C5b-9 and interleukin-6 in chronic hepatitis C. Surrogate markers predicting short-term response to interferon alpha-2b.
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.


CONCLUSIONS
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.
Bíró
L
L
National Institute of Hematology and Immunology, Budapest, Hungary.
Varga
L
L
Pár
A
A
Nemesánszky
E
E
Telegdy
L
L
Ibrányi
E
E
Dávid
K
K
Horváth
G
G
Szentgyörgyi
L
L
Nagy
I
I
Dalmi
L
L
Abonyi
M
M
Füst
G
G
Horányi
M
M
Csepregi
A
A
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015938:Complement Membrane Attack Complex / Q000032:analysis*; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D016896:Treatment Outcome
D015415:Biomarkers; D015938:Complement Membrane Attack Complex; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D015850:Interleukin-6; D012367:RNA, Viral; D011994:Recombinant Proteins; D016753:Interleukin-10