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,
  AT def,
1
 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
 Unconjugated/Indirect Bil, pale urine
 Hepatic – Viral, alcohol, toxins, drugs
 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 Impaired conjugation or obstruction.
Dark urine Conjugated hyperbil (vs. acholuric)
Pale stools Biliary obstruction
Oedema Low albumin – low oncotic pressure.
Steatorrhoea Bile obstruction.
Pruritis Bile obstruction  Bile salt in blood.
Ascitis Portal hypert, low alb, hyper aldosterone
Bleeding Coag. factor synthesis
Haematemesis Oesophageal varices. (hemorrhoids)
Encephalopathy Toxic nitrogen products – gut bacteria.
Foetar hepaticus Musty odor (mercaptans by gut bacteria)
 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, pseudo-glands
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 Hep-C

agent ssRNA dsDNA ssRNA

Transm. Feco-oral Parenteral Parenteral

Carrier None 0.1-1.0% 0.2-1.0%

state
Chronic None 5-10% >50%
Hepatitis
 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)