Pathological of the liver- Hepatitis (Objectives)
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 Suggested reading: Robbin’s Basic Pathology, 8 th Ed. Page-
639-648

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HEPATITIS is a serious GLOBAL health problem, used as general term to describes inflammation of the liver. The condition can be self-limiting or can progress to fibrosis (scarring), cirrhosis, liver failure or liver cancer and death.
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Presentation?
Hepatitis may occurs with limited or no symptoms .
Hepatitis also may occurs in Acute form when it lasts less than six months and
Chronic when it persists longer .
 Generally caused by different insulting agents:
1.
Infectious agents: [ Viral, bacterial, fungal &parasitic ].
2.
Non- infectious agents: [ Autoimmune, alcohol, drugs&toxin ) .
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 Viral hepatitis is most commonly caused by hepatitis viruses.

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2.
Infections- (5 main types of Viral hepatitis, others infections:
Bacterial –salm./staph, parasitic & helminthes)
Alcohol Hepatitis
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Non-alcoholic fatty liver disease Obesity, diabetes, and hyperlipidemia.
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5.
Toxic Hepatitisdrugs, herbal and chemicals.
Drugs-induced Hepatitis-.
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7.
Ischemic Hepatitis.
Acute liver vascular disease.
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Autoimmune Hepatitis
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Metabolic liver diseases and other Hereditary disorders.

 ACUTE:
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Acute viral hepatitis (e.g. HAV,
HEV)
Toxic hepatitis- drug, chemicals.
Acute metabolic hepatitis
Ischemic hepatitis.
 CHRONIC :
1.
Viral hepatitis (HCV, HBV,..)
2.
Alcohol hepatitis .
3.
Drugs (acetaminophen, αmethyldopa, etc..)
4.
Non-alcoholic fatty liver dis.
5.
Autoimmune hepatitis
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Heredity- α1-antitrypsin deficiency

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Infected blood and blood product.
Needle stick injury- health care worker
Employment in medical or dental fields.
Intravenous drug abuse .
Un-protected sex, multiple sex partners.
Having had surgery or history of transfusion-6\12
Received a piercing or tattoo in unclean environment
Contaminated water and food , Traveler (ora-fecal)
Unknown

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The specific mechanism varies and depends on the underlying cause for the condition.
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Mechanism of Autoimmune and alcoholic Hepatitis and other types will be cover in the coming sessions.
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The outcome of infection by a hepatitis virus depends on :
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1) Viral factors (viral load, genotype, mutations, Expression of proteins etc.).
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2) Virus–host interactions.
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3) Host characteristics (age, gender, general condition, lifestyle, alcohol abuse, etc.).
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4) Nature of the host immune response, patterns of cytokines, etc.,
• which will finally determine the histologic alterations.

 Three mechanisms seem to be involved in liver cell injury during HBV infections:
 I. The first- due to a restricted cytotoxic T-cell ( CTL ) response directed at HBcAg / HBeAg on HBVinfected hepatocytes . ( immune mediated cells injury )
 II. A secondpossible mechanism is direct cytopathic effect of HBcAg expression in infected hepatocytes . ( Cytopathic )
 III. A thirdpossible mechanism is high-level expression and inefficient secretion of HBsAg .

HOW THE VIRUS REPRODUCES ?? Pathogenesis
1) First the virus attached to a liver cell membrane
2)The virus is then transported into the liver cell.
3) The core particle releases it’s contents of DNA and DNA polymerase into the liver cell nucleus.

The potential outcomes of hepatitis B infection in adults

Hepatitis A virus : fecal-oral route, intestine
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Hematogenous
Spread. N ot seem to be cytopathic, cellular immunity e.g. Antigenspecific T cells, plays a key role in hepatocellular injury
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Hepatitis C virus :
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1) Cellular -mediated Immunity: strong virus specific responses by cytotoxic & helper T cell enhanced cell injury by secreting different cytokines
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2) Fibrogenesis-collagen deposition>> with persistent infection
>> fibrosis and cirrhosis.
Hepatitis D virus :HBV-HDV Coinfection& Superinfection, both humoral & cellular immune mediate Cell injury
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 The morphologic changes in acute and chronic viral hepatitis can be mimicked by drug reactions or autoimmune liver disease.
 Liver biopsy: Tissue alterations caused by acute infection with HAV, HBV,
HCV, and HEV are generally similar, as is the chronic hepatitis caused by SAME
VIRSUSES.
 Proper assessment of morphological changes needed:
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Clinical information\presentation - correlation
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Liver Function Tests.
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Serological investigations (Viral markers)

1 ) Hepatocyte injurydiffuse swelling (ballooning degeneration)
 Hydropic cytoplasm , granular eosinophilic, Councilman bodies.& Necrosis.
2) Bile plugs brown pigmentation in canaliculi & hepatocytes- indicate cholestasis, this due to cessation of the contractile activity of the pericanalicular actin microfilament web.
3) Lobular inflammation with inter-phase & ductular reaction.
(centrolobular region in HBV and HCV, periportal zone in HAV)
4) Morphological types of Hepatocytes death: a) Focal loss of hepatocytes& cell death, due to rupture of cell membrane.
b) The sinusoidal collagen reticulin framework collapses and scavenger MQ aggregates at sites of cell loss.
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 c) Apoptosis, caused by anti-viral cytotoxic (effector) T cells, shrunken in size, phagocytes.
c) Confluent necrosis of hepatocytes may lead to bridging necrosis(portal-toportal, central-to-central, or portal-to-central regions of adjacent lobules (in severe cases)

Acute hepatitis- MORPHOLOGY cells injury& ballooning Lobular inflammation
Acute Hepatitis ; Cholestasis& MQ reaction

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Liver architecture is well preserved.
Portal Inflammation : lymphpcytes, MQ, plasma cells, Neutrophils or eosinophils.
Interface hepatitis and bridging necrosis(portal-to-portal& portal-toterminal hepatic veins.
The hallmark of chronic liver damage is the deposition of fibrous tissue.- portal fibrosis, linking of fibrous septa (bridging fibrosis),.
Liver cirrhosis : fibrosis results in cirrhosis
 varying sizes nodules, broad scars.
HBV-infected hepatocytes - show a cytoplasm packed with spheres and tubules of HBsAg, producing a finely granular cytoplasm
(“ ground-glass hepatocytes ).
HCV-infected livers frequently show lymphoid aggregates within portal tracts, ductular reactive change and focal lobular regions of hepatocyte macrovesicular steatosis .

HBV infection : parenchyma showing hepatocytes with diffuse granular cytoplasm,(ground glass )

 HBV, HAV, HCV, Herpes, toxin& drugs.
 Severe necrotizing process.
 Entire liver or only random areas may be involved.
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 little inflammatory reaction.
Massive influx of macrophages for phagocytosis
If pt. survive hepatocytes replication started with ductular reaction

HEPATITIS – Clinical feature symptoms
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I. Acute asymptomatic
II. Acute symptomatic
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Malaise.
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Muscle and join ache\ Fever\ Nausea or vomiting
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Malaise, tiredness, weakness
Weight loss
Peripheral oedema
Ascites
Jaundice (+\-)
Loss of apetite
Abdominal pain The Carrier State.
Dark urine -reservoirs for infection
Jaundice (+\-) -“healthy carrier” without
HBeAg

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: 
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 Fulminant hepatitis with confluent necrosis-
HAV, HBV, HDV, HEV
 Chronic hepatitis-HAV
 Scarring of the liver
( cirrhosis )( HBV, HCV,HDV )
 Liver cancer.
 Liver failure.
 Co-Hepatitis :e.g HDV infection following HBV
 Kidney GN
 PAN - VASCULITIS
 Neurologic complications.
 Co –infection HIV