Drug-Resistant Bacterial Infections in End-Stage Liver Disease: Immune Imbalance and Intervention Advances

Patients with end-stage liver disease (ESLD) face a markedly elevated risk of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria. This vulnerability worsens prognosis and severely limits therapeutic options. The underlying mechanisms extend beyond hepatic synthetic and detoxification failure to encompass a complex and multifaceted state of immune dysfunction.

In this review, the authors synthesize current evidence on how ESLD-associated immune defects drive susceptibility to drug-resistant infections. They examine key abnormalities across multiple interconnected domains: depletion and dysfunction of Kupffer cells, complement deficiency, T-cell exhaustion with regulatory T-cell expansion, disruption of the gut-liver axis, immunometabolic reprogramming driven by hyperammonemia and lactate accumulation, and upregulation of immune checkpoint molecules such as PD-1/PD-L1.

These pathways collectively promote colonization, persistence, and therapeutic refractoriness of MDR pathogens. The authors also evaluate emerging therapeutic strategies targeting these immune defects, including checkpoint inhibitors, cytokine and cellular therapies, microbiome modulation, and metabolic interventions, while acknowledging the challenges that limit their clinical translation.

By proposing an integrated framework that links distinct immune defects to MDR infection pathogenesis, the paper aims to guide the development of biomarker-driven, personalized immunomodulatory approaches that complement antimicrobial therapy. Ultimately, this work seeks to improve outcomes in this high-risk population through targeted interventions addressing specific immune dysfunctions rather than relying solely on traditional antibiotic regimens.