Abstract
INTRODUCTION: Despite achieving sustained viral response (SVR) after treatment with direct-acting antivirals (DAAs), the risk of liver disease progression and extrahepatic complications in chronic hepatitis C (CHC) remains. We aimed to determine the role of residual HCV-RNA in peripheral blood mononuclear cells (PBMCs), a condition known as occult hepatitis C (OCI), and systemic inflammatory markers as predictors of long-term outcomes in patients treated with DAAs. METHODS: We followed 42 patients treated with DAAs with OCI status determined after therapy, for a median of 6.3 years. Plasma levels of 16 cytokines and chemokines were measured in samples collected 12-15 months after end of treatment. Samples from 10 patients with CHC and 8 healthy controls were used for comparison. RESULTS: The presence of HCV-RNA in PBMCs correlated with adverse outcomes [odds ratio (OR) 17.6, confidence interval (CI) 1.8-175); p = 0.011], and an elevated platelet-to-lymphocyte ratio (PLR) was associated with mortality. Patients with residual HCV-RNA had higher levels of macrophage-derived chemokine (MDC/CCL22) (p = 0.026) and interleukin-18 (IL-18) (p = 0.009), but lower levels of fractalkine/CX3CL1 (p = 0.007), interferon gamma (IFNγ) (p = 0.016), IL-13 (p = 0.009), and lymphotoxin alpha (LTα) (p = 0.007) compared to those without OCI. The profile of immune mediators in patients with OCI differed more from healthy controls than from patients without OCI. CONCLUSIONS: These findings suggest that residual HCV-RNA and elevated PLR are potential predictors of poor long-term outcomes in patients treated with DAAs, possibly linked to an altered cytokine/chemokine response.