Hepatitis C Virus-related chronic liver disease in elderly patients: an Italian cross-sectional study.

Chronic hepatitis C virus (HCV) infection has been poorly investigated in the elderly. The aim of this study was to identify the age-specific characteristics of chronic hepatitis C by comparing patients > or =65 years with those <65 years. A cross-sectional study was performed on data collected from consecutive outpatients referred for the first time to two tertiary outpatient clinics for liver diseases located in Bologna (Northern Italy) and Paola, Cosenza (Southern Italy) over a two-year period. A total of 560 anti-HCV and HCV-RNA positive patients were enrolled, of whom 174 (31%) were 65 years or older. The proportion of older patients was significantly higher in the Southern Italy centre, accounting for more than 40%. Comparison of younger and older groups showed that 51% patients > or =65 years had advanced liver disease (liver cirrhosis or hepatocellular carcinoma) compared with 26% younger patients (P < 0.0001). About half of the patients > or =65 years were not aware of their anti-HCV positive status, even if they tended to be more symptomatic than the younger group. By multivariate analysis, age > or = 65 years, alcohol consumption and diabetes were independently associated with advanced liver disease. Overall, 34 out of 174 patients (20%) > or =65 years had received antiviral treatment compared with 122 out of 386 (32%) younger patients (P = 0.003). Our results further emphasize the notion that chronic hepatitis C is becoming a disease of the elderly and that elderly patients with chronic HCV infection often have severe and underestimated disease.

Thymosin-alpha 1 plus interferon-alpha for naive patients with chronic hepatitis C: results of a randomized controlled pilot trial.

In this pilot study, we evaluated the efficacy of interferon-alpha (IFN) plus Thymosin-alpha 1 (TA1) to that of IFN alone in naive patients with chronic hepatitis C. Twenty-two patients were randomized to receive interferon-alpha 2b (3 million units three times a week) plus thymosin-alpha l (900 microg/m2 body surface area) and 19 received interferon-alpha 2b alone at the same dose. Patients were treated for 6 months and followed up for another 6 months. Biochemical (alanine aminotransferase values) and virological (hepatitis C virus-RNA) responses to treatment were determined. Combination treatment showed significantly higher efficacy than monotherapy in achieving virological end-of-treatment response (P = 0.03). At 6-month follow up, the sustained biochemical and virological response was not different between the two groups. Our results indicate that the immune modulator TA1 may enhance the end-of-treatment response in naive patients with chronic hepatitis C. Higher doses and/ore more prolonged courses as well as the association with new interferon formulation such as pegylated interferons could improve the sustained response rates to this treatment.

In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C.

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.

Interferon-alpha combined with ketoprofen as treatment of naïve patients with chronic hepatitis C: a randomized controlled trial.

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.