Presentation on Approach to HbsAg Positive.

1. A PRACTICAL APPROACH TO A
PERSON WITH POSITIVE HBsAG
-Dr.Yugandhar Tummala

2. STRUCTURE OF HBV

3. LIFE CYCLE OF HBV

4. Pathogenesis
Endocytosis
Release of cytokines (T Lymphocytes)
Hepatocellular Damage
Inflammation
Release of Liver
Enzymes in blood

5. VIROLOGY

6. PHASES OF CHRONIC HBV
• Immune tolerance phase
• Immune Clearance phase
• Non Replicative phase
• HBeAg negative immune reactivation phase

7. IMMUNE TOLERANCE PHASE:-
• Highly replicative and low inflammatory phase
• Elevated HBV DNA levels and normal ALT
levels
• Highly variable duration ranging from 10-30
years
• With increasing age lies increasing chance of
transition to active phase

8. IMMUNE CLEARANCE PHASE:-
• Hallmark is sero-conversion of HBeAG to Anti HBe
• Elevated ALT and HBV DNA levels
• Median age of onset 30 years
• Most exacerbations are asymptomatic and are
discovered during routine follow-up.
• However, some are accompanied by symptoms of
acute hepatitis and may lead to the incorrect
diagnosis of acute hepatitis B patients who are
not previously known to have chronic HBV
infection

9. NON REPLICATIVE PHASE
• Undetectable HBV DNA levels
• Normal ALT levels
• HBeAg negative and anti-HBe positive
• 70-80% remains in inactive CHB phase
• 10-20% chances of reversion back to HBeAg
positive

10. HBeAG NEGATIVE IMMUNE
REACTIVATION PHASE
• Some patients continue to have moderate levels
of HBV replication and active liver disease but
remain HBeAg negative
• They have a residual wild-type virus or HBV
variants that cannot produce HBeAg due to
precore or core promoter genetic variations
• Patients are older and have more advanced liver
disease.
• They also tend to have fluctuations in HBV DNA
and ALT levels.

11. CLINICAL FEATURES
• ACUTE HEPATITIS
70% patients are sub clinical while 30%
develop icteric hepatitis
• CHRONIC HEPATITIS
Most patients are asymptomatic
Some develop decompensated liver cirrhosis
and extra hepatic manifestations

12. SIGNS AND SYMPTOMS
• Fever with chills and rigor
• Myalgia
• Headache
• Loss of appetite
• Nausea, vomiting
• Right hypochondrium pain, Jaundice, Tender
hepatomegaly seen in icteric hepatitis

13. INVESTIGATIONS
Hepatitis B surface antigen (HBsAg):
• A Simple and Rapid Test-card Method
• Sensitivity 88.8% and the specificity 100%
• It can be detected in high levels
in serum during acute or chronic hepatitis B
virus infection.
• If negative, chronic HBV infection is typically
ruled out

14. HBeAG
• Can be detected in the early phase of hbv
becomes undetectable in acute hbv as the virus
clears and hbeab is detected
• Can persist in carriers and is usually associated
with detectable hbv dna
• During the immune-active phase in hbv carriers a
seroconversion occurs when hbeag becomes not
detected as hbeab becomes detected
• Presence of hbeag is not required for infectivity
or replication. It is not part of the structure of the
virus.

15. Anti-HBc IgG
• Solid-phase enzyme immunoassay
• Detection of anti-HBc is indicative of exposure
to HBV and thus of infection by this virus.

16. HBV DNA
• RT-PCR for HBV DNA detecting.
• Presence indicates infectivity and active viral
replication
• High levels may be present in carriers with no evidence
of liver damage
• The sensitive and specificity of HBV DNA is 60.63% and
100% respectively
• Patients should be considered for treatment when
HBV-DNA levels are > 2000 IU/mL.
• <103 IU/ml is likely to be associated with disease
resolution

17. USG ABDOMEN

18. LIVER BIOPSY

19. BLOOD INVESTIGATIONS
• ALT
• AST
• ALKALINE PHOSPHATASE
• TOTAL BILIRUBIN
• ALBUMIN
• PROTHROMBIN TIME, INR
• CBC- ANAMEIA AND THROMBOCYTOPENIA

20. DRUGS
• PEG-IFN-Used in adults
-dose= 180 mcg weekly for 48 weeks
-Adv Effects- Flu like symptoms, Fatigability, Cytopenias.
Contra indicated in Autoimmune disorders, cardiac
diseases
• Lamivudine : Reverse transcriptase inhibitor
Dose -150 mg/300mg daily.
HbeAg positive chronic hepatitis : > 1year until
seroconversion HbeAg and undetectable serum HBV DNA
levels
-HbeAg negative : > 1 year until surface antigen clearance
Adv effects- Pancreatitis, lactic acidosis.

21. • Telbivudine : Reverse transcriptase inhibitor
Dose-600 mg daily until seroconversion of HbeAg and
undetectable serum HBV DNA levels
-to be continued for 6 months after sero conversion.
• Adefovir:
Dose-10mg daily.
HbeAg positive chronic hepatitis : Treat until
seroconversion , treat for more than 1 year.
HbeAg negative > 1 year until surface antigen clearance
- Adv effects- Acute renal failure, Fanconis syndrome,
Lactic acidosis.

22. • Nucleotide reverse transcriptase inhibitor with activity
against HBV and HIV
– Considered as first line agents for patients with chronic
HBV because the virological efficacy is high and risk of
HBV resistance is low
– It is available in two preperations : TDF and Tenofovir
alafenamide (TAF)
- Dose-300 mg daily.
- Pts with HbeAg positive : it is characterized by
suppression of HBV DNA levels less than 400IU/ml
- Adv effects- Nephropathy, Fanconis syndrome,
Osteomalacia.
Tenofovir

23. • Entecavir : Potent inhibitor of hepatitis B
polymerase
Dose-0.5 to 1 mg daily
-without cirrhosis : minimum of 12 months Is
required until seroconversion of HbeAg and
undetectable HBV DNA levels
- In HbeAg negative the dosage is given until
the loss of HbsAg is seen.
Adv. Effects- lactic acidosis.

24. TREATMENT-IMMUNE TOLERANCE
PHASE
• ALT levels to be tested once in every 6 months
in immune tolerance phase to monitor
potential transition to immune active or
inactive CHB.
• Antiviral therapy to be given in adults of age
more than 40 with normal ALT levels and
elevated HBV DNA levels (More than
1,000,000 IU/ml) and features showing
moderate to sever fibrosis in liver biopsy.

25. Treatment in pregnancy
Treatment starts at 28 to 32 weeks of gestation
• Anti viral therapy was discontinued at birth to
3 months post partum
• HBV DNA values should me more than
200000 IU/ml.

26. Treatment in children
• Treatment to be started 2-18 years of age
• Elevated alt levels, elevated HBV DNA levels
and seroconversion of HBeAg – interferon
alpha 2b is given.
• Tenofovir is approved for children 12 years of
age.

28. Treatment in drug resistance

29. Prophylaxis of HBV vaccine
• 2 Vaccine formulations are there
– 1.Engerix –B :
– 2. Recombivax HB.

31. Hepatitis B positive mother :
• Risk of transmission is 90%
– Infants of HbsAg positive mothers should receive
monovalent HepB vaccine and HBIG 0.5ml as soon as
delivery as possible ( < 12hrs)
• The schedule of subsequent doses depend upon
the infants birth weight
– Wt> 2kgs : 2nd and 3rd doses should be given at 1 and
6 months of age
– Wt < 2ks : three additional doses should be given at 1
,2-3 , 4-6 weeks of age

32. THANK YOU