137 - Patterns of liver injury 3: Cirrhosis and Portal Hypertension

Question 1

Autoimmune hepatitis
1
2 a, b, c, d, e

Answer 1

1) Aggressive form of chronic hepatitis
2) Features of autoimmune conditions:
a) Mostly female (80%)
b) Genetic predisposition
c) Association with other autoimmune diseases
d) Presence of serum autoantibodies
e) Therapeutic response to immune suppression.

Question 2

Progression rate of autoimmune hepatitis to cirrhosis

Answer 2

85% over 5 years

Question 3

Types of autoimmune hepatitis
1
2

Answer 3

• Type 1 (most common) occurs in adult women and associated with anti-smooth muscle antibodies (ASMA)
• Type 2 occurs in children and teenagers associated with anti-liver kidney microsome (LKM-1)

Question 4

Patterns of injury of autoimmune hepatitis
1
2

Answer 4

• Severe early phase with destruction of liver cells: presents as acute hepatitis clinically and pathologically.
• Fibrosis (scarring) develops rapidly in the areas of collapse (unlike most cases of chronic viral hepatitis, where fibrosis accumulates slowly).

Question 5

How is the fibrosis in autoimmunehepatitis unlike other cases of chronic hepatitis?

Answer 5

Fibrosis develops rapidly in areas of collapse (unlike most cases of chronic viral hepatitis, where fibrosis accumulates slowly)

Question 6

Definition of cirrhosis
1
2
3

Answer 6

• Conversion of the liver into nodules of regenerating hepatocytes surrounded by bands of fibrous (scar) tissue
• Diffuse (involves the whole liver)
• Vascular shunting
An anatomical term describing the end-state of many chronic liver conditions

Question 7

End-stage chronic liver failure

Answer 7

Liver can no longer perform its functions

Question 8

Differences between end-stage liver failure and cirrhosis
1
2

Answer 8

The two are often associated, however:
• Not all patients with ESCLF have cirrhosis (e.g. primary sclerosing cholangitis)

• Not all patient with cirrhosis have ESCLF (treated AIH, suppressed HBV or cured HCV may be clinically stable even when cirrhosis is present)

Question 9

Gross appearance of a cirrhotic liver
1
2
3

Answer 9

1) Coarsely nodular surface (nodules up to 2cm)
2) Nodules are well-demarcated
3) Nodules can be green from marked cholestasis

Question 10

Adult causes of cirrhosis
1
2
3
4
5
6
7

Answer 10

• Alcoholic liver disease
• Non-alcoholic steatohepatitis
• Chronic viral hepatitis B and C
• Autoimmune hepatitis
• Chronic biliary disease – primary sclerosing cholangitis and primary biliary cirrhosis
• Metabolic – Wilson’s disease (genetic copper toxicosis) Haemochromatosis, alpha-1-antitrypsin deficiency
• Drugs – methotrexate, methyldopa

Question 11

Variables in cirrhosis appearance

Answer 11

1) Nodule size
2) Pattern of scarring
3) Degree of liver tissue destruction (parenchyma extinction).
4) Thrombosis of vessels especially portal veins is common and this varies in degree and the size of vessel involved.

Question 12

What can differences in cirrhosis appearance tell us?

Answer 12

Little about the cause of the cirrhosis

Question 13

More recent concept of cirrhosis pathogenesis
1
2
3

Answer 13

• In chronic liver disease, hepatocellular death due to the direct effect of the insult itself is relatively unimportant, as these cells can be replaced by mitotic division of hepatocytes
• Scars and fibrous septa develop in the areas where the hepatocytes have dropped out as a result of inflammatory injury to the portal veins.
• Progression to cirrhosis is driven by “parenchymal extinction” caused by vascular inflammation and thrombosis.

Question 14

Which types of cirrhosis have the greatest risk of hepatocellular carcinoma?

Answer 14

Cirrhosis due to alcohol, chronic viral hepatitis B and C, haemochromatosis

Question 15

Amount of hepatic blood flow from portal vein

Answer 15

2/3

Question 16

Amount of hepatic oxygen supplied by portal vein

Answer 16

Under 50% (most is supplied by the hepatic artery)

Question 17

Definitions of portal hypertension
1
2

Answer 17

1) Absolute increase of over 8mmHg of portal vein pressure

2) Increase in the pressure gradient between the portal vein and hepatic vein of 5mmHg or more

Question 18

What causes portal hypertension?

Answer 18

Obstruction to flow somewhere within the portal system

Question 19

Most common cause of portal hypertension

Answer 19

Cirrhosis

Question 20

Pathogenesis of portal hypertension in the context of liver cirrhosis 
1
2
3
4
5

Answer 20

1. Splanchnic circulation in cirrhosis is hyperdynamic, resulting in increased portal vein and hepatic arterial blood flow
2. Vascular smooth muscle and stellate cells contract even before fibrosis has advanced
3. Hepatic vein is directly compressed by regenerating nodules
4. Small portal vein branches are trapped, narrowed and distorted by scar tissue
5. Hepatic arterial blood shunts into portal vein via arteriovenous anastomoses in fibrous septa

Question 21

Clinical features of portal hypertension
1
2
3
4

Answer 21

1) Ascites
2) Formation of porto-systemic anastomoses
3) Congestive splenomegaly
4) Hepatic encephalopathy

Question 22

Main sites of portosystemic communication (venous anastamoses)

Answer 22

Oesophagus, rectum, around the umbilicus

Question 23

Vascular effects of dilated portosystemic venous anastamoses

Answer 23

Oesophageal varices, anorectal haemorrhoids

Question 24

Essential test in someone who has cirrhosis

Answer 24

Endoscope for oesophageal varices