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In this randomized controlled study, we evaluated the efficacy and safety of interferon-alpha combined with ketoprofen to that of interferon-alpha alone in naïve patients with chronic hepatitis C. Forty patients were randomized to receive Interferon-alpha2a (3 million units three times a week) and ketoprofen (150 mg twice a day) and 40 to receive only interferon-alpha2a at the same dose. Patients were treated for 6 months and followed up for 6 months. Response was defined by undetectable HCV-RNA in serum at the end-of-treatment and after 6 months from the completion of therapy (long term response). At the end of treatment the response was similar in the two group. However, combination treatment showed significantly higher efficacy than monotherapy in achieving long term response (10%vs 32.5%; P = 0.014). Overall adverse events were similar in the two groups. 'Flu-like syndrome was significantly less common in the ketoprofen plus interferon group which experienced a significantly higher incidence of epigastric pain'. Our results indicate that the combination of ketoprofen plus interferon is significantly more effective than interferon alone in the treatment of naïve patients with chronic hepatitis C and is well tolerated. However this combined treatment appears to be less effective than the association of pegylated IFN and ribavirin which represent the current standard treatment. Thus, the role of ketoprofen in the treatment of chronic hepatitis C needs to be further evaluated against such a treatment.

Current evidence suggests that increased expression of Th1-associated cytokines is important for immune-mediated eradication of hepatitis C infection, while an increase in Th2-associated cytokines is associated with persistence of infection. In this study we evaluated the effects of thymosin-alpha1 (TA1), a naturally occurring thymic peptide, and interferon-alpha (IFN-alpha) on cytokine production in peripheral blood mononuclear cells from untreated patients with chronic hepatitis C. We examined the effect of incubation with TA1, IFN-alpha, or both, on production of Th1-associated cytokines (IL-2, IFN-gamma), Th2-associated cytokines (IL-4, IL-10), and synthesis of the antiviral protein 2',5'-oligoadenylate synthetase. TA1 treatment induced a significant increase in production of IL-2 and 2',5'-oligoadenylate synthetase. Smaller increases were also seen after treatment with IFN-alpha, while incubation with TA1 and IFN-alpha together led to an additive or synergistic effect. Incubation with TA1 resulted in a decrease in IL-4 and IL-10, whereas IFN-alpha increased these cytokines. The addition of TA1 to IFN-alpha significantly reversed this IFN-alpha-induced increase. Hence, TA1 treatment could benefit patients with hepatitis C infection by increasing the Th1-type response, fundamental for sustained clearance of hepatitis C; and by decreasing the Th2-type response, associated with persistence of viraemia.