THE EFFECT OF SUCCESSFUL ANTI·VIRAL THERAPY ON HEALTH·RELATED QUALITY OF LIFE FOR PATIENTS WITH CHRONIC HEPATITIS C AND CIRRHOSIS. Graham Cooksley, Graham Foster. Jesse Green. Leah Kleinman, Zafar Hakim, Dennis Revicki, Royal Brisbane Hosp, Herston, Australia; ICSM,
NONDETECTION OF HEPATITIS C VIRUS IN PARAFFIN·EM· BEDDED LIVER BIOPSIES OF PATIENTS WITH NEGATIVE VI· RAL RNA IN SERUM AFTER ANTIVIRAL THERAPY.
St Mary's Campus. London, United Kingdom; Hoffmann-La Roche. Nutley, NJ; MEDTAP Inti Inc, Bethesda, MD; Hoffmann-La Roche, Palo Alto, CA. Background: Chronic hepatitis C (CHC) can have a profound effect on health-related quality of life (HRQL). Interferon alfa-2a (IFNa-2a) is widely used to treat patients with CHC but has limited effectiveness, especially among cirrhotic patients. A new form of interferon - 40 kDa pegylated interferon alfa-2a (PEG[40K]-IFNa-2a) - recently was shown to yield higher sustained response rates compared to standard IFNa-2a (30% versus 8%, respectively, after 48 weeks of treatment plus 24 weeks of follow up) in patients with CHC and cirrhosis. The impact of sustained response on HRQL warranted evaluation. Methods: HRQL was assessed in a randomized controlled clinical trial (n = 250) comparing PEG(40K)IFNa-2a to standard IFNa-2a. Therapeutic responders were identified using the combined clinical efficacy measures of viral suppression and hepatic biochemical normalization. Sustained response was characterized by normal liver enzymes and undetectable hepatitis C virus (HCV) RNA six months posttreatment. HRQL was assessed with the standardized 36-question short form (SF-36) Health Survey. Results: From pretreatment baseline to status at end of treatment, the SF-36 physical component summary (PCS) scores of sustained responders improved from 46.1 to 48.9. while the PCS scores of non-responders diminished from 44.5 to 43.9. Therapeutic responders noted greater improvement compared to non-responders for all scales within the PC domain; ie, Vitality, Physical Functioning, Bodily Pain, General Health, and Social Functioning. No meaningful differences were seen between the responder and the nonresponder mental health component summary scores for Role-Physical. Role-Emotional, and Mental Health scales. Forty-eight percent (48%) of patients treated with PEG(40K)-IFNa-2a, compared to 26% of patients treated with standard IFN a- 2a, reported feeling better or much better when asked to rate their general health at the time of questioning compared to one year before. Conclusions: PEG(40K)-IFNa-2a is associated with a particularly marked increase in self-rated health improvement compared to standard IFNa-2a as measured by the SF-36 Health Survey. Moreover, lasting improvement in HRQL, extending> 24 weeks beyond cessation of therapy, is reported by patients with CHC and cirrhosis who have sustained responses to treatment.
mea DOSE INDUCTION THERAPY WITH INTERFERON AL· PHA FOLLOWED BY COMBINATION THERAPY FOR NAIVE HEPATITIS C PATIENTS· RESULTS OF A MULTICENTER RAN· DOMIZED CONTROLLED STUDY. S. Kaiser. C. Kreysel, M. Zeitz, W. Schneider, M. Gregor, Univ of Tuebingen, Tuebingen, Germany; Univ of Hamburg. Homburg, Germany. Attempts to improve the sustained response (SR) rate of interferon (lFN) therapy for chronic HCV have been concentrated in optimizing dosage and using adjuncts to IFN. Recent data have suggested that high-dose induction therapy and addition of ribavirin both may improve SR in HCV. We sought to determine the effectiveness as determined by viral eradication and normalization of serum aminotransferases of high dose induction IFN therapy in comparison to standard therapy in naive patients with chronic HCV. A multicenter, randomized, controlled trial was initiated in which patients with HeV (positive HCV RNA and elevated serum aminotransferases) were randomized to receive either high dose (HD) IFN alpha (5 MU, 7.5 MU or to MU daily for 21 days then 5 MU TlW for 9 weeks) or standard dose (SD) (3 MU TIW forl2 weeks). After the induction period, each group received IFN 3 MU TIW and ribavirin for 36 weeks. This report constitutes an interim analysis of the biochemical and virological parameters of 112 patients (76 in HD and 36 in SD) who have completed the treatment phase. 52 patients in the HD group and 16 in the SD group (p=S) had eradicated the virus after 48 weeks. When the results were further analyzed according to genotype, a significant effect of HD versus SD therapy could only be demonstrated for genotype I regardless if 5MU, 7.5 MU or tOMU were used. An additional effect of 10 MU versus 5 or 7.5 MU could only be seen in patients with a high viral load of > 2 Mio viral copies Iml serum. In this HD group a minimum of a I log decrease in viral titer within the first 4 weeks was observed in 42% of patients. Response rates in genotype 2 and 3 patients were not significantly different in the HD and SD groups. The results so far obtained of an analysis within a large multicenter, randomized, controlled trial comparing HD and SD IFN in naive HCV patients revealed differences in viral eradication at the end of treatment only for genotype I patients. This effect appears to be due to daily dosing, whereas an additional effect of higher dosing increases response rates only in patients with higher viral titers. Results regarding a larger number of naive HCV patients and the effect on sustained response rates will soon be available.
Xiaoli Ma, Rebecca Thomas, Martin Black, Monika Burke, GI Section, Temple Univ Hosp, Philadelphia, PA; Dept of Pathology, Temple Univ Hosp, Philadelphia, PA. Background: Up to four million Americans are infected with Hepatitis C (HCV), and approximately 20% of these patients will progress to cirrhosis. Diagnosis of the condition is based on the presence of antibodies and the detection of HCV RNA by PCR in the serum. Up to 20% of anti-HCV positive individuals have no detectable HCV RNA in the serum, despite the presence of elevated aminotransferases. In addition, inflammation has been detected on liver biopsies of patients without detectable serum HCV RNA. In a recent study, HeV RNA was detected in the liver of at least 60% of patients who were anti-Hf'V positive with negative serum HCV RNA. Aim: Because serum HeV RNA peR is used to assess response to antiviral therapy, we designed a study to determine whether HeV RNA was detectable in the liver following antiviral therapy in patients with negative serum HeV RNA. Methods: Eight patients who cleared HCV RNA after six to 12 months of interferon or interferonlribavirin therapy and six randomly chosen control patients who remained viremic following therapy were studied. HCV RNA (by RT-PCR) was performed on all liver biopsy samples before therapy and six months after completing therapy. Serum ALT and AST were measured before and after therapy. Results: All patients with positive serum HCV RNA before therapy had detectable virus in the liver. HCV RNA was not detected in the liver in the 8 patients who were serum HeV RNA negative following therapy. All of these patients remained serum HCV RNA negative six months to two years following liver biopsy. All non-responders had detectable virus in the liver after antiviral therapy. All sustained responders normalized their serum ALT and AST following therapy (166 :t 24 vs. 19 :t 3 and 97 :t 12 vs. 23 :t 2.4 Ilf/L, both p
240 THE OPTIMAL STRATEGY TO IDENTIFY HEPATITIS CPA· TIENTS WHO REQUIRE TREATMENT. A COST·MINIMIZA· TION ANALYSIS. Ann M. Borzecki, Irena Lendel, Spencer Lee, Kevork M. Peltekian, Dalhousie Univ, Halifax, NS, Canada. Background: Chronic hepatitis C infection affects nearly 4 million people in the United States. Diagnosis of hepatitis C virus (HeV) infection involves screening using enzyme-linked immunosorbent assay (ELISA) followed by confirmation with recombinant immunoblot assay (RIBA) for detection of anti-HCV antibody or polymerase chain reaction (PCR) assay for detection of HCV RNA. PCR is considered the gold standard for diagnosis of HCV infection and identification of cases for treatment. Despite this, many laboratories still do RIBA first and then perform PCR only when treatment is being considered at a later date. With recent therapeutic advances, there is a growing need to identify patients who may benefit from treatment (PCR +) rather than just identifying patients who have been exposed to HCV (RIBA +). Objective: To assess the cost of two different strategies for diagnosis of HeV infection in patients with elevated liver enzymes who will require treatment. Methods: A cost minimization analysis was performed using decision analysis. Our decision tree was developed using investigator expertise and literature review. Probabilities were obtained from our institutional data. Direct medical costs were estimated using the Nova Scotia Department of Health fee schedule (CDN$). The prototype patient had elevated liver enzymes followed by a positive enzyme-linked immunosorbent assay (ELISA) for anti-HCV. Strategy A involved initial RIBA testing followed by peR testing in RIBA positive and indeterminate patients. Strategy B involved PCR testing only. The outcome measure was cost per case identified for treatment. Sensitivity analysis was performed by varying the baseline probability and cost estimates. Results: Strategy A, initial RIBA testing, cost $309, while strategy B, initial PCR testing, cost $192 per case of HCV identified. One way sensitivity analysis revealed that the model was robust; strategy B remained dominant in almost all cases. Only if the probability of the initial RIBA being negative was greater than 64% was strategy A less expensive. Conclusions: Initial HeV RNA peR testing is a less costly strategy compared with initial RIBA testing in patients with elevated liver enzymes who are ELISA positive for anti-HCV. These results may help laboratories and clinicians be more judicious in their choice of tests for identification of patients requiring treatment.