Neonatal Hepatitis B Virus Infection

Neonatal hepatitis B virus infection is usually acquired during delivery. It is usually

asymptomatic but can cause chronic subclinical disease in later childhood or adulthood.
Symptomatic infection causes jaundice, lethargy, failure to thrive, abdominal distention, and
clay-colored stools. Diagnosis is by serology. Rarely, severe illness may cause acute liver failure
requiring liver transplantation. Less severe illness is treated supportively. Active and passive
immunization help prevent vertical transmission.
Of the recognized forms of primary viral hepatitis, only hepatitis B virus (HBV) is a major cause
of neonatal hepatitis. Infection with other viruses (eg, cytomegalovirus, herpes simplex virus)
may cause liver inflammation along with other manifestations.

Etiology
HBV infection occurs during delivery from an infected mother. The risk of transmission is 70 to
90% from women seropositive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen
(HBeAgsee Serology) at the time of delivery. Women without the e antigen or with anti-HBe
transmit the infection only 5 to 20% of the time.
Motherinfant HBV transmission results primarily from maternofetal microtransfusions during
labor or contact with infectious secretions in the birth canal. Transplacental transmission is
identified in < 2% of infections. Postpartum transmission occurs rarely through exposure to
infectious maternal blood, saliva, stool, urine, or breast milk. Up to 90% of infants infected
perinatally will develop chronic infection, and neonatal HBV infection may be an important viral
reservoir in certain communities.

Symptoms and Signs

Most neonates with HBV infection are asymptomatic but develop chronic, subclinical infection
characterized by persistent HBsAg antigenemia and variably elevated transaminase activity.
Many neonates born to women with acute hepatitis B during pregnancy are of low birth weight,
regardless of whether they are infected.
Infrequently, infected neonates develop acute hepatitis B, which is usually mild and self-limited.
They develop jaundice, lethargy, failure to thrive, abdominal distention, and clay-colored stools.
Occasionally, severe infection with hepatomegaly, ascites, and hyperbilirubinemia (primarily
conjugated bilirubin) occurs. Rarely, the disease is fulminant and even fatal. Fulminant disease
occurs more often in neonates whose mothers are chronic carriers of hepatitis B.

Diagnosis
Diagnosis is by serologic testing ( Acute Viral Hepatitis : Diagnosis), including measurement of
HBsAg, HBeAg, antibody to hepatitis B e antigen (anti-HBe), and quantitation of HBV DNA in
blood. Other initial tests include CBC with platelets, ALT and -fetoprotein levels, and liver
ultrasonography. Family history of liver cancer or liver disease is noted because of the long-term
risk of hepatocellular carcinoma. If testing suggests HBV infection, consultation with a pediatric
hepatologist is recommended.

Prognosis
Long-term prognosis is not predictable, although chronic HBV infection early in life increases
the risk of subsequent liver disease including chronic hepatitis, cirrhosis, end-stage liver disease,
and hepatocellular carcinoma.

Treatment

Supportive care

Symptomatic care and adequate nutrition are needed. Neither corticosteroids nor hepatitis B
immune globulin (HBIG) is helpful for acute infection. No therapy prevents the development of
chronic, subclinical hepatitis once infection is acquired.
All children with chronic HBV infection should be immunized with hepatitis A vaccine. Children
with chronic HBV infection may benefit from antiviral drugs (eg, interferon alfa) but these
should be used only in consultation with a pediatric hepatologist.

Prevention
Pregnant women should be tested for HBsAg during an early prenatal visit. Failing that, they
should be tested when admitted for delivery. Some women who are HBsAg-positive are treated
with lamivudine or telbivudine during the 3rd trimester, which may prevent perinatal
transmission of HBV.
Neonates whose mothers are HBsAg-positive should be given 1 dose of HBIG 0.5 mL IM within
12 h of birth. Recombinant HBV vaccine should be given IM in a series of 3 doses, as is
recommended for all infants in the US. (N ote : Doses vary among proprietary vaccines.) The
first dose is given concurrently with HBIG but at a different site. The 2nd dose is given at 1 to 2
mo, and the 3rd dose is given 6 mo after the first. If the infant weighs < 2 kg, the first dose of
vaccine may be less effective. Subsequent vaccine doses are given at age 30 days (or when
discharged from the hospital), and then 2 other doses are given at 1 to 2 mo and 6 mo after the
30-day dose. Infants born to mothers with unknown HBsAg status at the time of delivery should
receive their first dose of vaccine within 12 h of birth and receive HBIG 0.5 mL IM as soon as
possible (up to 7 days) after delivery if maternal testing is positive for HBsAg. Testing for

HBsAg and anti-HBs at 9 to 15 mo is recommended for all infants born to HBsAg-positive

mothers.
Separating a neonate from its HBsAg-positive mother is not recommended, and breastfeeding
does not seem to increase the risk of postpartum HBV transmission, particularly if HBIG and
HBV vaccine have been given. However, if a mother has cracked nipples, abscesses, or other
breast pathology, breastfeeding could potentially transmit HBV.

Key Points

Only HBV is a major cause of neonatal hepatitis; it is typically transmitted during

delivery.

Most neonates are asymptomatic but develop chronic, subclinical HBsAg antigenemia
and elevated transaminase levels.

Some infants develop mild hepatitis, and a few have fulminant liver disease.

Do serologic testing of infant and mother.

Neonates whose mothers are HBsAg-positive should be given 1 dose of HBIG 0.5 mL IM
and HBV vaccine within 12 h of birth.

HBV-infected children should be immunized with hepatitis A vaccine; anti-HBV drugs

(eg, interferon alfa) may help but should be used only in consultation with a pediatric
hepatologist.

Hepatitis in Children

What is hepatitis?
Hepatitis is an inflammation of the liver and can result in liver cell damage and destruction.

What causes hepatitis?

Hepatitis in children has many different origins or causes. A child may contract hepatitis from
exposure to a viral source. The following is a list of some of the viruses associated with hepatitis:

Hepatitis viruses. Five main types of the hepatitis virus have been identified, including
hepatitis A, B, C, D, and E.

Cytomegalovirus (CMV). This virus is a part of the herpes virus family that can be
transmitted from person to person.

Epstein-Barr virus (EBV). The virus most commonly associated with infectious
mononucleosis.

Herpes simplex virus (HSV). Herpes can involve the face and skin above the waist, or the
genitalia.

Varicella zoster virus (VZV). Also known as chickenpox, a complication of VZV is

hepatitis, although these very rarely cause hepatitis in children or infants.

Enteroviruses. A group of viruses commonly seen in children such as coxsackie

viruses and echoviruses.

Rubella. Caused by the Rubivirus, rubella is a mild disease that causes a rash.

Adenovirus. A group of viruses that commonly cause colds, tonsillitis, and ear infections
in children. They can also cause diarrhea.

Parvovirus. A virus referred to as fifth disease, which is characterized by a facial rash that
is described as having a "slapped-cheek" appearance.

The following is a list of some of the diseases that may cause acute or chronic hepatitis in
children:

Autoimmune liver disease. The body's immune system develops antibodies that attack the
liver causing an inflammatory process that leads to hepatitis.

What are the different types of hepatitis viruses?

Hepatitis A
This type of hepatitis is usually spread by fecal-oral contact, or fecal-infected food and water,
and may also be spread by blood-borne infection (which is rare). The following is a list of modes
of transmission for hepatitis A:

Consuming food made by an infected person who did not wash his or her hands well after
using the bathroom

Drinking water that is contaminated by infected feces a problem in developing

countries with poor sewage removal

Getting your hands contaminated by an infected person's feces or dirty diaper, and then
transmitting the infection to yourself by putting your hands near or in your mouth

Outbreaks may occur in child care centers especially when there are children in diapers

International travel to areas where hepatitis A is common

Sexual contact with an infected person

Use of illegal drugs

Blood transfusions (very rare)

The CDC now recommends the vaccine for hepatitis A to children at age 1. Please consult your
physician if you have questions about its use. The vaccine is especially recommended for the
following children:

Children who live in areas where there has been a community outbreak

Children who have a blood clotting disorder, such as hemophilia

Children who attend child care centers that have had outbreaks of hepatitis A

Children with chronic liver disease

The vaccine is not recommended for children younger than age 12 months.
Hepatitis B
Hepatitis B (HBV) has a wide range of clinical presentations. It can be mild, without symptoms,
or it may cause chronic hepatitis. In some cases, when infants and young children acquire
hepatitis B, they are at high risk for chronic liver disease and liver failure. Transmission of
hepatitis B virus occurs when blood from an infected person enters another person's body.
Needle sticks, sharp instruments, sharing items (razors, toothbrushes), and sex with an infected
person are primary modes of transmission. Infants may also develop the disease if they are born
to a mother who has the virus. Infected children often spread the virus to other children if there is
frequent contact (i.e., household contact) or a child has many scrapes or cuts. The following
describes persons who are at risk for developing hepatitis B:

Children born to mothers who have hepatitis B

Children who are born to mothers who have immigrated from a country where hepatitis B
is widespread such as southeast Asia and China

Children who live in long-term care facilities or who are disabled

Children who live in households where another member is infected with the virus

Children who have a blood clotting disorder such as hemophilia and require blood
products

Children who require dialysis for kidney failure

Adolescents who may participate in high-risk activities such as IV drug use and/or
unprotected heterosexual or homosexual contact

A vaccine for hepatitis B does exist and is now widely used for routine childhood immunization.
The CDC now recommends that all infants receive hepatitis B vaccination at birth, except in rare
circumstances. It is also recommended for older children, under the age of 19, who have not been
previously vaccinated.

Hepatitis C
The symptoms of hepatitis C are usually mild and gradual. Children often show no symptoms at
all. Transmission of hepatitis C occurs primarily from contact with infected blood, but can also
occur from sexual contact or from an infected mother to her baby. Although hepatitis C has
milder symptoms initially, it leads to chronic liver disease in a majority of people who are
infected. According to the CDC, hepatitis C is the leading indication for liver transplantation in
adults. With some cases of hepatitis C, no mode of transmission can be identified. The following
describes persons who may be at risk for contracting hepatitis C:

Children born to mothers who are infected with the virus

People who have a blood clotting disorder such as hemophilia and received clotting
factors before 1987

Children who require dialysis for kidney failure

Individuals who received a blood transfusion before 1992

Adolescents who participate in high-risk activities such as IV drug use and/or unprotected
heterosexual or homosexual contact with an infected person.

There is no vaccine for hepatitis C. People who are at risk should be checked regularly for
hepatitis C. People who have hepatitis C should be monitored closely for signs of chronic
hepatitis and liver failure.
Hepatitis D
This form of hepatitis can only occur in the presence of hepatitis B. If an individual has hepatitis
B and does not show symptoms or shows very mild symptoms, infection with D can put that
person at risk for liver failure that progresses rapidly. Hepatitis D can occur at the same time as
the initial infection with B, or it may show up much later. Transmission of hepatitis D occurs the
same way as hepatitis B, except the transmission from mother to baby is less common. Hepatitis
D is rare in children born in the U.S. due to the common use of hepatitis B vaccine in infancy.
Hepatitis E
This form of hepatitis is similar to hepatitis A. Transmission occurs through fecal-oral
contamination. It is less common in children than hepatitis A. Hepatitis E is most common in
poorly developed countries and rarely seen in the United States. There is no vaccine for hepatitis
E at this time.

How often does hepatitis occur?

In the U.S.:

Hepatitis A rates have declined by 95 percent since the hepatitis A vaccine first became
available in 1995

An estimated 800,000 to 1.4 million people have chronic hepatitis B infections

An estimated 3.2 million people have chronic hepatitis C infections

Why is hepatitis a concern?

Hepatitis is a concern because it often originates from a virus and is communicable (can be
spread from your child to others). In some cases, liver failure or death can occur. However, not
everyone who is infected will experience symptoms.

What are the symptoms of hepatitis?

The following are the most common symptoms for hepatitis. However, each child may
experience symptoms differently and some children may experience no symptoms at all.
Symptoms of acute (abrupt onset) hepatitis may include the following:

Flu-like symptoms

Jaundice (yellow color in the skin and/or eyes)

Fever

Nausea and/or vomiting

Decreased appetite

Not feeling well all over

Abdominal pain or discomfort

Diarrhea

Joint pain

Sore muscles

Itchy red hives on skin

Clay-colored stools

Dark urine

Later symptoms include dark-colored urine and jaundice (yellowing of the skin, and eyes). The
symptoms of hepatitis may resemble other conditions or medical problems. Always consult your
child's doctor for a diagnosis.

How is hepatitis diagnosed?

In addition to a complete medical history and examination by your doctor, diagnostic procedures
and other tests to determine the extent of the disease may include the following:

Blood testing for the following:

o

Liver enzymes

Liver function studies

Antibody and polymerase chain reaction (PCR) studies (to check for the type of
viral hepatitis if present)

Cellular blood counts

Coagulation tests, such as an international normalized ratio (INR)

Computed tomography scan (CT scan). This diagnostic imaging procedure uses a
combination of X-rays and computer technology to produce horizontal, or axial, images
(often called slices) of the body. A CT scan shows detailed images of any part of the
body, including the bones, muscles, fat, and organs. CT scans are more detailed than
general X-rays.

Magnetic resonance imaging (MRI). MRI is a diagnostic procedure that uses a

combination of large magnets, radiofrequencies, and a computer to produce detailed
images of organs and structures within the body. The patient lies on a bed that moves into
the cylindrical MRI machine. The machine takes a series of pictures of the inside of the
body using a magnetic field and radio waves. The computer enhances the pictures
produced. The test is painless, and does not involve exposure to radiation. Because the
MRI machine is like a tunnel, some people are claustrophobic or unable to hold still
during the test, and may be given a sedative to help them relax. Metal objects cannot be
present in the MRI room, so persons with pacemakers or metal clips or rods inside the
body cannot have this test done. All jewelry must be removed before the procedure.

Liver biopsy. A small sample of liver tissue is obtained with a special biopsy needle and
examined for abnormalities.

What is the treatment for hepatitis?

Specific treatment for hepatitis will be determined by your child's diagnosis and health care
provider based on:

Your child's age, overall health, and medical history

Extent of the disease

Your child's tolerance for specific medications, procedures, or therapies

Expectations for the course of the disease

Your opinion or preference

Treatment for hepatitis varies depending on the underlying cause of the disease. The goal of
treatment is to stop damage to the liver and alleviate symptoms. Treatment may include one, or
more, of the following:

Antiviral medications if it is a virus

Immune drugs if the diagnosis is an autoimmune disease

Supportive care (healthy diet and rest)

Medications (to help control itching)

Maintaining adequate growth and development

Avoiding alcohol and drugs

Preventing the spread of the disease (if the cause is viral hepatitis)

Interferon drug therapy (a medication referred to as a "biologic response modifier" that

can affect the immune system and has virus-fighting activities)

Frequent blood testing (to determine disease progression)

Hospitalization (may be required in more severe cases)

Liver transplantation (may be recommended for end-stage liver failure)

Proactive nutrition support

How can viral hepatitis be prevented?

Proper hygiene is the key to preventing the spread of many diseases, including hepatitis. Other
preventive measures include:

Vaccinations. Vaccinations are available for hepatitis A and B.

Blood transfusion. Blood transfusions are routinely screened for hepatitis B and C to
reduce the risk of infection.

Antibody preparation. If a person has been exposed to hepatitis A or B, an antibody

preparation (immunoglobulin) can be administered to help protect them from contracting
the disease.

Neonatal Hepatitis

What is neonatal hepatitis?

Neonatal hepatitis is an inflammation of the liver that occurs in early infancy, usually one to two
months after birth. About 20 per cent of infants who develop neonatal hepatitis were infected
with a virus causing inflammation of the liver either before birth through their mother, or shortly
after birth. Viruses which can cause neonatal hepatitis in infants include cytomegalovirus, rubella

(measles), and hepatitis A, B and C. In the remaining 80 per cent of affected infants, no specific
cause can be identified, but many experts suspect a virus is to blame.
What are the symptoms of neonatal hepatitis?
An infant with neonatal hepatitis usually has jaundice (yellow eyes and skin) that appears at one
to two months of age. Jaundice occurs when the flow of bile from the liver is blocked due to an
inflammation or obstruction of the bile ducts. Since bile is essential in the digestion of fats and
absorption of fat soluble vitamins, a child with neonatal hepatitis may fail to gain weight and
grow normally. The infant will also have an enlarged liver and spleen.
How is neonatal hepatitis diagnosed?
The diagnosis of neonatal hepatitis is initially based on blood tests aimed at identifying possible
viral infections leading to the disease. In cases where no virus is identified, a liver biopsy is
performed. This involves the removal of a small piece of the liver using a special syringe for
examination under a microscope.
Biopsy results will often show that groups of four or five liver cells have joined together to form
larger cells. Although these large cells continue to function, they do so at a lesser rate than
normal liver cells. This type of neonatal hepatitis is sometimes called giant cell hepatitis.
The symptoms of neonatal hepatitis are similar to those associated with another infant liver
disease called biliary atresia. In infants with biliary atresia however, bile ducts are progressively
destroyed for reasons that are poorly understood. Although an infant with biliary atresia is also
jaundiced with an enlarged liver, there is generally normal growth and the spleen is not inflamed.
In addition to symptoms, a liver biopsy and blood tests are needed to distinguish biliary atresia
from neonatal hepatitis.
What complications are associated with neonatal hepatitis?
Infants with neonatal hepatitis caused by rubella or cytomegalovirus are at risk of developing an
infection of the brain that could lead to mental retardation or cerebral palsy. Many of these
infants will also have permanent liver disease due to the destruction of liver cells and the
resulting scarring (cirrhosis).
The majority of infants with giant cell hepatitis will recover with little or no scarring to the liver.
Their growth pattern will also normalize as bile flow improves. However, about 20 per cent of
affected infants will go on to develop chronic (ongoing) liver disease and cirrhosis. In these
children, the liver becomes very hard due to scarring, and the jaundice does not dissipate by six
months of age. Infants who reach this point in the disease eventually require a liver transplant.

Infants with chronic neonatal hepatitis will not be able to digest fats and absorb fat soluble
vitamins (A, D, E and K) as a result of insufficient bile flow and the damage caused to liver cells.
The lack of vitamin D will lead to poor bone and cartilage development (rickets). A deficiency in
vitamin A may affect normal growth and vision. Vitamin K deficiency is associated with easy
bruising and a tendency to bleed, whereas the lack of vitamin E results in poor coordination.
Since bile is responsible for the elimination of many toxins in the body, chronic neonatal
hepatitis can also lead to a buildup of toxins in the blood which in turn may result in itching, skin
eruptions and irritability.
How is neonatal hepatitis treated?
There is no specific treatment for neonatal hepatitis. Vitamin supplements are usually prescribed
and many infants are given medications which improve bile flow. Formulas containing fats more
easily digested by the body are also given.
Can neonatal hepatitis be spread to others?
Infants with neonatal hepatitis caused by the cytomegalovirus, rubella or viral hepatitis may
transmit the infection to others who come in close contact with them. These infected infants
should not come into contact with pregnant women because of the possibility that the woman
could transmit the virus to her unborn child.