Emergence of hepatitis B virus S gene mutants in patients experiencing HBsAg seroconversion after peginterferon therapy

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Emergence of hepatitis B virus S gene mutants in patients experiencing HBsAg

seroconversion after peginterferon therapy

Hepatology, 04/26/2011

Hsu CW et al. - During peginterferon antiviral therapy, achievement of

anti-hepatitis B virus (HBV) surface antigen (HBsAg) seroconversion not

necessarily indicated viral eradication. Emergence of the S gene mutants was an

alternative possibility and relapse with “HBsAg-negative hepatitis†could

occur.

Methods

• 245 consecutive chronic hepatitis B patients received peginterferon therapy

• The coding regions of HBV pre-S/S gene derived from serial serum samples

were analyzed.

• Site directed-mutagenesis experiment was performed to verify the phenotypic

alterations in Huh-7 cells.

Results

• 8 (3.27%) achieved HBsAg seroclearance.

• 2 of the 8 patients remained viremic by standard HBV-DNA assays

• In patient-1:

â—¦ sT125A mutant developed in the HBsAg-negative stage, constituting 11.2% of

the viral population

◦ HBV-DNA level was 2.73 × 104 IU/mL at the time of detection

â—¦ This mutant was not detectable in the HBsAg-positive stages

â—¦ Phenotypic study in Huh-7 cells showed significantly reduction of

antigenicity

• In patient-2:

â—¦ sW74* truncation mutation was found in the HBsAg-negative stage,

constituting 83.1% of the viral population

◦ HBV-DNA level was 4.12 × 104 IU/mL at the time of detection

â—¦ Phenotypic study in Huh-7 cells showed a complete loss of the antigenicity

â—¦ subsequently experienced an episode of hepatitis relapse 7 months after the

end of treatment with negative HBsAg throughout the hepatitis flare

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http://onlinelibrary.wiley.com/doi/10.1002/hep.24363/abstract

Viral Hepatitis

Emergence of hepatitis B virus S gene mutants in patients experiencing HBsAg

seroconversion after peginterferon therapy†

Chao-Wei Hsu1,*,‡, Chau-Ting Yeh1,2,¶DOI: 10.1002/hep.24363

Copyright © 2011 American Association for the Study of Liver Diseases

Issue

Hepatology

Accepted Article (Accepted, unedited articles published online for future

issues)

Abstract

In anti-hepatitis B virus (HBV) therapy using peginterferon, seroconversion of

HBV surface antigen (HBsAg) can be achieved in a small percentage of patients,

which is considered a cure of the disease. Of 245 consecutive chronic hepatitis

B patients receiving peginterferon therapy in our center, 8 (3.27%) achieved

HBsAg seroclearance. Surprisingly, 2 of the 8 patients remained viremic by

standard HBV-DNA assays. The coding regions of HBV pre-S/S gene derived from

serial serum samples were analyzed. Site directed-mutagenesis experiment was

performed to verify the phenotypic alterations in Huh-7 cells. In patient-1, an

sT125A mutant developed in the HBsAg-negative stage, constituting 11.2% of the

viral population. HBV-DNA level was 2.73 × 104 IU/mL at the time of detection.

This mutant was not detectable in the HBsAg-positive stages. Phenotypic study in

Huh-7 cells showed significantly reduction of antigenicity. In patient-2, an

sW74* truncation mutation was found in the HBsAg-negative stage, constituting

83.1% of the viral population. HBV-DNA level was 4.12 × 104 IU/mL at the time

of detection. Phenotypic study in Huh-7 cells showed a complete loss of the

antigenicity. Patient-2 subsequently experienced an episode of hepatitis relapse

7 months after the end of treatment with negative HBsAg throughout the hepatitis

flare. In conclusion, during peginterferon antiviral therapy, achievement of

HBsAg seroconversion not necessarily indicated viral eradication. Emergence of

the S gene mutants was an alternative possibility and relapse with

“HBsAg-negative hepatitis†could occur. (HEPATOLOGY 2011.)