Research Group Heussler (Malaria I) - Bernhard-Nocht-Institut für ...

Clinical Department
Persistence and Reactivation of the Hepatitis B Virus
Zusammenfassung
Die Infektion mit Hepatitis B-Virus muss selbst bei
fehlendem Nachweis von Hepatitis B Oberflächen-
Antigen (HBs-Ag) als nicht ausgeheilt angesehen
werden. In den meisten dieser Fälle treten bis ans
Lebensende keine klinischen Symptome mehr auf.
Bei verschiedenen Formen der Immunsuppression
kann es jedoch zu einer Reaktivierung und unter bestimmten
Bedingungen sogar zu einer fulminanten
Hepatitis kommen.
Summary
Even in case of missing evidence of hepatitis B surfaceantigen
(HBs-Ag), a former infection with hepatitis B virus
cannot be considered to be irreversibly cured. In
most of these cases there are no clinical symptoms for
the rest of the patient’s life. There is, however, the possibility
of reactivation and, under certain circumstances,
even a fulminant hepatitis in cases of various forms of
immunosuppression may occur.
Introduction
For long time it was believed that HBs-negative serology
after infection with hepatitis B-virus (HBV) did
mean that the infection is cured. There were, however,
cases of reactivation, some even accompanied by fulminant
hepatitis in cases of simultaneous chemotherapy
or in cases of immunosuppression by drugs or
by HIV-infection. Modern PCR screening methods have
been developed in the meantime to detect even lowest
virus concentrations.
Project Description and Results
Based on a group of five own cases of acute hepatitis
in HIV-infected patients these cases were analysed systematically
using stored serum samples. It could be
shown that the hepatitis reaction had been caused by a
preceding highly replicative HBV reactivation.
Two further study groups were investigated.
In the first group we used unselected hepatitis B-coreantibody
(anti-HBc)-positive and HBs-Ag-negative analytical
samples. These samples were tested for the frequency
of HBV DNA detection and possible related cofactors.
As a result, in about 12% of the cases HBV replication
was detected, generally at a low level. A simultaneous
chronic hepatitis C but not a concomitant HIVinfection
was a significant risk factor for HBV DNA detection.
The second group consists of an anti-HBc-positive HIV
cohort (504 patients, up to 20 years observation time).
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Aim of this investigation is a longitudinal analysis of hepatitis
B serum markers and hepatic reactions. Until
now, there are only few published longitudinal data.
Preliminary analyses show a high degree of fluctuation
of the HBs serum markers. This has not been described
so far. Furthermore, the data structure will help to
quantify the number and degree of hepatic reactions in
correlation with certain risk factors such as hepatitis C
co-infection or antiretroviral medication.
Selected Publications
• Christoph Manegold, Anani Apedjinou (2004):
High incidence of fluctuations of hepatitis B
serum markers in HIV-infected patients.
11th Conference on Retroviruses and Opportunistic
Infections, San Francisco 8.-11.2.2004
• Drosten C, Nippraschk T, Manegold C, Meisel H,
Brixner B, Roth WK, Apedjinou A, Günther S (2004):
Risk factors for detection of hepatitis B virus (HBV)
DNA in HBsAg-negative/anti-HBc-positive sera and
analysis of terminal protein sequence of the circulating
HBV DNA. Clin Virol. 29(1): 59-68
• Vieth S, Manegold C, Drosten C, Nippraschk T,
Günther S (2002): Sequence and phylogenetic analysis
of hepatitis B virus genotype G isolated in Germany.
Virus Genes 24 (2): 153-6
• Manegold C, Hannoun C, Wywiol A, Dietrich M,
Polywka S, Chiwakata CB, Gunther S (2001): Reactivation
of hepatitis B virus replication accompanied
by acute hepatitis in patients receiving highly active
antiretroviral therapy. Clin Infect Dis 32 (1): 144-148
Cooperating Partners
• Christian Drosten, Stephan Günther,
Department of Virology, BNI
Investigators
• Christoph Manegold
• Manfred Dietrich