Practical session 15 -Pathology of Liver
Practical session -Pathology of Liver
(Objectives)
• By the end of this session, students will
be able to:
• Identify morphological changes (gross
and microscopic) in Hepatitis, Alcoholic
liver disease and Hepatocellular
carcinoma
• Suggested reading: Robbin’s Basic Pathology,
8th Ed. Page-639-648, 663-666 & 671-672
Case No 1
• A 30-year-old man presented to the local clinic
complaining of anorexia, nausea, vomiting, and
malaise. He had a history of intravenous drug use.
He admitted to drinking alcohol.
• Physical examination revealed a thin man who
looked ill. His BP-110/80 lying down,
which decreased to 90/60 upon sitting. His T37.5C, and his RR was 20. His eyes were yellow.
There was mild right UQ abdominal tenderness.
The liver is slightly enlarged 3 cm below the costal.
No spleen was palpated. Cardiac, respiratory, and
other parts of the examination were normal.
PT =
13 second
Aspartate aminotransferase : 1240 U/L
Alanine aminotransferase = 1650 U/L
Alkaline phosphatase =
198 U/L
Total bilirubin=
12.0 mg/dL
Direct bilirubin=
Anti-HAV
HBsAg
Anti-HBs
Anti-HBc
Anti-HCV
Anti-delta virus
Anti-HIV
8.0 mg/dL
(11–15 s)
(8–20 U/L)
(8–20 U/L)
(20–70 U/L)
(0.1–1.0 mg/dL)
(0.0–0.3 mg/dL)
Total - positive; IgM
fraction - negative
Positive
Negative
Total - positive; IgM
fraction - positive
Negative
Sent to outside lab
Negative
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
Lobular inflammation
Acute Hepatitis ; Cholestasis& MQ reaction
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?
Questions
• From history what’ the most likely diagnosis?
• Acute fulminant hepatitis with massive hepatic necrosis.
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.
Questions
• ◆ What is the etiology of this condition?
• ◆ Can you name some causes, other than
hepatotropic virus infections, that can cause a
similar clinical picture?
• ◆ Describe the morphologic features of this
condition?
• ◆ What’s the complications of this condition?
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………….
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
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- portal inflammation
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.
Case No 4
• A 27-year-old man with a history of intravenous drug
use has been known to be infected with hepatitis B
virus for the past 6 years and not ill. He is seen in the
emergency department because he has had nausea,
vomiting, and passage of dark-colored urine for the
past week.
• Physical examination shows scleral icterus and mild
jaundice. There are recent and healed track marks in
the right antecubital fossa. Neurologic examination
shows a confused, oriented only to person.
• Laboratory studies show total protein, 5 g/Dl
(decreased); albumin, 2.7 g/dL (decreased) ; ……………
PT =
13 second
Aspartate aminotransferase : 1240 U/L
Alanine aminotransferase = 1650 U/L
Alkaline phosphatase =
198 U/L
Total bilirubin=
12.0 mg/dL
Direct bilirubin=
Anti-HAV
HBsAg
Anti-HBs
Anti-HBc
Anti-HCV
Anti-delta virus
Anti-HIV
8.0 mg/dL
(11–15 s)
(8–20 U/L)
(8–20 U/L)
(20–70 U/L)
(0.1–1.0 mg/dL)
(0.0–0.3 mg/dL)
Total - positive; IgM
fraction - negative
Positive
Positive
Total –IgG positive ; IgM
fraction - Negative
Negative
Pending??
Negative
Hepatitis: Areas of necrosis &collapse of lobules:
ill-defined areas ( pale yellow& Hemorrhagic)
Liver biopsy: Chronic viral hepatitis (HBV)
Hepatocytes nuclei Immune-stained positive for HBc
- HBV
Ground-glass appearance- Hepatitis B virus
Immune-stain positive for HBsAg (right) : hepatocytes
show diffuse granular cytoplasm=(ground glass )
Questions
• ◆ What is the most likely diagnosis?
• ◆ What are the possible etio-pathogenesis of this
disorder?
• ◆ What other tests would be appropriate?
• ◆ Mention the factor (s) predisposing to the poor
prognostic outcome of this condition?
• ◆ What amount of alcohol consumption is
required to develop alcoholic cirrhosis?
• ◆ What are the possible complications?
• ◆ Describe the morphologic features of this
condition?
Questions
• ◆ What is the most likely diagnosis?
• Chronic viral hepatitis (HBV) with Super-infection by
HDV
• ◆ What are the possible etiology?
• HBV infection (chronic) with HDV
• ◆ What other tests would be appropriate?
• Confirmatory- Recent infection by HDV infection-antiHDV IgM antibodies
• ◆ What are the possible complications?
• Cirrhosis, Liver failure, HCC
• ◆ Describe the morphologic features of this
condition? …………………….
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
Alcoholic Fatty Liver: Lipid droplets accumulate in
hepatocytes (around hepatic venule) microvesicular or macrovesicular
macrovesicular steatosis
Alcoholic hepatitis: Mallory's hyaline (Globular red hyaline
material within hepatocytes(
Questions
• ◆ What is the most likely diagnosis?
• ◆ What are the possible etio-pathogenesis of this
disorder?
• ◆ What other tests would be appropriate?
• ◆ Mention the factor (s) predisposing to the poor
prognostic outcome of this condition?
• ◆ What amount of alcohol consumption is
required to develop alcoholic cirrhosis?
• ◆ What are the possible complications?
• ◆ Describe the morphologic features of this
condition?
Questions
◆ What is the most likely diagnosis?
Chronic alcoholic hepatitis
◆ What are the possible etiologies of this disorder?
Excess consumption of alcohol lead to………………………..
◆ What other tests would be appropriate?
VIRAL MARKER (HBV, HCV) - “ELISA+ PCR”
Screening for AIH- (ANA, Liver kidney microsome (LKM-1)
antibody (IgG):
“ELISA+IF”
◆ Mention the factor (s) predisposing to the poor prognostic
outcome of this condition?
The severity &prognosis depends on the amount, pattern and
duration of alcohol consumption.
◆ What are the possible complications?
Liver cirrhosis, Hepatic failure, HCC
◆ Describe the morphologic features of this condition? …….
Alcoholic hepatitis- morphology
• Macroscopic -varying from liver with steatosis to
cirrhotic liver
• The liver is enlarged, yellow, soft, and greasy, due to
accumulation of fat in the hepatocytes.
• Microscopic:
• Lipid droplets accumulate in hepatocytes (around
hepatic venule) microvesicular or macrovesicular.
• Cells injury
• Intra-cellular accumulation (hemosidrin)+ cholestasis
• Mallory bodies
• Neutrophilic reaction.
• Fibrosis
Alcoholic Liver Injury: Pathogenesis
• Daily intake of 80 gm or more of ethanol generates
significant risk for severe hepatic injury, and daily
ingestion of 160 gm or more for 10 to 20 years is
associated more consistently with severe injury.
• Hepatic steatosis lead to :
1. Excess reduced NADH producton by the two major
enzymes : Alcohol dehydrogenase and acetaldehyde
dehydrogenase;   triglycerides synthesis
2. Impaired production and secretion of lipoproteins by
hepatocytes.
3. Increased catabolism of fat throughout the body
• Liver cell necrosis
• Acute Inflammation
• Stimulates collagen synthesis – fibrosis.
• Micronodular cirrhosis.
• Case No 6
• A 57-year-old man presents with fatigue for
several months. He does not take any medications
and denies using illegal drugs. He underwent a
blood transfusion with several units in 1982 after
an automobile accident.
• Physical examination reveals generalized jaundice,
a firm nodular liver edge just below the right costal
margin, and a mildly protuberant abdomen with a
fluid wave.
Laboratory study
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Patient’s Value Reference Range
RR
Alanine aminotransferase (ALT): 80 U/L (8–20 U/L)
Alkaline phosphatase:
60 U/L (20–70 U/L)
Aspartate aminotransferase(AST): 50U/L (8–20 U/L)
Albumin:
2.0 g/dl (3.5–5.5g/dL)
Bilirubin, serum, total:
5 mg/dL (0.1–1.0 mg/dL)
Bilirubin, serum, direct: 4.2 mg/dL (0.0–0.3 mg/dL)
Prothrombin time (PT):
28 s (11–15 s)
Partial thromboplastin time (PTT): 50 s (28–40 s)
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?
Post-hepatitis cirrhosis
Mixed mcaro-and micro- cirrhotic nodules
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.
Morphology of cirrhosis
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Nodules and fibrosis (defining features)
Fragmentation of the specimen
Abnormal structure (reticulin)
Clonal variation in hepatocyte size
Evidence of hyperplasia
Large-cell and small-cell change (dysplasia)
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 tumour - 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.
Liver: Large whitish mass with satellite extension to
adjacent tissue
B. well-differentiated tumor cells are arranged in
nests\acinar with bile pigmentation
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?
• …………………………………