Interferon versus ribavirin plus interferon in chronic hepatitis C previously resistant to interferon: a randomized trial.

BACKGROUND: More than 70% of patients with chronic hepatitis C are resistant to interferon therapy. Ribavirin, in association with interferon, has been demonstrated as effective, at a dose of 800-1200 mg/day, but the efficacy of a lower dose has not been established. METHODS: We assessed the effectiveness of the combination of 600 mg/day of ribavirin plus 3 MU of interferon over a period of 6 months, in a group of patients previously resistant to interferon. Sixty-two patients with chronic hepatitis C with serum and hepatic HCV RNA relapsers or non-responders to interferon, were randomly divided into two groups: group A received 3 MU of interferon alpha-2b, three times a week for 6 months; group B was given the same dose plus 600 mg per day of ribavirin for 6 months. Two patients from each group dropped from therapy. One patient from group A and two from group B withdrew from treatment because of adverse effects. RESULTS: Mean alanine aminotransferase levels were similar in both groups throughout the study. A sustained response was observed in 7% and 7.4% of groups A and B with short-term response in 39% and 59%, and no response in 54% and 34% from both groups respectively (non-significant). At 12 months, 4 and 7 patients from groups A and B respectively, cleared serum HCV RNA however, only one sustained responder from each group cleared HCV RNA from peripheral blood mononuclear cells. At 18 months, 3 patients remained serum HCV RNA negative. Adverse effects were similar. Only haemoglobin values were lower in group B in the first month of therapy (p<0.05). CONCLUSION: In conclusion, the combination of 3 MU of interferon plus 600 mg of ribavirin is not effective in chronic hepatitis C resistant to interferon.     

A randomized, double-blind controlled trial of interferon alpha-2b and ribavirin vs. interferon alpha-2b and amantadine for treatment of chronic hepatitis C non-responder to interferon monotherapy

BACKGROUND/AIMS: Interferon-based regimens (alone or with ribavairin) are standard therapies for chronic hepatitis C. The aim of this study was to compare a 24-week regimen of interferon alpha-2b + ribavirin (IFN + RIBA) to interferon alpha-2b + amantadine (IFN + AMANT) in non-responders to previous interferon monotherapy. METHODS: In a multi-center, double-blind clinical trial, 118 patients (non-responders to previous interferon monotherapy) were equally randomized into the two arms: interferon alpha-2b (3 MU thrice weekly) and ribavirin (800 mg daily) vs. interferon alpha-2b (3 MU thrice weekly) and amantadine (200 mg daily). RESULTS: After 24 weeks of therapy, HCV RNA became undetectable in 34.8% (95% CI: 23.7-49.2) of IFN + RIBA and 19.6% (95% CI: 10.6-34.7) of IFN + AMANT (P = 0.10). This response was sustained in 3.9% (95% CI: 1.0-14.9) of IFN + RIBA and 0% of IFN + AMANT (P = 0.16). Ten patients from IFN + AMANT (17%) and 12 patients (20%) from IFN + RIBA were discontinued before completion of therapy. Of these, 7% in IFN + AMANT and 12% in IFN + RIBA were discontinued due to adverse effects. CONCLUSIONS: Re-treatment of interferon non-responders with a 24-week course of IFN + AMANT was not associated with any sustained viral eradication. Although IFN + RIBA in this group was associated with a reasonable end of treatment response, relapses were common and sustained responses were low.     

A randomized trial of induction doses of interferon alone or in combination with ribavirin or ribavirin plus amantadine for treatment of nonresponder patients with chronic hepatitis C

Background Efficacy and safety of interferon induction therapy alone or in combination with ribavirin or ribavirin plus amantadine were evaluated in chronic hepatitis C patients who were nonresponders to primary antiviral treatment. Methods The study was designed to have 225 HCV nonresponder patients, but at an interim analysis the response rate difference between groups was lower than expected and the enrollment was stopped when 75 patients had been randomized to receive interferon-α2a (group A, n = 26), interferon-α2a plus 15 mg/kg per day of ribavirin (group B, n = 24), or interferon-α2a plus ribavirin plus 200 mg/day of amantadine hydrochloride (group C, n = 25). Treatment duration was 48 weeks. The dose of interferon was 6 MU/day for 4 weeks followed by 3 MU/day for the remaining 44 weeks. Results On intention-to-treat, the sustained virological response at 24 weeks of follow-up was 11.5% in group A, 12.5% in group B, and 12% in group C. Therapy was discontinued because of adverse effects in three patients in group A (11.5%), three in group B (12.5%), and two in group C (8%). Conclusions Nonresponders with chronic hepatitis C may achieve a sustained virological response rate of approximately 12% if retreated with interferon induction treatment followed by administration of a daily dose. The addition of ribavirin or amantadine did not seem to improve the response rates.     

Induction doses of interferon-alpha-2a in combination with ribavirin and/or amantadine for the treatment of chronic hepatitis C in non-responders to interferon monotherapy: a randomized trial

The benefit of the triple therapy (interferon + amantadine + ribavirim) is still unknown. The efficacy of induction doses of interferon-alpha-2a monotherapy or in combination with ribavirin and/or amantadine was evaluated in interferon non-responders with chronic hepatitis C. A total of 378 patients were randomized. All the groups received the same doses and duration of interferon-alpha-2a: (i) interferon 9 MUI/day for 4 weeks and then 3 MUI/3 t.i.w. for 44 weeks (n = 53); (ii) interferon in combination with amantadine 100 mg twice daily for 48 weeks (n = 111); (iii) interferon in combination with ribavirin 1000-1200 mg (n = 106); (iv) interferon in combination with amantadine and ribavirin (n = 108). Baseline parameters were similar in the four groups. Sustained virological and biochemical responses were 13%, 6%, 18% and 22% respectively. No significant differences were found between double ribavirin arm vs triple therapy, but the difference was significant between interferon-amantadine (P = 0.008) and triple therapy (P = 0.0005). Hence, the induction doses of interferon in combination with ribavirin or ribavirin plus amantadine showed encouraging results in patients with chronic hepatitis C who were resistant to interferon. However, triple therapy is not superior to double.     

Interferon versus ribavirin plus interferon in chronic hepatitis C previously resistant to interferon: a randomized trial

Abstract: Background: More than 70% of patients with chronic hepatitis C are resistant to interferon therapy. Ribavirin, in association with interferon, has been demonstrated as effective, at a dose of 800–1200 mg/day, but the efficacy of a lower dose has not been established. Methods: We assessed the effectiveness of the combination of 600mg/day of ribavirin plus 3 MU of interferon over a period of 6 months, in a group of patients previously resistant to interferon. Sixty-two patients with chronic hepatitis C with serum and hepatic HCV RNA relapsers or non-responders to interferon, were randomly divided into two groups: group A received 3 MU of interferon alpha-2b, three times a week for 6 months; group B was given the same dose plus 600 mg per day of ribavirin for 6 months. Two patients from each group dropped from therapy. One patient from group A and two from group B withdrew from treatment because of adverse effects. Results: Mean alanine aminotransferase levels were similar in both groups throughout the study. A sustained response was observed in 7% and 7.4% of groups A and B with short-term response in 39% and 59%, and no response in 54% and 34% from both groups respectively (nonsignificant). At 12 months, 4 and 7 patients from groups A and B respectively, cleared serum HCV RNA however, only one sustained responder from each group cleared HCV RNA from peripheral blood mononuclear cells. At 18 months, 3 patients remained serum HCV RNA negative. Adverse effects were similar. Only haemoglobin values were lower in group B in the first month of therapy (p<0.05). Conclusion: In conclusion, the combination of 3 MU of interferon plus 600 mg of ribavirin is not effective in chronic hepatitis C resistant to interferon.     

Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies (ANRS HC 03 BITRI)

BACKGROUND/AIMS: To determine whether addition of amantadine to pegylated interferon/ribavirin improved response rates among chronic hepatitis C patients, non-responders to interferon/ribavirin and study the dynamic of response. METHODS: In a double blind, multicenter, randomized trial, 200 non-responder patients received pegylated interferon 1.5 microg/kg per week and ribavirin 800-1200 mg/day, plus either amantadine 200 mg/day or placebo for 48 weeks. Endpoints were virological responses, ALT normalization, and histological benefit overtime. RESULTS: Twenty percent of all patients achieved a sustained virological response (SVR). This rate was 8% higher in the triple therapy group (24%) compared with the double therapy group (16%) (P = 0.22). A better virological response rate at week 24 was observed in the triple regimen group (43 vs 29%; P = 0.06), which was lost at week 48 suggesting viral escape. The biochemical response rate was also significantly higher with triple therapy at week 12 (63 vs 49%; P = 0.05) and week 24 (64 vs 49%; P = 0.03). Fibrosis stabilized or improved in 77% of all patients. CONCLUSIONS: Re-treatment of interferon/ribavirin non-responder patients should be encouraged since a substantial proportion benefits from re-treatment with pegylated interferon/ribavirin +/- amantadine. In triple therapy involving amantadine, a time wise response and an increased SVR rate in subgroups less prone to viral breakthrough suggest clues for existing controversies.     

Daily or three times per week interferon alpha-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C not responding to previous interferon alone

BACKGROUND/AIMS: We compared the efficacy and safety of the combined therapy of daily interferon alpha-2b and ribavirin with those of interferon alpha-2b three times per week alone or in combination with ribavirin in non-responder patients with hepatitis C virus (HCV) infection.METHODS: A total of 376 patients were randomly assigned to receive interferon alpha-2b (6 MU three times per week for 24 weeks followed by 3 MU three times per week for 24 weeks) alone (group A) or in combination with ribavirin for 48 weeks (group B), or daily interferon alpha-2b (3 MU per day for 24 weeks followed by 3 MU three times per week for 24 weeks) and ribavirin (group C).RESULTS: After 24 weeks of therapy, HCV RNA was undetectable in 11.7, 24.0, and 37.8% for groups A, B, and C, respectively. Sustained virological response was more frequent in patients who received combination therapy with three times weekly interferon (20.9%) or daily interferon (26.0%) than in patients who received interferon alone (5.8%) (P<0.001). The predictive HCV parameters for sustained response were a low viral load on day 7 and a negative HCV RNA on week 12.CONCLUSIONS: In conclusion, in non-responder patients with chronic hepatitis C, virological response with daily interferon and ribavirin, compared to interferon monotherapy, was significantly improved during treatment, although sustained virological response was similar for both combination therapies with ribavirin and three times a week or daily interferon.     

Triple antiviral therapy in HCV positive patients who failed prior combination therapy

INTRODUCTIONWhile advances in the treatment of HCV chronic hepatitis have markedly improved outcomes for treatment-na?ve patients, a large number of patients still fail to eradicate HCV infection[1-4], and improving the re-treatment success rates of these…     

Randomized,controlled trial with IFN-alpha combined with ribavirin with and without amantadine sulphate in non-responders with chronic hepatitis C

BACKGROUND/AIMS: Efficacy and safety of interferon-alpha (IFN-alpha)/ribavirin retreatment with or without amantadine sulphate were evaluated in non-responders with chronic hepatitis C. METHODS: Two hundred twenty five consecutive non-responders to previous antiviral treatment(s) with IFN-alpha alone or in combination with ribavirin or amantadine were treated with IFN-alpha 2b 5 MU daily for 4 weeks, 5 MU tiw for 20 weeks, followed by 3 MU tiw for additional 24 weeks combined with ribavirin 1000-1200 mg/d. One hundred fifteen of 225 patients were randomized to receive amantadine sulphate 100 mg bid for 48 weeks. Treatment was discontinued in patients with detectable serum hepatitis C virus (HCV)-RNA at treatment week 24. RESULTS: An overall sustained virologic response with undectable serum HCV-RNA levels was observed in 49/225 patients (22%). Patients infected with HCV-genotype non-1 (P<0.001), low viremia (P=0.011) and only one previous antiviral treatment (P=0.032) were more likely to respond to antiviral retreatment. There was a trend towards higher sustained virologic response rates in patients receiving triple retreatment compared with those treated with IFN-alpha/ribavirin alone (25 versus 18%, P=0.172). CONCLUSIONS: The addition of amantadine was well tolerated and led to an improvement of sustained virologic responses compared with retreatment with IFN-alpha/ribavirin alone, in particular in patients with low baseline viremia.     

Sustained response to combination therapy in patients with chronic hepatitis C who failed to respond to interferon

BACKGROUND/AIMS: The best treatment for chronic hepatitis C patients who do not respond to interferon is still unknown. Reported rates of response to treatment vary as the result of heterogeneous definitions of non-responders and small study size. METHODS: One hundred nineteen hepatitis C virus (HCV) RNA-positive non-responders to high-dose interferon monotherapy received alpha-interferon, 5 MU tiw plus oral ribavirin, 1000-1200 mg/day for 48 weeks (Group A, n=74) or alpha-interferon, 5 MU daily for 4 weeks, followed by 5 MU tiw plus oral ribavirin, 1000-1200 mg/day for 44 weeks (Group B, n=45) according to the Institution where they were followed. Persistently normal alanine aminotransferase and negative HCV RNA up to 72 weeks from treatment onset defined a sustained response. RESULTS: Eighteen patients discontinued treatment (13 developed anemia, two mucositis, one granulocytopenia; two were dropouts), none for serious adverse events. There were 24 (20%) sustained responders, with similar final response rates in Groups A and B. Sustained response was more frequent in patients aged 相似文献   

Triple antiviral therapy as a new option for patients with interferon nonresponsive chronic hepatitis C

The aim of the study was to evaluate the efficacy of triple antiviral therapy with interferon, ribavirin, and amantadine in comparison with interferon and ribavirin combination treatment in patients with interferon-nonresponsive chronic hepatitis C. We performed an open-label, prospective randomized controlled trial at a secondary referral center. We used a 2:1 ratio, patients received interferon, ribavirin, and amantadine, or interferon and ribavirin for 12 months, and were followed up for an additional 6 months. Ninety-four consecutive adult interferon nonresponders with chronic hepatitis C were screened. Sixty consecutive elected patients entered the study. No patients withdrew because of adverse effects. Forty patients received interferon alfa (5 megaunits on alternate days), ribavirin (800-1,000 mg daily), and amantadine (200 mg daily) for 12 months, and 20 patients received the same treatment without amantadine. At the end of follow-up, alanine transaminase (ALT) level normalization was maintained in 23 of 40 patients (57%) after triple therapy, but in 2 of 20 patients (10%) after double therapy (P <.001, RR = 2.11, 95% CI, 1.43-3.12), whereas disappearance of serum HCV RNA persisted in 19 of 40 patients (48%) and in 1 of 20 patients (5%), respectively (P <.001, RR = 1.81, 95% CI, 1.32-2.47). The safety profile was similar in the 2 groups. In conclusion, in patients with interferon-nonresponsive chronic hepatitis C, triple antiviral therapy for 1 year results in a high rate of sustained biochemical and virologic responses.     

Triple combination of interferon alpha-2b,ribavirin, and amantadine for treatment of chronic hepatitis C

Retreatment of interferon-resistant chronic hepatitis C represents a significant clinical challenge. In an open-label, pilot study, the safety and efficacy of interferon alpha-2b, ribavirin, and amantadine were assessed. Twenty patients with chronic hepatitis C who had previously failed to respond to a course of interferon monotherapy followed by a course of combination therapy (10 patients received interferon alpha-2b [3 million units three times a week] plus ribavirin [800 mg/d] and 10 patients received interferon alpha-2b [3 million units three times a week] plus amantadine [200 mg/d]) were enrolled in this retreatment protocol. One month after discontinuation of their last regimen, patients started treatment with interferon alpha-2b (3 million units three times a week), ribavirin (1,000-1,200 mg/d), and amantadine (200 mg/d). Biochemical and virologic end points were monitored. Patients with hepatitis C virus (HCV) RNA levels of <100 copies/mL at the end of 24 weeks of therapy completed a 48-week course of interferon alpha-2b, ribavirin, and amantadine treatment. Of the enrolled subjects, 60% were male, 85% were white, 85% had HCV genotype 1, and 20% had histologic cirrhosis. The mean age +/- SD of the patients was 44.1 +/- 4.9 years, the mean baseline HCV RNA level +/- SD was 1,845,150 +/- 1,279,069 copies/mL, and the mean baseline alanine aminotransferase level +/- SD was 130 +/- 100 U/L. Five patients (25%) became HCV RNA negative (<100 copies/mL) after 24 weeks of treatment, with only three patients (15%) remaining HCV RNA negative at the end of 48 weeks of treatment. This end of treatment response was sustained 6 months after the discontinuation of treatment in only two patients (10%). In this interferon-resistant group, a treatment regimen of interferon alpha-2b, ribavirin, and amantadine was associated with only a 10% sustained viral eradication rate.     

Daily dose of interferon alpha-2b and ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection: a randomised controlled study

OBJECTIVE: The treatment of patients with hepatitis C virus (HCV) genotype 1 infection remains disappointing. METHODS: In 1999, we started a multicentre study comparing two regimens of recombinant interferon (IFN) alpha-2b plus ribavirin. Group A (90 patients) received ribavirin plus IFN alpha-2b 5 MU/day for 1 month (induction therapy) followed by IFN alpha-2b 5 MU thrice weekly for 5 months. Group B (85 patients) received ribavirin plus IFN alpha-2b 5 MU thrice weekly for 6 months. Responders in both arms received IFN alpha-2b 3 MU thrice weekly for a further 6 months. A follow-up evaluation was performed at 18 months. RESULTS: One hundred and seventy-five consecutive treatment-naive patients with HCV genotype 1 infection were enrolled in the study. A sustained virological response (SVR) was obtained in 51 (29%) patients: 28 in group A (31%) and 23 in group B (27%). HCV-RNA clearance was greater at 3 months among patients who received induction therapy (57 vs 39%; p < 0.02). Age, sex, and initial viral load did not influence the achievement of a SVR. HCV clearance at the end of the study was lower in cirrhotic patients (3/26 vs 48/149; p < 0.05). The only SVR in patients with cirrhosis occurred in those from group A (p < 0.05). Both regimens were well tolerated. CONCLUSIONS: This study confirms the low rate of SVR in treatment-naive patients with HCV genotype 1 infection treated with IFN alpha-2b plus ribavirin. A 4-week induction regimen was slightly superior to standard IFN alpha-2b plus ribavirin. Although the number of patients with cirrhosis was low, induction therapy seemed to be more effective in cirrhotics. Given its safety and tolerability, the induction regimen evaluated here may be a therapeutic option in treatment-naive patients with HCV genotype 1 infection.     

Daily or three times per week interferon α-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C not responding to previous interferon alone

Background/Aims: We compared the efficacy and safety of the combined therapy of daily interferon α-2b and ribavirin with those of interferon α-2b three times per week alone or in combination with ribavirin in non-responder patients with hepatitis C virus (HCV) infection.Methods: A total of 376 patients were randomly assigned to receive interferon α-2b (6 MU three times per week for 24 weeks followed by 3 MU three times per week for 24 weeks) alone (group A) or in combination with ribavirin for 48 weeks (group B), or daily interferon α-2b (3 MU per day for 24 weeks followed by 3 MU three times per week for 24 weeks) and ribavirin (group C).Results: After 24 weeks of therapy, HCV RNA was undetectable in 11.7, 24.0, and 37.8% for groups A, B, and C, respectively. Sustained virological response was more frequent in patients who received combination therapy with three times weekly interferon (20.9%) or daily interferon (26.0%) than in patients who received interferon alone (5.8%) (P<0.001). The predictive HCV parameters for sustained response were a low viral load on day 7 and a negative HCV RNA on week 12.Conclusions: In conclusion, in non-responder patients with chronic hepatitis C, virological response with daily interferon and ribavirin, compared to interferon monotherapy, was significantly improved during treatment, although sustained virological response was similar for both combination therapies with ribavirin and three times a week or daily interferon.     

Interferon-α plus amantadine in chronic hepatitis C resistant to interferon alone: a pilot randomized study

The optimal therapy for patients with chronic hepatitis C who have not responded to interferon (IFN) is still an unsolved issue. The aim of this study was to evaluate the efficacy and tolerability of a high dose of IFN-α2a plus amantadine for chronic hepatitis C patients who were non-responders to a previous course of IFN.
Forty consecutive patients with chronic hepatitis C, genotype 1b, who had not responded to IFN-α, were randomized to receive: (i) IFN 4.5  M U daily plus amantadine 200 mg/day for 4 weeks and then IFN 6  M U thrice weekly plus amantadine 200 mg/day for an additional 5 months (group A) or (ii) IFN alone at the same dosage and duration (group B). After 1 month of therapy, normal alanine aminotransferase (ALT) values were observed in three of 21 (14.3%) patients in group A and in three of 19 (15.8%) in group B; serum hepatitis C virus (HCV)-RNA clearance was observed in one patient (4.8%) in group A and in six (31.6%) in group B. At the end of treatment, six patients (28.6%) in group A and three (15.8%) in group B had normal ALT levels; however, HCV-RNA in serum was detectable in all of them at levels comparable to the basal values; an ALT relapse occurred within 3 months of stopping therapy. The combination of daily IFN plus amantadine was ineffective in this setting.     

Interferon and amantadine in combination as initial treatment for chronic hepatitis C patients.

BACKGROUND/AIMS: To evaluate the efficacy and tolerance of amantadine in combination with interferon in the treatment of chronic hepatitis C. METHODS: Multi-centre trial including 180 chronic hepatitis C patients without cirrhosis, randomly enrolled to receive interferon 6 MU every other day for 6 months followed by 3 MU for further 6 months (group A, 90 patients), or the same schedule plus amantadine 200 mg/day (group B, 90 patients). Primary end-point was a sustained virological and biochemical response, secondary end-points were on-treatment (third month) and end-of-treatment response rates. RESULTS: The two groups had similar demographic, biochemical and virological characteristics. A sustained response after 6 months follow-up was observed in 17% of group A and 24% of group B patients (P not significant), an end-of-treatment response was observed in 37% in group A and 47% in group B (P not significant), an on-treatment response was observed in 46% in group A and 61% in group B patients (P < 0.05). No major side effects due to amantadine administration were observed. CONCLUSIONS: Adding amantadine to interferon did not improve the sustained treatment efficacy. However, the rate of early response at the third month of therapy was significantly higher in the combination therapy group.     

Interferon alfa2a induction therapy in combination with ribavirin and amantadine for the treatment of naive patients with chronic HCV infection

Summary.  Pilot studies have suggested that the addition of amantadine to interferon (IFN) is effective against hepatitis C virus (HCV). Furthermore, IFN induction therapy seems to improve virological response rates. In this open, randomized, multicentre trial we compared safety and efficacy of a triple therapy comprising IFN α 2a, ribavirin and amantadine using high induction doses (6 MU IFN α daily for the first 6 weeks) against a therapy with standard IFN α dosages over the entire treatment period plus amantadine and ribavirin. A total of 158 naive patients with chronic HCV infection were randomized 1:1. Group A ( n  = 81): induction therapy with 6 MU IFN α daily for 6 weeks, followed by 6 MU three times a week (tiw) for 18 weeks and then 3 MU tiw until week 48. Group B ( n  = 77): standard therapy with 6 MU IFN α tiw for 24 weeks, followed by 3 MU until week 48. All patients received oral ribavirin (10 mg/kg/day) and amantadine (200 mg/day). The triple therapy was safe and well tolerated. There were no significant differences between the groups with respect to biochemical response rates. Groups A and B did not differ in virological response rates at the end of treatment (33% vs 35%) or at the end of the 6 month follow up period (37% vs 39%). We could not detect favourable effects on sustained virological response rates using induction therapy, in either genotype 1 or non-1 infected patients. In summary, induction therapy with 6 MU IFN α daily did not result in increased overall response rates compared with standard IFN α dosages of 6 MU tiw.     

Randomised, double blind, placebo controlled trial of interferon, ribavirin, and amantadine versus interferon, ribavirin, and placebo in treatment naïve patients with chronic hepatitis C

BACKGROUND AND AIM: In this study, we compared the efficacy of triple therapy (interferon alfa, ribavirin, and amantadine) with standard therapy (interferon alfa and ribavirin) in treatment na?ve patients with chronic hepatitis C virus (HCV). METHODS: In this prospective, randomised, double blind, placebo controlled, multicentre study, 85 patients (amantadine group) received a three drug regimen of interferon alfa-2b 3 million units three times per week, ribavirin 1000-1200 mg daily in divided doses, and amantadine 100 mg twice daily, and 86 patients (placebo group) received interferon alfa-2b, ribavirin, and identical placebo. Treatment was discontinued at 24 weeks if patients had detectable HCV RNA by polymerase chain reaction (PCR). All patients were followed for 24 weeks after completion of treatment. The primary end point was undetectable HCV-RNA by PCR at 24 weeks (sustained viral clearance) after completion of treatment. RESULTS: At the end of treatment, HCV RNA clearance was seen in 32.9% of the amantadine group and 38.4% of the placebo group (p=0.3). Sustained virological response was seen in 24.7% of the amantadine group and in 27.9% of the placebo group by intention to treat analysis; response rate was 30.4% and 34.8%, respectively, in those who completed 24 weeks of treatment. Poor response was seen in both groups among cirrhotics, African-Americans, genotype 1, and those with a higher viral load. By multivariate analysis, genotype 1, high viral load, and low serum albumin were the only predictors of poor response. Addition of amantadine to the standard regimen did not result in any unexpected side effects. CONCLUSION: Response to triple therapy of interferon alfa, ribavirin, and amantadine was similar to standard therapy of interferon alfa and ribavirin. Our results suggest that amantadine has no role in the management of HCV.     

Efficacy of prolonged 5 million units of interferon in combination with ribavirin for relapser patients with chronic hepatitis C

summary.  Retreatment of relapser patients with chronic hepatitis C with the standard dose of interferon (IFN) of 3 million units (MU) thrice weekly (tiw) plus ribavirin for 24 weeks achieves a sustained response in 30 and 73% of patients with genotype 1 and 2 or 3, respectively. The aim of this study was to evaluate the efficacy and safety of IFN α -2b induction therapy, followed by prolonged treatment with a high dose of IFN α -2b plus ribavirin in relapser patients. A total of 119 patients were randomized to receive IFN α -2b 5 MU daily (Group A: 59 patients) or IFN α -2b 5 MU tiw (Group B: 60 patients) for 4 weeks followed by IFN (5 MU tiw) and ribavirin (1000–1200 mg/day) for 48 weeks in both groups. The primary end point was hepatitis C virus (HCV)-RNA clearance at week 24 after the end of treatment. A sustained virological response (SVR) was achieved in 68 and 60% of Group A and B patients, respectively ( P  = 0.37). Logistic regression analysis identified genotype 2 or 3 as the only independent factor associated with response, whereas induction regimen and baseline viraemia levels did not affect the response. The overall SVR was 53 and 72% in patients with genotype 1 or 4 and 2 or 3, respectively. In conclusion, induction IFN therapy does not enhance the SVR to a 48-week combination therapy. Our study suggests that relapsed patients with genotype 1 or 4 may achieve significant response rates of approximately 50%, if retreated with 5 MU tiw IFN plus ribavirin for 48 weeks.     

Re-treatment of previous non-responders and relapsers to interferon plus ribavirin with peginterferon alfa-2a (40KD), ribavirin ± amantadine in patients with chronic hepatitis C: randomized multicentre clinical trial

Introduction. A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care (pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after ≥ 24 weeks of treatment with conventional interferon plus ribavirin.Material and methods. Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (40KD) 180 μg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/ day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin).Results. The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (< 50 lU/mL) at end of follow-up (week 72). Among patients with a previous non-response, 12/53 (22.6%; 95% confidence interval [CI] 12.3-36.2%) randomized to triple therapy achieved an SVR compared with 16/52 (30.8%; 95% CI 18.7-45.1%) randomized to the standard of care. Among patients with a previous relapse 22/39 (56.4%; 95% CI 39.6-72.2%) randomized to triple therapy achieved an SVR compared with 23/38 (60.5%; 95% CI 43.4-76.0%) randomized to the standard of care. Undetectable HCV RNA (< 50 IU/mL) at week 12 had a high positive predictive value for SVR. A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin.Conclusion. Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting.