Viral and Toxic Hepatitis: Etiology, Pathogenesis, and Clinical Features, Schemes and Mind Maps of Pathology

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The Liver 2

Dr. N. R. Rajesh kanna

Professor in Pathology

CHRI

PA25.3. Describe the etiology and pathogenesis

of viral and toxic hepatitis: distinguish the causes

of hepatitis based on the clinical and laboratory

features. Describe the pathology, complications

and consequences of hepatitis.

Hepatitis viruses

HAV

Picornavirus

HBV

Hepadnavirus

HCV

Hepacivirus

HDV HEV

calicivrus

HGV

Flavivirus

Agent ss RNA ds DNA ss RNA ss RNA ss RNA ss RNA

Route Fecal-

oral

Parenteral Parenteral Parenteral Water Parenteral

Incubation 2-

weeks

4-

weeks

2-

weeks

4-

Weeks

2-

Weeks

Not

known

Carrier

state

none 01-1%

donors

0.2-1%

donors

1-10% 1-2%

donors

chronic None 5-10% >50% <5% None None

Cancer No Yes Yes - - none

Hepatitis A

• (^) “Infectious hepatitis” - 25% of clinically evident

acute hepatitis worldwide;

• (^) In countries with substandard hygiene ; Rare

after childhood - spread by close contact

• (^) Fecal – oral route ; virus is shed in feces 2-

weeks before & I week after onset of jaundice

• (^) Incubation 2-6 weeks;
• (^) No carrier state or chronicity
• (^) Mild or asymptomatic in most cases; Rarely

fulminant hepatitis; fatality ~0.1%

• (^) IgM antibody in serum is reliable marker for

infection; IgG antibody provides lifelong

immunity

Hepatitis B virus

• (^) Causes “Serum hepatitis”
• (^) Clinical spectrum caused by HBV
  • (^) Acute hepatitis
  • (^) Chronic non-progressive hepatitis
  • (^) Progressive chronic hepatitis ending in

cirrhosis

• (^) Asymptomatic carrier state
• (^) Backdrop for hepatitis D

Hepatitis B

Non progressive

Polymerase

HBsAg

HBeAg

HBxAg

HBcAg

Hepatitis B virus infection

• (^) Proliferative phase
  • (^) DNA seen in episomal form with formation of

complete virions & all antigens

• (^) Cell surface expression of HBsAg & HBcAg

lead to activation of CD8+ T cells

• (^) Integrative phase
  • (^) Virus DNA is incorporated into the host cell

DNA.

• (^) Antiviral antibodies ends infectivity & liver

damage subsides.

• (^) But risk of HCC persists.

Hepatitis B

P

P

Immune Response

Vaccination

Weak

HBsAg – appears before onset of

symptoms, peaks during overt disease &

declines in 3-6 months – active infection.

HBeAg, HBV DNA, DNA polymerase

appear after HBsAg & indicate

replication

Anti HBe(strong) denotes disease is in wane

• (^) IgM anti-HBc becomes detectable after

onset of symptoms co insides with Sr

transenzymes followed by IgG anti HBc.

• (^) IgG anti-HBsAg appears after the

disappearance of HBsAg and provides

lifelong protection

Hepatitis B

Appearance of HBs Ag for 6 months and

a symtomatic denotes carrier state.

Persistence of circulating HBsAg, HBeAg &

HBV DNA usually (with anti-Hbc and occasionally

with anti-HBs) is associated with progressive

disease

Loss of HBeAg with failure to form Anti-

HBeAg is associated with fulminant course

Acute infection

Resolution 15% Chronic hepatitis 85% Fulminant hepatitis

Stable disease 80% Cirrhosis 20%

Stable cirrhosis 50%

Death 50%

HCC

Hepatitis C

• (^) Incubation – 2 to 26 weeks
• (^) HCV RNA is detectable for 1-3 weeks
• (^) Circulating RNA persists even in the

presence of antibodies

• (^) Clinical course is milder than Hepatitis B
• (^) Persistent infection & chronic hepatitis are

hallmarks ; cirrhosis in 5-10 years

• (^) Persistent transaminasemia in chronic cases

• (^) Because of HCV RNA polymerase (NS5B), virus give rise to

Xle genotypes & subtypes.

• (^) Within an individual HCV circulates as a population of

variants known as quasispecies.

• (^) The E2 protein of the envelope is the target of many anti-HCV

antibodies (against E2).

• (^) So elevated titers of anti-HCV IgG occurring after an active

infection do not consistently confer effective immunity

• And its (E2) the most variable region of the entire viral

genome, enabling emergent virus strains to escape from

neutralizing antibodies.

• (^) This genomic instability and antigenic variability have seriously

hampered efforts to develop an HCV vaccine.

Genetic structure of C

General Facts

Hepatitis D

• (^) Hepatitis Delta virus – Replication defective virus
• (^) Absolutely dependent on HBV for multiplication

and causes hepatitis only in the presence of HBV

• (^) Two types of infection
  • (^) Co-infection --- 90% recovery IgM HDV & IgM HBcAg
  • (^) Superinfection ---- 90% chronic disease ---- cirrhosis
    • (^) HBsAg & IgM HDV
• (^) Rarely simultaneous infection leads to more

fulminant course

• (^) IgM anti-HDV is a good marker for recent HDV

exposure

Hepatitis D Virus Coinfection and Superinfection

Francesco Negro. Cold spring Harb perspect Med. 2014 Nov; 4(11)