Logo Parade
Nutrition
Medicine
Exercise
Complementary
Professional and Personal Alliances
Quality of Life
Message from White House
Sponsors
HIV & Conference News
Founders Speak Out
Hope In Africa
Internet and Community Resources
Dosing Chart
Survey
Free Subscriptions
Copyright Information
Back Issues On Line
Letters to the Editor
Patients Assistance Program
Sponsorship and Media Guide
Enter Keywords

 

Hepatitis C Update: Report from the 51st Annual AASLD

The 51st Annual Meeting of the American Association for the Study of Liver Disease (AASLD) was held in Dallas on October 27-31, 2000. A number of themes became prominent in this years annual session. Issues regarding Hepatitis C included quality of life for those chronically infected, the interplay between diagnostics and therapeutics and the growing excitement over pegylated interferons all came into sharper focus in the poster and oral presentations.

Khozema B. Hussain and Robert J. Fontana discussed "Psychiatric Symptoms in Chronic Hepatitis C (CHC) Patients Not Receiving Antiviral Therapy (Abstract #487). They note that many studies have shown that CHC patients have impaired health-related quality of life (HRQOL) as compared to age matched controls. Depression is frequently present in CHC patients prior to initiation of antiviral therapy. The relationship of psychiatric symptoms to health-related quality of life in CHC patients has not been studied. The aim of their study was to determine the type and severity of emotional distress in an unselected population of CHC patients not on antiviral therapy (interferon therapy has been associated with eliciting depression) and its impact on health-related quality of life. They found that approximately 50% of patients with compensated Chronic Hepatitis C not receiving antiviral therapy reported moderate to severe emotional distress as compared to the general population. The frequent occurrence of emotional distress may contribute to the poor health related quality of life seen in Chronic Hepatitis C patients. This observation is very important in that the focus on a patients emotional health with CHC has usually been during the treatment phase and beyond. Many patients and their physicians do not opt for early antiviral treatment. This study makes clear that even without antiviral treatment, patients with Chronic Hepatitis C must be evaluated for early mental health interventions and appropriate support systems must be in place.

In Abstract 486, "Impact of HIV Infection on Health-Related Quality of Life in Patients with Chronic Hepatitis C: An Unexpected Finding," Edmund J. Bini and colleagues found that patients with CHC have a significantly reduced HRQOL compared to those with HIV. Surprisingly, the health-related quality of life in patients who are co-infected with HCV and HIV is not worse than those with HCV alone and falls somewhere between the health-related quality of life of patients with HCV and those with HIV. Again, this study explodes the preconceived notion that HIV/HCV co-infection will lead to an exponential decrease in the patients health-related quality of life. The main driving force for health-related quality of life appears to be infection with Chronic Hepatitis C. Therefore, comprehensive evaluation of Hepatitis C as well as timely and appropriate mental health interventions must be offered to the co-infected patient.

New Hepatitis C diagnostic tests are poised to come to market as they have been submitted to the FDA. The question has been how will these new tests extend the clinicians powers in Hepatitis C? A study from Mitchell Shiffmann and colleagues, "Clinical Utility of HCV RNA Quanitification Using the Cobas Amplicor HIV Monitor Test, Version 2.0, as an Early Predictor of Sustained Response to Interferon Alfa-2A (Roferon) or Pegylated (40kda) Interferon Alfa-2A (Pegasys) Therapy (Abstract #802). The objectives of this study were to evaluate whether quantifying hepatitis C virus RNA (HCV viral load) prior to, and during the first 16 weeks of antiviral therapy could be used to predict at an early time point sustained virologic, biochemical and histologic responses (as determined 6 months after therapy had completed) in patients treated for chronic HCV infection. The primary focus of therapy for Hepatitis C is eradication of the virus. It is one thing to seemingly eradicate virus by an undetectable HCV viral load during therapy, it is quite another to have sustained viral response (SVR) that is, the maintenance of an undetectable HCV viral load off therapy. Therapy is never less than 6 months and is often at least one year in duration. If a test could predict which patients would benefit from completing a course of therapy then those patients whose test results predicted failure could have changes made in their therapeutic regimen at an earlier and, hopefully, more treatable time.

In this study, sera were obtained for HCV RNA testing from 122 patients enrolled in a randomized open label study comparing interferon a-2a to four doses (45, 90 180 and 270 mg) of PEG (40kDa) IFN a-2a in patients with chronic HCV infection. Patients were treated for 48 weeks and followed post-treatment for 24 weeks (ie, 72 week study period). The COBAS AMPLICOR HCV MONITOR Test (an automated version of the Roche PCR based Hepatitis C assay), version 2.0, was used to quantify HCV RNA at baseline and at various intervals during and after treatment. A Logistic Regression Model was used to describe the relationship between sustained response and HCV RNA levels prior to and during the first 16 weeks of therapy.

The authors reported that HCV RNA levels at weeks 8, 12, and 16 were highly predictive of sustained virologic response (SVR) and/or sustained biochemical response (SBR) at 6 months post-therapy. HCV RNA levels at these time points were also predictive of histologic improvement, however the predictive power was less than virologic or biochemical response. Baseline HCV RNA levels (prior to therapy) were somewhat less predictive. The authors concluded that early HCV RNA levels quantified using the COBAS AMPLICOR HCV MONITOR Test, version 2.0, at weeks 8, 12 or 16 of therapy are predictive of a sustained histologic response and are highly predictive of SVR and/or SBR. These early viral load measurements appeared to have greater prognostic utility than pre-treatment HCV RNA levels in predicting response to standard IFN or PEG (40kDa) IFN a-2a therapy. Such information may improve patient management by individualizing therapeutic regimens (e.g., adopting a more effective therapy at an earlier point in time) resulting in greater compliance and improved outcome.

This is an interesting time in Hepatitis C diagnostics and therapeutics. The era of pegylated, once-a-week interferons is poised for fruition. Pegylation refers to the addition of a polyethylene glycol moiety to alpha-interferon. This addition changes the pharmacokinetics of the agent so that a once weekly injection yields therapeutic blood levels throughout that time. This obviates the dilemma with current therapy wherein the customary use of alpha-interferon, thrice weekly subcutaneous injection, creates a therapeutic milieu wherein blood levels are, more often than not, insufficient for treatment purposes.

In Abstract 1131, "Efficacy of Pegylated (40kda) Interferon Alfa-2A (Pegasys™) in Randomized Trials of Patients with Chronic Hepatitis C, With and Without Cirrhosis: Correlation of Virologic Responses with Baseline Liver Histology and Genotype," Paul J. Pockros and colleagues evaluated the sustained virologic response (SVR) in patients treated with PEG (40kDa) IFN a-2a or IFN a-2a across 3 large pivotal trials with similar entry criteria, according to HCV genotype and baseline histology. A total of 63% of patients were infected with genotype 1; 18% had established cirrhosis (fibrosis score 4) and 11% had transition to cirrhosis (fibrosis score 3). Across all patient subgroups, according to genotype and fibrosis score, treatment with PEG (40kDa) IFN a-2a yielded significantly higher SVR than did standard IFN a-2a. Most dramatic were PEG (40kDa) IFN a-2a results in patients with cirrhosis and patients infected with genotype 1. SVR results are summarized in the table below. Conclusion: These results demonstrate the superior efficacy of PEG (40kDa) IFN a-2a compared with IFN a-2a in the treatment of CHC including difficult-to-treat patients, ie those with cirrhosis and those infected with genotype 1. This superiority is achieved despite nearly half of the control patients having received high dose IFN induction therapy.

This study points to the extraordinary increase in efficacy of pegylated interferon as compared to conventional interferon. Especially notable is the increase in sustained virologic response in the most difficult HCV genotype to treat, Genotype 1.

 

Back to top | back to HCV
CVS ProCare Pharmacies BMS Virology MTI Biotech Roche Laboratories GlaxoSmithKline Ortho-Biotech Roche Diagnostics