Hepatitis B virus (HBV) is a significant global health concern that can lead to chronic liver disease and hepatocellular carcinoma, with over 248 million chronic infections worldwide. Transmission occurs through sexual contact, sharing of needles, and from mother to child, particularly affecting high-risk groups like IV drug users and infants of HBV-positive mothers. Diagnosis involves serologic testing for various antigens, and while no specific therapy exists, vaccination campaigns since 1991 have significantly reduced acute cases.

1. HEPATITIS
B

2. HEPATITIS B:
• Hepatitis B virus (HBV) is a common viral infection
worldwide.
• HBV is one of the 5 human DNA viruses implicated in the
causation of human cancer.
• It can be transmitted sexually, parenterally, or perinatally.
• HBV and Hepatitis C-virus, cause of between 70-85% of
hepatocellular carcinomas worldwide.
• Chronic hepatitis infection with HBV or HCV is the leading
cause of liver cancer.
• 5% of all adult patients & 90% of infants born to a hepatitis
B-positive mother develop chronic hepatitis.

3. EPIDEMIOLOGY:
• More than 248 million people worldwide are chronically
infected.
• One third of the world population (2 billion people) have
been infected with HBV & 400 million have chronic
infection.
• ~ 600,000 deaths annually from HBV-related liver disease.
• High prevalence in Asia, Africa, & the Amazon basin.
• United States:
• In 2014, there were 20,000 new hepatitis B infections and
~ 2 million people with chronic hepatitis B.
• Acute hepatitis B has declined by ~ 82% after the
introduction of the hepatitis B vaccine in 1991.

4. ETIOLOGY:
Hepatitis B virus
• Different forms of virus
particles present.
• Circular particles are
infectious virus particles
which consist of a
nucleocapsid & core
proteins.
• The filamentous & spherical
particles only consist of the
lipid envelope & are
therefore noninfectious.

5. TRANSMISSION:
The frequency & patterns of transmission vary worldwide.
i. Sexual
• Virus may be transmitted when bodily fluids come in contact
with broken skin or mucous membranes (mouth, genitals, or
rectum).
ii. Parenteral:
• Needlestick injury
• Transmission rate: ~30% for HBV and ~0.3% for HIV. The virus can
survive for 7 days or more outside of the body!
• Contaminated instruments & shared needles
• *e.g. IV drug use, acupuncture, body piercing, tattooing,
haemodialysis.
• Contaminated blood products.
iii. Perinatal
• Usually postnatal transmission in maternal milk. (Others
transmitted in this fashion include: cytomegalovirus & HIV).

6. HIGH-RISK GROUPS:
• IV drug users.
• Individuals whose close contacts have chronic HBV infection.
• Infants of HBV-positive mothers.
• Professions with exposure to human blood and/or seminal/vaginal fluids.
• Individuals with multiple sex partners or sex partners of HBV-positive
people.
• Patients undergoing hemodialysis; organ or blood transfusion
recipients.
• Hepatitis C virus (HCV) or HIV-positive individuals.
• NB: *Individuals whose medical history indicates a high risk for HBV infection
should be tested!

7. PATHOPHYSIOLOGY:
Acute infection:
• Hepatocytes infected by the HBV express viral peptides on
their surfaces lymphocytes recognize HBV-derived peptides
& become activated lymphocytes attack liver cells (cellular
immune response) hepatic inflammation with destruction of
hepatocytes.
Chronic infection:
• If clearance fails (*persons with impaired immune response at greater
risk of developing chronic infection).
• Persistent hepatic inflammation with necrosis, mitosis, &
regeneration process cirrhosis, cellular dysplasia HCC.
• Integration of HBV DNA into the host genome altered
expression of endogenous genes, chromosomal instability
HCC.

8.  After exposure HBV passes through bloodstream to the
liver infects hepatocytes & multiplies.
 Infection usually self-limiting, with most patients mounting
an effective immune response.
 Approx. 6% to 10% of infected adults cannot eradicate the
virus & become chronic carriers of HBV.
 There is an inverse relationship between age & chronic
carrier status, with younger individuals at greater risk of
infection.
PATHOPHYSIOLOGY:

9. HEPATITIS B VIRUS:
Hepatitis B virus (HBV) can produce:
i. Acute hepatitis followed by recovery & clearance of virus.
ii. Non-progressive chronic hepatitis
iii. Progressive chronic disease ending in cirrhosis
iv. Acute hepatic failure with massive liver necrosis
v. Asymptomatic “healthy” carrier state.
• HBV-induced chronic liver disease is also an important
precursor in the development of hepatocellular
carcinoma even in the absence of cirrhosis.
• HBV has an incubation period of 1-6 month(s).

10. CLINICAL FEATURES:
Acute infection:
• Serum sickness-like syndrome can develop during the
prodromal (pre-icteric) period: rash, polyarthritis, fever.
• Subclinical hepatitis (70% of cases).
• Symptomatic hepatitis (30% of cases)
• Fever, rash, arthralgias, myalgias, fatigue.
• Nausea
• Jaundice
• RUQ tenderness
• Symptoms usually resolve after 1-3 months
• Fulminant hepatitis (~ 0.5% of cases)
• Most adults will clear infection.
• *Recovery rates in adults are VERY GOOD!

11. CLINICAL FEATURES:
Chronic infection:
• Defined as infections persisting for more than 6 months
with detection of HBsAg & possibly symptoms of liver
damage.
• Most patients are inactive, non-contagious carriers.
• Potential reactivation of chronic inactive hepatitis: may be
asymptomatic, imitate acute hepatitis, or result in hepatic
failure.
• Cirrhosis, stigmata of chronic liver disease (25% of cases).
• Extrahepatic manifestations (10-20% of cases).
• Polyarteritis nodosa.
• Membranous glomerulonephritis.

12. DIAGNOSIS:
Antigens, DNA, and antibodies:
• HBsAg – Hepatitis B surface antigen
• Protein on the surface of HBV; first evidence of infection.
• Can be detected as early as 1-2 weeks & as late as 11-12
weeks after infection.
• HBcAg – Hepatitis B core antigen
• Protein of the nucleocapsid.
• Indicates active viral replication.
• Does not circulate in blood & is only detected in hepatocytes
following a liver biopsy.
• HBeAg – Hepatitis B envelope antigen
• Protein secreted by virus indicating viral replication &
infectivity.
• Unlike HBcAg, it is present in blood.

13. DIAGNOSIS:
• Anti-HBs:
• Indicates immunity to HBV due to vaccination or resolved infection.
• Usually appears 1-3 months after infection.
• Anti-HBc:
• Anti-HBc IgM indicates recent infection with HBV (<6 months).
• Anti-HBc IgG indicates resolved or chronic infection.
• Anti-HBe:
• Indicates long term clearance of HBV.
• HBV DNA:
• DNA of HBV – marker of active HBV replication, viremia, and
infectivity in acute & chronic hepatitis.

14. DIAGNOSIS:
Testing algorithm:
i. Screening: HBsAg (detectable 1-5 months after infection)
& anti-HBc IgM.
ii. If HBsAg is positive – measure HBeAg & HBV DNA.
• Positive HBeAg suggests viral persistence & a high degree of
infectivity. Seroconversion to anti-HBe indicates a low viral load
& therefore suggests a better prognosis.
• If it (HBV DNA) persists >6 weeks, development of chronic
hepatitis likely.
iii. Seroconversion of HBsAg to anti-HBs indicates acute
hepatitis resolution.

15. DIAGNOSIS –
ADDITIONAL TESTS:
Laboratory studies:
• Transaminases (AST, ALT)
• Acute hepatitis: increased with AST/ALT ratio of <1 (>1 in fulminant
infection).
• Chronic hepatitis: variable values with AST/ALT ratio of ≥1.
• ↑ γ-GT, bilirubin, GLDH, and/or AP.
• In cirrhosis:↓albumin, CHE
Abdominal ultrasound:
• Acute hepatitis - ↑Brightness of portal vein radicle walls.
• ↓ Echogenicity of the liver.
• Chronic hepatitis - ↓Brightness of portal vein radicle walls.
• ↑Liver echogenicity.
Liver biopsy
Test of common coinfections (e.g. hepatitis C/D, syphilis, HIV).

16. PATHOLOGY:
I. Acute hepatitis B:
• Eosinophilic single-cell necrosis (Councilman body).
• Kupffer cell proliferation.
• Bridging necrosis.
• Occurs btw blood vessels in the liver, forming a flat area of necrosis.
II. Chronic hepatitis B:
• Formation of lymphoid follicles & mononuclear infiltrates.
• Piecemeal necrosis: periportal liver cell necrosis with lymphocytic
infiltration – indicates chronic active hepatitis & poor prognosis.
• Fibrous septa – results from parenchymal collapse secondary to extensive
bridging necrosis with accompanying fibrous tissue deposition.
• Ground glass hepatocytes:
• Hepatocytes with swollen transparent cytoplasm due to hyperplasia
of the endoplasmic reticulum.
• Only in hepB.
• Result from an increased production of viral membrane particles
(HBsAg).

17. TREATMENT:
HBV infection clinically indistinguishable from other types of
hepatitis.
 Diagnosis can be made only through serologic testing.
 No specific therapy exists for HBV infection in adults.
 Treatment consists of supportive care & relief of
symptoms.
 Since 1991, CDC has promoted aggressive vaccination
campaign & recommends vaccination for all infants,
children, & adolescents & a diversity of high-risk adults.
 The three-injection vaccine series is begun at birth for all
infants.

18. ACUTE HEPATITIS B:
• Supportive care
• Acute liver failure treatment:
• Early transfer to a liver transplant canter.
• IV N-acetylcyteine
• Address/prevent complications (e.g. infection, renal failure,
coagulopathy, encephalopathy, cerebral edema).
• Address underlying cause (e.g. antiviral tx for hepatitis B,
steroids for autoimmune hepatitis)
• Liver transplantation is the only therapeutic option for patients
without sufficient regeneration of hepatocytes.
TREATMENT:

19. CHRONIC HEPATITIS B:
A. Antiviral treatment:
• Nucleoside analogs: indicated for pts with both decompensated &
compensated liver disease & non-responders to interferon treatment.
• Tenofovir, Entecavir
• Pegylated interferon alpha (PEG-IFN-a): especially in younger
patients with compensated liver disease.
• NB: *Co-infection with HDV is best treated with PEG-IFN-a.
B. Surgical treatment:
• Liver transplantation:
• In cases of end-stage liver disease due to HBV.
• In cases of fulminant hepatic failure (emergent
transplantation).
TREATMENT:

20. Chronic Hepatitis B Treatment Goals:
 Reduce HBV DNA below detectable levels.
 Seroconversion of HBeAg to anti-HBe.
 Reverse liver disease.
NB: *interferon treatment is contraindicated in pregnancy!
TREATMENT:

21. COMPLICATIONS:
a. Hepatitis D virus infection.
b. Acute liver failure.
c. Liver cirrhosis.
d. Hepatocellular carcinoma.
e. Reactivation of previous HBV
infection.
Long term
complications

22. PREVENTION:
Pre-exposure vaccination:
• Recommended for all unvaccinated individuals.
Post-exposure prophylaxis (PEP):
• Goal: Prevention of HBV infection.
• Indication: exposure to HBV (e.g. percutaneous, ocular,
mucosal)
• Unvaccinated individuals or incompletely vaccinated:
simultaneous administration of HepB immune globulin
(HBIG) or HepB vaccine & completion of original
vaccination series.
• Vaccinated with 3 doses of hepatitis B.