8. Hepatitis

Question 1

what is hepatitis?

Answer 1

inflammation of the liver

Question 2

what kind of viruses cause liver damage?

Answer 2

1. many systemic viruses cause ‘collateral’ liver damage, e.g. EBV, CMV, VZV
2. hepatitis viruses
   - replicate specifically in hepatocytes (hepatotropic)
   - destruction of hepatocytes - replication causes fibrosis and inflammation… cirrhosis and liver cancer

Question 3

How are HepB and HepC transmitted, how long incubation, and acute or chronic illness?

Answer 3

HepB

• blood/sex/vertical transmission
• 6wks-6mths incubation
• acute or chronic illness

HepC

• blood/sex transmission
• 6-12wks incubation
• chronic illness

Question 4

What type of virus are hepB and hepC

Answer 4

• HepC= RNA virus

- HepB = DNA virus

Question 5

what causes jaundice in hepatitis patients?

Answer 5

accumulation of bilirubin due to liver dysfunction

Question 6

how is bilirubin produced and excreted?

Answer 6

1. haemoglobin in aged RBCs broken down by reticuloendothelial system to produce bilirubin
2. transported in bloodstream to liver via albumin
3. conjugation of bilirubin in liver by UDP glucuronyl transferase to make it soluble
4. a) some excreted in urine (yellow)
   b) some added to bile and excreted in faeces (brown) via GI tract

Question 7

where is bile produced, stored and released?

Answer 7

produced in liver, stored in gallbladder and released into duodenum for fat digestion

Question 8

what is cholestasis?

Answer 8

• reduction or stoppage of bile flow

- can be intrahepatic (in liver) or extrahepatic (ducts, gallbladder or pancreas)

Question 9

what are the 3 main types of jaundice? how is each caused?

Answer 9

1. Prehepatic
   - increased haemolysis
2. Cholestatic - intrahepatic
   - viral hepatitis
   - drugs
   - alcoholic hepatitis
   - cirrhosis
   - autoimmune cholangitis
   - pregnancy
   - …
3. Cholestatic - extrahepatic
   - common duct stones
   - carcinoma (bile duct, head of pancreas, ampulla)
   - biliary stricture
   - …

Question 10

which liver function tests (LFTs) are used to test for cellular integrity?

Answer 10

1. bilirubin
2. liver transaminases
   - alanine transaminase (ALT) - more sensitive
   - aspartate aminotransferase (AST)
3. alkaline phosphatase (ALP) - produced by cells of biliary tree

Question 11

which LFT would indicate hepatocyte damage/decreased cellular integrity?

Answer 11

increased alanine transaminase (ALT) or aspartate aminotransferase (AST)

Question 12

which LFT would indicate biliary tract cell damage/cholestasis?

Answer 12

increased alkaline phosphatase (ALP)

Question 13

which LFTs are used to assess liver function?

Answer 13

1. albumin (protein synthesised in liver so decreased in fibrosis/cirrhosis)
2. coagulation tests (clotting factors synthesised in liver)
   - INR (international normalised ratio)
   - prothrombin time (PT)

Question 14

What are the symptoms of acute hepB infection?

Answer 14

Up to 50% have no/vague symptoms

1. jaundice
2. fatigue
3. abdominal pain, nausea and vomiting
4. arthralgia

Question 15

What are the 3 possible consequences of acute hepB infection?

Answer 15

1. infection clearance within 6 mths - lifelong immunity
2. chronic infection (<10% adult infections, 90% infancy infections)
3. fulminant hepatic failure (1%)

Question 16

What are the possible complications of chronic hepB?

Answer 16

• cirrhosis (25%)

- hepatocellular carcinoma (5%)

Question 17

Name 3 diagnostic measures for hepB.

Answer 17

• AST/ALT in 1000s
• serology: detection of Ag and Ab
• PCR for HepB DNA

Question 18

Describe the appearance of Ag and Ab in hepB infection (in order).

Answer 18

1. surface antigen (HBsAg)
2. e-antigen (HBeAg) - highly infectious
3. core antibody (IgM) - in resp. to HBcAg (not detectable)
4. e-antibody - indicates disappearance of e-antigen and infectivity
5. surface antibody - last antibody to appear, indicates virus clearance/recovery
6. core antibody (IgG) - persists for life

Question 19

Describe the treatment of chronic HepB infection.

Answer 19

No cure as viral DNA integrates into host genome - life-long anti-virals to suppress viral replication.

Not required for everyone: ‘inactive’ carriers - low viral load, normal LFTs, no liver damage (but require monitoring).

Question 20

How likely is chronic disease dev. after acute HepC infection?

Answer 20

80%

Question 21

What is the consequence of some chronic HepC infections?

Answer 21

Chronic liver disease/cirrhosis resulting in:

• decompensated liver disease
• hepatocellular carcinoma
• death

May require transplant.

Question 22

What are the symptoms of HepC infection?

Answer 22

80% have no symptoms (acute or chronic), 20% have vague symptoms:

• fatigue
• nausea & anorexia
• abdominal pain (RUQ)

Question 23

Name 2 diagnostic measures for HepC.

Answer 23

• serology: anti-HepC antibody only (remains +ve life long even after clearance, but not protective)
• PCR for HCV DNA

Question 24

Describe the treatment of HepC infection.

Answer 24

> 90% cured with directly acting antiviral drug combination (but expensive and can get re-infected)

Question 25

Describe the vaccination strategies for HepB and HepC.

Answer 25

- HepB: genetically engineered surface antigen (3 doses + boosters if required) - effective in most people. Produces surface Ab response (>10 adequate, >100 long-term protection) - HepC: no vaccine