Practical session [14]-Pathology of Liver
(Objectives)
• Identify morphological changes (gross
and microscopic) in Hepatitis, Alcoholic
liver disease and Hepatocellular
carcinoma
Acute
Hepatitis
LIVER BIOPSY:
The diagnosis
is usually based on the
clinical presentation and laboratory results, serologic tests.
a cellular infiltrate throughout the hepatic lobule-
chronic, inflammatory cellular infiltrate and Kupffer
cell hypertrophy and hyperplasia.
Acute hepatitis- MORPHOLOGY
cells injury& ballooning
Cholestasis& MQ reaction
Lobular inflammation
Councilman, or acidophilic, bodies
Questions
• ◆ What is the most likely diagnosis?
• ◆ What are the possible etiologies of this
disorder?
• ◆ What other tests would be appropriate?
• ◆ What are the possible complications?
• ◆ Describe the morphologic features of this
condition?
Questions
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◆ What is the most likely diagnosis?
Acute viral hepatitis (hepatitis B virus)
◆ What are the possible etiologies of this disorder?
Hepatitis B virus- acute infection
◆ What other tests would be appropriate?
PCR
◆ What are the possible complications?
Progress to Chronic hepatitis or Fulminant hepatitis
with confluent necrosis
• ◆ Describe the morphologic features of this
condition? >>>>………………………………
Acute hepatitis B virus- morphology
• Lobular hepatitis: a cellular infiltrate throughout the
hepatic lobule
• Chronic, inflammatory cellular infiltrate .
• Loss of normal architecture .
• Ballooning of the cytoplasm in degenerating
hepatocyte.
• Kupffer cell hypertrophy and hyperplasia.
• Hepatocyte necrosis - individually necrotic or
apoptotic hepatocytes= Councilman bodies
• Regenerating hepatocytes are large, frequently
containing multiple nuclei.
• Cholestasis
Case No 2
• Over the past 4 days, a previously healthy, 38-yearold woman has become increasingly obtunded.
• On physical examination, she has scleral icterus.
She is afebrile, and her BP is 110/55 mm Hg.
• Laboratory findings show a PT of 38 seconds,
serum ALT of 1854 U/L, AST of 1621 U/L, albumin of
1.8 g/dL, and total protein of 4.8 g/dL withraised
plasma ammonia (> 100 IU/L) “hyperammonemia”?
• From history what’ the most likely diagnosis?
• Mention other helpful serological investigations?
• Describe the expected liver morphologic changes?
Case 2: Fulminant hepatitis: liver is smaller than
normal, due to extensive areas of liver necrosis. The surface is
soft with a wrinkled capsular surface.
Acute fulminant hepatitis with massive hepatic necrosis.
Fulminant Hepatitis morphology
• FH-indicates that the liver has sustained severe
damage (loss of function of 80-90% of liver cells)
• Location: Entire liver or only random areas may be
involved.
• Severe necrotizing process.
• Inflammatory response: little inflammatory
reaction.
• Macrophages response: Massive influx of
macrophages for phagocytosis
• Ductular reaction: If pt. survive hepatocytes
replication started with ductular reaction
Questions
• ◆ What is the most likely diagnosis?
Fulminant hepatitis with massive hepatic necrosis
• ◆ What are the possible etiologies of this disorder?
Acute hepatitis A, acute HBV (+\- HDV), other viruses.
• ◆ Can you name some causes, other than hepatotropic virus infections,
that can cause a similar clinical picture?
1- Toxin- excessive alcohol intake(severe alcoholic hepatitis.
2- Drugs(paracetamol , Aspirin overdose).
3-Hereditary copper accumulation (Wilson's disease)
4- Infection (bacterial….)
• ◆ What’s the complications of this condition?
Renal failure, coagulopathy, cerebral edema, encephalopathy
Haemodynamic distrubance, Adrenal insufficiently-hepatorenal syn
• ◆ Describe themorphologic features of this condition?
There is massive necrosis of hepatocytes throughout the lobules in fulminant
hepatitis………….
Case No 3
• A 34-year-old woman known case of Hepatitis
C virus- HCV presented with fatigue for month
ago. LFT along with liver biopsy done for
follow-up, staging and grading:
_____________________________________
• 1- describe the morphologic features?
• 2- mention other differentials for similar changes?
• 3- What’s the commonest complications of this
conditions?
Chronic Hepatitis: HCV infection
Liver biopsylower +power
Portal hepatitis
focal steatosis
Cells necrosis+ inflammation + focal steatosis
Chronic Hepatitis: Piecemeal necrosis
Fibrosis with incomplete septa
Answers-HCV
I. Describe the morphologic features?
1- Portal hepatitis with acinar extension (chronic
inflammatory cells infiltrates).
2- Cells death.
3-Steatosis (focal, diffuse) (mild, moderate, severe)
4- Interphase hepatitis (piecemeal necrosis).
5- Degree of fibrosis
II. Mention other differentials for similar changes?
• Alcohol, DM, Obesity, Malnutrition, AIH, Idiopathic.
III. What’s the commonest complications?
Cirrhosis, Liver failure, hepatocellular carcinoma.
Liver biopsy: Chronic viral hepatitis (HBV)
Immune-stain positive for HBsAg (right) : hepatocytes
show diffuse granular cytoplasm=(ground glass )
Hepatocytes nuclei Immune-stained positive
for HBc - HBV
Ground-glass appearance- Hepatitis B virus
Morphologic features of HBV-HDV:
1- Hepatocytes cells injury- necrosis (some time
progress to form Fulminant-confluent necrosis).
2- Ballooning hepatocytes degeneration with
eosinophilic "councilman body"
3- Inter-phase reaction\necrosis (piecemeal necrosis)
4- Hepatocytes- ground glass appearance, indicate
intra-cytoplasmic accumulation of HBsAg
5- Mixed chronic inflammatory cells infiltrates.
6- Fibrosis- varying degree
Case No 5
• A 41-year-old man has a history of drinking 1 to 2
liters of whisky per day for the past 20 years. He has
had numerous episodes of nausea and vomiting in
the past 5 years. He now experiences a bout of
prolonged vomiting, followed by massive
hematemesis. On physical examination his vital signs
are: T 36.9°C, P 110/min, RR 26/min, and BP 80/40 mm Hg
lying down. His heart has a regular rate and rhythm with no
murmurs and his lungs are clear to auscultation. There is
NO abdominal tenderness OR distension. Bowel sounds are
present. His stool is negative for occult blood.
1- LIVER US? 2- LFT? 3- VIRAL MARKER? 4-LIVER BIOPSY
Gross findings:
Liver is enlarged (hepatomegaly) and tender.
Alcoholic Fatty Liver: Lipid droplets accumulate in
hepatocytes (around hepatic venule) microvesicular or macrovesicular
macrovesicular steatosis
Fatty change: liver
Oil Red O stain for fat
Fall 10
A Jalan
26
Alcoholic Hepatitis:
The hallmark is the presence of neutrophils surrounding
Fall 10
necrotic hepatocytes + Mallory bodies.
27
Alcoholic hepatitis: Mallory's hyaline (Globular red hyaline
material within hepatocytes(
Alcoholic hepatitis
Neutrophils
Fall 10
Mallory body
A Jalan
29
Perivenular fibrosis
Alcoholic Hepatitis (Alcoholic
Steatohepatitis)- Morphology
• Gross findings:
– Liver is enlarged (hepatomegaly) and tender.
• Microscopic findings:
1. Hepatocyte swelling
2. Focal liver cell necrosis.
3. Mallory bodies* -characteristic
• Damaged cytokeratin intermediate filaments in hepatocytes
4. Fatty change
5. Neutrophilic infiltration
6. Perivenular fibrosis* : fibrosis developing around terminal hepatic
venule  by prominent activation of sinusoidal stellate cells and
portal tract fibroblasts.
Questions
• ◆ What is the most likely diagnosis?
• ◆ What are the possible etiologies of this
disorder?
• ◆ What other tests would be appropriate?
• ◆ What are the possible complications?
• ◆ Describe the morphologic features of this
condition?
Gross: Post-hepatitis cirrhosis
The characteristic diffuse nodularity of the surface reflects the
interplay between nodular regeneration and scarring [mixed
nodularity= macro& micronodularity].The greenish tint of some
nodules is due to bile stasis
Microscopic: Diffuse nodularity [mixed nodularity= macro&
micronodularity], varying entrapped in blue-staining fibrous tissue.
Bridges extend through sinusoids from central to portal regions as well
as from portal tract to portal tract.
Answers
• ◆ What is the most likely diagnosis?
Chronic hepatitis/with transition to cirrhosis.
• ◆ What are the possible etiologies of this disorder?
Most commonly caused by:
• Progressive Alcohol hepatitis
• chronic viral infection (HCV, HBV)or;
• chronic toxin exposure (alcohol), (Drugs), ect..
• ◆ What other tests would be appropriate?
1-Hepatitis virus serologies: ICT-rapid, ELISA, PCR.
2- Liver biopsy
• ◆ What are the possible complications?
• 1. Hepatic failure, 2.gastrointestinal bleeding, 3. HCC.
Case No 7
• A 56-year-old man from China, has experienced
fatigue and a 10-kg weight loss over the past 3
months.
• Physical examination yields no remarkable findings.
Laboratory test results revealed increase level of
AFP (650 nanograms per milliliter (ng/mL)) and
positive for HBsAg& Anti HBs.
• Negative for HBc Ag, Anti HBc, anti- HCV and antiHAV.
• Abdominal CT scan shows a 10-cm solid mass in
the nodular liver.
Questions
• ◆ What is the most likely diagnosis?
• ◆ What are the possible etiologies of this
disorder?
• ◆ Which of the following mechanisms is most
likely responsible for the development of this
lesion?
• ◆ What other tests would be appropriate?
• ◆ What are the possible complications?
• ◆ Describe the morphologic features of this
condition?
Liver tumor - GROSS
Neoplasm is large and bulky and has a greenish cast because
it contains bile. To the right of the main mass are smaller
satellite nodules, indicate local aggressiveness.
Liver tumor - GROSS
Liver: Large whitish mass with satellite extension to
adjacent tissue
Microscopic app.: B. well-differentiated tumor cells
are arranged in nests\acinar with bile pigmentation
Liver tumour - GROSS
Hepatocellular carcinoma
Hepatocellular carcinoma
Microscopic app.: Section of liver nodule: malignant
cells in Branching trabeculae
HCC-Fibrolamellar carcinoma
A specimen showing a demarcated hard, Scirrhous nodule
B, nests& cords of malignant polygonal hepatocytes
separated by dense bundles of collagen
Questions
• ◆ What is the most likely diagnosis?
1-Hepatocellular carcinoma, 2- Fibrolamellar type
• ◆ What are the possible etiologies of this disorder? 1chronic viral hepatitis HBV
• ◆ Which of the following mechanisms is most likely
responsible for the development of this lesion? repeated
cycles of liver cell death and regeneration. This repeated
cycling increases the risk of accumulating mutations during
several rounds of cell division.
• ◆ What other tests would be appropriate? AFP level
• ◆ What are the possible complications?
• …………………………………..
• ◆ Describe the morphologic features of this condition?
• …………………………………