Reuters Health Information (2013-08-02): Knowledge of HBV genotype "mandatory"
Knowledge of HBV genotype "mandatory"
Last Updated: 2013-08-02 13:20:30 -0400 (Reuters Health)
NEW YORK (Reuters Health) - The hepatitis B virus (HBV) genotype is linked with response to interferon therapy, new data show.
"The key message for clinicians is that ... it is mandatory to know the HBV genotype" in patients undergoing pegIFN treatment," Dr. Maurizia Brunetto of Azienda Ospedaliero Universitaria Pisana in Pisa, Italy, told Reuters Health by email.
Dr. Brunetto's group found that genotype significantly influences hepatitis B surface antigen (HBsAg) levels before and during peginterferon treatment, and it also influences end-of-treatment HBsAg levels that are associated with long term virological response.
"Overall our findings suggest that a cost-effective response-guided therapy may be possible by using combined on-treatment and end-of-treatment genotype-specific HBsAg thresholds," Dr. Brunetto said.
The investigators performed a retrospective analysis of serum HBsAg levels in a group of HBeAg-negative chronic hepatitis B patients who entered a long-term observational study after treatment with pegIFN with or without lamivudine in a phase III trial.
They assessed genotype-specific end-of-treatment HBsAg levels associated with long-term virological response five years after treatment in 199 patients with HBsAg measurements available at baseline and end-of-treatment.
They also assessed HBsAg kinetics according to genotype and long-term virological response in 117 patients with additional samples available at weeks 12, 24 and 72.
HBV genotype was a significant factor in HBsAg serum level both before and during pegIFN treatment, the researchers said online July 22 in the Journal of Hepatology.
Although the number of patients with genotype A was low, these patients had baseline HBsAg serum levels significantly higher than patients infected with other genotypes, with the major difference observed when comparing genotype A with genotype C (14,816 vs 3155 IU/mL, p=0.006).
In terms of on-treatment profiles, HBsAg kinetics were genotype-specific and "quite intriguing," the investigators say.
"The mean HBsAg decline from baseline to end of treatment in responders was the highest for genotype A- and lowest for genotype C-infected patients, in whom it was not possible to differentiate responders from non-responders based on HBsAg levels only, because of the minimal reduction observed in responders," Dr. Brunetto and colleagues report.
They also found that the time frame during which HBsAg decline was most likely to be informative differed considerably by genotype. "The greatest difference in HBsAg decline between responders and non-responders was observed between weeks 12 and 24 for genotype A-infected patients and between baseline and week 12 for genotypes B and D.
They say a decline in HBsAg levels from the start of treatment occurred in all patients with HBV genotype A or B, with a more pronounced decline in responders. In contrast, a reduction of HBsAg levels from the start of treatment occurred only in genotype D-infected patients who were responders; HBsAg levels remained steady or increased slightly in non-responders, the investigators say.
The researchers identified genotype-specific cutoffs that substantially improved the positive predictive value of HBsAg quantification at end of treatment for long-term virological response. Positive predictive values, and cutoffs, are: 75% (<400 IU/mL) for genotype A, 47% (<50 IU/mL) for genotype B, 71% (<75 IU/mL) for genotype C and 75% (<1000 IU/mL) for genotype D.
"Of course our data need to be confirmed in larger studies," Dr. Brunetto said, "but the findings indicate the way for a further personalization of antiviral treatment according to on-treatment genotype-specific HBsAg kinetics and shed the light on the controversies raised previously by the simple quantification of HBsAg without stratification by HBV genotype."
Dr. Brunetto added that patient management "can be improved" not only by an early change in treatment in non-responders, "but also by motivating long-term responders to complete the 48 weeks of therapy and optimizing treatment in the remaining patients with new/innovative approaches such as treatment extension, combination or sequential therapies."
The study was funded by Roche, which makes the Amplicor HBV test used in the study. Several of the authors have disclosed relationships with Roche, as well as Abbott, Bristol Myers Squibb and others, all listed with the original paper.
J Hepatol 2013.