"With ordinary talent and

extraordinary perseverance, all

things are attainable."
- Thomas E. Buxton

"Achievement is connected
with action, not in genes..…!”
- Conrad Hilton
 Pathology of
Hepatitis & Cirrhosis

Venkatesh Murthy Shashidhar

Associate Professor of Pathology
Fiji School of Medicine

A Commitment to Excellence…
Normal Liver
 Autopsy
 1.5 kg, wedge shape
 4 lobes, Right, left,
Caudate, Quadrate.
 Double blood supply
 Hepatic arteries
 Portal – Venous blood
 Acini / Portal triad.
 Lobules – central. V
Normal Liver - Infant
CT Upper abdomen - Normal
VHP- Upper abdomen
Normal Liver - Microscopy
 Liver Functions:
 Metabolism – Carbohydrate, Fat & Protein
 Secretory – bile, Bile acids, salts & pigments
 Excretory – Bilirubin, drugs, toxins
 Synthesis – Albumin, coagulation factors
 Storage – Vitamins, carbohydrates etc.
 Detoxification – toxins, ammonia, etc.
 Jaundice
 Yellow discoloration of skin & sclera due to
excess serum bilirubin. >40umol/l, (3mg/dl)
 Conjugated & Unconjugated types
 Obstructive & Non Obstructive (clinical)
 Pre-Hepatic, Hepatic & Post Hepatic types
 Jaundice - Not necessarily liver disease *
Pathology of
Hepatitis
 Hepatitis:

 Hepatitis: Inflammation of Liver

 Viral, Alcohol, immune, Drugs & Toxins
 Biliary obstruction – gall stones.
 Acute, Chronic & Fulminant - types
 Viral Hepatitis –
 Specific – Heptitis A, B, C, D, E, & other
 Systemic - CMV, EBV, other.
 Pattern of Viral Hepatitis:
 Carrier state / Asymptomatic phase
 Acute hepatitis
 Chronic Hepatitis
 Chronic Persistent Hepatitis (CPH)
 Chronic Active Hepatitis (CAH)

 Fulminant hepatitis
 Cirrhosis
 Hepatocellular Carcinoma
Acute - Hepatitis - Chronic
 Acute Hepatitis:

 Swelling and Apoptosis

 Piecemeal or Bridging, panacinar necrosis
 Inflammation – lymphocytes, Macrophages
 Ground glass hepatocytes – HBV
 Mild fatty change – HCV
 Portal inflammation and Cholestasis
 Fulminant Hepatitis:
 Hepatic failure with in 2-3 weeks.
 Reactivation of chronic or acute hepatitis
 Massive necrosis, shrinkage, wrinkled
 Collapsed reticulin network
 Only portal tracts visible
 Little or massive inflammation – time
 More than a week – regenerative activity
 Complete recovery – or - cirrhosis.
 Chronic Hepatitis:

 Persistent & Active types. CPH/CAH

 Lymphoid aggregates
 Periportal fibrosis
 Necrosis with fibrosis – bridging fibrosis.
 Cirrhosis – regenerating nodules.
Acute viral Hepatitis:
Acute viral Hepatitis:
Acute viral Hepatitis:
Acute viral Hepatitis C:
Liver Biopsy – CPH:
Liver Biopsy – Cirrhosis
 Viral Hepatitis: Microbiology
Virus Hep-A Hep-B Hep-C

agent ssRNA dsDNA ssRNA

Transm. Feco-oral Parenteral Parenteral

Carrier None 0.1-1.0% 0.2-1.0%

state
Chronic None 5-10% >50%
Hepatitis
Pathology of
Alcoholic
Liver Disease
 Alcoholic Liver Injury:
 Ethyl alcohol : Common cause of
acute/Chronic liver disease
 Alcoholic Liver disease - Patterns
 Fatty change,
 Acute hepatitis (Mallory Hyalin)
 Chronic hepatitis with Portal fibrosis
 Cirrhosis, Chronic Liver failure

 All reversible except cirrhosis stage.

 Alcoholic Liver Injury: Pathogenesis

 Acetaldehyde – metabolite – hepatotoxic

 Diversion of metabolism – fat storage.
 Oxidation of ethanol NAD to NADH. NAD is
required for the oxidation of fat..
 Increased peripheral release of fatty acids.
 Inflammation, Portal bridging fibrosis
 Stimulates collagen synthesis – fibrosis.
 Micronodular cirrhosis.
Alcoholic Liver Damage
Alcoholic Fatty Liver
Steatosis in Alcoholism
Alcoholic Fatty Liver
Alcoholic Fatty Liver
Cirrhosis in Alcoholism
Alcoholic Cirrhosis
 Bilirubin
Metabolism
•Blood
•Conjugated &
Conjugated
•Urine – Urobilinogen
•Stool – Stercobilin
 Common Causes of Jaundice

 Pre Hepatic (Acholuric) - Hemolytic

 Unconjugated/Indirect Bil, pale urine
 Hepatic – Viral, alcohol, toxins, drugs
 Liver damage - unconjugated
 Swelling, canalicular obstruction - Conjugated
 Post Hepatic (Obstructive) – Stone, tumor
 Conjugated/Direct Bil, High colored urine,
Jaundice
Jaundice
 ‘Time’ is the best kept
secret of the rich..!
– Jim Rohn
Pathology of
Alcoholic
Liver Disease
 Definition:

1. Diffuse disorder of liver characterised by;

2. Complete loss of normal architecture,
3. Replaced by extensive fibrosis with,
4. Regenerating parenchymal nodules.
 Introduction

 Cirrhosis is common end result of many

chronic liver disorders.
 Diffuse scarring of liver – follows
hepatocellular necrosis of hepatitis.
 Inflammtion – healing with fibrosis -
Regeneration of remaining hepatocytes form
regenerating nodules.
 Loss of normal architecture & function.
Normal Liver
Cirrhosis
Normal Liver Histology

CV

PT
 Cirrhosis

Fibrosis

Regenerating Nodule
 Etiology of Cirrhosis
 Alcoholic liver disease 60-70%
 Viral hepatitis 10%
 Biliary disease 5-10%
 Primary hemochromatosis 5%
 Cryptogenic cirrhosis 10-15%
 Wilson’s, 1AT def rare
 Pathogenesis:
 Hepatocyte injury leading to necrosis.
 Alcohol, virus, drugs, toxins, genetic etc..

 Chronic inflammation - (hepatitis).

 Bridging fibrosis.
 Regeneration of remaining hepatocytes
Proliferate as round nodules.
 Loss of vascular arrangement results in
regenerating hepatocytes ineffective.
 Cirrhosis Features:
 Liver Failure
 Parenchymal regeneration but why …..??.
 Portal obstruction, Porta systemic shunts…
 Portal hypertension, Splenomegaly
 Jaundice, Coagulopathy, hypoproteinemia,
toxemia, Encephalopathy,
Pathogenesis of Hepatic Encephalopathy

BRAIN

Porta systemic
shunts

LIVER

Toxic N2 metabolites
From Intestines
Micronodular cirrhosis
Ascitis in Cirrhosis
Ascitis in Cirrhosis
Micronodular cirrhosis:
Micronodular cirrhosis:
Alcoholic Hepatitis
Macronodular Cirrhosis
Liver Biopsy – Cirrhosis
Liver Biopsy – Cirrhosis:
Nutmeg Liver-Cardiac Sclerosis
 Clinical Features
 Hepatocellular failure.
 Malnutrition, low albumin & clotting factors,
bleeding.
 Hepatic encephalopathy.

 Portal hypertension.
 Ascites, Porta systemic shunts, varices,
splenomegaly.
 Bleeding in Liver disease:
 vitamin K – in liver gamma-carboxyglutamic
acid – for coagulation factors II, VII, IX, and X.
 Liver disease  factor VII is the first to go 
so the defect will appear initially in the
extrinsic pathway, i.e., abnormal PT. When
severe it affects both pathways.
Cirrhosis
Clinical
Features
Gynaecomastia in cirrhosis
Porta-systemic anastomosis:
Prominent abdominal veins.
MRI Cirrhosis
 Complications:

 Congestive splenomegaly.
 Bleeding varices.
 Hepatocellular failure.
 Hepatic encephalitis / hepatic coma.
 Hepatocellular carcinoma.
Hepatocellular Carcinoma
 Conclusions:
 Common end result of diffuse liver damage.
(Viral hepatitis, Alcohol, congenital, drugs, toxins & Idiopathic)

 Characterised by diffuse loss of architecture.

 Fibrous bands & regenerating nodules distort
and abstruct blood flow. (inefficient function)
 Hepatocellular insufficiency & portal
hypertension.
 Shrunken, scarred liver, ascitis,
spleenomegaly, liver failure, CNS toxicity.
 Conclusions: Hepatitis.
 Hepatitis – Alcohol, Virus (ABCD), Drugs…
 Hepatocyte damage – inflammation
 Acute / Chronic (Active / Persistent)
 Fever, Jaundice, Malaise, Fat intolerance.
 Complications.
 Alcohol – NAD, Acetaldehyde – metabolism
 Fatty liver  Necrosis  Cirrhosis.
Learn from the
mistakes of others.
You can't live long
enough to make them
all yourself…!