hepatitis b and d

Co infection

HEPATITIS B and DASHLY ALEX

HARISREE

HEPATITIS B

DNA Virus

Hepadnaviridae class

Hepatitis B virus is 100 times more infectiouss than HIV

virus

TRANSMISSION

• Vertical transmission : from mother to child in utero during

parturition or soon after birth is the usual means of

transmission world wide .

• It is related to the replicative state of the mother .

• 90% HbeAg + or 30% HbeAg -.

• HBV is not transmitted by breast feeding .

• Horizontal transmission :occurs particularly in children via

minor abrasions or close contact with other children .

• HBVcan survive on household articles eg toys ,tooth brushes

for prolonged periods.

• Inravenous route (infected blood or blood product

,contaminated needles etc )

• Close personal (sexual intercourse ).

• Virus can be found in semen saliva and vaginal fluids .

Clinical presentation

• Acute Hepatis B:

Loss of apetite

Nausea

Vomiting

Body aches

Dark urine

Jaundice

Ichy skin

Fulminant hepatic failure may arise. infection may be

entirely asymptomatic and may go unrecognized .

• Chronic hep B:

Asymptomatic

Or associated with chronic inflammation of liver .

• Extra hepatic manefestations are seen in 1-10 % of patients

• Serum sickness like syndrome .

• Rashes (urticaria or maculopapular rash )

• Polyarteritis nodusa

• Membranous glomerulonephritis

•

• Incubation period ranges from 45-180 days, average is

60-90 days

Onset is insidious

• Clinical illness (jaundice): <10% for <5 yr olds

30%-50% for >5 yrs

• Acute case-fatality rate: 0.5%-1%

• Chronic infection: <5 yrs old, 30%-90%

>5 yrs old, 2%-6%

• Premature mortality from chronic liver disease: 15%-25%

Pathogenesis

• Hbv virons (dane particles)bind to the host cell via preS domain of

the viral surface antigen and are internalized by endocytosis .

• preS and IgA are accused of this interaction .

• HBV preS receptors are primarily expressed on hepatocytes .

• During HBV inf the host immune response cause both

hepatocellular and viral clearence .

• Adaptive immune response ,particulary virus specific cytotoxic T

lymphocytes,contributes to most of the liver injury associated with

HBV infection .by antiviral cytokines.

Investigations

• LFT s

• Serological

• ANTIGENS :

HBsAg

HBeAg

HBV DNA

ANTIBODIES :

Anti –HBs

Anti –HBc

Anti -HBe

• Goals of Treatment in Children

Suppression of viral replication

Seroconversion from e Ag to e Ab

Reduction in long-term sequelae of

HBV-associated liver disease

TREATMENT

• Approved Antiviral Agents

• – Lamivudine*

• – Adefovir dipivoxil

• – Interferon alfa*

• – Entecavir

• – Pegylated interferon

• – Telbivud

Treatment

• Alfa interferons were the first drug approved in US for

the treatment of chronic hep B

Prevention

• Pregnant women should be tested for HBsAg during an early

prenatal visit.

• Failing that, they should be tested when admitted for delivery.

• Some women who are HBsAg-positive are treated

with lamivudine or telbivudine during the 3rd trimester, which

may prevent perinatal transmission of HBV.

Prevention

• Neonates whose mothers are HBsAg-positive should be

given 1 dose of HBIG 0.5 mL IM within 12 h of birth.

• Recombinant HBV vaccine should be given IM in a

series of 3 doses, as is recommended for all infants in the

US.) The first dose is given concurrently with HBIG but

at a different site.

• The 2nd dose is given at 1 to 2 mo, and the 3rd dose is

given 6 mo after the first.

HEPATITIS D – An Introduction

• Caused by Hepatitis Delta Virus – a defective RNA virus.

• HDV requires the help of a hepadnavirus like hepatitis

B virus (HBV) for its own replication.

• HDV is transmitted percutaneously or sexually

through contact with infected blood or blood products.

Who is at risk for

infection?

• Chronic HBV carriers are at risk for infection with HDV.

• Individuals who are not infected with HBV, and have not

been immunized against HBV, are at risk of infection

with HBV with simultaneous or subsequent infection

with HDV.

Where is HDV a problem

globally?

• The hepatitis delta virus is present worldwide and in all

age groups.

• Its distribution parallels that of HBV infection, although

with different prevalence rates.

• The natural reservoir of hdv is man.

When is a HDV infection

life-threatening?

• HDV infection of chronically infected HBV-carriers may

lead to fulminant acute hepatitis or severe chronic active

hepatitis, often progressing to cirrhosis.

• Chronic hepatitis D may also lead to the development of

hepatocellular carcinoma.

Why is there no treatment

for the disease?

• Hepatitis D is a viral disease, and as such, antibiotics are

of no value in the treatment of the infection.

• There is no hyperimmune D globulin available for pre- or

postexposure prophylaxis.

• Disease conditions may occasionally improve with

administration of a-interferon.

• Liver transplantation may be considered for cases

of fulminant acute and end-stage chronic hepatitis D.

THE DISEASE

An HDV infection absolutely requires an associated HBV

infection.

• Coinfection of HBV and HDV :

• results in both acute type B and acute type D hepatitis.

• The incubation period depends on the HBV titre of the

infecting inoculum.

• Coinfections of HBV and HDV are usually acute, self-

limited infections

• In patients with acute, self-limiting infection,

convalescence begins with the disappearance of clinical

symptoms.

• Superinfection of HBV and HDV

• causes a generally severe acute hepatitis with short

incubation time that leads to chronic type D hepatitis in

up to 80% of cases.

• associated with fulminant acute hepatitis and severe

chronic active hepatitis, often progressive to cirrhosis.

• During the acute phase of HDV infection, synthesis of

both HBsAg and HBV DNA are inhibited until the HDV

infection is cleared.

• Fulminant viral hepatitis is rare, but still about 10 times

more common in hepatitis D than in other types of viral

hepatitis.

• It is characterized by hepatic encephalopathy showing

changes in personality, disturbances in sleep, confusion

and difficulty concentrating, abnormal behavior,

somnolence and coma.

• The mortality rate of fulminant hepatitis D reaches 80%.

• Liver transplantation is indicated.

• Chronic viral hepatitis D is usually initiated by a

clinically apparent acute infection.

• Symptoms are less severe than in acute hepatitis, and

while serum ALT and AST levels are elevated, bilirubin

and albumin levels and prothrombin time may be normal.

• In chronic hepatitis D, the HBV markers are usually

suppressed.

• Progression to cirrhosis usually takes 5 - 10 yrs, but it can

appear 2 years after onset of infection.

• Hepatocellular carcinoma (HCC) occurs in chronically

infected HDV patients with advanced liver disease.

• There are 3 phases of chronic hep D :

a) an early active phase with active HDV replication and

suppression of HBV,

b) a second moderately active one with decreasing HDV and

reactivating HBV,

c) a third late one with development of cirrhosis and

hepatocellular carcinoma caused by replication of either virus or

with remission resulting from marked reduction of both viruses

• The mortality rate for HDV infections lies between 2%

and 20%, values that are ten times higher than for

hepatitis B.

Diagnosis

• Hepatitis D should be considered in any individual who is

HBsAg positive or has evidence of recent HBV infection.

• Total anti-HDV are detected by commercially available

radioimmunoassay (RIA) or enzyme immunoassay (EIA)

kits.

• The method of choice for the diagnosis of ongoing HDV

infection should be RT-PCR, which can detect 10 to 100

copies of the HDV genome in infected serum.

• Each of the markers of HDV infection, including IgM and

IgG antibodies, disappears within months after recovery.

• In contrast, in chronic hepatitis D, HDV RNA, HDAg,

and IgM and IgG anti-HD antibodies persist.

Host immune response

• Both humoral and cellular immunity are induced in

patients infected with HDV.

• Anti-HD antibodies do not always persist after acute

infection is cleared.

• The serological evidence of past HDV infection is

therefore not easy to demonstrate.

Risk groups

• Intravenous drug users using HDV-contaminated

injection needles

• Promiscuous homosexual and heterosexual groups

(although HDV infections are less frequent than HBV or

HIV infections)

• People exposed to unscreened blood or blood products

• Haemophiliacs

• Persons with clotting factor disorders

Treatment

• For infected patients, massive doses of a-interferon (9

million units three times a week for 12 months or 5

million units daily for up to 12 months) have yielded

remissions, but most patients remained positive for HDV

RNA despite the improved disease conditions.

• Liver transplantation has been helpful for treating

fulminant acute and end-stage chronic hepatitis.

Guidelines for epidemic

measures

1.) When two or more cases occur in association with some

common exposure, a search for additional cases should be

conducted.

2.) Introduction of strict aseptic techniques. If a plasma

derivative like antihaemophilic factor, fibrinogen, pooled plasma

or thrombin is implicated, the lot should be withdrawn from use.

3.) Tracing of all recipients of the same lot in search for

additional cases.