Hepatitis A,B and C Viruses

1. Hepatitis A,B & CHepatitis A,B & C
VirusesViruses

2. IntroductionIntroduction
Hepatitis is a disease of the liver that causes inflammation and
swelling, potentially resulting in permanent damage. It can be
quite painful and its effects can make its victims feel weak.
Hepatitis infections can be acute or chronic, and people can
die from them.
The disease can be caused by many different factors, including
infectious organisms, chemical toxins, poisons, drugs, and
alcohol. Unlike non viral hepatitis, which can be caused by
any number of noninfectious means, viral hepatitis is caused
by one of six different viruses: hepatitis A, hepatitis B,
hepatitis C, hepatitis D, hepatitis E, or hepatitis G.

3. Differential Diagnosis of Acute HepatitisDifferential Diagnosis of Acute Hepatitis
Autoimmune diseases
Viral infections
Bacterial infections
Parasitic infections
Drugs
Toxins
hepatitis A, B, C, D, and E,
CMV, EBV, HSV, VZV, yellow fever
typhoid fever, Q fever,
leptospirosis, secondary syphillis,
sepsis
toxocariasis, liver flukes
ASA (Aspirin ), acetaminophen,rifampin,
oral contraceptives, sulfonamides, etc
Alcohol, carbon tetrachloride
Autoimmune hepatitis, SLE

4. Classification of Hepatitis VirusesClassification of Hepatitis Viruses
*linear, single strand; ** circular, double strand;
Virus
HAV
HBV
HCV
DNA or RNA
RNA*
DNA**
RNA*
Family
Picornaviridae
Hepadnaviridae
Flaviviridae
Envelope
no
yes
yes

5. Clinical Manifestations ofClinical Manifestations of
Acute Viral HepatitisAcute Viral Hepatitis
Asymptomatic Symptomatic Fulminant liver failure
and death
• Jaundice
• Scleral icterus
• Abdominal/RUQ pain
• Hepatomegaly
• Arthritis
Typical Signs and Symptoms
•
FeverFever
•
MalaiseMalaise
•
AnorexiaAnorexia
•
NauseaNausea
•
VomitingVomiting

6. Laboratory Findings in Acute ViralLaboratory Findings in Acute Viral
HepatitisHepatitis
• Elevated ALT (SGPT) and AST (SGOT).
• Elevated bilirubin.
• Elevated alkaline phosphates.
Laboratory indicators of liver pathologyLaboratory indicators of liver pathology
Laboratory indicators of infectionLaboratory indicators of infection
• Increased WBC.

7. Immunologic Markers Used forImmunologic Markers Used for
Serologic DiagnosisSerologic Diagnosis
Immune globulin of the G subclass (IgG):
• Produced in later infection
Total immune globulin (Total Ig):
• Combination of IgM and IgG
Immune globulin of the M sublcass (IgM):
• Produced in early infection

8. Source of
virus
feces blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
Route of
transmission
fecal-oral percutaneous
permucosal
percutaneous
permucosal
Chronic
infection
no yes yes
Prevention
pre/post-
exposure
immunization
pre/post-
exposure
immunization
blood donor
screening;
risk behavior
modification
Type of Hepatitis
A B C

9. Hepatitis A VirusHepatitis A Virus
Hepatitis A is a very infectious viral cause of acute hepatitis. It
is an acute illness, which means that the symptoms can come
on suddenly and sharply, causing a range of clinical problems
from mild illness with no symptoms to more severe illness and
even, on rare occasion, acute liver failure and death. Hepatitis
A eventually goes away and does not cause chronic problems .
At one time, hepatitis A was referred to as "infectious
hepatitis" because it could be spread from person to person
like other viral infections.

10.  Incubation period: Average 30 days
Range 15-50 days
 Jaundice by <6 yrs, <10%
age group: 6-14 yrs, 40%-50%
>14 yrs, 70%-80%
 Complications: Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
 Chronic sequelae: None
Hepatitis A - Clinical
Features

11. Fecal
HAV
Symptoms
0 1 2 3 4 5 6 1
2
2
4
Hepatitis A Infection
Total anti-
HAV
Titre ALT
IgM anti-HAV
Months after exposureMonths after exposure
Typical Serological Course

12. 
NauseaNausea

Loss of appetiteLoss of appetite

VomitingVomiting

FatigueFatigue

FeverFever

Dark urineDark urine

Pale stoolPale stool

JaundiceJaundice

Stomach painStomach pain

Side painSide pain
A person may have all, some or none of these
Hepatitis AHepatitis A
SymptomsSymptoms

13. Close personal contact
(e.g., household contact, sex contact, child
day care centers)
Contaminated food, water
(e.g., infected food handlers, raw shellfish)
Blood exposure (rare)
(e.g., injecting drug use, transfusion)
Hepatitis A Virus Transmission

14. Laboratory DiagnosisLaboratory Diagnosis
Acute infection is diagnosed by the detection ofAcute infection is diagnosed by the detection of
HAV-IgM in serum by EIAHAV-IgM in serum by EIA..
Past Infection i.e. immunity is determined by thePast Infection i.e. immunity is determined by the
detection of HAV-IgG by EIAdetection of HAV-IgG by EIA..

15. Many cases occur in community-wideMany cases occur in community-wide
outbreaksoutbreaks
 no risk factor identified for most casesno risk factor identified for most cases
 highest attack rates in 5-14 year oldshighest attack rates in 5-14 year olds
 children serve as reservoir of infectionchildren serve as reservoir of infection
Persons at increased risk of infectionPersons at increased risk of infection

Travelers to endemic countriesTravelers to endemic countries

homosexual menhomosexual men

injecting drug usersinjecting drug users
Hepatitis A Vaccination
Strategies
Epidemiologic Considerations

16. -Pre-exposure-Pre-exposure
travelers to intermediate and hightravelers to intermediate and high
HAV-endemic regionsHAV-endemic regions
-Post-exposure (within 14 days)-Post-exposure (within 14 days)
RoutineRoutine
household and other intimate contactshousehold and other intimate contacts
Selected situationsSelected situations
institutions (e.g., day care centers)institutions (e.g., day care centers)
common source exposure (e.g., food prepared bycommon source exposure (e.g., food prepared by
infected food handler)infected food handler)
Hepatitis A Prevention -
Immune Globulin

17. Hepatitis B VirusHepatitis B Virus
Type B hepatitis was at one time referred to as "serum
hepatitis," because it was thought that the only way hepatitis B
virus (HBV) could spread was through blood or serum ) the
liquid portion of blood) containing the virus. The course of
hepatitis B may be extremely variable. Hepatitis B virus
infection has different clinical manifestations depending on the
patient’s age at infection and immune status, and the stage at
which the disease is recognized.

18.  Incubation period: Average 60-90 days
Range 45-180 days
 Clinical illness (jaundice): <5 yrs, <10%
5 yrs, 30%-50%
 Acute case-fatality rate: 0.5%-1%
 Chronic infection: <5 yrs, 30%-90%
5 yrs, 2%-10%
 Premature mortality from
chronic liver disease: 15%-25%
Hepatitis B - Clinical
Features

19. Spectrum of Clinical Manifestations ofSpectrum of Clinical Manifestations of
Hepatitis B DiseasesHepatitis B Diseases
The spectrum of clinical manifestations of hepatitis B
virus (HBV) infection varies in both acute and chronic
disease. During the acute phase, manifestations range
from subclinical or anicteric hepatitis to icteric hepatitis
and, in some cases, fulminant hepatitis; during the chronic
phase, manifestations range from an asymptomatic carrier
state to chronic hepatitis, cirrhosis, and hepatocellular
carcinoma. Extrahepatic manifestations can also occur
with both acute and chronic infection

20. Healthy Liver Cirrhosis Liver

21. Patient with Liver cirrhosisPatient with Liver cirrhosis

22. Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBsHBsAg
0 4 8 12 16 20 24 28 32 36 52 100
Acute Hepatitis B Virus Infection withAcute Hepatitis B Virus Infection with RecoveryRecovery
Typical Serologic CourseTypical Serologic Course
Weeks after Exposure
Titre

23. IgM anti-HBc
Total anti-HBc
HBsAg
Acute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure
Titr
e
Progression to Chronic Hepatitis B Virus InfectionProgression to Chronic Hepatitis B Virus Infection
Typical Serologic CourseTypical Serologic Course

24. 
NauseaNausea

Loss of appetiteLoss of appetite

VomitingVomiting

FatigueFatigue

FeverFever

Dark urineDark urine

Pale stoolPale stool

JaundiceJaundice

Stomach painStomach pain

Side painSide pain
A person may have all, some or none of these
Hepatitis BHepatitis B
SymptomsSymptoms

25. High Moderate
Low/Not
Detectable
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
Concentration of Hepatitis B
Virus in Various Body Fluids

26.  Sexual - sex workers and homosexuals are
particular at risk.
 Parenteral - IVDA, Health Workers are at
increased risk.
 Perinatal - Mothers who are HBeAg positive are
much more likely to transmit to their offspring
than those who are not. Perinatal transmission is
the main means of transmission in high
prevalence populations.
Hepatitis B Virus
Modes of Transmission

27. Who is at Risk for HBV InfectionWho is at Risk for HBV Infection??
High-risk heterosexual men and women
Sexually active homosexual men
Injection drug users
Health care workers
Household and sex partners of persons with chronic
infection
Hemodialysis patients
Recipients of blood products
Clients and employees of institution for developmentally
disabled
Families of adoptees from HBV endemic countries
Inmates of correctional facilities

28. DiagnosisDiagnosis
--A battery of serological tests are used for the diagnosis ofA battery of serological tests are used for the diagnosis of
acute and chronic hepatitis B infectionacute and chronic hepatitis B infection..
HBsAgHBsAg - used as a general marker of infection- used as a general marker of infection..
HBsAbHBsAb - used to document recovery and/or immunity to- used to document recovery and/or immunity to
HBV infectionHBV infection..
anti-HBc IgManti-HBc IgM - marker of acute infection- marker of acute infection..
anti-HBcIgGanti-HBcIgG - past or chronic infection- past or chronic infection..
HBeAgHBeAg - indicates active replication of virus and therefore- indicates active replication of virus and therefore
infectivenessinfectiveness..
Anti-HbeAnti-Hbe - virus no longer replicating. However, the patient- virus no longer replicating. However, the patient
can still be positive for HBsAg which is made bycan still be positive for HBsAg which is made by
integrated HBVintegrated HBV..
HBV-DNAHBV-DNA - indicates active replication of virus, more- indicates active replication of virus, more
accurate than HBeAg especially in cases of escapeaccurate than HBeAg especially in cases of escape
mutants. Used mainly for monitoring response tomutants. Used mainly for monitoring response to

29. TreatmentTreatment
InterferonInterferon - for HBeAg +ve carriers with chronic- for HBeAg +ve carriers with chronic
active hepatitis. Response rate is 30 to 40%active hepatitis. Response rate is 30 to 40%..
LamivudineLamivudine - a nucleoside analogue reverse- a nucleoside analogue reverse
transcriptase inhibitor. Well tolerated, most patientstranscriptase inhibitor. Well tolerated, most patients
will respond favorably. However, tendency towill respond favorably. However, tendency to
relapse on cessation of treatment. Another problemrelapse on cessation of treatment. Another problem
is the rapid emergence of drug resistanceis the rapid emergence of drug resistance..
Successful response to treatment will result in theSuccessful response to treatment will result in the
disappearance of HBsAg, HBV-DNA, anddisappearance of HBsAg, HBV-DNA, and
seroconversion to HBeAgseroconversion to HBeAg..

30. PreventionPrevention
Vaccination - highly effective recombinant vaccines are now available.
Vaccine can be given to those who are at increased risk of HBV
infection such as health care workers. It is also given routinely to
neonates as universal vaccination in many countries.
Hepatitis B Immunoglobulin - HBIG may be used to protect persons who
are exposed to hepatitis B. It is particular efficacious within 48 hours of
the incident. It may also be given to neonates who are at increased risk
of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg
positive.
Other measures - screening of blood donors, blood and body fluid
precautions.

31. Hepatitis C VirusHepatitis C Virus

Type C hepatitis was previously referred to as "non-A, non-B
hepatitis," because the causative virus had not been identified, but it
was known to be neither hepatitis A nor hepatitis B. The hepatitis C
virus (HCV) usually is spread by shared needles among drug abusers,
blood transfusion, hemodialysis, and needle sticks. Approximately
90% of transfusion-associated hepatitis is caused by hepatitis C.
Transmission of the virus by sexual contact has been reported, but is
considered rare. An estimated 50-70% of patients with acute hepatitis
C infection develop chronic HCV infection. Patients with chronic
hepatitis C infection can continue to infect others. Patients with chronic
hepatitis C infection are at risk for developing cirrhosis, liver failure,
and liver cancer.

32. Features ofFeatures of
HCV InfectionHCV Infection
 Incubation periodIncubation period Average, 6–7 wkAverage, 6–7 wk
Range, 2–26 wkRange, 2–26 wk
 Acute illness (jaundice)Acute illness (jaundice) Mild (20%–30%)Mild (20%–30%)
 Persistent infectionPersistent infection 75%–85%75%–85%
 Chronic hepatitisChronic hepatitis 70%70%
 ImmunityImmunity No protective antibodyNo protective antibody
response identifiedresponse identified

33. Cirrhosis
17
Chronic
85
Risk of Fatal Outcome in Persons WhoRisk of Fatal Outcome in Persons Who
Develop Hepatitis C InfectionDevelop Hepatitis C Infection
Courtesy of Seeff, LB and Alter, HJ.
100
Resolve
15
Stable
68 Stable
13
Mortality
4
80%
20%
75%
25%
15%
85%

34. Chronic Hepatitis C InfectionChronic Hepatitis C Infection
The spectrum of chronic hepatitis C infection isThe spectrum of chronic hepatitis C infection is
essentially the same as chronic hepatitis Bessentially the same as chronic hepatitis B
infectioninfection..
All the manifestations of chronic hepatitis BAll the manifestations of chronic hepatitis B
infection may be seen, albeit with a lowerinfection may be seen, albeit with a lower
frequency i.e. chronic persistent hepatitis, chronicfrequency i.e. chronic persistent hepatitis, chronic
active hepatitis, cirrhosis, and hepatocellularactive hepatitis, cirrhosis, and hepatocellular
carcinomacarcinoma..

35. Symptoms
anti-
HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Hepatitis C Virus Infection
Typical Serologic Course
Titr
e
Mont
hs
Years
Time after
Exposure

36. 
NauseaNausea

Loss of appetiteLoss of appetite

VomitingVomiting

FatigueFatigue

FeverFever

Dark urineDark urine

Pale stoolPale stool

JaundiceJaundice

Stomach painStomach pain

Side painSide pain
Hepatitis CHepatitis C
SymptomsSymptoms
3 out of 4 persons have no symptoms and can
infect others without knowing it

37.  Transfusion or transplant from infected donor
 Injecting drug use
 Hemodialysis (yrs on treatment)
 Accidental injuries with needles/sharps
 Sexual/household exposure to anti-HCV-positive
contact
 Multiple sex partners
 Birth to HCV-infected mother
Risk Factors Associated
with Transmission of HCV

38. Laboratory DiagnosisLaboratory Diagnosis
HCV antibodyHCV antibody - generally used to diagnose hepatitis- generally used to diagnose hepatitis
C infection. Not useful in the acute phase as itC infection. Not useful in the acute phase as it
takes at least 4 weeks after infection beforetakes at least 4 weeks after infection before
antibody appearsantibody appears..
HCV-RNAHCV-RNA - various techniques are available e.g.- various techniques are available e.g.
PCR and branched DNA. May be used toPCR and branched DNA. May be used to
diagnose HCV infection in the acute phase.diagnose HCV infection in the acute phase.
However, its main use is in monitoring theHowever, its main use is in monitoring the
response to antiviral therapyresponse to antiviral therapy..
HCV-antigenHCV-antigen - an EIA for HCV antigen is available.- an EIA for HCV antigen is available.
It is used in the same capacity as HCV-RNAIt is used in the same capacity as HCV-RNA
tests but is much easier to carry outtests but is much easier to carry out..

39. TreatmentTreatment
InterferonInterferon - may be considered for patients with- may be considered for patients with
chronic active hepatitis. The response rate ischronic active hepatitis. The response rate is
around 50% but 50% of responders will relapsearound 50% but 50% of responders will relapse
upon withdrawal of treatmentupon withdrawal of treatment..
RibavirinRibavirin - there is less experience with ribavirin- there is less experience with ribavirin
than interferon. However, recent studies suggestthan interferon. However, recent studies suggest
that a combination of interferon and ribavirin isthat a combination of interferon and ribavirin is
more effective than interferon alonemore effective than interferon alone..

40. • There is no vaccination to protect against hepatitis C, but there
are ways to reduce your risk of becoming infected.
• Injecting drug users are most at risk of contracting the
infection. Never share any injecting equipment, such as
needles, syringes and filters.
• Also, do not share razors, toothbrushes or towels that might be
contaminated with blood. Use a condom if you are having sex
with a new partner.
 Screening of blood, organ, tissue donors
 Blood and body fluid precautions
 Be cautious about body piercing and tattooing
Prevention of Hepatitis CPrevention of Hepatitis C

41. ElecsysElecsys
The roche diagnostic Elecsys immunoassay system is a fully
automated system that we use for testing serological
investigation (HIV,HBV,HCV) (for donors and patients who
shows positive results by card) and Hormones Thyroid
hormones FT3,FT4,TSH)
Only HBsAg and anti Hepatitis C are screened by Elecsys for
donors and not Hepatitis A because Hepatitis A transmitted by
food and not blood and is an acute infection that eventually
goes away and does not cause chronic problem, so we just ask
the donors if they had jaundice before.

42. Every day before we start the Elecsys we have toEvery day before we start the Elecsys we have to
check the followingcheck the following::
Water level.Water level.
Check the clean cell & the pro cell level.Check the clean cell & the pro cell level.
Empty the liquid waste.Empty the liquid waste.
Empty the solid waste.Empty the solid waste.
Then open the machine and make the dailyThen open the machine and make the daily
maintenance.maintenance.
Place the reagent bottles and make reagentPlace the reagent bottles and make reagent
scan.scan.

43. Calibration & Q.CCalibration & Q.C
Controls must be done every time we use theControls must be done every time we use the
machine.machine.
If the control is not within range we changeIf the control is not within range we change
the control with a new one (possiblethe control with a new one (possible
contamination).contamination).
If it still not good we make calibration.If it still not good we make calibration.
Calibration is also require when the reagent isCalibration is also require when the reagent is
new and need calibration.new and need calibration.

44. When finish working on the machine make
finalization and take the reagent out of the
machine but them on the fridge, and shut down
the machine.