مرض/HEPATITIS/ B

1-
Antibodies to the preS2
region of the hepatitis B virus (HBV) envelope protein and to human
serum albumin (HSA) were allegedly detected at about the same level in
sera of humans with acute or chronic hepatitis B [Hellström et al.,
1986]. It was claimed that anti-HSA arises as a result of an immune
response to the preS2 sequence and that it was involved in
hepatocellular damage. Over 100 sera from animals and humans
immunized
with HBsAg containing preS2 sequences, or with synthetic peptides from
the preS1, preS2, and S regions of the HBV env protein were assayed for
anti-HSA. The results revealed the following: 1) Immunization with the
native preS2 sequence or with unconjugated synthetic peptides derived
from that sequence does not result in elicitation of anti-HSA. Therefore
the alleged appearance of anti-HSA during hepatitis B cannot be
directly related to an anti-preS2-specific immune response. 2) Some
synthetic peptides, whether or not they were derived from the preS2
sequence, when linked to certain carriers, but not to others, elicited
in rabbits an anti-HSA response, which was markedly lower than the
response to the homologous peptide. These anti-HSA antibodies could be
separated from anti-preS2-specific antibodies by affinity chromatography
and did not recognize the synthetic peptide used for immunization. The
use in active immunoprophylaxis of hepatitis B of unconjugated peptides
from the preS2 sequence with proven high immunogenicity will avoid
carrier/linker-mediated induction of antibodies not relevant to
protection against HBV.
The indication for antiviral
treatment of patients with chronic hepatitis B is based on serum HBV
DNA levels, transaminases, and histological grade and stage. The
relation of liver fibrosis and inflammation to ALT activity in chronic
hepatitis B infection was investigated in a non-endemic, European
setting. A total of 253 patients with chronic hepatitis B who had
undergone liver biopsy at the Clinic of Gastroenterology, Hepatology,
and Infectious Diseases, Düsseldorf, Germany over the past 19 years
(1990–2009) were evaluated. Thirty-nine patients had persistently normal
transaminases, 86 patients had ALT with 1–2 × ULN (upper limit of
normal) and 128 patients had ALT >2 × ULN. Liver fibrosis or
inflammation was defined as significant for stages or grades ≥ 2
according to the Desmet/Scheuer score. Significant liver fibrosis
(F ≥ 2) was found in 36%, cirrhosis in 18%, and significant inflammation
(G ≥ 2) in 27% of patients with normal transaminases. There was no
difference in the stage of liver fibrosis and the frequency of cirrhosis
between patients with normal and elevated transaminases. The most
important factor associated with the presence of cirrhosis in
multivariate analysis was age ≥40 years (P < 0.003). If
concomitant factors like elevated GGT or male sex were furthermore
present high prevalences of significant liver disease were found. The
data indicate that, in a European setting, patients with chronic
hepatitis B infection, and normal transaminases frequently have
significant liver fibrosis or cirrhosis. Therefore, liver biopsy or
liver stiffness measurement (LSM) should be performed in these patients
to determine the stage of liver fibrosis. J. Med. Virol. 83:968–973,
2011. © 2011 Wiley-Liss, Inc.
Little is known about differences between
individual hepatitis B genotypes and mutation patterns associated with
lamivudine resistance. This study analyses the lamivudine-associated
mutation pattern in relation to the four major HBV genotypes A–D. The
PubMed database was screened for keywords “HBV OR Hepatitis B,” “YMDD,”
“genotype,” and “lamivudine”; all identified publications published till
June 2009 were analyzed for differences in mutation pattern. To confirm
the literature-based findings the databases of two reference
laboratories in Tübingen (Germany), and Melbourne (Australia) were
analyzed. Twenty-nine studies were identified reporting 827 patients
with known hepatitis B genotype who underwent lamivudine treatment and
developed resistance mutations. The literature data revealed that
genotype A favors the rtM204V mutation unlike the other major genotypes (P 
< 0.001), which corresponds to a significant difference in the
mutation pattern of genotypes endemic in Asian countries and those found
in the rest of the world. These significant findings of the
literature-review could be reproduced in the analysis of the databases
from Tübingen and Melbourne. Furthermore, the rtL180M mutation is
significantly connected to the rtM204V mutation in genotypes A, B, and
C, respectively. It is concluded that there is proof that HBV genotypes
differ in their mutation pattern of lamivudine resistance. Future
studies will need to evaluate whether this will translate into
genotype-specific differences in resistance emergence on either
entecavir or telbivudine as these antivirals differ in their mutation
profile, rtM204V for entecavir and rtM204I for telbivudine. J. Med.
Virol. 82:1850–1858, 2010. © 2010 Wiley-Liss, Inc.Keywords:

• genotype;
  
• hepatitis
  B virus;
  
• interferon;
  
• mutation;
  
• natural history;
  
• nucleotide
  analogue
  

Recently, much
progress has been made in the field of hepatitis B, such as natural
history of the disease in relation to the amount of hepatitis B virus
(HBV) DNA, genotypes of HBV influencing the natural course and treatment
effects, mutations of HBV influencing the severity of the disease and
development of hepatocellular carcinoma, and antiviral treatment such as
nucleos(t)ide analogues and pegylated interferon. To make the consensus
for the diagnosis, management and treatment of hepatitis B, a meeting
was held during 45th annual meeting of Japan Society of Hepatology (JSH)
in June 2009. In the meeting, recommendations and informative
statements were discussed on the following subjects: (i) natural history
of HBV infection; (ii) clinical implication of HBV genotypes; (iii) HBV
mutations and their potential impact on pathogenesis of HBV infection;
(iv) indications for antiviral treatment of chronic hepatitis B; (v)
nucleos(t)ide analogues for chronic hepatitis B; and (vi) interferon
therapy for chronic hepatitis B. The presenters reviewed the data on
these subjects and proposed the consensus statements and
recommendations. These statements were discussed among the organizers
and presenters, and were approved by the participants of the meeting. In
the current report, the relevant data were reviewed and the 12
consensus statements and nine recommendations on chronic hepatitis B
were described.Background

Hepatitis B vaccine and hepatitis B immunoglobulin are
considered for newborn infants of HBsAg-positive mothers to prevent
hepatitis B infection.

Objectives

To assess the beneficial and harmful effects of
hepatitis B vaccines and hepatitis B immunoglobulin in newborn infants
of HBsAg-positive mothers.

Search strategy

Trials were
identified through The Cochrane Neonatal Group Controlled Trials
Register, The Cochrane Hepato-Biliary Group Controlled Trials
Register, The Cochrane Central Register of Controlled Trials in The
Cochrane Library, MEDLINE, and EMBASE (until February
2004), authors of trials, and pharmaceutical companies.

Selection criteria

Randomised clinical trials comparing: plasma-derived
vaccine (PDV) or recombinant vaccine (RV) versus no intervention,
placebo, or other active vaccines; hepatitis B immunoglobulin versus no
intervention, placebo, or other control immunoglobulin; as well as PDV
or RV plus hepatitis B immunoglobulin versus no intervention, placebo,
or other control vaccines or immunoglobulin.

Data collection and analysis

Outcomes are assessed at maximal follow-up. The primary
outcome measure was hepatitis B occurrence, based on a blood specimen
positive for HBsAg, HBeAg, or antibody to hepatitis B core antigen
(anti-HBc). Binary outcomes are reported as relative risks (RR) with 95%
confidence interval (CI). Subgroup analyses were performed with regard
to methodological quality of the trial, mother's HBe-Ag status, and time
of immunisation after birth.

Main results

We identified 29
randomised clinical trials, five of which were considered high quality.
Only three trials reported inclusion of hepatitis B e-antigen negative
mothers. Compared with placebo/no intervention, vaccine reduced
hepatitis B occurrence (RR 0.28, 95% confidence interval (CI) 0.20 to
0.40, 4 trials). No significant differences of hepatitis B occurrence
were found comparing recombinant vaccine (RV) versus plasma-derived
vaccine (PDV) (RR 1.00, 95% CI 0.71 to 1.42, 4 trials) and high-dose
versus low-dose vaccine (PDV: RR 0.97, 95% CI 0.55 to 1.68, 3 trials;
RV: RR 0.78, 95% CI 0.31 to 1.94, 1 trial). Compared with placebo/no
intervention, hepatitis B immunoglobulin or the combination of vaccine
plus hepatitis B immunoglobulin reduced hepatitis B occurrence
(hepatitis B immunoglobulin: RR 0.50, 95% CI 0.41 to 0.60, 1 trial; PDV
plus hepatitis B immunoglobulin: RR 0.08, 95% CI 0.03 to 0.17, 3
trials). Compared with vaccine, vaccine plus hepatitis B immunoglobulin
reduced hepatitis B occurrence (RR 0.54, 95% CI 0.41 to 0.73, 10
trials). Hepatitis B vaccine and hepatitis B immunoglobulin seem safe,
but few trials reported on adverse events.

Authors' conclusions

Vaccine, hepatitis B immunoglobulin, and vaccine plus
hepatitis B immunoglobulin prevent hepatitis B occurrence in newborn
infants of HBsAg positive mothers.

Plain language summary

Hepatitis
B vaccine, hepatitis B immunoglobulin, and hepatitis B vaccine plus
immunoglobulin prevent perinatal transmission of hepatitis B
Hepatitis B vaccination and hepatitis B immunoglobulin
are considered as preventive measures for newborn infants of HBsAg
positive mothers. When all the identified trials were combined,
hepatitis B vaccine alone, hepatitis B immunoglobulin alone, and
hepatitis B vaccine plus hepatitis B immunoglobulin reduced perinatal
transmission of hepatitis B compared with placebo or no intervention.
Hepatitis B vaccine plus hepatitis B immunoglobulin were superior to
hepatitis B vaccination alone. Adverse events were rare and mostly
non-serious.