Different core-specific T cell subsets are expanded in chronic hepatitis C with advanced liver disease

Thrombocytopenia is the most common hematological abnormality in patients with chronic, advanced liver disease. In these patients, the presence of severe thrombocytopenia is an obstacle to the performance of invasive diagnostic and therapeutic procedures, and the current standard treatment for these patients is platelet transfusions, a remedy whose characteristics are far from being ideal. Furthermore, thrombocytopenia in patients with chronic hepatitis C virus infection may render the patients ineligible to antiviral treatment or may limit its efficacy because of premature discontinuation. Although the cause of thrombocytopenia in patients with chronic liver disease is likely multi-factorial, decreased thrombopoietin production by the liver undoubtedly plays a significant role. In this regard, eltrombopag, a non-peptide, orally bioavailable thrombopoietin receptor agonist has been shown to safely increase platelet count in a dose-dependent fashion in both healthy subjects and thrombocytopenic patients with chronic hepatitis C. Furthermore, in this latter group of patients, it has been shown to be superior to placebo in counteracting the myelosuppressive effect of short-term pegylated interferon treatment.

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Observed Changes in Natural Killer and T cell Phenotypes with Evaluation of Immune Outcome in a Longitudinal Cohort Following Sofosbuvir-Based Therapy for Chronic Hepatitis C Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz223 ◽

2019 ◽

Vol 6 (6) ◽

Cited By ~ 3

Author(s):

Timothy J Stevenson ◽

Youssef Barbour ◽

Brian J McMahon ◽

Lisa Townshend-Bulson ◽

Annette M Hewitt ◽

...

Keyword(s):

T Cells ◽

Chronic Hepatitis ◽

Hepatitis C ◽

T Cell ◽

Natural Killer ◽

Chronic Hepatitis C ◽

Nk Cell ◽

Cell Subset ◽

T Cell Subsets ◽

Immune Marker

Abstract Background Chronic hepatitis C virus (HCV) infection diminishes immune function through cell exhaustion and repertoire alteration. Direct acting antiviral (DAA)-based therapy can restore immune cell subset function and reduce exhaustion states. However, the extent of immune modulation following DAA-based therapy and the role that clinical and demographic factors play remain unknown. Methods We examined natural killer (NK) cell, CD4+, and CD8+ T cell subsets along with activation and exhaustion phenotypes across an observational study of sofosbuvir-based treatment for chronic HCV infection. Additionally, we examined the ability of clinical variables and duration of infection to predict 12 weeks of sustained virologic response (SVR12) immune marker outcomes. Results We show that sofosbuvir-based therapy restores NK cell subset distributions and reduces chronic activation by SVR12. Likewise, T cell subsets, including HCV-specific CD8+ T cells, show reductions in chronic exhaustion markers by SVR12. Immunosuppressive CD4+ regulatory T cells decrease at 4-weeks treatment and SVR12. We observe the magnitude and direction of change in immune marker values from pretreatment to SVR12 varies greatly among participants. Although we observed associations between the estimated date of infection, HCV diagnosis date, and extent of immune marker outcome at SVR12, our regression analyses did not indicate any factors as strong SVR12 outcome predictors. Conclusion Our study lends further evidence of immune changes following sofosbuvir-based therapy. Further investigation beyond SVR12 and into factors that may predict posttreatment outcome is warranted.

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