HEPATITIS

INTRODUCTION:
- Viral Hepatitis is a systemic disease with primary inflammation in the liver
- Five medically important viruses are commonly described as ‘Hepatitis virus’,because their main
site of infection in the liver
- Heavy alcohol use, toxins,drugs,some medications & certain medical conditions can cause hepatits
- Despite their biological & morphological differences many of the clinical symptoms caused by the
different hepatitis viruses are similar
- The word hepatitis comes from the Ancient Greek word ‘Hepar’ meaning ‘Liver’ & the latin ‘itis’
meaning ‘inflammation’
- World Hepatitis Day (WDH) is on 28th July, the birthday of Dr. Baruch Blumberg (He discovered
hepatitis-B virus in 1967 & 2 years later he developed the first hepatitis-B vaccine

KEY POINTS :
- There are 6 hepatitis viruses i.e, A,B,C,D,E&G
- The infection caused by hepatitis B is most severe and at times fatal
- Hepatitis B&C viruses are also responsible for many cases of primary Hepatocellular carcinoma
- Hepatitis B is a DNA virus while others (A,C,D,E,G) contain RNA genome

HEPATITIS-A VIRUS (HAV)

(INFECTIOUS HEPATITIS)
- Also called infectious hepatitis
- Infectious hepatitis is a sub-acute disease occurring mainly in children and young adults
- The hepatistis A virus enters the body by oral route, multiplies in the intestinal epithelium &
reaches the liver by hematogenous spread

Morphology :
- It is 27nm, non-enveloped, single stranded RNA virus with an icosahedral symmetry
- It belongs to the picrnavirus family
- It was originally designated as ‘Enterovirus 72’ & is now recognized as the prototype of a genus ‘
Hepatovirus’
Laboratory Diagnosis:
Laboratory Diagnosis can be made by
 Demonstration of virus
 Detection of antibody
 Biochemical test

Demonstrsation of virus :
The virus maybe demonstrated by the following methods –
i. Immunoelectron microscopy (IEM)
The virus can be visualized by IEM in faeces during the late incubation period and
preicteric phase but seldom later
ii. Enzyme Linked Immunosorbent Assay (ELISA)
HAV maybe detected in faeces by ELISA
iii. Isolation
The virus has been grown in human & simian cell cultures but it is not possible to grow
them routinely from feaces of patients

Detection of Antibody :
Because of difficulties of isolation & detection of virus, diagnosis depends on the demonstration
of specific IgM antibody to HAV in the blood. Antibody appears early in the clinical illness & certainly by the
time Jaundice appears

Biochemical Test :
Liver function test such as ALT & Bilirubin supplement the diagnosis
i. Alanine aminotransferase (ALT)
ii. Bilirubin & Protein

PATHOGENECITY :
HAV is typically acquired through ingestion & replicates in the liver. After 10-12 days, virus is present in
blood & is excreted via the billiary system into the faeces
The virus probably replicates in the gastro-Intestinal tract & spreads to the liver via the blood.
Hepatocytes are infected but the mechanism by which cell damage occurs is unclear.Most infected persons no
longer excrete virus in the faeces by the 3rd week of illness.

TRANSMISSION :
- Transmitted primarily by fecal-oral route ; when an uninfected person injest food or water that has
been contaminated with the faeces of an infected person
- Spread is most commonly seen in person to person (including sexual contact)
- It also occurs as food borne & water borne transmission, drugs users & rarely by infected blood
products

CULTURAL CHARACTERISTICS :
- HAV is stable to treatment with 20% ether, acid(pH 1.0 for 2 hrs), heat(60°C for 1 hr)
- The virus is destroyed by autoclaving (121°C for 20 mins), by boiling in water for 5 mins, by dry heat
(180°C for 1 hr),or by treatment with formalin of chlorine.
- The incubation period of the disease is 2-6 weeks
- Symptoms include : Fever, Malaise, Nausea, Vomiting & Liver tiredness
- Recovery occurs over a period of 4-6 weeks
TREATMENT : No antiviral treatment is available, supportive measures includes adequate nutrition and rest.
Avoidance to exposure to contaminated food or water are important measures to reduce the risk of hepatitis
infection.
- Passive Immunisation : Immune serum globulin (ISG), manufactured from pool’s of plasma from
large segments of the general population, is protective if given before or during the incubation
period of the disease. (Immune serum globulin provides temporary protection.)

- Active immunization : For hepatitis A, Live attenuated vaccines have been evaluated but have
demonstrated poor immunogenicity and have not been effective when given orally. Formalin –
killed vaccines induces antibody titers similar to those of wild – vaccines infections are almost 100%
protective. (Inactivated virus vaccines confers long-term protection)

SYMPTOMS: - Fatigue, Fever, Abdominal pain, Nausea, Diarrhoea, Loss of appetite, Depression, Jaundice,
Sharp pain in the right – upper quadrant of the abdomen, weight loss, itching.

HEPATITIS-B VIRUS (HBV)

(SERUM HEPATITIS)
- Also called serum hepatitis.
- Is a member of the hepadnavirus group.
- It belongs to the family ‘ Hepadnaviridae’.
- It is a double stranded DNA virus which replicate, usually by reverse transcription.
- It can leads to cirrhosis of the liver, liver failure or liver cancere, which can cause severe illness and
even death.
- It was discovered in 1965 by Dr. Baruch Blumberg who won the nobel prize.
- Originally, the virus was called the ‘Australia antigen’ because it was named for an Australian
aborigine’s blood sample that reacted with an antibody in the serum of an American hemophilia
patient.

MORPHOLOGY :
- HVB is a complex 42 nm double shelled particles.
- The virus consist of an inner shell composed of HBcAg (core) protein, surrounded by an outer
surface coat composed of several Hepatitis B surface antigen (HBsAg).
- It has a neucleocaspid core and lipoprotein coat.
PATHOGENESIS :
Hepatitis B was known as post transfusion hepatitis or as hepatitis associated with the use of illicit
parenhedral drugs (serum hepatitis).
After entering the blood, the virus infects hepatocytes, and viral antigens are displayed on the surface
of the cells. Cytotoxic T cells mediate and immune attack against the viral antigens and inflammation and
necrosis occurs. The pathogenesis of hepatitis B is probably the result of this cell mediated immune injury,
because HBV itself does not cause a cytopathic effects antigen antibody complex cause some of the early
symptoms. Eg – Arthristis
About 50% of the patients with HBV infection becomes chronic carriers. A chronic carrier is someone
who has HBsAg persisting in their blood for atleast 6 months.

Hepatitis B carriers : There are two types of Hepatitis B carriers –

i) Super carriers
ii) Simple carriers
i ) Super carriers :
- Have HBeAg in blood
- High titre of HbsAg in blood
- DNA polymerase in blood
- Mild increase in ALT levels
ii ) Simple carriers :
- No HBeAg in blood
- Low levels of HBsAg in blood
- HBV and DNA polymerase are absent

LABORATORY DIAGNOSIS :
Laboratory Diagnosis of HBV infections can be carried out by detection of Hepatitis B antigens and
antibody. These can be detected by sensitive and specific test like ELISA and RIA.
The presence of HBsAg in a patients serum indicates that the patients may have an active infection,
carriers or is in incubation period.
IgM anti-HBc indicates an acute infection and appears early in the course of the disease anti-HBs in
the serum indicates a past infection or immunity following vaccination.
The presence of HBsAg after 6 months of acute infection indicates that the patient is a chronic carrier.
The appearance of HBcAg along with HBeAg positivity is an indication of chronmic infection and high
infectivity.
1. Dectetion of viral markers
i ) HBsAg : It is recognized as a specific marker for HBV infection. It is the first marker to appear in blood
after infection. It is detectable in blood even before elevation of transaminases and onset of clinical
illness.
ii ) HBeAg : It appears in the serum at the same time as HBsAg, but in most cases it disappears in a few
weeks.The presence of HBeAg iis thought to be an adverse prognostic sign.
The disappearance of HBeAg is followed by appearance of anti-HBe.
iii ) HBcAg : It is not ndetectable in the serum but can be demonstrated in the liver cells by
immunofluorescence.
It is the earliest antibody to appear in the blood.
2. Viral DNA polymerase
It appears transiently in serum during pre-icteric phase.
3. Polymerase Chain Reaction (PCR)
HBV DNA levels can be detected in the serum by PCR. It is a highly sensitive test.
4. Biochemical Tests
 In acute viral hepatitis caused by hepatitis A,B,C,D or E viruses, transaminase values range
between 500 – 2000 units.
Serum blilrubin indicates the degree of jaundice and may rise upto 25 fold.

TRANSMISSION:
The virus is highly infectious and minute amount as little as 0.00001 ml can transmit the injection. HBV
is mainly parental route which involves direct contact with the body fluids.
Common routes:
i. HIV infected blood, contaminated syringe, needle & knives
ii. Sexual contact
iii. Vertical transmission

TREATMENT:
No specific anti-viral treatment is available, Interferon – α alone or in combination with other antiviral
agents.
Blood should no be transmit or prevent transmission of delta hepatitis.

SYMPTOMS: Synptoms are variable. Jaundice, Abdominal pain & dark urine. Particularly children didn’t
experience any symptoms. In chronic cases, Liver failure and cancer can occur.

Differences beteen Hep. A & Hep. B

Features Hep. A Hep. B

1. Virus
-Diameter 27 nm 42 nm
-Genome RNA DNA
-Envelope Non-envelope Envelope
2. Mode of infection Faecal/Oral Par-enteral
3. Age incidence Children&Young adults All ages: common in adults
4. Lab Diagnosis
-HBsAg Absent Present

HEPATITIS-C VIRUS (HCV)

MORPHOLOGY:
- It belongs to the family flaviviridae (eg. Yellow fever, dengue)
- It is a 50-60 nm virus with a linear single stranded RNA of positive polarity.
- It is enclosed within a core.
- It is surrounded by an enveloped carrying glycoprotein spikes.
- It has a very simple consisting of just 3 structural and 5 non-structural genes.
PATHOGENECITY:
HCV infects hepatocytes primarily, but there is no evidence for a virus – induced cytopathic effect on
the liver cells. Alcoholism greatly enhances the rate of hepatocellular carcinoma in HCV-infected individuals.
Hepatitis C was the major cause of post transfusion hepatitis until a serologic test for screening blood donors
was developed.
HCV is the leading cause of liver transplantation in US. The rate of chronic carriage of HCV is much
higher than the rate of chronic carriage of HBV.
About 50-80% of patients developed chronic hepatitis with some developing cirrhosis & hepatocellular
carcinoma.

LAB DIAGNOSIS:
It can be established by the detection of anti-HCV (antibody) by ELISA which is available as screening
test.
Antibody detection becomes positive only months after the infection and shows non-specific reactions.
Confirmation by immune blot assay is therefore recommended
A recombinant immuno blot assay (RIBA) can be performed to confirm the positive results obtained
with a screening test such as ELISA.
Viral genome (HCV RNA) can be detected by polymerase chain reaction (PCR) & by
immunofluorescence.
It can be detected in-situ on biopsy & autopsy specimen.

TREATMENT:
Treatment with inmterferon -α, either alone or in combination with antiviral agents such as Ribavarin
has been found to be useful in some cases.

TRANSMISSION:
It is transmitted by needlestick injuries, use of contaminated needles and syringes, transfusion infected
blood & blood products & sexual intercourse.
HCV infection is seen only in humans & occurs throughout the world. The source of the infection is the
large number of carriers.

CLINICAL FEATURTES:
- Incubation period varies from 15 – 160 days, with an average of 50 days
- About 75% infection are sub-clinical
 - Cirrhosis can be present at the time of diagnosis or may develop after a period of 5-10 years.

SYMPTOMS: Have similar symptoms with HAV & HBV. It includes abdominal pain, bleeding, blotting, swollen
blood vessels, yellow skin & eye.

HEPATITIS-D VIRUS (HDV)

DELTA ANTIGEN
- It belongs to the genus ‘Deltavirus’
- It is a defectivre virus as it is dependent on the helper function of HBV for its replication &
expression.
- It is caused by defective RNA viruses that is unable to produce its own protein coat and thus coat
ifself with HBV surface antigen.

MORPHOLOGY:
- It is spherical in shape
- It is 36-38 nm in diameter
- RNA particle is surrounded by HBsAg envelope
- The genome is single stranded, small circular molecule of RNA
- It encodes its own nucleoprotein, the delta antigen on HDAg , But the outer envelope (HBsAg) of
HDV is encoded by the genome of HBV containing same cell.
- HDV is an incomplete virus, because the DNA and Delta antigen do not constitute a complete viral
particle – an outer protein coat is required.
- It use the Hepatitis B virus surface antigen as its outer coat.

PATHOGENESIS:
It is similar to the pathogenesis of hepatitis caused by HBV i.e the virus infected hepatocytes are
damaged by cytotoxic T-cells.
IgG antibody against delta antigen is not detected for long periods after infection. Persons with chronic
hepatitis B who acquire infections with hepatitis D suffers relapses of jaundice & have a high livelihood of
developing chronic cirrhosis.

LAB DIAGNOSIS:
Diagnosis can be made by detecting the IgM anti-delta antibody in serum. ELISA & RIA kit are
commercially available for detection of antibodies to HDV.
The IgM antibody appears 2-3 weeks after infection and is soon replaced by the IgG antibody in acute
Infections.
HDV RNA can be detected by hybridization using a radiolabelled probe.
TRANSMISSION:
HDV infection can occur in presence of HBV under two situations:
1. Simultaneous infection with both HDV & HBV
2. Superinfection of an HBsAg carrier by HDV
Transmisson occurs parenteerally. Once infection due to HDV is established, in interferes with
HBV multiplication and utilizes HBV for its own replication.

TREATMENT:
As for HDV interruption of HBV replication will also have the effect of stopping HDV replication.
Response to treatment with interferon – alpha in patients with delta hepatic is less than in those with hepatitis
B alone.

SYMPTOMS: Similar with HAV & HBV.

HEPATITIS-E VIRUS (HEV)

MORPHOLOGY:
- Hepatitis E virus belongs to family ‘Heperividae’ & genus ‘Hepevirus’
- They are spherical, non-enveloped
- They are 27-28 nm in diameter.
- They possess single stranded RNA genome, which is surrounded by icosahedral capsid with
characteristic surface depression

PATHOGENESIS:
Hepatitis E has been shown to occur in epidemic, endemic & sporadic forms almost exclusively in
developing countries.
It is primarily associated with ingestion of faecally contaminated drinking water. It occurs
predominantly in young to middle- age adults.
Incubation period ranges from 2-8 weeks, with an average of 6 weeks. Clinically it resembles hepatitis
A virus
The disease is generally mild and self limiting. Like Hepatitis A, Hepatitis E does not lead to chronic
Hepatitis cirrhosis, cancer or carrier state
LAB DIAGNOSIS:
1. Exclusion of hepatitis A & Hepatitis B
Hepatitis A can be excluded by IgM serology & Hepatitis B by absence of HBsAg & anti HBc-IgM.
2. Immunoelectron Microscopy
Faeces is examined by electron microscopy for aggregated hepevirus virus particles, using
monoclonal antibodies
3. ELISA tests & western blot assay
These are used for detection of IgM & IgG antibodies.
4. Polymerase Chain reaction (PCR)
HEV RNa can be detected in faeces or acute phase sera qof patients by RT-PCR. It is a gold
standard test for a diagnosis of acute HEV infection.

TREATMENT:
Treatment is supportive only – there are no effective antiviral agents. There is also no vaccine at
present.

HEPATITIS-G VIRUS (HGV)

- This virus was isolated from a patient with chronic hepatitis in 1996.
- It has been placed in family ‘flaviviridae’ & genus ‘hepacivirus’.
- HGV RNA has been found in patients with acute, chronic & fulminant hepatitis, haemophiliacs,
patients with multiple transfusion, blood donors & intravenous drug addicts.
- Its role in hepatitis is not clear
- The genome of HGV consist of single stranded RNA
- HGV replicates in peripheral blood cells.
- The virus is transmitted parenterally, sexually & from mother to child.

LAB DIAGNOSIS:
- HGV infection can be detected by reverse transcriptase polymerase chain reaction (RT-PCR)
- Recently an immunoassay has been developed to detect antibody against hepatitis G enveloped
- Serum HGV RNA indicates viraemia while antibody is associated with recovery

Features Hep. A Hep. B Hep. C Hep. D Hep. E Hep. G

Family Picornaviridae Hepadnaviridae Flaviviridae Unclassifie Calcivirida Flaviviridae
d e
Genus Hepatovirus Orthohepadna Hepacivir Deltavirus Calcivirus Hepacivirus
virus
Genome ssRNA dsDNA ssRNA ssRNA ssRNA ssRNA
Viron 27 nm, 42 nm, spherical 50-60 nm, 36-38 nm, 27-38 nm, 50-60 nm,
icosahedral spherical spherical icosahedral spherical
Envelope No Yes (HBsAg) Yes Yes No Yes
(HBsAg)
Stability Heat & acid stable Acid sensitive Ether & acid Acid – Heat Ether & acid
sensitive Sensitive stable sensitive
Transmission Faecal / Oral Perenteral, sexual Parental, Parenteral Fecal/Oral Parenteral,
& perinatal sexual & sexual &
parinatal perinatal