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Hepatitis B

AASLD 2011: Natural History of Hepatitis B Infection and Role of HBV Genotype


People with hepatitis B "e" antigen (HBeAg) positive and negative disease have different levels of hepatitis B surface antigen (HBsAg), variable extent of liver fibrosis, and different distribution of HBV genotypes, according to a study presented at the American Association for the Study of Liver Disease (AASLD) Liver Meeting last month in San Francisco.

While the importance of viral genotypes and human IL28B gene patterns has been well established for hepatitis C virus (HCV) infection, their influence on the course of hepatitis B virus (HBV) infection has not been well studied.

In this natural history study, Michelle Martinot-Peignoux from Université de Paris and colleagues looked at the relationship between HBV genotype, HBeAg status, HBsAg levels, HBV DNA viral load, IL28B (rs12979860) pattern, and severity of liver disease in a cohort of patients infected with HBV genotypes A, B, C, D, or E.

The analysis included 374 treatment-naive chronic hepatitis B patients assessed at the university hospital between 2000 and 2008. Participants had known HBeAg status and were scheduled to undergo liver biopsy. People with HCV, hepatitis delta (HDV), or HIV were excluded.


  • 97 patients were HBeAg positive and 277 were HBeAg negative.
  • Among HBeAg positive participants, 27% had HBV genotype A, 9% had genotype B, 29% had genotype C, 15% had genotype D, and 20% had genotype E.
  • Among HBeAg negative patients, the corresponding frequencies were 25%, 12%, 2%, 28%, and 33%, respectively.
  • Among HBsAg positive people, 49% had the IL28B CC pattern (associated with favorable interferon responsiveness in patients with HCV), 33% had the mixed CT pattern, and 18% had the TT pattern.
  • Among HBeAg negative people, the distribution was 41%, 33%, and 26%, respectively.
  • HBV DNA levels were 2 to 3 log IU/mL higher among HBeAg positive patients compared with HBeAg negative patients, but within these groups viral load did not differ significantly according to HBV genotype.
  • Average HBsAg levels were also higher among HBeAg positive compared with HBeAg negative patients, regardless of HBV genotype.
  • However, within the HBeAg negative group, the mean HBsAg level was significantly lower among people with HBV genotype B.
  • Within the HBeAg positive group, HBV genotype A was associated with more advanced fibrosis, half of those with severe liver disease carried this genotype.

"HBsAg and HBV DNA levels were lower in HBeAg [negative] patients than in HBeAg [positive] patients regardless of HBV genotype," the investigators concluded. "In HBeAg [positive] patients, advanced fibrosis was associated with a lower HBsAg levels and infection with HBV genotype A. The IL28B genotype CC was underrepresented in patients infected with genotype E."

Investigator affiliations: INSERM U-773, Centre de Recherche Biomédicale Bichat-Beaujon, Université Paris VII, Clichy, France; Service d’Hépatologie, Hôpital Beaujon, Clichy, France.



M Martinot-Peignoux, M Lapalus, O Lada, et al. Natural history of hepatitis B virus (HBV) infection: role of HBV genotypes (A to E) assessed in a large cohort. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 506.