HEPATITIS VIRUSES

3.6
December 3, 2014
Dr. Bunyi

Approximately 40% of acute cases of hepatitis are caused

REFERENCE/S: by HAV
Jawetz chap 35, Trans 2016 Most infected people are contagious 10 to 14 days before
symptoms occur
OUTLINE: Children are asymptomatic (90%); adults have inapparent
I. Hepatitis Viruses but productive infections (25-50%)
II. Hepatitis A Spread via fecal-oral route - in contaminated water, food,
III. Hepatitis B and dirty hands
IV. Hepatitis C Raw or improperly treated sewage can taint the water
V. Hepatitis D supply and contaminate shellfish (which are filter feeders
VI. Hepatitis E that concentrate viral particles)
VII. Hepatitis virus infections in humans
HAV outbreaks originate from a common water source
a. Pathology
b. Clinical Findings Because children are usually do not show symptoms, the
c. Virus-Host Interactions number of contacts at risk for HAV infection from day-
VIII. Treatment and Prevention cares are great
IX. Tables, Figures Poor hygiene and overcrowding - increased risk of spread

HEPATITIS VIRUSES CONTROL, PREVENTION, AND TREATMENT

Produces acute inflammation of the liver Avoiding potentially contaminated water
o Fever Cook shellfish properly
o Nausea & vomiting Proper hand washing
o Icteric symptoms of jaundice Chlorine treatment of water is sufficient
o Release of liver enzymes Prophylaxis with immune serum globin before the
HAV infectious hepatitis incubation period
HBV serum hepatitis Inactivated HAV vaccine
HCV post-transfusion hepatitis
HDV defective virus dependent on HBV HEPATITIS TYPE B
HEV -- agent of enterically transmitted hepatitis
Regardless of the virus type histopathologic lesions are Properties, Laboratory Features, Epidemiology
identical in acute disease
PROPERTIES
HEPATITIS TYPE A Classified as hepadnavirus
Distinct member of picornaviruses Establishes chronic infections, especially those infected as
Genus Hepatovirus infants
Major factor in the development of liver disease and
PROPERTIES hepatocellular carcinoma
27-32 nm spherical virions with cubic symmetry
Naked, icosahedral capsid Heat and acid stable Structure and Composition
(+) ssRNA Has three morphologic forms
One serotype One time infection causes lifelong Most numerous are spherical particles measuring 22nm in
immunity diameter
Seven genotypes Made up exclusicely of HBsAg- as are tubular or
5 end VPg protein filamentous forms
3 end polyadenylate sequence Larger, 42nm spherical virions (aka Dane Particles) are
Stable to treatment with 20% ether, acid (pH 1.0 for 2 less frequently observed
hours), and heat (60C for 1 hour), Envelope contains HBsAg and surrounds a 27-nm inner
Infectivity can be preserved for at least 1 month after nucleocapsid core that contains hepatitis B core antigen
being dried and stored at 25C or for years at 20C. (HBcAg)
Susceptible to: high temperature, UV, formalin, and Viral genome consists if partially ds circular DNA, 3200 bp
chlorine in length
Most HBV isolates share 90-98% nucleotide sequence
PATHOGENESIS homology
Virions are ingested and enter bloodstream The full-length DNA (-) strand is complementary to all HBV
Reach liver parenchyma mRNAs
Replicate in hepatocytes and Kupffer cells producing insults The (+) strand (S or short strand) is variable and between
Virions are released into the bile and to the stool 50% and 80% of unit length
Features are indistinguishable from HBV infection
No chronic infection and not associated with cancer
CLINICAL FINDINGS
CLINICAL FINDINGS Incubation Period: 50-180 days (Ave. 60-90 days)
Initial symptoms include fever, fatigue, nausea, loss of Principal age distribution: 15-29 years, babies
appetite, and abdominal pain Seasonal incidence: Throughout the year
Dark urine (bilirubinuria), pale stool, and then jaundice Route of Infection: Predominantly parenteral
may be accompanied by abdominal pain and itch. Occurence of Virus:
Symptoms wane during the jaundice period. Blood- Months to years
Viral shedding in the stool precedes the onset of Stool- Absent
symptoms by approximately 14 days but stops before the Urine- Absent
cessation of symptoms. Saliva, semen- Frequently present
Complete recovery occurs 99% of the time within 2 to 4 Clinical and laboratory features
weeks of onset. o Onset- Insidious
Mortalities are due to fulminant hepatitis which occur in o Fever > 38 degrees Celsius (100.4 degrees
2-3/1000 with HAV (80% mortality) Fahrenheit)- Less common
o Duration of aminotransferase elevation- 1-6+
EPIDEMIOLOGY months

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MICROBIOLOGY // Hepatitis Viruses 3.6
o IgM Levels- Normal to slightly elevated As adults, they are subject to liver disease and are at
o Complications- Chronicity in 5-10% (95% of high risk of developing hepatocellular carcinoma
neonates) There is a high burden of HBV infections among HIV-
o Mortality rate (icteric cases)- <1-2% infected people
o HBsAg- Present Major modes of transmission during infancy:
o From infected mother to her newborn during
Immunity delivery
o From an infected household contact to an
o Homologous- Yes infant
o Heterologous- No There is no seasonal trend for HBV infections and no
o Duration- Probably lifetime high predilection for any age group
High risk groups:
Immune globulin intramuscular- Prevents jaundice o Parenteral drug users
only if immune globulin is of sufficient potency against o Institutionalized people
HBV o Health care personnel
o Multiply transfused patients
o Organ transplant patients
o Hemodialysis patients and staff
LABORATORY FEATURES o Highly promiscuous persons (*ehem*)
o Newborn infants born to mothers with
ASSAY RESULTS INTERPRETATION hepatitis B
HBsAg Anti-HBs Anti-HBc
Positive Negative Negative Early acute HBV FEATURE Transmission
infection. VERTICAL CONTACT PARENTERAL
Confirmation is (ASIA) (AFRICA) , SEXUAL
required to exclude AGE AT Newborns, Young Teenagers,
nonspecific INFECTION infants children Adults
reactivity
Positive (+) Positive HBV infection ,
either acute or RECOVERY 5 20 90-95
chronic. FROM ACUTE
Differentiate with INFECTION
IgM anti-HBc. (%)
Determine level of
replicative activity
(infectivity) with PROGRESSIO 95 80 5-10
HBeAg or HBV N TO
DNA CHRONIC
Negative Positive Positive Indicates previous INFECTION
HBV infection and (%)
immunity with
hepatitis B
Negative Negative Positive Possibilities
CHRONIC 10-20 10-20 0.5
include: HBV
CARRIERS
infection in remote
(%TOTAL
past; low level
POPULATION)
HBV carrier;
window between
disappearance of
HBsAg and
appearance of anti-
HBs; or false-
positive or non-
specific reaction.
Investigate with
IgM anti-HBc .
When present, anti-
HBe helps validate
the anti-HBc
reactivity HEPATITIS TYPE C
Negative Negative Negative Never infected with Family Flaviviridae (genus
HBV. Possibilities Hepcivirus)
include another Genome (+) RNA, 9.4 kb in size and
infectious agent, encodes a core protein, two
toxic imjury to liver, envelope glycoproteins and
disorder of several nonstructural
immunity, proteins
hereditary disease Most cases of post transfusion NANB (non A or non B)
of the liver , or were caused by HCV.
disease of the
Most new infections with HCV are subclinical.
biliary tract
Majority (70 90%) of HCV patients develop chronic
Negative Positive Negative Vaccine-type
hepatitis, and many are at risk of progressing to chronic
response
active hepatities and cirrhosis (10- 20%)
Displays a genomic diversity, with different types (clades)
EPIDEMIOLOGY
predominating in different parts of the world.
Undergoes sequence variation during chronic infections
Worldwide in distribution Quasi- species (complex viral population in the host)
Transmission modes and response to infection vary, JAPAN: leads to Hepatocellular carcinoma
depending on the age at the time of infection CLINICAL FEATURES
Most individuals infected as infants develop chronic Incubation period Average: 6- 7 weeks
infections Range: 2- 26 weeks

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MICROBIOLOGY // Hepatitis Viruses 3.6
Clinical illness 30- 40% (20- 30%) HCV was found in saliva from more than a third of
(jaundice) patients with HCV and HIV coinfections.
Chronic hepatitis 70 90% HCV has been transmitted by commercial intravenous
immune globulin preparations, including an outbreak
Persistent infection 85- 100% in the United States in 1994.
Immunity No protective antibody response HCV infection has been associated with tattooing and,
identified in some countries, with folk medicine practices.
IP: 6-7wks
Clinically mild, with only minimal to moderate elevation of
The average time from exposure to seroconversion is
liver enzymes
89 weeks, and about 90% of patients are anti-HCV-
Most patients are asymptomatic, (20-30% have jaundice,
positive within 5 months
10-20% have only nonspecific symptoms such as anorexia,
malaise, and abdominal pain) HEPATITIS TYPE D
End-stage liver disease assoc with HCV is the most Family No assigned family
frequents indication for adult liver transplant Deltavirus genus
CHRONIC HEPATITIS C INFECTION Genome Single stranded, circular,
negative-sense RNA, 1.7
The spectrum of chronic hepatitis C infection is essentially
the same as chronic hepatitis B infection kb in size
Other characteristics Defective virus that acquires
All the manifestations of chronic hepatitis B infection may
be seen, albeit with a lower frequency HBsAg coat for transmission
i.e. chronic persistent hepatitis, chronic active hepatitis, Smallest known human pathogens and resembles
cirrhosis and hepatocellular carcinoma subviral plant pathogens (viroids)
Diseases associated: Mixed cryoglobulinemia and GN HDAg (Hepa D Antigen) is the only protein coded for by
HDV RNA and is distinct from the antigenic determinants of
Laboratory HBV.
HCV Generally used to diagnose hepatitis C It is associated with the most severe forms of hepatitis in
antibody infection HbsAg- positive patients
Not useful in the acute phase as it takes at
least 4 weeks after infection before antibody CLINICAL FEATURES
appears 1. Coinfection
Severe acute disease
HCV-RNA Various techniques are available e.g. PCR Low risk of chronic infection
and branched DNA 2. Superinfection
May be used to diagnose hcv infection in the
May present as an acute hepatitis
acute phase
Usually develop chronic HDV infection
However, its main use is in monitoring the
response to antiviral therapy High risk of severe chronic liver disease
Laboratory
Hcv-antigen An EIA for HCV antigen is available Depends on HBV infection
It is used in the same capacity as HCV-RNA o Occurs either as a simultaneous infection
tests but is much easier to carry out (couinfection) with HBV or as a
superinfection of aperson chronically
EIA detects antibodies to HCV but do not distinguish
between acute, chronic, or resolved infection. Coinfection
Anti-HCV abs can be detected in 50-70% of patients at Antibody to HDAg develops late in the acute phase of
onset of symptoms, whereas in others antibody infection and may be of low titer
appearance is delayed 3-6 weeks. All markers of HDV replication disappear during
Abs are directed against core, envelope and NS3 and convalescence
NS4 proteins and tend to be relatively low in titer HDV abs may disappear within months to years
Nucleic-acid based assays (reverse transcription Superinfection
polymerase chain reaction) detect the presence of Results in persistent HDV infection (over 70% cases)
circulating HCV RNA and are useful for monitoring patients High levels of both IgM and IgG anti- HD persist, as
on antiviral therapy; also used to genotype HCV isolates do levels of HDV RNA and HDAg.
Occult (those in which the patients lack detectable HbsAg May be associated with fulminant hepatitis.
but HBV DNA can be identified in liver or serum samples)
HBV infections occur frequently in patients with chronic Interpretation of HAC, HCV and HDV Serologic Markers in
HCV liver disease. Patients with Hepatitis
ASSAY RESULTS INTERPRETATION
Epidemiology Anti-HAV IgM (+) Acute infection with HAV
Transmission Anti-HAV IgG (+) Past infection with HAV
Risk factors
Anti-HCV (+) Current or past infection with
o Transfusion or transplant from infected donor
HCV
o Injecting drug use
o Hemodialysis (years on treatment) Anti-HDV (+), Infection with HDV
o Accidental injuries with needle sharps HBsAg (+)
o Sexual household exposure to anti-HCV-positive Anti-HDV (+), Coinfection with HDV and
contact anti-HBc IgM (+) HBV
o Multiple sex partners
o Birth to HCV-infected mothe Anti-HDV (+), Superinfection of chronic
anti-HBc IgM ( ) HBV infection with HDV
HCV is transmitted primarily through direct
percutaneous exposures to blood, though in 1050% Epidemiology
of cases the source of HCV cannot be identified
Found throughout the world but with nonuniform distribution
In roughly decreasing order of prevalence of infection
Persons who have received multiple transfusions,
are injecting drug users (about 80%), hemophiliacs
intravenous drug abusers and their close contacts are at
treated with clotting factor products before 1987,
high risk
recipients of transfusions from HCV-positive donors,
Primary routes of transmission similar to HBV although it
chronic hemodialysis patients (10%), persons who
does not appear to be a sexually transmitted disease.
engage in high-risk sexual practices, and health care
workers (1%). Infecton depends on HBV replication because HBV
probides an HBsAg envelope for HDV.
No risk of transmission has been associated with
breast feeding.

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MICROBIOLOGY // Hepatitis Viruses
IP: 2-12 weeks being shorter in HBV carriers who are
superinfected with the agent than in susceptible persons
who are simultaneously infected with both HEV and HDV.
Transmitted perinatally but not prevalent in regions (eg
Asia) where perinatal transmission of HBV occurs
frequently.
In nonendemic areas, US and norther Europe, delta
infection is confined to persons exposed frequently to blood
and blood products primarily drug addicts and individuals
with hemophilia
In Mediterranean countries:
o Delta infection is endemic among persons wit heap
B and most infections are thought to be transmitted
by intimate contact.
Occurs in explosive outbreaks and affect entire localized
pockets of hepatitis B carriers.
Outbreaks of seere, often fulminant and chronic delta
hepatitis have occurred for decades in isolated populations
in the Orinoco and Amazon basins of South America
HEPATITIS TYPE E
Family Hepeviridae, Hepevirus genus
Genome Positive sense, single stranded RNA
7.2 kB in size
Other
Resembles calciviruses
characteristics
Transmtted enterically and occurs in
epidemic form in developing countries,
where water or food supplies are
sometimes fecally contaminated
Pregnant women may have a high (20%) mortality rate if
fulminant hepatitis develops.
There is evidence of HEV or HEV- like infections in rodents,
pigs, sheep and cattle in the US.
There is the possibility of spread of virus from animals to
humans.
Laboratory Features
Minimal person-to-person transmission
CLINICAL FEATURES
Incubation period Average: 40 days
Range: 15- 60 days
Case- fertility rate Overall 1-3%
Pregnant women 15- 20%
Chronic sequelae None identified
Epidemiology
Most outbreaks associated with faecally contaminated
drinking water.
Several other large epidemics have occurred since in the
Indian subcontinent and the USSR, China, Africa and
Mexico.
In the United States and other nonendemic areas, where
outbreaks of hepatitis E have not been documented to occur,
a low prevalence of anti-HEV (<2%) has been found in
healthy populations. The source of infection for these
persons is unknown.
HEPATITIS VIRUS INFECTIONS IN HUMANS
PATHOLOGY
Hepatitis general term for inflammation of theliver
Microscopic: spotty parenchymal celldegeneration,
necrosis of hepatocytes, diffuse lobularinflammatory
reaction, and disruption of liver cell cords
Parenchymal changes are accompanied by
reticuloendothelial(Kupffer) cell hyperplasia, periportal
infiltration bymononuclear cells, and cell degeneration
Localized areas ofnecrosis are frequent
Later in its course, there is an accumulation of
macrophages near degeneratinghepatocytes
Preservation of the reticulum frameworkallows hepatocyte
regeneration so that architecture of the liver lobule can be
regained
Damaged hepatic tissue is usually restored in 812 weeks
Chronic carriers of HBsAg may or may not
havedemonstrable evidence of liver disease
o Persistent (unresolved)viral hepatitis
o Mild benign disease that mayfollow acute hepatitis
B in 810% of adult patients
Balamban, Bolintiam, Brodith, Dueas, Justo, Parugao, Yu
3.6
o Sporadically abnormal aminotransferase values
and hepatomegaly
o Lobular architectureis preserved, with portal
inflammation, swollen and palehepatocytes
(cobblestone arrangement), and slight to
absentfibrosis
o Lesion is frequently observed in
asymptomaticcarriers, usually does not progress
toward cirrhosis, favorable prognosis
Chronic active hepatitis
o Inflammation, necrosis, collapse of thenormal
reticulum framework with bridging between the
portaltriads or terminal hepatic veins
o HBV is detected in 1050% ofthese patients
Fulminant or massive hepatocellular necrosis
o Occasionally during acute viral hepatitis, more
extensivedamage occurs that prevents orderly liver
cell regeneration
o Seen in 12% of jaundiced patients with HBV
o 10 times more common in those coinfected with
HDV
o None of the hepatitis viruses are typically
cytopathogenic,it is believed that the cellular
damage is immune-mediated
Both HBV and HCV have significant roles in the
developmentof hepatocellular carcinoma that may appear
many(1560) years after establishment of chronic infection
CLINICAL FINDINGS
Viral Hepatitis
Onset of jaundice often precededby gastrointestinal
symptoms such as nausea, vomiting,anorexia, and mild
fever
Jaundice may appear within a fewdays of the prodromal
period, but anicteric hepatitis is morecommon
Uncomplicated viral hepatitis rarely continues for more
than 10 weeks without improvement
Relapses occur in 520% of cases manifested by
abnormalities in liver function with or without the
recurrence of clinical symptoms
Median incubation period is different for each type of viral
hepatitis, but there is overlap, and the patient may not
know when exposure occurred, so the incubation period is
not useful in determining the specific viral cause
In individual cases, it is not possible to make a reliable
clinical distinction among cases caused by the hepatitis
viruses
Extrahepatic manifestations of viral hepatitis
(primarilyHBV) include a transient serum sickness-like
prodromeconsisting of fever, skin rash, and polyarthritis;
necrotizingvasculitis (polyarteritis nodosa); and
glomerulonephritis
o Circulating immune complexes have been
suggested as thecause
HAV
Extrahepatic manifestations are unusual
Complete recovery occurs in most cases; chronicity has
not been observed
More severe in adults;often unnoticed in children
Relapses of HAV infection can occur14 months after
initial symptoms have resolved
HBV
Outcome varies, rangingfrom complete recovery to
progression to chronic hepatitis,anddeath from fulminant
disease
In adults, 6580%of infections are inapparent, with 90
95% of all patientsrecovering completely
8095% of infants andyoung children infected become
chronic carriers, and their serum remains positive for
HBsAg
Majority of chronic HBV remain asymptomaticfor many
years; there may or may not be biochemicaland histologic
evidence of liver disease
Chronic carriers are athigh risk of developing
hepatocellular carcinoma
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MICROBIOLOGY // Hepatitis Viruses
HCV
Usually clinically mild
Minimal tomoderate elevation of liver enzymes
Hospitalization is unusual,and jaundice occurs in fewer
than 25% of patients
7090% of cases progress to chronicliver disease
40% of chronic liver disease is HCV related
Most are asymptomatic, but histologicevaluation reveals
evidence of chronic active hepatitis,especially ifacquired
after transfusion
Many develop cirrhosis and are at high riskfor
hepatocellular carcinoma decades later
End-stageliver disease associated with HCV is the most
frequent indicationfor adult liver transplants
Diseases associated with chronic HCV infections include
mixed cryoglobulinemia and glomerulonephritis
Fulminant Hepatitis
Occasionally develops during acute viral hepatitis
Hepatic encephalopathy within the first 8 weeks of disease
in patients without preexisting liver disease
Fatal in 7090% of cases, survival uncommon after the
age of 40 years
Fulminant HBV disease is associated with superinfection
by other agents, including HDV
In most who survive, complete restoration of the hepatic
parenchyma and normal liver function is the rule
Rarely occurs with HAV or HCV infections
Other viral diseases that may present as hepatitis:
infectious mononucleosis, yellow fever, cytomegalovirus
infection, herpes simplex, rubella, and some enterovirus
infections
Hepatitis may occasionally be a complication of
leptospirosis, syphilis, tuberculosis, toxoplasmosis, and
amebiasis, all of which susceptible to specific drug therapy
Noninfectious causes: biliary obstruction, primary biliary
cirrhosis, Wilson disease, drug toxicity, and drug
hypersensitivity reactions
VIRUS-HOST INTERACTIONS
There is evidence for five hepatitis virusestypesA, B, C,
D, and E
A single infection with any is believed toconfer
homologous but not heterologous protection
againstreinfection
o Exception may be HCV; reinfectionwith HCV may
occur
HAV
Most cases of hepatitis type A presumably occur
withoutjaundice during childhood, and by late adulthood
thereis a widespread resistance to reinfection
Serologicstudies indicate that incidence of infection may
be decliningas a result of improvements in sanitation
commensuratewith a rise in the standard of living coupled
with expandeduse of the vaccine
HBV
Infection with HBV of a specific subtype (eg,
HBsAg/adw)appears to confer immunity to other HBsAg
subtypes, probablybecause of their common group
aspecificity
Immunopathogeneticmechanisms that result in viral
persistenceand hepatocellular injury in type B hepatitis
remain to beelucidated
Not cytopathic
Believed thathepatocellular injury during acute disease
represents a hostimmune attack against HBV-infected
hepatocytes
Host responses, immunologic and genetic, are proposed
to account for the frequency of HBV chronicityin those
infected as infants
95% of newbornsinfected at birth become chronic carriers
of the virus, oftenfor life
Hepatocellular carcinoma is most likely to occur inadults
who experienced HBV infection at a very early age
andbecame carriers
For vaccination to be maximallyeffective against the
carrier state, cirrhosis, and hepatoma, itmust be carried
out during the first week of life
Balamban, Bolintiam, Brodith, Dueas, Justo, Parugao, Yu
3.6
HCV
HCV genotypes 14 are predominant in Western countries
and display some differential characteristics
Genotype 1 is predominant in North America,Japan, and
Western Europe
o Poorest responseto interferon (IFN) therapy and
may have more effect on the progression of HIV
type 1 disease than other HCV genotypes
Genotype 2 - responds the best to IFN-based therapies
Genotype 3 - highest rate of spontaneous clearance
Genotype 4 - highest frequency leading to chronic
infection after acute infection
Less is known about host immune responses to HCV
Majority of acute infections are asymptomatic or mild, and
chronic infections usually progress slowly and insidiously
Immune response is slow to develop andrelatively weak,
reflecting the fact that HCV has particularly effective
immune evasion mechanisms
TREATMENT, PREVENTION, CONTROL
TREATMENT
Treatment of patients with hepatitis is supportive and
directedat allowing hepatocellular damage to resolve and
repair itself
Only HBV and HCV have specific treatments, and those
are only partially effective
Recombinant IFN- and pegylated IFN- -- proven benefit
in treatment of chronic HBV or HCV
o Many who responded clinically and biochemically
relapsed after cessation of treatment
o Only 35% of chronic HBV infections have long-
lasting remissions, and only 25% of chronic HCV
infections have a sustained response
o IFN-based therapy is associated with many side
effects
Several antiviral drugs are available for use against
chronic hepatitis infections
With nucleoside and nucleotideanalogs, such as
lamivudine, HBV DNA levelsare reduced, but it is rarely
eliminated and viral replicationresumeswhen treatment is
stopped
Emergence of drug-resistant virus mutants inlong-term
therapy is a major problem
Combination therapyof IFN- and ribavirin against chronic
HCV gives asustained response rate of up to 50%, but
itsless successful in patients with genotype 1
Two new hepatitisC drugs, boceprevir and telaprevir (both
protease inhibitors),were approved in the US in 2011
Orthotopic liver transplantation is a treatment forchronic
hepatitis B and C end-stage liver damage
o Risk of reinfection on the graft is 80% with HBVand
50% with HCV, presumably from extrahepatic
reservoirs
PREVENTION & CONTROL
Viral vaccines and protective IG preparations are
availableagainst HAV and HBV
Neither type of reagent is currently available to prevent
HCV infections
Standard Precautions
All blood and body fluids andmaterials contaminated with
them are treated as if they areinfectious for HIV, HBV,
HCV, and other bloodborne pathogens
Exposures that might place workers at risk: percutaneous
injury (eg, needlestick) or contactof mucous membrane or
nonintact skin (eg, chapped, cuts,dermatitis) with blood,
tissue, or other body fluids that arepotentially infectious
Methods are devised to prevent contactwith such samples
Examples of specific precautions:
o Gloves should be used when handling
o Protective garmentsshould be worn and removed
before leaving the work area
o Masks and eye protection should be worn
whenever splashesor droplets from infectious
material pose a risk
o Only disposableneedles should be used
o Needles should be discardeddirectly into special
containers without resheathing
Page 5 of 8
MICROBIOLOGY // Hepatitis Viruses 3.6
o Worksurfaces decontaminated using bleach Persons exposed to HBV percutaneouslyor by
solution contamination of mucosal surfaces
o Lab personnel should refrain from mouth o Immediatelyreceive both HBIG and HBsAg vaccine
pipetting,eating, drinking, and smoking in the work administered simultaneouslyat different sites
area o Immediate protectionwith passively acquired
o Metalobjects and instruments disinfected by antibody followed by active immunity with the
autoclaving orby exposure to ethylene oxide gas vaccine
IG isolated from plasma by cold ethanol fractionationhas
Hepatitis A not been documented to transmit HBV,HAV, HCV, or HIV
Formalin-inactivated HAV vaccines made from cell in the U.S.
cultureadaptedvirus were licensed in the United States in o IGs prepared outsideby other methods have been
1995 -- safe, effective, and recommended for implicated inoutbreaks of hepatitis B and C
personsmore than 1 year of age The high cost of HBIG precludes its use in most countries
Routine vaccination recommended:all children, persons at Women who are HBV carriers or who acquire type
increased risk, including internationaltravelers, men who Bhepatitis while pregnant can transmit the disease to
have sex with men, and drug users theirinfants
Until all susceptible at-risk groups are immunized,control Patients with acute type B hepatitis generally need notbe
of HAV still must emphasizeinterrupting the chain of isolated as long as blood and instrument precautions
transmission and using passiveimmunization arestringently observed
Hepatitis in camps or institutionsis often an indication of Spouses and intimate contactsneed to be informed about
poor sanitation and poor personalhygiene practicesthat might increase the risk of infection or
Control measures directed toward preventionof fecal transmission
contamination of food, water, or other sourcesby the No evidence that asymptomatic HBsAg-positive
individual foodhandlers pose a health risk to the general public
Essential in preventing spread during acute phase of
illness: reasonable hygienesuch as handwashing,use of Hepatitis C
disposable plates & eating utensils, use of 0.5% sodium No vaccine yet
hypochlorite (eg, 1:10 dilution of chlorinebleach) as a Focus on preventionactivities that reduce risks for
disinfectant contracting HCV:
Immune () globulin (IG) is prepared from largepools of o Screening and testing blood, plasma, organ, tissue,
normal adult plasma andsemen donors
o Confers passive protectionin those exposed when o Virus inactivation of plasma-derived products
given within 12weeks after exposure o Counseling of persons with high-risk drug or sexual
o Prophylactic valuedecreases with time practices
o Administration more than2 weeks after exposure or o Implementation of infection control practices in
after onset of clinical symptomsis not indicated health careand other settings
o IG doesnot prevent infection but rather makes the o Professional and public education
infection mild orsubclinical and permits active
immunity to develop Hepatitis D
HAVvaccine produces a more enduring immunity and Delta hepatitis can be prevented by vaccinating
shouldreplace the use of IG HBVsusceptiblepersons with hepatitis B vaccine
However,vaccination does not protect hepatitis B carriers
Hepatitis B from superinfectionby HDV
A vaccine has been available since 1982
Initial vaccine was prepared by purifying HBsAg
associatedwith the 22-nm particles from healthy HBsAg-
positive carriersand treating the particles with virus-
inactivating agents(formalin, urea, heat)
o Preparations with intact 22-nmparticles have been
highly effective in reducing HBV infection
Plasma-derived vaccines (still used in certaincountries)
have beenreplaced by recombinant DNA-derived vaccines
o Consistof HBsAg produced by a recombinant DNA
in yeast cells orin continuous mammalian cell lines
o HBsAg expressedhas morphologiccharacteristics of
free surface antigen in plasma,although the
polypeptide antigen produced by recombinantyeast
is not glycosylated
o Potency similar to that of vaccinemade from
plasma-derived antigen
Preexposure prophylaxis with hepatitis B vaccine is
recommended by WHO, CDC, and the Advisory
Committee on ImmunizationPractices for all susceptible,
at-risk groups
In the US, HBV vaccine is recommended for all children
Hepatitis B vaccination is the most effective measure
toprevent HBV and its consequences
Strategy to eliminate HBV transmission in theUS:
o universal vaccination of infants
o routine screening of all pregnant women for HBsAg
o postexposureimmunoprophylaxis of infants born to
HBsAg-positivemothers
o vaccination of children and adolescentsnot
previously vaccinated
o vaccination of unvaccinatedadults at increased risk
for infection
Immunosuppressed groups respond to vaccination less
well than healthyindividuals
Passive immunization using specific hepatitisB immune
globulin (HBIG) are protective ifgiven soon after exposure
HBIG is not recommended forpreexposure prophylaxis
because the HBV vaccine is availableand effective

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 HEPATITIS VIRUSES
3.6
December 3, 2014
Dr. Bunyi

TABLES / FIGURES

VIRUS HAV HBV HCV HDV HEV

Family Picornaviridae Hepadnaviridae Flaviviridae Unclassified Hepeviridae

Genus Hepatovirus Orthohepadnavirus Hepacivirus Deltavirus Hepevirus

30-32 nm,
Virion 27 nm, icosahedral 42 nm, spherical 60 nm, spherical 35 nm, spherical
icosahedral
Envelope No Yes (HBsAg) Yes Yes (HBsAg) No
Genome ssRNA dsDNA ssRNA ssRNA ssRNA
Genome size (kb) 7.5 3.2 9.4 1.7 7.2
Heat- and acid- Ether-sensitive,
Stability Acid-sensitive Acid-sensitive Heat-stable
stable acid-sensitive
Transmission Fecal-oral Parenteral Parenteral Parenteral Fecal-oral
Prevalence High High Moderate Low, regional Regional
Fulminant disease Rare Rare Rare Frequent In pregnancy
Chronic disease Never Often Often Often Never
Oncogenic No Yes Yes ? No
Blood/blood-derived Blood/blood- Blood/blood-
Source of virus Feces Feces
body fluids derived body fluids derived body fluids
Route of Percutaneous Percutaneous Percutaneous
Fecal-oral Fecal-oral
transmission Permucosal Permucosal Permucosal
Chronic infection No Yes Yes Yes No
Blood donor Pre/post-exposure
Pre/post-exposure Pre/post-exposure screening; risk immunization; rish Ensure safe
Prevention
ummunization ummunization behavior behavior drinking water
modification modification

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MICROBIOLOGY // Hepatitis Viruses 3.6

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