So How Long Do You Really Need to Treat Hepatitis C Genotypes 2 and 3?
Abstract & Commentary
By Alan D. Tice, MD, FACP, Infectious Disease Consultant, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, Section Editor, Managed Care, is Associate Editor for Infectious Disease Alert
Dr. Tice does research for Merck, Roche, and Schering, is a consultant for Merck and Vicuron Pharmaceuticals, and is on the speaker’s bureau for Merck and Roche.
Synopsis: Patients with genotype 2 or 3 only need 12 weeks of therapy with pegylated interferon and ribavirin if their viral load is undetectable after 4 weeks of therapy.
Source: Mangia A, et al. Peginterferon Alfa-2b and Ribavirin for 12 vs 24 Weeks in HCV Genotype 2 or 3. N Engl J Med. 2005;352:2609-2617.
Mangia and colleagues in italy evaluated treatment of 283 patients with chronic hepatitis due to hepatitis C virus genotypes 2 and 3. They used a relatively select group of patients, and were able to follow them closely over the year of the study. The patients—all of whom had not been treated before—had elevated aminotransferase levels and ranged in age from 18 to 70.
They took a relatively novel approach that to the duration of treatment. Instead of simply assigning patients to a standard 24-week course of therapy with interferon and ribavirin, they assigned only one-third of their patients to that regimen. The other two-thirds were randomized to receive either 12 or 24 weeks of therapy, depending on whether their viral load was undetectable at after 4 weeks of therapy.
Treatment was with 1 mg/kg of pegylated interferon alfa-2b (Schering product) plus 1000 to 1200 milligrams of ribavirin daily.
The results of 12 weeks of therapy for those who leared their virus at 4 weeks were good and comparable to those treated for 24 weeks (76% and 77%). But for those who did not clear the virus at 4 weeks, the response rates were 43% and 41% after 24 weeks of therapy. For those who relapsed after 12 weeks of therapy, 9 out of 13 responded to another 24 weeks of therapy.
One hundred thirty three (62%) of the 213 patients assigned to the variable duration group were negative for hepatitis virus at week 4.
The rate of relapse after 24 weeks of therapy was 3.6% in the standard duration group and 8.9% in the variable duration group. The figures were not statistically different. The overall rate of sustained virologic response was 80% for those with genotype 2 and 66% among those with genotype 3—a difference that was statistically significant.
There were no distinguishing or apparently significant factors that could explain the rapid response or clinical outcomes for the group that was negative for 4 weeks, except for a relatively low viral load at the initiation of the study.
As expected, the 12-week therapy group had fewer side effects and was more likely to complete the assigned duration of therapy, compared with the 24-week therapy group. But, there was only one drop out in the 12 weeks of therapy group and there were 4 in the 24-week group.
Commentary
This article is very helpful in trying to define how long people with HIV genotypes 2 and 3 need to be treated. It is good news for patients with these infections and for their third party payers, who do not have to foot the bill for the extra 12 weeks of therapy (at an approximate cost of $500 per week). The economic burden of treating a significant number of the 4 million Americans affected is a staggering one, and one that is often dependent on public funding, as hepatitis C affects a disproportionate number of people dependent on federal and state funds—for example, approximately one-third of those incarcerated are infected and likely spreading it among their colleagues.
The side effects of therapy are also less with the shorter course of therapy and may not evolve into the psychiatric realm with chronic depression and lack of mental clarity. Hopefully, the expected adverse effects will resolve more rapidly, as well as with the shorter course of therapy.
The possibility that the strains treated in Italy may be more susceptible to treatment than those in other parts of the world must be considered, but with the allowance of up to 20 grams of alcohol daily, any advantage should be balanced out. It’s hard to expect more abstinence in Italy, although criteria for therapy are more stringent in the United States. On the other hand, there are some who would treat patients with some ongoing substance abuse in the United States, although they were rejected in the study reported. It would seem abstinence from alcohol would be more important than substance abuse from a liver standpoint, but cultural factors need to be considered, and both are a problem. The more important aspect of treating the drug abusers to try to reduce the number of people infected, and spreading it to others through sharing needles and paraphernalia, must be considered.
To what extent treatment courses can be shortened even more or predictions be made more accurate is uncertain, but there are promising efforts in place. Perhaps the drop in viral load at 2 or 3 weeks could be used as a predictor. Perhaps these viruses can be characterized even more specifically and correlations found with outcomes. We shall see with the help of our co-workers in Italy.
Mangia and colleagues in italy evaluated treatment of 283 patients with chronic hepatitis due to hepatitis C virus genotypes 2 and 3. They used a relatively select group of patients, and were able to follow them closely over the year of the study.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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