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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

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 agent Hep-A ssRNA Hep-B dsDNA Hep-C ssRNA

Transm.
Carrier state Chronic Hepatitis

Feco-oral
None None

Parenteral
0.1-1.0% 5-10%

Parenteral
0.2-1.0% >50%

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
Biliary disease

10%
5-10%

Primary hemochromatosis
Cryptogenic cirrhosis

5%
10-15%

Wilsons, 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.

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