Abstract / Summary
Background and objectives Interleukin-6 is a proximal inflammatory cytokine implicated in cirrhosis decompensation, yet its incremental prognostic value over established severity scores remains unclear. Methods In this prospective, purely observational study (April 2022 to October 2023), 489 consecutive patients hospitalized with cirrhosis at a tertiary hepatology center were enrolled, and serum interleukin-6 was measured at admission. Results Median interleukin-6 was 23.8 pg/mL, in-hospital mortality was 9.0%, and overall mortality was 70.6%. Interleukin-6 independently predicted in-hospital mortality after adjustment for age, sex, and disease severity (adjusted odds ratio 1.34, 95% confidence interval 1.08–1.67), supported by Bayesian analysis (posterior probability 99.6%). Adding interleukin-6 to conventional severity scores modestly but significantly improved discrimination for in-hospital mortality, with the combined organ failure score plus interleukin-6 model achieving the highest area under the curve (0.802). The prognostic impact of interleukin-6 was substantially stronger in alcohol-associated liver disease compared with metabolic dysfunction-associated steatotic liver disease. Infection mediated 17.3% of the interleukin-6–mortality association. In sub-cohort analyses, the etiology-specific effect persisted after adjustment for infection and after exclusion of severe alcohol-associated hepatitis; infection mediated 23% of the interleukin-6–mortality association in alcohol-associated liver disease but 2% in metabolic dysfunction-associated steatotic liver disease, and the incremental value of interleukin-6 over MELD-3.0 was confined to alcohol-associated disease and to infected patients. MELD-3.0 remained the dominant prognostic determinant, and interleukin-6's independent prognostic signal attenuated for longer-term outcomes. Conclusions Admission interleukin-6 did not outperform established severity scores but provided modest, statistically significant incremental discrimination that was confined to the in-hospital window and concentrated in alcohol-associated disease. These findings do not support routine interleukin-6 measurement in unselected admissions but identify alcohol-associated cirrhosis, particularly with infection or intermediate MELD-3.0 scores, as the setting in which interleukin-6-informed risk stratification merits prospective validation and economic evaluation.