Hepatitis B - a viral infection affecting hepatocytes and can lead to cirrhosis and at times, hepatocellular carcinoma. Adios amigos!

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.