ACUTE VIRAL HEPATITIS

1. CHAIRPERSON: DR.SANTOSH VASTRAD
STUDENT: DR.BASITH LATEEF

2. What is Viral Hepatitis ?
Viral hepatitis is a systemic disease
with primary inflammation of the
liver by any one of a heterogenous
group of hepatotropic viruses

3. Clinical Terms
 Hepatitis: inflammation of liver
 Acute Viral Hepatitis: symptoms last less than 6 months
 Acute Hepatic Failure: is the appearance of severe complications rapidly
after the first signs of liver disease (such as jaundice), & indicates that the
liver has sustained severe damage (loss of function of 80-90% of liver
cells).Massive hepatic necrosis with impaired consciousness within 8
weeks of onset of illness.
 Chronic Hepatitis: Inflammation of liver for at least 6 months
 Cirrhosis: Replacement of liver tissue fibrosis(scar tissue).These changes
lead to loss of liver function.
 Fulminant Hepatitis: severe impairment of hepatic functions or severe
necrosis of hepatocytes in the absence of preexisting liver disease.

8. ACUTE VIRAL HEPATITIS
Acute Viral Hepatitis is a systemic infection
with mainly involvement of liver & rarely can
cause extrahepatic manifestation.
 Hepatitis A and E viruses commonly cause
acute viral hepatitis.
 Other infections like CMV ,EB virus,
coxsackie virus and adeno virus can cause
acute hepatitis.

9. • About 15 to 30% of acute cases in india are
caused by HBV.
• HDV is found in 10% of patients with HBV.
• HCV is a rare cause of acute hepatitis.
• Majority of AVH are self limiting.
• Chances of fulminant liver failure varies
from 0.01 to 1%

11. Hepatitis A
 Hepatitis A (formerly known as ―infectious hepatitis or
epidemic jaundice) is an acute infectious disease caused by
Hepatitis A virus (HAV).
 Originally called as enterovirus 72
 The disease is benign with complete recovery in several weeks.
 It is the only human hepatitis virus which can be cultivated in
vitro.
 M/C of hepatits in children. transmission by feco-oral route.
 Virus is shed in feces during the late Incubation period &
prodromal phase of illness.

12. EPIDEMIOLOGY
• It has worldwide distribution and highly
endemic in developing countries
• India is hyperendemic.
• Most of the cases occur in areas of poor
hygeine and sanitation.

13. Geographic Distribution of HAV
Infection
Anti-HAV Prevalence
High
Intermediate
Low
Very Low
Dr.T.V.Rao MD 13

15. Agent factors
a) AGENT: The causative agent, the hepatitis A virus, is an
enterovirus of the Picornaviridae family. It multiplies
only in hepatocytes.
STRUCTURE
•Picorna virus
•Single stranded RNA virus
•Measures 27-28nm.
•Icosahedral shape
•Non enveloped.
•Has one serotype & more than three genotypes.

16. b) RESISTANCE:
The virus is fairly resistant to heat and chemicals.
Withstands heating to 60 deg C for 1 hr.
It is not affected by chlorine in doses usually employed for
chlorination.
 Formalin is stated to be an effective disinfectant.
The virus is inactivated by ultraviolet rays and by boiling
for 5 minutes or autoclaving.
It survives exposure to ether and acid at pH 3.
Inactivated by heat at 85 deg C for 1 min.
Survives in sea water & dried feces for 4 weeks.

17. c) RESERVOIR OF INFECTION: The human cases are
the only reservoir of infection.
d) PERIOD OF INFECTIVITY : The risk of transmitting
HAV is greatest from 2 weeks before to 1 week after the
onset of jaundice.
e) INFECTIVE MATERIAL : Mainly man’s faeces.
f) VIRUS EXCRETION: HAV is excreted in the faeces
for about 2 weeks before onset of jaundice and for up to 2
weeks thereafter.

18. Host factors
a) AGE: Infection with HAV is more frequent among children
than in adults. However, people from all ages may be infected
if susceptible.
b) SEX: Both sexes are equally susceptible.
c) IMMUNITY: Immunity after attack probably lasts for life.
Environmental factors
• Cases may occur throughout the year.
• In India the disease tends to be associated with periods of
heavy rainfall.

19. Routes of transmission
1. Feaco-oral transmission
2. Intra familial sexual contact with an infected person
3. Rarely parenteral
4. Ingestion of contaminated food.
Persons at risk
1. Travellers to endemic areas
2. Sexual contacts of infected persons
3. Household members
4. Men having sex with men
5. Drug abusers.
INCUBATION PERIOD : 15-50 DAYS

20. Detetction and Infectivity of HAV

22. Replication cycle of HAV

23. CLINICAL FEATURES
• CLINICAL PATTERNS.
1. Asymptomatic without jaundice
2. Symptomatic with jaundice and self limiting after 8
weeks.
3. Cholestatic with jaundice lasting 10 weeks or more.
4. Relapsing (10%)
5. Fulminant hepatic failure.

24. Nausea
Loss of appetite
Vomiting
Fatigue
Fever
Liver enlargement
Dark urine
Pale stool
Jaundice
Stomach pain
diarrhea
Cervical lymphadenopathy
A person may have all, some or none of these
Symptoms

25. Approach to Diagnosis
Hepatitis A (HAV)
IgM anti-HAV
Negative Positive
Assay “total” anti-HAV as clinically
indicated
(-)
Not immune to
HAV
Acute HAV
infection
(+)
Immune to HAV

26. DIAGNOSIS
1. Demonstration of Virus in feces, blood, bile:
By: Immunoelectron microscopy
2. Virus Isolation:
3. Detection of Antibody :By ELISA
4. Biochemical tests:
i) Alanine aminotransferase (ALT)
ii) Bilirubin
iii) Protein
5. Molecular Diagnosis : RT PCR of feces

27. INVESTIGATIONS
URINE AND FEACES
• Bilirubin appears in urine before jaundice.
• Urobilnogen is found in late pre icteric phase it
disappears at the height of jaundice ,its
reappearence indicates recovery.

28. LIVER BIOCHEMISTRY
• Conjugated bilirubin rises early even before total
bilirubin.
• A raised serum AST or ALT, which can sometimes be
very high, precedes the jaundice.
• ALP level is usually < 3 times elevated. Serum albumin
globulin are unchanged.
• In the icteric stage the serum bilirubin reflects the level
of jaundice.
• Serum AST reaches a maximum 1-2 days after the
appearance of jaundice, and may rise above 500 IU/L,
the aminotransferases may remain elevated for some
weeks and occasionally for up to 6 months.

29. HAEMATOLOGICAL CHANGES
• Leucopenia,and neutropenia is seen in pre icteric
phase.
• Aplastic anemia is rare.
• PT is prolonged.
• An INR of >1.5 is considered severe acute hepatitis.
• ESR is raised in preicteric phase falls to normal
during jaundice and rises again during recovery &
returns to normal after recovery.

30. VIRAL MARKERS :
• IgM anti HAV indicates acute infection
• IgG anti HAV suggests previous infection or vaccination.
• HAV RNA can be detected in blood, stools and liver but it
is not used.
• IgG antibodies are common in the general population over
the age of 50 years, but an anti- HAV IgM means an acute
infection.
• In areas of high prevalence most children have antibodies
by the age of 3 years following asymptomatic infection.

32. • Treatment has little effect in altering the course.
• It is wise to treat all attacks as fatal.
• Bed rest is advised till jaundice disappears, a less
strict regime if patient is young
• Rest after each meal is advised.
• The traditional low fat & high carb diet is
advised.
Treatment

33. • When appetite returns, high proteins are
advised.
• Corticosteroids are not indicated except
occasionally in cholestatic hepatitis A.
• Follow up is advised till three months.
• Alcohol denied for 6 months preferably 1 year

34. Complications
Acute fulminant hepatitis.
Cholestatic hepatitis
Nephrotic syndrome
Chronic autoimmune hepatitis.
Relapsing hepatitis.
Extra hepatic manifestations are rare

35. Extra hepatic manifestations
Rash
Artharlgias
Leucocytoclastic vasculitis
Glomerulonephritis
Cryoglobinemia
TEN
Renal failure
Aplastic anemia
Optic neuritis
Red cell aplasia
Thrombocytopenia

36. PREVENTION
 Provision of clean drinking water
 Proper sewage disposal
 Public education about hygeine
 Highly effective active and passive
immunisation are available.

37. PROPHYLAXIS
1. IMMUNE SERUM GLOBULIN
o ISG is being replaced by vaccine
o ISG is still used in those with acutely exposed
o It is ineffective in hyperendemic areas or in interrupting
common source outbreaks.
2. VACCINATION
o Pre exposure prophylaxis with inactivated vaccines can
give protection till 20 years
o Passive immunisation is used in post exposure
prophylaxis-0.02ml/kg BW on deltoid within two
weeks along with active immunisation.

40. Immunization against HAV in chronic illnesses
Pre-exposure prophylaxis recommended :
• Chronic liver disease (risk of HAV-related morbidity
& mortality)
• Patients awaiting liver transplantation
• Patients already undergone liver transplantation.
• HIV patients (response to vaccination may be reduced
because of a blunted immune system)

41. OUTCOME
Recovery in > 99%
Clinical relapse in 4-20%
Rarely need to hospitalize or transplant
Fulminant hepatitis <0.35%

42. HEPATITIS E
Also known as enterically transmitted non-A non-
B(NANB) virus or epidemic NANB.
 Classified in the genus HERPES virus under the family
CALIVIRIDAE.
 Single stranded +sense RNA virus.
 The viral particles in stool are spherical, 27 to 34 nm in
diameter with icosahedral symmetry, and unenveloped,
and they exhibit spikes on their surface.

44.  A unique feature is the clinical severity and high case
fatality rate of 15-25% in pregnant women, especially in
the last trimester of pregnancy.
 Highest attack rates among young adults 15-40 years
with relative sparing of children.
 Characteristically associated with cholestasis
 There are 4 Genotypes in india.
 Genotype 1 is common in india.
 It is highly endemic
 Faecoral transmission is common.
 Rarely parentrally transmitted.

45. SIMILARITIES IN HAV & HEV:
1. Both have acute onset with mild illness.
2. Both are transmitted by feco-oral route.
DIFFERENCES IN HAV & HEV:
1. HAV is more common in children. While HEV is more
common in young adult.
2. HEV can cause fulminant hepatitis in pregnant women
( not HAV).
3. Secondary attack rate of HEV is very low (2-3%) as
against 10-20% in HAV.

46. DR.T.V.RAO MD 46

48. • Travellers to endemic areas
• Sexual contacts of infected persons
• Household members
• Men having sex with men
• Drug abusers.
No potential for chronicity.
ANIMAL RESEVOIRS : Pigs
INCUBATION PERIOD : 2-9 WEEKS
PERSONS AT RISK

49. Clinical features
Varying clinical manifestations.
1. Anicteric
2. Icteric hepatitis
3. Fulminant hepatic failure.
4. Asymptomatic infection

50. Pathogenesis

52. Treatment and prevention
• Acute hepatitis E is self limiting.
• Supportive care and no specific intervention
• Isolation of infected persons is not indicated.
• Patients with fulminant hepatitis require anti
edema measures and liver transplantation is to
be considered.
• In pregnant women no proven evidence of
terminating pregnancy is documented.

53. • A vaccine using a recombinant truncated form of
HEV capsid protein, produced in Spodoptera
frugiperda cells infected with a recombinant
baculovirus and adsorbed on aluminium
hydroxide, has undergone phase 2 trails.
• Vaccine showed 95.5% protective efficacy
against hepatitis E disease among those who
received three doses and 88.5% efficacy in an
intention-to-treat analysis among those who had
received only the first dose.

54. • The vaccine may be useful for travelers to
HEV-endemic regions and for pregnant women
and persons with chronic liver disease who
reside in such regions.
• Finally, cost considerations will determine
whether this new and promising vaccine can
be used

55. 1. Maintaining quality standards for public water
supplies
2. Establishing proper disposal systems to eliminate
sanitary waste.
3. Maintaining hygienic practices such as hand washing
with safe water, particularly before handling food;
4. Avoiding drinking water and/or ice of unknown
purity;
5. Avoiding eating uncooked shellfish, and uncooked
fruits or vegetables that are not peeled or that are
prepared by people living in or travelling in highly
endemic countries
Prevention
Dr.T.V.Rao MD 55

56. FULMINANT HEPATITIS
Trey and Davidson define ALF as occurrence of
encephalopathy with or without coagulopathy within 8
weeks of onset of symptoms of acute hepatitis in an
individual without any history of pre-existing liver
disease.
Rapid development of severe acute liver injury with
impaired function and encephalopathy in previously
normal liver(8 weeks) or (2 weeks)with underlying
liver dysfunction.

58. • Fulminanat hepatitis is associated with A,B and
E.
• Pyrexia is more frequent with type A
• The duration of illness before encephalopathy is
more with non A non B non C.
• Prothombin time is greatest with type B.

60. Clinical features
• It occurs within 10 days
• Disease can be confused with psychosis and
meningoencephalitis
• Patient becomes deeply jaundiced, has
repeated vomiting, fetor hepaticus, confusion
and drowsiness
• Flapping tremor is transient but rigidity is
usual
• Coma superveins
• Widespread haemorrhages may develop

61. • Leucocytosis can occur in contrast to leucopenia
of viral hepatitis.
• The rise of bilirubin and transaminases are poor
indicators of prognosis.
• Transaminases may fall when patients condition
deteriorates.
• Blood coagulation is grossly deranged
• Prothrombin time is best indicator of prognosis.

62. • Hepatic encephalopathy
• Cerebral edema
• Sepsis
• Renal failure(30-70%)
• Cardiovasular dysfunction :arrythmias, hyperdynamic
circulation.
• Coagulopathy
• Gastrointestinal bleeding
• Pulmonary complication:ARDS ,pulmonary edema,
aspiration.
• Metabolic disturbance : metabolic acidosis,
hypoglycemia, hypophosphatemia,hypokalemia.
FHF complication

64. KING’S COLLEGE CRITERIA FOR PROGNOSIS

67. MANAGEMENT OF COMPLICATION
CEREBRAL EDEMA:
• Positioning of head and trunk at 35° to 40° angle
above horizontal,
• Avoiding unnecessary motions of the head and
• Avoiding hypoxaemia, hypercapnoea, fluid
overload and acidbase imbalance.
• Rapid infusion of mannitol (20%) at a dose of 100
ml is the first step.
• Induction of barbiturate coma may be used as a
rescue therapy, if mannitol fails.

68. Sepsis:
• Sepsis is the second major cause of death among
Indian patients with ALF.
• Gram-negative bacteria are the major cause of
sepsis in these patients.
• Prophylactic parenteral antibiotics using third
generation cephalosporins.
Renal Failure : low dose dopamine (2 µg/kg/hr to
2.5 µg/kg/hr) may be beneficial.
• The mainstay of management of renal failure in
patients with ALF however is haemodialysis.

69. Coagulopathy:
• Coagulopathy associated with ALF is currently
not preventable.
• Prophylactic use of fresh frozen plasma (FFP)
and vitamin K has not been shown to prevent
bleeding.

70. LIVER TRANSPLANTATION
• Urgent OLT is now the standard therapy for ALF
in individuals who, on clinical and laboratory
criteria, have a less than 20% chance of survival.
Contraindications to OLT include
1. Irreversible brain damage,
2. Uncontrolled bacteraemia,
3. HIV
4. concurrent malignant disease
• Auxiliary liver transplantation is another
treatment option for ALF.

73. Acute hepatitis in HBV and HCV
Clinical features and management are similar as
acute hepatitis caused by HAV.
The course may be anicteric.
Sub-clinical episodes are extremely frequent.
The non-icteric case is more liable to become
chronic than the icteric one.
The usual acute clinical attack, diagnosed in the
adult , tends to be more severe than for HAV
infections.

74. Benign course is marked by increased serum
transaminase values for more than 100 days.
Relapses are rare.
Cholestatic hepatitis with prolonged deep
jaundice is unusual.
Acute hepatitis B is self-limited in 95–99%
while hepatitis C is self-limited in only 15%

75. Treatment
• SELF LIMITING
• Does not require any specific treatment.
• Patients should be followed up to detect
chronicity particularly in children.
• Treatment with lamivudine,telbivudine or
entacavir is indicated in patients with
fulminant hepatitis, proctracted severe
infection.

76. Extra hepatic manifetations
• Polyarteritis. This involves largely medium and small
arteries and appears early in the course of the disease.
 Plasmapheresis and adenine arabinoside have been
used for treatment
• Glomerulonephritis. This has been associated with HBV
infection, largely in children .
• Essential mixed cryoglobulinaemia is a rare association
of HBV infection although very frequent in HCV
• The Guillain–Barré syndrome has been reported with
HBsAg-containing immune complexes in serum and
cerebrospinal fluid.

78. Hepatitis D
•DELTA agent is single stranded , circular, antisense
RNA
•HDV is considered to be a subviral satellite because it
can propagate only in the presence of the hepatitis B virus
(HBV).
• It is highly infectious

79. VIRION: spherical, 36-38 nm particle with an outer
coat composed of the HBsAg surrounding ssRNA
genome.
Satellite virus : replicates only in the presence of HBV

80. Incubation Period : 2-12 weeks
Mode of Transmission: The primary route of
Transmission are believed to be similar to those of
HBV, though HDV does not appear to be sexually
transmitted disease.

81. Risk factors
 Intravenous drug abuse (strongly associated )
 Homosexual men (infrequent)
 Health-care workers
 Transfusion recipients
 Haemophiliacs
 Immigrants
 Developmentally disabled .
 HDV can spread heterosexually .
 Intrafamily spread has been noted in southern Italy .
 Children can be affected.
 HDV infection may be reactivated by HIV infection

82. CLINICAL FEATURES
Infection is dependent on HBV replication, as HBV
provides an HBsAg envelop for HDV.
Two types of infection are recognised:
coinfection and superinfection.
In Coinfection, delta and HBV are transmitted together
at the same time.
In Superinfection, delta infection occurs in a person
already harbouring HBV.

83. DIAGNOSIS
Delta antigen is primarily expressed in liver cell nuclei,
where it can be demonstrated by immunofluorescence.
 Anti-delta antibodies appear in serum and can be
identified by ELISA.
IgM antibody appears 2-3 weeks after infection and is
soon replaced by the IgG antibody in acute delta infection.

84. Co-infection
 It is diagnosed by finding serum IgM anti-HDV in the presence of
high-titre IgM anti-HBc.
 These markers appear at 1 week, and IgM anti-HDV is gone by 5–
6 weeks but may last for up to 12 weeks
 Self limited as HDV cannot outlive the transient HBs
antigenemia.
Superinfection
 It is marked by the early presence of serum IgM anti-HDV, usually
at the same time as early IgG anti-HDV and both antibodies
persist.
 IgM anti-HBc negative
 the acute attack may be severe and even fulminant, or may be
marked only by a rise in serum transaminase levels

85. Prevention
• Vaccination against hepatitis B makes the
recipient immune to HBV infection and
protects against HDV infection.
Treatment
• Treatment is unsatisfactory.
• High doses of interferon given for long periods
result in reductions of AST but recurrence is
usual

86. Hepatitis G virus
• GB virus C (GBV-C)
• HPgV
• It is a virus in the Flaviviridae family and a
member of the Pegivirus genus, is known to infect
humans, but is not known to cause human disease.
• HGV RNA has been found in patients with acute,
chronic and fulminant hepatitis, hemophiliacs,
patients with multiple transfusions and
hemodialysis, intravenous drug addicts and blood
donors.

87. Yellow fever
• This acute infection is
due to a group B arbovirus
transmitted to man by the
bite of infected mosquitoes.
• The virus cycle is a direct human one in urban
yellow fever, or may involve wild monkeys in the
jungle variety

88. Clinical features
• Incubation period of 3–6 days
• Onset is sudden with fever, chills, headache,
backache, prostration and vomiting, often of
altered blood.
• The blood pressure falls, haemorrhages become
widespread
• Jaundice and albuminuria are conspicuous
• Delirium proceeds to coma
• Death may occur within 9 days.

90. Diagnosis
• Demonstrating specific IgM antibodies to
yellow fever virus.
• Prothrombin deficiency parallels the severity
of the liver lesion.
• The serum cholesterol and glucose levels fall
in the fatal case.
• Serum transaminases are increased relative
to severity.

91. Treatment
• There is no specific treatment.
• Death results principally from renal damage.
• The hepatic lesion is self-limited and short-
lived and does not demand special treatment.

92. Epstein barr virus
• Primary infection in children is usually asymptomatic.
• In adolescents and young people, it causes a hepatitis which
may mimic HAV, HBV or HCV hepatitis.
• Presentation, particularly in adults, may be as fever with
right, upper quadrant, abdominal discomfort. Pharyngitis and
lymphadenopathy may be absent.
• It can cause fulminant hepatitis in elderly people
• It may be a trigger autoimmune hepatitis in susceptible
people such as the immunosuppressed.
• EBV infection may be associated with lymphoproliferative
disorders.

93. Diagnosis
• The serum albumin level may be slightly decreased and
the serum globulin value slightly elevated.
• Hyperbilirubinaemia is present in about one-half of
patients.
• Serum transaminase values are raised to about 20 times
the normal in 80% of patients.
• In about one-third the serum alkaline phosphatase value
is increased, often more so than that of bilirubin.
• The monospot reaction is positive.
• The disease is diagnosed conclusively by an increase in
serum IgM antibodies against EBV capsid antigens.

95. CMV:
• The picture may simulate type A, B or C hepatitis, having a
similar onset but with failure of the pyrexia to subside with the
onset of jaundice.
• Icterus lasts 2–3 weeks and even up to 3 months. Occasionally,
massive hepatic necrosis may be fatal.
• Granulomatous hepatitis can develop in a previously normal
adult.
• Cholangitis, papillary stenosis and sclerosing cholangitis can
accompany cytomegalovirus infections in patients with AIDS
• Rarely cause posttransfusion hepatitis.
• Causes real problem in adult and paediatric recipients of kidneys
and liver transplants

96. • Diagnosis is by isolation of virus from urine or
saliva.
• Complement-fixing antibodies rise and
cytomegalovirus IgM antibodies can be found.
• The virus cannot usually be shown in liver
biopsy but direct hepatic involvement has been
confirmed by demonstrating nuclear and
cytoplasmic inclusions in hepatocytes

97. HERPES SIMPLEX.
• Human herpes virus types I and II affect all humans at
some time during their lives.
• In infants, herpes hepatitis may be part of generalized
herpetic disease.
• In adults, disseminated herpes simplex is very rare.
• It can affect those with underlying diseases
e.g. ulcerative colitis , AIDS , those receiving
immunosuppressive treatment or having organ
transplants.

98. • Fulminant hepatic failure can also affect the
previously normal and immunocompetent .
• The onset is with fever, prostration, marked
elevation of transaminases and leucopenia.
• Jaundice is absent.
• Fulminant liver failure with fatal coagulopathy can
develop.

99. HEPATITIS DUE TO EXOTIC VIRUSES
• These very dangerous viruses have the liver as the
primary target .
• They include Marburg, Lassa and Ebola
viruses.
Lassa fever
• It is due to an arenavirus transmitted from rodents to man
or from man to man.
• It is largely found in West Africa. The case fatality rate is
36–67%.
• Diagnosis is made by demonstrating virus in the blood
during the first few days and by IgM antibodies from the
fifth day.
• It has been successfully treated with ribavirin

100. Marburg virus disease
• It is due to an RNA virus transmitted by Vervet monkeys.
• After an incubation period of 4–7 days the patients
present with headache, pyrexia, vomiting, a characteristic
rash, a haemorrhagic diathesis and central nervous system
involvement.
• Serum transaminase levels are very high
Ebola virus infection
• It resembles Marburg in clinical course, hepatic
histology and electron microscopy
• It has been reported from Zaïre and the Sudan and
has been transmitted to biologists working with it.

101. Treatment :
• There is no specific treatment for these
exotic virus infections.
• Symptomatic measures are used and very
strict precautions are necessary to avoid
spread to contacts