Efficacy of pegylated interferon alfa-2a or alfa-2b in combination with ribavirin in the treatment of chronic hepatitis caused by hepatitis C virus genotype 1b.

INTRODUCTION: Treatment of chronic hepatitis C (CHC) with pegylated interferon (Peg-IFN) and ribavirin leads to sustained virological response (SVR) in approximately 50% of the patients. SVR depends on hepatitis C virus (HCV) and host factors, including IL28B genotypes. OBJECTIVES: The aim of the study was to investigate the therapeutic efficacy of the difficult-to-treat HCV genotype 1b in patients from the south of Poland. PATIENTS AND METHODS: A total of 260 adult patients with CHC and HCV genotype 1b were treated with Peg-IFN alfa-2a or Peg-IFN alfa-2b with ribavirin for 48 weeks. Efficacy was assessed at 12 weeks (early virological response - EVR), 48 weeks (end-of-treatment response - ETR), and at 6 months (SVR). HCV-RNA, alanine transaminase (ALT), and other biochemical parameters were measured in serum at baseline and at 12, 48, and 72 weeks of therapy. RESULTS: HCV-RNA levels were 3.72 ±1.17 × 106 IU/ml at baseline and decreased significantly at 12 weeks (0.02 ±0.17 × 106 IU/ml); there were no differences between the group treated with Peg-INF alfa-2a and the group treated with Peg-INF alfa-2b. ALT was 94.1 ±7.6 IU/l at baseline and decreased significantly at 12 weeks (42.5 ±3.1 IU/l). The overall EVR, ETR, and SVR were achieved by 63.9%, 77.7%, and 48.1% of the patients, respectively. Tolerance of therapy was similar in both groups. CONCLUSIONS: Efficacy of Peg-IFN alfa-2a with ribavirin is not significantly different from that of Peg-IFN alfa-2b with ribavirin, and SVR was achieved in 48.3% and 44.3% of the patients, respectively. Our study confirms that the efficacy of treatment of patients with HCV genotype 1b from the southern region of Poland is similar to that observed in the overall Polish population.

[Changes of lipid metabolism in patients with chronic viral hepatitis treated with interferon alpha]. / Zaburzenia przemiany lipidów u chorych z przewleklym wirusowym zapaleniem watroby w przebiegu leczenia interferonem alfa.

UNLABELLED: Changes of lipid metabolism are often observed in patients (pts) with chronic viral hepatitis during interferon therapy. Many studies show changes in blood lipids including increase of triglycerides level, decrease of total cholesterol as well as HDL lipoprotein levels. This study was an attempt to widen our knowledge about additional factors responsible for changes in lipid metabolism of pts with chronic viral hepatitis during interferon therapy. The aim of this study was to assess the changes of total cholesterol, triglycerides and LDL-, HDL-lipoproteins levels in blood serum in comparison to: activity of hepatic inflammation, degrees of fibrosis, type of hepatotropic viruses and response to antiviral treatment. MATERIAL AND METHODS: In the group of 53 pts (18 female, 35 male), age 16-61 years old with chronic hepatitis B (13 pts) and chronic hepatitis C (40 pts) treated with interferon alpha we examined the cholesterol, HDL, LDL-lipoproteins and TG levels in blood serum at the beginning of therapy and in the sixth month. Changes of lipids values at the beginning and in the sixth month of therapy were assessed in respect to: necro-inflammatory changes of the liver in histopathological examination, degrees of fibrosis, obesity, loss of the weight during IFN therapy, response to treatment, type of hepatotropic viruses (HBV, HCV), sex and age. RESULTS AND CONCLUSIONS: During sixth month of interferon therapy there was significant decrease of total cholesterol level (before treatment 4.1 +/- 1.0, after treatment 3.8 +/- 0.9, p < 0.05) and HDL-lipoproteins level (before treatment 1.3 +/- 0.35, after treatment 1.1 +/- 0.35, p < 0.05). Increase of TG level was not statistically significant. The necro-inflammatory changes in the liver correlated with the values of TG level. Low activity of hepatic inflammation correlated with the increased TG level at sixth month of therapy. There was not observed effect of any other factors on the lipid metabolism.

[Clinical manifestations and effect of early therapy with interferon-alpha on the course of acute hepatitis C]. / Manifestacja kliniczna i wplyw wczesnego leczenia interferonem alfa na przebieg ostrego wirusowego zapalenia watroby typu C.

UNLABELLED: The aim of the study was to estimate the course of acute hepatitis C and efficacy of 24 weeks monotherapy with interferon alpha 2b (IFN). METHODS: Twenty one patients with acute hepatitis C (age between 26 and 79; 17 females, 4 males) treated in the University Hospital between March 2000 and December 2004 were included into this study. Acute phase of hepatitis C was diagnosed on the basis of HCV-RNA presence by PCR, seroconversion to anti-HCV, clinical symptoms of acute hepatitis and clinical view with epidemiological anamnesis. Biochemical, serological and virusological parameters as well as complete blood count were examined during observation. The efficacy of antiviral treatment with IFN (5 MU daily for 30 days, then 3 MU tiw for 24 week) was studied in 8 patients. Loss of HCV viremia after 24 weeks of treatment and sustained response after the next 24 weeks of follow-up were examined. RESULTS: Jaundice, the main clinical symptom, was observed in 17 (81%) patients, with mean bilirubin level of 147.7 micromol/l. Dyspeptic symptoms were noticed in 71% patients, arthralgia 24%, fatigue in 19% patients. The maximal ALT activity was 1744 U/l, AST 1235 U/l and GGT 372 U/l. The course subsequent to the acute phase was analyzed in 18 patients. Spontaneous loss of viremia was observed in 28% patients. Among the 8 patients included to the therapy early response was observed in 88% and sustained viral response in 75% of them. CONCLUSIONS: Early initiation of interferon alpha therapy in patients with acute hepatitis C significantly reduced the rate of chronicity and was well tolerated by patients.

[Pegylated interferon-alfa 2a with ribavirin in chronic viral hepatitis C (final report)]. / Pegylowany interferon alpha-2a z rybawiryna w leczeniu przewleklego wirusowego zapalenia watroby typu C (raport koncowy z badan).

UNLABELLED: We evaluated the efficacy and safety of peginterferon alfa-2a [40KD] (Peg-IFNalpha-2a) plus ribavirin in patients with chronic hepatitis C in an open-label programme in a routine clinical setting in Poland. Patients received Peg-IFNalpha-2a 180mg/week plus ribavirin 800-1200 mg/d for 48 weeks. Sustained virological response (SVR) was defined as undetectable HCV RNA (<50IU/mL) at the end of follow-up (week 72). 466 adults were enrolled. Most patients (87.3%) had genotype 1 infection. 440 subjects (94,4%) completed treatment. The overall SVR rate was 55.7%. A higher SVR rate was obtained in treatment-naïve patients (58.7%) than in relapsers (47.8%; p=0,048). SVR rates in genotype 1 and non-1 patients were 51.1% and 88.5%, respectively (p<0.001). There were significant higher SVR rates in patients with lower baseline fibrosis (p=0,01). There were no differences in SVRs by gender or viral load. Hemoglobin, leukocyte and neutrophil levels decreased significantly during treatment, but returned to baseline after the end of treatment. ALT levels decreased significantly during treatment in patients with and without an SVR. 38.4% of patients experienced adverse events like neutropenia, anemia, thrombocytopenia, and other. There was one death (severe thrombocytopenia). CONCLUSIONS: The overall SVR achieved in this predominantly genotype 1 population was 55.7%. SVR rates were significantly higher in treatment-naïve patients, those with non-1 genotypes, and in patients with lower baseline fibrosis scores.

[Peginterferon alpha-2b in patients with chronic hepatitis C]. / Pegylowany intefeon alpha-62b i rybawiyna w leczen przewlekllego wirusoweg zapalenia watroby typu C.

150 adult patients were assigned pegylated interferon alpha-2b (once weekly 1.5 microg/kg) plus ribavirin (800-1200 mg depending on bodyweight). The treatment lasted 52 weeks and was completed by 139 persons (92.7%). Because of adverse events the treatment was interrupted in 7 persons, 4 other persons resigned. Periodical reduction of pegylated interferon doses was necessary in 19% and the reduction of ribavirin in 21% of patients. Six months after the completion of treatment HCV-RNA was negative in 82 (59%) patients. Neither hepatitis C virus genotype, nor viremia was marked in the study. The negative correlation between the degree of fibrosis in the liver tissue and the results of sustained virological response was stated. Degree of inflammation at liver tissue, sex, age over and less than 40 years did not correlate with the final virological results. The recurrence of infection happened at 7% of the treated persons (negative HCV-RNA directly after the treatment--positive 6 months after the completion). During the treatment period, and comparison with the results obtained before its implementation, statistically significantly decreased: hemoglobin concentration, the number of leukocytes, granulocytes and thrombocytes. They returned to the referential values half a year after the completion of treatment. The activity of enzymes (AIAT, AspAT, GGTP) was decreasing statistically significantly since the first weeks of the treatment till the end and remained significantly lower after 6 months. In both sexes statistically significant reduction of bodyweight was stated, while it increased during the six months after the completion of treatment. Adverse events, which mostly were mild and were not the cause of interruption of treatment, were numerous and occurred at different frequency, in the range from over 50% (flu-like) to 0.7%.