In these three studies, the use of peginterferon was compared to the use of unmodified interferon either with or without the addition of ribavirin. All three studies showed a significant improvement in sustained virologic response with the use of peginterferon versus unmodified interferon, particularly in the Fried study that used combinations of peginterferon with ribavirin. 

In the first study presented in this Journal Club (Zeuzem et al.), 39% treated with peginterferon compared to 19% treated with unmodified interferon experienced a sustained response at the end of the follow-up period (p=0.001). Results were more favorable in this study, the authors finding that "once weekly administration of peginterferon alfa was associated with a significantly higher rate of sustained virologic response than was a regimen of interferon-alfa given three-times weekly" and that the "improved efficacy of peginterferon alfa may be due to the sustained antiviral effect associated with the enhanced pharmacokinetics of this molecule." The authors also noted that the patients in the peginterferon group experienced a higher rate of relapse during the observational phase of the study.  

The second study (Heathcote et al.) compared peginterferon with unmodified interferon in patients with cirrhosis or bridging fibrosis. Like the Zeuzem study, peginterferon was found to better achieve a desirable histologic response, which correlated to a significantly increased virologic and biochemical response. The virologic response achieved by week 12 in the Heathcote study was strongly predictive of a sustained virologic response 23 of the 26 patients receiving 180μg peginterferon once weekly had no detectable HCV RNA, and at end of treatment--week 48. The 180μg peginterferon group had a higher number of participants with undetectable HCV RNA than did the lower dose peginterferon group or the unmodified interferon group (44% compared to 42% and 14%).  The researchers also noted that although the virologic rate of response was similar at the end of treatment, the 180μg peginterferon group was more likely to sustain the response.

The third study in this Journal Club (Fried et al) compared peginterferon plus ribavirin to peginterferon alfa and unmodified interferon. The authors stated that 56% of those treated with peginterferon alfa and ribavirin, compared to 44% of those treated with unmodified interferon alfa (p<0.001) and 29% of those treated with peginterferon alfa, (p<0.001) showed a sustained virologic response through the post-therapy observational segment of the study (defined as 24 weeks post-treatment). Pegylated interferon plus ribavirin was superior to peginterferon alone or unmodified interferon plus ribavirin at achieving a sustained virologic response. Of the 1121 patients in the study, the authors noted that the peginterferon plus daily ribavirin group experienced a "considerable clinical advantage" over those in the unmodified interferon plus ribavirin group. 

The three studies in the Journal Club all demonstrated the efficacy of peginterferon plus daily ribavirin over peginterferon alone or unmodified interferon both with ribavirin and without.  In the Zeuzem study, measurements taken at the end of the follow-up period showed 39% of peginterferon treated patients versus 19% of unmodified interferon treated patients showed a sustained virologic response.  Fried et al. found peginterferon plus ribavirin to be more effective at sustaining a virologic response in patients versus unmodified interferon or peginterferon alone at end of treatment (56% versus 44% and 29%). The Heathcote study found the 180μg peginterferon group had a higher number of participants with undetectable HCV RNA than did the lower dose peginterferon group or the unmodified interferon group (44% compared to 42% and 14%) at end of treatment (week 48).

In a review of the potential for adverse effects it should be emphasized that there was a continued need to assess the patients undergoing treatment for signs and symptoms. Reported effects with the use of interferon include psychiatric disorders and especially depression, which has been seen on a regular basis. It was also apparent that close monitoring of laboratory values, with particular emphasis on Complete Blood Count with differential should be included in monitoring protocols for interferon therapies.

These studies concurred that peginterferon alfa, preferably in combination with ribavirin, should be the treatment of choice in patients with chronic hepatitis C. Moreover, when comparing sustained virologic responses, pegylated interferon alfa in combination with ribavirin was superior to peginterferon alone or unmodified interferon with ribavirin. Table 1 below summarizes the findings on virologic responses for the studies presented. 

Table 1. Sustained Virologic Response Summary

Hepatitis C is a chronic and progressive illness. Home care services can and should be effectively employed to administer treatments, provide patient education, and assess patient compliance to the weekly therapy of peginterferon and daily ribavirin. Clearly, compliance is a key to peginterferon plus ribavirin therapy's success. The homecare clinician should be skilled in assessing for signs and symptoms of complications related to the disease process, the side effects of treatment (regularly checking for signs of depression), and monitoring adherence to prescribed therapy.

Implications for Social Workers

References:

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