hepatitis viruses

2. Hepatitis viruses
 The causes of hepatitis are varied and include viruses,
bacteria, and protozoa, as well as drugs and toxins (eg,
isoniazid, carbon tetrachloride, and ethanol). The
clinical symptoms and course of acute viral hepatitis
can be similar, regardless of etiology, an determination
of a specific cause depends primarily on the use of
laboratory tests.

3. Hepatitis viruses
 Hepatitis may be caused by at least five different
viruses
 Non-A, non-B hepatitis is a term previously used to
identify cases of hepatitis not due to hepatitis A or B
 With the discovery of the hepatitis viruses C, E, and G,
virtually all the viral etiologies of non-A, non-B disease
can be specifically identified
 Other viruses, such as Epstein–Barr virus and
cytomegalovirus, can also cause inflammation of the
liver, but hepatitis is not the primary disease caused by
them

4. Hepatitis A Virus
 Hepatitis A virus is an unenveloped, single-stranded
RNA virus with cubic symmetry
 Hepatitis A Viruses is classified in a separate genus
(hepatovirus) of picornaviruses

5. Hepatitis A transmission
 Hepatitis A virus is spread by the fecal–oral route, and
outbreaks may be associated with contaminated food
or water

6. Pathogenesis & Clinical manifestation
 The virus is believed to replicate initially in the enteric
mucosa
 Multiplication in the intestines is followed by a period
of viremia with spread to the liver
 The response to replication in the liver consists of
lymphoid cell infiltration, necrosis of liver
parenchymal (Hepatocytes) cells, and proliferation of
Kupffer cells
 The extent of necrosis often coincides with the severity
of disease

7. Pathogenesis & Clinical manifestation cont…
 It can be demonstrated in feces for 10 to 14 days before
onset of disease
 In most patients with symptoms of the disease, virus is
no longer found in fecal specimens
 Contagion is greatest 10–14 days before symptoms
appear

8. Pathogenesis & Clinical manifestation cont…
 In hepatitis A virus infection, an incubation period of
10 to 50 days is usually followed by the onset of fever;
anorexia (poor appetite); nausea; pain in the right
upper abdominal quadrant; and, within several days,
jaundice
 The liver is enlarged and tender, and serum
aminotransferase and bilirubin levels are elevated as a
result of hepatic inflammation and damage
 Recovery occurs in days to weeks

9. Lab Diagnosis
 Antibody to hepatitis A virus can be detected during early
illness, and most patients with symptoms or signs of acute
hepatitis A already have detectable antibody in serum
 Early antibody responses are predominantly IgM, which can be
detected for several weeks or months
 During convalescence, antibody of the IgG class predominates.

10. Hepatitis B Virus
 Hepatitis B virus is an enveloped DNA virus belonging to
the family Hepadnaviridae
 The complete virion is a spherical particle that
consists of an envelope around a core. The core comprises a
nucleocapsid that contains the DNA genome
 Other components of the core are a hepatitis B core antigen
(HBcAg) and the hepatitis B e antigen (HBeAg), which is a
low-molecular-weight glycoprotein
 The envelope of the virus contains the hepatitis B surface
antigen (HBsAg)

12. Transmission
 It has become clear that the major mode of acquisition
is through close personal contact with body fluids of
infected individuals
 HBsAg has been found in most body fluids, including
saliva, semen, and cervical secretions
 Under experimental conditions, as little as 0.0001 mL
of infectious blood has produced infection
 Transmission is therefore possible by vehicles such as
inadequately sterilized hypodermic needles or
instruments used in tattooing and ear piercing

13. Pathogenesis and clinical manifestation cont…
 The clinical picture of hepatitis B is highly variable
 The incubation period may be as brief as 7 days or as long
as 160 days (mean, approximately 10 weeks)
 Liver injury appears to occur from a cell-mediated immune
system attack on HBV. Viral antigens on the surface of
infected hepatocytes are targets for cytotoxic T-cells
 Immune complexes of antibody and HBsAg can deposit in
tissues and activate the immune system, resulting in
arthritis, as well as skin and kidney damage
 Patients who have immunosuppressed states, such as
malnutrition, AIDS, and chronic illness, are more likely to
be asymptomatic carriers because their immune system
does not attack

14. Pathogenesis and clinical manifestation cont…
 HBV can cause acute and chronic hepatitis
 The following are disease states caused by HBV:
1) Acute hepatitis
2) Fulminant hepatitis: Severe acute hepatitis with rapid destruction
of the liver
3) Chronic hepatitis:
a) Asymptomatic carrier: The carrier patient never develops
antibodies against HBsAg (anti-HBsAg) and harbors the virus without
liver injury. There are an estimated 200 million carriers of HBV in the
world
b) Chronic-persistent hepatitis: The patient has a low-grade
"smoldering" hepatitis
c) Chronic active hepatitis: The patient has an acute hepatitis state
that continues without the normal recovery (lasts longer than 6-12
months)

15. Pathogenesis and clinical manifestation cont…
 Acute hepatitis B is usually manifested by the gradual
onset of fatigue, loss of appetite, nausea and pain, and
fullness in the right upper abdominal quadrant
 With increasing involvement of the liver, there is
increasing cholestasis and, hence, clay-colored stools,
darkening of the urine, and jaundice

16. Complications
 Primary hepatocellular carcinoma: With chronic
infection the HBV DNA becomes incorporated into
the hepatocyte DNA and triggers malignant growth.
There is a 200X increase in the risk of developing
primary hepatocellular carcinoma in HBV carriers as
compared to non carriers.
 Cirrhosis: Infection with HBV can result in
permanent liver scarring and loss of hepatocytes

17. Lab Diagnosis
Many antigens and antibodies are simpler than they
seem, as follows:
1) HBsAg: The presence of HBsAg always means
there is LIVE virus and infection, either acute, chronic,
or carrier. When anti-HBsAg develops, HBsAg
disappears and the patient is protected and immune.
a) HBsAg = DISEASE (chronic or acute)
b)Anti-HBsAg = IMMUNE, CURE, NO ACTIVE
DISEASE!!!

18. Lab Diagnosis
2) HBcAg: Antibodies to HBcAg are not protective
but we can use them to understand how long the
infection has been ongoing
 With acute illness we will see IgM anti-HBcAg
 With chronic or resolving infection IgG anti-HBcAg
will develop
a) IgM anti-HBcAg = NEW INFECTION
b) IgG anti-HBcAg = OLD INFECTION

19. Lab Diagnosis
3) HBeAg: The presence of HBeAg connotes a high
infectivity and active disease
 Presence of anti-HBeAg suggests lower infectivity
a) HBeAg = HIGH INFECTIVITY, virus going wild!
b) anti-HBeAg = LOW INFECTIVITY

20. Serology of Hepatitis B

21. Prevention
 Safe sex practices and avoidance of needle stick injuries or
injection drug use are approaches to diminishing the risk of
hepatitis B infection
 Serologic tests on donor blood to remove HBV contaminated
blood from the donor pool
 Active immunization: The vaccine is a recombinant vaccine. The
gene coding for HBsAg is cloned in yeast and used to produce
mass quantities of HBsAg, used as vaccine. There is no risk of
developing disease from the vaccine because it contains only the
surface envelope and proteins (HBsAg = no DNA or capsid)
 The HBV vaccine is now given to all infants at birth, 2, 4, and 15
months
 It is also given as 3 injections to adolescents and high-risk adults
(health care workers, IV drug users, etc.)

22. Prevention
 Administration of HBIG soon after exposure to the
virus greatly reduces the development of symptomatic
disease
 Post exposure prophylaxis with HBIG should be
followed by active immunization with vaccine

23. Delta Hepatitis (Hepatitis D)
 Hepatitis D is found only in hepatitis B–infected
persons
 HDV uses HBsAg for assembly
 Hepatitis D virus is a small single-stranded RNA
virus with helical nucleocapsid
 Infection occurs in 2 ways:
1) Co-infection: HBV and HDV both are transmitted
together parenterally (IV drug use, blood transfusions,
sexual contact, etc.) and cause an acute hepatitis
similar to that caused by HBV. Antibodies to HBsAg
will be protective against both, ending the infection

24. Delta Hepatitis (Hepatitis D)
 2) Super infection: HDV infects a person who has
chronic HBV infection (like the 200 million worldwide
HBV carriers)
 This results in acute hepatitis in a patient already
chronically infected with HBV. This HDV infection is often
severe, with a higher incidence of fulminant hepatitis,
cirrhosis, and a greater mortality (5-15%)
 Diagnosis is made most commonly by demonstrating IgM
or IgG antibodies, or both, to the delta antigen in serum
 IgM antibodies appear within 3 weeks of infection and
persist for several weeks. IgG antibodies persist for years

25. Hepatitis C Virus
 Hepatitis C virus is an RNA virus in the flavivirus
family
 There are at least six major genotypes, with multiple
subtypes
 The genotypes have different geographic distributions
and may be associated with differing severity of
disease as well as response to therapy

26. Hepatitis C Disease
 Hepatitis C is an insidious disease in that it does not
usually cause a clinically evident acute illness
 Instead, its first manifestation (in 25% of those
infected) may be the presence of smoldering chronic
hepatitis that may ultimately lead to liver failure. Its
transmission is less well understood than for hepatitis
A, B, and D

27. Pathogenesis and clinical manifestation
 The transmission of hepatitis C by blood is well
documented: indeed, until screening blood for
transfusions was introduced, it caused the great
majority of cases of posttransfusion hepatitis
 Hepatitis C may be sexually transmitted but to a much
lesser degree than hepatitis B. Needle sharing accounts
for up to 40% of cases

28. Pathogenesis and clinical manifestation
 The incubation period of hepatitis C averages 6–12
weeks
 The infection is usually asymptomatic or mild and
anicteric but results in a chronic carrier state in up to
85% of adults of patients
 The average time from infection to the development of
chronic hepatitis is 10–18 years
 Cirrhosis and hepatocellular carcinoma are late
sequelae of chronic hepatitis

29. Lab Diagnosis
 Antigens of hepatitis C are not detectable in blood, so
diagnostic tests attempt to demonstrate antibody
 Unfortunately, the antibody responses in acute disease
remain negative for 1 to 3 weeks after clinical onset and
may never become positive in up to 20% of patients
with acute, resolving disease
 Quantitative assays of hepatitis C RNA may be used for
diagnosis

30. Hepatitis E
 Hepatitis E is a small, single-strand, non-enveloped RNA
virus that is similar to but distinct from caliciviruses
 Transmission is by the faecal–oral route.
 Outbreaks occur after contamination of water supplies or
food
 It is found in Asia, Africa and Central America.
 It usually causes a self-limiting hepatitis of varying severity
 Diagnosis is by IgM or NAAT.
 Infection is prevented by hygiene measures.

31. Hepatitis G
 Hepatitis G is an RNA virus similar to hepatitis C and members of the
flavivirus family
 An antibody assay can detect past, but not present, infection, and
detection of acute infection with hepatitis G requires a PCR assay for
viral RNA in serum.
 Up to 2% of volunteer blood donors are seropositive for hepatitis G
RNA, which is a blood-borne virus
 In addition to being closely related to hepatitis C, data suggest that the
majority of patients infected by hepatitis C are also infected by
hepatitis G. Given this association, it has been difficult to ascertain the
contribution of hepatitis G to clinical disease
 Patients infected with both viruses do not appear to have worse disease
than those infected by hepatitis C virus only
 Currently, there is no useful serologic test and no therapy is established