Instructions

  Take Another Course

Post-Test

Resources

Click on the link at left to go to your desired page: Introduction  Page 2  Page 3  Study 1  Study 2  Study 3   Conclusion  Implication for Social Workers  Post-Test

Abstract:

Peginterferon has shown significant treatment advantage over unmodified interferon treatments in patients with chronic hepatitis C viral (HCV) infection. Some histologic improvements have been documented in past studies. This study was conducted to compare the effects of two levels of dosing with pegylated interferon to unmodified interferon therapy in patients with liver histologic changes due to cirrhosis or bridging fibrosis. 271 patients were randomized to receive subcutaneous injections of 3 million units of interferon alfa-2a three times per week (n=88), 90 μg peginterferon once per week (n=96), or 180 μg peginterferon once per week (n=87) for a 48-week treatment period followed by a 24-week post-treatment observation period. Endpoints included alanine aminotransferase, HCV RNA levels (viral load), and histologic changes on liver biopsy. The higher dose of peginterferon showed significant improvement over the unmodified interferon regimen for achieving undetectable viral load (p=0.001) and normalization of liver function tests (p=0.004). Better results were also seen in the 184 patient subgroup that had paired biopsies available for comparison for the higher dose of peginterferon (p=0.02). Results for all three groups are shown in the table below.

Table 1. Summary of Results on Study Endpoints

All three groups had a similar number and severity of adverse events.  The overall conclusion of the study is that peginterferon alfa is more effective in patients with chronic hepatitis C with cirrhosis or bridging fibrosis, particularly in the higher dose group. In this study, the researchers found that 180 μg of peginterferon alfa once weekly is significantly more effective than 3 million units of interferon alfa three times weekly.

cirrhosis, bridging fibrosis, peginterferon alfa, chronic hepatitis C infection, HCV

Discussion:

Concerns over complications have tempered the use of interferon, either with or without ribavirin, in the treatment of chronic hepatitis C with cirrhosis. While unmodified interferon has played a key role in the treatment of chronic hepatitis C infection, concerns, such as the potential for the exacerbation of pre-existing neutropenia or thrombocytopenia, have warranted cautious use of unmodified therapies.

Peginterferon (such as pegylated interferon alfa) is accepted as efficacious in providing a sustained virologic response not seen with the use of unmodified interferon alone. The response is similar to that seen with combined interferon and ribavirin therapy. Tolerability has been found to be on par with regular interferon.

While other trials of peginterferons have shown favorable results in chronic HCV, the authors note that patients with chronic HCV infection usually have a poor response to unmodified interferon if they also have advanced liver disease, such as cirrhosis and bridging fibrosis.

Results:

Of the 271 patients enrolled in the study, most had cirrhosis at the start of the trial.

The researchers concluded that 180 mg of peginterferon alfa-2a once weekly was significantly more effective than 3 million units of unmodified interferon alfa-2a three times weekly at the completion of the treatment and post-treatment segments of the study (week 72).

Dose modifications were required due to adverse events, neutropenia, and thrombocytopenia. During the treatment phase 24/88 in the unmodified interferon group, 18/96 in the lower dose peginterferon, and 20/87 in the higher dose peginterferon groups discontinued their participation. Reasons for therapy discontinuation included adverse events (8%, 7%, and 11% in the unmodified interferon, lower dose pegylated interferon, and higher dose pegylated interferon groups respectively), laboratory abnormality (2%, 4%, 1%), lack of virologic or other therapeutic response (6%, 2%, 1%), and other reasons such as refusal of treatment or protocol violations (11%, 5%, 8%). The researchers reported that the adverse effects in patients assigned to the peginterferon alfa groups at either dose were typical of those seen in patients receiving unmodified interferon. Patients who discontinued therapy were asked to continue participation for the 24 week observational phase of the study. Thus, 68/88 unmodified, 79/96 lower dose pegylated, and 74/87 higher dose pegylated group participants completed the observational phase of the study. 

Table 2. Therapy Discontinuation by Group

Histologic response was compared in participants who had paired biopsies available for evaluation. Trials that include a liver biopsy might experience a fairly high rate of attrition. Nearly 30% of participants did not return for their second liver biopsy. A histologic response was seen in 26%, 33% and 35% of patients in the unmodified, lower dose pegylated, and higher dose pegylated interferon groups respectively. Histologic responses were lower among those patients assigned to receive unmodified interferon (31%) than among those assigned to the higher doses peginterferon groups (54%; p=0.02).  The difference between the unmodified (31% response) and lower dose pegylated (44% response) groups was not statistically significant (p=0.22). Histologic responses were related to sustained virologic responses. The virologic response rate was similar between patients with bridging fibrosis or cirrhosis.

This study demonstrated that two different doses of peginterferon alfa were more effective than unmodified interferon to produce a higher level of desired virologic, biochemical, and histologic results. Interestingly, in most patients that had sustained virologic responses when measuring HCV RNA at week 72, these results could be predicted from measurements taken at week 12. More than half the study participants had a histologic response at week 72, regardless of their virologic or biochemical response. The authors concluded that because of results seen with those participants that did not have a virologic response, (among those patients that did not have a virologic response, more than 1/3 saw histologic improvement) peginterferon alfa-2a may benefit these patients.

The authors suggested that more research is justified, particularly a comparison of peginterferon alfa and ribavirin versus unmodified interferon and ribavirin to determine efficacy, safety, and tolerability comparisons.

Summary of Study 2