Q. What are the causes of COL?

Discuss on pathogenesis, clinical

manifestations and laboratory investigations of cirrhosis due to viral
hepatitis.

Pathogenesis of Cirrhosis of Liver

 Central pathogenetic process is progressive fibrosis.

 Intertitial collagen (type I & III) is normally existing in portal tract and
around the central vein ; occasion bundle are in the space of Disse.
 A delicate reticulin (Type IV) is in the space of Disse.
  In cirrhosis, type I & III collagen are deposited in allportion of lobules
and sinusoidal endothelial cells lose fenestration. (capillarization of
sinusoids)
 Major source of excess collagen - Ito cell.
 Ito cells may become activated & transform to myofibroblast like cells.
 Collagen synthesis is stimulated by
o Chronic inflammatory conditions with cytokine generation such as
TNFα, TGFβ & IL 1.
o Release of cytokines by other stimulated cells (Kuffer cells,
endothelial cells, hepatocytes, bile duct epithelial cells).
o Disruption of normal extracellular matrix.
o Direct stimulation of stellate cells by toxins.

Laboratory Diagnosis of Hepatitis B Viral Infection

Specific Tests

Serologic detection of HBV Ag and Ab

HBs Ag or Anti-HBs - by Radioimmunoassay and ELISA.
- practical agglutination.
HBV DNA in serum - by PCR (polymerase chain reaction).

Supportive Tests
Tests for abnormal liver function - ALT usually higher than AST.
- A gradual rise of ALT with
prolongation.
Liver biopsy - Tissue diagnosis
White cell count - Leucopenia followed by relative
lymphocytosis.

Interpretation with HBV serologic markers in patient with hepatitis

Assay results
HBs Ag Anti-HBs Anti-HBc Interpretation
(+)ve (-)ve (-)ve  Early acute HBV infection.
 Confirmation required to exclude non specific
reactivity.
(+)ve (+/-)ve (+)ve  Acute or chronic HBV infection.
 Determine level of replicative
activity(infectivity) with HBe Ag or HBV DNA.
(-)ve (+)ve (+)ve  Indicates previous HBV infection and immunity
to Hepatitis B.
(-)ve (-)ve (+)ve  Possibilities
  HBV infection in remote past;
 “low level” HBV carrier;
 “window” between disappearance of HBs Ag &
appearance of anti HBs; or
 False positive or non specific reaction.
 Investigate with IgM anti-HBc.
 When presence anti-HBe helps validate the anti-
HBc reactivity.
(-)ve (-)ve (-)ve  Never infection with HBV.
 Possibilities include another infectious agent,
toxic injury to liver, disorder of immunity,
hereditary disease of the liver, or disease of the
biliary tract.

(-)ve (+)ve (-)ve  Vaccine – type response.

Seromarkers of HBV

No Markers Characteristics

1. HBs Ag  First marker to appear.

 Disappear with clinical improvement.
 HBs Ag with IgM Anti-HBc Ab indicates acute infection.
 Persistance beyond 6 minths indicates chronic infection or carrier
state.
2. IgM Anti-HBc Ab  Marker of recent infection.
 It help to distinguish acute from chronic infection.
 Usually presence for upto six months.
 Then become undetectable.
 Simultaneous presence with HBs Ag indicates acute infection.
3. HBe Ag  Marker of infectivity
 Detectable in acute or chronic HBV.
 Persistence beyond 10 weeks indicate likely chronic liver
diseases.
 Associate with HBV replication
 Associate with high titer of HBV in serum.
 Associate with infectivity of serum.
4. Anti HBe Ab  Presence in serum of HBs Ag carrier.
 It suggest lower titer of HBV.
 Indicates lower infectivity.
5. Anti-HBc Ab  Indicate current or previous infection.
  Not associate with recovery or immunity.

6. Anti-HBs Ab  Marker of recovery and immunity.

 Detectable after HBs Ag disappear and recovery is complete.
 It indicates immunity after inoculation with hepatitis B vaccine or
a presence of Ab from HBIG.

Laboratory Diagnosis of Hepatitis C Viral Infection

Serology
o anti-HCV Ab testing by ELISA or Practicle agglutination Test.
Simple Rapid Test for HCV Ab.
Liver Function Tests
o Bilirubin, ALT, AST, ALP, GGT, T&DP
Recombinant immunoblot assay
Test for HCV RNA (PT-PCR)
HCV genotyping
Clinical relevance of HCV Genotypes
o Patients with genotypes 1 are less responsive to treatment with
interferon-alpha compared type 2 or 3.
o Genotype 1 is also found to be predominant in patients with
cirrhosis and hepatocellular carcinoma.