9,26.2) 26.5 (25.8,27.2) Q4 22.3 (21.2,23.3) 22.8 (18.5,27.1) 22.3 (21.3,23.3) Comorbidities NASH 0.9 (0.8,1.1) 2.2 (0.8,3.6) 0.9 (0.8,1.1) 0.0105 Pancreatic insufficiency 32.6 (30.9,34.3) 22.2 (18.0,26.4) 32.5 (30.8,34.2) < .0001