Pegylated interferon and ribavirin in re-treatment of responder-relapser HCV patients.

BACKGROUND: The re-treatment of patients who relapse after a course of standard interferon and ribavirin with pegylated interferon alfa-2b plus ribavirin is an open issue. AIMS: To evaluate efficacy and safety of treatment with pegylated interferon alfa-2b plus ribavirin and the role of early HCV-RNA assessment as a predictor of sustained response. PATIENTS: Between May 2001 and December 2002, 242 consecutive patients with chronic hepatitis C were enrolled in an open, regional, multicentre study. Seventy-eight of them were responder-relapsers to a previous course of combination therapy. METHODS: Patients were treated with pegylated interferon alfa-2b (1 microg/kg/week) plus ribavirin (800-1200 mg daily). Qualitative HCV-RNA was performed at week 2. Genotypes 1-4 were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. RESULTS: We obtained an overall sustained virological response rate of 41.0% (78.6% for patients with genotypes 2-3). CONCLUSION: This treatment schedule prove to be safe and effective in relapsers with genotype non-1 while genotype 1-4 patients had a low rate of sustained virological response. Qualitative virological assessment after 2 weeks may identify patients who are more likely to reach sustained virological response, but it is not a valid tool for a stopping rule approach.

A randomized trial of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in the re-treatment of patients with chronic hepatitis C not responding to standard interferon and ribavirin.

BACKGROUND: There is yet no established treatment for chronic hepatitis C patients non-responder to standard interferon and ribavirin. AIM: To evaluate efficacy and safety of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in such patients. METHODS: 161 non-responders to standard interferon and ribavirin were randomized into two groups: 81 patients (Group 1) were given weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily for 12 months, 80 patients (Group 2) received weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily and amantadine 200 mg/daily for 12 months. RESULTS: At the end of follow-up, HCV-RNA was negative in 29.6% of Group 1 and in 21.2% of Group 2 patients (P = 0.22). Patients with genotypes 1 and 4 responded better to bi-therapy (21.7%) than to triple therapy (17.3%, P = 0.5) while among patients with genotypes 2 and 3 there was a trend towards a higher sustained virological response rate when retreated with triple treatment (80% vs. 75%, P = 0.82). On multivariate analysis, genotype 1 or 4, high body mass index and >20% reduction of Peg-interferon were associated with the treatment failure. CONCLUSIONS: The addition of amantadine does not improve the overall SVR rate in non-responder patients retreated with Peg-IFN and ribavirin; however, about 30% of non-responders may achieve a sustained response, in particular patients with genotypes 2 and 3 show a high SVR (75%).

Analysis of the distribution and genetic variability of viral isolates in a cohort of HCV-positive hepatopathic patients.

The genotyping of the hepatitis C virus (HCV) by viral nucleic acids sequencing allows accurate epidemiological evaluation of a cohort of patients suffering from HCV-related chronic hepatopathy. The identification of viral isolates, which can be generally associated with hepatic damage or, vice versa, which are more responsive to pharmacological treatment, might enhance clinical interest on the nature of the infecting genotypes. We, therefore, draw attention to those viral genotypes that are characterised by significantly high or altered viremic and enzymatic levels.

Role of viral isolate in the etiopathogenetic determinism of HCV infection: diagnostic and epidemiological evaluation.

HCV genotyping by nucleic acid sequencing emphasizes the difficulties involved in carrying out a more precise determination of the infectant viral population, probably due in part to the finding of still unknown isolates. Signs of heterogeneity in the genotype composition of the viral quasi-species and its evolutionary dynamism over time, together with the role played by some, more potentially aggressive, isolates in causing hepatic damage, encourage a more in-depth study of such topics.

Evaluation of antisecretory activity of misoprostol in duodenal ulcer patients using long-term intragastric pH monitoring.

The effect of the new synthetic prostaglandin E1 analog, misoprostol, on intragastric acidity was evaluated by means of 24-hr intraluminal pH monitoring of 16 duodenal ulcer patients. They were randomly allocated into two groups: eight received no medication and misoprostol 400 micrograms bid and eight received ranitidine 150 mg and misoprostol 400 micrograms bid not less than one week apart. The comparison of the 24-hr areas under the curve related to the median pH values showed that no difference existed between misoprostol and untreated patients in the first group, while ranitidine was significantly more effective (P = 0.00003) than misoprostol in the second group. The analysis of arithmetic differences between the 24-hr median pH values showed that misoprostol increased pH values by at least one unit compared to the untreated subgroup for about 3.5 hr, while the antisecretory action of ranitidine was far superior to that of misoprostol throughout the whole 24-hr period. It can be concluded that the effect of twice daily doses of misoprostol 400 micrograms on 24-hr intragastric pH is small and not at all comparable to that of the well-known potent H2 blocker ranitidine.

Famotidine has no significant effect on gonadal function in man.

The effect of a single bedtime dose of famotidine 40 mg on gonadal function was studied in 8 male duodenal ulcer patients. The drug was orally administered for 4 weeks. Our results show that this new H2 blocker influences basal and stimulated serum levels of neither testosterone nor gonadotrophins (LH, FSH). Besides, no significant variations were observed before and after famotidine treatment in seminal fluid characteristics evaluated in 5 out of 8 cases. It can be concluded that famotidine appears to leave gonadal function unaffected in man.

24-H comparison between pH values of continuous intraluminal recording and simultaneous gastric aspiration.

This study was undertaken to show whether the correlation between pH values indicated by an intraluminal pH electrode and those simultaneously recorded for gastric aspirates is not only linear but also proportional, so that the two measurement techniques can be considered alternative. A 24-h intragastric pH-monitoring with an antimony electrode, to which a nasogastric tube for hourly aspiration of gastric juice was closely attached, was performed on 20 duodenal ulcer patients. Our data show that the slope of the straight line related to 335 pH pairs is virtually equal to 1, whereas the elevation is almost equal to zero, and this result strongly suggests that a proportional relationship exists between intragastric and aspirate pH levels throughout the whole 24-h period. Besides, in the majority of cases (81%) the pH pairs differ by no more than 1 pH unit. It can be concluded that these two pH monitoring methods may be alternative.

Continuous 24 hour intragastric pH monitoring: focus on reproducibility in duodenal ulcer patients. A preliminary report.

Continuous 24 h intragastric pH monitoring is increasingly recommended for deciding which is the most appropriate regimen and dosage of new gastric antisecretory drugs. In order to assess its reproducibility, we have repeated the test twice on consecutive days in six patients with endoscopically proven duodenal ulcers because this type of patient seems to be the most suitable for studies on the efficacy of the above mentioned therapy. No patient received medication during the two examination days. Our data showed there was no significant difference (t = 0.31, p = 0.76) between the 24 h areas under the curve of pH profiles of the first day compared with those of the second (mean +/- SD : 3.152 +/- 681 vs 3.073 +/- 1,122). The lack of significant difference (p = 0.20) between the mean times elapsed at the various pH levels during the first and second days was further proof of the reproducibility of the method. As wells these results suggest that day-to-day reproducibility of the technique is good in duodenal ulcer patients. Therefore, its repeated use on the same patient to investigate the effects of various drugs and their different dosages on gastric acidity appears to be reliable.