HEPATITIS

HEPADNAVIRIDAE
 Hepadnaviridae[a] is a family of viruses. Humans, apes,
and birds serve as natural hosts. There are currently 18
species in this family, divided among 5 genera.
 Its best-known member is hepatitis B virus. Diseases
associated with this family include: liver infections, such as
hepatitis, hepatocellular carcinomas (chronic infections),
and cirrhosis. It is the sole family in the order Blubervirales.
 Only DNA virus that causes hepatitis, specifically hepatitis
B

GENERAL CHARATERISTICS
 Hepatitis viruses share the same tissue tropism (liver)
 HBV, TTV and SEN virus have DNA genomes, others have
RNA genome
 Hepatitis viruses are grouped together because they share
the same tissue tropism, which is the liver.
 HBV, TTV and SEN virus have DNA genomes whereas the
others have RNA genome.
Classifications of Hepatitis
 Structure of HBV
 It is an enveloped virus  Infectious Hepatitis – caused by microbial pathogens
 This is a DNA virus and called a Dane particle.  Viral Hepatitis
 It has an inner core surrounded by an outer capsule  HAV, HBV, HCV, HDV, HEV
 Bacterial Hepatitis
GENERAL CHARACTERISTICS OF HEPATITIS
 Leptospirosis, syphilis
 The term “hepatitis” refers to inflammation of the liver  Parasitic Hepatitis
 The condition can be self-limiting or can progress to fibrosis  Amebiasis, fascioliasis, toxoplasmosis,
(scarring), cirrhosis or liver cancer opistorchiasis
 Viral Hepatitis  Toxic Hepatitis
 Hepatotropic viruses  Alcoholic Hepatitis
 Hepatitis A virus (HAV)  Induced by alcoholism
 Hepatitis B virus (HBV)  Medical Hepatitis
 Hepatitis C virus (HCV)  Drug intoxication
 Hepatitis D virus (HDV)  Chemical Hepatitis
 Hepatitis E virus (HEV)  In case of poisoning with other substances
 Hepatotoxic chemical agents
PATHOLOGY
 All hepadnaviruses cause hepatitis
 Acute Hepatitis
 Fulminant Hepatitis – Severe Acute Hepatitis with rapid
destruction of liver
 Chronic Hepatitis
 Primary Hepatocellular Carcinoma
 All of the known hepadnaviruses are hepatotropic, infecting
liver cells, and all can cause hepatitis in their known host
 Most common symptoms:
 Fatigue
 Headache
 Anorexia
 Nausea
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HEPATITIS

 Vomiting HBV can be found in:

 Abdominal pain
 Saliva
 Jaundice
 Semen
 Itchy skin
 Breastmilk
 Dark colored urine
 Tears
 Sweat
HEPATITIS B  Other biological fluids of HBV carriers
 Urine and wound exudate are capable of harboring
Etiology HBV
 HBV is the classic example of a virus acquired through STAGES OF HBV INFECTION
blood transfusion. Carrier State  A HBV carrier is one
 Hepatitis B is a complex DNA virus who has HBsAg in
 A member of family Hepadnaviridae blood for 6 months with
 HBV relies on a retroviral replication strategy (reverse normal liver function
transcription from RNA to DNA) test results
 The virus specifically infects human hepatocytes by binding Chronic Persistent  The patient has
to the cell receptor called your sodium taurocholate Hepatitis abnormal liver
cotransporting polypeptide (NTCP) function test results
with a normal liver
 dsDNA virus that belongs to Group VII of Baltimore
biopsy specimen
Classification
Chronic Active Hepatitis  The patient has
Epidemiology abnormal liver
function test results
Persons at risk of exposure to HBV, including those mentioned and abnormal liver
earlier, include members of the following groups: biopsy.
• Heterosexual men and women
Viral Proteins
• Homosexual men with multiple partners
1. Hepatitis B Core Antigen (HBcAg)
• Household contacts and sexual partners of HBV  Core protein
carriers  Structural nucleocapsid
• Infants born to HBV-infected mothers
2. Hepatitis B e antigen (HBeAg)
• Patients and staff in custodial institutions for  Nucleocapsid
developmentally disabled persons  It is inside the virus particle
• Recipients of certain plasma-derived products,  Cannot be seen though the antibody can be
including patients with congenital coagulation defects detected
3. Hepatitis B surface antigen (HBsAg)
• Health care and public safety workers who may be in  Also called Australia antigen
contact with infected blood  Discovered in 1966
 Envelope protein (seen inside virus’
• Persons born in HBV-endemic areas and their
envelope)
children
 Hallmark of active hepatitis B infection
Mode of Transmission
Order of Appearance of Serological Markers (SEC-CES)
1. via percutaneous or permucosal routes
Antigen Antibody
2. infective blood or body fluids can be introduced at birth
3. through sexual contact 1. HBsAg 4. Anti-HBc (1st antibody to be detected)
4. by contaminated needles 2. HBeAg 5. Anti-HBe
5. settings of continuous close personal contact 3. HBcAg 6. Anti-HBs
Note: HBcAg is not detected serologically, it do not go out in the
liver cells
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HEPATITIS

SIGNIFICANCE OF SEROLOGICAL MARKERS - Anti-HbS is a marker Safety Status (immune)

Markers Detected Significance - Anti-HbE is a marker of rEcovEry!
1. HBsAg 2-10 weeks after  Infection
DIAGNOSIS OF ACUTE/CHRONIC HEPATITIS
exposure to HBV/ (Acute/chronic)
Acute Chronic
2 weeks- 2  Acute (HBsAg is
months before seen 4-6 months)  + Anti-HBc IgM  + HBsAg;
clinical symptoms  Chronic (HBsAg is + HBeAg;
seen >6 months) + HBV DNA
Note: any 1 sample na
2. HBeAg Shortly after  The virus is
positive ana sa taas, pero
HBsAg actively
dapat negative sa Anti IgM
replicating
HBc
 Patient is
infectious
 Marker of Prevention
INFECTIVITY
3. Anti-  Onset of  Infection is in the  Hepatitis B Vaccine
HBc IgM symptoms acute stage  Anti-HBs will yield positive result if you are
 Predominant vaccinated
Ab in primary  How will we know if the anti-HBs is due to
immune vaccine or from real infection? We test for
response anti-HBc
 Natural Hepatitis B infection will yield positive
Anti-  Persists for  Past infection
result in anti-HBc; while in vaccination,
HBc IgG life, past
infection negative result
4. Anti-  Detected  Starting to  Screening for prenatal infants
HBe after HBeAg RECOVER  Screening for Hb antigen in blood banks
disappears  Recovery phase
 Marker of
convalescence LABORATORY
 Less infective
5. Anti-  Detected  Immune/recovered DIAGNOSTIC INFORMATION
HBs during  Marker of PROCEDURE
recovery immunity The following blood tests in the laboratory
phase are performed to check for signs of liver
disease:
Note: • Albumin: low albumin can be a sign of
liver disease
- Total anti-HBc= IgM +IgG (IgG mas daghan)
• ALP, ALT, AST: high levels may signal
- Anti-HBc: the only marker during the window period
hepatitis
 Time frame wherein HBsAg disappears • Bilirubin: elevated bilirubin levels can
 This is the time when one is positive with the cause jaundice (yellowing of the skin and
infection but tested serologic negative to the the whites of the eyes)
presence of antibodies • Viral serology or Hepatitis Panel: a
 Two periods may be considered as Window group of blood tests that determines
Period in hepatitis B infection: whether you have hepatitis, which train it is,
1. The period that elapses during HBsAg and the severity of illness
to HBs antibody seroconversion, which is
between the disappearance of HBsAg from
serum and the appearance of your HBs Typically, blood is tested for:
antibody; and • Hepatitis A antigen
Blood Tests • Hepatitis B antigens (surface and core
2. The period between infection and the
antigens
appearance of your HBsAg • Antibody against hepatitis C
- Anti-HbC is a marker of aCute and Chronic Hepatitis B

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HEPATITIS

DNA test for Hepatitis B  Resolving acute

• Measures the DNA in the body infection
• DNA is the genetic material or blueprint of - - - +  Immunity from
hepatitis B virus vaccine
• How much you have indicates how rapidly
the virus is making copies of itself in the live
• Low levels (less than 300 copies/mL) – GENERATION TESTS FOR HBsAg DETECTION
virus is inactive First Second Generation Third Generation
• High levels (100,000 – a billion or more) – Generatio
virus is active and rapidly replicating n
Ouchterlo 1. Counterelectrophor 1. RIA:
Rapid Tests for Hepatitis C ny Double esis Radioimmunoa
• Can be done with blood from a finger stick, Diffusion 2. Rheophoresis ssay
and reliable results available within 20 (Agar Gel 3. Complement 2. RPHA:
minutes Diffusion) Fixation ReversePassiv
• For 15 years old and older who are at risk e
for infection Hemagglutinati
on
Hepatitis C RNA testing 3. ELISA: Enzyme
• Hepatitis C RNA qualitative is a molecular Linked
test that tells whether the hepatitis virus is Immunosorbent
present in the bloodstream. Assay
• A qualitative test is more accurate than a 4. RPLA: Reverse
quantitative test. Passive Latex
• Able to detect very low levels of the virus Agglutination
• Often used for screening and to determine
if treatment is working
MISCELLANEOUS LABORATORY DIAGNOSIS

HEPATITIS B PANEL (SEROLOGIC MARKERS  Molecular Methods

HBsAg Total IgM Anti- Interpretation  Detect HBV DNA in serum or plasma
Anti- Anti- HBs 1. Target amplification
HBc HBc 2. Branched DNA signal
- - - -  Not infected 3. Hybridization
 Susceptible to 4. Real-time PCR
Hepatitis o most sensitive
+ - - -  Early infection o can detect as few as 10 copies of HBV
(Acute hepatitis
infection)
 Vaccinated
- + + -  Acute infection HEPATITIS A
(Only in the
window period)  HAV, a single-stranded icosahedral RNA virus that belongs
- + - +  Past infection to the Picornaviridae Family
(w/ recovery, or  It multiplies only in hepatocytes and is transmitted via fecal-
presence of oral route
immunity)  the only hepatitis virus that has been successfully grown in
+ + - -  Chronic culture
infection
- + - -  False-positive Epidemiology
(susceptible)
 Past infection  HAV was formerly called:
(resolved)  Infectious hepatitis
 Low level  Short-incubation hepatitis
chronic infection  Is primarily a disease of young children
 HAV is transmitted almost exclusively by a fecal-oral route

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HEPATITIS

 most frequently identified risk factor for hepatitis A RNA Total Anti- Anti-HAV Interpretation
 international travel HAV IgM
+ + + Acute HAV
Signs and Symptoms - + - Recovered
HAV/Vaccinated
 Nonimmune adult patients infected with HAV
 Develop clinical symptoms within 2 to 6 weeks
after exposure HEPATITIS C
 Clinically apparent cases show elevated serum liver
function enzyme and bilirubin levels, with jaundice  Enveloped single-stranded (+) sense RNA virus classified
developing several days later under the Family Flaviridae
 Atypical presentations include:  Along with hepatitis B, they are screened in blood donors
 Prolonged intrahepatic cholestasis, relapsing  Previously called:
course, and extrahepatic immune complex  Non-A, Non-B Hepatitis
deposition, all of which resolve spontaneously.  HCV have at least 6 major genotypes:
 Genotype 1: represents most infection in North
Immunoglobulins Detected Significance and South America, and Europe
IgM antibody Detectable in the
 Genotypes la and lb: are the most common
serum shortly
after the onset of genotypes in the United State
fecal shedding  Genotypes 2 and 3: have a more favorable
IgG antibody Seen few days prognosis and are more likely to respond to
after appearance treatment.
of IgM antibody
Epidemiology
IgM anti-HA Always Acute HAV
detectable in  A leading cause of chronic hepatitis, cirrhosis, and liver
patients with cancer
Acute HAV  Primary indication for liver transplantation in Western
IgG anti-HAV Remains  Previous countries.
detectable, infection
lifelong  Manifestation
of immunity Viral Transmission
 Spread primarily by percutaneous contact with infected
LABORATORY blood or blood products
 Serological Test  Risk factors:
 Common Test for HAV  Workers with needlestick injuries
 IgM anti-HAV: Solid phase antibody capture  infants born to HCV-infected mothers
ELISA  multiple sexual partners
 IgG anti-HAV: Competitive Inhibition ELISA  recipients of unscreened donor blood
 Ab Capture ELISA  injectable drug abuse (most common risk factor)
 To detect IgM inpatient sample Signs and Symptoms
 Anti-IgM is immobilized on solid phase
 Sample is added (look for IgM)  serum liver enzyme levels in the range of 200 to 800 U/L
 Conjugate is added (Ag bound to
LABORATORY DIAGNOSIS
antibody to antibody conjugated to
enzyme)  HCV has not been grown in culture
 Amount of labeled Ab bound is  HCV genomes can be amplified by recombinant technology
proportional to the amount of IgM in the  Major diagnostic test for HCV infection has been the
sample second-generation anti-HCV, which detects the presence
of antibody to one of four different viral antigens at an
average of 10 12 weeks after infection
 Third generation anti HCV assay detects antibody at an
average of 7 9 weeks after infection

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HEPATITIS

 IgM anti HCV is present in both acute and chronic HCV  The presence of two bars from the control is interpreted as
infection and is therefore not helpful diagnostically a positive result. These bonds resulted due to the presence
 Total anti HCV typically persists for life although it may of antibodies against C33-C and C22-C
disappear with recovery from HCV infection
Laboratory Diagnosis
 Detection of the unique nucleic acid sequences of each
HCV PANEL strain by one of several nucleic acid methods is the most
Anti-HCV Recombinant Ag reliable means to identify
RN Screenin 5- c100 c33 c22 Interpretatio  With acute infection, HCV RNA is typically present within 2
A g EIA 1- -3 c -3 n weeks of infection but falls with development of antibody
1  The primary test for confirming persistence of HCV infection
+/- + N/A Possible is HCV RNA, detected by a variety of amplification
acute or techniques
chronic
infection
- + - - - - False HEPATITIS D
positive
+/- + + + - -  possible Etiology
false-
negative  Initially called Delta agent
(if RNA  first described in 1977 as a pathogen that superinfects
is some patients already infected with HBV
negative  HBV is required as a so-called helper to initiate infection
)  HDV is a replication defective or incomplete RNA virus that
 possible by itself, is unable to cause infection
acute  A single-stranded, circular RNA coated with HBsAg
infection
+/- + - - + +  Early Epidemiology
acute or
chronic  originally described in Italy
infection  is a severe and rapidly progressive liver disease
(if RNA  no therapy has proven effective
is
Transmission
positive)
 False-  spread chiefly by direct contact of HBsAg carriers with
positive HDV- or HBV-infected individuals
 Late  IV drug users and individuals with multiple sex partners
recover
(if RNA Immunologic Manifestations
is
negative  Hepatitis D infection is diagnosed by the appearance of
) HDV antigen in serum
+ + + + + + Acute/chroni  Development of IgM or IgG HDV antibodies
c
- + +/ +/- + + Recovered LABORATORY DIAGNOSIS
-  The major diagnostic test is the presence of anti-HDV
 The simultaneous assessment of anti-HBc IgM will help
Recombinant Immunoblot Assay differentiate coinfections (present) from superinfections
(absent)
 RIBA detects more specific HCV antibodies. Test is  Incomplete without hepatitis B
interpreted as positive (2 or more antigens) indeterminate  Anti-HBc IgM is present if there is coinfection and absent
(1 antigen), negative (0 antigens). when there is superinfection
 More specific than ELISA
 HCV-RNA has now replaced the importance of RIBA

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HEPATITIS

HEPATITIS E HEPATITIS G
 Caused by HEV Etiology
 Infection is usually the result of poor sanitation conditions
 Cause of hepatitis G is the hepatitis G virus (HGV )
 responsible for large, water-borne outbreaks of hepatitis
 an RNA virus
Transmission  Almost identical to a viral agent called GB virus type C
(GBV-C).
 Fecal-oral route
Epidemiology
Signs and Symptoms
 HGV is a bloodborne agent
 Incubation period: 2-9 weeks, average of 6 weeks
 HGV infection frequently occurs as a coinfection with HCV
 10% to 20% of HEV infections in pregnant women about
result in fulminant hepatitis, especially in the third trimester
of pregnancy TRANSFUSION-TRANSMITTED VIRUS
Immunologic Manifestations Etiology
 IgM anti-HEV has been found in acute-phase sera  more recent addition to the infectious hepatitis family
 IgG anti-HEV appears and replaces IgM anti-HEV about 2  a nonenveloped, single-stranded DNA virus
to 4 weeks after symptoms subside  most remarkable feature of TTV:
Diagnostic Evaluation  extraordinarily high prevalence of chronic viremia
in apparently healthy people
 can be diagnosed by performing immunoelectron
microscopy on a stool specimen Epidemiology
 Elevated liver serum enzyme levels are indicative of the  associated with posttransfusion hepatitis of unknown
acute phase of the infection. etiology (non–A-G)
Treatment  Transmission:
 Parenteral exposure to blood
 Supportive care  Fecal-oral route
 No effective vaccine has been developed  Mother to child
LABORATORY DIAGNOSIS -----------------------------------------------------------------------------------
 Serological test
 Both IgM and IgG antibody to HEV (anti-HEV) may
occur following HEV infection
 The titer of IgM anti-HEV declines rapidly during early
convalescence
 IgG anti-HEV persists and appears to provide at least short-
term protection against disease
 Antibodies are usually identified using highly sensitive
enzyme immunoassays that are recombinant and synthetic
HEV antigens
 A PCR amplification of an HEV RNA-specific product using
serum, plasma, bile, or feces becomes the definitive
indicator of acute infection

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HEPATITIS

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