Efficacy of high dose of recombinant alpha 2b interferon on long term response in chronic hepatitis C and cirrhosis: prospective randomized multicentre study.

BACKGROUND/AIMS: The long-term response to alpha-Interferon in HCV-related chronic liver diseases is disappointing. A randomized controlled trial was conducted to investigate: 1) if doubling the standard regimen of 3 MU recombinant alpha 2b-interferon thrice weekly for one year could improve the long-term response, and 2) the efficacy of these two schedules in cirrhotic patients. PATIENTS AND METHODS: A series of 80 anti-HCV positive patients with biopsy proven liver disease (52 chronic hepatitis and 28 cirrhosis) were randomized to receive either 3 MU or 6 MU alpha 2b-interferon. RESULTS: Based on "intention-to-treat analysis", 38% in the 3 MU group and 53% in the 6 MU group had end-of-treatment response. After 24 months, 18% had long-term response: 5% in 3 MU group and 30% in 6 MU group (p < 0.008). HCV genotype had no influence on the response rate. Thirty-eight percent of the cirrhotics treated with 6 MU had long-term response, while none of those treated with 3 MU had long-term response (difference 38%; 95% confidence internal 10%-67%; p = 0.03). At the end of treatment, 38% of patients lost HCV-RNA. After 24 months only 19% remained HCV-RNA negative: 12 patients (31%) in the 6 MU group and 2 (6%) in the 3 MU group (p < 0.05). CONCLUSIONS: 6 MU of alpha 2b-interferon thrice weekly for 12 months is significantly better than 3 MU in inducing a long-term response and permanent loss of HCV-RNA. This result is particularly striking in the subgroup of cirrhotics.

[The peripheral blood lymphocyte subpopulations in chronic anti-HCV-positive liver disease: their significance and correlation with liver function]. / Sottopopolazioni linfocitarie ematiche nella malatta epatica cronica anti-HCV positiva: significato e correlazione con la funzione epatica.

To evaluate the role played by the immune system in the outcome of chronic C virus infection, we studied the peripheral blood lymphocyte subsets in patients with chronic hepatitis C and the correlation with the hepatic function assessed by the lidocaine test. To this end the peripheral lymphocyte subpopulations were enumerated by flow cytometry in 36 patients we had undergone a liver biopsy, prior the interferon therapy. The patients were classified as having severe chronic hepatitis with or without cirrhosis (17 subjects = group A) and mild/moderate chronic hepatitis without cirrhosis (19 subjects = group B). Twelve patients in group A and 9 in group B underwent the lidocaine test. The mean percentages of the lymphocyte subsets were not different in the two groups and in comparison with a standard healthy population, with the exception of okdr+ lymphocytes; they were significantly increased in group A (p = 0.04). The production of the lidocaine metabolite at 30 minutes prove, significantly decreased in patients with severe hepatic disease (p = 0.02), but there is no correlation between the decline of liver function and the peripheral increase of the okdr+ lymphocytes (r = 0.1877). It is probable that the increase in okdr+ lymphocytes, due to activated T-cells, is subordinated to the persistent viremia but it is independent of histological damage.

Monoethylglycinexylidide production as a measure in predicting hepatic histology.

To clarify whether monoethylglycinexylidide (MEGX) production can be useful in predicting the severity of chronic liver disease, 51 subjects were enrolled in this study: 13 mild-moderate CAH (group A), 9 severe CAH (group B), 29 cirrhosis, 18 compensated and 11 decompensated disease (group C). The patients were injected with a 1 mg/Kg lidocaine bolus i.v. and serum-sampled for MEGX values (time 15, 30 and 60 minutes), determined by TDX-immunoassay. MEGX formation was significantly different (Mann-Whitney U test) in the three groups at each time interval, especially at 30 min: group A = 70.5 +/- 9.9 ng/ml (mean +/- SD); group B = 49.7 +/- 7.2; group C = 37.2 +/- 19.5 (in A vs B, p = 0.0003; in A vs C, p < 0.0001; in B vs C, p = 0.0237). The difference between compensated and decompensated cirrhosis was always significant (p = 0.0099, 0.0005, 0.0113 respectively) but between severe CAH and compensated cirrhosis it was marginal only at 15min (p = 0.0763) and absent at 30 and 60min. At 30min MEGX values > 60 suggest mild-moderate CAH, < 40 cirrhosis, < 30 decompensated cirrhosis, between 40 and 60 severe CAH or compensated cirrhosis. We are of the opinion that the MEGX test could be utilized to predict hepatic histology.