L37. Patterns of chronic liver injury

Question 1

What is the clinical definition of chronic hepatitis?

Answer 1

Peristance of liver injury with raised serum aminotransferase levels for >6 months

Question 2

What are the causes of chronic hepatitis?

Answer 2

Most commonly HBV and HVC

also (less commonly) autoimmune hepatitis and (occasionally) drugs and very rarely idiopathic causes

Question 3

What is the inflammatory cell infiltrate in chronic hepatitis?How is this different to acute hepatitis?

Answer 3

T cell lymphocytes and plasma cells

This is the case for BOTH ACUTE AND CHRONIC

the difference between them lies in the PATTERN of injury

Question 4

Compare the hallmark feature of acute hepatitis with that of chronic hepatitis

Answer 4

ACUTE:
Lobular disarray

CHRONIC:
inflammation in the portal tracts and peri-portal liver tissue (with lobular parenchyma looking relatively normal) - the portal tracts have irregular shapes

Question 5

What is interface hepatitis?

Answer 5

A pattern of injury that occurs in chronic hepatitis: pattern of liver cells.

Where there is PERIPORTAL hepatocellular injury accompanied by the LYMPHOPLASMACYTIC inflammation.

Lymphocytes emerge from the portal tracts and infiltrate BETWEEN hepatocytes and surround individual groups of liver cells with apoptotic bodies being seen. The interface is between the inflamed portal tract and the parenchyma and this is irregular.

Question 6

What is the grade of chronic hepatitis dependent on?

what is it an important determinant of?

Answer 6

The DEGREE of interface hepatitis

It is an important determinant of the rate of which fibrosis develops.

Question 7

Can lobular changes be seen in chronic hepatitis?

Answer 7

Not usually. Only in the case of severe disease after which it can be difficult to distinguish it from acute hepatitis.
However the major difference between them in this case is FIBROSIS (only for chronic)

Question 8

What is fibrosis?

Describe it in the context of chronic hepatitis

Answer 8

The deposition of scar tissue in the liver

Fibrosis can be progressive and eventually can become cirrhosis.

Question 9

Describe how fibrosis occurs in the liver cells

Answer 9

Chronic injury of hepatocytes can cause kupffer cells to release cytokines. This leads to a phenotypic switch of portal fibroblasts and epatic stellate cells to become activated and secrete collagen (fibroblastic phenotpe)
= proliferation and conversion of hepatic stellate cells into fibrogenic fibroblasts (spindle shaped)

This leads to formation fibrous spurts extending out of the portal tract in a stellate manner.

Question 10

Where is the collagen deposited into by the stellate cells?

Answer 10

The space of Disse

Question 11

Describe the four stages of chronic hepatitis

Answer 11

The stages represent the degree of fibrosis

Stage 1: Enlarged portal tracts by collagen deposition
Stage 2: Portal strands cause portal tracts to have spider like appearance as collagen form septa between tracts
Stage 3: Portal-portal bridging of collagen occurs between portal tracts
Stage 4: nodules of hepatocytes are completely surrounded by bridging fibrotic septa = cirrhosis

Question 12

Is alcoholic liver disease considered to be chronic hepatitis?

Answer 12

by convention it is NOT considered chronic hepatitis.

It is a chronic hepatic injury but not called chronic hepatitis.

Question 13

Describe the pathogenesis of alcoholic liver disease

Answer 13

Hepatocellular damage from the metabolic product of alcohol acetyaldehyde leads to

• oxidative stress
• impaired carbohydrate and fat metabolism
• stimulation of collagen synthesis (direct and indirect)
• can have a component of genetic susceptibility

these all lead to the fibrotic changes and cirrhosis.

Question 14

What are the three histological components seen in alcoholic liver disease

Answer 14

1. Fatty change (abnormal accumulation of lipid in hepatocytes) - this is reversible
2. Alcoholic steatohepatitis - hepatocellular death and early stages of fibrosis
3. Alcoholic cirrhosis - progressing fibrosis leading to cirrhotic changes

Question 15

What is macrovesicular steatosis?

Describe the histological appearance of this

Answer 15

This is the infiltration of liver cells with fat, associated with disturbance of the metabolism.

The fat displaces nuclei to the edge and cells appear as large, fat vacuoles in perivenular hepatoxytes

Question 16

What is the difference between steatosis and steatohepatitis?

Answer 16

Steatosis is fat and nothing else while steatohepatitis is fat AND HEPATOCELLULAR INJURY

Question 17

What is a hallmark feature of steatohepatitis?

Answer 17

Ballooning, severe swelling of the hepatocytes

Formation of MALLORY-DENK BODIES

Question 18

What are Mallory-Denk Bodies?

Answer 18

Hepatocytes with collapsed hepatic cytoskeleton with visible intermediate filaments (cytokeratin 8 & 18) and other proteins.

They attract neutrophils (chemotactic form them)

Appear in a ropey C shape countour partially surrounding the hepatocyte nucleus

Question 19

What are the features of severe alcoholic steatohepatitis (acute alocholic hepatitis)?

Answer 19

Jaundice
Fever
Hepatosplenomegaly
Marked impaired liver function
Leuckocytosis
Tender liver 
The disease carries a 50% 30 day mortality

Question 20

What is non-alcoholic fatty liver disease (NAFLD)?

Answer 20

Pathology that looks the same as ALD but is due to obesity, metabolic syndrome and diabetes.
- thus accumulation of fat in the liver

Question 21

If histologically, there is very severe steatohepatitis and mallory-denk bodies, what is the cause more likely to be?ALD or NAFLD?

Answer 21

Most likely alcoholic

Question 22

Is the differential between ALD and NAFLD made clinically or pathologically? How is it done?

Answer 22

Clinically

Based on drinking history

Question 23

How do the appearances of alcoholic steatohepatitis ASH compare with non-alcoholic steatohepatitis NASH?

Answer 23

they look the same