DR. ROOPAM JAIN PROFESSOR & HEAD DEPARTMENT OF PATHOLOGY & BLOOD BANK

1. THE LIVER
& GALLBLADDER
PATHOLOGY
DR ROOPAM JAIN
PROFESSOR & HEAD, PATHOLOGY

2. Infectious Disorders
VIRAL
HEPATITIS

3. CLINICOPATHOLOGIC
SPECTRUM
• The various clinical patterns and pathologic consequences of different
hepatotropic viruses can be considered under the following headings:
• i) Carrier state
• ii) Asymptomatic infection
• iii) Acute hepatitis
• iv) Chronic hepatitis
• v) Fulminant hepatitis (Submassive to massive necrosis)

4. 1. Carrier State
• An asymptomatic individual without manifest disease, harbouring
infection with hepatotropic virus and capable of transmitting it is called
carrier state.
• There can be 2 types of carriers:
• 1. An ‘asymptomatic healthy carrier’ who does not suffer from ill-eff ects
of the virus infection but is capable of transmitting.
• 2. An ‘asymptomatic carrier with chronic disease’ capable of transmitting
the organisms.

5. 2. Asymptomatic Infection
• These are cases who are detected incidentally to have infection with
one of the hepatitis viruses
• raised serum transaminases
• detection of the presence of antibodies but are otherwise
asymptomatic.

6. 3. Acute Hepatitis
The most common consequence of all hepatotropic viruses is acute
inflammatory involvement of the entire liver.
Clinically, acute hepatitis is categorised into 4 phases:
incubation period, pre-icteric phase, icteric phase and posticteric phase

7. 3. Acute Hepatitis
MORPHOLOGIC FEATURES
• Grossly - liver is slightly enlarged, soft and greenish.
• Histologically, (Fig):
• 1. Hepatocellular injury - liver cell injury but it is most marked in zone
3 (centrilobular zone):
• ballooning degeneration
• Councilman body or acidophil body
• dropout hepatocellular necrosis
• Bridging necrosis is a more severe form of hepatocellular injury in
acute viral hepatitis and may progress to fulminant hepatitis or
chronic hepatitis

8. • 2. Inflammatory infiltrate - There is infiltration by mononuclear
inflammatory cells, usually in the portal tracts, but may permeate into the
lobules.
• 3. Kupffer cell hyperplasia - There is reactive hyperplasia of Kupffer
cells
• 4. Cholestasis - Biliary stasis is usually not severe in viral hepatitis
• 5. Regeneration - As a result of necrosis of hepatocytes,

9. Acute viral hepatitis
The predominant histologic changes are: variable degree of necrosis of
hepatocytes, most marked in zone 3 (centrilobular); & mononuclear cellular
infiltrate in the lobule.
Mild degree of liver cell necrosis is seen as ballooning degeneration while
acidophilic Councilman bodies (inbox) are indicative of more severe liver cell injury.

10. 4. Chronic viral hepatitis:
• Symptomatic, biochemical or serologic evidence of continuing or relapsing
disease for > 6 months with histologic documentation of inflammation and
necrosis.
• Majority of cases of chronic hepatitis are the result of infection with hepato
tropic viruses
• hepatitis B,
• hepatitis C &
• combined hepatitis B and hepatitis D infection.
• some non-viral causes of chronic hepatitis include:
• Wilson’s disease,
• alpha-1-antitrypsin deficiency,
• chronic alcoholism,
• drug-induced injury
• autoimmune diseases

11. 4. Chronic viral hepatitis:
• Chronic hepatitis constitutes a “Carrier State”.
• Healthy carriers are individuals having the virus without adverse effects.
• Vertical transmission with HBV produces carrier in 90-95% cases.
• The most common symptom is fatigue;
• less common symptoms are malaise, loss of appetite, and occasionally
mild jaundice.

13. The portal tract is expanded due to increased lymphomononuclear
inflammatory cells which are seen to breach the limiting plate
(i.e. hepatocytes at the interface of portal tract and lobule are destroyed)

14. 4. Chronic viral hepatitis:
MORPHOLOGIC FEATURES
• The pathologic features are common to both HBV and HCV infection
• 1. Piecemeal necrosis
• i) Necrosed hepatocytes
• ii) infiltration of lymphocytes, plasma cells and macrophages
• 2. Portal tract lesions
• i) Inflammatory cell infiltration by lymphocytes, plasma cells and
macrophages (triaditis).
• ii) Proliferated bile ductules in the expanded portal tracts.

15. 4. Chronic viral hepatitis:
MORPHOLOGIC FEATURES
• 3. Intralobular lesions
• i) focal areas of necrosis & inflammation within the hepatic parenchyma.
• ii) Scattered acidophilic bodies in the lobule.
• iii) Kupffer cell hyperplasia.
• iv) bridging necrosis
• v) Regenerative changes
• 4. Bridging fibrosis

16. 4. Chronic viral hepatitis:
• A histologic grading of chronic hepatitis:
A. Necroinflammatory activity:
Periportal necrosis
Intralobular necrosis, focal or confluent
Extent and depth of portal inflammation
B. Stage of fibrosis:
• Extent and density of fibrosis (ranging from score 0 as ‘no fibrosis’ to
score 6 as ‘cirrhosis’).

17. 4. Chronic viral hepatitis:
CLINICAL FEATURES
• The clinical features of chronic hepatitis are quite variable ranging from
mild disease to fullblown picture of cirrhosis.
• i) Mild chronic hepatitis shows only slight but persistent elevation of
transaminases (‘transaminitis’) with fatigue, malaise and loss of appetite.
• ii) mild hepatomegaly, hepatic tenderness and mild splenomegaly.
• iii) Laboratory fi ndings - prolonged prothrombin time,
hyperbilirubinaemia, hyperglobulinaemia and markedly elevated alkaline
phosphatase.

18. 5. Fulminant Hepatitis
(Submassive to Massive Necrosis)
• Fulminant hepatitis is the most severe form of acute hepatitis in which
there is rapidly progressive hepatocellular failure.
• Two patterns are recognised
• submassive necrosis having a less rapid course extending up to 3
months
• massive necrosis in which the liver failure is rapid and fulminant
occurring in 2-3 weeks

19. Fulminant hepatitis
wiping out of liver lobules with only collapsed reticulin framework

20. Clinicopathologic course of HBV and HCV infection

21. CHOLANGITIS
• inflammation of the extrahepatic or intrahepatic bile ducts, or both.
• two main types of cholangitis—
• Pyogenic cholangitis
• Primary sclerosing cholangitis

22. Pyogenic Cholangitis
• Cholangitis occurring secondary to obstruction of a major extrahepatic
duct causes pyogenic cholangitis.
• Most commonly, the obstruction is from impacted gallstone; other causes
are carcinoma arising in the extrahepatic ducts, carcinoma head of
pancreas, acute pancreatitis and inflammatory strictures in the bile duct.
• Bacteria gain entry to the obstructed duct and proliferate in the bile.
• Infection spreads along the branches of obstructed duct and reaches the
liver, termed ascending cholangitis.
• common infecting bacteria are - E. coli, Klebsiella & Enterobacter

23. PYOGENIC LIVER ABSCESS
• Most liver abscesses are of bacterial (pyogenic) origin
• less often they are amoebic, hydatid and rarely actinomycotic.
• uncommon due to improved diagnostic facilities & early use of antibiotics.
• Incidence is higher in old age & in immunosuppressed patients such as in
AIDS, transplant recipients and those on intensive chemotherapy

24. PYOGENIC LIVER ABSCESS
• modes of entry:
• 1. Ascending cholangitis through ascending infection in the biliary
tract due to obstruction
• 2. Portal pyaemia by means of spread of pelvic or GI infection
resulting in portal pylephlebitis or septic emboli
• 3. Septicaemia through spread by hepatic artery.
• 4. Direct infection resulting in solitary liver abscess
• 5. Iatrogenic causes
• 6. Cryptogenic from unknown causes, especially in the elderly.

25. PYOGENIC LIVER ABSCESS
• The commonest infecting organisms are
• gram-negative bacteria chiefly E. coli
• Pseudomonas,
• Klebsiella,
• Enterobacter
• number of anaerobic organisms, bacteroides and actinomyces

26. PYOGENIC LIVER ABSCESS

27. PYOGENIC LIVER ABSCESS
• clinically characterised by
• pain in the right upper quadrant,
• fever,
• tender hepatomegaly and
• sometimes jaundice.
• Laboratory examination reveals
• leucocytosis,
• elevated serum alkaline phosphatase,
• Hypoalbuminaemia
• positive blood culture

28. PYOGENIC LIVER ABSCESS
• occur as single or multiple yellow abscesses, 1 cm or more in diameter
• abscesses are particularly common in right lobe of the liver
• adjacent viable area shows pus and blood clots in the portal vein,
inflammation, congestion and proliferating fibroblasts.

29. AMOEBIC LIVER ABSCESS
• less common than pyogenic liver abscesses and have many similar
features.
• caused by the spread of Entamoeba histolytica from intestinal lesions.
• The trophozoite form of amoebae in the colon invade the colonic mucosa
forming flask-shaped ulcers.
• Amoebae multiply and block small intrahepatic portal radicles resulting in
infarction necrosis of the adjacent liver parenchyma.
• Cysts of E. histolytica in stools are present in only 15% of patients of
hepatic amoebiasis.

30. AMOEBIC LIVER ABSCESS
• Intermittent low-grade fever, pain and tenderness in the liver area
are common presenting features.
• A positive haemagglutination test (sensitive & diagnosis of amoebic
liver abscess)

31. AMOEBIC LIVER ABSCESS
Commonly solitary & its wall is irregular & necrotic

32. AMOEBIC LIVER ABSCESS
MORPHOLOGIC FEATURES
Grossly
• Amoebic liver abscess may vary greatly in size but is generally of the
size of an orange.
• centre of the abscess contains large necrotic area having reddish-
brown, thick pus resembling anchovy or chocolate sauce.
Histologically,
• The necrotic area consists of degenerated liver cells, leucocytes, red
blood cells, strands of connective tissue and debris.
• Amoebae are most easily found in the liver tissue at the margin of
abscess.
• PAS-staining is employed to confirm the trophozoites of E. histolytica.

33. HYDATID DISEASE (ECHINOCOCCOSIS)
• infection by the larval cyst stage of the tapeworm, Echinococcus
granulosus.
• dog is the common definite host,
• man, sheep and cattle are the intermediate hosts.
• dog is infected by eating the viscera of sheep containing hydatid cysts
• The infected faeces of the dog contaminate grass and farmland from
where the ova are ingested by sheep, pigs and man.
• man can acquire infection by handling dogs as well as by eating
contaminated vegetables.

34. HYDATID DISEASE (ECHINOCOCCOSIS)
• uncomplicated hydatid cyst of the liver may be silent or may produce dull
ache in the liver area and some abdominal distension.
• Complications of hydatid cyst include its rupture (e.g. into the peritoneal
cavity, bile ducts and lungs), secondary infection and hydatid allergy due
to sensitisation of the host with cyst fluid.
The diagnosis
• peripheral blood eosinophilia,
• radiologic examination and
• serologic tests such as indirect haemagglutination test & Casoni skin test

35. HYDATID DISEASE (ECHINOCOCCOSIS) MORPHOLOGIC
FEATURES
• Hydatid cyst grows slowly and may eventually attain a size over 10 cm in
diameter in about 5 years.
• E. granulosus generally causes unilocular hydatid cyst while E.
multilocularis results in multilocular or alveolar hydatid disease in the
liver.
• The cyst wall is composed of 3 distinguishable zones—
• outer pericyst,
• intermediate characteristic ectocyst
• inner endocyst

36. HYDATID DISEASE (ECHINOCOCCOSIS) MORPHOLOGIC
FEATURES
• Hydatid sand is the grain-like material composed of numerous scolices
present in the hydatid fluid.
• Hydatid fluid, also contains antigenic proteins so that its liberation into
circulation gives rise to pronounced eosinophilia or may cause
anaphylaxis.

37. HYDATID DISEASE (ECHINOCOCCOSIS) MORPHOLOGIC
FEATURES

38. Microscopy shows 3 layers in the wall of hydatid cyst
Inbox in the right photomicrograph shows a scolex with a
row of hooklets