Spontaneous Undetectable Hepatitis B Virus DNA Is Uncommon, especially without HBeAg Clearance

		SUMMARY: Clearance of hepatitis B virus (HBV) DNA from the blood seldom occurs without treatment even after a decade, researchers reported at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) last month in Vienna. Among people who experience hepatitis B "e" antigen (HBeAg) clearance, however, the likelihood of also achieving undetectable viral load was higher, approaching 50% at 10 years.

By Liz Highleyman

C-J. Chen from National Taiwan University and colleagues assessed the likelihood and factors associated with spontaneous clearance of HBV viral load in a sub-study of the large REVEAL-HBV trial, which looked at long-term outcomes including liver cancer among people with chronic hepatitis B.

The sub-study included 1289 participants with high HBV DNA levels (> 10,000 copies/mL) but no evidence of cirrhosis at study entry.

Results

	199 participants (15.4%) achieved undetectable HBV DNA (< 100 copies/mL) during follow-up.
	HBV DNA became undetectable after an average of 7.8 years, for a clearance rate of 19.7 per 100,000 person-years.
	Overall, the cumulative likelihood of achieving undetectable HBV DNA was 5.2% at 5 years and 14.5% at 10 years.
	Looking only at participants who experienced HBeAg clearance, however, cumulative HBV DNA clearance rates were higher, 11.5% at 5 years and 45.5% at 10 years.
	In a multivariate analysis, having a baseline viral load of 100,000-999,999 copies/mL (versus > 1 million copies/mL) and abdominal obesity were associated with greater likelihood of spontaneous HBV DNA clearance.
	In contrast, elevated alanine aminotransferase (ALT) -- both 15-44 U/L and > 45 U/L versus < 15 U/L -- was associated with lower likelihood of achieving undetectable HBV DNA.
	Most participants (89%) who were initially HBeAg seropositive had already cleared HBeAg by the time they achieved undetectable HBV DNA.
	Conversely, a majority of participants had viral load > 10,000 copies/mL at the time of HBeAg clearance.

"Spontaneous seroclearance of HBV DNA was a rare event, even after HBeAg seroclearance," the investigators concluded. "Lower baseline viral load and central obesity [were] associated with higher possibility of decreasing HBV DNA to undetectable level, whereas higher serum ALT level during follow-up associated with a lower possibility of HBV DNA decline."

Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan ROC; Research and Development, Bristol-Myers Squibb Company, Willingford, CT.

5/14/10

Reference
C-J Chen, H-I Yang, C-L Jen, and others. Incidence and determinants of spontaneous decline of HBV DNA to undetectable level in patients with high viral load. 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract).