EBV and CMV Seroprevalence and Liver Injury Patterns Among Clinical Patients in Beijing: Differential Impact of Immunosuppression Status

ABSTRACT Non‐hepatotropic viruses (NHVs), as a category of pathogens not primarily targeting the liver, can also cause hepatic injury. Liver injury associated with Epstein‐Barr virus (EBV) and cytomegalovirus (CMV) infections, in particular, often attracts significant clinical attention. This retrospective cohort study analyzed the seroprevalence and clinical features of EBV and CMV infections among patients in Beijing from 2020 to 2024, with a focus on the impact of immunosuppression status on liver injury patterns. The CMV IgM positivity rate was 4.00% (646/16,201), and the EBV IgM positivity rate was 7.84% (1007/12,838), both showing significant upward annual trends ( p < 0.001). Analysis of 236 IgM‐positive inpatients revealed a “bifurcation phenomenon”: the non‐immunosuppressed group exhibited more severe hepatocellular injury (e.g., ALT levels 6.5‐ to 10.9‐fold higher) and cholestatic damage (e.g., CMV group: TBIL increased 7.8‐fold), yet had better clinical outcomes (adverse outcome rate: 0–4.8%) compared to the immunosuppressed group (adverse outcome rate: 18.4–27.8%, p < 0.05). Further analysis of 125 patients with confirmed liver injury demonstrated that the immunosuppressed group had severe CD4 + T‐cell depletion and inverted CD4 + /CD8+ ratios. During EBV and CMV co‐infection, the immunosuppressed group showed higher CMV DNA detection rates (66.7% vs. 20.0%, p = 0.0097) and viral loads (median 2675 vs. 625 copies/mL, p = 0.002). Within the immunosuppressed group, patients with CD4 + T‐cell counts > 300 cells/μL had higher ALT and AST levels, supporting an immune‐mediated injury mechanism. These findings indicate that immune status and virus type jointly shape the clinical spectrum of EBV/CMV‐related liver injury. The dissociation between severe liver injury and favorable prognosis in non‐immunosuppressed patients underscores the role of immune pathology, while poorer outcomes in immunosuppressed patients are driven by CD4 + T‐cell depletion, impaired viral clearance, and extrahepatic complications.