Long-term clearance of hepatitis C virus following interferon α-2b or peginterferon α-2b, alone or in combination with ribavirin.

Sustained virologic response (SVR) is the standard measure for evaluating response to therapy in patients with chronic hepatitis C (CHC). The aim of this study was to prospectively assess the durability of SVR in the pivotal studies of peginterferon (PEG-IFN) α-2b or IFN α-2b. We conducted two phase 3b long-term follow-up studies of patients previously treated for CHC in eight prospective randomized studies of IFN α-2b and/or PEG-IFN α-2b. Patients who achieved SVR [undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of treatment] were eligible for inclusion in these follow-up studies. In total, 636 patients with SVR following treatment with IFN α-2b and 366 with SVR following treatment with PEG-IFN α-2b were enrolled. Definite relapse (quantifiable serum HCV RNA with no subsequent undetectable HCV RNA) was reported in six patients treated with IFN α-2b and three patients treated with PEG-IFN α-2b. Based on these relapses, the point estimate for the likelihood of maintaining response after 5 years was 99.2% [95% confidence interval (CI), 98.1-99.7%] for IFN α-2b and 99.4% (95% CI, 97.7-99.9%) for PEG-IFN α-2b. Successful treatment of hepatitis C with PEG-IFN α-2b or IFN α-2b leads to clinical cure of hepatitis C in the vast majority of cases.

Impact of interferon alfa-2b and ribavirin on progression of liver fibrosis in patients with chronic hepatitis C.

The extent of liver fibrosis is an important prognostic factor in patients infected with hepatitis C virus. Administration of a combination of interferon and ribavirin produces a superior viral clearance response rate than interferon alone. The effect of this combination regimen on hepatic fibrosis has not been established. To determine the impact of combination regimen or interferon alone on the progression of liver fibrosis we pooled individual data of 1,509 patients with pretreatment and post-treatment biopsies from 3 randomized trials. Fibrosis progression and regression rates between biopsies were calculated by the Kaplan-Meier method and by the fibrosis progression rate per year. The percentage of patients without significant fibrosis (stage 0 or 1) at 96 weeks was 68 +/- 4% (mean +/- SE) when treated by combination regimen for 48 weeks, 64 +/- 4% by interferon alone for 48 weeks, 42 +/- 7% by combination regimen for 24 weeks (lower than both 48-week regimens P <.001), and 24 +/- 9% interferon alone for 24 weeks (lower than the combination regimen for 24 weeks; P =.02). Three factors were independently associated with fibrosis reduction: sustained viral response, duration of treatment, and baseline fibrosis stage (all P <.001 in proportional hazards regression model). These results show that interferon and ribavirin combination therapy significantly reduces the rate of fibrosis progression in patients with hepatitis C. This effect was most prominent in patients who achieved a virologic response, those receiving 48 weeks of therapy, and in patients with significant fibrosis at baseline.

Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[The response of the hepatitis C and hepatitis G viruses to treatment with recombinant interferon alfa-2b]. / Respuesta del virus de la hepatitis C y del virus de la hepatitis G al tratamiento con interferon alfa-2b recombinante.

OBJECTIVE: The efficacy of recombinant alfa-2b interferon therapy in C-virus (HCV) and G-virus (HGV) in children with chronic hepatitis C was evaluated. PATIENTS AND METHODS: Fifteen patients, between 6 and 16 years of age and positive for HCV of which four were also infected with HGV, were treated with interferon (3 M three times a week for 6 months). The responders were treated for 12 months. HCV RNA, antibodies to HCV, HVC viral genome (expressed as 1000 copy equivalents of HCV genome = 1 keq), HGV RNA (RT/PCR, 5'NCR-NS5), and E2-HGV antibodies were determined before treatment and at 3 and 6 months in all patients and at 12-24 months in the responders. RESULTS: Four HCV patients (27%) with low viral load (mean 36 keg/ml) showed good results after interferon treatment and two of them (13%) with genotypes 1b and 3 according to Simmond's classification showed a maintained response. The four HGV children also showed the same good results and the RNA was negative without sero-conversion to anti-E2 after 12 months of interferon treatment. In the post-interferon treatment period, the HGV RNA appeared again in the serum in 3 of the 4 children. In the child with a maintained response, serum conversion to anti-E2 was not detected. CONCLUSIONS: 1) The current results, with only 13% of the patients reaching a sustained response, question the systematic treatment of all children affected with hepatitis C virus. Since the cost-benefit ratio is not yielding the expected results, such therapy may be reserved for patients with genotype other than 1b and a low level of viral genome. 2) HGV is sensitive to treatment with interferon, although the infection frequently appears again once the treatment is over.

Effects of different dose levels and vaccination schedules on immune response to a recombinant DNA hepatitis B vaccine in haemodialysis patients.

Hepatitis B is a frequent complication in haemodialysis patients because of their repeated exposure to blood products, and their impaired cellular and humoral response; trials with plasma-derived hepatitis B vaccine (PDV) show lower immune responses than those in healthy adults. Using a yeast-derived hepatitis B vaccine (YDV), the immunogenicity of two different dose levels (20 and 40 micrograms) and three vaccination schedules were compared in over 270 seronegative dialysis patients. Vaccination with 40 micrograms gave slightly better results than with the 20 micrograms dose. Seroconversion rates were higher with four dose, 40 micrograms vaccination schedules than a three dose schedule, and ranged from 80 to 86%. As the 40 micrograms, 0, 1, 2, 6 month schedule leads to a more rapid rise in antibody levels than the 40 micrograms, 0, 1, 2, 12 month schedule, it appears to be the most appropriate schedule in this patient group.

[Pyogenic liver abscess. Review of 33 cases]. / Absceso piógeno hepático. Revisión de 33 casos.

Thirty three cases of pyogenic liver abscess, (24 single and 9 multiple), diagnosed in our department during the past 6 years, were reviewed. Mean patient age was 54 years with a male predominance over females (1.5:1). The most frequently encountered underlying pathology was bile duct disease (33%), followed by previous liver disease (21%). Causal pathology could not be found in 4 cases (12%). The most frequent sign was fever (76%). Diagnosis was made by clinical picture and complementary exam (echography, CT scan and hepatic gammagraphy) in 29 cases (88%). Blood and pus cultures were positive in 47 and 67% of cases respectively. Thirty nine per cent of microbial abscesses were polymicrobial. E. coli and S. milleri were the most frequently isolated. No micro-organism were identified in 5 cases (15%). Antibiotic treatment was given to 33 patients. Surgical drainage was performed in 24 cases and percutaneous drainage in 7 patients. Two patients received antibiotics exclusively. Five patients died (15%), three of whom had a multiple abscess (33%) and the other two had a single abscess (8%). The efficacy of percutaneous drainage for diagnosis and treatment is analyzed reviewing recent literature.

Immunogenicity of a yeast-derived hepatitis B vaccine in hemodialysis patients.

In a multicenter study of hemodialysis patients in Spain, the immunogenicity of a yeast-derived recombinant deoxyribonucleic acid hepatitis B vaccine was evaluated. Two different vaccination schedules were examined: zero, one, two, six months and zero, one, two, 12 months. Two different dose levels (20 micrograms and 40 micrograms) were also compared. No serious adverse effects were reported by any of the vaccinees; the most frequently reported reaction was soreness at the injection site. This study also indicated that higher concentrations of antibodies are attained when more frequent doses of vaccine are administered. The yeast-derived vaccine produced an immune response similar to that of the plasma-derived vaccines.