Prognosis of Chronic Hepatitis C Patients Correlates with Circulating Monocyte/Macrophage Function

Maintenance of normal systemic defence and bioregulatory reaction, mainly of macrophages and lymphocytes, is an important influential factor for the prognosis of chronic active hepatitis C patients [l-51. We investigated the cytokine production capability of circulating monocytes/macrophages in 30 hepatitis C virus (HCV)-positive chronic hepatitis patients and 20 healthy adults. The 30 patients were histologically confirmed to have hepatitis C in the active stage before starting interferon therapy. Ten patients had not received interferon therapy yet. Twenty patients had received subcutaneously 10 MU of interferon-a-2b for 4 weeks (everyday) followed by another 22 weeks (three times per week), and the therapy was completed at least 6 months before this study. In 11 of the 20 patients, serum HCV-RNA disappeared and serum alanine transaminase levels were normalized (good responders), whereas for nine patients the therapy was not efficacious (poor responders). As reported previously [l, 61, the monocyte/macrophage fraction was separated from the peripheral blood mononuclear cell fraction by cell adhesion. The purity of the monocyte fraction was confirmed by using a flow cytometer. The fractions were cultured for 2 days without stimulation and the levels of five cytokines in the supernatants were measured by an ELISA. In comparison with healthy subjects, the ten chronic active hepatitis C patients, before starting interferon therapy, showed significantly lower levels of interleukin (IL)-la, IL-lp, IL-6 and IL-10 (Table 1, P<0.05, P<O.Ol). Between the good and poor responders, production levels of the five cytokines were significantly higher in the good responders (Table 1, P<0.05), and their IL-12 levels were slightly higher than the healthy subjects (I‘ = 0.3124). There were no significant difference in five cytokines between the good responders and the healthy subjects. Our findings demonstrate that cytokine production capacity, mainly IL-12 production, of circulating monocytes/macrophages is improved in patients who have a good clinical outcome. Possible causes of the increased IL-12 production in good responders are the direct effects of interferon, elimination of HCVRNA from the blood and cessation of hepatitis; however, we cannot determine the true mechanism. We consider that induction of IL-12 in patients could be quite important to obtain a better therapeutic outcome.