Ogbu, Chukwuemeka E.

Importance: Chronic liver disease requires sustained engagement with the health system, which co-occurring social and functional risks may disrupt. Whether these risks form reproducible patterns with different mortality associations is uncertain. Objective: To identify social and functional risk patterns among US adults with chronic liver disease and evaluate their associations with all-cause mortality. Design, Setting, and Participants: Nationally representative cohort study of National Health Interview Survey sample adults interviewed from 2011 through 2018 and linked to the National Death Index through 31 December 2019. Participants were aged 18 years or older, eligible for mortality linkage, reported a chronic liver condition, and had no baseline liver cancer. Exposures: Latent class membership derived from 7 binary indicators: poverty, food insecurity, uninsurance, cost-related delayed care, no usual place of care, single-adult household status, and activity limitation. A complete 0- to 7-item count was a secondary exposure. Main Outcomes and Measures: All-cause mortality. Survey-weighted Cox models estimated hazard ratios (HRs) with sequential demographic, clinical, and liver-specific adjustment. Prespecified sensitivity analyses used 20 multiple imputed data sets, sampling-weighted pseudo-likelihood latent class models, complete-case re-estimation, a fixed 5-year horizon, and class-by-age interaction testing. Results: Among 3407 adults (weighted mean age, 54.0 years; 49.4% female), 529 deaths occurred over 17,297.6 person-years (median follow-up, 5.0 years [IQR, 3.0–7.0]). Four classes were retained: low social and access burden (weighted prevalence, 63.1%); functional limitation with financial strain (13.2%); poverty, single-adult household, and functional limitation (15.0%); and uninsurance with major access barriers (8.7%). Compared with the low-burden class, the functional-limitation/financial-strain class had higher adjusted mortality (HR, 1.95; 95% CI, 1.34–2.82; p < 0.001); the other 2 classes did not differ significantly. Sampling-weighted latent class analysis after multiple imputation reproduced 97.2% of modal assignments, and the association persisted with attenuation (HR, 1.55; 95% CI, 1.08–2.22; p = 0.02). Each additional risk was associated with higher mortality (exact count: HR, 1.24 [95% CI, 1.13–1.36]; imputed count: HR, 1.19 [95% CI, 1.10–1.29]). The class-by-age interaction was not significant (p = 0.41). Conclusions and Relevance: Among US adults with self-reported chronic liver disease, social and functional adversity was both cumulative and patterned. A profile combining functional limitation, food insecurity, and cost-related delayed care had the clearest independent mortality association despite largely retained insurance coverage. These profiles are not a validated clinical score, but the findings argue against reliance on any single indicator, particularly insurance status, as a marker of vulnerability.

Objectives: Diabetes mellitus and chronic pancreatitis are established risk factors for pancreatic ductal adenocarcinoma (PDAC). The co-occurrence of exocrine and endocrine pancreatic dysfunction may increase the risk of progression to PDAC and could play a role in early detection. We sought to explore this hypothesis by comparing PDAC risk among patients with diabetes mellitus (DM) and low fecal elastase (FE) in a real-world cohort of patients. Materials and Methods: A retrospective cohort study was conducted using the TriNetX research network including adults with continuous follow-up from 2016 to 2023. The cohort was stratified into 4 groups based on the presence or absence of DM, and normal FE (>200 µg/g) or low FE (<200 µg/g). The 4 groups included: (1) low FE and DM, (2) low FE without DM, (3) normal FE and DM, (4) normal FE without DM. Propensity score matching was performed to balance covariates including age, sex, race, comorbidities to allow for a 6-way comparison of PDAC risk between groups. Time-to-event analyses were conducted with Kaplan-Meier curves and Cox proportional hazards models to estimate hazard ratios (HR) and 95% CIs for the primary outcome of PDAC incidence. Results: Of the study cohort, 29,207 had fecal elastase levels. Low FE (<200 µg/g) was observed in 33% (n = 9585) of these patients. After 6-way comparisons, we observed a higher PDAC risk among individuals with both DM and low FE compared with other groups. The highest PDAC risk was observed in patients with both a low FE (<200 µg/g) and DM compared with those with a normal FE and without a history of DM (HR: 3.68; 95% CI, 2.07–6.53; P < 0.001). Sensitivity analysis using a stricter fecal elastase cutoff of <100 µg/g showed a similar finding, with the highest hazard ratio for PDAC among patients with both DM and very low FE levels (HR: 3.07, 95% CI, 1.37–6.91; P = 0.004). Conclusions: The coexistence of low fecal elastase and DM amplifies the risk of pancreatic ductal adenocarcinoma in our cohort of patients. These results suggest that fecal elastase values may be used to enrich the diabetic population for future PDAC risk stratification, though more studies are needed to validate these findings.