hepatitis a-e
TRANSCRIPT
VIRAL Hepatitis Dr. Arifa Akram BarnaMBBS, MD (Virology)
Department of VirologyInstitute of Epidemiology, Disease Control and
Research (IEDCR)
HEPATITIS = inflammation of liver
Hepatitis viruses: Hepatitis virus A,B, C, D,E Other Viruses: Cytomegalovirus Echo virus EBV Rubella virus HSV Coxsackie-B Yellow fever virus Marburg virus VZV Lassa fever virus Paramyxovirus Adeno virus Enterovirus Rift valley fever
virus
Source ofvirus
feces blood/blood-derived
body fluids
blood/blood-derived
body fluids
blood/blood-derived
body fluids
feces
Route oftransmission
fecal-oral percutaneouspermucosal
percutaneouspermucosal
percutaneouspermucosal
fecal-oral
Chronicinfection
no yes yes yes no
Prevention pre/post-exposure
immunization
pre/post-exposure
immunization
blood donorscreening;
risk behaviormodification
pre/post-exposure
immunization;risk behaviormodification
ensure safedrinking
water
Type of HepatitisA B C D E
Feco-oral contamination of food, water
(e.g., infected food handlers, raw shellfish, travel to endemic area)
Close personal contact(e.g., household contact, sex contact,child day care centers)
Blood exposure (rare) (e.g., injecting drug use, transfusion)
Hepatitis A & E Virus Transmission
Complications: Fulminant hepatitis (<1%)
Cholestatic hepatitis Relapsing hepatitis
Chronic sequelae: None Case fatality rate : 0.1% - 2.7%.
FecalHAV
Symptoms
0 1 2 3 4 5 6 12
24
Hepatitis A Infection
Total anti-HAV
Titre ALT
IgM anti-HAV
Months after exposure
Typical Serological Course
Symptoms
ALT IgG anti-HEV
IgM anti-HEV
Virus in stool
0 1 2 3 4 5 6 7 8 9 10
11
12
13
Hepatitis E Virus Infection
Titer
Weeks after Exposure
Presence of virus:Blood -2 weeks before to < 1 week after jaundice Stool -2 weeks before to 2 weeks after jaundice Urine -Rare Saliva, semen –Rare
PreventionHAV Vaccine:Available: contains inactivated HAV.Dose: 2 doses, an initial dose followed by a Booster dose at 6-12 months.Immune globulin must be administered within 2 weeks after exposure for maximum protection. HEV Vaccine : Clinical trial in progress
Hepatitis B
Replication of Hepatitis B Virus
Spectrum of Chronic Hepatitis B Diseases
1. Chronic Persistent Hepatitis - asymptomatic
2. Chronic Active Hepatitis - symptomatic exacerbations of hepatitis
3. Cirrhosis of Liver
4. Hepato cellular Carcinoma
Clinical outcomes of Hepatitis B infections
High ModerateLow/Not
Detectable
blood semen urineserum vaginal fluid feces
wound exudates saliva sweattears
Breast milk
Concentration of Hepatitis B Virus in Various Body Fluids
HBV Sources of InfectionHousehold, 3%
Other, 23%
IDU, 20%Multiple sexpartners, 24%
Sexcontact, 23%
MSM, 23%
Centers for Disease Control and Prevention. Hepatitis B. In: Atkinson W et al, eds. Epidemiology & Prevention of Vaccine-Preventable Diseases. 8th ed Washington DC: Public Health Foundation; 2005:191-212.
Many patients do not reveal IDU as source of infection
Diagnosis A battery of serological tests are used for the
diagnosis of acute and chronic hepatitis B infection. HBsAg - used as a general marker of infection. HBsAb - used to document recovery and/or immunity
to HBV infection. anti-HBc IgM - marker of acute infection. anti-HBcIgG - past or chronic infection. HBeAg - indicates active replication of virus and
therefore infectiveness. Anti-Hbe - virus no longer replicating. However, the
patient can still be positive for HBsAg which is made by integrated HBV.
HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.
SymptomsHBeAg 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 with Recovery Typical Serologic
Course
Weeks after Exposure
Titre
IgM anti-HBc
Total anti-HBcHBsAg
Acute(6 months)
HBeAg
Chronic(Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52 YearsWeeks after Exposure
Titre
Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course
Treatment Aim is to halt the progression of liver damage by
› Suppressing viral replication› Eliminating the infection
› Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.
Treatment
Interferon alpha-2b Lamivudine - a nucleoside analogue reverse
transcriptase inhibitor. Well tolerated, most patients will respond favorably. However, tendency to relapse on cessation of treatment. Another problem is the rapid emergence of drug resistance.
Hepsera (Adefovir Diivoxil) : nucleotide analogue that inhibit HBV DNA polymerase (RT)
Prevention Vaccination 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.
Recommended PEP of HBV
CDC, 2006
Immune tolerance phaseHBeAg positive; high HBV DNA (105-10 copies/mL) normal ALT
HBeAg-positive chronic hepatitis (immune clearance)High HBV DNA (105-10 copies/mL) high or fluctuating ALT; active inflammation on liver biopsy
Inactive HBsAg carrier (non-replication)HBeAg negative; low HBV DNA (<104 copies/mL)normal ALT
HBeAg-negative chronic hepatitisIntermediate to high HBV DNA (104-8 copies/mL) high or fluctuating ALT; active inflammation on liver biopsy
4 Phases of Chronic HBV Infection
Hepatitis C Virus
Virology HCV is a member of flavi virus family, Genus:
Hepacivirus Enveloped. HCV genome is a single stranded positive-sense
RNA and contains 9.4kb. Genotype: Six genotype and more than 100
serotypes.
Consequences-1. •Acute Hepatitis C
2. •Chronic Infection C 60-85%
3. •Chronic Hepatitis 70%
4. •Cirrhosis 20%
5. •HCC
• Decompensation
Resolved
Symptoms
anti-HCV
ALT
Normal
0 1 2 3 4 5 6 1 2 3 4
Hepatitis C Virus InfectionTypical Serologic Course
Titre
Months
YearsTime after Exposure
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
Transmission Transfusion or transplant from infected
donor Sexual/household exposure to anti-
HCV-positive contact Multiple sex partners Needle stick injury
Laboratory Diagnosis
Hepatitis C virus Antibody test HCV-RNA Test ( Qualitative & Quantitative) Genotyping 1,4 - 48weeks 2,3- 12 weeks
.
Anti HCV test Does not distinguish between IgG & IgM or
between acute, chronic or resolved infection. Since false positive results can occur in ELISA, a
Recombinant Immunoblot Assay (RIBA) should be performed as a confirmatory test.
If RIBA is positive, a PCR based test that detects viral RNA in serum should be done to determine active disease.
HCV RNA TestHCV-RNA may be detected from blood or liver
tissue, it’s the direct evidence of infectivity Confirms diagnosis of HCV infection. Useful in the early diagnosis of acute hepatitis –
C. Demonstrates the presence of active infection. Gold standard- For documenting response to
treatment.
Treatment Interferon Pegylated IFN (alpha interferon) conjugated to
polyethylene glycol is used to treatment of chronic Hepatitis C.
Ribavirin - recent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone.
New Drug-Protease Inhibitor(Simeprivir),Polymerase Inhibitor(Sofosbuvir)from 2013 for all
genotype.
Screening of blood, organ, tissue donors
High-risk behavior modification
Blood and body fluid precautions
Infection control practices in health care and other settings.
Counsel person with high risk, drug or sexual practice.
Prevention of Hepatitis C
HBsAg
RNA
antigenHepatitis D (Delta) Virus
Percutaneous exposures injecting drug use
Permucosal exposuressex contact
Hepatitis D Virus Modes of
Transmission
Coinfection Infection with both HDV and HBV at the same
time.› severe acute disease.› low risk of chronic infection.
Superinfection Previous infection with HBV and then
superinfected with HDV.› usually develop chronic HDV infection.› high risk of severe chronic liver disease.› may present as an acute hepatitis.
anti-HBs
Symptoms
ALT Elevated
Total anti-HDV
IgM anti-HDV
HDV RNA
HBsAg
HBV - HDV Coinfection
Typical Serologic Course
Time after Exposure
Titre
JaundiceSymptoms
ALT Total anti-HDV
IgM anti-HDV
HDV RNAHBsAg
HBV - HDV SuperinfectionTypical Serologic
Course
Time after Exposure
Titre
Diagnosis Anti-HDV can be detected by RIA or ELISA in
serum HDV RNA may be detected from liver cells, blood.
Treatment There is no specific anti viral therapy against
HDV. There is no vaccine against HDV, persons
immunised with HBV will be protected against HDV as surface antigen is same.
Hepatitis G virus Member of flavi virus family. Isolated from pt with post transfusion hepatitis in
1996. Transmission: via sexual and parenteral route. Patients coinfected with HIV and HGV have a
lower mortality rate and have less HIV in their blood than those infected with HIV alone. It is hypothesized that HGV may interfere with the replication of HIV.