This document discusses viral hepatitis, caused by hepatitis viruses A, B, C, D, E, and G. It provides information on the structure, transmission, clinical features, diagnosis, and prevention of each type of viral hepatitis. Hepatitis A virus is enterically transmitted while hepatitis B, C, and D are typically transmitted parenterally. Hepatitis B and C can cause chronic infection and lead to cirrhosis or liver cancer, while hepatitis A and E do not typically cause chronic infection. Diagnosis involves testing for viral markers and antibodies. Prevention strategies include vaccination, blood donor screening, and risk behavior modification.

2.  EBV
 CMV
 Rubella
 Rubeola
 Mumps
 Coxsackie B
 Yellow Fever (severe
hepatitis)
 Sepsis
 Leptospirosis
 Syphilis
 Q fever
 Medications
 Alcohol/drugs
 Sickle cell crisis
 Anoxia

3.  Viral hepatitis is a systemic disease with primary
inflammation in the liver.
 Caused by Hepatitis viruses A,B,C,D,E,G
 Infection caused by hepatitis B – most severe
 Hepatitis B & C viruses also responsible for many cases of
primary hepatocellular carcinoma.
 Hepatitis B is a DNA virus while others(A,C,D,E,G)
contain RNA genome.

4. 0%
5%
10%
15%
20%
25%
30%
35%
0.30%
3%
30%
Hepatitis B Virus Hepatitis C Virus HIV

5. Viral Hepatitis - Historical Perspective
A“Infectious”
“Serum”
Viral hepatitis
Enterically
transmitted
Parenterally
transmitted
F, G,
? other
E
NANB
B D C
Source: CDC

6. Features HAV HBV HCV HDV HEV HGV
Genome RNA DNA RNA RNA RNA RNA
Nomenclat
ure
Picrornavi
ridae
hepadnavir
idae
Flavivirida
e
Deltavirus Calcivirida
e
Flavivirida
e
Mode of
transmissi
on
Enteric Parenteral
Sexual
Perinatal
Parenteral
Sexual
Parenteral enteric Parenteral
Sexual
Perinatal
Ag in
blood
HAV HBsAg,
HBeAg
HCV HDAg HEV ?
Abs in
blood
Anti HAV Anti HBs
Anti HBe
Anti HBc
Anti-HCV Anti-HDV Anti-HEV Anti-HGV
envelope
Chronic
carrier
state
No Yes Yes Yes No ?
Hepatic Ca No Yes Yes No No No

7. Features Hepatitis A Hepatitis B
Virus
Diameter 27nm 42nm
Genome RNA DNA
Symmetry Icosahedral Icosahedral
Envelope Non-enveloped Enveloped
Stability 60° C x 60 mnts Survives Survives
100° C x 5 mnts Inactivated Inactivated
usual mode of infection Faeco-oral Pareneral
Clinical features
IP 2-6 wks 2-6 mnths
Onset Usually acute Insidious
Fever < 38° C Usual Rare
Chronicity Rare Common
Age incidence Children & young adults All ages
Seasonal distribution Post monsoon in India
Autumn, winter
All year around

8. Features Hepatitis A Hepatitis B
Lab diagnosis
HBs Ag Absent Present
Raised serum IgM Common Rare
Raised serum transaminase For few days For many weeks
Virus in faeces Present early Absent
Mortality 0.1% 1-10%
Carrier state
Blood Upto 8 mnths Upto 5 yrs
Faeces Upto 1-3 mnths Not known

9. Viral Hepatitis - Overview
A B C D E
Source of
virus
feces blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
feces
Route of
transmission
fecal-oral percutaneous
permucosal
percutaneous
permucosal
percutaneous
permucosal
fecal-oral
Chronic
infection
no yes yes yes no
Prevention pre/post-
exposure
immunization
pre/post-
exposure
immunization
blood donor
screening;
risk behavior
modification
pre/post-
exposure
immunization;
risk behavior
modification
ensure safe
drinking
water
Type of Hepatitis
Source: CDC

11.  Family- Hepadnaviridae
 Genus- Orthohepadnavirus
 Morphology
• Complex 42nm double shelled particle.
• Outer surface/envelope of virus contains
hepatitis B surface antigen(HBsAg).
• It encloses an icosahedral 27nm nucleocapsid
(core),which contains hepatitis B core antigen(HBcAg)

13.  Inside the core is genome, a circular double stranded DNA
and a DNA polymerase.
 Australia antigen- surface component of hepatitis B
virus(HBsAg)
 Electron microscopy – shows 3 types of particles.
 Most abundant –spherical particle (22nm in diameter)
 Tubular(22nm diameter) particle of varying length
 Double shelled spherical structure(42nm) – this particle is the
complete hepatitis B virus or Dane particle.

14.  HBsAg – surface antigens (envelope protein)
 HBcAg - core (nucleocapsid) antigen of the virus.
It contains group specific protein & is not detectable in
patient’s blood
 HBeAg – appears in serum along with HBsAg but
disappears within a few weeks. it is the hidden
antigenic component of core.
 HBcAg & HBeAg though immunologically distinct
are coded by the same gene.

15.  HBsAg carries group specific antigen ‘a’ and two
types of specific antigens ,d or y and w or r.
 4 antigenic types of HBsAg – adw, adr, ayw and ayr.
 Type adw is predominant in Europe and USA
 Type adr in Asia.
 Type ayw is predominant in Africa, Russia and India.
 Additional surface antigens of HBV (q,x,f,t,j,n,g) are
described,but they have not been characterized

16.  Consists of two linear strands of DNA held in a circular
configuration.
 One of the strands (plus strand) is incomplete while other is
complete.
 This gives the appearance of partially double strand and
partially single stranded DNA.
 Associated with the plus strand is a viral DNA polymerase.
 It can repair the gap in the incomplete (plus strand) and
render the genome fully double stranded.

17.  Genome has four genes (with different regions ) coding for
different antigens.
 S gene encodes major HBsAg, consists of S region & 2 pre S
regions
 C gene encodes HBcAg & HBe protein, has 2 regions C &
pre C
 P gene is largest & codes for DNA polymerase
 X codes for non particulate protein HBxAg.
 HBxAg & its antibody are found to be present in patients with
severe chronic hepatitis & hepatocellular carcinoma.

18. S gene
C gene
P gene
X

20.  HBV has not been cultivated in the laboratory.
 Limited production of the virus and its proteins can be
obtained from cell lines transfected with HBV DNA.
 HBV proteins have been cloned in yeast and bacteria.
 The virus survives heating of 60 C for 60 min but gets
inactivated at 100 C for 5min.
 Inactivated by formaldehyde (1:4000) and 2% gluteraldehyde.

21.  Parenteral transmission – result from accidental
inoculation of minute amounts of blood, blood products
or fluid containing HBV during medical,surgical or
dental procedures.
 Perinatal transmission – occurs when carrier mother’s
blood contaminates the mucus membranes of the
newborn during birth.
 Sexual transmission – HBV is present in body fluids i.e.
semen & vaginal secretions, hence can be transmitted by
sexual contact. Male homosexuals are at higher risk of
acquiring infection.

22.  Slow onset
 IP -6weeks-6months
 Pre-icteric phase-malaise, anorexia, weakness, myalgia,
nausea & vomiting.
 Few patients develop arthralgia, serum sickness, polyarteritis
nodosa and glomerulonephritis.
 Icteric phase-jaundice, pale stools & dark urine
(bilirubinemia).
 Convalescent phase- long. The duration of uncomplicated
hepatitis is usually 8-10 weeks, but mild symptoms may
persist for more than one year.

23.  Super carriers – have HBeAg in blood & are highly
infectious. their blood contains high titre of HBsAg
and DNA polymerase.
 HBV may also be demonstrable in blood.
 Very minute amount of serum/blood can transmit the
infection.
 Simple carriers – more common.
 Have no HBeAg and a low level of HBsAg in blood.
 HBV and DNA polymerase are absent.
 They transmit the infection only when large volumes
of blood/serum are transferred ,as in blood transfusion.

24. Humoral response
 Antibody to HBsAg –associated with resistance to
infection.
 useful indication of past infection or recent immunity.
 Antibody to HBcAg-rises rapidly following infection.
 Not protective. Appears to be related to the amount and
duration of replication of the virus. The highest titre of
anti-HBc are found in persistent HBsAg carriers.
 Antibody to HBeAg-seen in sera of patients with low
infectivity.
Cell mediated immunity
 Defective function of T-cell may favor development of
chronic liver damage.

25.  Detection of viral markers
 HBsAg-specific marker for HBV infection.
 First marker to appear in blood after infection.
 Peak levels- in pre icteric phase
 Remains in circulation throughout the icteric or
symptomatic course of the disease.
 HBsAg disappears with recovery from clinical disease in
most patients, however,it persists for years in carriers.
 Antibody to HBsAg appears within weeks after the
disappearance of HBsAg and persists for very long periods.
 Anti HBs is the protective antibody

26.  Appears in serum at the same time as HBsAg, but
disappears within a few weeks.
 Sera containing HBeAg – highly infectious.
 Indicator of active intra-hepatic viral replication and
presence in blood of HBV DNA, virions & DNA
polymerase.
 Disappearance of HBeAg is followed by appearance
of anti-HBe.

27.  Not detectable in serum.
 Can be demonstrable in liver cells by mmunoflorescence
 Anti –HBc antibody usually appears in serum a week or
two after the appearance of HBsAg.
 Earliest antibody to appear in blood.
 Remains lifelong-useful indicator of prior infection

29. Clinical condition
HBsAg HBE
Ag
Anti
HBs
Anti
Hbe
Anti HBc
IgM IgG
Late IP or early hepatitis + + _ _ _ _
Acute hepatitis + + _ _ + _
Late or Chronic HBV infection + +/_ _ _ _ +
Simple carrier + _ _ _ _ +
Super carrier + + _ _ _ +
Past infection _ _ + + _ +
Immunity following vaccination _ _ + _ _ _

31.  Viral DNA polymerase
Appears transiently in serum during preicteric phase
 Polymerase chain reaction
HBV DNA detected by PCR
HBV DNA is indicator of viral replication in liver and so
helps to assess the progress of patients under antiviral
chemotherapy.
 Biochemical tests
Acute viral hepatitis –transaminases b/w 500-2000 units.
Serum bilirubin –may rise upto 25 fold

32. General preventive measures
 Health education, improvement of personal hygiene and sterility.
 Screening of HBsAg & HBeAg in blood donors.
 Avoid unsterile needles, syringes
Immunisation
1. Passive immunisation
 Employed following any accidental exposure to HBV infection.
 HBIG prepared from donors with high titres of anti HBs.
 Dose-300-500 IU i/m
 Administered preferably within 48 hrs
 2nd dose usually given at interval of 4 weeks after the 1st dose.

33. 2. Active immunisation
 Plasma derived vaccine - Prepared by purifying 22nm particle
of HBsAg from plasma of healthy carriers.
 Separated by ultracentrifugation & inactivated with
formaldehyde.
 Recombinant yeast hepatitis B vaccine - Produced by
recommbinant DNA in yeasts in which a plasmid containing
the gene of HBsAg has been incorporated
 Doses – 0 – 1- 6 months I/M into deltoid muscle
 Recombinant Chinese hamster ovary cell hepatitis B vaccine
 Synthetic peptide vaccine – under experimental stage

34.  IFN α alone or in combination with antiviral like
lamivudine & famcyclovir has been beneficial in
some hepatitis cases

36.  Family flaviviridae 50-60nm
 SSRNA-Core- envelope
 Glycoprotein spikes
 Mutability-6 genotypes subtypes

37.  Risks: IDU, recipients of blood transfusions
prior to 1992
 20-30% of those with HIV also have HCV

38.  Needle stick injury
 Blood
 Sex

39.  IP-6-8 wks
 Subclinical/clinical
 Mild symptoms
 Less jaundice
 Cirrhosis carcinoma

40.  Elisa –anti HCV ANTIBODY
 IMMUNOBLOT
 IF-HCVRNA
 PCR –HCVRNA-BIOPSY
 VIRAL-GENOME-BLOOD

41. HCV Pathogenesis
CD8+ CD4+
Cell killing
Kupffer cell
Hepatocytes
Hepatic stellate
cells
TGF-β
Activation
FIBROSIS
Death
Cytokines
(IL-2, IFN-γ, TNF, ? TGF- β,?PDGF)

43. Symptoms +/-
Time after Exposure
Titer
anti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
YearsMonths
HCV RNA
Serologic Pattern, Acute HCV Infection
w/Recovery

44. Serologic Pattern: Acute HCV Infection w/
Progression to Chronic Infection
Time after Exposure
Symptoms +/-
Titer
anti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
YearsMonths
HCV RNA

46.  Essential mixed cryoglobulinemia
 Membranoproliferative glomerulonephritis
 Porphyria cutanea tarda

47.  Screening test: highly sensitive enzyme-linked
immunoassay (EIA)
 Confirmation can be with recombinant
immunoblot assay (RIBA), but HCV RNA
confirms presence of infection & that it is active

48. Chronic HCV Infection Causes Hepatic Fibrosis
Normal Mild Chronic Hepatitis
Moderate Chronic Hepatitis Cirrhosis

49.  Indications for tx: based on liver biopsy, not liver
enzyme abnormalities or quantitative HCV levels
 HCV genotypes vary in their response to tx
 Pegylated INF + ribavirin is current most effective tx
strategy
 Tx in collaboration with GI specialist

51.  Etiology: defective RNA virus; uses HBsAg so can
only occur with acute or chronic HBV
 Mode of transmission: blood
 Incidence: localized outbreaks among IDU
 Spectrum of illness: acute hepatitis, can be
fulminant, chronic hepatitis with usual sequelae

52.  Potential for chronicity: more than 70% of super-
infections of chronic HBV lead to chronic HDV
 Diagnosis: HDVab, HDV RNA, HBVsAg
 Treatment: supportive care
 Prevention: prevention of HBV, treatment of HBV

55.  Etiology: RNA virus
 Non-enveloped
 Mode of transmission: fecal-oral
 Spectrum of illness: acute hepatitis, mild to fulminant
 Potential for chronicity: none
 Treatment: supportive care
 Prevention: pre-exposure (immunization), post-
exposure (immune globulin)

56.  IP 2-6wks
 Preicteric,icteric stage
 Fever,anorexia,malaise,nausea,vomiting,liver
tenderness
 jaundice

57.  HAV 27nm nonenveloped ssRNA-icosahedral
symmetry
 Picornavirus
 Enterovirus-72

58.  Prevalent worldwide
 Childhood infection less common in U.S.
 Only 15-25% of U.S. adults immune → large
susceptible population
 Oral-fecal spread, including contaminated food &
water, makes avoidance difficult

59.  Compatible clinical syndrome
 Total HAV antibody (HAVAB) tests for both IgG &
IgM; does not distinguish between acute & prior
Hepatitis A
 + HAVAB, - HAV IgM → prior infection
 + HAVAB, + HAV IgM → acute infection

60.  Havrix (GlaxoSmithKline)
 Vaqta (Merck)
 Both: two shots 6-12 mo apart
 Twinrix (GlaxoSmithKline) contains both HAV &
HBV vaccines; given in series of 3 shots at 0, 1 mo,
& 6 mo

61.  Recommended those at  risk of infection & for
those wishing to obtain immunity
 U.S. moving toward universal childhood
immunization

62.  Children living in US areas with incidence >
20/100,000
 Travel/residence in  incidence country
 Men who have sex with men
 Injection drug users
 People with clotting disorders
 Occupational risk
 Chronic liver disease

63.  Follows recognition of active case
 Immune globulin: 0.02 ml/kg IM
 Give ASAP & within 2 weeks
 Target those with close contact (household &
sexual), Day Care staff & attendees, common-source
exposures (e.g. food handler)

65.  FAMILY CALCIVIRIDAE
 27-38nm-nonenveloped ssRNA
 ICOSAHEDRAL-surface-depressions
 Etiology: RNA virus
 Mode of transmission: Fecal-oral
 Spectrum of illness: acute, self-limited hepatitis;
mortality in pregnant women

66.  MOI –contaminated water
 IP -2-8wks
 Mild selflimiting,epidemics
 No cirrhosis,chronic hepatitis

71.  IEM-monoclonal antibodies
 Elisa
 Western blot-IgM, IgG
 PCR –HEVRNA-faeces, sera

73. Weeks after Exposure
Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc
anti-HBsHBsAg
0 4 8 12 16 20 24 28 32 36 52 100
Titer
Acute Hepatitis B Virus Infection with Recovery

74. IgM anti-HBc
Total anti-HBc
HBsAg
Acute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52
Weeks after Exposure
Progression to Chronic Hepatitis B Virus Infection