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

Abstract

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% CI 1.014-1.055). 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. Impact and implications: This study explores the role of soluble PD-L1 as a biomarker of immune dysfunction and its association with clinical outcomes in patients with chronic liver disease. Our findings demonstrate that soluble PD-L1 levels increase with the progression of liver disease and they are independently associated with an increased risk of bacterial infection development and mortality. These results could help physicians identify high-risk individuals earlier and implement preventive strategies.