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Dr. G.

Thiruvenkadam Post Graduate Dept of Pediatric & Preventive Dentistry

Synopsis
Introduction Classification Structure of Hepatitis B Life cycle Causes of infection Risk factors Signs and symptoms Pathology Lab diagnosis Prophylaxis Immunisation Antiviral therapy conclusion

Hepatitis & Hepatotrophic viruses


Hepatitis inflammation of the liver 11 viruses causes hepatitis 2 + 9 Which specifically targets the hepatocytes There are nine hepatotrophic viruses, but only five are well characterized Hepatotrophic viruses:
Hepatitis A ( infectious hepatitis) Hepatitis B (serum hepatitis) Hepatitis C ( non-A non-B hepatitis) Hepatitis D (Delta Hepatitis) Hepatitis E

Hepatitis B
Small,Enveloped, doublestranded circular DNA virus of complex structure Class: Orthohepadnavirus Family:Hepadnaviridae HBV DNA has compact genomic structure, with overlapping genes, permits HBV to code for multiple proteins

Four GENES
HBV achieves its genomic economy by relying on an efficient strategy of encoding proteins from four overlapping genes : S, C, P, X

S
C

Codes for the Major envelope protein

Codes for two nucleocapsid proteins HBeAg, a soluble, secreted protein HBcAg, the intracellular core protein

P
X

The largest gene, codes for DNA Polymerase

Codes for HBxAg, which can transactivate the transcription of cellular and viral genes

Viral genome

Particulate forms of HBV


Three particulate forms of HBV can be demonstrated by electron microscopy

22nm

Most numerous Appear as spherical or long filamentous forms They represent the excess envelope protein

42nm

They are double shelled spherical particles Represent the intact hepatitis B virion (dane particle)

27nm

Represent the nucleocapsid core

Life cycle ..

Antigenicity
HBsAg, which is highly immunogenic and induces antiHBs (humoral immunity). Structural viral proteins induce specific T-lymphocytes, capable of eliminating HBV-infected cells (cytotoxic Tcells; cellular immunity) HBsAg is heterogeneous antigenically, with a common antigen designated a, and two pairs of mutually exclusive antigens, d and y, and w and r, resulting in 4 major subtypes: adw, ayw, adr and ayr. Because of the common determinants, protection against one subtype appears to confer protection to the other subtypes, and no difference in clinical features have been related to subtypes. In India, ayw and adw are the most common subtypes

Mutant forms
Two types of mutant:
HBeAg negative phenotype
Most common mutant Results in severe chronic infection

Escape mutant
This is due to change in HBsAg

Causes
spread through having contact with the blood, semen, vaginal fluids, and other body fluids of someone who already has a hepatitis B infection
Blood transfusions (not common in the United States) Direct contact with blood in health care settings Sexual contact with an infected person Tattoo or acupuncture with unclean needles or instruments Shared needles during drug use Shared personal items (such as toothbrushes, razors, and nail clippers) with an infected person The hepatitis B virus can be passed to an infant during childbirth if the mother is infected

Risk factors
Being born, or having parents who were born in regions with high infection rates (including Asia, Africa, and the Caribbean) Being infected with HIV Being on hemodialysis Having multiple sex partners Homosexuals

Signs and Symptoms


After you first become infected with the hepatitis B virus:
You may have no symptoms You may feel sick for a period of days or weeks You may become very ill (called fulminant hepatitis)

Acute symptoms
Early symptoms may include:
Appetite loss Fatigue Fever, low-grade Muscle and joint aches Nausea and vomiting Yellow skin and dark urine due to jaundice

People with chronic hepatitis may have no symptoms, even though gradual liver damage may be occurring. Over time, some people may develop symptoms of chronic liver damage and cirrhosis of the liver.

Fulminant hepatitis
Clinical syndrome developing as a result of massive necrosis of liver cells or following any other cause of sudden and severe impairment of hepatic function
Hyperacute
encephalopathy within 7 days of onset of jaundice very high risk of cerebral oedema

Acute
jaundice to encephalopathy: 8-28 days high risk of cerebral oedema

Subacute
jaundice to encepalopathy: 5-26 weeks low risk of cerebral oedema

Pathology
Acute hepatitis Signs of inflammation in the portal traid The Infiltrate is mainly lymphocytic Healthy carriers The inflammatory response is mild The affected hepatocytes are pale staining and glassy Chronic hepatitis Damage extends out of the portal triad Piecemeal necrosis appearance As the disease progresses, fibrosis develops and eventually cirrhosis

Laboratory diagnosis
1. Liver function test 2. Serology Liver function test Increased alanine transaminase and aspartate transaminase Increased bilirubin levels Prothrombin time is prolonged, signifies hepatocellular necrosis and indicate worst prognosis

HBsAg
HBsAg is the first marker to appear in blood after infection It remains in circulation throughout the icteric or symptomatic course of the disease Actually it disappears within 2 months of the start of clinical disease, but may last for 6 months and even beyond. When its no longer available, anti-HBs appears and remains for longer periods. Anti HBs is a protective antibody

HBcAg
Not demonstrable in circulation because it is enclosed within the HBsAg coat Its antibody, Anti HBc appears in the serum a week or two after the appearance of HBsAg So, its the earliest antibody marker to be seen in the blood It remains lifelong and serves as a useful indicator of prior infection Initially, anti HBc is predominantly IgM, but after about 6 months, its mainly IgG.

HBeAg
HBeAg appears in blood concurrently with HBsAg, or soon afterwards Circulating HBeAg is an indicator of active intrahepatic viral replication Presence of DNA polymerase, HBV DNA and virions reflects high infectivity disappearance of HBeAg is followed by the appearance of anti - HBe

How to diagnose
For diagnosis of HBV infection, detection of HBsAg in blood is necessary Presence of IgM anti HBc indicates recent infection Presence of IgG anti HBc indicates remote infection HBeAg provides information about relative infectivity
Presence denotes high infectivity Its absence, along with the presence of anti Hbe, indicates low infectivity

It is invariably present during acute hepatitis, so its testing is indicated only in chronic infection and carriers

How to diagnose
HBV DNA is also an indicator of viral replication and infectivity DNA:DNA hybridisation and PCR used for HBV DNA testing are highly sensitive and quantitative

Prophylaxis
General prophylaxis consists of
Avoiding promiscuous sex Avoiding injectable drug abuse Avoiding direct / indirect contact with blood, semen or other body fluids of patients and carriers

Immunisation
Passive and active immunisation methods are available Passive immunisation:
Hyper immune hepatitis B immune globulin (HBIG) prepared from human volunteers with high titre anti HBs, administered IM in a dose of 300 500 IU constitutes passive immunisation It may not prevent infection, but protects against illness and carrier state

Active immunisation
More effective First vaccine was introduced in 1982 Prepared from pooled plasma of healthy human carriers with high level of antigenemia 22 nm HBsAg particles separated by ultracentrifugation were treated with proteinase, urea and formaldehyde Disadvantages:
Source was human plasma, limited in availability Not totally free from unknown pathogens

Current vaccine
Genetically engineered by cloning the S gene of HBV in bakers yeast Contains only nonglycosylated HBsAg particles Given in IM, with alum as adjuvant Seroconversion occurs in about 90 % of the vaccines Three doses given at 0, 1 and 6 months constitute the full course For babies born to carrier mothers, a single injection of 0.5 ml of HBIG given immediately(within 12 hours of birth) in IM, followed by full course of vaccine is advisable.

Patient Group Children Adults (20 yrs)

Recombivax HB 5mcg* 10mcg

Engerix-B 10mcg 20mcg

Twinrix*** 20mcg

Pediarix**** 10mcg

Immunocompromised or dialysis patients

40mcg

40mcg**

*Adolescents ages 10-15 yrs can receive an alternate regimen of 10mcg given in 2 doses at months 0 and 4-6 **Dosing regimen of 40mcg given in 4 doses at months 0, 1, 2, and 6 ***Combined hepatitis A and hepatitis B vaccine. Approved for adults (>18 yrs). Alternate accelerated regimen involves 20mcg given in 4 doses at days 0, 7, 21 to 30, and at one year ****Combined hepatitis B vaccine with diphtheria, tetanus, pertussis, and poliomyelitis vaccines; approved for ages 0-6 yrs given in 3 doses at 0, 2, and 4 months

Antiviral drugs
Antiviral agent Entecavir* Tenofovir* Lamivudine Adefovir Drug class Nucleoside analogue Nucleotide analogue Nucleoside analogue Nucleotide analogue Nucleoside analogue Immune modulator Immune modulator Dose 0.5 mg daily 300 mg daily 100 mg daily 10 mg daily Duratio n Variable Variable Variable Variable

Telbivudine
Interferon alfa-2b

600 mg daily
5 million IU daily or 10 million IU three times weekly

Variable
48 weeks

Pegylated interferon alfa*

1.5 mcg/kg weekly** 48 weeks (or) 180 mcg weekly***

EXCELLENCE HAS NO FINISHING CURVE.. THERES ALWAYS A BETTER WAY