VIRAL HEPATITIS

BY
Dr. Hantash Hamoury
 There are five types of viral hepatitis: hepatitis A (HAV), B (HBV), C
(HCV), D (HDV), and E (HEV).
 These types may present as either acute or chronic illnesses, which are
primarily differentiated based on disease duration.
 Acute hepatitis may be associated with all five types of hepatitis and
rarely exceeds 6 months in duration.
 Chronic hepatitis (disease lasting longer than 6 months) is usually
associated with hepatitis B, C, and D.
 Chronic viral hepatitis may lead to the development of cirrhosis, which
may induce end-stage liver disease (ESLD).
 Complications of
 ESLD include ascites, edema, jaundice, hepatic encephalopathy,
infections, and bleeding esophageal varices.
 Therefore, prevention and treatment of viral hepatitis may prevent
ESLD.iral hepatitis can occur at any age and is the most common cause
of liver disease in the world. The true prevalence and incidence may be
underreported because most patients are asymptomatic.
 HBsAg….Active infection
 Anti-HBc Ig ….IgM…..IgG
 HBe Ag↑ Infec
 HBs AB…..Immunity to Hep B
 Hbe AB Low infectivity
 HBc IGg\ HBsAg chronic infection
 HBc Igg\Anti HBs AB …Resolved infection
 (anti-HBe) and (anti-HBs and HBV DNA levels become undetectable????
 anti-HEV antibodies……???/
 Patients who are hepatitis B carriers (defined as having a positive HBsAg,
normal alanine aminotransferase (ALT) levels, and negative HBeAg)
 HEPATITIS A
 Epidemiology and Etiology
 Hepatitis A affects 1.4 million people yearly worldwide.
 The prevalence is highest in underdeveloped countries including Africa,
parts of South America, the Middle East, and Southeast Asia.
 In contrast, developed parts of the world including Australia, parts of
western and northern Europe, Japan, and the United States have a lower
prevalence.
 Thirty-one percent of the American population has been infected with
the HAV.
 Overall, Mexican Americans are at greatest risk for HAV infection, and
African Americans are more likely to be infected than Caucasians.
 The hepatitis A virus is primarily detected in contaminated feces and
infects people via the fecal-oral route.
 Outbreaks occur primarily in areas of poor sanitation.
 Approximately 50% of the reported cases have no identifiable risk factors.
 To date, there are no documented cases of chronic hepatitis A.
 Death associated with HAV is rare and is mostly associated with fulminant
hepatitis, with which approximately 100 people die annually.
 Pathophysiology
 Hepatitis A is a non-enveloped single-stranded ribonucleic acid (RNA) virus
classified as the Hepatovirus genus under the Picornaviridae family.
 The only host for the HAV is humans, with hepatic cells as the primary
site for viral replication.
 As part of the viral degradation process, the HAV is released into the biliary
system causing elevated concentrations of the virus in the feces.
 HEPATITIS B
 Epidemiology and Etiology
 Hepatitis B is a blood-borne infection affecting more than 2 billion
people in the world.
 Approximately 350 million people have chronic infection, which may
lead to cirrhosis and complications of ESLD.
 Deaths related to hepatitis B range from 500,000 to 750,000
yearly.
 Despite having an effective vaccine against HBV, more than 300,000
newly-diagnosed infections emerge each year.
 The prevalence of chronic hepatitis B is geographically dependent; the
rate is about 1% in North America and Western Europe compared to
10% to 15% in developing areas such as Southeast Asia.
 The highest concentration of the HBV is found in blood and serous fluids.
 Therefore, the primary mode of hepatitis B transmission is either by blood or
body fluids through perinatal, sexual, or percutaneous exposure.
 Infants born of mothers who are infected with HBV that is actively replicating
have a 90% risk of developing chronic hepatitis B.
 If an infant residing in an endemic area is not infected at birth, the risk of
acquiring chronic hepatitis B is still 30% to 60% within the first 5 years of life
from horizontal transmission.
 Approximately 33% of the reported hepatitis B cases have no identifiable risk
factors.

 Pathophysiology
 The HBV is unique in that it is a partially double-stranded deoxyribonucleic acid
(DNA) virus with a phospholipid layer containing hepatitis B surface antigen
(HBsAg) that surrounds the nucleocapsid.
 The nucleocapsid contains the core protein that produces hepatitis B core
antigen (HBcAg), which is undetectable in the serum.
 The exact mechanism of hepatocellular injury from hepatitis B is still
being investigated but it is thought that a cytotoxic immune reaction
occurs when HBcAg is expressed on the surface of the hepatic cells
 Fortunately, antibodies against hepatitis B core antigen (anti-HBc) are
measurable in the blood, where anti-HBc to immunoglobulin M (IgM)
indicates active infection and anti-HBc to IgG relates to either chronic
infection or possible immunity against HBV.
 Viral replication occurs when hepatitis B envelope antigen (HBeAg) is
present and circulating in the blood.
 HBV DNA is utilized to measure viral infectivity and assess and quantify
viral replication.
 Once the hepatitis B infection resolves, antibodies against
hepatitis B envelope (anti-HBe) and antibodies against hepatitis B
surface antigen (anti-HBs) develop, and HBV DNA levels become
undetectable
 However, if these antibodies do not develop, then the likelihood of
developing chronic hepatitis B increases.
 This is primarily dependent on the host’s immune system at the time the
infection was attained.
 If an individual is immunocompetent, the disease resolves
spontaneously in most cases with no further sequelae.
 In an immunocompromised person, the infection is less likely to be
eradicated.
 Natural History of Hepatitis B
 Approximately 90% of adults infected with HBV develop anti-HBs
resulting in lifelong immunity.
 About 2% develop acute infections leading to fulminant hepatitis,
which has a 60% to 90% mortality rate.
 Fifteen percent of individuals who do not develop anti-HBs develop
chronic hepatitis B.
 Of this population, the chance of developing chronic disease is less than
20% if the infection was acquired during adulthood.
 The risk of developing chronic hepatitis B increases to greater
than 40% if the infection occurred perinatally.
 It may take 20 to 40 years from the time cirrhosis is confirmed before
signs and symptoms associated with ESLD develop.
 HEPATITIS C
 Epidemiology and Etiology
 More than 170 million people are infected with hepatitis C worldwide,
and more than 4 million have the disease in the United States.
 The prevalence is higher among non-Hispanic blacks (3.2%) than non-
Hispanic whites (1.5%), and men are more likely to be infected than
women.
 Additionally, genotypes are geographically specific.
 For example, genotype 1 is commonly found in patients in the USA
whereas genotype 4 is common in the Middle East.
 Approximately 75% of those infected with HCV in the United States have
genotype 1, and about 14% and 5% have genotypes 2 and 3, respectively
 Genotype does not dictate disease severity or clinical outcomes but is
used to determine the duration of therapy and the likelihood of
therapeutic response.
 Prior to routine screening of blood products in the early 1990s, the
primary route of transmission of the HCV was blood transfusions, when
the risk was 0.02% per unit transfused.
 Since then, the risk has decreased significantly (0.001% per unit
transfused).
 Today, intravenous drug users utilizing contaminated paraphernalia are
responsible for most HCV transmission.
 Approximately 10% of the individuals infected with HCV have no
identifiable risk factors.
 Pathophysiology
 Hepatitis C, first known as non-A, non-B hepatitis, is a blood borne
infection that is a single-stranded RNA virus belonging
to the Flaviviridae family and the Hepacivirus genus.
 The true mechanism of hepatic injury is still in question, but it is
theorized that structural and nonstructural (NS) peptides may be
responsible for RNA viral replication, specifically the NS5 peptide
 Currently, there are six genotypes (numbered 1 to 6) and more than 90
subtypes (genotype 1a, 1b, 2a, 3b, etc.) that are unique to hepatitis C.
 Antibodies against HCV (anti-HCV) in the blood indicate infection with
the HCV.
 If the infection persists for more than 6 months and viral replication is
confirmed by HCV RNA levels, then the person has chronic hepatitis C.
 Chronic disease may be due to an ineffective host immune system
against the HCV.
 Cytotoxic T lymphocytes are ineffective in eradicating the HCV, thus
allowing persistent damage to hepatic cells.
 Therefore, immunocompromised individuals are less likely to eliminate
HCV.
Natural History of Hepatitis C
 Only 10% to 15% of patients have acute hepatitis C that resolves without
any further sequelae.
 In more than 85% of cases, hepatitis C develops into a chronic disease.
 Approximately 70% of chronic HCV cases progress to mild, moderate, or
severe hepatitis.
 While the natural history of the progression to cirrhosis is not clear, it is
estimated that 10% to 20% of cases may take up to 20 to
40 years from the time of exposure to advance from fibrosis to cirrhosis.
 Fifteen to twenty percent of patients infected with HCV develop
complications associated with cirrhosis.
 Once cirrhosis is confirmed, the rate of developing hepatocellular
carcinoma increases to 1% to 4% per year.
 The estimated death rate from HCV infection is 1.8 deaths per
100,000 persons per year
 HEPATITIS D
 Epidemiology and Etiology
 Hepatitis D affects approximately 15 million people worldwide.
 The highest prevalence is in southern Italy, parts of Russia, and Romania;
prevalence is moderate in northern Italy, Spain, Turkey, and Egypt.
 Southeast Asia and China have the lowest prevalence of HDV despite
having the highest prevalence of HBV infections.
 There are three major HDV genotypes that are geographically specific
 Genotype 1a primarily affects those residing in the United States, and
genotype 1b affects the Asian population.
 Both 1a and 1b are equally represented in the Mediterranean Basin.
Individuals residing in Japan and Taiwan are mostly diagnosed with
genotype 2.
 Patients in South America (specifically Colombia, Venezuela, and Peru)
are mostly infected with genotype 3.
 The most likely modes of transmitting the HDV are similar to those of HBV,
including intravenous drug users using unsterilized needles and recipients
of contaminated blood products.
 Sexual and perinatal transmission are rare for HDV.
 Pathophysiology
 Hepatitis D (originally referred to as delta hepatitis) belongs to the genus
Deltavirus of the Deltaviridae family.
 The HDV virion is a defective single-stranded circular RNA virus
that requires the presence of HBV for HDV viral replication.
 This is because the hepatitis D virus antigen (HDVAg) is coated by
the hepatitis B surface antigen (HBsAg).
 The exact mechanism of hepatic damage induced by HDV is still being
investigated, but it is known that replication of HDV cannot occur without
HBV being present causing either co-infection (both hepatitis B and D
infection occurring simultaneously) or superinfection (acquiring HDV after
having long-standing disease with HBV).
 HEPATITIS E
 Epidemiology and Etiology
 Hepatitis E is associated with more than 50% of the acute hepatitis cases
in endemic areas (Afghanistan, Bangladesh, Burma, China, India,
Indonesia, Kazakhstan, Kyrgyzstan, Malaysia, Mongolia , Nepal , Pakistan,
Tajikistan, Turkmenistan , Uzbekistan, Mexico, the Middle East, Northern
Africa, and sub-Saharan Africa).
 The virus is primarily transmitted by the fecal-oral route.
 Transmission of HEV is more prominent in underdeveloped countries
where sanitation is poor.
 The mortality rate in pregnant women with acute infections may
reach 25%.
 Rarely does HEV cause endemics in industrialized countries, where the
prevalence rate is 1% to 5%.
 Pathophysiology
 Hepatitis E is a non-enveloped single-stranded messenger RNA virus of
unclassified genus.
 The HEV is similar to HAV in that the virus is harvested in contaminated
feces, thus infecting people via the fecal-oral route.
 High HEV levels in the bile often prompt viral shedding in the feces.
 The severity of hepatic damage is dependent on the HEV strain: Mex 14,
Sar 55, or the US 2 strain.
 No cases of chronic hepatitis E have yet been documented
 CLINICAL PRESENTATION AND DIAGNOSIS
 Diagnosis of Viral Hepatitis
 Diagnosing viral hepatitis may be difficult because most infected
individuals are asymptomatic.
 Because symptoms cannot identify the specific type of hepatitis,
laboratory serologies must be obtained
 In addition, liver function tests may be obtained to assess the extent of
cholestatic and hepatocellular injury.
 However, the definitive test to determine the amount of damage and
inflammation of hepatic cells is a liver biopsy.
 Hepatitis A
 The diagnosis of hepatitis A is made by detecting immunoglobulin
antibody to the capsid proteins of the HAV.
 The presence of IgM anti-HAV in the serum indicates an acute infection.
 IgM appears approximately 3 weeks after exposure and becomes
undetectable within 6 months.

 In contrast, IgG anti-HAV appears in the serum at approximately the
same time IgM anti-HAV develops but indicates protection and lifelong
immunity against hepatitis A.
 Hepatitis B
 Hepatitis B is diagnosed when HBsAg is detectable in the serum.
 The nucleocapsid of the HBsAg contains the core protein that produces
HBcAg, which is undetectable in the serum.
 The presence of antibodies against anti-HBc to IgM indicates active
infection, and anti-HBc to IgG relates to either chronic infection or
possible immunity against HBV.
 Viral replication occurs when HBeAg is present
 Measurement of HBV DNA is used to determine viral infectivity and
assess and quantify viral replication.
 Once the hepatitis B infection resolves, anti-HBe and anti-HBs develop,
and HBV DNA levels becomes undetectable.
 Hepatitis C
 Hepatitis C is diagnosed by testing for anti-HCV in the serum.
 The disease is confirmed by the presence of HCV RNA.
 HCV RNA levels quantify viral replication and are used to determine
if antiviral treatment for HCV is effective.
 Hepatitis D
 Hepatitis D infection requires the presence of HBV for HDV viral
replication.
 Measuring HDV RNA levels in the serum by polymerase chain reaction
(PCR) confirms the presence of HDV and is the most accurate diagnostic
test.
 The presence of IgM antibodies to HDV Ag (IgM anti-HD) indicates active
disease, and IgG anti-HD also becomes detectable if the infection
does not resolve spontaneously.
 Unlike the antibodies developed against HAV, HDV antibodies do not
confer immunity.
 Hepatitis E The diagnosis of hepatitis E is based on the presence of
anti-HEV antibodies.
 A test for hepatitis E RNA levels is not yet available for commercial use
but is used in clinical trials.
 PREVENTION AND TREATMENT OF VIRAL HEPATITIS
 Desired Outcomes
 General outcomes for treating hepatitis are to: (1) prevent the spread of
the disease; (2) prevent and treat symptoms; (3) suppress viral
replication; (4) normalize hepatic aminotransferases; (5) improve
histology on liver biopsy; and (6) decrease morbidity and mortality by
preventing cirrhosis, hepatocellular carcinoma, and ESLD.
 For hepatitis B, additional treatment goals include: (1) seroconversion
or loss of HBsAg; (2) seroconversion or loss of HBeAg; and (3) achieving
undetectable HBV DNA levels.
 Additional goals for chronic hepatitis C include: (1) achieving
undetectable HCV RNA; and (2) obtaining a sustained virologic response.
 General Approach
 Managing viral hepatitis involves both prevention and treatment.
 Prevention of hepatitis A and B (and indirectly for hepatitis D) can be
achieved with immune globulin or vaccines.
 There is no specific pharmacologic treatment for acute viral hepatitis A,
B, C, D, or E; only supportive care is available.
 Individuals with mild to moderate symptoms rarely require
hospitalization.
 Occasionally, hospitalization is required in individuals experiencing
significant nausea, vomiting, diarrhea, and encephalopathy.
 Liver transplantation may be required in rare instances if fulminant
hepatitis develops.
 Patients with viral hepatitis B, C, and D may develop chronic
disease leading to ESLD.
 Treatment is only available for chronic liver disease associated with
HBV, HCV, and HDV.
 Hepatitis A Prevention
 Good personal hygiene and proper disposal of sanitary waste are required to
prevent the fecal-oral transmission of the HAV.
 This includes frequent hand washing with soap and water after
using the bathroom and prior to eating meals.
 Drinking bottled water and avoiding fruits, vegetables, and raw shellfish
harvested from sewage-contaminated water in areas where HAV is most
endemic will also minimize the risk of becoming infected with hepatitis A
 Individuals at high risk of acquiring hepatitis A should receive either serum
immune globulin or the hepatitis A vaccine,
 Immune Globulin Immune globulin (IG) is a solution containing antibodies
from sterilized pooled human plasma that provides passive immunization
against various infectious diseases, including hepatitis A.

 Immune globulin is available for either intravenous (IVIG) or
intramuscular (IGIM) administration, but only IGIM is used for
prevention of hepatitis A.
 IGIM does not confer lifelong immunity, but it is effective in providing
pre-exposure and post exposure prophylaxis against HAV.
 Adverse effects of IGIM are rare.
 There have been reports of anaphylaxis in individuals who have
immunoglobulin A deficiency after receiving repeated IG administration
 Therefore, these patients should not receive IGIM.
 IGIM is not contraindicated in pregnant or lactating women or infants
requiring hepatitis A immunization.
 The thimerosal-free preparation should be used in infants.
 IGIM should be injected into a deltoid or gluteal muscle.
 It does not affect the immune response of inactivated vaccines, oral
polio virus, or yellow fever vaccine.
 The administration of live vaccines [e.g., measles, mumps, rubella (MMR)
vaccine] concomitantly with IGIM may decrease the immune response
significantly; thus, MMR and varicella vaccine should be
delayed for at least 3 and 5 months, respectively, after IGIM has been
administered.
 Additionally, IGIM should not be given within 2 weeks of the MMR
administration or within 3 weeks of the varicella vaccine to maximize the
efficacy of the immunization
 Pre-exposure Prophylaxis
 Pre-exposure prophylaxis with IGIM is indicated for individuals at high risk
of acquiring the HAV who cannot receive the hepatitis A vaccine (e.g.,
because of allergy to the components alum or 2-phenoxyethanol).
 Additionally, travelers who plan to depart for endemic areas within 2
weeks and have not yet received the hepatitis A vaccine should receive
IGIM because active vaccine immunity takes several weeks to develop.
 The dose of the IGIM determines the duration of coverage.
 A dose of 0.02 mL/kg confers immunity against hepatitis A for
less than 3 months and doses of 0.06 mL/kg provide immunity up to 5 m
 If protection against HAV is required beyond 5 months, then
readministration of IGIM may be indicated.
 Postexposure Prophylaxis
 Individuals in contact with people infected with acute HAV, including
household and sexual partners, staff and children from day care facilities,
and food handlers of restaurant establishments may be candidates for
postexposure prophylaxis.
 The risk of infection may be decreased by 90% if IGIM is given within 2
weeks of being exposed to the hepatitis A virus.
 IGIM may still be beneficial if it is given more than 2 weeks after xposure
to a known case of HAV, as it may decrease the severity of hepatic damage
 Hepatitis A Vaccine
 Persons at risk of acquiring the HAV should receive the hepatitis A vaccine
when appropriate.
 There is no benefit in administering the vaccine after a person has been
exposed to the HAV.
 Two inactivated hepatitis A vaccines , Havrix and VAQTA, are available in
the United States and are effective in providing active immunization.
 The major difference between the two vaccines is that HAVRIX contains
2-phenoxyethanol as a preservative whereas VAQTA is preservative-
free
 Either vaccine is effective in providing active pre-exposure prophylaxis
when given in two injections 6 months apart (referred to as months 0
and 6).
 The two vaccines are considered interchangeable, and doses are
 dependent on age
 Efficacy is defined by measuring antibody response.
 For HAVRIX, levels greater than 20 mIU/mL measured with the modified
enzyme immunoassay, and for VAQTA, levels greater than 10 mIU/mL
measured with the modified radioimmunoassay are considered
protective
 After the first dose of vaccine has been administered, 94% to 100% of
adults and 97% to 100% of children and adolescents develop protective
antibody concentrations against the HAV.
 All recipients over the 2 years of age receiving the second dose at month
6 have 100% antibody coverage, √√ therefore, post vaccination
measurement of antibody response is not required.
 The hepatitis A vaccine may provide effective immunity for 8 years in
adults and children.
 Additionally, kinetic models have theorized that immunity with the
vaccine may be longer than 20 years, but this has not been confirmed in
clinical trials.
 The most common adverse effects in adults include injection site
reactions (e.g., tenderness, pain, and warmth), headaches within 5 days
after vaccination, and fatigue.
 Local reactions may be minimized by using an appropriate needle length
based on the person’s age and size and by administering the injection
intramuscularly in the deltoid muscle.
 Children may also have feeding disturbances.
 Hepatitis A vaccine given during pregnancy has not been evaluated in
clinical trials.
 Since both brands of vaccine are made from inactivated HAV, the risk of
developing fetal complications should be minimal.
 Hepatitis B Prevention
 Individuals may minimize their risk of acquiring the hepatitis B infection
by avoiding contaminated blood products or indulging in high-risk
behavior such as intravenous drug use.
 In addition, those who are at high risk of acquiring the HBV should be
vaccinated with the hepatitis B vaccine.
 In some cases, postexposure prophylaxis with hepatitis B immune
globulin (HBIG) may be recommended to prevent the development of
acute infection and complications associated with HBV.
 Hepatitis B Vaccine
 The two hepatitis B vaccines available in the United States are
Recombivax HB and Engerix-B.
 These vaccines are produced with recombinant DNA technology by
inserting the gene for HBsAg into the plasmid that is synthesized by
Saccharomyces cerevisiae cells.
 Both vaccines are effective in providing protection against acquiring the
HBV when the immunization is given at months 0, 1, and 6.
 The two non-dialysis formulations of the hepatitis B vaccines are
considered interchangeable, but the same brand should be used for the
entire three-dose series.
 Additionally, the doses depend on the person’s age .
 The difference between the two vaccines is that Engerix-B contains trace
amounts of thimerosal that is not used as a preservative but is produced
during the manufacturing process; Recombivax HB is completely free of
thimerosal.
 For optimal response, the hepatitis B vaccine should be administered
intramuscularly only (into the anterolateral thigh region in neonates and
infants; the deltoid region in adults) and not IV or intradermally.
 The vaccine should not be given in the gluteal region, as it may
result in lower rates of immunity.
 In rare cases, the vaccine may be given subcutaneously in individuals at
risk for hemorrhage (e.g.,hemophiliacs ); however, this route of
administration should be used with caution, as subcutaneous nodules
have developed when other similar vaccines have been used.
 The efficacy of the hepatitis B vaccine is established when antibody
concentrations are greater than 10 mIU/mL.
 After completing the vaccination series given at months 0, 1, and 6, 96%
of recipients obtain adequate antibody levels; for this reason, post
vaccination testing is not usually recommended.
 However, protective antibody levels may be decreased in
immunocompromised patients (e.g., human immunodeficiency virus
(HIV)-positive, hemodialysis, or immunosuppressive therapy); post
vaccine testing may be warranted 1 to 6 months after completing the
vaccination series in these patients.
 The duration of immunity and whether a booster dose of the hepatitis
B vaccine is required are still being investigated.
 The most frequent adverse effects are local reactions at the injection site
(pain, tenderness, erythema, swelling, and pruritus), fevers (greater than
37.5°C or 99.5°F), headaches, dizziness, and irritability.
 Anaphylaxis and hypersensitivity reactions have been reported rarely and
occur within a few hours after vaccine administration.
 In rare instances, a serum sickness–like apparent hypersensitivity
syndrome (arthralgia, urticaria, ecchymoses, erythema multiforme, and
erythema nodosum) has been reported days to weeks postvaccination
 Hepatitis B vaccine given during pregnancy has not been evaluated in
clinical trials.
 However, if the mother is at risk of acquiring the hepatitis B virus,
then vaccination should be considered.

 Hepatitis A and B Combination Vaccine

 A vaccine that combines both inactivated hepatitis A and recombinant
hepatitis B (Twinrix) is approved for immunizing individuals greater than
18 years of age with indications for both hepatitis A and B vaccines.
 A 1 mL dose of Twinrix contains the antigenic components of not less
than 720 ELISA units of Havrix and 20 mcg of recombinant HBsAg protein
of Engerix-B and should be administered at months 0, 1, and 6.
 2-Phenoxyethanol is used as a preservative, and trace amounts of
thimerosal are present due to the manufacturing process.
 Antibody seroconversion for hepatitis A and B was greater than 98% in
adult volunteers tested 1 month after a three-dose vaccine series.
 The side-effect profile of Twinrix is similar to giving each vaccine separately.
 Postexposure Prophylaxis
HBIG and hepatitis B vaccine are indicated after exposure to the
HBV to prevent chronic hepatitis B disease. The dose and
immunization regimen depend on how the individual acquired
the virus.8 Adults acutely exposed to blood containing HBsAg
from an accidental needlestick, sexual contacts, or intravenous
drug use should be immunized based on the source of exposure
and the vaccination status of the exposed person (Table 21–5).A
single dose of HBIG of 0.06 mL/kg is 75% effective in preventing
chronic hepatitis B infections if administered within 14 days
of exposure.
 Postexposure prophylaxis for perinatal exposure depends upon the
mother’s HBsAg status.
 Mothers who are HBsAg positive should have their newborns
immunized with both the hepatitis B vaccine and HBIG 0.5 mL.
 This regimen is 85% effective in preventing the hepatitis B carrier
status if administered within 24 hours of birth.
 If the mother is HBsAg negative, the newborn should be given only the
hepatitis B vaccine
 Chronic Hepatitis B Treatment
 Persons with confirmed chronic hepatitis B should be evaluated for
treatment, which may include interferon, pegylated interferon,
lamivudine, adefovir dipivoxil, or entecavir.
 The drug of choice for chronic hepatitis B depends on the patient’s past
medical history, aminotransferase level, HBV DNA level, and most
importantly, HBeAg status.
 Patients who are hepatitis B carriers (defined as having a positive HBsAg,
normal alanine aminotransferase (ALT) levels, and negative HBeAg)
should not be treated because hepatitis B antiviral agents rarely
result in HBeAg seroconversion, and long-term treatment leads to drug
resistance.
 Patients with elevated ALT and HBV DNA levels (regardless of the
presence or absence of HBeAg) require treatment to delay progression
to cirrhosis and prevent the development of ESLD.
 The treatment response for a patient who is positive for HBeAg is
different from that of a patient who is negative for HBeAg because
obtaining seroconversion is less likely to occur.
 Interferon and Peyglated Interferon
 Interferon alfa is an antiviral agent that is effective in suppressing
hepatitis B viral replication.
 Interferon alfa-2b and pegylated interferon alfa-2a are the only
interferon therapies approved for the treatment of chronic hepatitis B.
 Interferon therapy has an advantage over other antiretroviral treatment
in that it is effective in suppressing, and in some cases ceasing, viral
replication without inducing resistance.
 Approximately one-third of HBsAg-positive patients become
seronegative after 4 to 6 months of treatment.
 The HBeAg seroconversion rate is 18% greater than those who are not
treated.
 Additionally, the durability (likelihood of developing and sustaining
HBeAg seroconversion) is greater than 80% after treatment has been
discontinued.
 If interferon treatment duration is extended to 12 to 24 weeks, HBsAg
loss is observed in about 10% of patients.
 Pegylated interferon is interferon that is attached to a PEG molecule
that increases the half-life of the drug, thus allowing once-weekly
dosing versus thrice-weekly administration required for the unmodified
formulation.
 Pegylated interferon is well tolerated and is superior in efficacy
to unmodified interferon for the treatment of chronic hepatitis B.
 Patients with chronic hepatitis B who are HBeAg-negative may achieve
undetectable HBV DNA levels and normalize ALT levels during treatment with
any of the antiviral therapies; however, once treatment has ceased, these
endpoints return to pretreatment values.
 Patients treated with unmodified interferon have an end-of-treatment
response (defined as undetectable HBV DNA and normal ALT levels) ranging
from 60% to 70%; however, the rate of sustaining virologic
response once therapy has been discontinued is approximately 20%
 Patients with HBeAg-negative chronic hepatitis B should be treated with
more than 12 months of therapy.
 When the duration of interferon therapy is prolonged beyond 12 months,
undetectable HBV DNA may be sustained, as well as increasing the chance of
losing HBsAg.
 Factors associated with a higher likelihood of response to interferon therapy
are baseline HBV DNA levels less than 200 pg/mL and ALT concentrations
greater than 5 times the upper limit of normal.
 The subcutaneous dose of interferon alfa-2b (Intron A) in patients who
are HBsAg-positive is either 5 million units daily (better tolerated) or 10
million units three times weekly.
 The dose for HBsAg-negative patients is 5 to 6 million units three times
weekly.
 The approved dose for pegylated interferon alfa-2a (Pegasys) for
chronic hepatitis B is 180 mcg subcutaneously once weekly.
 Interferon doses may need to be adjusted in patients with renal
impairment.
 Even though the advantages of interferon therapy include a finite
duration of treatment, lack of resistance, and possible HBsAg loss or
seroconversion (development of anti-HBs), there are several significant
disadvantages.
 These include the need for subcutaneous injections, and more
importantly, the pronounced adverse-effect profile that may require
treatment discontinuation.
 The most common complaints include injection site reactions and flulike
symptoms of fevers, chills, joint pain, and muscle aches.
 Systemic adverse effects include anorexia, nausea, diarrhea, fatigue,
headache, insomnia, irritability, depression, alopecia, and dermatitis.
Hematologic abnormalities are common including neutropenia, anemia,
and thrombocytopenia, which require either a dose reduction or
treatment discontinuation.
 Uncommon side effects include cardiac arrhythmias, diabetes, thyroid
disorders, amenorrhea, and vision disturbances.
 Lamivudine
 Lamivudine (Epivir-HBV) is an oral synthetic cytosine nucleoside analogue
having antiviral effects against HIV and hepatitis B virus.
 In patients with chronic hepatitis B, lamivudine is effective in suppressing
hepatitis B viral replication, normalizing ALT levels, and improving liver
histology.
 Patients with HBeAg-positive chronic hepatitis B may have a similar or a
superior response in achieving these endpoints when compared
to interferon.
 A significant loss of serum HBV DNA level was observed in 44% of
subjects receiving lamivudine compared to 16% receiving placebo.
 Normalization of ALT levels and improvement in histology occurred in
approximately 50% of patients with HBeAg-positive hepatitis B.
 HBeAg loss, 18% at the end of 52 weeks of treatment, is quite similar
between interferon and lamivudine.
 However, prolonged lamivudine therapy may be needed to sustain
seroconversion, as durability of response is only 50% to 80%.
 Extending the duration of treatment is not without consequences, as
lamivudine resistance has been reported at 14% after 1 year of treatment
and increases to 70% at 5 years.
 Compared to those treated with placebo, 60% to 70% of patients with
HBeAg-negative hepatitis B treated with lamivudine for 52 weeks have
undetectable HBV DNA levels and normalization of ALT levels.
 However, the rate of relapse is 80% to 90% once the treatment has been
discontinued.
 Lamivudine therapy beyond 12 months may be considered to sustain
response, but biochemical and virologic breakthrough commonly occurs
due to the development of drug resistance.
 Adverse effects are minimal and include fatigue, diarrhea, nausea,
vomiting, and headaches.
 In rare cases, pancreatitis, hepatomegaly, and potentially fatal lactic
acidosis have been reported.
 ALT levels should be monitored carefully, especially when lamivudine has
been discontinued, as an elevation may indicate a flare in disease activity
that may lead to liver failure.
 The advantages of lamivudine over interferon are oral administration and
low drug cost with minimal adverse effects.
 The major disadvantage is the prolonged treatment duration required to
achieve and sustain HBeAg and HBsAg seroconversion.
 Even so, this approach increases the drug resistance rate significantly
with each additional year of treatment.
 Adefovir Dipivoxil
 Adefovir dipivoxil (Hepsera) is a prodrug of adefovir, an adenosine
nucleotide analog that inhibits DNA polymerase.
 It is effective against HIV and HBV, specifically lamivudine resistant HBV
 Unlike lamivudine, extending the duration of adefovir dipivoxil therapy
resulted in a relatively low resistance rate, approximately 11% after 3
years.
 The percentage of seroconversion and loss of HBeAg are comparable
to patients who received lamivudine.
 The dose of adefovir dipivoxil is 10 mg once daily.
 The most common side effects include asthenia, abdominal pain,
diarrhea, dyspepsia, headaches, nausea, and flatulence. Lactic acidosis,
pancreatitis, and hepatomegaly have been reported rarely.
 Unlike lamivudine, adefovir dipivoxil is associated with dose-related
nephrotoxicity, which was most commonly seen in HIV patients receiving
doses larger than 60 mg
 Entecavir
 Entecavir (Baraclude) is a guanosine nucleoside analogue that inhibits
HBV DNA polymerase, thereby inhibiting DNA replication.
 Unlike the other two oral antiretroviral agents, entecavir has no activity
against HIV and is only effective against HBeAg-positive, HBeAg-negative,
and lamivudine-resistant chronic hepatitis B.
 Hepatitis C Prevention
 The risk factors for hepatitis C and hepatitis B are quite similar; thus, the
risk of acquiring the HCV is minimized by avoiding contaminated blood
products and high-risk behaviors such as sharing needles among
intravenous drug users.
 No vaccines are available for preventing hepatitis C.
 However, individuals at high risk should be tested for the hepatitis C virus
because the disease presents asymptomatically.
 Chronic Hepatitis C Treatment
 Individuals with confirmed chronic hepatitis C should be evaluated for
treatment with pegylated interferon with or without ribavirin.
 Interferon or Peyglated Interferon plus Ribavirin
 Interferon alfa-2a (Roferon A), interferon alfa-2b (Intron-A),and
interferon alfacon-1 (Infergen) are approved for chronic hepatitis C.
 However, they are not prescribed alone because only 12% to 16% of
patients achieve a sustained virologic response (SVR).
 Adding ribavirin, a synthetic guanosine analogue that inhibits viral
polymerase, increases the SVR rate to 35% to 45%.
 At present, pegylated interferon plus ribavirin is the regimen
of choice for the treatment of hepatitis C.
 Most patients treated with either interferon or pegylated interferon
experience flulike symptoms (fevers, chills, rigors, and myalgias).
 These symptoms may be mild to moderate in severity and usually occur
with the first injection and diminish as the treatment continues.
 The flulike symptoms may be minimized by premedication with
acetaminophen or a nonsteroidal anti-inflammatory drug.
 Psychiatric adverse effects occur frequently and may include irritability,
depression, and rarely, suicidal ideation.
 Individuals with a history of uncontrolled psychiatric disorders must
weigh the risk versus benefit of treatment, as interferon may exacerbate
or worsen the psychiatric condition.
 Patients who develop mild to moderate symptoms may require
antidepressants or anxiolytics.
 Prevention and treatment of viral hepatitis may prevent progression
to chronic hepatitis, cirrhosis, and end-stage liver disease.
 There is no specific pharmacologic treatment for acute viral hepatitis A,
B, C, D, or E; only supportive care is available.
 Good personal hygiene and proper disposal of sanitary waste are
required to prevent the fecal-oral transmission of the hepatitis A virus.
 Individuals may minimize their risk of acquiring both hepatitis B
and C infection by avoiding contaminated blood products and
not indulging in high-risk behavior such as intravenous drug use.
 Persons at high risk of acquiring the hepatitis B virus should be
vaccinated with the hepatitis B vaccine at months 0, 1, and 6.
 A vaccine that combines both inactivated hepatitis A and recombinant
hepatitis B (Twinrix) is approved for immunizing individuals greater than
18 years of age with indications for both hepatitis A and B vaccines.
 The drug of choice for chronic hepatitis B depends on the patient’s past
medical history, aminotransferase level, HBV DNA level, and most
importantly, HBeAg status.
 Hepatitis D infection is possible only if the patient also has the hepatitis
B virus present; therefore, hepatitis B vaccination can indirectly prevent
hepatitis D infection.