Hepatitis Virus - introduction, categorize and epidemis

hepatitis virus

1. Hepatitis Virus

2. What is Hepatitis?

Hepatitis is a general term used to describe
inflammation of the liver.

Liver inflammation can be caused by:
•several viruses (viral hepatitis),
•chemicals,
•drugs,
•alcohol,
•genetic disorders or by an overactive immune system that mistakenly
attacks the liver, called autoimmune hepatitis.

Depending on its course, hepatitis can be acute, which
flares up suddenly and then goes away, or chronic, which
is a long-term condition usually producing more subtle
symptoms and progressive liver damage.

3. ACUTE: re-stabilization
of liver function
CHRONIC: possible
liver damage persists

4. comparison between a healthy liver and a damaged and
suffering one, following hepatitis

5. 
The World Health Organization (WHO), data report that
in 2020, 325 million people in the world live with
chronic hepatitis B or C infection and 1,300,000 people
die every year due to liver complications caused by
infections.

There are five different types of hepatitis: A, B, C, D,
and E.

Hepatitis infections are caused by viruses that enter
the body through different routes and attack the liver,
which acts as a filtering unit within the body.

When hepatitis infects this vital organ, the liver cannot
do its job and toxins accumulate.

Also, the liver is responsible for clotting factors, and
infection impairs this function. As such, many of the
signs and symptoms are related to these processes.

7. Hepatitis in history Hepatitis in history

The first cases of hepatitis can be traced back to China in The first cases of hepatitis can be traced back to China in
the sixth millennium BC, although clinical cases of jaundice the sixth millennium BC, although clinical cases of jaundice
have always accompanied the history of humanity.have always accompanied the history of humanity.

However, the isolation and classification of viruses A and B However, the isolation and classification of viruses A and B
only occurred in 1942, when an epidemic struck the US only occurred in 1942, when an epidemic struck the US
military after vaccination of yellow fever. military after vaccination of yellow fever.

Virus C was isolated in 1989 by molecular biologists of the Virus C was isolated in 1989 by molecular biologists of the
Chiron Corporation.Chiron Corporation.

In 1977 Professor Mario Rizzetto identified, through In 1977 Professor Mario Rizzetto identified, through
immunofluorescence, the antigen-antibody system of a immunofluorescence, the antigen-antibody system of a
particular form of hepatitis which, later, he discovered to particular form of hepatitis which, later, he discovered to
be Delta hepatitis.be Delta hepatitis.

8. spherical shape, 28 nm, no envelope
Positive ssRNA

9. Hepatitis A

Hepatitis A is contracted through the ingestion of food or
water contaminated with feces

People suffering from this infection are very contagious and
it can also be transmitted from person to person such as
kissing or sharing cups or eating contaminated food or
drinks.

This type of infection usually clears up without treatment,
and individuals with hepatitis A rarely suffer from chronic
liver failure or disease.

Prevention is possible through vaccination.

Treatments for hepatitis A are rest, limiting things the liver
processes like drugs and alcohol, and treatments to reduce
nausea.

10. HEPATITIS A VIRUS (HAV)HEPATITIS A VIRUS (HAV)

Transmission: fecal-oral (contaminated food and water)Transmission: fecal-oral (contaminated food and water)

The incubation period is between 20 and 40 days.The incubation period is between 20 and 40 days.

The virus is eliminated in the feces with a conc. maximum The virus is eliminated in the feces with a conc. maximum
in the period preceding the symptoms (jaundice) or the in the period preceding the symptoms (jaundice) or the
possibility of detecting specific Ab.possibility of detecting specific Ab.

In childhood, the disease is usually without jaundice.In childhood, the disease is usually without jaundice.

The infection rarely evolves into fulminate hepatitis and The infection rarely evolves into fulminate hepatitis and
never becomes chronic.never becomes chronic.

Pathogenesis: virus HAV multiplies in liver cells Pathogenesis: virus HAV multiplies in liver cells
poured into the bile poured into the bile faecal material faecal material

HAV HAV replicate slowly without cytopathic damagereplicate slowly without cytopathic damage

12. 
HAV resists detergents, acids (pH = 1), temperature of 60 ° C, HAV resists detergents, acids (pH = 1), temperature of 60 ° C,
can survive for months in fresh or salt water can survive for months in fresh or salt water
infection of bivalves/clam and other molluschinfection of bivalves/clam and other mollusch
Clinical syndromes: fever, loss of appetite, abdominal pain,
jaundice.
People at risk: people in overcrowded and unhealthy areas
children living in communities
pregnant women (high mortality when associated
with HEV)
PATHOGENESIS
HAV replicates slowly in the liver
The virus establishes persistent infection (no cytolysis)
Cytotoxic T cells and NK lyses infected cells although interferon
limits viral replication.

13. DIAGNOSIS HAVDIAGNOSIS HAV

Direct: demonstration of virus (no longer done)Direct: demonstration of virus (no longer done)
•On infected fecal material (On infected fecal material (6-7 days before the onset of symptoms)6-7 days before the onset of symptoms)
•On infected blood (in the acute phase)On infected blood (in the acute phase)

Indirect (sierological diagnosis)Indirect (sierological diagnosis)
•research in the blood for research in the blood for Ab anti-HAV by ELISA testAb anti-HAV by ELISA test

Early phase of the infection: IgM appears 3-4 weeks after Early phase of the infection: IgM appears 3-4 weeks after
infection and can remain in the bloodstream for up to 12 infection and can remain in the bloodstream for up to 12
monthsmonths

Convalescent phase: anti-HAV IgG appear and persist for over Convalescent phase: anti-HAV IgG appear and persist for over
6 months and even for life.6 months and even for life.
Anti HAV-IgM: ongoing hepatitis
Anti HAV-IgG: precedent immunity
Prophylaxis vaccine: virus killed or inactivated

14. HEPATITIS B Virus (HBV)HEPATITIS B Virus (HBV)
Characteristic:Characteristic:
•Family: Hepadnavirus Family: Hepadnavirus
•Structure: Icosahedral symmetry, with pericapsidStructure: Icosahedral symmetry, with pericapsid
•Genome: DNA partially double-stranded. Genome: DNA partially double-stranded. Viral DNA Viral DNA
polymerase is linked to one end of the genome. The polymerase is linked to one end of the genome. The
genome consists of 3020-3320 bp (for the full-length genome consists of 3020-3320 bp (for the full-length
strand) and 1700-2800 bp (for the shorter strand).strand) and 1700-2800 bp (for the shorter strand).
•DNA has 4 ORFs:DNA has 4 ORFs:

the pre-S / S regionthe pre-S / S region (surface Ag) (surface Ag)

the pre-C / C regionthe pre-C / C region (core Ag) (core Ag)

the ORF P the ORF P (DNA polymerase)(DNA polymerase)

the ORF X (the ORF X (transactivating protein)transactivating protein)

16. 
The pre-S/S region is The pre-S/S region is
made by 2 sequences: made by 2 sequences:
pre-S1 and pre-S2 that pre-S1 and pre-S2 that
precede the S gene. precede the S gene.
There is one single There is one single
common stop codon and common stop codon and
3 different start codons, 3 3 different start codons, 3
different envelope different envelope
proteins are formed proteins are formed
during translation: the during translation: the
large (L) protein, the large (L) protein, the
middle (M) and the small middle (M) and the small
protein (S) called S protein (S) called S
antigen or HBsAg= is also antigen or HBsAg= is also
called major because it is called major because it is
expressed on the expressed on the
envelope in greater envelope in greater
amount than the othersamount than the others The external envelope of the virus is
a mosaic of these 3 proteins.

17. The pre-C /C region codified for

the core protein HBcAg

the HBeAg protein
.

18. 1) The HBV replication cycle begins with attachment to the hepatocyte
membrane, via the pre-S1 region of the virion envelope HBsAg
2)The viral genome enters the hepatocyte nucleus where positive stranded
HBV DNA synthesis occurs and the viral genome is converted into covalently
closed circular DNA (CCC DNA).
HBV Replication

19. 
3) cccDNA acts as a template for the transcription of genomic 3) cccDNA acts as a template for the transcription of genomic
and subgenomic transcripts, by the action of RNA polymerase and subgenomic transcripts, by the action of RNA polymerase
II of cell host.II of cell host.

4) these are transported into the cytoplasma where there are 4) these are transported into the cytoplasma where there are
the synthesis of the functional and structural proteins of the the synthesis of the functional and structural proteins of the
virion. The envelope proteins and protein X, and HBeAg, are virion. The envelope proteins and protein X, and HBeAg, are
encoded by the subgenomic transcripts.encoded by the subgenomic transcripts.

5) The pregenomic mRNA encodes the viral polymerase and 5) The pregenomic mRNA encodes the viral polymerase and
acts also as a template for RT.acts also as a template for RT.

6) The pregenomic RNA and the polymerase are assembled and 6) The pregenomic RNA and the polymerase are assembled and
incorporated with the core proteins to form the nucleocapsid.incorporated with the core proteins to form the nucleocapsid.

7) In the nucleocapsid by RT, a DNA-RNA hybrid is generated 7) In the nucleocapsid by RT, a DNA-RNA hybrid is generated
which leads to the formation of the L (-) strand.which leads to the formation of the L (-) strand.

8) Then the S (+) strand is synthesized on the L (-) strand only 8) Then the S (+) strand is synthesized on the L (-) strand only
after the pregenomic mRNA has been degraded by an RNA H.after the pregenomic mRNA has been degraded by an RNA H.

20. 9) The nucleocapsid is then internalized in the endoplasmic
reticulum where it acquires the HBsAg envelope proteins,
and finally the mature virion escapes from the liver cell.

21. 
The mature and complete virion has a diameter of 42 nm and is The mature and complete virion has a diameter of 42 nm and is
also called Dane particlealso called Dane particle

In addition to the Dane particle, other subviral particles are In addition to the Dane particle, other subviral particles are
produced in the infected cells with a filamentous shape with a produced in the infected cells with a filamentous shape with a
diameter of around 40 nm and with a spherical shape of 22 nm in diameter of around 40 nm and with a spherical shape of 22 nm in
diameter.diameter.

These are not infectious because they do not have the genome These are not infectious because they do not have the genome
but only the envelope with viral antigens.but only the envelope with viral antigens.

22. /

23. HBV antigens and antibodies

Dane particle (Virion) has a double-shell structure that contains
several different antigens

The outer envelope is called a surface antigen (HBsAg), also called
the Australian antigen.
•The inner core contains HBV core antigen (HBcAg), and HBV e
antigen (HBeAg).
•There Are Three Antigens and Three
 Antibodies
•HBsAg Anti-HBsAb
•HBcAg Anti-HBcAb
•HBeAg Anti-HBeAb

Hepatitis B Surface Antibody (Hepatitis B Surface Antibody (HBsAbHBsAb) appears after roughly 4 ) appears after roughly 4
weeks, after the disappearance of HBsAg.weeks, after the disappearance of HBsAg.

It indicates the end of the acute phase and the patient’s complete
recovery from the infection.

It is the only protective antibodyIt is the only protective antibody

24. Antigens and MarkersAntigens and Markers

HBsAg:HBsAg: the presence indicates the state of infection. the presence indicates the state of infection.
HBsAg positive patients are considered infectiousHBsAg positive patients are considered infectious

HBcAg: HBcAg: present only in Dane particle . It is the Ag of the present only in Dane particle . It is the Ag of the
core, it is not found in the bloodstrem but is present only core, it is not found in the bloodstrem but is present only
in the liver tissue.in the liver tissue.

HBeAg: HBeAg: it is the smallest of the virus nucleocapsid it is the smallest of the virus nucleocapsid
antigens (core) and is associated with active viral antigens (core) and is associated with active viral
replication. It is found in the initial phase of acute infection replication. It is found in the initial phase of acute infection
and in some forms of chronic hepatitis.and in some forms of chronic hepatitis.

HBV-DNA: HBV-DNA: it is the genome of the virus, it is the most it is the genome of the virus, it is the most
sensitive and fastest indicator of viral replication. Its sensitive and fastest indicator of viral replication. Its
presence always indicates active infectionpresence always indicates active infection

25. ANTIBODIES AND VIRAL MARKERSANTIBODIES AND VIRAL MARKERS

HBcAb –IgMHBcAb –IgM: : the early non-protective antibody is found the early non-protective antibody is found
only in the phases of active viral replication therefore it is only in the phases of active viral replication therefore it is
found in the acute forms and in the chronic forms in found in the acute forms and in the chronic forms in
exacerbationexacerbation

HBcAb –IgGHBcAb –IgG:: This Ab appair after contact with the virus This Ab appair after contact with the virus
end remains present for life, regardless of the outcome of end remains present for life, regardless of the outcome of
the infection. So it indicates that it has been contacted with the infection. So it indicates that it has been contacted with
the virus.the virus.

HBsAbHBsAb:: is the antibody against HBsAg. The presence of this is the antibody against HBsAg. The presence of this
Ab indicates protection against infection (immunization). It Ab indicates protection against infection (immunization). It
is found after recovery from an infection or after is found after recovery from an infection or after
vaccination. vaccination. It is the protective antibodyIt is the protective antibody

HBeAbHBeAb:: is the antibody against HBeAg. The presence of this is the antibody against HBeAg. The presence of this
Ab does not prevent the evolution towards croncizationAb does not prevent the evolution towards croncization

28. Epidemiology of HBVEpidemiology of HBV

Hepatitis B
 occurs when an individual is exposure to
Hepatitis B
 occurs when an individual is exposure to
blood or body fluids containing the virus blood or body fluids containing the virus

The virus is trasmitted by sexual contact and The virus is trasmitted by sexual contact and
percutaneous transmission (eg, intravenous drug use) percutaneous transmission (eg, intravenous drug use)

Sexual trasmission account more than 25% of casesSexual trasmission account more than 25% of cases

Sexual partners of HBV-infected people are at risk of Sexual partners of HBV-infected people are at risk of
infection, even in the absence of high-risk behavior.infection, even in the absence of high-risk behavior.

Since many patients with chronic HBV infection are Since many patients with chronic HBV infection are
unaware of their infection, sexual contact is likely to be unaware of their infection, sexual contact is likely to be
an important mode of transmission worldwide.an important mode of transmission worldwide.

In the USA and Western Europe, injection drug use In the USA and Western Europe, injection drug use
remains a very important mode of HBV transmission remains a very important mode of HBV transmission
(23% of all cases).(23% of all cases).

29. The pathogenesis of HBVThe pathogenesis of HBV

The pathogenesis of HBV-related liver disease is
generally believed to be related to T-cell-mediated
cytotoxic lysis of infected hepatocytes.

Chronic hepatitis B patients who clear HBeAg have more
vigorous cytotoxic responses to HBV antigens than those
who remained HBeAg positive.

It is hypotised that complete HBV eradication rarely
occurs after recovery from acute hepatitis and that
traces of the virus can maintain the T cell response for
decades after clinical recovery, which in turn keeps the
virus in check..

30. Acute HBV InfectionAcute HBV Infection

In primary infection, HBsAg becomes detectable in the blood after In primary infection, HBsAg becomes detectable in the blood after
an incubation period of 4 to 10 weeks, shortly followed by an incubation period of 4 to 10 weeks, shortly followed by
antibodies to the HBcAb antigen.antibodies to the HBcAb antigen.

A serum sickness-like syndrome may develop during the A serum sickness-like syndrome may develop during the
prodromal period, followed by symptoms such as anorexia, prodromal period, followed by symptoms such as anorexia,
nausea, jaundice, and right upper quadrant discomfort.nausea, jaundice, and right upper quadrant discomfort.

Viremia is well established by the time HBsAg is detected and Viremia is well established by the time HBsAg is detected and
virus titers in acute infections are very high.virus titers in acute infections are very high.

As the infection clears, the HBsAg and HBeAg viral antigens As the infection clears, the HBsAg and HBeAg viral antigens
disappear from the circulation and free anti-HBs antibodies disappear from the circulation and free anti-HBs antibodies
become detectable.become detectable.

About 70% of patients with acute hepatitis B have subclinical or About 70% of patients with acute hepatitis B have subclinical or
anitteric hepatitis, while 30% develop jaundice hepatitis.anitteric hepatitis, while 30% develop jaundice hepatitis.

The disease may be more severe in patients coinfected with other The disease may be more severe in patients coinfected with other
hepatitis viruses or with underlying liver diseasehepatitis viruses or with underlying liver disease

31. Clinical Outcomes of Acute HBV Infections in adultClinical Outcomes of Acute HBV Infections in adult

32. 
The most feared complication of acute HBV infection is fulminant The most feared complication of acute HBV infection is fulminant
hepatic failure, defined as the onset of hepatic encephalopathy hepatic failure, defined as the onset of hepatic encephalopathy
within 8 weeks of the onset of symptoms. within 8 weeks of the onset of symptoms.

The prognosis is poor once encephalopathy has developed. The prognosis is poor once encephalopathy has developed.

Fulminant hepatic failure is unusual, occurring in approximately Fulminant hepatic failure is unusual, occurring in approximately
0.1 to 0.5 percent of patients. 0.1 to 0.5 percent of patients.

Fulminant hepatitis B is believed to be due to massive immune-Fulminant hepatitis B is believed to be due to massive immune-
mediated lysis of infected hepatocytes. This explains why many mediated lysis of infected hepatocytes. This explains why many
patients with fulminant hepatitis B have no evidence of HBV patients with fulminant hepatitis B have no evidence of HBV
replication at presentation.replication at presentation.

The reasons that HBV has a fulminant course in some patients are The reasons that HBV has a fulminant course in some patients are
not well-understood. not well-understood.
Fulminat Hepatitis

33. Chronic HBV infectionChronic HBV infection

Chronic HBV infection is defined by detecting HBsAg in the Chronic HBV infection is defined by detecting HBsAg in the
blood for a period >6 months (or more) blood for a period >6 months (or more)

The natural course of chronic hepatitis B virus infection is The natural course of chronic hepatitis B virus infection is
determined by the interplay between virus replication and determined by the interplay between virus replication and
the host immune response. the host immune response.

The risk of chronic infection is related to two major factors: The risk of chronic infection is related to two major factors:
the age at which infection is acquired the age at which infection is acquired

the immune state of the host.the immune state of the host.

The risk of developing chronic HBV infection after acute The risk of developing chronic HBV infection after acute
exposure ranges from exposure ranges from
90% in newborns of HBsAg-positive mothers90% in newborns of HBsAg-positive mothers
to 25 to 30% in infants and children <5 years old to 25 to 30% in infants and children <5 years old
less than 10% in adultsless than 10% in adults

34. 
About 50% of patients with chronic HBV hepatitis will
resolve the viral liver infection without long-term
sequelae.

20% of patients with chronic HBV hepatitis will become
chronic asymptomatic carriers of the virus or patients
with persistent chronic hepatitis and may develop
extrahepatic diseases (eg, glomerulonephritis,
polyarteritis nodosa).

The remaining 30% of patients with chronic HBV
develop chronic active hepatitis and may develop liver
cirrhosis, primary hepatocellular carcinoma, or
extrahepatic disease.

Many patients with chronic hepatitis B are
asymptomatic while others have nonspecific symptoms
such as fatigue.

35. It is well known that the risk of persistent infection is much greater in
infants than in adults. Babies of HBsAg-positive mothers who become
infected at birth have a probability of about 80-90% of having a chronic
infection.

37. Prevention of HBVPrevention of HBV

Three main strategies exist for the prevention of HBV Three main strategies exist for the prevention of HBV
infection:infection:
• 1) behavior modification to prevent disease transmission, 1) behavior modification to prevent disease transmission,
• 2) passive immunoprophylaxis, 2) passive immunoprophylaxis,
• 3) active immunization.3) active immunization.

Patients with chronic HBV infection should be informed Patients with chronic HBV infection should be informed
about lifestyle changes and prevention of transmission. about lifestyle changes and prevention of transmission.
Carriers of HBV should be informed about the risk of Carriers of HBV should be informed about the risk of
transmission to others.transmission to others.

Counseling should include precautions to prevent sexual Counseling should include precautions to prevent sexual
transmission, perinatal transmission, and risk of transmission, perinatal transmission, and risk of
inadvertent transmission via environmental contamination inadvertent transmission via environmental contamination
from a blood spill. from a blood spill.

38. 
Because HBV can survive on environmental surfaces for Because HBV can survive on environmental surfaces for
at least 1 week, family members are at increased risk of at least 1 week, family members are at increased risk of
HBV infection and therefore should be vaccinated if they HBV infection and therefore should be vaccinated if they
test negative for HBV serological markers.test negative for HBV serological markers.

Effective vaccines have been available since the early to Effective vaccines have been available since the early to
mid-1980s.mid-1980s.

It is the first recombinant vaccine and is based on the It is the first recombinant vaccine and is based on the
hepatitis B surface antigen (HBsAg) gene inserted in hepatitis B surface antigen (HBsAg) gene inserted in
yeast cells (yeast cells (Saccharomyces cerevisiaeSaccharomyces cerevisiae) free from human ) free from human
blood products. blood products.

This allows the yeast to produce only the non-infectious This allows the yeast to produce only the non-infectious
surface protein, without any introduction of the viral surface protein, without any introduction of the viral
particleparticle

The HBV vaccine is highly effective. The HBV vaccine is highly effective.

Anti-HBs develops in over 95% of vaccineesAnti-HBs develops in over 95% of vaccinees

39. HBV marker interpretationHBV marker interpretation
Interpretation HBsAg HBsAb HBcAb-
IgG
HBcAb-
IgM
HBV-DNA
Acute Hepatitis + - + + +
Infected + - +/- + +
Healed with
immunization
- + + +/- -
Chronic infection + - + - +
Passed
infection
- + + - -
Vaccination - + - - -

41. HEPATITI D Virus (HDV)HEPATITI D Virus (HDV)

Genome: RNA cGenome: RNA codin for 1 antigenic protein = odin for 1 antigenic protein = δ δ antigenantigen

The hepatitis D virus is a defective virus (satellite virus) The hepatitis D virus is a defective virus (satellite virus)
because need the presence of HBV virus for multipliedbecause need the presence of HBV virus for multiplied

It multiplies only in the presence of HBVIt multiplies only in the presence of HBV

It is found in 5% of chronic hepatitis B cases. In this way, It is found in 5% of chronic hepatitis B cases. In this way,
the Delta virus is able to co-infect or enhance the action the Delta virus is able to co-infect or enhance the action
of the B virus which acts as a support for replication.of the B virus which acts as a support for replication.

HBV-HDV co-infection aggravates the disease (fulminant HBV-HDV co-infection aggravates the disease (fulminant
hepatitis)hepatitis)

TRANSMISSION: parenteral (blood and human biological TRANSMISSION: parenteral (blood and human biological
fluids)fluids)

Vaccination against HBV also protects against HDVVaccination against HBV also protects against HDV

42. 
The D virus cell resembles plant viroids due to the presence of The D virus cell resembles plant viroids due to the presence of
circular RNA.circular RNA.

The envelope is not capsidic, but is made up externally of the The envelope is not capsidic, but is made up externally of the
surface antigen of the virus B (HBsAg) and, internally, of the surface antigen of the virus B (HBsAg) and, internally, of the
antigen of the virus D (HDAg) that surrounds the genetic material.antigen of the virus D (HDAg) that surrounds the genetic material.

Although the structure of these viruses recalls that of plant Although the structure of these viruses recalls that of plant
viruses, in reality the identified nitrogenous bases are 1700, a viruses, in reality the identified nitrogenous bases are 1700, a
greater number than the viroid specimens that have been isolated greater number than the viroid specimens that have been isolated
in plantsin plants..

43. HDV replicationHDV replication

During the replication cycle, the HDV virus behaves like a parasite During the replication cycle, the HDV virus behaves like a parasite
by exploiting the antigens of the B virus. by exploiting the antigens of the B virus.

At the same time, some of the RNA nucleotide sequences are At the same time, some of the RNA nucleotide sequences are
capable of autonomously replicating the genomic material. capable of autonomously replicating the genomic material.

This type of replication occurs because in the same segment there This type of replication occurs because in the same segment there
is an endonucleasis that "cuts" the portion of RNA to be replicated is an endonucleasis that "cuts" the portion of RNA to be replicated
and the genetic information. and the genetic information.

These sequences consist of about 100 nucleotides and are termed These sequences consist of about 100 nucleotides and are termed
autocatalytic segments.autocatalytic segments.

The replication cycle takes place by exploiting a process of The replication cycle takes place by exploiting a process of
elimination of cellular waste called autophagy.elimination of cellular waste called autophagy.

44. 
The processes of transcription and replication are unusual. The processes of transcription and replication are unusual.
The RNA genome is replicated (rolling circle) and The RNA genome is replicated (rolling circle) and
transcribed in the nucleus by a cellular enzyme (RNA transcribed in the nucleus by a cellular enzyme (RNA
polymerase II),probably modified following the formation of polymerase II),probably modified following the formation of
a complex with the Delta protein.a complex with the Delta protein.

The genome with the Delta protein then binds to HBsAg to The genome with the Delta protein then binds to HBsAg to
form a virion, and the virus is then released from the cell.form a virion, and the virus is then released from the cell.

45. CLINIC of HEPATITI DCLINIC of HEPATITI D

Co-infection = HBV+ HDV in the same timeCo-infection = HBV+ HDV in the same time
•severe acute hepatitissevere acute hepatitis
•low risk of chronic infectionlow risk of chronic infection

Super-infection =Super-infection =Initial HBV infection and Initial HBV infection and
then HDVthen HDV
•high probability of chronic infectionhigh probability of chronic infection
•high probability of severe liver diseasehigh probability of severe liver disease

46. HDV: diagnosis, therapy and preventionHDV: diagnosis, therapy and prevention

Diagnosis: HDV infection is usually diagnosed by detect in Diagnosis: HDV infection is usually diagnosed by detect in
the circulation different markers:the circulation different markers:

Ag delta Ag delta

Ab delta Ab delta

HDV-RNA HDV-RNA

Therapy: No specific treatment is available for HDV Therapy: No specific treatment is available for HDV
infection. However, since it depends on HBV for replication, infection. However, since it depends on HBV for replication,
the methods useful against HBV are also effective against the methods useful against HBV are also effective against
HDV.HDV.

Prevention: There is no specific vaccine against HDV, Prevention: There is no specific vaccine against HDV,
however individuals vaccinated for HBV are also protected however individuals vaccinated for HBV are also protected
against any infection with HDV.against any infection with HDV.

47. HEPATITIS C VIRUSHEPATITIS C VIRUS

Hepatitis C (non-A non-B transfusional hepatitis) is caused by HCVHepatitis C (non-A non-B transfusional hepatitis) is caused by HCV

FLAVIVIRIDAE family, genus Flavivirus (identified in 1989)FLAVIVIRIDAE family, genus Flavivirus (identified in 1989)

Icosahedral capsid surrounded by envelope (55-60 nm diameter)Icosahedral capsid surrounded by envelope (55-60 nm diameter)

Linear ssRNA (+) genome (9.1 kb)Linear ssRNA (+) genome (9.1 kb)

Variable Virus: identified at least 6 different genotypes and Variable Virus: identified at least 6 different genotypes and
numerous subtypesnumerous subtypes

It is mainly transmitted through infected blood and sexually It is mainly transmitted through infected blood and sexually
contact contact

Viremia 1-3 weeks after infection: lasts 4-6- months in the Viremia 1-3 weeks after infection: lasts 4-6- months in the
infectionacute and> 10 years in the persistent oneinfectionacute and> 10 years in the persistent one

Causes 3 diseases: acute with healing (15%), acute with Causes 3 diseases: acute with healing (15%), acute with
cirrhosis(15%), persistent (70%)cirrhosis(15%), persistent (70%)

Associated with primary hepatocellular carcinomaAssociated with primary hepatocellular carcinoma

48. Hepatitis C

Hepatitis C 
is contracted when someone comes in
contact with blood infected by the virus.

Many times, individuals do not have symptoms
until severe damage has been done to the liver.

Approximately 75-85% of individuals suffering
from hepatitis C will suffer from a chronic
infection, according to the CDC. This type of
hepatitis is considered the most deadly.
Medications such as anti-viral and interferon drugs
are a primary treatment for hepatitis C. Currently
no vaccine exists for this deadly disease.

49. STRUCTURE and MORPHOLOGY STRUCTURE and MORPHOLOGY

Genome is provided with a single-stranded RNA with Genome is provided with a single-stranded RNA with
positive polarity of 9.5 kb positive polarity of 9.5 kb

The genome consists of a large central region encoding a The genome consists of a large central region encoding a
viral polyprotein which is then cut to give rise to: viral polyprotein which is then cut to give rise to:
●●3 structural proteins such as Core (C) and the 3 structural proteins such as Core (C) and the
glycoproteins of the viral envelope, E1 and E2glycoproteins of the viral envelope, E1 and E2
●●non-structural proteins such as NS2, NS3, NS4A, non-structural proteins such as NS2, NS3, NS4A,
NS4B, NS5A, NS5B involved in viral replication NS4B, NS5A, NS5B involved in viral replication

the genome is flanked by 2 non-coding regions with the genome is flanked by 2 non-coding regions with
regulatory function: 5 ′ UTR and 3 ′ UTRregulatory function: 5 ′ UTR and 3 ′ UTR

50. 
The RNA of the virus is enclosed in an icosahedral capsid The RNA of the virus is enclosed in an icosahedral capsid
(core) outside of which there is the phospholipid bilayer (core) outside of which there is the phospholipid bilayer
containing E1 and E2.containing E1 and E2.

There is also the P7 protein, a small membrane polypeptide There is also the P7 protein, a small membrane polypeptide
with ion channel activity, still being studied today, which with ion channel activity, still being studied today, which
plays an important role in the assembly and infection of the plays an important role in the assembly and infection of the
virus to specific cells.virus to specific cells.

51. HCV REPLICATIONHCV REPLICATION

The virus binds to CD81 The virus binds to CD81
receptors, expressed on both receptors, expressed on both
hepatocytes and B hepatocytes and B
lymphocytes and enters via lymphocytes and enters via
endocytosisendocytosis

Into the cell it releases its Into the cell it releases its
ssRNA + which functions as ssRNA + which functions as
mRNA, binds to the ribosomes mRNA, binds to the ribosomes
and start the translation, with and start the translation, with
production of the viral production of the viral
proteins necessary for proteins necessary for
replicationreplication

The genome is replicated The genome is replicated
starting from the NS5B starting from the NS5B
protein, an RNA-dependent protein, an RNA-dependent
RNA polymerase.RNA polymerase.

At the end of the replication At the end of the replication
cycle, the virion is released by cycle, the virion is released by
exocytosisexocytosis

52. VARIABILITYVARIABILITY

The HCV virus has extensive genetic recombinationThe HCV virus has extensive genetic recombination

This determines the presence of at least 6 different genotypes This determines the presence of at least 6 different genotypes
indicated 1, 2, 3, 4, 5, 6indicated 1, 2, 3, 4, 5, 6

These genotypes differ from each other by geographical These genotypes differ from each other by geographical
distribution but above all by subclass and greater virulence: in distribution but above all by subclass and greater virulence: in
fact, among these, the main subclasses 1a, 1b, 2a, 2b, 3a, 4c and fact, among these, the main subclasses 1a, 1b, 2a, 2b, 3a, 4c and
4d are known. 4d are known.

In each infected individual there is a polymorphic "quasispecies" In each infected individual there is a polymorphic "quasispecies"
viral population with a dominant genotype but also with a large viral population with a dominant genotype but also with a large
number of viral mutants.number of viral mutants.
The high mutation rate The high mutation rate
Allows the virus to evade the Allows the virus to evade the
immune system and immune system and
create chronic infectionscreate chronic infections

54. 
TrasmissionTrasmission
•Blood and other biological fluids (parenteral)Blood and other biological fluids (parenteral)
•Vertical: from infected mother to fetus via transplacentalVertical: from infected mother to fetus via transplacental

People at riskPeople at risk
•medical / health personnel, polytransfusion subjects, dialysis medical / health personnel, polytransfusion subjects, dialysis
patients, drug addicts, people with many sexual partners.patients, drug addicts, people with many sexual partners.

There is no vaccine due the high variabilityThere is no vaccine due the high variability

Therapy:interferon or multiple therapy with multiple Therapy:interferon or multiple therapy with multiple
antiviralsantivirals

DiagnosisDiagnosis
•anti-HCV antibodies researchanti-HCV antibodies research
•Search for HCV-RNA in the patient's blood for infection Search for HCV-RNA in the patient's blood for infection
monitoring.monitoring.

56. HCV

About 15% of patients with HCV infection will develop
symptomatic acute hepatitis after an incubation period
of 14-180 days and then fully recover without
developing chronic hepatitis.

The acute form of HCV hepatitis is similar to HBV but the
inflammatory response is less and as a result symptoms
are usually milder.

Approximately, 70% of those infected with HCV will be
asymptomatic and they will become chronic persistent
hepatitis patients

57. 
Chronic persistent HCV hepatitis is defined as the presence
of HCV RNA in the bloodstream for at least 6 months .

The predominant symptom is chronic fatigue.

Chronic persistent HCV hepatitis patients oftentimes progress to
chronic active HCV hepatitis in 10-15 years leading to cirrhosis
(20% of the cases) and liver failure (20% of cirrhotic cases) after
20 years.

Alcohol consumption, certain medications, and other hepatitis
viruses can exacerbate HCV-induced liver damage to promote
cirrhosis of the liver.

HCV chronic hepatitis infections results in primary hepatocellular
carcinoma in around 5% of these patients after around 30 years.
 

Lastly, around 15% of those infected with HCV develop rapid onset
cirrhosis of the liver.

58. Natural History Hepatitis CNatural History Hepatitis C
Chronic with
hepatic
normal
enzymeAcute
Hepatitis
CHRONIC
HEPATITIS
Chronic
infection
(40-70%)
healing with
elimination of
the virus (20-
40%)

60. HEPATITIS E VIRUS (HEV)HEPATITIS E VIRUS (HEV)

Structure: HEV virus Structure: HEV virus is a spherical particle of 30-is a spherical particle of 30-
34 nanometer diameter without outer coating34 nanometer diameter without outer coating. .

Genome: single helical RNA molecule of Genome: single helical RNA molecule of
approximately 7.6 kilobases, was cloned and approximately 7.6 kilobases, was cloned and
sequenced in 1990sequenced in 1990. .

Although HEV has not been classified with Although HEV has not been classified with
certainty, its morphological, physico-chemical certainty, its morphological, physico-chemical
and genomic characteristics suggest its and genomic characteristics suggest its
belonging to the Hepeviridae familybelonging to the Hepeviridae family..

It is very dangerous in pregnant women, where It is very dangerous in pregnant women, where
the death rate occurs on a 20% of cases the death rate occurs on a 20% of cases
manifested, especially during the second and manifested, especially during the second and
third trimesters of pregnancy when associated third trimesters of pregnancy when associated
with HAVwith HAV. .

61. 
HEV is an RNA virus belonging to HEV is an RNA virus belonging to
the family Hepeviridae, which the family Hepeviridae, which
includes two genera:includes two genera:
•Orthohepevirus (which has a host Orthohepevirus (which has a host
spectrum) mammals and birds andspectrum) mammals and birds and
•Piscihepevirus (which it infects trout). Piscihepevirus (which it infects trout).

To the genus Orthohepevirus To the genus Orthohepevirus
belong the species, A, B, C and D. belong the species, A, B, C and D.

The Orthohepevirus A species in The Orthohepevirus A species in
turn includes more genotypes:turn includes more genotypes:
• • 2 genotypes (HEV-1 and HEV-2)2 genotypes (HEV-1 and HEV-2)
encountered only in man;encountered only in man;
• • 2 genotypes (HEV-3 and HEV-4)2 genotypes (HEV-3 and HEV-4)
found both in humans and animals.found both in humans and animals.

Other genotypically related strains Other genotypically related strains
though of minor importance from though of minor importance from
the point of view of health found in the point of view of health found in
several animals including the wild several animals including the wild
boar (HEV-5 and HEV-7), the rabbit boar (HEV-5 and HEV-7), the rabbit
(HEV-3ra) and the camel (HEV-8)(HEV-3ra) and the camel (HEV-8)

62. HEPATITIS E VIRUSHEPATITIS E VIRUS

HEV HEV is a potential emerging pathogen of food source, in is a potential emerging pathogen of food source, in
fact, an increase in human infection has been observedfact, an increase in human infection has been observed

The virus is transmitted via feco-oral.The virus is transmitted via feco-oral.

HEV is the first cause of viral HEV is the first cause of viral acute hepatitis in acute hepatitis in
developing countries (Asia, Africa and Latin America)developing countries (Asia, Africa and Latin America)

More recently sporadic cases in developed countries but More recently sporadic cases in developed countries but
it is not certain whether these cases have been spread it is not certain whether these cases have been spread
through water or foodsthrough water or foods..

Incubation: 25-55 days. The infection occurs with Incubation: 25-55 days. The infection occurs with
epidemic cases in communities where there is poor epidemic cases in communities where there is poor
hygiene (contaminated water).hygiene (contaminated water).

HEV is present in the intestines of pigs and other HEV is present in the intestines of pigs and other
domestic animals (chickens and turkeys) in different domestic animals (chickens and turkeys) in different
countries (in the Netherlands the nucleotide sequencing countries (in the Netherlands the nucleotide sequencing
data indicate that animal and human HEV strains are data indicate that animal and human HEV strains are
closely relatedclosely related) )

The people that working with pigs have a higher The people that working with pigs have a higher
prevalence of Ab anti HEVprevalence of Ab anti HEV

64. HEV Infection in pregnancy HEV Infection in pregnancy

Pregnant women show a more severe course of infection Pregnant women show a more severe course of infection
than other populations. than other populations.

Hepatic failure with mortality rates of 20% to 25% has been Hepatic failure with mortality rates of 20% to 25% has been
reported from HEV genotype 1 and 2 outbreaks in developing reported from HEV genotype 1 and 2 outbreaks in developing
countries. countries.

In addition to the signs of an acute infection, adverse effects In addition to the signs of an acute infection, adverse effects
on the mother and fetus can include preterm delivery, on the mother and fetus can include preterm delivery,
miscarriage, stillbirth and neonatal death.miscarriage, stillbirth and neonatal death.

The pathological and biological mechanisms underlying the The pathological and biological mechanisms underlying the
adverse outcomes of infections in pregnancy remain largely adverse outcomes of infections in pregnancy remain largely
unclear. unclear.

It is suggest that increased viral replication and the influence It is suggest that increased viral replication and the influence
of hormonal changes on the immune system contribute to of hormonal changes on the immune system contribute to
worsening the course of the infectionworsening the course of the infection