Residual HCV-RNA and Elevated Platelet-to-Lymphocyte Ratio Predict Poor Long-Term Outcomes in Patients with Chronic Hepatitis C After Treatment

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 blo...

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Main Authors: Anna Wróblewska, Mateusz Gliwiński, Magda Rybicka, Małgorzata Cheba, Beata Lorenc, Piotr Trzonkowski, Krzysztof P. Bielawski, Katarzyna Sikorska
Format: Article
Language:English
Published: Adis, Springer Healthcare 2024-12-01
Series:Infectious Diseases and Therapy
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Online Access:https://doi.org/10.1007/s40121-024-01101-2
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author Anna Wróblewska
Mateusz Gliwiński
Magda Rybicka
Małgorzata Cheba
Beata Lorenc
Piotr Trzonkowski
Krzysztof P. Bielawski
Katarzyna Sikorska
author_facet Anna Wróblewska
Mateusz Gliwiński
Magda Rybicka
Małgorzata Cheba
Beata Lorenc
Piotr Trzonkowski
Krzysztof P. Bielawski
Katarzyna Sikorska
author_sort Anna Wróblewska
collection DOAJ
description 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.
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spelling doaj-art-8a59e1ecc77e412895f5b3e689016c562025-02-02T12:35:21ZengAdis, Springer HealthcareInfectious Diseases and Therapy2193-82292193-63822024-12-0114130531510.1007/s40121-024-01101-2Residual HCV-RNA and Elevated Platelet-to-Lymphocyte Ratio Predict Poor Long-Term Outcomes in Patients with Chronic Hepatitis C After TreatmentAnna Wróblewska0Mateusz Gliwiński1Magda Rybicka2Małgorzata Cheba3Beata Lorenc4Piotr Trzonkowski5Krzysztof P. Bielawski6Katarzyna Sikorska7Laboratory of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of GdanskDepartment of Medical Immunology, Faculty of Medicine, Medical University of GdanskLaboratory of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of GdanskPomeranian Center of Infectious Diseases and TuberculosisPomeranian Center of Infectious Diseases and TuberculosisDepartment of Medical Immunology, Faculty of Medicine, Medical University of GdanskLaboratory of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of GdanskDivision of Tropical Medicine and Epidemiology, Division of Tropical and Parasitic Diseases, Institute of Maritime and Tropical Medicine, Faculty of Health Sciences, Medical University of GdanskAbstract 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.https://doi.org/10.1007/s40121-024-01101-2Directly-acting antiviralsHCV-RNALong-term outcomesOccult hepatitis C infectionPlasma cytokinesPlatelet-to-lymphocyte ratio
spellingShingle Anna Wróblewska
Mateusz Gliwiński
Magda Rybicka
Małgorzata Cheba
Beata Lorenc
Piotr Trzonkowski
Krzysztof P. Bielawski
Katarzyna Sikorska
Residual HCV-RNA and Elevated Platelet-to-Lymphocyte Ratio Predict Poor Long-Term Outcomes in Patients with Chronic Hepatitis C After Treatment
Infectious Diseases and Therapy
Directly-acting antivirals
HCV-RNA
Long-term outcomes
Occult hepatitis C infection
Plasma cytokines
Platelet-to-lymphocyte ratio
title Residual HCV-RNA and Elevated Platelet-to-Lymphocyte Ratio Predict Poor Long-Term Outcomes in Patients with Chronic Hepatitis C After Treatment
title_full Residual HCV-RNA and Elevated Platelet-to-Lymphocyte Ratio Predict Poor Long-Term Outcomes in Patients with Chronic Hepatitis C After Treatment
title_fullStr Residual HCV-RNA and Elevated Platelet-to-Lymphocyte Ratio Predict Poor Long-Term Outcomes in Patients with Chronic Hepatitis C After Treatment
title_full_unstemmed Residual HCV-RNA and Elevated Platelet-to-Lymphocyte Ratio Predict Poor Long-Term Outcomes in Patients with Chronic Hepatitis C After Treatment
title_short Residual HCV-RNA and Elevated Platelet-to-Lymphocyte Ratio Predict Poor Long-Term Outcomes in Patients with Chronic Hepatitis C After Treatment
title_sort residual hcv rna and elevated platelet to lymphocyte ratio predict poor long term outcomes in patients with chronic hepatitis c after treatment
topic Directly-acting antivirals
HCV-RNA
Long-term outcomes
Occult hepatitis C infection
Plasma cytokines
Platelet-to-lymphocyte ratio
url https://doi.org/10.1007/s40121-024-01101-2
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