This document discusses viral hepatitis, summarizing the key points about hepatitis A-E viruses. It covers their virology, epidemiology, clinical features, pathogenesis, diagnosis and complications. The main points are: 1. Hepatitis A-E viruses are the primary causes of viral hepatitis. They produce similar illnesses but differ in modes of transmission, incubation periods and likelihood of chronic infection. 2. Hepatitis A and E are typically self-limited and do not usually lead to chronic liver disease. Hepatitis B and C have higher rates of chronic infection. 3. Acute viral hepatitis presents with non-specific symptoms but laboratory tests can identify the specific virus through detection of viral antigens or antibodies. Ful

2. • Systemic infection affecting the liver predominantly
• Almost all cases are caused by one of five viral agents:
1. hepatitis A virus (HAV),
2. hepatitis B virus (HBV),
3. hepatitis C virus (HCV),
4. HBV-associated delta agent or hepatitis D virus (HDV),
5. hepatitis E virus (HEV).
• All types of viral hepatitis produce clinically similar
illnesses

3. Virology and epidemiology

4. Incubation period
• Hepatitis A : 15–45 days (mean, 4 weeks)
• Hep B,D:
30–180 days (mean, 8–12
weeks)
• Hepatitis C : 15–160 days (mean, 7 weeks),
• Hepatitis E : 14–60 days (mean, 5–6 weeks)

5. Hepatitis A
• RNA virus in the Hepatovirus genus of the
picornavirus family.
• This agent is transmitted almost exclusively by the
fecal-oral route.
• In developing countries, exposure, infection, and
subsequent immunity are almost universal in
childhood.
• Frequency of subclinical childhood infections
declines in developed countries.
• Hepatitis A tends to be more symptomatic in
adults

6. • Antibodies to HAV (anti-HAV) can be detected during
acute illness when fecal HAV shedding is still occurring.
• Therefore, the diagnosis of hepatitis A is made during
acute illness by demonstrating anti-HAV of the IgM class.
After acute illness, anti-HAV of the IgG class remains
detectable indefinitely

7. Hepatitis B
• Hepatitis B virus is a DNA virus
• is classified as hepadnavirus type 1

8. • Percutaneous inoculation has long been recognized as a major
route of hepatitis B transmission.
• In approximately two-thirds of patients with acute type B
hepatitis, no history of an identifiable percutaneous exposure
can be elicited
• many cases of hepatitis B result from less obvious modes of
nonpercutaneous or covert percutaneous transmission.
• HBsAg has been identified in almost every body fluid from
infected person
• The two nonpercutaneous routes considered to have the
greatest impact are intimate (especially sexual) contact and
perinatal transmission.
• Oral ingestion has been documented as a potential but
inefficient route of exposure

9. Viral Particles.
• Spherical and filamentous forms(22 nm)
• Most Numerous.(exess viral coat material)
• Contains HbsAg
• Nucleocapsid Core(27nm)
• Contains HbcAg and HbeAg
• Virion(47nm)
• Contains HbsAg ,HbcAg and HbeAg.

10. HBsAg
• Product of S gene.
• Surface antigen
• After infection it is the first virological marker to
appear: within 1-12 weeks.
• Precedes clinical symptoms and transaminases
by 2-6 weeks
• rarely persists beyond 6 months.
• After HBsAg disappears, antibody to HBsAg (antiHBs) becomes detectable in serum and remains
detectable indefinitely thereafter.

11. HbcAg
• Proguct of C Gene.
• Naked core particles do not circulate in serum and,
therefore, HBcAg is not detectable routinely in the
serum.
• But, anti-HBc is readily demonstrable in serum,
beginning within the first 1–2 weeks after the
appearance of HBsAg.
• Patients with current or recent acute hepatitis B, have
IgM anti-HBc in their serum.
• In patients who have recovered from hepatitis B in the
remote past as well as those with chronic HBV
infection, anti-HBc is predominantly of the IgG class

12. HbeAg
• Soluble product of C gene.
• HBeAg, appears concurrently with or shortly after HBsAg.
• Reflects high levels of viral replication and the presence of
circulating intact virions and detectable HBV DNA.
• HBeAg becomes undetectable, before the disappearance of
HBsAg.(In self limiting Acute hepatitis)
• HBsAg-positive serum containing HBeAg is more likely to be
highly infectious.
• HBsAg carrier mothers who are HBeAg-positive almost have
(>90%) transmission to their offspring, whereas HBsAg
carrier mothers with anti-HBe rarely (10–15%) infect their
offspring.

14. Pre-core Mutants.
• These variants have mutation in the Pre-C region
of Gene-C.
• Thus HBeAg is not synthesised.
• Despite its absence, the patients may develop
chronic hepatitis.
• The affected patients tend to have severe liver
disease that progresses more rapidly to cirrhosis.
• In addition, clusters of fulminant hepatitis B in
Israel and Japan have been attributed to
common-source infection with a precore mutant.

15. Hepatitis D
• The only member of the genus Deltavirus.
• Defective RNA virus
• Requires the helper function of HBV for its replication and
expression.
• HDV can infect a person simultaneously with HBV
(co-infection).
• Infect a person already infected with HBV (super-infection).
• In Endemic areas the disease is transmitted predominantly by
nonpercutaneous means, especially close personal contact.
• In nonendemic areas, HDV infection is confined to persons
exposed frequently to blood and blood products, primarily
injection drug users and hemophiliacs.

16. • During acute HDV infection, anti-HDV of the
IgM class predominates.
• Anti HDV may be delayed for upto 30-40 days
after onset of symptoms.
• In self-limited infection, anti-HDV is low-titer.
• Undetectable beyond the clearance of HBsA,
in most cases.

17. Hepatitis C
• HCV is the only member of the genus
Hepacivirus.- RNA virus.
• Its high mutation rate, interferes with effective
humoral immunity.
• immunity does not appear to develop after
acute HCV infection.

18. • Third-generation anti-HCV assays and automated
PCR testing has resulted in a reduction in the risk
of transfusion-associated HCV infection to 1 in 2.3
million transfusions
• Hepatitis C can be transmitted by other
percutaneous routes, such as injection drug use.
• Can be transmitted sexually and perinatally;
however, both of these modes of transmission
are inefficient for hepatitis C.
• Transmission of HCV infection is rare between
stable, monogamous sexual partners.
• Breast-feeding does not increase the risk of HCV
infection between an infected mother and her
infant

19. • Anti HCV antibodies are detectable in serum
during acute infection.
• The most sensitive indicator of HCV infection
is the presence of HCV RNA, which requires
molecular amplification by PCR .
• HCV be detected within a few days of
exposure, well before the appearance of antiHCV— and persists for the duration of HCV
infection.

21. Hepatitis E
• HEV is an enterically transmitted virus that occurs
primarily in India, Asia, Africa, and Central America.
• Epidemiologic features resemble those of hepatitis A.
• Animal reservoirs, most notably in swine cause
persistence of the virus.
• Immune responses to viral antigens occur very early
during the course of acute infection.
• Both IgM anti-HEV and IgG anti-HEV can be detected,
but both fall rapidly after acut.e infection

22. Pathogenesis

23. • None of the hepatitis viruses is known to be
directly cytopathic to hepatocytes.
• Clinical outcomes are determined by the
immunologic responses of the host.
• Typical morphologic lesions of all types of viral
hepatitis are similar and consist of:
1. Panlobular infiltration with mononuclear cells,
2. Hepatic cell necrosis,
3. Hyperplasia of Kupffer cells, and
4. Variable degrees of cholestasis.

24. • In massive hepatic necrosis (fulminant
hepatitis, "acute yellow atrophy"), the striking
feature at postmortem examination is the
finding of a small, shrunken, soft liver.
• Histologic examination reveals massive
necrosis and dropout of liver cells of most
lobules with extensive collapse and
condensation of the reticulin framework

25. Clinical and Laboratory Features

26. Prodromal symptoms
• Constitutional symptoms of anorexia, nausea and
vomiting, fatigue, malaise, arthralgias, myalgias,
headache, photophobia, pharyngitis, cough, and
coryza.
• A low-grade fever between 38° and 39°C is more
often present in hepatitis A and E than in
hepatitis B or C
• May precede the onset of jaundice by 1–2 weeks.
• Dark urine and clay-colored stools may be
noticed by the patient from 1–5 days before the
onset of clinical jaundice.

27. • With the onset of clinical jaundice, the
constitutional prodromal symptoms usually
diminish.
• The liver becomes enlarged and tender and
may be associated with right upper quadrant
pain and discomfort.
• Splenomegaly and cervical adenopathy are
present in 10–20% of patients with acute
hepatitis.

28. • During the recovery phase, constitutional
symptoms disappear, but usually some liver
enlargement and abnormalities in liver
biochemical tests are still evident.
• The duration of the posticteric phase is
variable, ranging 2–12 weeks.

29. • Complete clinical and biochemical recovery is
to be expected:
 1–2 months after jaundice in all cases of hepatitis A and E
 3–4 months after the onset of jaundice in three-quarters of
uncomplicated, self-limited cases of hepatitis B and C. In the
remaining, biochemical recovery may be delayed.
• Acute hepatitis B is self-limited in 95–99%
while hepatitis C is self-limited in only 15%

30. Extrahepatic Manifestations
• Serum sickness–like syndrome observed in acute
hepatitis B : arthralgia or arthritis, rash,
angioedema, and rarely, hematuria and
proteinuria.
o Deposition in tissue blood vessel walls of HBsAganti-HBs circulating immune complexes,
o Leads to activation of the complement system .
o Reduced Serum Complement levels are seen.

31. Amino transferases.
• The serum aminotransferases aspartate
aminotransferase (AST) and ALT increase
during the prodromal phase of acute viral
hepatitis and precede the rise in bilirubin
level.
• Peak levels vary from 400–4000 IU or more;
• Level of these enzymes, does not correlate
well with the degree of liver cell damage

32. Bilirubin
• The serum bilirubin typically rises to levels
ranging from (5–20 mg/dL).
• In most instances, the total bilirubin is equally
divided between the conjugated and
unconjugated fractions.
• Bilirubin levels (20 mg/dL) extending and
persisting late into the course of viral hepatitis
are more likely to be associated with severe
disease.

33. Prothrombin Time.
• Measurement of the prothrombin time (PT) is
important in patients with acute viral
hepatitis, for a prolonged value may reflect a
severe hepatic synthetic defect, signify
extensive hepatocellular necrosis, and indicate
a worse prognosis

34. Others…
• Neutropenia and lymphopenia are transient.
• It is followed by relative lymphocytosis.
• Serum alkaline phosphatase may be normal or
only mildly elevated.
• Prolonged nausea and vomiting, inadequate
carbohydrate intake, and poor hepatic
glycogen reserves may contribute to
HYPOGLYCEMIA in patients with severe viral
hepatitis.

35. Viral Markers.
• A patient with acute hepatitis should undergo
four serologic tests:
1. IgM anti-HAV,
2. HBsAg
3. IgM anti-HBc,
4. anti-HCV

36. • The presence of HBsAg, with or without
IgM anti-HBc, represents HBV infection.
• If IgM anti-HBc is present, the HBV infection is
considered acute; if IgM anti-HBc is absent,
the HBV infection is considered chronic.
• A diagnosis of acute hepatitis B can be made
in the absence of HBsAg when IgM anti-HBc is
detectable.

37. • A diagnosis of acute hepatitis A is based on
the presence of IgM anti-HAV.
IgM anti-HAV + HBsAg + IgM anti HBcAg =
simultaneous acute hepatitis A and B.
 If IgM anti-HBc is undetectable, the patient
has acute hepatitis A superimposed on
chronic HBV infection.

38. • The presence of anti-HCV supports a diagnosis of
acute hepatitis C.
• Occasionally, testing for HCV RNA or repeat antiHCV testing later during the illness is necessary to
establish the diagnosis.
• Absence of all serologic markers is consistent
with a diagnosis of "non-A, non-B, non-C"
hepatitis, if the epidemiologic setting is
appropriate.

39. Complications and Sequelae

40. Hepatitis A
1. relapsing hepatitis weeks to months after
apparent recovery from acute hepatitis.
2. cholestatic hepatitis, characterized by
protracted cholestatic jaundice and pruritus.
Even when these complications occur, hepatitis
A remains self-limited and does not progress to
chronic liver disease

41. Hepatitis B
• Chronic hepatitis is an important late
complication of acute hepatitis B occurring in
a small proportion of patients with acute
disease (1%)
• More common in those who present with
chronic infection without having experienced
an acute illness, as occurs typically after
neonatal infection or after infection in an
immunosuppressed host.

42. • Hepatitis D infection does not increase the
likelihood of chronicity of simultaneous acute
hepatitis B
• Hepatitis D has the potential for contributing
to the severity of chronic hepatitis B.
• After acute HCV infection, the likelihood of
remaining chronically infected approaches 85–
90%.

43. Fulminant hepatitis
• Fulminant hepatitis is primarily seen in
hepatitis B and D, as well as hepatitis E.
• Fulminant cases of hepatitis A occur primarily
in older adults and in persons with underlying
chronic liver disease.(Very rare)
• Hepatitis E, can be complicated by fatal
fulminant hepatitis in 1–2% of all cases and in
up to 20% of cases in pregnant women.

44. The mortality rate is exceedingly high (>80% in
patients with deep coma
• Signs and symptoms of encephalopathy that may
evolve to deep coma.
• The liver is usually small
• PT excessively prolonged.
• Ascites, and edema.
• Cerebral edema, brainstem compression,
• gastrointestinal bleeding, sepsis, respiratory
failure, cardiovascular collapse, and renal failure
are terminal events.

45. Differential Diagnossis.
• Infectious mononucleosis; cytomegalovirus,
herpes simplex, and coxsackieviruses; and
toxoplasmosis.
• Leptospira, Candida, Brucella, Mycobacteria,
and Pneumocystis.
• Toxic and Drug induced hepatitis, Alcoholic
hepatitis
• Chronic Hepatitis(Ask for previous episodes of
Jaundice).

46. • Because acute hepatitis may present with
right upper quadrant abdominal pain,, fever,
and icterus, it is often confused with acute
cholecystitis, common duct stone, or
ascending cholangitis.
• Right ventricular failure with passive hepatic
congestion .
• Acute fatty liver of pregnancy, cholestasis of
pregnancy, eclampsia, and the HELLP
syndrome can be confused with viral hepatitis
during pregnancy

47. Treatment.
• In most cases of typical acute viral hepatitis, specific
treatment generally is not necessary.
• Hospitalization may be required for clinically severe illness,
• A high-calorie diet
• Intravenous feeding is necessary in the acute stage if the
patient has persistent vomiting and cannot maintain oral
intake.
• Drugs capable of producing adverse reactions such as
cholestasis and drugs metabolized by the liver should be
avoided.
• If severe pruritus is present, the use of the bile saltsequestering resin cholestyramine is helpful.

48. • In Severe acute hepatitis B, treatment with a
nucleoside analogue at oral doses may be
beneficial.
• In Acute Hepatitis C, Antiviral therapy with
interferon alfa (3 million units SC three times
a week) is beneficial, reducing the rate of
chronicity considerably by inducing sustained
responses in 30–70% of patients.

49. • In fulminant hepatitis, the goal of therapy is to support
the patient by maintenance of fluid balance, support of
circulation and respiration,
• Control of bleeding,
• Correction of hypoglycemia,
• Treatment of other complications of the comatose
state in anticipation of liver regeneration and repair.
• Protein intake should be restricted.
• Oral lactulose or neomycin administered.
• Meticulous intensive care that includes prophylactic
antibiotic coverage is the one factor that does appear
to improve survival.
• Orthotopic liver has excellent results, in patients with
fulminant hepatitis.

50. • Hepatitis A vaccines are approved for use in
persons who are at least one year old and
appear to provide adequate protection
beginning 4 weeks after a primary inoculation.
• Three IM (deltoid, not gluteal) injections of
hepatitis B vaccine are recommended at 0, 1,
and 6 months Pregnancy is not a
contraindication to vaccination.