Does Attainment of Sustained Virologic Response (SVR) from Treatment of HCV Constitute a Cure?

There has been controversy and misunderstanding about whether the current standard of care for the treatment of chronic hepatitis C, peginterferon plus ribavirin, is capable of producing a “cure” for the disease.

Most experts in the field have regarded the attainment by patients of a sustained virologic response (SVR), defined as undetectable HCV for 6 months after completion of therapy, as the definition of a “cure” for the infection. However, there have been documented, but rare instances of individuals who relapsed following achievement of SVR.

Sustained virologic response (SVR) rates of about 50% have been reported in patients with genotype 1 HCV monoinfection, the most difficult form of the virus to treat successfully.

The durability of SVR is being investigated in a long-term follow-up multi-national study of patients treated for chronic HCV infection treated with peginterferon alfa-2a (Pegasys) plus ribavirin. Preliminary results of the study were presented at the DDW 2007 meeting in Washington D.C. this week.

Patients who took part in one of nine randomized trials of peginterferon alfa-2a (Pegasys) as monotherapy or in combination with ribavirin, and who were negative for serum HCV-RNA (<50 IU/mL) at the final virologic assessment were eligible for inclusion in the long-term follow-up study.

Serum HCV-RNA levels were determined annually for 5 years from the date of last treatment.

Results

• To date 997 patients are undergoing long-term follow-up, including 163 HCV mono-infected patients treated with peginterferon alfa-2a monotherapy, 741 mono-infected patients treated with combination therapy, and 93 HIV-HCV co-infected patients treated with either monotherapy or combination therapy.

• The overwhelming majority of patients (989/997; >99%) remain HCV-RNA negative at a mean of 4.1 (range 0.4-7) years after treatment cessation (an outcome we consider to be consistent with a cure).

• Eight patients became HCV-RNA positive (>50 IU/mL) between 1.1-2.9 (mean 2.0) years after completing treatment.

• There were no consistent patterns in terms of age, gender or HCV genotype among these 8 patients and none showed evidence of liver cirrhosis.

• Two patients had low baseline viral load (<400,000 IU/mL) while the remaining 6 patients had a baseline viral load ranging from 700,000–12 million IU/mL.

• The proportion of these incidents representing new infections or true ‘relapse’ is currently unknown.

Based on their findings, the study authors conclude, “These results show that an SVR following treatment with peginterferon alfa-2a alone or in combination with ribavirin is durable in almost all (>99%) patients with chronic HCV infection, validating the use of the word ‘cured’ for those achieving an SVR.”

Commentary

“The results announced today are encouraging because it is rare in the treatment of life-threatening viral diseases that can we tell patients they have the chance for a cure,” said Dr. Mitchell L. Shiffman, Professor of Medicine, Chief of Hepatology and Medical Director of the Liver Transplant Program, Virginia Commonwealth University Medical Center, and study author. “But in hepatitis C today, we are able to help some patients achieve an outcome that effectively enables them to put their disease behind them.”

05/25/07

Source
M G Swain, M Lai, M L Shiffman, and others. Sustained Virologic Response (SVR) Resulting From Treatment with Peginterferon Alfa-2a (40KD) (Pegasys®) Alone or in Combination with Ribavirin (Copegus®) is Durable and Constitutes a Cure: an Ongoing 5-year Follow-up. DDW 2007. May 19-24, 2007. Abstract 444.

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