Patterns of Liver Injury - Chronic Hepatitis

Question 1

What is the clinical definition of chronic hepatitis?

Answer 1

persistence of liver injury with raised serum aminotransferase levels for more than 6 months

Question 2

What are the causes of chronic hepatitis?

Answer 2

• chronic HBV and HCV
• autoimmune hepatitis (less common)
• drugs
• NASH can present as elevated levels of ALT (to a lesser extent)

Question 3

What is the differential diagnosis for chronically elevated ALT?

Answer 3

chronic hepatitis or NASH

Question 4

What are the presenting symptoms of chronic hepatitis?

Answer 4

• can be asymptomatic
• not generally unwell; typically outpatients
• non-specific sysmptoms like fatigue and loss of appetite

Question 5

What are the risk factors for NASH?

Answer 5

• obesity
• diabetes
• metabolic syndrome

Question 6

What is the hallmark histological feature of chronic hepatitis?

Answer 6

periportal inflammation/interface hepatitis:

• apoptosis of hepatocytes at the interface between portal tracts and lobular parenchyma
• associated with lymphoplasmacytic inflammation
• not specific for chronic hepatitis; must fit clinical dx
• degree = grade of chronic hepatitis
  
  • determines rate of fibrosis

Question 7

What is the major mode of cell death in chronic hepatitis?

Answer 7

apoptosis

Question 8

Apoptosis is a hallmark feature of

Answer 8

acute and chronic hepatitis

Question 9

How is chronic hepatitis diagnosed?

Answer 9

biopsy: degree of interface hepatitis (grade) and fibrosis (fibrous septa)

Question 10

What forms the fibrous septa in chronic hepatitis?

Answer 10

• diffuse, persistent chronic inflammation
• causes deposition of abnormal collagen (scar tissue)
• pattern is septal fibrosis
• stellate pattern of bands or plates of scar tissue that radiate from portal tracts outward into the parenchyma
• can lead to cirrhosis

Question 11

What is septal fibrosis?

Answer 11

stellate formations of scar tissue radiating from portal tracts

Question 12

How does fibrosis develop in chronic hepatitis?

Answer 12

• portal tracts enlarge (contain more scar tissue/collagen)
• strands of collagen begin to extend outwards towards central veins
  
  • occasionally link up = bridging fibrosis
    
    • marker for treatment institution
• portal to portal bridging of fibrous septa
  
  • contracts, distorts liver anatomy and tf function
  • lobules and sinusoids filling with collagen
  • overtly symptomatic
• fibrosis = network of nodules separated by fibrous septae

Question 13

What is fibrosis (histologically)?

Answer 13

network of nodules separated by bands of fibrous scar tissue

Question 14

What is non-alcoholic fatty liver disease?

Answer 14

• previously crytogenic cirrhosis (unknown cause)
• important differential diagnosis of impaired liver function (children and adults)
• two components:
  
  • steatosis (fat, nothing else), or
  • steatohepatitis and fibrosis = NASH

Question 15

What is NASH?

Answer 15

• non-alcoholic steatohepatitis
  
  • steatohepatitis + fibrosis
• associated with obesity, metabolic syndrome, and diabetes

Question 16

What is steatosis?

Answer 16

• aka fatty liver, fatty change, steatosis
• accumulation of abnormal amounts of lipid in hepatocytes
• two types:
  
  • macrovesicular - large droplet, very common
  • microvesicular - small droplet, very rare (acute fatty liver of pregnancy, Reye’s syndrome

Question 17

What are the histological features of macrovesicular steatosis?

Answer 17

• large droplets of fat that displace nuclei to one side of cells
• well-delineated fat vacuoles

Question 18

What is macrovesicular steatosis?

Answer 18

• caused by an abnormality of triglyceride synthesis
  
  • increased synthesis or decreased excretion
• very common

Question 19

How is macrovesicular steatosis diagnosed?

Answer 19

• severe: non-invasive imaging (ultrasound)
• LFT may be normal or mildly abnormal
• not possible to determine cause from histology alone, need clinical information
  
  • related to obesity and alcohol

Question 20

What is steatohepatitis?

Answer 20

• steatosis with inflammation and injury of hepatocytes
  
  • significant risk of fibrosis –> cirrhosis
• hallmark feature: hepatocellular ballooning degeneration
  
  • ​also present in alcoholic steatohepatitis/alcoholic hepatitis

Question 21

How are non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) differentiated?

Answer 21

• clinically:
  
  • is the patient drinking at a toxic level?
  • do they have risk factors for NASH?
• essential histological features are identical (ASH tends to be more severe):
  
  • hepatocellular ballooning degeneration (blue arrows) due to accumulation of water (hydropic swelling) - diffuse
  • apoptosis

Question 22

What is the pattern of fibrosis in steatohepatitis?

Answer 22

• pericellular fibrosis
• scar tissue surrounds individual or small groups of hepatocytes
• fills sinusoids, isolates hepatocytes
• same pattern in ASH and NASH

Question 23

What is the pathogensis of NASH vs macrovesicular steatohepatitis?

Answer 23

• macrovesicular steatohepatitis occurs as a result of increased storage of triglyceride in the liver
  
  • increased triglycerides due to insulin resistance, dietary factors, or poorly controlled diabetes
  • FFAs diverted to liver for storage
  • this is SAFE steatosis (no inflammation or fibrosis)
• NASH results when this pathway is overloaded and lipotoxic metabolites form
  
  • cause cellular stress, inflammation, apoptosis, and necrosis
  • develops into NASH - causes fibrosis and cirrhosis