Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group. Hepatitis C in adults and adolescents with hemophilia: a randomized, controlled trial of interferon alfa-2b and ribavirin. Improved response to ribavirin interferon combination compared with interferon alone in patients with type 4 chronic hepatitis C without cirrhosis. High sustained response rate in patients with histologically mild (low grade and stage) chronic hepatitis C infection. A randomized, double blind, placebo controlled trial of interferon alpha-2b with and without ribavirin. The effect of interferon alfa and ribavirin combination therapy in naive patients with chronic hepatitis C. Interferon-alpha 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: a randomized study. Interferon versus ribavirin plus interferon in chronic hepatitis C previously resistant to interferon: a randomized trial. Ribavirin and interferon-alpha combination therapy vs interferon-alpha alone in the retreatment of chronic hepatitis C: a randomized clinical trial.
Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy. We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C.
                We randomly assigned 912 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin (1000 or 1200 mg orally per day, depending on body weight) for 24 or 48 weeks. Efficacy was assessed by measurements of serum hepatitis C virus (HCV) RNA and serum aminotransferases and by liver biopsy.
                The rate of sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was higher among patients who received combination therapy for either 24 weeks (70 of 228 patients, 31 percent) or 48 weeks (87 of 228 patients, 38 percent) than among patients who received interferon alone for either 24 weeks (13 of 231 patients, 6 percent) or 48 weeks (29 of 225 patients, 13 percent) (P<0.001 for the comparison of interferon alone with both 24 weeks and 48 weeks of combination treatment). Among patients with HCV genotype 1 infection, the best response occurred in those who were treated for 48 weeks with interferon and ribavirin. Histologic improvement was more common in patients who were treated with combination therapy for either 24 weeks (57 percent) or 48 weeks (61 percent) than in those who were treated with interferon alone for either 24 weeks (44 percent) or 48 weeks (41 percent). The drug doses had to be reduced and treatment discontinued more often in patients who were treated with combination therapy.
                In patients with chronic hepatitis C, initial therapy with interferon and ribavirin was more effective than treatment with interferon alone. Interferon alfa is the only effective treatment for patients with chronic hepatitis C. Forty percent of patients have an initial response to this therapy, but most subsequently relapse. We compared the effect of interferon alone with that of interferon plus oral ribavirin for relapses of chronic hepatitis C.
                We studied 345 patients with chronic hepatitis C who relapsed after interferon treatment. A total of 173 patients were randomly assigned to receive standard-dose recombinant interferon alfa-2b concurrently with ribavirin (1000 to 1200 mg orally per day, depending on body weight) for six months, and 172 patients were assigned to receive interferon and placebo.
                At the completion of treatment, serum levels of hepatitis C virus (HCV) RNA were undetectable in 141 of the 173 patients who were treated with interferon and ribavirin and in 80 of the 172 patients who were treated with interferon alone (82 percent vs. 47 percent, P<0.001). Serum HCV RNA levels remained undetectable 24 weeks after the end of treatment in 84 patients (49 percent) in the combination-therapy group, but in only 8 patients (5 percent) in the interferon group (P<0.001). Sustained normalization of serum alanine aminotransferase concentrations and histologic improvement were highly correlated with virologic response. Base-line serum HCV RNA levels of 2 x 10(6) copies per milliliter or less were associated with higher rates of response in both treatment groups. Viral genotypes other than type 1 were associated with sustained responses only in the combination-therapy group. Combined therapy caused a predictable fall in hemoglobin concentrations but otherwise had a safety profile similar to that of interferon alone.
                In patients with chronic hepatitis C who relapse after treatment with interferon, therapy with interferon and oral ribavirin results in higher rates of sustained virologic, biochemical, and histologic response than treatment with interferon alone. Adolescents and adults with inherited disorders of coagulation have one of the highest prevalence rates of hepatitis C among known risk groups. Few data are available on the use of combination therapy with interferon and ribavirin in this population. Patients 13 years of age and older who were positive for hepatitis C virus (HCV) RNA by polymerase chain reaction and negative for human immunodeficiency virus were randomized to receive interferon alfa-2b (3 million units 3 times a week) plus ribavirin (1,000 mg/day) or interferon alfa-2b alone for 48 weeks with 24 weeks of posttreatment follow-up. Patients started on interferon alone who remained positive for HCV RNA at week 12 crossed over to treatment with interferon plus ribavirin. A total of 113 patients were treated. Thirty-seven patients were younger than 18 years. At the end of treatment, 18 of 56 (32%) treated with interferon plus ribavirin and 6 of 57 (11%) treated with interferon alone were negative for HCV RNA (P =.005). Sustained virologic response in the combination arm was 29% (16 of 56) compared with 7% (4 of 57) for those started on interferon alone (P =.027). Among adolescents younger than 18 years who were treated with combination therapy, 10 of 17 (59%) had sustained response compared with 6 of 39 (15%) of adult patients on the same regimen (P =.001). In conclusion, in this U.S. multicenter, randomized trial of therapy for HCV in patients with inherited bleeding disorders, sustained virologic response rate was significantly improved for patients treated with interferon and ribavirin compared with those started on interferon alone. Adolescents treated with combination therapy had a significantly higher sustained response than adults did on the same regimen. Response to treatment with alpha interferon with or without concomitant ribavirin varies according to the viral genotype in patients with chronic hepatitis C.
                This study was undertaken in order to determine the response of genotype 4 chronic hepatitis C to interferon and ribavirin combination compared to interferon alone in patients without cirrhosis.
                Fifty-two patients were given interferon alone at a dose of 5 million units, 3 times a week and another 60 patients were administered with interferon combined with ribavarin (1,000-1,200 mg/ day) for 24 weeks. Sustained biochemical response was defined as normal ALT, 6 months after end of therapy. Sustained virologic response was defined as negative HCV RNA, 6 months after the end of therapy.
                Only 10/52 (19%) patients showed sustained biochemical response after interferon alone, while 31/60 (52%) showed sustained biochemical response after interferon combined with ribavirin (p<0.01). Only 4/52 (8%) patients showed sustained virologic response after interferon alone, while 25/60 (42%) showed sustained virologic response after interferon combined with ribavirin (p<0.001).
                These results show that patients with chronic hepatitis due to hepatitis C virus type 4 show a poor response to interferon alone but a better response to interferon combined with ribavirin. To evaluate the efficacy and safety of therapy for patients with histologically mild hepatitis C virus (HCV) liver disease.
                A randomized, double blind, placebo controlled trial of interferon alpha-2b with or without ribavirin.
                Regional and university hospitals.
                One hundred and sixteen treatment naive patients with mild chronic HCV infection. Mild HCV infection was defined according to Knodell as a grade score of > or = 1 and < or = 6 and a stage score of < or = 1.
                Interferon alpha-2b (3 MU three times weekly) for 52 weeks in combination with either ribavirin or a matched placebo.
                The study endpoint was the absence of HCV RNA in plasma and liver tissue 26 weeks post-treatment. In addition, liver histology was compared pre- and post-treatment.
                Combination therapy was superior to interferon monotherapy, with a virological sustained response rate of 54% (31/57) and 20% (12/59), respectively, in both serum and liver tissue (P = 0.001). The sustained response rate was higher with combination therapy than monotherapy both in genotype non-1 (81% vs 36%) and in genotype 1 (28% vs 4%). There was a significant improvement in mean grade score in all sustained responders, irrespective of treatment arm.
                Combination therapy with interferon and ribavirin was safe and as effective in patients with histologically mild HCV infection as previously reported for more advanced disease. Chronic hepatitis C may lead to cirrhosis and hepatocellular carcinoma in a subset of patients. Because response rates with interferon alfa therapy are unsatisfactory, new therapies are needed.
                We conducted a three-arm, randomized trial in 45 interferon-naive men (mean age 40.6 +/- 12 years) with chronic hepatitis C to compare treatments: group A, ribavirin alone (15 mg/kg daily for 6 months); group B, interferon alone (3 MU thrice weekly for 6 months); and group C, interferon plus ribavirin at the above doses. Histologic outcomes of therapy were assessed by pretreatment and post-treatment liver biopsies.
                In group A, alanine aminotransferase levels normalized during therapy in 66% of those with HCV-1b and 34% of those with HCV-2a, but all patients relapsed after treatment ended. In group B, alanine aminotransferase levels normalized during treatment in 66%, 75%, and 100% of patients infected with HCV-1b, HCV-2a, and HCV-3, respectively; however, a sustained response was noted in only 25% of those with HCV-3. In group C, a sustained normalization of alanine aminotransferase with negative serum HCV RNA was seen in 20% of those with HCV-1b, 40% of those with HCV-2a, and 75% of those with HCV-3 12 months after therapy. One year after therapy ended, group C demonstrated a significant sustained response (47%) as well as a significant reduction in piecemeal necrosis and portal inflammation (p < 0.05).
                Combination therapy was significantly superior to ribavirin or interferon monotherapy in producing a sustained response in interferon-naive patients with chronic hepatitis C (p < 0.05). The results of our study suggest that ribavirin potentiates the effect of interferon therapy in chronic hepatitis C. Hepatitis C virus (HCV) reinfection after liver transplantation is frequent and leads to chronic hepatitis and cirrhosis. The use of antiviral therapy in this situation remains controversial. This study aimed to assess the safety and efficacy of interferon alfa-2b plus ribavirin for recurrent hepatitis C following liver transplantation.
                Transplant recipients with recurrent chronic hepatitis C were randomized to receive either no treatment or therapy with interferon alfa-2b (3 MU 3 times a week) plus 1000-1200 mg/day ribavirin for 1 year. Patients were followed up for 6 months after the end of treatment. The primary end point was loss of HCV RNA 6 months after the end of treatment.
                Fifty-two patients were randomized (treatment, 28; placebo, 24). Sixteen patients were withdrawn from the study; 12 (43%) were from the treated group (mainly for anemia [7 patients]) and 4 (17%) from the control group. In the treated group, serum HCV RNA was undetectable in 9 patients (32%) at the end of treatment and 6 (21.4%) at the end of the follow-up period, whereas no patient in the control group lost HCV RNA at any point (P = 0.036 at the end of follow-up). However, there was no significant histologic improvement.
                The combination of interferon alfa-2b plus ribavirin induced a sustained virologic response in 21% of transplant recipients with recurrent hepatitis C. However, 43% discontinued therapy due to adverse events (primarily severe anemia). Strategies to enable treatment with lower doses of ribavirin need to be explored. 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.
                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.
                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).
                In conclusion, the combination of 3 MU of interferon plus 600 mg of ribavirin is not effective in chronic hepatitis C resistant to interferon. Interferon-alpha (IFN-alpha) induces sustained remission of chronic hepatitis C in approximately 25% of patients. In patients who are non-responders to the first course of therapy, retreatment with IFN-alpha is of limited efficacy. Ribavirin has also been used to treat chronic hepatitis C, but it induces only a transient response. In this study, we evaluated the efficacy of ribavirin and IFN-alpha combination therapy for IFN-alpha resistant chronic hepatitis C. Twenty-four IFN-alpha non-responders and 24 relapsers were randomized to receive either ribavirin (1000 mg per day) together with IFN-alpha (3-6 million units (MU) thrice weekly) or the same dose of IFN-alpha alone, for 6 months. Both at the end of treatment and 6 months later, normal transaminase levels were more common in the patients receiving combination therapy than in the group receiving IFN-alpha alone: 17 (70.8%) vs seven (29.2%) patients (P = 0.009) and six (25%) vs one (4.2%) patient (P = 0.034), respectively. At the end of treatment and 6 months later, serum HCV RNA was no longer detectable in eight (33.3%) and five (20.8%) patients in the combination therapy group and in six (25%) and one (4.2%) patient in the IFN-alpha therapy group, respectively. Three patients (12.5%) were withdrawn prematurely from combination therapy because of side-effects; ribavirin therapy was ceased or dosage reduced in six other patients (25%), again because of side-effects. In conclusion, this combination treatment was more effective than retreatment with IFN-alpha, alone, in inducing sustained biochemical remission of chronic hepatitis C that was resistant to a previous course of IFN-alpha. The combination treatment, however, was frequently associated with significant side-effects.
Compared with interferon alone, ribavirin plus interferon is more effective in clearing hepatitis C virus from the blood. Combination therapy may reduce liver-related morbidity and all-cause mortality, but we need more evidence. The number needed to treat to obtain a beneficial effect is considerable considering the increased risk of several severe adverse reactions and costs.