L11: Blood borne viruses: Viral hepatitis

Question 1

What is the global prevalence of Hep B and C?

Answer 1

Hep B
–> 400 million people total, new cases 4 million
–> untreated develop liver cirrhosis (10%)–> hepatocellular carcinoma
Hep C
–> 200 million people total, liver cirrhosis (80%)–> hepatocellular carcinoma

Question 2

What is the prevalence of Hep B and C in the UK?

Answer 2

Hep B
–> 1/1000 people, 500 new cases

Hep C
–> 1/200 people

Question 3

Define hepatitis?

Answer 3

Inflammation of the liver

Viruses cause systemic damage which causes ‘collateral’ liver damage

Question 4

What is hepatitis viruses?

Answer 4

Replication specifically in the hepatocytes (hepatotropic)

Destruction of hepatocytes –> cirrhosis –> liver dysfunction

Question 5

What are the different types of hepatitis? Which are most dangerous?

Answer 5

A–> faeco-oral transmission, 2-6 week incubation period, no chronic illness
B–> blood, sex, vertical, 6 week to 6 months incubation, yes chronic illness
C–> blood, sex, 6-12 weeks incubation, yes chronic illness
D–> blood, sex, vertical, 6 week to 6 months, yes if with HepB
E–> faeco-oral transmission, 2 to 6 weeks incubation, uncommon but possible chronic illness

Hep B and C

Question 6

What is the structure of Hep B and C?

Answer 6

Hep B–> dsDNA–> enveloped

HepC–> ssRNA–> enveloped

Question 7

What are the main functions of the liver?

Answer 7

Glycogen storage
Clotting factor 
Metabolise drugs  
Hormone production 
Produce bile --> metabolise fats in the GI tract --> complication in production--> jaundice

Question 8

How is bile produced and excreted?

Answer 8

RBC die release bilirubin
Binds to albumin to be transported in the blood- Bilirubin-albumin
Bilirubin taken up by the liver
Becomes conjugated bilirubin using UDP glucuronyl transferase enzyme (conjugated to glucaronic acid)
Conjugated bilirubin released as bile into small intestines

Question 9

What is jaundice?

Answer 9

Build up of bilirubin

Question 10

What are the different types of jaundice?

Answer 10

Depends where problems occur
Prehepatic or cholestatic
Prehepatic–> before bilirubin has reached the liver–> excess haemolysis –> ↑ bilirubin

Cholestatic
Intrahepatic–> inside the lobules, hepatocyte inflammation e.g. viral hepatitis–> blockage of the biliary tracts–> ↑ bilirubin

Extrahepatic–> outside the liver, block the outflow tracts, ↑ bilirubin

Question 11

How can you determine what type of jaundice is present?

Answer 11

Blood test–> Liver function tests
↑ Bilirubin = jaundice
Cholestatic intrahepatic –> ALT (alanine transaminase increased), AST (aspartate aminotransferase increased)
–> produced by hepatocytes
Cholestatic extrehepatic–> ALP (alkaline phosphatase increased)
–> produced by biliary tract cells

Hb level normal then no problem with RBC lysis (haemolysis)–> not prehepatic

Question 12

What other proteins can be tested to give you an idea about liver function?

Answer 12

Albumin–> protein synthesised in the liver
Test of coagulation–> clotting factors synthesised, INR, prothrombin time (PT)

Severe liver damage–> decreased

Question 13

How is Hep B transmitted?

Answer 13

Vertical transmission - 75% of global cases
Sexual contact
People who inject drugs
Close household contacts–> significant blood exposure
Healthcare worker via needlestick injuries

Question 14

What are the acute symptoms of Hep B?

Answer 14

Jaundice
Fatigue
Abdominal pain 
Anorexia/ nausea/ vomitting 
Arthralgia 
May have no symptoms at all or may not link it to Hep B

Question 15

What would you expect a liver function test of a Hep B patient to show?

Answer 15

AST and ALT in the 1000s

Question 16

What is the difference between developing Hep B as a child and as an adult?

Answer 16

Adult <10% develop chronic Hep B

Child - 90% develop chronic Hep B

Question 17

What is the natural progression in the serology of Hep B that gets cleared?

Answer 17

1- Surface antigen appear first–> within 6/52, along with ALT/DNA rise
2- E-antigen then increases –> highly infectious stage
3- Core antibody IgM appear–> first sign of trying to clear infection
4- Followed by E-antibody–> Heralds disapperarance of E-antigen and infectivity–> clearing of infection going well
5- Surface antibody–> last antibody to appear, clear surface antigen, clearance of virus/ recovery
6- Core antibody IgG produced–> persists for life

Question 18

What happens if the Hep B infection isn’t cleared?

Answer 18

Chronic Hep B
Persitence of HBsAg after 6 months
25% leads to liver cirrhosis, 5% will develop hepatocellular carcinoma!

Question 19

What is the treatment for Chronic Hep B?

Answer 19

No cure
Integrates into genome
Life long anti-virals to suppress replication
Not required for everyone–> some inactive carriers–> low viral load, normal LFTs and no liver damage (no symptoms)

Question 20

How does the Hep B vaccination work?

Answer 20

Genetically engineered surface antigen --> induces surface antibody response
3 doses and booster sometimes required 
>10 adequate 
>100 life long protection
Effective in most people

Question 21

Who is at risk of transmission of Hep C?

Answer 21

People who inject drugs >90%
--> IV heroin, crack, metamphetamines 
--> crack or heroin smokers
Sexual contact <1% but higher if HIV infected
Infants born to HCV positive mothers <5%
Blood transfusion prior to 1991
Needlestick injuries

Question 22

How does Hep C normally progress?

Answer 22

80% develop chronic Hep C–> not a naturally cleared
Some will develop chronic liver disease/cirrhosis–> decompensated liver disease, Hepatocellular carcinoma, transplant, death

Question 23

What are the symptoms associated with Hep C?

Answer 23

80% no symptoms acute or chronic–> no jaundice

20% vague symptoms –> fatigue, anorexia, nausea and abdominal pain

Question 24

What test can be done to diagnose Hep C?

Answer 24

Serology–> Anti-Hep C antibody
–> lifelong positive, even after clearance/cure
–> not protective–> re-infection possible
Viral PCR
–> If positive confirms on-going/ chronic infection

Question 25

What treatment is there for Hep C?

Answer 25

Can be cured (anti-hep C antibody remains)
Directly acting antiviral drug combination
–> 8-12 week course
–> very expensive £10,000-£60,000
–> can be re-infected
No vaccination