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.