This document summarizes information about Hepatitis virus prepared by Abubakr Sdiq Sargaty. It provides an overview of different Hepatitis viruses including HAV, HBV, HCV, HDV and HEV. Key details include their nucleic acid, mode of transmission, severity and chronicity. The document also discusses viral replication, geographic distribution, clinical features, pathogenesis, diagnosis and treatment of Hepatitis B virus in more depth. It emphasizes the importance of vaccination programs in eliminating HBV transmission.

1. University of sulaimani
Collage of science
Department of biology
SIMINAR ABOUT :
Hepatitis virus
Prepared by:
Abubakr Sdiq Sargaty

2. Hepatitis virus

3. Overview of Hepatitis Virus
Virus Virus group Nucleic Mode of infection Severity
acid (chronicity)
HAV Enterovirus RNA Fecal-oral +(acute)
72(heptovirus)
HBV hepadnavirus DNA Percutaneous; ++(chronic)
Permucosal
HCV Flavivirus RNA Blood(transfusion- + (chronic)
associated)
HDV B-dependent RNA blood + (chronic)
small virus
HEV Calicivirus RNA Fecal-oral +(acute)
HGV ? RNA Blood ?

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

5. 
Human cytomegalovirus

Epstein-Barr virus
 Herpes simplex virus
 Yellow fever virus

Rubella.

6. Hepatitis A virus

7. Structure

Small, non-
enveloped
icosahedral
particle,

27 nm in
diameter
 ssRNA

9. Replication

Unlike other picornaviruses, however, HAV is not
cytolytic and is released by exocytosis.
 Laboratory isolates of HAV have been adapted to
growth in primary and continuous monkey kidney cell
lines, but clinical isolates are very difficult to grow in
cell culture.

10. Resistance
Stable to:
acid at pH 3
Solvents(ether,chloroform)
detergents
saltwater,groundwater(months)
drying(stable)
temperature
4℃ : weeks
56℃ for 30minutes: stable
61℃ for 20minutes: partial inactivation

11. Resistance
Inactivated by:
chlorine treatment of drinking water
formalin(0.35%,37℃ ,72hours)
acetic acid(2%,4hours)
B-propiolactone 丙内酯 (0.25%,1hours)
Ultraviolet radiation(2μW/ ㎝ 2/min)

12. Hepatitis A Virus Transmission

Virus can be transmitted via fecal-oral route
ingestion of contaminated food and water can
cause infection

HAV in shellfish is from sewage-contaminated
water

Virus can be transmitted by food handlers, day-
care workers, and children.

13. Concentration of Hepatitis A Virus
in Various Body Fluids
Feces
Body Fluid
Serum
Saliva
Urine
100 102 104 106 108 1010
Infectious Doses per ml
Source: Viral Hepatitis and Liver Disease 1984;9-22
J Infect Dis 1989;160:887-890

14. Geographic Distribution of HAV
Infection
Anti-HAV Prevalence
High
Intermediate
Low
Very Low

15. Age-specific Mortality Due to Hepatitis A
Age C as e-
group
(ye ars Fatality
(per
) 1000)
<5 3.0
5-14 1.6
15-29 1.6
30-49 3.8
>49 17.5
Total 4.1
Source: Viral Hepatitis Surveillance Program, 1983-1989

16. Hepatitis A - Clinical
Features
Average 30 days
Incubation period Range 15-50 days
Jaundice by <6 yrs <10%
age group
6-14 yrs 40%-50%
>14 yrs 70%-80%

17. Hepatitis A - Clinical Features
 Milder disease than Hepatitis B;

asymptomatic infections are very common,
especially in children.
 Adults, especially pregnant women, may develop
more severe disease
 no chronic form of the disease.

Complications:
Fulminant hepatitis is rare: 0.1% of cases

18. Pathogenesis

19. Pathogenesis of HAV
 HAV replicates slowly in the liver without
producing apparent cytopathological effects
(CEPs). In the absence of cytolysis, the virus
readily establishes a persistent infection.

Jaundice, resulting from damage to the liver
 Antibody is detected and cell-mediated immune
responses to the virus

20. For example
 An epidemic of HAV that occurred in Shanghai, China,
in 1988 in which 300,000 people were infected with the
virus resulted from eating Anadara subcrenata
obtained from a polluted river.

21. Time course of HAV infection

23. Immunity

Antibody protection against reinfection is lifelong

24. Laboratory Diagnosis
 Viral particles in the stool, by electron microscopy

Specific IgM in serum

PCR HAV-specific sequences in stool

25. Treatment, Prevention and Control
 Prophylaxis with immune serum globulin given before
or early in the incubation period
 A killed HAV vaccine has been approved and is
available for use in children and adults at high risk for
infection.
 A live HAV vaccine has been developed in China.

26. Hepatitis B virus

27. Introduction

approximately 350 million people are infected
globally with HBV.

28. Structure
 Small, enveloped DNA
 The genome: a small, circular, partly double-stranded
DNA of 3200 base

Although a DNA virus, it encodes a reverse transcriptase
and replicates through an RNA intermediate.

29. Structure
 Dane particle, is 42 nm in
diameter.

Resist to treatment with: ether, a
low pH, freezing, and moderate
heating. This helps transmission
from one person to another.

30. Decoy Particles

HBsAg-containing particles
are released into the serum of
infected people and
outnumber the actual virions.

Spherical or filamentous

They are immunogenic and
were processed into the first
commercial vaccine against
HBV.

33. Structure  HBcAg HBsAg HBeAg

34. 15-25nm
42nm
HBsAg 20×20×200nm
28nm
HBcAg
DNA
HBeAg

35. Replication

HBV has a very defined tropism for the liver.
 Its small genome also necessitates economy, as
illustrated by the pattern of its transcription and
translation.

In addition, HBV replicates through an RNA
intermediate and produces and release antigenic
decoy particles.

39. Replication
 The entire genome can also be integrated into the host
cell chromatin.

HBsAg, but not other proteins, can often be detected in
the cytoplasm of cells containing integrated HBV DNA.
 The significance of the integrated DNA in the replication
of the virus is not known, but integrated viral DNA has
been found in hepatocellular carcinomas.

40. Global Patterns of Chronic HBV Infection
 High (>8%): 45% of global population
– lifetime risk of infection >60%
– early childhood infections common

Intermediate (2%-7%): 43% of global population
– lifetime risk of infection 20%-60%
– infections occur in all age groups

Low (<2%): 12% of global population
– lifetime risk of infection <20%
– most infections occur in adult risk groups

42. High-risk groups for HBVinfection
 People from endemic regions
 Babies of mothers with chronic HBV
 Intravenous drug abusers

People with multiple sex partners

Hemophiliacs and other patients requiting blood
and blood product treatments
 Health care personnel who have contact with blood

Residents and staff members of institutions for the
mentally retarded

43. Concentration of Hepatitis B Virus
in Various Body Fluids
High Blood ,Serum, Wound exudates
Moderate Semen, vaginal and menstrual secretions,
Saliva, amniotic fluid
Low/Not Urine , Feces, Sweat , Tears , Breast milk
Detectable

44. What determines the development of chronic vs.
acute infection

Age (chronic infections decrease with increasing age)
 Sex:
Syndrome: Males : Females
Chronic Infection: 1.5 : 1
Cirrhosis: 3:1
PHC: 6:1
 Route of infection (oral/sexual infections give rise to
less chronic cases than serum infection

45. Hepatitis B - Clinical
Features
• Incubation period: Average 60-90 days
Range 45-180 days
• Clinical illness (jaundice): <5 yrs, <10%
>5 yrs, 30%-50%
• Acute case-fatality rate: 0.5%-1%
• Chronic infection: <5 yrs, 30%-90%
>5 yrs, 2%-10%
• Premature mortality from
chronic liver disease: 15%-25%

46. Outcome of Hepatitis B Virus Infection 100
100
by Age at Infection
Symptomatic Infection (%)
80 80
Chronic Infection (%)
60 60
Chronic Infection
40 40
20 20
Symptomatic Infection
0 0
Birth 1-6 months 7-12 months 1-4 years Older Children
and Adults
Age at Infection

47. Pathogenesis(1)
 The virus starts to replicate within 3 days of its
acquisition,

Symptoms may not be observed for 45 days of
longer, depending on the infectious dose, the
route of infection, and the person.

49. Pathogenesis(2)
 Hypoimmune response.
IFN↓,HLA-I↓→CTL↓(An insufficient T-cell response )
 Cell mediated immunopathogenic damage.
CTL →acute hepatitis/chronic hepatitis

50. Pathogenesis (3)
 Immune complexes formed between HBsAg and anti-
HBs contribute to the development of hypersensitivity
reactions, leading to problems such as vasculitis 血管炎 ,
arthralgia 关节痛 , rash, and renal damage.

51. Pathogenesis(4)
 Pathogenic damage caused by autoimmunity
liver specific protein(LSP)
 Viral variation
HBeAg

52. Clinical Syndromes

53. Major
eterminants of
acute and chronic
HBV infection

54. Acute Infection

55. Symptoms of Acute Infection

56. Clinical
outcomes of
acute
hepatitis B
infection

57. The serological events associated with the typical course of acute
HBV disease

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

60. Chronic Infection

Chronic hepatitis occurs in 5% to 10% of people
with HBV infections, usually after mild or
inapparent initial disease.
 Detected by the finding of elevated liver enzyme
levels

61. Development of the chronic HBV carrier state

63. Typical Serologic Course
Progression to Chronic HBV Infection
Acute Chronic
(6 months) (Years)
HBeAg anti-HBe
HBsAg
Total anti-HBc
Titer
IgM anti-HBc
0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure

64. Primary Hepatocellular Carcinoma

The WHO estimates that 80% of all cases of
PHC can be attributed to chronic HBV
infections.
 HBV may induce PHC by promoting
continued liver repair and cell growth in
response to tissue damage or by integrating
into the host chromosome and stimulating cell
growth directly.

65. Lab. Diagnosis

The initial diagnosis of hepatitis can be made on
the basis of the clinical symptoms and the
presence of liver enzymes in the blood.
 The serology of infection describes the course
and the nature of the disease.

Acute and chronic HBV infect. Can be
distinguished by the presence of HBsAg and
HBeAg in the serum and the pattern of Ab to the
individual HBV antigens.

66. Diagnosis

During the symptomatic phase of infection,
detection of antibodies to HBeAg and HBsAg is
obscured because the antibody is complexed
with antigen in the serum.
 The best way to diagnose a recent acute
infection, especially during the period when
neither HBsAg nor anti-HBs can be detected,
is to measure IgM anti-HBc.

68. Diagnosis

Detection of serum HBVDNA: nucleic
hybridization; PCR.
 Detection of viral DNA polymerase.

69. Treatment

Interferon-alpha may be effective for treating
a chronic HBV infection.
 Hepatitis B immune globulin may be
administered within a week of exposure and to
newborn infants of HBsAg-positive mothers.

70. Elimination of Hepatitis B Virus Transmission
Objectives
• Prevent chronic HBV Infection
• Prevent chronic liver disease
• Prevent primary hepatocellular carcinoma
• Prevent acute symptomatic HBV infection

71. Elimination of Hepatitis B Virus Transmission
Strategy
• Prevent perinatal 围产期的 HBV transmission
• Routine vaccination of all infants
• Vaccination of children in high-risk groups
• Vaccination of adolescents
– all unvaccinated children at 11-12 years of
age
– “high-risk” adolescents at all ages
• Vaccination of adults in high-risk groups

72. 病毒抗原抗体系统检测结果分析
HBsAg HBeAg 抗- HBs 抗- HBe 抗- HBc 结果分析
＋ － － － － HBV感染或无症状携带
者
＋ ＋ － － － 急性或慢性乙型肝炎，
或无症状携带者
＋ ＋ － － ＋ 急性或慢性乙型肝炎
（ 传 染性强，“大三阳”）
＋ － － ＋ ＋ 急性感染趋向恢复
（“小三阳”）
－ － ＋ ＋ ＋ 既往感染恢复期
－ － ＋ ＋ － 既往感染恢复期
－ － － － ＋ 既往感染或“窗口期”
－ － ＋ － － 既往感染或接种过疫苗

73. Hepatitis C Virus

74. Introduction

The major cause of parenterally transmitted
non A non B hepatitis. It eluded identification
for many years. In 1989, the genome was
cloned from the serum of an infected
chimpanzee.

75. Features of Hepatitis C Virus Infection
Incubation period Average 6-7 weeks
Range 2-26 weeks
Acute illness (jaundice) Mild (<20%)
Case fatality rate Low
Chronic infection 75%-85%
Chronic hepatitis 70% (most asx)
Cirrhosis 10%-20%
Mortality from CLD 1%-5%
(chronic liver disease )

76. Common characteristics
 Putative Togavirus related to the Flavi and
Pesti viruses.Thus probably enveloped.

Has a ssRNA genome
 Does not grow in cell culture, but can infect
Chimpanzees

78. Transmission

Blood transfusions, blood products

organ donation
 Intravenous drug abusers
 community acquired: mechanism unclear. ?

Vertical transmission ?

sexual intercourse

79. Epidemiology

Causes a milder form of acute hepatitis than
does hepatitis B
 But 50% individuals develop chronic infection,
following exposure.
 Incidence endemic world-wide; high incidence
in Japan, Italy and Spain

80. Clinical syndromes

HCV can cause acute infections but is more
likely to establish chronic infections.
 Viremia
 Chronic persistent hepatitis

Chronic active hepatitiw

Cirrhosis
 Liver failure

81. Chronic Hepatitis C
Factors Promoting Progression or Severity
 Increased alcohol intake

Age > 40 years at time of infection

HIV co-infection
 ?Other
– Male gender
– Other co-infections (e.g., HBV)

82. Serologic Pattern of Acute HCV Infection
with Recovery
anti-HCV
Symptoms +/-
HCV RNA
Titer
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Months Years
Time after Exposure

83. Serologic Pattern of Acute HCV Infection with
Progression to Chronic Infection
anti-HCV
Symptoms +/-
HCV RNA
Titer
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Months Years
Time after Exposure

85. HCV Prevalence by Selected Groups
United States
Hemophilia
Injecting drug users
Hemodialysis
STD clients
Gen population adults
Surgeons, PSWs
Pregnant women
Military personnel
0 10 20 30 40 50 60 70 80 90
Average Percent Anti-HCV Positive

86. Laboratory diagnosis

1) Serology
Reliable serological tests have only recently
become available.
HCV-specific IgG indicates exposure, not
infectivity

2) PCR detects viral genome in patient's serum

89. Treatment, Prevention, and Control

Recombinant interferon-alpha is the only
known effective treatment for HCV.
 Illicit drug abuse and transfusion are the most
identifiable sources of HCV viruses.

90. Hepatitis D virus

91. Introduction

Defective virus which requires Hepatitis B virus
as a helper virus in order to replicate. Infection
only occurs in patients who are already infected
with Hepatitis B.

92. Structure

Virus particle 36
nm in diameter
encapsulated with
HBsAg, derived
from HBV

Delta antigen is
associated with
virus particles
ssRNA genome

93. Hepatitis D (Delta) Virus
δ antigen HBsAg
RNA

94. Replication

Transcription and replication of the HDV
genome are unusual. Specifically, the host
cell’s RNA polymerase II makes an RNA copy,
replicates the genome, and makes mRNA.

95. Geographic Distribution of HDV Infection
Taiwan
Pacific Islands
HDV Prevalence
High
Intermediate
Low
Very Low
No Data

96. Pathogenesis

Spread in blood, semen, and vaginal secretion.

It can replicate and cause disease only in
people with active HBV infections.
 Replication of the delta agent results in
cytotoxicity and liver damage.

97. Clinical Syndromes

Increases the severity of HBV infections.

Fulminant hepatitis

98. Hepatitis D - Clinical
Features
• Coinfection
– severe acute disease
– low risk of chronic infection
• Superinfection
– usually develop chronic HDV infection
– high risk of severe chronic liver disease

99. HBV - HDV Coinfection
Symptoms Typical Serologic Course
ALT
Elevated
anti-
Titer
IgM anti-HDV HBs
HDV RNA
HBsAg
Total anti-
HDV
Time after
Exposure

100. HBV - HDV Superinfection
Jaundice
Typical Serologic Course
Symptoms
Total anti-HDV
ALT
Titer
HDV RNA
HBsAg
IgM anti-HDV
Time after
Exposure

101. Laboratory Diagnosis

Detect the delta antigen of antibodies

ELISA and RIA

102. Hepatitis D - Prevention
• HBV-HDV Coinfection
Pre or postexposure prophylaxis to prevent
HBV infection
• HBV-HDV Superinfection
Education to reduce risk behaviors among
persons with chronic HBV infection

103. Hepatitis E Virus

104. Structure and Genome

30-32nm non-enveloped particle

s/s (+)sense RNA genome , ~7.5Kb.
 Genetic organization similar (not identical) to
Caliciviruses

106. Hepatitis E - Clinical
Features
• Incubation period: Average 40 days
Range 15-60 days
• Case-fatality rate: Overall, 1%-3%
Pregnant women, 15%-25%
• Illness severity: Increased with age
• Chronic sequelae: None identified

107. Geographic Distribution of Hepatitis E

109. Hepatitis E -
Epidemiologic Features
• Most outbreaks associated with
fecally contaminated drinking water
• Minimal person-to-person transmission

110. Prevention and Control Measures for
Travelers to HEV-Endemic Regions
• Avoid drinking water (and beverages with ice) of
unknown purity, uncooked shellfish, and
uncooked fruit/vegetables not peeled or prepared
by traveler
• IG prepared from donors in Western countries
does not prevent infection
• Unknown efficacy of IG prepared from donors in
endemic areas
• Vaccine?

111. Epidemiology

The delta agent infects children and adults
with underlying HBV infection, and people
who are persistently infected with both HBV
and HDV are a source for the virus.