HEPATITIS B VIRUS.

Discovery and Development.

Baruch S. Blumberg
Fox Chase Cancer Center, Philadelphia PA, USA
 HEPATITIS B VIRUS MORPHOLOGY

Characteristics
Nucleic acid: DNA
Classification:
hepadnavirus type 1
Serotypes: multiple
22 nm In vivo replication:
reverse transcription in
liver and other tissues
In vitro propagation:
42 nm
primary hepatocyte
culture and transfection
by cloned HBV DNA
HBsAg
C

HBV DNA HBcAg

HBV is one of the most common infections in the world.
About 600,000 to 1,000,000 deaths per year
are attributable to the diseases associated with HBV.
 PREDICTED DEATHS FROM
PREVALENT CARRIERS OF HIV AND HBV

(H. Margolis, Center for Disease Control. Paper presented at Third

International Conference on Therapies for Viral Hepatitis, Maui, 12/12/99)

Number Case Total

Virus Infected Fatality Deaths
(Millions) Rate (Millions)
HIV 34 100% 34
HBV 371 High 25% 92.8
Low 15% 55.7
MORTALITY BY AGE GENDER AND HBV RESPONSE
HAIMEN CITY, CHINA

2500
M HBV+ M HBV- F HBV+ F HBV-
Mortality per 100,000 py

2000

1500

1000

500

0
25-34 35-44 45-54 55-64 65-74
Age group (years)

G. Chen, W. Lin, F. Shen, U. Iloeje, T. London and A. Evans

Inter. J. of epid. 2004, in print
 CONTROL OF HEPATITIS B VIRUS IN CHINA

Z.Y. Xu, T.Q. Yan, S.J. Zhao, et al. Shanghai Medical University

“Infant HBV immunization has been implemented

into public health service in China since 1986…
the seropositivity for HBsAg was reduced from
16.3% (879/5397) of historical controls to 1.43%
(70/4886) in cross-sectional study and 1.81%
(210/11582) in a cohort study.”
 HBV VACCINATION IN ITALY

 A vaccination program was initiated in 1983 in Afragola, Italy, a

community with very high rates of HBV infection and of
morbidity and mortality from liver disease (Da Villa, et al.,
1992, Da Villa, et al., 1995).
 The prevalence of HBsAg in males up to 12 years dropped from
10.5% in 1978 to 0.8 % in 1993 after the vaccination
program was in place for ten years.
 The prevalence of anti-HBc in dropped from 52.6% to 1.2%.
 There was also a drop in the prevalence of HBsAg in the mostly
unvaccinated population i.e., males age 13-60. HBsAg
dropped from 17.97% in 1978 to 5.5% in 1989. This implies
that the reduction of the carrier prevalence in the vaccinated
group has an indirect effect on unvaccinated carriers and
susceptibles, and suggests that there may an amplification
characteristic to the vaccination program.
 STUDIES ON TAIWAN

Hepatocellular Carcinoma:

Average annual incidence in the age range 6-14 fell from

0.7/100,000 in 1981-1986 (before vaccination) to 0.36/100,000 in
1990-1994 (after vaccination) (p < 0.01)

The annual incidence in children aged 6-9 years fell from

0.52/100,000 in those born in 1974-1984 (pre-vaccination program),
to 0.13/100,00 in those born in 1986-1988, (post-vaccination
program) (p<0.001)
The probability of male or female patients in a single hemodialysis
unit remaining HBsAg+ after infection. Males have a 68% probability
of becoming chronic carriers when first detected HBsAg-, whereas
female patients have a 33% chance.
The probability of patients not developing ant-HBs once detected
HBsAg+. About 55% of the female patients are likely to eventually
develop ant-HBs compared with 30% of males.
 PLATI, GREECE. NUMBER OF MALE AND FEMALE LIVE BIRTHS
ACCORDING TO THE RESPONSES TO HBV OF PARENTS

Parent’s response Couples Live births

To HBV (No.) Sex ratio
Male Females

Either parent HBsAg + : 33 60 (1.8 ± 24 (0.7 ± 0.1) 250 (161,429)*

0.2)
anti-HBs –
Both parents HBsAg - : 29 35 (1.2 ± 0.2) 146 (96,230)*
51 (1.8 ±
anti-HBs –
0.2)
Both parents HBsAg - : 154 22 (1.4 ± 0.1) 109 (91,131)*
either parent anti-HBs +
24 (1.6 ±
0.1)
*In parentheses, the 5 percent confidence limits.
Blumberg, B.S. Sex differences in response to Hepatitis B Virus,
Arthritis and Rheumatism,22, 1261, 1979
 Hepatitis B and Sex Ratio
Location HBV Status Sons Daughters Sex Ratio
Greenland Positive 64 60 1.07
Greenland Negative 174 194 0.90
Kar Kar Island Positive 63 54 1.17
Kar Kar Island Negative 163 206 0.79
Greece 1 Positive 85 46 1.85
Greece 1 Negative 287 255 1.13
Philippines Positive 66 41 1.61
Philippines Negative 304 301 1.01
Greece 2 Positive 52 30 1.73
Greece 2 Negative 1006 955 1.05
France Positive 20 12 1.66
France Negative 149 122 1.22
Notes: This table shows sex ratios among the children of carrier and non-carrier parents in four
regions. Data were collected by testing married women and, in all cases except for Greenland,
their husbands for HBV. Detailed reproductive histories were also collected. The table represents
all births to women in those samples, with generally more than one birth to each women. The
last two studies (Greece 2 and France) were designed specifically to test the hypothesis that
HBV affects offspring sex ratio, and were run after the original theory was expressed.

From Oster, E. 2005