Acute Viral Hepatitis Anti-HBs: protective antibody

Dr. Joyce Madayag HBeAg: high levels of virus replication and reflects the
IM 3 presence of circulating virions and detectable HBV DNA
Variants
HEPATITIS A VIRUS o Precore mutant HBV: lower HBV DNA,
Nonenveloped 27-nm, heat/acid/ether resistant RNA virus fluctuating aminotransferase levels
Inactivation: boiling for 1 minute, contact w/ o Escape mutants: conformational change leading
formaldehyde & chlorine, UV irradiation to loss of neutralizing activity by anti-HBs
Incubation period: 4 weeks Extrahepatic sites
Site: liver, bile, blood, stools o Lymph nodes
o Bone marrow
o Circulating lymphocytes
o Spleen
o Pancreas
Spectrum of Chronic Hepatitis B Diseases
Chronic persistent hepatitis asymptomatic
Chronic active hepatitis symptomatic exacerbations of
hepatitis
Cirrhosis of lover
Hepatocellular carcinoma

HEPATITIS D VIRUS

HEPATITIS B VIRUS
Four genes: S, C, X, P
Replicate in the liver but exist in extrahepatic sites
DNA polymerase, double and single stranded genomes
HBsAg: envelope proteins expressed on the outer surface Defective RNA virus that coinfects with and requires the
of the virion & on smaller spherical & tubular structures helper function of HBV for its replication and expression
Genotypes Formalin-sensitive, 35-37 nm virus with a hybrid structure
o A: US and Europe Delta core is encapsidated by an outer envelope og
o B and C: Asia HBsAg
S gene product: HBsAg Infect a person simultaneously with HBV (co-infection) or
P gene: largest superinfect a person already infected with HBV
HBsAg: first virologic marker to be detectable in the serum (superinfection)
(8-12 weeks)
o Undetectable 1-2 months after the onset of HEPATITIS C VIRUS
jaundice Non-A, non-B hepatitis
Anti-HBc: seen in serum 1-2 weeks after appearance of Linear, single-strand RNA virus
HBsAg & precedes anti-HBs detection by weeks to months Genus Hepacivirus
o Window period Replication rate is very high, 1012 virions per day

HEPATITIS E
Epidemic or enterically transmitted non-A. non-B
hepatitis
Five genotypes
o Genotypes 1 and 2: more virulent
o Genotypes 3 and 4: more attenuated and
account for subclinical infection
Symptoms and Signs
Constitutional symptoms may precede the onset of
jaundice by 1-2 weeks
Low-grade fever (A and E)
 Dark urine and clay-colored stools 1-5 days before the PROPHYLAXIS
onset of clinical jaundice Hepatitis A
Clinical jaundice: mild weight loss, hepatomegaly, o Postexposure prophylaxis of intimate contacts:
splenomegaly, cervical adenopathy 0.02 mL/kg
Recovery phase: constitutional symptoms disappear o Travelers to tropical countries: IG prophylaxis < 3
Complete clinical and biochemical recovery months, 0.02 mL/kg; for longer travel, 0.06 ml/kg
o 1-2 months in hepatitis A and E and every 4-6 months
o 3-4 months after the onset of jaundice in of o 4 weeks of an expected exposure: hepatitis A
uncomplicated, self-limited cases of hepatitis B vaccine is preferred as preexposure
and C immunoprophylaxis
Laboratory Features o If travel is imminent, IG (0.02 ml/kg) should be
AST and ALT levels increase during prodromal phase & admninistered at a different injection site
precede rise in bilirubin level starting with first dose of vaccine
Jaundice is visible in the sclera when the bilirubin is >43 HEPATITIS A VACCINATION SCHEDULES
umoL/L (2.5 mg/dL) Age, years No. of Dose Schedule,
Neutropenia and lymphopenia followed by lymphocytosis doses months
HAVRIX (GlaxoSmithKline)
1-18 2 720 ELU 0.6-12
COMPLICATIONS and SEQUELAE
(0.5 mL)
Hepatitis A 19 2 1440 ELU 0.6-1.2
o Relapsing hepatitis: recurrence of symptoms, (1.0 mL)
aminotransferase elevations, occasional VAQTA (Merck)
jaundice, and fecal excretion of HAV 1-18 2 25 units 0.6-18
o Cholestatic hepatitis (0.5 mL)
: protracted cholestatic jaundice and pruritus 19 2 50 units 0.6-18
(1.0 mL)
Hepatitis B
Hepatitis B
o Serum sickness-like syndrome (arthralgia,
o Unvaccinated persons exposed to HBV: HBIG and
arthritis, rash, angioedema, hematuria,
hepatitis B vaccine
proteinuria): 5-10%
o Infants born to HBsAg-positive mothers: a single
Fulminant hepatitis: hepatitis B >50%
dose og HBIG, 0.5 ml is given immediately after
o Hepatic failure
birth followed by a complete course of
Chronic hepatitis
vaccination to be started within the first 12
o Lack of complete resolution of clinical symptoms
hours of life
o Bridging/interface or multilobular hepatic
o Percutaneous inoculation/transcutaneous
necrosis on liver biopsy during severe acute viral
exposure: single IM dose of HBIG, 0.06 ml/kg is
hepatitis
administered followed by complete vaccination
o Failure of serum aminotransferases, bilirubin, &
to begin within the first week
globulin to return to normal within 6-12 months
o Sexual exposure: single IM dose of HBIG 0.06
o Persistence of HBeAg for >3 months of HBsAg for
ml/kg is given within 14 days of exposure,
> 6 months
followed by complete course of vaccination

PREEXPOSURE HEPATITS B VACCINATION

Recombivax-HB (Merck)
Engerix-B (GlaxoSmithKline)
NOMENCLATURE AND FEATURES OF HEPATITIS VIRUSES

Hepatitis Virus particle, Morphology Genome Classification Antigen Antibodies Remarks

Type nm
HAV 27 Icosahedral 7.5-kb Hepatovirus HAV Anti-HAV Early fecal shredding
Nonenveloped RNA, Diagnosis: IhM anti-HAV
linear, ss Previous infection: IgG
ani-HAV
HBV 42 Double-shelled 3.2 kb Hepadnavirus HBsAg Anti-HBs Bloodborne virus: carrier
virion (surface DNA HBcAg Anti-HBc state
and core) circular, HBeAg Anti-HBe Acute diagnosis: HBsAg,
spherical ss/ds IgM, anti-HBc
Chronic diagnosis: IgG,
anti-HBc, HBsAg
Markers of replication:
HBsAg, HBV, DNA
Liver, lymphocytes, other
organs
27 Nucleocapsid HBcAg Anti-HBc Nucleocapsid contains
core HBeAg Anti-HBe DNA and DNA
polymerase: present in
hepatocyte nucleus;
HBcAg does not circulate;
HBeAg (soluble,
nonparticulate) and HBV
DNA circulate correlate
with infectivity and
complete virions
22 Spherical and HBsAg Anti-HBs HBsAg detectable in >
filamentous; 95% of patients with
represents acute hepatitis B; found
excess virus coat in serum, body fluids,
material hepatocyte cytoplasm;
anti-HBs appears
following infection --
protective antibody
HCV Approximately Enveloped 9.4-kb Hepacivirus HCV Anti-HCV Bloodborne agent,
40-60 RNA, C100-3 formerly labeled non-A,
linear, ss C33c non-B hepatitis
C22-3 Acute diagnosis: anti-HCV
NSS (C33c, C22-3, NSS), HCV
RNA
Chronic diagnosis: anti-
HCV (C100-3, C33c, C22-3,
NSS) and HCV RNA;
cytoplasmic location in
hepatocytes
HDV 35-37 Enveloped 1.7-kb Resembles HBsAg Anti-HBs Defective RNA
hybrid particle RNA, viroids and HDV Anti-HDV virus, requires
with HBsAg circular, plant satellite antigen helper function of
coat and HDV ss, viruses HBV
core (hepadnaviruses);
HDV antigen
present in
hepatocyte
nucleus
Diagnosis: anti-
HDV, HDV RNA;
HBV/HDV
coinfectionIgM
anti-HBc and anti-
HDV; HDV
superinfection
 IgG anti-HBc
and anti-HDV
HEV 32-34 Nonenveloped 7.6-kb Hepevirus HEV Anti-HEV Agent of
icosahedral RNA, antigen enterically
linear, ss, transmitted
+ hepatitis; rare in
USA; occurs in
Asia,
Mediterranean
countries, Central
America
Diagnosis:
IgM/IgG anti-HEV
(assays not
routinely
available); virus in
stool, bile,
hepatocyte
cytoplasm

CLINICAL AND EPIDEMIOLOGIC FEATURES OF VIRAL HEPATITIS

Feature HAV HBV HCV HDV HEV

Incubation (days) 15-45, mean 30 30-180, mean 60-90 15-160, mean 50 30-180, mean 60-90 14-60, mean 40
Onset Acute Insidious or acute Insidious Insidious or acute Acute
Age preference Children, young Young adults (sexual Any age, but more Any age (similar to Young adults (20-40
adults and percutaneous), common in adults HBV) years
babies, toddlers
Transmission
Fecal-oral +++ - - - +++
Percutaneous Unusual +++ +++ +++ -
Perinatal - +++ +/- + -
Sexual +/- ++ +/- ++ -
Clinical
Severity Mild Occasionally severe Moderate Occasionally severe Mild
Fulminant 0.1% 0.1-1% 0.1% 5-20% 1-2%
Progression to None Occasional (1-10%) Common (85%) Common None
chronicity (90% of neonates)
Carrier None 0.1-30% 1.5-3.2% Variable None
Cancer None +(neonatal infection) + +/- None
Prognosis Excellent Worse with age, Moderate Acute, good Good
debility Chronic, poor
Prophylaxis IG, inactivated HBIG, recombinant None HBV vaccine (none Vaccine
vaccine vaccine for HBV carriers)
Therapy None Interferon Pegylated interferon Interferon +/- None
Lamivudine plus ribavirin
Adefovir telaprevir boceptrevir
Pegylated interferon
Entecavir
Telbivudine
Tenofovir
COMMONLY ENCOUNTERED SEROLOGIC PATTERNS OF HEPATITIS B INFECTION
HBsAg Anti-HBs Anti-HBc
+ -
+ -
+ -
+ +
- -
- -
- +
- +
--END--
HBeAg Anti-HBe Interpretation
IgM + - Acute hepatitis B, high infectivity
IgG + - Chronic hepatitis B, high infectivity
IgG - + 1. Late acute or chronic hepatitis B,
low infectivity
2. HBeAg-negative (precore-mutant)
hepatitis B (chronic or, rarely,
acute)
+ +/- +/- 1. HBsAg of one subtype and
heterotypic anti-HBs (common)
2. Process of seroconversion from
HBsAg to anti-HBs (rare)
IgM +/- +/- 1. Acute hepatitis B
2. Anti-HBc window
IgG - +/- 1. Low-level Hepatitis B carrier
2. Hepatitis Bin remote past
IgG - +/- Recovery from hepatitis B
- - - 1. Immunization w/ HBsAg (after
vaccine)
2. Hepatitis B in remote past (?)
3. False-positive