CRITICAL REVIEW TOWARDS HEPATITIS B VACCINATION FOR NEWBORN BABIES AROUND THE WORLD

T. MUDWAL

Two billion people around the world have been infected with Hepatitis B [1]. Among those two billion,
400 million people will chronically be infected with hepatitis B [1]. 20 30 % of the 400 million will then
develop into chronic hepatitis, hepatic cirrhosis, or hepatoma.

Hepatitis B causes approximately 780 thousand deaths annually around the world [2]. Currently the
world is divided into 3 areas concerning the hepatitis B which is High Endemic, Intermediate endemic,
and low endemic. A country is considered high endemic if more than 8% of the people have Hepatitis B
(HbsAg+), intermediate if 2 8 % and low if less than 1% has hepatitis B [2]. Less than 1% people in West
Europe and North America suffers from chronic hepatitis B [2]. Meanwhile Indonesia is considered a
high endemic country. This is based on a statement by Tjandra Yoga Aditama, dirjen P2PL Depkes, that
says 1 in 10 people in Indonesia has hepatitis B (9,4%) [3].

Hepatitis B Infection; Course of Disease.

The incubation period of hepatitis B virus is around 30 180 days, and it can be detected in the blood 30
60 days after infection [2]. The hepatitis B virus can be transmitted parenterally, for example through
needles, blood transfusion, hemodialysis, tattoo, shaving razors or aiding in childbirth. It can also be
transmitted sexually and perinatal, from a mother to her newborn baby.

Our immunity holds an important role in the sign and symptoms development and the duration in which
the hepatitis B virus can survive in the human body. If the hepatitis B virus (HBsAg +) can still be
detected for more than 6 months after the infection, the virus is considered to be chronic. If it is only
detected for less than 6 months, the virus is considered to be in the acute phase. An interesting point is
that the hepatitis B virus usually becomes chronic in children. In babies under 1 year old, 90% of them
with hepatitis B virus will develop into chronic hepatitis B [4]. Meanwhile only 30 50 % children under
6 years old who will develop chronic hepatitis B [2]. Only 10% resolves by itself or it may become acute
hepatitis presenting with/without symptoms (such as icteric). It may also become severe acute hepatitis
fulminant hepatitis). Fulminant hepatitis B only happens around 1% [5]. The number of acute hepatitis B
in children and adults is around 4 million, that is 0.2% of all 2 billion people infected with hepatitis B [6].
Aging lowers the chance of the hepatitis B virus becoming chronic. A child aged 1 5 years old infected
with hepatitis B has 25 50% chance of it becoming chronic. 6 10 % for children above 5 years old and
only 5% for adults (above 18 years old) [2]. Most hepatitis B infections in adults will resolve by
themselves [7]. If someone once has acute hepatitis B infection, the chance of it becoming chronic
hepatitis is only 10% [8]. Even so, 30 50 % of acute hepatitis B infection in adults will present with
icteric [9].

Discussion

It is mentioned above that there are as many as 400 million people with chronic hepatitis B (HBsAg + for
more than 6 months). It can also be seen in the diagram that hepatitis B becomes chronic especially in
children under 1 years old (90%). Logically, this means that hepatitis B vaccination should be given
before 1 year of age.

On the other hand, if a baby is born with HBsAg -, that baby has a really small chance of contracting
hepatitis B, until he/she comes of age, or is 15 years old. A 15 year old who contracts hepatitis B is more
likely to get infected from sexual contact [10]. Other causes such as injections, blood transfusions,
hemodialysis, tattoo, razors, or perinatal rarely happens. With that knowledge, is there an advantage in
vaccinating a newborn baby, and will the advantage be seen for a long time? Is there any difference in
vaccinating a baby with a positive Hbs Ag and a negative HbsAg. This article is written to answer that
question.

WHO does not prohibit vaccinating someone with a positive HBsAg [1]. Therefore, newborn babies do
not need a serologic testing before hepatitis B vaccination. This is what is done in the US [11]. With that
in mind, Indonesia and other countries made the policy to vaccinate newborn babies without conducting
a serologic testing. There are no contraindications for hepatitis B vaccination, except in patients with a
previous allergic response towards vaccines or fungi [11]. Even immunocompromized patients, (such as
patients with HIV) who is vaccinated is given a higher dose of hepatitis B vaccination [10]. Nothing
should be feared in vaccinating a HBsAg+ person. Vaccinating a person who has previously suffered from
a hepatitis B infection does not have any risk; in fact it is only a waste of money [11]. Those facts are, in
my opinion, a strong argument for the WHO to allow vaccinations on children with HBsAg +.

Serologic testing to check for immunity towards hepatitis B is not needed except for:

Newborn babies from HBsAg + mothers

Medical staff or people who is exposed to hepatitis B + patients

Immunocompromized patients

Husband or wife whose partners suffers from chronic hepatitis B.

Based on that above, Indonesia and other countries do not check IgM anti HBc and anti HBs after
hepatitis B vaccination in newborn babies.

Immunity towards hepatitis B virus is marked with titer anti HBs 10 miu/ml. HBsAg + babies born from
HBsAg+ mothers needs hepatitis B immunoglobulin within the first 12 hours after birth. This is to
eradicate hepatitis B virus that enters the baby from the mother.

The Conclusion about the Hepatitis B Vaccination Program for Newborn Babies

Newborn babies with HBsAg -, needs to be vaccinated in order to prevent that baby from contracting
acute, chronic hepatitis B, hepatic chirrosis, and hepatoma. On the other hand, HBsAg + babies should
still be vaccinated. A positif HBsAg will stimulate the immune cells to form immunity, but it may not be
strong enough, because HBsAg + does not always represent a whole hepatitis B virus. There is no
correlation between a positive HBsAg and HBV DNA [12]. So there might be a chance that HBsAg+ does
not mean that there is a live virus, but only pieces of a dead hepatitis B virus. The hepatitis B virus is
considered dangerous if the Hbv DNA is above 2000 IU/ml [13]. Therefore it is normal that a positive
HBsAg doesnt spark an adequate response from the antibodies. In my opinion, this is another reason
why WHO does not prohibit vaccination in HBsAg + people. On the other hand, almost all HbsAg+ babies
are born from HBsAg+ mothers. Almost all of the HBsAg+ mothers do not have any symptoms; this can
mean that there is no viremia happening in the mother. It could also mean that the positive HBsAg is
caused by pieces of dead virus, or if there happens to be a live virus, it is only in a small amount. Even
so, the live virus from the mother may cause an acute or even chronic hepatitis in a newborn baby. This
is caused by the immature immunity system in newborn babies. Therefore, besides giving a vaccination,
a hepatitis B immunoglobulin (HBIg) needs to be given to prevent the occurrence of acute hepatitis and
to also boost an adequate immunity towards the hepatitis virus in newborn babies. This HBig is aimed to
prevent the blow from the virus (formation of antigen-antibody complex which is then destructed by
macrophages). HBIg should be given within the first 12 hours of life. Those are the reasons to why
newborn babies need to be vaccinated whether they have a positive or negative HBsAg.

On the other hand, if we look at the diagram, the virulence of the hepatitis B virus seems to be weak.
Only 10% of newborns infected with hepatitis B virus will develop into an acute hepatitis infection.
Ninety percent of that 10% will recover. Only 1% of the rest 10% (0.1% of all newborns infected with
hepatitis B) will suffer from severe acute hepatitis (fulminant hepatitis). Meanwhile, 90% adults (above
18 years old) infected by acute hepatitis B will fully recover. Only 0.1% of all adults with acute hepatitis
will have fulminant acute hepatitis.

The hepatitis B virus will cause a release of IL6 [14], a cytokine that stimulates the plasma cells. The
human body also responds by releasing IL10 [14] which causes the macrophage cells to be less active
[15]. Compare this to the reaction caused by the dengue virus where the body releases a huge amount
of cytokines also known as the cytokine storm (IL1, IL2, IL4, IL5, IL12, IL13, IL18) [16]. In a Hepatitis B
infection, the human body thinks that releasing IL 6 is enough to destroy the virus. Unfortunately, that
immunologic capability is not yet mature enough in children 0 1 year old. The same thing happens in
the childrens immunoglobulin abilities to catch the hepatitis B virus. This is the reason why the virus
survives and lives chronically without producing significant symptoms. Consistent with the development
of a childrens immunity, 90% of the 90% children with a chronic virus will fully recover, while the other
10% will still be infected by the virus. Ninety percent of the 10% will also fully recover. The opposite
thing happens in adults (>18 years old). Their mature immunity will destroy the virus completely earning
a full recovery (90%). 70% of the remaining 10% will also have a full recovery. Because of this, nothing
should be feared from an acute hepatitis B viremia in newborns. Only 0.1% will become a severe acute
hepatitis. The 1% chance of it developing into chronic hepatitis, hepatic chirosis, and hepatoma happens
mostly in children aged 1 5 years. Vaccinating children between the age of 1 5 years old will prevent
50% at maximal of them getting chronic hepatitis, hepatic chirosis and hepatoma. The effectiveness of
the vaccine will continue to decline after the age of 5 years old, which is only around 5 10%, or around
0.05 0.1% of all babies suffering from acute babies after birth (refer to the diagram).

Without a mature immunity (babies 0 -1 years old) acute symptoms only happens in 10%. 90% of that
10% will fully recover. In conclusion, the babys immunity failed to destroy the virus, but the virus also
failed to ail the baby. In adults (>18 years old), the acute symptoms can be seen in 90% people, and only
5% becomes chronic. Of this 95%, 90% fully recovers, or managed to destroy the virus completely.

With that in mind, it becomes clearer that there is nothing to be afraid of when a baby is born with
hepatitis B, even though that baby is in a state of viremia. Or in other words, hepatitis B vaccination is
not cost-effective. Moreover, vaccination using Hepatitis B immunoglobulin (HBIg).

But even so, we have found data that having a mass hepatitis B vaccine program gives an advantage to
countries that does so. Hepatitis B and the Need for A Booster Dose journal, Elke Leuridan, Pierre Van
Damme states that for example Malaysia reports a decline in HBsAg+ from 1.6% to 0.3% in 2003, in
children aged 7 -12 years, since the vaccination program in 1990. Thailand reported a decline in
Hepatocellular Carcinoma cases in children aged 6 14 years, from 0.7 cases per 100.000 population to
0.36 per 100.000 population (7 cases in 1.000.000 people to 3.6 cases). The number of children and
adult patients with acute hepatitis declined from 4.5 per 100.000 people to 0 case per 100.000 people in
Hawai. Gambia stated that the percentage of children with HBsAg + declined from 10% to 0.6% since a
mass vaccination in 1990. US said that as much as 94% cases of acute hepatitis has declined since the
mass vaccination program [17].

From those data, we can see that hepatitis B vaccination in newborn babies, whether they are HBsAg
or +, has an advantage. But in my opinion, there are some things to be noted from those successes.

If the goal of vaccination is to speed up the formation of anti HBs or to lower the percentage of acute
hepatitis B infection in children, then the goal has been achieved. But if we look at the diagram and see
that only 10% of the acute hepatitis in children becomes icteric, then the effectiveness of the
vaccination to prevent acute hepatitis is only 1%. In other words, without vaccination, 99% of children
aged 0 -1 years old with hepatitis B will fully recover. Another point of view is by predicting the chance
of severe acute hepatitis (fulminant acute hepatitis). Children with icteric acute hepatitis will mostly
have a full recovery. Referring to the 0.1% probability of children having fulminant acute hepatitis, it
would mean that without vaccination, 99.9% children can avoid death caused by acute hepatitis. With
that in mind, the cost-effectiveness of the hepatitis B vaccine should be questioned. The decline in
HBsAg percentage in the countries mentioned above may be caused by something other than
vaccination in children. It may be caused by vaccination in adults. The high amount of adults given the
hepatitis B vaccination would decrease viral transmission from a mother to child. This immunization that
is given to adults is the reason there is a decline in adult HBsAg percentage, thus a decline in HBsAg
percentage in newborns in the US. This proves that a hepatitis B vaccination for newborns is not cost-
effective. Giving the HBIg immunization to HBsAg+ newborns from HBsAg + mothers also has minimal
use. This is based on the fact that patients who previously had a hepatitis B infection, and who is then
given another vaccination, did not have any risk [11]. Immunocompromized patients should be given a
higher dose of vaccine [11]. Even though babies do not have a mature immunity, only 10% suffers acute
hepatitis B after being infected with the hepatitis B virus, and only 0.1% becomes severe. In other
words, a strong hepatitis B virus is needed to stimulate the formation of anti HBS, or to cause an
antigen-antibody reaction. That is why we dont need to destruct the hepatitis B virus by giving
immunoglobulin. Just give the baby the hepatitis B vaccination, without the HBIg. In conclusion, if we
want vaccinate newborn babies, we dont need to see whether the mother has HBsAg or not, and we do
not need to give HBIg.

How long is a vaccinated person protected from a hepatitis B virus?

The longest study that I know of is a study conducted in Gambia [18]. In this study, without a booster,
the number of anti HBs above or equal 10 mIU/ml is only 17.8%. This shows that the majority of people,
who were given a hepatitis B vaccination after birth, now at the age of 24, had already lost the immunity
against the hepatitis B virus (82.2%). This could mean that by the age of 30, an adult wouldnt have a
memory immunity towards the hepatitis B virus and they should be given a booster if they wanted to
have an effective anti HBs.

In general, vaccination given to newborns with a and + HBsAg compared to children not vaccinated,
then the number of children contracting chronic hepatitis, hepatic cirrhosis and hepatoma only
decreases by 17.8% after 24 years. So the effectiveness of hepatitis B vaccination in newborns to
prevent a chronic liver disease is only as much as 17.8% (until the age of 24). Meanwhile, after 30 years
old, I assumed that everyone either vaccinated or not, has the same chance in getting a chronic
hepatitis, hepatic cirrhosis and hepatoma. What if childrens arent vaccinated since birth? We can see in
the diagram that at the end only 5% of the children will suffer a chronic hepatitis during adulthood. Even
though their anti HBs is negative. The study in Gambia that stated the effective anti HBs is only 17.8%
doesnt mean that the number of chronic hepatitis is lower than in the unvaccinated newborns. It only
shows that vaccinated people had a higher anti HBs compared to those not vaccinated. If so, how high is
the percentage that vaccinated children will not get chronic hepatitis B during their adulthood? The
chance could be lower, equal, or higher. This is because the hepatitis B virus has a weak virulence, and
adults have a mature immune system. However, the percentage of children with chronic hepatitis is
lower in children who were vaccinated. This is because the vaccination causes the immune system to
mature quicker. This is proven in Thailand with the decrease of hepatocellular carcinoma cases in
children. A study in Italy reported that 79.2% HBsAg + newborns, from HBsAg + mothers, who were
vaccinated, had an effective immunity against the hepatitis B virus (anti HBs 10 mIU/mm) 9 years after
vaccination. Or in general, a hepatitis B vaccination given right after birth is effective until the children is
9 years old [19].

A study conducted in Italy, reported that a hepatitis B vaccination gives a protective effect for 10 years
post-vaccination as much as 60%, 66%, 56% in 3 different samples [9]. In hepatitis during adulthood, we
should consider that a low religious knowledge and sexual behavior may result in another type of
hepatitis B virus, or a mutant hepatitis B virus that may cause a child to suffer acute/chronic hepatitis B,
hepatic cirrhosis, and hematoma before the child turns 30. So, hepatitis B vaccination cannot prevent
chronic hepatitis B, hepatic cirrhosis, and hematoma after the age of 30. Meanwhile, in adults before 30
years old (15 29 years old), religion and nutrition can lessen the number of hepatitis B infections,
instead of vaccinations in newborns. On the other hand, a weak virulence, and a mature immunity
during adulthood lowers the advantage of vaccinations after birth. Hepatitis b vaccinations in newborns
gives a significant advantage in preventing chronic hepatitis, hepatic cirrhosis, and hepatoma during
childhood. For example: the number of Indonesias citizens is 250 million. Adult citizens (age 15 44)
150 million. Prediction of hepatitis B in adults is 4% or 6 million. If a vaccination is given to all newborns,
then at the age of 15 29 years old, the number of people with chronic hepatitis B, in general decreases
by 17.8% or 20% or becomes 4.8 million people. If a vaccination is not given then the number of adults
with hepatitis B is still 6 million. Or we can say that the advantage of vaccination is a decrease in the
number of people suffering from chronic hepatitis, hepatic cirrhosis, and hepatoma as much as 1.2
million people before 30 years old. But if a vaccinated person still has a bad sexual behavior, then that
1.2 million advantage may not be fulfilled. And the number of people with chronic hepatitis B, hepatic
cirrhosis, and hepatoma (predicted to be 6 million) may be higher if the people has bad nutrition or
behavior. On the contrary, if someone is not vaccinated at birth but is given proper education, nutrition,
and has a good behavior, then the number of people with chronic hepatitis B, hepatic cirrhosis, and
hepatoma may be lower than 4.8 million people. Furthermore, if we remember that adults have a
mature immune system and the virus is relatively weak, the number may be even lower. Meanwhile, at
the age of 30 years old and above, there is no difference whether they were vaccinated at birth or not. If
we see that children are most likely to get infected after puberty (>15 years old) and the majority of the
cause is free sex, then we must be thankful if our newborn baby has a negative HBsAg. If the child
behaves well and is given enough nutrition, then hopefully the child will not suffer from hepatitis B,
cirrhosis and hepatoma during his/her life. But if the child is born with HBsAg+ then anything can
happen, as explained above, whether or not they behave/eat well. Therefore, the person who needs to
be vaccinated are adult females (>15 years old). In conclusion, the effectiveness of vaccination in
newborns to prevent a chronic liver disease is only 17.8%, and this number can be lower if everyone
behaves and is given enough nutrition.

Summary

Hepatitis B vaccination given 3 times before 1 year of age, and without booster is not cost-effective,
especially in poor to developing countries. This is based on the fact that hepatitis B vaccination is only
effective in preventing acute hepatitis in children 1 5 years old. The number of hepatitis B cases in
children <1 years and >5 years old is low. The percentage of severe acute hepatitis in children is only
0.1%. meanwhile, preventing chronic hepatitis with hepatitis B vaccination is only effective until the
child is 10 years old. The vaccination is considered effective if more than 50% vaccinated children were
found to have anti HBs 10 mIU/ml. Vaccination in adults is the reason why there is a decline in the
percentage of HBsAg in newborns and adults (and not caused by a mass vaccination in newborn babies).
Even so, we need to admit that a mass hepatitis B vaccination does lower the percentage of HBsAg
(even though it is not cost-effective). The weird thing is Indonesia reported an increase in acute hepatitis
B in patients all age. Riset Kesehatan Dasar (Riskesda) Health Department RI 2013 reported that there
was an increase in Hepatitis B prevalence in all age groups, compared to the hepatitis B prevalence in
2007. This happened even though the mass hepatitis B vaccination program has been going on since
1992.

We must be thankful if a baby is born with HBsAg -, and they should not be given vaccination. They must
be given enough nutrition and be taught to behave well. The weak virulence of Hepatitis B and the
developing immunity are the reasons why. If we give a HBsAg + baby a hepatitis B vaccination then the
baby no longer needs HBIg.

The protection properties of hepatitis B vaccinations in newborns only lasts around 10 years. The
protection effects means that the anti Hbs 10mIU/ml was found in >50% samples vaccinated with
Hepatitis B after birth. A booster is needed after that.