A. The document discusses viral hepatitis, providing information on the different types of hepatitis viruses (A, B, C, D, E). It describes the viruses' characteristics such as their structure, incubation period, transmission route, and ability to cause chronic infection. B. Diagnosis of the hepatitis viruses involves detecting viral antigens, antibodies, RNA, or DNA in blood or liver tissue. Some types like hepatitis A can be prevented through vaccination and hygiene practices. Treatment focuses on suppressing viral replication through antiviral drugs. C. While most hepatitis viruses cause acute, self-limiting illness, hepatitis B and C frequently result in chronic infection and long-term complications like cirrhosis if left untreated.

3. 3

4. Viral hepatitis
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5. Normal liver
What is hepatitis?
What is viral hepatitis?
Clinicopathology of viral hepatitis
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6. Normal liver
Normal anatomy
-the largest parenchymal organ
-The liver has a dual blood supply:
the portal vein provides 60% to 70%
the hepatic artery supplies 30% to 40%.
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7. *FUNCTIONS OF THE LIVER:
1-Carbohydrate
metabolism :
Glycogenesis
Glycogenolysis
Gluconeogenesis
8
3-Protein metabolism :
 anabolism
 deamination
 urea formation
4-Secretion of bile.
5-Detoxification
2-fat metabolism:
6-Metabolism of
Ketogenesis.
vitamins A,D,K,B
Cholesterol synthesis.
7-Clotting factors 25 October 2013
Viral hepatitis

8. hepatic microarchitecture is based on
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9. 12
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10. -Hepatitis means inflammation in the liver
-can be caused by variety of exposure to:
1-hepatitis virus
2-toxins
3-drugs
4- Bacteria
5- Parasites
- Can be both acute and chronic
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11. *Systemic viral infections can involve the liver as in :
I.
infectious mononucleosis (Epstein-Barr virus) which may
cause a mild hepatitis during the acute phase.
II. cytomegalovirus infection, particularly in the newborn or
immunosuppressed patient.
III. yellow fever (yellow fever virus), which has been a major
and serious cause of hepatitis in tropical countries.
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12. I.
Infrequently, in children and immunosuppressed patients, the
liver is affected in the course of rubella, adenovirus, herpes
virus, or enterovirus infections.
II. However, unless otherwise specified, the term viral hepatitis is
applied for hepatic infections caused by a group of viruses
known as hepatotropic virus (hepatitis viruses A, B, C, D, and
E) that have a particular affinity for the liver .
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14. an acute infectious disease of the liver caused by the
hepatitis A virus (HAV).
Type of virus: ssRNA.
 Frequency of chronic liver disease:
Never
 Frequency of acute liver disease:
-Approximately 40% of all acute viral hepatitis is caused by
HAV.
incubation period:
-is between two and six weeks and the average incubation
period is 28 days.
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15. transmission:
-transmitted person-to-person by
 ingestion of contaminated food or water or
 through direct contact with an infectious person.
 Hepatitis A can be transmitted by the parenteral route but very
rarely by blood and blood products.
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17. Unlike other members of the Picornaviruses this virus requires
an intact eukaryote initiating factor 4G (eIF4G) for the initiation
of translation. The requirement for this factor results in an
inability to shut down host protein synthesis unlike other
picornaviruses. The virus must then inefficiently compete for
the cellular translational machinery.
There is no apparent virus-mediated cytotoxicity
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18.  low-income regions (sub-Saharan Africa and
parts of South Asia) have high endemicity levels
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19. • specific diagnosis is made
by the detection of HAVspecific IgM antibodies in
the blood.
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20. A. Hepatitis A can be
prevented by
vaccination good
hygiene and
sanitation.
B. The vaccine protects
against HAV in
more than 95% of
cases for longer than
20 years.
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21. 24
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22. 25
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23.  Type of virus:
Hepatitis B virus is an hepadna virus from hepatotrophic
and DNA because it is a DNA virus
The viruses replicate through an RNA intermediate form by
reverse transcription.
Frequency of chronic liver disease
-10%
The acute illness causes liver inflammation, vomiting,
jaundice and rarely, death.
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24.  Mean incubation period:
1–4 months.
 Transmission:
 Transmission of hepatitis B virus results from exposure to
infectious blood or body fluids containing blood.
 Possible forms of transmission include:
sexual contact
blood transfusion
reuse of contaminated syringe
vertical transmission
between family members, possibly by contact of no intact
skin or mucous membrane with secretions or saliva containing
HBV.
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25. 28
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26. B
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27. 30
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28.  During HBV infection, the host immune response
causes both hepatocellular damage and viral
clearance.
 the adaptive immune response, particularly virus-specific
cytotoxic T lymphocytes (CTLs), contributes to most of the
liver injury associated with HBV infection.
 CTLs eliminate HBV infection by killing infected cells and
producing antiviral cytokines, which are then used to purge
HBV from viable hepatocytes.
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29.  high prevalence areas such as
china and South East Asia, Africa,
transmission during childhood is a
significant factor
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30. 33
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31.  assays, for detection of hepatitis B
virus infection involve serum or blood
tests that detect either viral antigens
(proteins produced by the virus) or
antibodies produced by the host.
 PCR tests have been developed to
detect and measure the amount of
HBV DNA.
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32.  Several vaccines have been developed by Maurice Hillman
for the prevention of hepatitis B virus infection.
 the avoidance of transmission: unprotected sexual contact,
blood transfusions, re-use of contaminated needles and
syringes, and vertical transmission during child birth. Infants
may be vaccinated at birth.
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33. A. Hepatitis B virus DNA persists in the body after
infection and in some people the disease recurs.
Although rare, reactivation is seen most often in
people with impaired immunity HBV goes
through cycles of replication and non-replication.
B. Patients who undergo chemotherapy are at risk
for HBV reactivation. The current view is that
immunosuppressive drugs favor increased HBV
replication while inhibiting cytotoxic T cell
function in the liver.
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34. Acute hepatitis B infection does not usually require treatment
because most adults clear the infection spontaneously. Early
antiviral treatment may only be required in fewer than 1% of
patients, whose infection takes a very aggressive course
(fulminant hepatitis) or who are immunocomprimised .
On the other hand, treatment of chronic infection may be
necessary to reduce the risk of cirrhosis and liver cancer.
Although none of the available drugs can clear the infection,
they can stop the virus from replicating,
Response to treatment differs between the genotypes.
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35. 38
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36. Type of virus:
-ssRNA
-HCV is a small-enveloped virus with one single-stranded
positive-sense RNA molecule
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37. Frequency of chronic liver disease:
Hepatitis C virus (HCV) is a major cause of liver disease
worldwide(∼80%).
 Acute disease:
Between 60% and 70% of people infected develop no symptoms
Persistent infection:
85-100%
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38. Clinical illness (jaundice):
30-40% (20-30%)
Incubation period :
Average 6-7 weeks
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39. Mode of transmission:
1. Parental: inoculations and blood transfusion
2. Vertical transmission
3. Close personal contact – sexual contact.
4. intranasal cocaine use is a risk factor
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40. 1) In primary HCV infection, liver cell damage correlates with the
development of the host immune response -- not with infection
and HCV viral replication.
2) Chronic HCV replication can occur without significant liver
cell damage.
3) HCV infection of liver cells does not appear to kill the infected
liver cells.
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41. 5) Immunosuppression of people with HCV infection results in
transient improvement in liver function tests, despite a surge
in HCV RNA levels.
6) Liver cell damage is associated with an inflammatory
infiltrate, and liver-infiltrating HCV immune cells associated
with areas of liver damage suggest a causative role.
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42.  Immune Responses to HCV Infection:
• neutralizing antibodies are produced during HCV infection,
but they do not appear to be protective against re-infection in
humans or in chimpanzees
• The more critical determinant seems to be the cell-mediated
immune response, or the T-cell (Cd4) response.
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43. o Prevalence is higher in some
countries in Africa and Asia.
o Egypt has the highest
seroprevalence for HCV, up to
20% in some areas.
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44. 47
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45.  HCV antibody - generally used to diagnose hepatitis C
infection. Not useful in the acute phase as it takes at least 4
weeks after infection before antibody appears.
 HCV-RNA - various techniques are available e.g. PCR and
branched DNA.
 HCV-antigen -
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46. Screening of blood, organ, tissue
donors.
High-risk behavior modification.
Blood and body fluid precautions
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47. 50
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48. Interferon
The response rate is around 50% but 50% of
responders will relapse upon withdrawal of
treatment.
Ribavirin
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49. 52
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50. Virus type:
unique RNA virus that is dependent for its life cycle on HBV.
Frequency of chronic liver disease:
% (coinfection); ≤70% for super infection.
Mean incubation period:
1–4 months.
Route of transmission:
Parenteral.
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51. Infection with HDV arises in the following settings:
Acute coinfection :
occurs following exposure to serum containing both HDV and HBV.
The HBV must become established first to provide the HBsAg
necessary for development of complete HDV virions.
Super infection:
occurs when a chronic carrier of HBV is exposed to a new inoculum
of HDV. This results in disease 30–50 days later.
Helper-independent latent infection :
observed in the liver transplant setting.
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52. HDV RNA detection.
IgM anti-HDV is the most reliable indicator of recent
HDV exposure.
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53. 56
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54.  limited to IFN-α.
 Other antiviral agents for HBV have
not shown effectiveness.
57
-HBV-HDV Coinfection:
Pre or post exposure prophylaxis to prevent HBV
infection.
-HBV-HDV Super infection
Education to reduce risk behaviors among persons
with chronic
HBV infection.
Vaccination for HBV can also prevent HDV
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infection.

55. 58
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56. Type of virus:
I. Un enveloped, positive-stranded RNA virus in the Hepevirus
genus .
 frequency of chronic liver disease: Never
In most cases the disease is self-limiting; HEV is not associated
with chronic liver disease or persistent viremia.
 Mean incubation period: 4–5 weeks
 Route of transmission: Fecal-oral.
 Illness severity: Increased with age
 Diagnosis:
 PCR for HEV RNA
 detection of serum IgM and IgG antibodies
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57. Hepatitis E is prevalent in most developing countries,
and common in any country with a hot climate.
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58.  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
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59. 62
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60.  type of virus:
A flavivirus bearing similarities to HCV
 Transmission:
HGV is transmitted by contaminated blood or blood
products, and via sexual contact.
 Liver diseases caused by the virus:
However, HGV is inappropriately named: it is not
hepatotropic and does not cause elevations in serum
aminotransferases. Instead, the virus appears to
replicate in the bone marrow and spleen.
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61. 64
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62. Each of the hepatotropic viruses can cause acute asymptomatic
or symptomatic infection.
A small number of HBV-infected adult patients develop
chronic hepatitis. In contrast, HCV is notorious(infamous) for
chronic infection.
HAV and HEV do not cause chronic hepatitis.
Although HBV and HCV are responsible for most cases of
chronic hepatitis.
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63. Yes, there are many other causes of
chronic hepatitis including :
i. chronic alcoholism.
ii. drugs (e.g., isoniazid, α-methyldopa,
methotrexate)
iii. toxins

64.  acute asymptomatic infection with recovery .
 Acute symptomatic hepatitis with recovery,
anicteric(without jaundice) or icteric (jaundiced ).
 Chronic hepatitis, without or with progression to
cirrhosis.
 Fulminant hepatitis with massive to submissive
hepatic necrosis.

65.  identified only incidentally on the basis of
minimally elevated serum transaminases or by the
presence of antiviral antibodies
 Worldwide, HAV and HBV infection are frequently
subclinical events in childhood, verified only in
adulthood by the presence of anti-HAV or anti-HBV
antibodies.

66.  acute asymptomatic infection with recovery .
 Acute symptomatic hepatitis with recovery,
anicteric(without jaundice) or icteric (jaundiced ).
 Chronic hepatitis, without or with progression to
cirrhosis.
 Fulminant hepatitis with massive to submissive
hepatic necrosis.

67. o Acute hepatitis is liver inflammation that lasts
less than six months and often is of sudden
onset.
o This type of hepatitis is most often caused by
infection with the hepatitis A virus, but it also
can occur as a result of infection with the
hepatitis viruses B, C, D or E.

68. An incubation period.
preicteric phase.
icteric phase.
Convalescence.

69. Anorexia
Headache
Malaise
General Fatigue
Influenza like symptoms
Muscle and joint pains
Discomfort in upper abdomen
Diarrhea
Distaste for cigarettes
Fever, rash and arthralgia , in case of Hepatitis B sue to
circulating immune complexes.

70. • It is usual in adult (but not children) with HAV but is absent in
about half of the cases of HBV and the majority of cases of
HCV.
• caused by conjugated hyperbilirubinaemia due to intra hepatic
cholestasis.
• Symptoms:
- Pain in Rt Hypochondrium
-Pruritus due to retention of bile salts
-High colored urine.

71.  The recovery phase begins with resolution of jaundice
which occurs about six to eight weeks after exposure.
 Symptoms typically diminish even though the liver still
may be tender and enlarged. In most cases, liver function
tests return to normal.

72.  Hepatitis and other causes of liver inflammation can damage the
liver in two different ways:
The first is
direct damage caused by infection of liver cells
The second mechanism
is mediated by the immune system’s inflammatory response to the
infection.

73. Macroscopically: The liver is enlarged and yellowish or
greenish in color.
Microscopically:
take the form of
 -diffuse swelling “ballooning
degeneration”
 An inconstant finding is cholestasis,
with bile plugs in canaliculi and brown
pigmentation of hepatocytes.
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74. 77
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75. Rupture of the cell membrane leads to cell death and focal loss
of hepatocytes. The sinusoidal collagen reticulin framework
collapses where the cells have disappeared, and scavenger
macrophage aggregates mark sites of hepatocyte loss.
Apoptosis, Apoptotic hepatocytes shrink, become intensely
eosinophilic, and have fragmented nuclei; Apoptotic cells are
rapidly phagocytosed by macrophages and hence might be
difficult to find, despite a brisk rate of hepatocyte injury.
Necrosis of Liver Cells : The necrosis is variable in extend
and degrees.

76. Necrosis of Liver Cells :
The necrosis is variable in extend and degrees.:
1. Necrosis of isolated liver cell or Piecemeal necrosis
2. Severe Necrosis
3. Bridging Necrosis:
Extensive necrosis connecting portal to portal , central to central
or portal to central parts of the adjacent lobule.
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78.  Hypertrophy and hyperplasia of Kupffer cells:
They often contain Lipofuscin derived from dead hepatocytes.
 Infiltration of portal tract with inflammatory cells:
Lymphocytes, plasma cells and macrophages.
 Evidence of hepatocytic regeneration:
during the recovery phase
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79. Detail of lobular parenchyma in mild acute viral hepatitis C.
Eosinophil condensation of hepatocellular cytoplasm (Mallory bodylike) and rounded eosinophil fragments of apoptotic hepatocyte, with
a few adjacent mononuclear inflammatory cells. (H&E)
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80. Acute viral hepatitis B. Centrilobular area of liver lobule,
characterized by liver cell pleomorphism (including ballooning
of hepatocytes), some canalicular bilirubin stasis, focal liver cell
loss, and mononuclear (mainly lymphocytic) inflammatory
infiltration. (H&E)
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81. 1. Acute liver failure (Fulminant Hepatitis)
2. Progression to chronic hepatitis
3. Post necrotic liver cirrhosis
4. Hepatocellular carcinoma
5. Aplastic Anemia
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82. 85
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83.  Chronic hepatitis is defined as symptomatic,
biochemical, or serologic evidence of continuing or
relapsing hepatic disease for more than 6 months.
 HCV infection causes chronic hepatitis at a high
frequency while only a small number of patients with
HBV infection develop chronic disease.
 The clinical features of chronic hepatitis are extremely
variable and are not predictive of outcome.
.

84.  In some patients the only signs of chronic disease are
persistent elevations of serum transaminases.
 The most common symptom is fatigue; less common
symptoms are malaise, loss of appetite, and occasional
bouts of mild jaundice.

85.  Occasionally, in cases of HBV and HCV, immune complex
disease may develop secondary to the presence of circulating
antibody-antigen complexes, in the form of vasculitis and
glomerulonephritis Cryoglobulinemia is found in about 35%
of individuals with chronic hepatitis C.
 Age at the time of infection is the best determinant of
chronicity. The younger the age at the time of infection, the
higher the probability of chronicity.

86.  HCV is by far the most common cause of chronic viral
hepatitis.
 HCV infection is potentially curable. Treatment is
currently based on combination of pegylated IFN-α and
ribavirin. The response to therapy depends on the viral
genotype; patients with genotype 2 or 3 infection
generally have the best responses.
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87. microscopically
 The histologic features of chronic hepatitis range from
exceedingly mild to severe.
 In the mildest forms, inflammation is limited to portal tracts and
consists of lymphocytes, macrophages, occasional plasma
cells, and rare neutrophils or eosinophils.
Liver architecture is usually well preserved but hepatocyte
apoptosis throughout the lobule may occur in all forms of chronic
hepatitis.

88.  In chronic HCV infection, common findings
(occurring in 55% of HCV infections) are
lymphoid aggregates and bile duct reactive
changes in the portal tracts, and focal mild to
moderate macrovesicular steatosis., continued
interface hepatitis and bridging necrosis
between portal tracts and portal tracts-toterminal hepatic veins, are harbingers of
progressive liver damage.
 The hallmark of chronic liver damage is the
deposition of fibrous tissue.

89. Liver biopsy specimen; chronic hepatitis
with fibrosis and porto-portal bridge
formation
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90. Liver biopsy specimen showing ground-glass
appearance of hepatocytes in a patient with
hepatitis B.
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91.  Continued loss of hepatocytes and
fibrosis results in cirrhosis
It is characterized by irregularly sized nodules
separated by variable but mostly broad scars,
(post-necrotic cirrhosis )
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92. 95
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93. Grossly:
I. macro nodular cirrhosis of the liver.
II. Macro nodular lesions are greater than 3 mm and have
thick septa as well as invasion of septa within the nodule.
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94. Macronodular Cirrhosis: Larger nodules separated by wider scars
and irregularly distributed throughout the nodular Cirrhosis:
Small rather uniform 3mm nodules separated by thin fibrous septa
usually due to a chemical agent as alcohol which diffuse uniformly
throught the liver.

95. 98
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96. Bridging confluent lytic necrosis in severe chronic viral hepatitis B.
Inflamed portal tract ‘bridged’ through area of necrosis with
centrilobular area (lower left). The upper right part corresponds to an
area of extensive lytic necrosis in phase of postnecrotic collapse of
the reticulin framework and early fibrosis. (H&E)
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97. Jaundice
the yellowing of some portions of your skin due to accumulation of
toxins that are easily released through the epidermal layer.
 fatigue and general weakness: your body does not function
normally, not being able to sort out the poisons from the useful
substances and it launches them all into the bloodstream,
destroying itself from within

98.  weight loss and lack of muscle control:
it is a natural consequence of the fatigue. Your system does not
process whatever food you ingest
if you do not eat, your muscle tone goes down and you start to
lose control over your limbs.
the presence of blood in your stool (turning the feces black and
frazzled) and in your vomit: it is a sure sign that the linings of
your stomach or the walls of the esophagus have been
perforated;

99. high temperature:
it is normal for a cirrhosis patient to be riddled with infectious
agents and to often suffer from fever attacks.
swelling in your abdominal cavity and your joints:
this is due to the accumulation of liquid that cannot be eliminated
because of the lack of proper function of the liver.

100.  acute asymptomatic infection with recovery .
 Acute symptomatic hepatitis with recovery,
anicteric(without jaundice) or icteric (jaundiced ).
 Chronic hepatitis, without or with progression to
cirrhosis.
 Fulminant hepatitis with massive to submissive
hepatic necrosis.

101.  Hepatic insufficiency that progresses from onset of
symptoms to hepatic encephalopathy within 2 to 3
weeks in individuals who do not have chronic liver
disease is termed fulminant hepatic failure.
 Viral hepatitis is responsible for about 12% of cases of
fulminant hepatic failure; of these 8% are caused by
HBV infection and the rest by HAV.
 The pathogenesis of fulminant hepatic failure varies
depending on etiology. In the case of HBV-induced
fulminant hepatitis, there is massive apoptosis

102. Grossly:
 The distribution of liver destruction is extremely
capricious, since the entire liver or only random
areas may be involved.
 With massive loss of mass, the liver may shrink to as
little as 500 to 700 gm., and becomes a limp, red
organ covered by a wrinkled, too-large capsule.
 On transection ,necrotic areas have a muddy red,
mushy appearance with hemorrhage.
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103. 106
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104. Microscopically:
 complete destruction of hepatocytes -a collapsed reticulin
framework and preserved portal tracts.
 little inflammatory reaction.
 Alternatively, with survival for several days, there is a
massive influx of inflammatory cells to begin the
phagocytic cleanup process.
 Survival for more than a week may permit the replication
of residual hepatocytes.
107
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105. 108
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108. 111
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109. -Asmaa Ismael Mohamed
-Asmaa Gamil Abdulkhaleh
-Eslam mohamed darahem
-Eslam Aziz
-Eslam Magdy
Asmaa gamil Abdeulkhalek
112
153
155
147
143
144
155
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110. 113
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111. 114
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112. 115
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