Hepatitis B, C & D Viruses

Dr. Masood Ahmad

Viral hepatitis B

Etiology Hepatitis B virus (HBV) HBV is a kind of hepadnavirus Three particles in serum: spherical particles and tubular particles with a

diameter of 20 nm, composed of HBsAg large particles with a diameter of 42 nm, named Dane

particle. It consists of an outer protein shell (envelope, contain HBsAg) and an inner body ( core, contain HBcAg, HBeAg, HBV-DNA and DNAP )

Hepatitis B Virus

pathology Three antigen-antibody system

HBsAg-- anti-HBs system: HBsAg appears 1-2 weeks (late up to 11-12 weeks) after

exposure, persists for 1-6 weeks( even 5 months) in acute hepatitis B.

In chronic patients or carrier, HBsAg persist many years HBsAg is the marker of infectivity HBsAg can be found in blood and secretions: saliva, urine,

semen, tears, sweat and breast milk Anti-HBs appear after HBsAg disappear several weeks (or

months) anti-HBs is protective antibody, can persist for many years

pathologyHBcAg—anti-HBc system HBcAg can be found in the nuclei of liver cells, no free

HBcAg in serum HBcAg is the marker of replication of HBV The stage called window phase Anti-HBc IgM is a marker of acute infection and acute

attack of chronic infection of HBV. Anti-HBc IgG is the marker of past infection, high titer means low level replication of HBV

pathology

HBeAg—anti-HBe system HBeAg is a soluable antigen HBeAg is a reliable indicator of active replication of

HBV Anti-HBe is a marker of reduced infectivity. If exist

long may be a marker of integration of HBV into liver cell

Pathogenesis Hepatitis B:

HBV invades into the human body by skin and mucosa, Via blood flow enters the liver and other organs such as pancreas, bile ducts, vessels, WBC, bone marrow, glomerular basement membrane

HBcAg,HBsAg,HBeAg and HLA- appear on the Ⅰliver cells infected with are recognized by CTL simultaneously and lead to the cytolysis of liver cells

Pathogenesis

Helper T cell are activated by the receptor of HLA- on its surface combing with HBsAg, HBcAg and HLA- antigen on the B cells promote B cell to release anti-HBs and clear HBV

The representation of HBcAg on the liver cells may cause cytopathy

Incubation period: Average 60-90 daysRange 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

Spectrum of Chronic Hepatitis B Diseases

1.Chronic Persistent Hepatitis - asymptomatic

2.Chronic Active Hepatitis - symptomatic exacerbations of hepatitis

3.Cirrhosis of Liver

4.Hepatocellular Carcinoma

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 with Recovery

Typical Serologic Course

Weeks after Exposure

Titre

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

Titre

Progression to Chronic Hepatitis B Virus Infection

Typical Serologic Course

Symptomatic Infection

Chronic Infection

Age at Infection

Chronic Infection (%)

Sym

pto

matic In

fection

(%)

Birth 1-6 months 7-12 months 1-4 years Older Childrenand Adults

0

20

40

60

80

100100

80

60

40

20

0

Outcome of Hepatitis B Virus Infection

by Age at Infection

Ch

ron

ic I

nfe

ctio

n

(%)

High (>8%): 45% of global population lifetime risk of infection >60% early childhood infections common

Intermediate (2%-7%): 43% of global population lifetime risk of infection 20%-60% infections occur in all age groups

Low (<2%): 12% of global population lifetime risk of infection <20% most infections occur in adult risk groups

Global Patterns of Chronic HBV Infection

High ModerateLow/Not

Detectable

blood semen urineserum vaginal fluid feces

wound exudates saliva sweat

tearsbreast milk

Concentration of Hepatitis B Virus in Various Body Fluids

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

Diagnosis. 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.

Treatment In acute hepatitis B the treatment is

basically symptomatic Rest Ant emetics to control vomiting Plenty of fluids and carbohydrates Hepatotropic agents

Treatment Chronic Hepatitis B Interferon - for HBeAg +ve carriers with chronic active

hepatitis. Response rate is 30 to 40%. 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.

Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.

Prevention 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.

Hepatitis C Virus

Hepatitis C virus (HCV) HCV is a member of flavivirus family. HCV genome is a single stranded positive-sense RNA and

contains 9.4kb HCV genome may be divided into many types and subtypes. Resistance Antigen-antibody system The concentration of HCV in blood is low, HCV Ag has not

be detected, anti-HCV is the indicator of infection and the marker of infectivity

HCV-RNA HCV-RNA may be detected from blood or liver tissue, it’s

the direct evidence of infectivity

Incubation period: Average 6-7 wks

Range 2-26 wks

Clinical illness (jaundice): 30-40% (20-30%)

Chronic hepatitis: 70%

Persistent infection: 85-100%

Immunity: No protective antibody response

identified

Hepatitis C - Clinical Features

Chronic Hepatitis C Infection

The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection.

All the manifestations of chronic hepatitis B infection may be seen, albeit with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.

Symptoms

anti-HCV

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4

Hepatitis C Virus InfectionTypical Serologic Course

Titre

Months

Years

Time 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

Laboratory Diagnosis HCV antibody - generally used to diagnose hepatitis C

infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears.

HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy.

Treatment

Acute infection

Chronic infection Interferon - may be considered for patients with

chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment. However addition of

Ribavirin – Improves the response rate to almost 70%.

Treatment Different genotypes of HCV have been identified and

have been named as genotype 1 to 8 and there are still many which presently are untypeable.

Many different types of interferons are also available including conventional, pegylated, and consensus interferon.

Genotype 2 & 3(common subtypes in Pakistan) respond well to conventional interferon

Screening of blood, organ, tissue donors

High-risk behavior modification

Blood and body fluid precautions

Prevention of Hepatitis C

Hepatitis D (Delta) Virus

Hepatitis D virus (HDV) HDV (Delta hepatitis virus) is a kind of defective virus HDV is found in the nuclei of infected hepatocytes and replicate HDV genome is a circular single strand RNA and contains 1.7kb The replication of HDV depends on HBV or other hepadnavirus,

coated by HBsAg in blood HDV has one antigen-antibody system No free HDAg is detected in blood, it’s in the nuclei of

hepatocytes; anti-HDV can be detected by RIA or ELISA in serum

HBV and HDV co-infection or superinfection may make the disease exacerbation and may lead to fulminant hepatitis

HDV RNA may be detected from liver cells, blood or humor.

HBsAg

RNA

antigen

Hepatitis D (Delta) Virus

Co-infection– severe acute disease.– low risk of chronic infection.

Super-infection– usually develop chronic HBV infection.– high risk of severe chronic liver disease.– may present as an acute hepatitis.

Hepatitis D - Clinical Features

Percutaneous exposures

injecting drug use

Per mucosal exposures sex contact

Hepatitis D Virus Modes of Transmission

anti-HBs

Symptoms

ALT Elevated

Total anti-HDV

IgM anti-HDV

HDV RNA

HBsAg

HBV - HDV CoinfectionTypical Serologic Course

Time after Exposure

Titre

Jaundice

Symptoms

ALTTotal anti-HDV

IgM anti-HDV

HDV RNA

HBsAg

HBV - HDV SuperinfectionTypical Serologic

Course

Time after Exposure

Titre

HBV-HDV Co-infection

Pre or post-exposure prophylaxis to prevent HBV infection.

HBV-HDV Super-infection

Education to reduce risk behaviors among persons with chronic HBV infection.

Hepatitis D - Prevention

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