Assessment of intestinal inflammation via fecal calprotectin for early prediction of adverse outcomes in advanced chronic liver disease

Background and aims: Intestinal inflammation assessed by fecal calprotectin (F-CAL) in advanced chronic liver disease (ACLD) may represent an early sign of intestinal barrier dysfunction. We aimed to explore the usefulness of F-CAL testing in ACLD in the prediction of adverse outcomes (AO, death, or LT) and refinement of prognostic stratification.

Patients and methods: We explored the RH7 cirrhosis registry comprising consecutive hospitalized patients and a control group with data on disease phenotype, demographics, anthropometrics, prognostic indices, and medication. The F-CAL was evaluated on admission and reported in multiples of the upper limit of normal or terciles. Predictive power was tested in the Cox model for AO over 180 days. Additional risk refinement by F-CAL was tested for both groups.

Results: We enrolled 263 cases in the study group with a median age of 57.2 years, M/F ratio 167/96, with alcohol, metabolic dysfunction-associated steatotic liver disease, MetALD, and viral etiologies in 72.2%, 9.1, 8.0, 3.4%. The median F-CAL was 3.92 × ULN. The control group comprised 108 cases. The adjusted Cox model confirmed F-CAL (hazard ratio [HR] = 1.05, p < 0.001) and F-CAL terciles (HR = 1.413, p = 0.009) as independent predictors of AO. F-CAL terciles had higher predictive accuracy in CLIF-C-AD<50 (HR = 2.49, p = 0.013) and Child stages A and B (HR = 1.706, p = 0.025), in whom high F-CAL (cut-off >11 × ULN) could identify patients having 2-3 times higher risk of AO. This approach has been validated in the control group.

Conclusion: Among hospitalized patients with ACLD, F-CAL values were independently proportional to the risk of AO, particularly in early disease stages when high F-CAL values could refine prognostic stratification.