PD-L1 and the risk of bacterial infection in patients with chronic liver diseases: An international multicohort study

Background & Aims: Impaired phagocytic capacity due to activation of the PD-1/PD-L1 pathway has been implicated in the development of bacterial infections in patients with cirrhosis. Soluble PD-L1 (sPD-L1) is easily measurable in plasma and has been proposed as a biomarker of sepsis. In the current study, we aim to evaluate the role of sPD-L1 as a biomarker of bacterial infection development in patients with cirrhosis. Methods: Plasma samples from 995 patients with chronic liver disease grouped in three cohorts were analyzed: an initial cohort of 268 hospitalized patients with acute decompensated cirrhosis, 327 out-patients with non-acute decompensated cirrhosis and finally 400 patients with high-risk alcohol consumption, including all stages of liver fibrosis, from mild/no fibrosis to cirrhosis (F0-F4). The main outcomes of the study were development of bacterial infection and mortality. Results: Patients who developed bacterial infections had higher median levels of sPD-L1 than those who did not (160 [IQR 116-221] vs. 136 [IQR 97-193] pg/ml, respectively, p value <0.001; hazard ratio 1.034, 95% CI1.014-1.055). Levels of sPD-L1 were associated with bacterial infection development after adjustment for confounding factors. During follow-up, patients who died had higher median sPD-L1 levels than survivors, after adjustment for MELD Na (180 [IQR 143-267] vs. 134 [IQR 97-187] pg/ml, respectively; p value <0.001; HR 1.066, 95% CI 1.043-1.089). These findings were observed in all cohorts. Conclusions: Plasma levels of sPD-L1 are associated with the risk of bacterial infection development irrespective of the stage of chronic liver disease. Furthermore, higher sPD-L1 levels are linked to increased mortality. Measurement of sPD-L1 levels may help identify patients at high risk of developing bacterial infections and guide the implementation of new preventive strategies. (c) 2025 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).