1. Liver cirrhosis is the end stage of many chronic liver diseases and is characterized by diffuse hepatic fibrosis and parenchymal nodule formation. 2. Liver abscesses can be caused by parasitic or pyogenic infections and present as solitary or multiple lesions on gross and microscopic examination. 3. Alcoholic liver diseases include fatty liver, alcoholic steatohepatitis (ASH), and alcoholic cirrhosis, progressing from steatosis to necroinflammation and fibrosis.

1. Title : Liver
Objectives : to
1. Describe liver cirrhosis.
2. Outline liver abscess.
3. Identify alcoholic liver diseases.
4. Study metabolic liver diseases.

2. Liver cirrhosis:
 End stage of many chronic liver diseases.
 Refers to diffuse hepatic fibrosis with replacement
of normal lobular architecture by parenchymal nodules
separated by fibrous tissue.
 suspected on clinical, laboratory, and imaging parameters,
but final diagnosis requires liver biopsy.
 Architectural changes best appreciated on reticulin stain.

3.  The morphologic classification of cirrhosis
is based on size of nodules:
o Micronodular : if nodules are less than 3 mm.
o Macronodular : if nodules are greater than 3 mm.
 The size of nodules can define etiology of cirrhosis ,
but this is relative since micronodular cirrhosis may
convert into macronodular type .

4.  Features indicating etiology of cirrhosis :-
• Biliary cirrhosis: garland-shaped nodules, and
clear halo in nodular periphery due to edema.
• Post hepatitic cirrhosis: necro inflammation.
• HBV : ground glass hepatocytes.
• HCV: lymphoid aggregates and lymphoid follicles.

5. • Autoimmune hepatitis: numerous plasma cells.
• Genetic hemochromatosis: severe parenchymal siderosis.
• a1-Antitrypsin deficiency: hepatocellular inclusions
which are eosinophilic, PAS positive.
 Hepatocellular carcinoma commonly arises in cirrhotic liver.
Its precancerous stages ( dysplastic foci , large and small
liver cell dysplasia) should be looked for.

7. Liver abscess :
 In developing countries: most liver abscesses
represent parasitic infections (amebic, echinococcal).
 In developed countries: most are pyogenic, the organism
reach liver by:
(1) portal vein.
(2) arterial supply.
(3) ascending cholangitis.
(4) direct invasion of liver from nearby source.
(5) penetrating injury.

8. Morphology :
 Liver abscesses can be solitary or multiple:
o Bacteremic spread: multiple small abscesses.
o Direct extension and trauma: solitary large abscesses.
o Biliary abscesses are usually multiple.
 Gross and microscopic features are those of any abscess.
 The causative organism can be identified in fungal or
parasitic abscesses .

9. The liver shows a small abscess filled with
many neutrophils.
Amoebic Liver abscess
amoebic Liver abscess- trophozoites

10. Alcoholic liver diseases:
Hepatic Steatosis (Fatty Liver):
 Fatty liver is large , soft , yellow and greasy.
 Small microvesicular lipid droplets in hepatocytes.
 With chronic intake of alcohol: large, clear macrovesicular.
 Initially is centrilobular, in severe cases involve entire lobule.
 Fatty change is completely reversible if there is abstention
from alcohol intake.

12. Alcoholic Steato Hepatitis- ASH:
 Grossly :
o liver is mottled red with bile-stained areas.
o it often contains visible nodules and fibrosis.
 Microscopically:
o Hepatocyte swelling and necrosis.
o Mallory bodies: cytokeratin intermediate filaments
visible as eosinophilic cytoplasmic inclusions.
o Neutrophilic reaction: around degenerating hepatocytes
particularly those with Mallory bodies.
o Fibrosis.

13. Common pathological findings in alcoholic steatohepatitis. A. Ballooning and Mallory
bodies in damaged hepatocytes . B. Steatosis and polymorphonuclear infiltration (arrow).
C. Centrilobular fibrosis. D. Bridging fibrosis in cases of advanced disease.

14. Alcoholic liver cirrhosis:
 Final and irreversible form of alcoholic liver disease,
usually evolves slowly.
 Initially cirrhotic liver is yellow-tan, fatty, and enlarged;
later on brown ,shrunken, non fatty organ.
 Uniformly sized micronodules , but with time scattered
larger nodules create a "hobnail" appearance.
 Mallory bodies rarely evident ,thus it resembles cirrhosis
developing from viral hepatitis and other causes.

15. Metabolic liver diseases:
Nonalcoholic fatty liver (NAFL) :
 Patients are not heavy drinkers.
 Men and women are equally affected.
 Strong association with obesity, dyslipidemia, and
insulin resistance (type 2) diabetes.
 Patients are largely asymptomatic, with abnormalities
only in lab. tests (elevated serum aminotransferases
and/or Ɣ- glutamyl transpeptidase ).

16.  Liver biopsy shows :
• Steatosis (Large and small vesicles of fat)
• No hepatic inflammation,No hepatocyte death, No fibrosis.
Nonalcoholic steatohepatitis, or NASH:
 Liver biopsy shows:
• Steatosis.
• multifocal parenchymal inflammation, Mallory body ,
hepatocyte death and sinusoidal fibrosis.
• Cirrhosis : may occur.

17. HEMOCHROMATOSIS :
 Excessive accumulation of body iron, deposited
in parenchymal organs such as liver and pancreas.
 Tow major types :
o Hereditary ( primary ) hemochromatosis :
• autosomal-recessive inherited disorder.
• gene located on chromosome 6 called HFE gene.
o Acquired ( secondary ) hemochromatosis: include:-

18. • Parenteral iron overload:
 Transfusions.
 Iron-dextran injections.
• Ineffective erythropoiesis:
 β-Thalassemia.
 Sideroblastic anemia.
• Increased oral intake of iron.
• Congenital atransferrinemia.
• Chronic liver disease:
 Chronic alcoholic liver disease.
 Porphyria cutanea tarda.

19.  Fully developed cases exhibit:
(1) micronodular cirrhosis in all patients.
(2) diabetes mellitus in 75% to 80% of patients.
(3) skin pigmentation in 75% to 80% of patients.
 Symptoms first appear in fifth to sixth decades of life.
 Males predominate (5 - 7:1).

20.  Death may result from cirrhosis or cardiac disease.
 Risk for hepatocellular carcinoma is 200-fold increased.
 Screening involves :
• very high levels of serum iron and serum ferritin.
• liver biopsy if indicated.
• identification of HFE gene for genetic screening.
 Treatment: regular phlebotomy.

21. Morphology:
 Liver is slightly larger than normal, dense,
and chocolate brown.
 Iron evident as golden-yellow hemosiderin granules
which stain blue with Prussian blue stain.
 Inflammation is absent.
 Fibrous septa develop slowly, leading ultimately
to micronodular type of cirrhosis .

22. The dark brown color
of liver, pancreas
(bottom center) and
lymph nodes
(bottom right) in
middle-aged man
with hereditary
hemochromatosis .
liver cells bear within them Hemosiderin
granules .
Iron(Prussian Blue ) staining: blue granules of hemosiderin

23. WILSON DISEASE :
 Autosomal-recessive disorder marked by
accumulation of toxic levels of copper in
many tissues and organs.
 The gene is ATP7B, located on chromosome 13.
 Morphology:
• Fatty change in hepatocyte.
• acute hepatitis.
• chronic hepatitis.
• with progression cirrhosis will develop.

24. • Excess copper deposition demonstrated by special stain:
rhodanine stain for copper.
Liver histology - rhodamine staining for copper

25.  Clinical Features:
• rarely manifests before 6 years of age.
• most common presentation is:
 acute or chronic liver disease.
 Neuropsychiatric manifestations (mild behavioral changes,
frank psychosis, or Parkinson disease-like syndrome).
 Eye lesions called Kayser-Fleischer rings:
green to brown deposits of copper in cornea.

26.  Diagnosis:
• decrease in serum ceruloplasmin.
• increase in hepatic copper content.
• increased urinary excretion of copper.
• Serum copper levels are of no diagnostic value,
since tmay be low, normal, or elevated, depending
on stage of evolution of disease.
 Treatment: copper chelation therapy (D-penicillamine).

27. Summary:
1. Liver cirrhosis is the end stage of many chronic
liver diseases.
2. Liver abscesses are either due to parasitic infection
or pyogenic.
3. Alcoholic liver diseases include steatosis , ASH ,
and alcoholic liver cirrhosis.
4. Metabolic liver diseases include NAFL , NASH,
hemochromatosis, and wilson disease.

28. Questions:
1. Enumerate alcoholic liver diseases, and write
short assay on one of them?
2. How you diagnose wilson disease?
THANK YOU