Pathology

of
Hepatitis

Normal Liver

1.5 kg, wedge

shape
4 lobes, Right, left,
Caudate, Quadrate.
Double blood supply
Hepatic arteries
Portal Venous
blood
Acini / Portal triad.
Lobules central. V

LIVER FUNCTIONS

Metabolism Carbohydrate, Fat &

Protein
Secretory bile, Bile acids, salts &
pigments
Excretory Bilirubin, drugs, toxins
Synthesis Albumin, coagulation factors
Storage Vitamins, carbohydrates etc.
Detoxification toxins, ammonia, etc.

CT Scan Normal Abdomen

Structure of Liver Lobule

Normal Liver - Microscopy

Disorders of liver

Acute Liver Disorder:

Viral, Drug, Gall stones, alcohol toxicity.
Chronic Liver Disease:
Chronic hepatitis, Cirrhosis, viral,
alcohol, cong.
Autoimmune hepatitis. PBS.
Congenital Disorders:
Haemochromatosis,
Wilsons,
1AT def,

Contd
Tumors:
Benign: Adenoma, angioma,
Nodular hyperplasia
Malignant: Hepatocellular
carcinoma, Cholangiocarcinoma,
Hepatoblastoma, Angiosarcoma.
Cysts: Simple, Hydatid

Introduction:

Hepatitis: Inflammation of Liver

Viral, Alcohol, immune, Drugs &
Toxins
Biliary obstruction gall stones.
Acute, Chronic & Fulminant - types
Viral Hepatitis

Specific Heptitis A, B, C, D, E, &

other
Systemic - CMV, EBV, other.

Ritesh kumar pandey

Yellow discoloration of skin & sclera due

to excess serum bilirubin.
>40umol/l, (3mg/dl)
Conjugated & Unconjugated types
Obstructive & Non Obstructive (clinical)
Pre-Hepatic, Hepatic & Post Hepatic
types
Jaundice - Not necessarily liver disease
*

Common Causes of Jaundice

Pre Hepatic (Acholuric) - Hemolytic

Hepatic Viral, alcohol, toxins, drugs

Unconjugated/Indirect Bil, pale urine

Liver damage - unconjugated
Swelling, canalicular obstruction Conjugated

Post Hepatic (Obstructive) Stone,

tumor

Conjugated/Direct Bil, High colored

urine,

Jaundice

Jaundice

Pathogenesis of clinical features:

Jaundice
Dark urine

Impaired conjugation or obstruction.

Conjugated hyperbil (vs. acholuric)

Pale stools
Oedema

Biliary obstruction
Low albumin low oncotic pressure.

Steatorrhoea
Pruritis

Bile obstruction.
Bile obstruction Bile salt in blood.

Ascitis

Portal hypert, low alb, hyper

aldosterone
Coag. factor synthesis

Bleeding
Haematemesis Oesophageal varices. (hemorrhoids)
Encephalopath Toxic nitrogen products gut
y
bacteria.
Foetar
Musty odor (mercaptans by gut

Viral hepatitis

Hepatotrophic viruses are A, B, C,

delta agent, E, G
May be self-limiting (hepatitis A),
chronic liver disease and cirrhosis
(hepatitis B and C),
massive necrosis and acute liver
failure (rare with hepatitis C)

Pattern of Viral Hepatitis:

Carrier state / Asymptomatic phase

Acute hepatitis
Chronic Hepatitis

Chronic Persistent Hepatitis (CPH)

Chronic Active Hepatitis (CAH)

Fulminant hepatitis
Cirrhosis
Hepatocellular Carcinoma

Carrier state:

virus present, but either no clinically

apparent disease or chronic hepatitis;
best characterized for hepatitis B;
Reservoir of infection
present in 90% infected early in life
or at childbirth versus 1-10% of adult
infections with hepatitis B;
associated with impaired immunity

Acute viral hepatitis

Phases:
incubation,
symptomatic preicteric,
symptomatic icteric,
convalescence
Peak infectivity is at end of
incubation period and early
symptomatic period

Preicteric phase

constitutional symptoms, malaise,

fatigue, loss of appetite;
serum-sickness like syndrome in 10%
(fever, rash, arthralgias due to
circulating immune complexes),
enlarged and tender liver,
elevated serum aminotransferases

Icteric phase:

severe symptoms (high fever,

shaking chills, headache, right upper
quadrant pain),
jaundice due to conjugated
hyperbilirubinemia (dark urine, light
stools, pruritis),
increased prothrombin time
Icteric phase common in acute phase
of hepatitis A, 50% of hepatitis B,
unusual in hepatitis C

Acute Hepatitis:

Swelling and Apoptosis

Piecemeal or Bridging, panacinar
necrosis
Inflammation lymphocytes,
Macrophages
Ground glass hepatocytes HBV
Mild fatty change HCV
Portal inflammation and Cholestasis

Pattern of Liver Damage

Zonal Toxin/Hypoxia
Bridging Viral
severe
Interface Immune
Apoptotic - Viral

Acute viral Hepatitis:

Acute viral Hepatitis:

Chronic Hepatitis:

Diagnosis requires symptomatic,

serologic or biochemical evidence of
continuing or relapsing hepatic disease
of 6 months or more, with histologically
documented necrosis and inflammation
Persistent & Active types. CPH/CAH
Terms chronic active hepatitis and
chronic persistent hepatitis, based on
presence (active) or absence
(persistent) of piecemeal necrosis,

Chronic hepatitis

Biopsy performed to confirm

diagnosis and assess inflammatory
grade and fibrotic stage of disease
Etiology (hepatitis C > hepatitis B) is
the most important predictive factor
for chronic hepatitis; clinical features
are not predictive

Micro

Lymphoid aggregates
Periportal fibrosis
Piecemeal Necrosis with fibrosis
bridging fibrosis.
Cirrhosis regenerating nodules.

Liver Biopsy - CAH:

Liver Biopsy CPH:

Symptoms:

spider angiomas,
palmar erythema,
mild hepatosplenomegaly,
hepatic tenderness,

increased prothrombin time and

partial thromboplastin time,
vasculitis due to immune complex
deposition (HBV, HCV),
glomerulonephritis, (35% of HCV)

Acute - Hepatitis - Chronic

Fulminant Hepatitis:

Hepatic failure with in 2-3 weeks.

Reactivation of chronic or acute hepatitis
Massive necrosis, shrinkage, wrinkled
Collapsed reticulin network
Only portal tracts visible
Little or massive inflammation time
More than a week regenerative activity
Complete recovery or - cirrhosis.

Hepatitis A virus (HAV)

Virology: due to Picornavirus, 27 nm

virion with single stranded RNA
Incubation period : 2-6 weeks
Fecal-oral transmission via
contaminated food or water;
associated with overcrowding or poor
sanitation; usually children
in adults, infection more severe with
malaise and jaundice for 7-10 days

May cause acute cholestatic hepatitis

with bile ductular proliferation,
neutrophils around ducts,
cholestasis, hepatocyte ballooning,
pseudo-glands around bile plugs
Does not produce chronic disease or
carrier state in immunocompetent
patients
Causes 50% of hepatitis cases in US;
effective vaccine available

Hepatitis B virus (HBV)

Usually subclinical disease, but may

lead to fulminant hepatic failure,
chronic liver disease and cirrhosis
Incubation period : 4 26 weeks
Lifetime risk for hepatocellular
carcinoma is 40% for men and 15%
for women

Spread

acutely infected patients or

chronic viral carriers through
intimate / sexual contact,
intravenous drug abuse,
contaminated blood or infected
instruments,
maternal to infant via delivery

Virology:

Hepadnavirus;
intact virus is known as Dane particle;
28 nm central nucleocapsid core enclosed
by outer surface envelope;
core contains DNA genome with DNA
polymerase,
hepatitis B core antigen and hepatitis B e
antigen;
viral envelope contains hepatitis B surface
antigen

Laboratory Ix

Hepatitis B surface antigen

(HBsAg): carries no particularly useful
clinical information, but is first serum
marker of active infection
Hepatitis B core antigen (HBcAg):
indicates active replication of virus,
patient is infective; present in
hepatocyte nuclei
Carrier: antigenemia > 6 months,
normal ALT and AST, no symptoms;
occurs in 10%

1. HBs antigen
If positive indicates
acute HBV infection (enzymes
elevated)
or
chronic HBV infection (enzymes
fluctuate)
or
HBV carrier (enzymes not elevated)

2. HBe antigen
This should be checked whenever
HBs antigen is positive.
If HBe antigen (Ag) is present, it
indicates greater infectivity of the
HBV infection towards sexual partner
or foetus and greater likelihood of
developing chronic hepatitis.
HBe Ag is found only in association
with Hbs Ag, never on its own.

3. Anti-HBs
Indicates immunity to HBV whether
naturally acquired or following
immunisation.

4. Anti-HBc IgM
Is measured when current HBV infection is
strongly suspected but HBs Ag and anti-HBs
are both negative.
Anti-HBc IgM rises early in HBV infection
and persists for about 6 months.
It fills the one month "window" between
disappearance of HBsAg and the
appearance of anti-HBs.
Positive anti-HBc does not confer immunity.

Hepatitis C virus (HCV)

Virion: a flavivirus, enveloped RNA

virus
0.2% incidence in US, 170 million
people infected worldwide
90% of non-A, non-B hepatitis cases,
75-95% of transfusion associated
hepatitis cases are due to Hepatitis C
Incubation period : 2 26 weeks

Liver Biopsy viral Hepatitis-C

Acute viral Hepatitis C:

Causes

35% IV drug abuse,

15% household contact or
heterosexual exposure,
5% blood transfusion,
45% unknown

50-80% develop chronic liver

disease,
20% of these develop cirrhosis;
high risk for hepatocellular
carcinoma, particularly with alcoholic
cirrhosis (57% at 10 years);
acute liver failure is rare

Complications:

deterioration of liver status with

cirrhosis in 20% and
improvement in 10% with chronic
hepatitis C;
Hepatocellular carcinoma

Hepatitis delta agent

(Hepatitis D)
Only occurs with hepatitis B virus

because delta agent is a defective

RNA virus that requires hepatitis B
infection for its own replication
May cause any clinical syndromes or
histologic patterns of hepatitis B
Incubation period : 4 -7 weeks

May also cause an acute hepatitis

with atypical biphasic pattern or a
chronic hepatitis that progresses
rapidly to cirrhosis in 15% of patients
Consider delta virus infection if
(a) recurrent acute hepatitis or
(b) sudden fulminant hepatitis in
chronic hepatitis B carrier

Hepatitis E virus

Fecal-oral transmission similar to

Hepatitis A, often through contaminated
water
Incubation period : 2-8 weeks
Associated with poor outcome in
pregnant women
(up to 22% fatality rate due to
disseminated intravascular coagulation
and fulminant hepatitis)

May cause acute cholestatic hepatitis

with bile ductular proliferation,
neutrophils around ducts,
cholestasis,
hepatocyte ballooning, pseudoglands around bile plugs
Due to Calicivirus

Hepatitis G virus

RNA virus that, like HCV, is member

of Flaviviridae family
Accounts for 10% of non A-E hepatitis
Identified in 1.5% of blood donors
with normal ALT
Spreads via transfusion, IV drug use,
multiple sexual partners

Liver Cirrhosis

Viral Hepatitis: Microbiology

Virus

Hep-A

Hep-B
dsDNA

Hep-C

agent

ssRNA

ssRNA

Transm.

Feco-oral Parenteral Parenteral

Carrier
state

None

0.1-1.0%

0.2-1.0%

Chronic
Hepatitis

None

5-10%

>50%

Conclusions

Common end result of diffuse liver

damage. (Viral hepatitis, Alcohol,
congenital, drugs, toxins &
Idiopathic)
Characterised by diffuse loss of
architecture.
Fibrous bands & regenerating
nodules distort and obstruct blood
flow. (inefficient function)