1. Pathological of the liver- Hepatitis (Objectives)
1- Discuss Hepatitis
2- The etio-pathogenesis of hepatitis
3- Morphologic features of hepatitis .
4- Clinical features& common
complications.
Suggested reading: Robbin’s Basic Pathology, 8th Ed. Page

2. WHAT IS HEPATITIS ?
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.
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:
Infectious agents: [Viral, bacterial, fungal &parasitic].
Non- infectious agents: [Autoimmune, alcohol, drugs&toxin).
Viral hepatitis is most commonly caused by hepatitis viruses.

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

4. HEPATITIS- ETIOLOGICAL FACTORS
ACUTE:
Acute viral hepatitis (e.g. HAV, HEV)
Toxic hepatitis- drug, chemicals.
Acute metabolic hepatitis
Ischemic hepatitis.
CHRONIC:
Viral hepatitis (HCV, HBV,..)
Alcohol hepatitis .
Drugs (acetaminophen, α-methyldopa, etc..)
Non-alcoholic fatty liver dis.
Autoimmune hepatitis
Heredity- α1-antitrypsin deficiency

5. VIRAL CAUSES OF HEPATITIS
1) VIRAL HEPATITIS: = Hepatotropic Virus
is term applied for infections caused by a group of viruses known as Hepatotropic Virus (hepatitis viruses A, B, C, D, E and G ) that have a particular affinity for the liver.
HGV: It is not hepatotropic, transmitted by contaminated blood or blood products, and via sexual contact, co-infects individuals infected with the HIV.
_________________________________________
Other Systemic viral infections:
(2) Infectious mononucleosis (EBV) - mild acute.
(3) CMV infection, -newborn& immunosuppression.
(4) Yellow fever (yellow fever virus) - serious.
5) Adenovirus, Herpesvirus, or enterovirus infections.

6. THE HEPATITIS VIRUSES

7. Common risk factors of viral hepatitis
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

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

10. Hepatitis B- Pathogenesis
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 HBV-infected hepatocytes. (immune mediated cells injury)
II. A second-possible mechanism is direct cytopathic effect of HBcAg expression in infected hepatocytes. (Cytopathic)
III. A third- possible mechanism is high-level expression and inefficient secretion of HBsAg.

11. HOW THE VIRUS REPRODUCES
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.
Once within the cell nucleus the hepatitis B DNA causes the liver cell to produce, via messenger RNA ; HBs protein , HB c protein , DNA polymerase, the HB e protein , and other undetected protein and enzymes
DNA polymerase causes the liver cell to make copies of hepatitis B DNA from messenger RNA.

12. The potential outcomes of hepatitis B infection in adults

13. Pathogenesis of viral Hepatitis
Hepatitis A virus : fecal-oral route, intestine  Hematogenous
Spread. Not seem to be cytopathic, cellular immunity e.g. Antigen-
specific T cells, plays a key role in hepatocellular injury
Hepatitis C virus :
1) Cellular -mediated Immunity: strong virus specific responses
by cytotoxic & helper T cell enhanced cell injury by secreting
different cytokines
2) Fibrogenesis-collagen deposition>> with persistent infection
>> fibrosis and cirrhosis.
Hepatitis D virus :HBV-HDV Coinfection& Superinfection,
both humoral & cellular immune mediate Cell injury

14. HEPTITIS-Morphological features
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:
Clinical information\presentation - correlation
Liver Function Tests.
Serological investigations (Viral markers)

15. Acute Hepatitis- Morphology
1) Hepatocyte injury- diffuse 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.
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-to-portal, central-to-central, or portal-to-central regions of adjacent lobules (in severe cases)

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

17. Chronic Hepatitis-morphology
Liver architecture is well preserved.
Portal Inflammation: lymphpcytes, MQ, plasma cells, Neutrophils or eosinophils.
Interface hepatitis and bridging necrosis(portal-to-portal& portal-to- terminal 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.

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

19. Chronic Hepatitis: HCV infection

20. Liver cirrhosis

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

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

23. HEPATITIS Common complications
ACUTE:
Fulminant hepatitis with confluent necrosis- HAV, HBV, HDV, HEV
Chronic hepatitis-HAV
CHRONIC:
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