Hepatitis - Quality of Life

The affect of hepatitis C on the quality of life is beginning to emerge as an important parameter in the evaluation of infected patients. Physicians have the perception that patients with hepatitis C are largely asymptornatic, and that having the disease seldom has an impact on patients’ lives. However, studies with large numbers of patients are showing that hepatitis C does indeed negatively affect quality of life.

Until recently, quality-of-life instruments were not validated for use in patients with chronic hepatitis C. Several instruments -- such as the hepatitis quality-of-life questionnaire (HQLQ) and the short-form 36 (SF-36) -- have now been validated for use in this setting. The SF-36 is a simple questionnaire that includes 36 questions that evaluate 8 domains of general well-being. Higher SF-36 scores represent better quality of life.

Foster and colleagues evaluated quality of life in non cirrhotic patients prior to initiation of treatment. In all 8 domains of the SF-36, hepatitis C patients reported a significantly lower quality of life than did controls. The subgroup of patients with hepatitis C who had used intravenous drugs in the past showed the greatest impairment in quality-of-life scores. The amount of inflammation on liver biopsy was not associated with the degree of impairment of quality of life. Bonkovsky and coworkers confirmed in a study of 642 patients that individuals with hepatitis C report lower quality-of-life scores than do healthy controls. Additionally, findings showed that patients who had a sustained response to IFN mono therapy experienced significant improvements in perceived wellness and functional status, which then translated into significant improvements in quality of life. Ware and colleaguest used the HQLQ to evaluate changes in quality of life in IFN mono therapy relapse patients treated with combination IFN and ribavirin therapy. A sustained virologic response was associated with improvements in vitality, social functioning, and health distress.

Antiviral therapies are associated with a decline in quality of life during therapy. This decline returns to baseline with cessation of therapy. This trend was recently demonstrated to be similar for newer agents as well, such as peginterferon-alfa-2a.

Hepatitis C patients have lower quality-of-life scores than the general population, and the evaluation of quality of life thus takes on greater importance in the care of hepatitis C patients. Abnormalities in quality of life are not entirely attributable to histologic disease severity. Newer therapies, such as the pegylated IFNs, may help improve quality of life both during and after therapy.

Hepatitis - Treatment by Liver Biopsy

One of the dilemmas facing clinicians is whether to treat a patient who has hepatitis C and mild disease on liver biopsy. Wong and colleagues evaluated this scenario from the perspective of cost-effectiveness. In a mathematical model, they compared the cost of immediate combination IFN and ribavirin therapy vs watchful waiting for patients with histologically mild disease. While this model suggested that periodic biopsies would avoid institution of therapy in many patients, immediate treatment of these patients was found to be cost-effective by eradicating virus and thereby potentially preventing disease progression.

Hepatitis - Treatment Plan

Several models have been developed in an effort to estimate the cost-effectiveness of both IFN mono therapy and combination IFN/ribavirin therapy for the treatment of patients with hepatitis C. Bennett and associates reported that when using a 5% discount rate, the marginal cost-effectiveness ratio of 6 months of IFN mono therapy in previously untreated patients with mild histologic disease was well within the range of other well-accepted medical interventions. Kim and colleagues, using a 3% discount rate, estimated the marginal cost-effectiveness ratio for 6 months of IFN mono therapy to be $4000 per quality-adjusted life year gained, and $5Q00 per quality-adjusted life year gained for 12 months of IFN mono therapy. Both of these figures are within the range of acceptability to our society, and therefore, therapy is considered cost-effective. This study also found that IFN mono therapy was not cost-effective in patients older than age 60.

Combination therapy with IFN and ribavirin is significantly more expensive than IFN mono therapy. Wong and colleagues evaluated the cost-effectiveness of combination therapy vs IFN mono therapy for treatment duration of 24 and 48 weeks. Both the 24- and 48-week IFN-plus-ribavirin regimens were more cost-effective than 48 weeks of IFN mono therapy. Combination therapy for duration of 24 weeks was found to be more cost-effective in patients with genotype 2 and 3 disease. In all other evaluated parameters, including viral load and underlying histology, combination therapy for a 48- week duration was more cost-effective than the 24-week regimen.

The advent of pegylated IFN has raised questions about its relative cost-effectiveness. This concept is difficult to analyze at present, because pegylated IFN has only just been approved for use in the United States, and therefore, its pricing is unknown. However, assuming that pegylated IFNs significantly improve sustained response rates, cost effectiveness can be estimated in the absence of pricing. Based on this assumption, Wong estimated that if peginterferon-alfa-2b increases the sustained response rate by
10% to 30% and increases relative costs by 10% to 30%, a 48-week course should both prolong life and be cost-effective.