Biomarker Assessment May be Useful in Monitoring Immunotherapy Outcomes in HCV Patients

Researchers have identified links between chemokine/cytokine levels and successful treatment of Hepatitis C Virus (HCV) with cytokine-based immunotherapy, which could potentially lead to the development of new immunotherapy-based treatment plans for HCV.

Researchers with the Viral Hepatitis Clinic at the Federal University of Minas Gerais (UMG) in Brazil, and colleagues with the Integrated Research Group on Biomarkers in Brazil and the US Food and Drug Administration (FDA) Center for Biologics and Evaluation Research conducted the study.

The study of 73 patients with HVC genotype one was conducted in order to assess patterns of serum biomarkers in HCV patients treated with interferon-alpha based immunotherapy. Nineteen healthy blood donors took part in the longitudinal, multidisciplinary study at the Outpatient Liver Unit of the Alpha Institute of Gastroenterology at UMG.

Lead researcher Erica Godinho Menezes, PhD, MD, and colleagues assessed each patient’s viral load at baseline and then divided patients into 3 subgroups: non-responders (NR) who showed no improvement after 12 weeks of treatment, relapsers (REL) who responded to treatment but showed virological breakthrough or resistance in the first six months post treatment, and sustained-virologic-responders (SVR) who were treated successfully and had no breakthrough in six months post treatment.

Samples from each of the 3 groups was tested for baseline viral loads — as well as serum levels of chemokines and cytokines — and retested during follow-ups at 12 weeks and 48 weeks after immunotheraphy treatment.

Menezes and colleagues noted that the “general therapeutic failure profiles (NR and REL) were associated with a prominent proinflammatory pattern” composed of increased levels of several cytokines.

The data also showed that NR patients with HCV displayed decreased baseline levels of interleukin-10, and REL patients with HCV displayed increased baselines of interleukin-6 when compared to SVR patients. Overall SVR patients showed “an evident and significant decrease of proinflammatory status as compared to NR and REL,” Menezes noted.

NR patients, according to study data, “lacked the ability to uphold” increased interferon-alpha levels as compared to SVR patients during the 12 and 48 week follow ups.

Results show that there are distinct patterns of immunotherapy response based on the baseline levels of serum chemokine/cytokine levels of patients in the 3 groups. Menezes notes that data supports the “deleterious effect of prominent proinflamatory status at baseline for achieving successful results upon immunotherapy.”

Menezes suggests that the ability to balance proinflammatory/regulatory responses in patients at the 12 week mark for treatment seems to “be critical to support the therapeutic success of SVR.”

The researchers believe that identifying biomarkers that signal increased serum chemokine/cytokine levels can be used as predictive tools in the treatment of HCV.

Understanding these chemokine/cytokine changes, Menezes said, “could provide insights to support the development of novel therapeutic strategies to minimize idiosyncratic effects.”

Menezes states that the development of new treatments for HCV which include anti-inflammatory therapy prior and during treatment may be the key in helping NR and REL patients achieve SVR.

The article "Strategies for Serum Chemokine/Cytokine Assessment as Biomarkers of Therapeutic Response in HCV Patients as a Prototype to Monitor Immunotherapy of Infectious Diseases" appeared in the May 2017 volume of Antiviral Research.

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