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C5b-9 and interleukin-6 in chronic hepatitis C. Surrogate markers predicting short-term response to interferon
Insights
Lower baseline levels of interleukin-6 (IL-6) and C5b-9 predict a better response to interferon alpha (IFN alpha) treatment in chronic hepatitis C patients. These biomarkers can guide therapy decisions for better outcomes.
Area of Science:
- Hepatology
- Immunology
- Virology
Background:
- Elevated interleukin-6 (IL-6) and -10, and complement factors may correlate with poor response to interferon alpha (IFN alpha).
- Baseline levels of C5b-9, IL-6, and IL-10 were investigated for their influence on IFN alpha treatment outcomes.
Purpose of the Study:
- To evaluate the impact of baseline C5b-9, IL-6, and IL-10 serum levels on the efficacy of IFN alpha treatment in chronic hepatitis C patients.
- To identify potential biomarkers for predicting treatment response.
Main Methods:
- Fifty-one chronic hepatitis C patients received IFN alpha-2b treatment for 12 weeks.
- Serum levels of IL-6, IL-10, C5b-9, and hepatitis C virus (HCV) RNA were measured pre- and post-treatment.
- Comparison with 46 healthy controls.
Main Results:
- Two-thirds of patients responded to IFN alpha therapy.
- Non-responders exhibited higher baseline IL-6 and C5b-9 levels compared to responders.
- Lower baseline IL-6 and C5b-9 levels significantly correlated with greater reductions in HCV RNA.
- Patients with low IL-6 and/or C5b-9 had a nearly 10-fold higher likelihood of responding to IFN alpha.
Conclusions:
- Baseline serum IL-6 and C5b-9 levels can serve as predictive biomarkers for IFN alpha monotherapy response in chronic hepatitis C.
- These markers may aid in selecting patients for IFN alpha monotherapy versus combination therapy (e.g., with ribavirin).
Background:
Available data and our observations suggest that elevated levels of interleukin (IL)-6 and -10 and some complement parameters may be associated with a poor response to IFN alpha. We evaluated how baseline levels of C5b-9, IL-6, and IL-10 influence the outcome of IFN alpha treatment.
Methods:
Fifty-one patients with established chronic hepatitis C were enrolled and treated with IFN alpha-2b. Before and after a 12-week-IFN-treatment (3 MU or 5 MU tiw) serum levels of IL-6, IL-10, C5b-9 and RNA of hepatitis C virus (HCV) were assessed. Sera of 46 sex- and age-matched, healthy blood donors served as control.
Results:
While two-thirds of patients was considered 'responder', 14 patients had no significant decrease either in HCV RNA or in ALT levels. In the responder's group lower baseline levels of IL-6 and C5b-9 were found than those in the 'non-responder' group. As a result of IFN therapy HCV RNA and C5b-9 levels significantly decreased. While the serum concentration of IL-6 increased during the follow-up period, regarding IL-10, no change was observed. In patients with 'low' baseline levels of C5b-9 (<2053 ng/ml) IFN alpha resulted in a significantly (P = 0.0005) higher decrease in HCV RNA level. Regarding 'low' IL-6 values (< 1.47 pg/ml) similar but somewhat less significant (P = 0.0039) difference was found if the change of HCV RNA was investigated. The odds ratio of patients with low IL-6 and/or C5b-9 to responding to IFN alpha treatment was almost 10 times (CI: 9.1 (1.8-50.9)) higher as compared with patients without 'low' levels of these parameters.
Conclusion:
Our data suggest that serum level(s) of IL-6 and/or C5b-9 taken prior to the initiation of IFN treatment may serve as surrogate marker(s) in evaluating patients with chronic hepatitis C whether to get IFN alpha in monotherapy or to consider having combination therapy in the form of IFN alpha-ribavirin.
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