Epidemiology

HbsAg plus HBV DNA help distinguish active from inactive carriers

Last Updated: 2010-06-11 13:23:28 -0400 (Reuters Health)

By Scott Baltic

NEW YORK (Reuters Health) - Measuring hepatitis B virus (HBV) DNA and surface antigen (HBsAg) levels can quickly distinguish active and inactive carriers of hepatitis B virus (HBV) genotype D, new research from Italy shows.

Currently, an adequate differential diagnosis between inactive carriers and patients with active HBeAg-negative chronic hepatitis B requires a year of monitoring, the lead author told Reuters Health. HBV DNA levels can fluctuate frequently and widely in HBV patients who are HBeAg-negative.

But measuring both HBsAg and HBV DNA in serum provides "the highest diagnostic accuracy in the identification of inactive carriers ... even at a single-point evaluation," Dr. Maurizia Brunetto of the University Hospital of Pisa told Reuters Health by e-mail.

The combination assessment works well, she explained, because the tests give complementary information. HBV DNA levels reflect HBV replication, while HBsAg levels reflect transcription of intrahepatic covalently closed circular DNA.

Although the method is not ready for clinical use, the combined results of HBsAg and HBV DNA testing could eventually help identify candidates for antiviral therapy and tailor the duration of treatment, Dr. Brunetto said.

Dr. Brunetto cautioned, however, that these data apply to patients with HBV genotype D only, and that "HBsAg thresholds of clinical relevance could vary according to genotype."

As reported online May 7th in Gastroenterology, the study involved 209 HBeAg-negative/anti-HBe-positive chronic HBsAg carriers infected with HBV genotype D. The median age was 48, and the population was evenly split between males and females. The median prospective follow-up was 34.5 months, with blood tests monthly for the first year and then every three months.

The researchers found that HBsAg serum levels vary during different phases of chronic infection. Levels are significantly lower in inactive versus active carriers, and in active carriers with HBV DNA persistently under 20,000 IU/mL versus active carriers with levels above that threshold.

The combined single-point quantification of HBV DNA less than 2,000 IU/mL and HBsAg less than 1,000 IU/mL identified inactive carriers with 94.3% diagnostic accuracy, 91.1% sensitivity, 95.4% specificity, 87.9% positive predictive value, and 96.7% negative predictive value, compared to a year of monthly monitoring.

"This approach represents a new means for an effective management of chronic HBV infection and disease," the authors conclude. "For a generalized use of quantitative HBsAg in clinical practice it is mandatory to proceed further with clinical validation."

This, they say, would involve testing reference panels of sera containing medium and high levels of HBsAg from patients with various genotypes and in various stages of infection.

http://www.gastrojournal.org/article/S0016-5085(10)00660-8/abstract

Gastroenterology 2010.