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Abstract 281. Durability of Sustained Virologic response in patients with Chronic Hepatitis c after treatment With Interferon 2b Alone or in Combination with Ribavirin
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This study looked at 400 patients in 3 studies who achieved a sustained response. The key findings were:
- late relapse (after achieving the sustained response) occurred only in 2.5% of patients
- the late relapsers occurred within the first 2 years. There were no relapsers after 2 years
- 2 relapsers had detectable HCV-RNA in the liver; 3 had detectable HCV-RNA in the liver and did not relapse
- the risk of relapse after achieving sustained response was 5%
The purpose of this study was to assess the durability of response in patients who were sustained responders 24 weeks after therapy. John McHutchison reported in an oral session on a analysis of 2089 patients from 3 large scale international studies comparing interferon alfa-2b alone to interferon alfa-2bplus ribavirin (Davis et al, NEJM 1998;339:1493, McHutchison et al NEJM 1998; 339:1485; Poynard et al, Lancet 1998;352:1426). Many of these patients have been followed for up to 4 years. This analysis looked at the 558 patients who achieved a sustained response to evaluate their rate of failure. Of the 558 SVRs 455 patients received IFN+RBV and 103 patients received IFN. 395 of the 558 agreed to participate in this long-term follow-up. All patients were treatment-naive or relapsers and received 24 or 48 weeks treatment. Of the 395 patients, 151 naive received IFN/RBV for 48 weeks, 112 naive patients received IFN/RBV for 24 weeks, 59 relapsers received IFN/RBV for 24 weeks, 61 received IFN alone for 48 weeks, and 12 received IFN alone for 24 weeks (4 naive 24 weeks, 61 naive 48 weeks, 8 relapse 24 weeks).
Serum HCV-RNA was measured by NGI LLQ 100 copies/ml. These patients are also assess yearly for disease progressionby physical exam and hemotological and biochemical (ALT/AST) testing. This analysis was completed as of February 2001 and the endpoint was viral relapse after achieving sustained response. About 2/3 of patients were male, 42-47 years of age, and about 74-79 kg. 37% were genotype 1, 26% genotype 2, 34% genotype 3, and 3% genotype 4/5. Although there is a low percentage of genotype 1 in this analysis McHutchison said that they found no difference in study outcomebetween genotyp 1 vs non-genotype 1. Baseline fibrosis Metavir Stage: 60-80% of patients had F0-F1. 12-29% had F3/F4. And 4-20% had missing information. Baseline viral load was 3.0-4.1 million copies/ml. ALT was 3.2 to 3.6 times the upper limit of normal.
RESULTS
· 59% of the 395 patients in the study have been followed for 4 years after the end of treatment, 3% for 5 years, 26% for 3 years, 8% for 2 years, and 3% for 1 year.
· Only 10 out of 395 patients (2.5%) who had a sustained response (24 weeks after ending treatment)--
- 7 had received IFN/RBV
- 5 of 7 were naive and relapsed in 3-24 weeks after stopping therapy
- 2 were relapsers
- 3 patients received IFN alone
· All 10 late relapsers reappearance of HCV-RNA within 2.5 years after stopping therapy or 2 years after the 24 week follow-up period.
· There have been no relapses after 2 years of follow-up.
· Researchers looked at naive vs relapser, 24 vs 48 weeks treatment, genotype 1 vs non-genotype 1, low vs high viral load, low vs higher fibrosis, and found no factor predicted relapse
· The overall risk for late relapse looking out to 4 years was <5%, when using Kaplan-Meier curve, except for the 12 patients who received IFN alone for 24 weeks who had a high risk for late relapse
--The corresponding actuarial likelihood (Kaplan-Meier) of maintaining response after 4 years in patients who initially achieved SR is: IFN/RBV 24 weeks therapy naive 97%, IFN/RBV 48 weeks therapy naive 99%, and IFN/RBV 24 weeks therapy relapsers 96%
· There were 5 patients who had HCV-RNA detected in their liver (not blood) in the 24 week post-treatment liver biopsy. These 5 patients were sustained responders so they had PCR negative in the blood. Two of the 5 subsequently relapsed
· 95% had normal ALT during the long-term follow-up of this study
· One patient developed liver cancer (hepatocellular carcinoma). He had pre-existing cirrhosis, was a sustained responder (I think he was a previous relapser IFN alone) who has not relapsed. HCC developed 39 months after treatment. Other than this 1 patient there was no evidence of hepatic decompensation as documented by physical exam
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