Symptomatic Hepatitis B Virus (HBV) Reactivation despite Reduced Viral Fitness Is Associated with HBV Test and Immune Escape Mutations in an HIV-Coinfected Patient

[Guest guest]

http://www.journals.uchicago.edu/doi/abs/10.1086/592987

The Journal of Infectious Diseases 2008;198:1620–1624

0022-1899/2008/19811-0007$15.00

DOI: 10.1086/592987

BRIEF REPORT

Symptomatic Hepatitis B Virus (HBV) Reactivation despite Reduced Viral Fitness

Is Associated with HBV Test and Immune Escape Mutations in an HIV-Coinfected

Patient

Cornelia Henke-Gendo,1

Samad Amini-Bavil-Olyaee,2

Deepthi Challapalli,1

Christian Trautwein,2

Heidi Deppe,1

F. Schulz,1

Albert Heim,1a and

Tacke2a

1Institute of Virology, Medical School Hannover, 2Medical Clinic III,

Rheinisch-Westfälische Technische Hochschule–University Hospital Aachen, Aachen,

Germany

Two sequential hepatitis B virus (HBV) strains obtained before and during an

icteric flare-up of an occult HBV infection in a patient coinfected with human

immunodeficiency virus revealed HBV surface antigen (HBsAg) test escape

mutations, although the patient had never received hepatitis B–specific

immunoglobulin. In contrast to the high HBV DNA loads, recurrence of HBsAg, and

resulting icteric hepatitis, phenotypic analysis of the mutated HBV strains

revealed significantly reduced replication efficacies in vitro, compared with

wild-type HBV. Therefore, immune escape in the transiently anti-HBs–positive

patient appeared to be crucial for persistence and reactivation. Immune escape

mutants evolved even without exogenous selective pressure, hampered detection in

HBsAg screening, and might be transmitted during reactivation with high HBV

loads.

Received 6 February 2008; accepted 12 June 2008; electronically published 9

October 2008.

Reprints or correspondence: Albert Heim, PD Dr. med, Institute of Virology,

Medical School Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

(Heim.Albert@...).

Potential conflicts of interest: none reported.

Presented in part: First annual meeting of the Arbeitskreis Klinische Virologie,

Schloss Zeilitzheim, Germany, 19 October 2007.

Financial support: German Network of Competence for Viral Hepatitis (BMBPTp 12.3

to C.T. and F.T.); EU VIRGIL grant (to C.T. and F.T., partner no. 60); German

Research Foundation (DFG Ta434/2–1 to F.T.); Iranian Ministry of Health (Ir2006

to S.A.).

aThese authors contributed equally to the work.

[Guest guest]

http://www.journals.uchicago.edu/doi/abs/10.1086/592987

The Journal of Infectious Diseases 2008;198:1620–1624

0022-1899/2008/19811-0007$15.00

DOI: 10.1086/592987

BRIEF REPORT

Symptomatic Hepatitis B Virus (HBV) Reactivation despite Reduced Viral Fitness

Is Associated with HBV Test and Immune Escape Mutations in an HIV-Coinfected

Patient

Cornelia Henke-Gendo,1

Samad Amini-Bavil-Olyaee,2

Deepthi Challapalli,1

Christian Trautwein,2

Heidi Deppe,1

F. Schulz,1

Albert Heim,1a and

Tacke2a

1Institute of Virology, Medical School Hannover, 2Medical Clinic III,

Rheinisch-Westfälische Technische Hochschule–University Hospital Aachen, Aachen,

Germany

Two sequential hepatitis B virus (HBV) strains obtained before and during an

icteric flare-up of an occult HBV infection in a patient coinfected with human

immunodeficiency virus revealed HBV surface antigen (HBsAg) test escape

mutations, although the patient had never received hepatitis B–specific

immunoglobulin. In contrast to the high HBV DNA loads, recurrence of HBsAg, and

resulting icteric hepatitis, phenotypic analysis of the mutated HBV strains

revealed significantly reduced replication efficacies in vitro, compared with

wild-type HBV. Therefore, immune escape in the transiently anti-HBs–positive

patient appeared to be crucial for persistence and reactivation. Immune escape

mutants evolved even without exogenous selective pressure, hampered detection in

HBsAg screening, and might be transmitted during reactivation with high HBV

loads.

Received 6 February 2008; accepted 12 June 2008; electronically published 9

October 2008.

Reprints or correspondence: Albert Heim, PD Dr. med, Institute of Virology,

Medical School Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

(Heim.Albert@...).

Potential conflicts of interest: none reported.

Presented in part: First annual meeting of the Arbeitskreis Klinische Virologie,

Schloss Zeilitzheim, Germany, 19 October 2007.

Financial support: German Network of Competence for Viral Hepatitis (BMBPTp 12.3

to C.T. and F.T.); EU VIRGIL grant (to C.T. and F.T., partner no. 60); German

Research Foundation (DFG Ta434/2–1 to F.T.); Iranian Ministry of Health (Ir2006

to S.A.).

aThese authors contributed equally to the work.