10-02-23 – Viral Hepatitis

Question 1

Learning outcomes

Answer 1

• Recognise the various stages of infection with the hepatitis viruses A-E
• Describe the treatment and prevention of hepatitis caused by hepatitis viruses A-E
• Identify the main features of the different hepatitis viruses A-E
• Recognise the importance of the use of serological markers for hepatitis B virus
• Explain how the different hepatitis viruses A-E are transmitted
• List the viruses which can cause hepatitis

Question 2

What is hepatitis?

What are 4 different types of causes of hepatitis?

Answer 2

• Hepatitis is liver inflammation
• 4 different types of causes of hepatitis:

1) Infectious
* Hepatitis A-E
* Cytomegalovirus
* Epstein barr virus

2) Drugs
* Alcohol
* Paracetamol overdose
* Co-amoxiclav

3) Autoimmune

4) Ischaemic

Question 3

What are 7 different functions of the liver?

Answer 3

• 7 different functions of the liver:
  1) Synthesis of clotting factors
  2) Production of complement factors
  3) Synthesis of albumin
  4) Production of bile salts
  5) Conjugation of bilirubin
  6) Metabolism of drugs and hormones and toxins
  7) Carbohydrate metabolism

Question 4

What are 6 symptoms of hepatitis?

Answer 4

• 6 symptoms of hepatitis:
  1) Asymptomatic
  2) Fever
  3) Jaundice
  4) Malaise
  5) Diarrhoea/Vomiting
  6) Acute liver failure – bruising (due to lack of clotting factor), ascites, encephalopathy

Question 5

What is liver cirrhosis?

Answer 5

• Liver cirrhosis is when normal liver tissue is replaced by fibrotic/scar tissue

Question 6

What are 4 risk factors for Liver Cancer/Hepatocellular carcinoma?

How can be detect liver cancer?

What is the most common cause of liver cancer in the world and in Europe?

Answer 6

• 4 risk factors for Liver Cancer/Hepatocellular carcinoma:
  1) Hepatitis B/C
  2) Alcohol
  3) Obesity
  4) Smoking
• We can detect liver cancer by measuring alpha fetoprotein, with elevated levels suggesting liver cancer
• Chronic hepatitis B infection is the most common cause of liver cancer worldwide.
• Hepatitis C infection is the most common cause of liver cancer in Europe

Question 7

What type of virus is hepatitis A?

How is it spread?

How can it be contracted from sea-life?

Where can there be Hep A endemics?

What are 5 common symptoms of Hepatitis A?

Answer 7

• Hepatitis A is a non-enveloped positive single stranded RNA virus
• Spread by faeco-oral route e.g contaminated water – can cause water borne epidemics
• Blood-borne transmission is rare
• Sometimes hepatitis A is associated with consuming undercooked shellfish
• There can be endemics of Hep A in countries with poor hygiene and sanitation
• 5 common symptoms of Hepatitis A:
  1) Hepatomegaly – 80%
  2) Jaundice – 70%
  3) Fatigue
  4) Arthralgia
  5) Poor appetite

Question 8

Hep A serology.

What do certain antibodies tell us about Hepatitis A infection?

How can vaccines for Hep A affect our immunity?

Answer 8

• Hep A serology
• Hep A IgM antibody detected – positive in acute Hep A infection
• Hep A IgG antibody detected – indicates Hep A immunity
• We can have life-long Hep A immunity with occasional vaccines
• These vaccines can be given more frequently to those at higher risk

Question 9

How is Hep A normally treated?

How often does Hep A cause liver failure?

Can Hep A infections be chronic?

How does lifelong immunity from Hep A occur?

Answer 9

• Hep A is normally a self-resolving infection, and is treated using supportive treatment (only affects symptoms – doesn’t cure)
• 0.1%-0.3% of those infected with Hep A develop acute liver failure, so a transplant is needed
• No cases of chronic hepatitis A
• Once infected, we develop lifelong immunity from Hep A

Question 10

What type of virus is Hepatitis B?

Where is the highest prevalence of Hep B?

How is it transmitted?

What are 4 methods of horizontal transmission of Hep B?

What is a vertical transmission method of Hep B?

Answer 10

• Hep B is a Partially double stranded DNA virus
• Highest prevalence in Africa, Asia and the Western Pacific Rim
• Also common in Sothern and Eastern Europe
• Hep B is a blood-borne virus
• 4 methods of horizontal transmission of Hep BL:
  1) Unprotected intercourse
  2) Contaminated needles – drug use, needlestick injuries, reuse of tatto needles
  3) Breaks in mucous membranes
  4) Blood transfusion
• Vertical transmission method of Hep B - From mother to child e.g. during childbirth

Question 11

Life cycle of Hep B diagram

Answer 11

Question 12

Describe 7 different markers that can be tested for in Hep B infections.

What interpretation can be drawn from each one (in picture)?

Answer 12

• 7 different markers that can be tested for in Hep B infections (in picture)
• Ab – antibody
• Ag – antigen
• HBc – Hep B core protein

Question 13

Describe the antibody graph for Self-limited hepatitis B infection (in graph)

Answer 13

Question 14

What is a chronic Hep B infection?

Describe the antibody graph for Chronic Hepatitis B infection?

Answer 14

• Chronic Hepatitis B infection is defined as infection persisting beyond 6 months of diagnosis It is usually characterized by persistent positive HBVsAg without development of sAb
• Antibody graph for Chronic Hepatitis B infection in picture

Question 15

What are 4 common serological profiles of Hep B to understand (in picture)

Answer 15

Question 16

What is the Severity of Hepatitis B infection based on?

What are complications of Hep B infection due to?

How does immune response affect damage to hepatocytes?

Answer 16

• The severity of Hep B infections I based on immune response
• Complications of hepatitis B are due to host T cell activity
• The better the immune response the more damage to hepatocytes

Question 17

When are babies vaccinated for Hep B?

When is there an accelerated and intensified vaccine schedule for babies?

What are 4 other reasons to vaccinate for Hep B?

Answer 17

• Since 2017 all new born children are vaccinated against Hepatitis B at 8, 12 and 16 weeks
• Babies born to hepatitis B infected mother have an accelerated and intensified schedule
• 4 other reasons to vaccinate for Hep B:
  1) Uninfected household contacts
  2) Occupational or travel risk
  3) Lifestyle risk
  4) Co-existing medical conditions

Question 18

What is the aim of Hep B treatment?

Why is it important that patients adhere to treatment?

What must we also remember to do regarding treatment of Hep B?

What are 2 different treatment options for Hep B.

What is their:
* Action
* Administration
* Drugs
* Side-effects
* Duration of treatment

Answer 18

• There is no ‘cure’ for hepatitis B.
• Treatment aims to suppress viral replication, as this can lower transmissibility and can potentially make the virus undetectable
• It is important that patients adhere to medications, as without medication, the infection can come back and potential be resistant to the medication
• Remember also to screen and vaccinate household contacts
• 2 treatment options for Hep B are nucleotide analogues and Pegylated alpha interferon (in photo)

Question 19

When is the likelihood of developing chronic hepatitis higher?

How does Hep B infection affect risk developing hepatocellular carcinoma?

Describe the complications flow chart for Hep B infection (in picture)

Answer 19

• The likelihood of developing chronic hepatitis is higher after vertical transmission
• The risk of developing hepatocellular carcinoma is 200 times higher in people who have had Hepatitis B infection
• Complications flow chart for Hep B infection (in picture)

Question 20

What type of virus is Hep C?

What is it the most common cause of?

What countries does it typically affect?

How is it transmitted?

Answer 20

• Hep C is an Enveloped single stranded RNA virus
• It is the Most common cause of chronic viral hepatitis
• Hep C typically affects Africa, Asia, Southern and Eastern Europe
• Hep C is a blood borne virus

Question 21

What % of Hep C cases are asymptomatic?

What are 5 symptoms of Hep C in those that are symptomatic?

Answer 21

• 85% of Hep C cases are asymptomatic
• 5 symptoms of Hep C in those that are symptomatic:
  1) Poor appetite
  2) Myalgia
  3) Fever
  4) Jaundice
  5) Tender hepatomegaly

Question 22

What 2 investigations can be done for Hepatitis C?

What can they indicate?

Answer 22

• 2 investigations can be done for Hepatitis C:
  1) Hepatitis C RNA – can indicate active infection
  2) Anti-Hepatitis C antibody – can indicate recovery or chronic Infection

Question 23

Describe the antibody graph for acute hepatitis C infection (in picture)

Answer 23

Question 24

What is defined as a chronic Hepatitis C infection?

Describe the antibody graph for chronic hepatitis C infection (in picture)

Answer 24

• Chronic Hepatitis C infection is defined as infection persisting beyond 6 months of diagnosis
• Antibody graph for chronic hepatitis C infection (in picture)

Question 25

What are 4 methods of horizontal transmission of Hepatitis C? What is a method of vertical transmission of Hepatitis C? What do a 1/3rd of those with hepatitis C not have?

Answer 25

* 4 methods of horizontal transmission of Hepatitis C: 1) Contaminated needles – drug use, needlestick injuries, reuse of tattoo needles 2) Blood transfusion 3) Breaks in mucous membranes 4) Unprotected intercourse * Method of vertical transmission of Hepatitis C - From mother to child e.g., during childbirth * 1/3 of people with Hepatitis C have no identifiable risk factors

Question 26

Describe the natural history of Hepatitis C flowchart (in picture)

Answer 26

* Natural history of Hepatitis C: * 80% chance of progression to chronic disease * 20% chance of cirrhosis due to chronic Hepatitis C * 2-5% a year chance of development to Hepatocellular carcinoma due to cirrhosis

Question 27

What are 5 different types of Extrahepatic manifestations of Chronic Hepatitis C?

Answer 27

* 5 different types of Extrahepatic manifestations of Chronic Hepatitis C: 1) Autoimmune * Thyroid disease 2) Haematological * Lymphoma 3) Pulmonary * Fibrosis 4) Renal * Membranous proliferative Glomerulonephritis 5) Skin * Lichen Planus * Porphyria Cunea Tardia

Question 28

What are 3 different types of anti-virals used to treat Hepatitis C? How effective are they? How long does treatment last? What % of cases are cured? Why is there no vaccine for hepatitis C?

Answer 28

* 3 different types of anti-virals used to treat Hepatitis C: 1) Protease Inhibitors * Paritaprevir 2) NS5A Inhibitors * Ledipasvir 3) RNA Polymerase inhibitors * Sofosbuvir * Direct acting antivirals are a highly effective new treatment * Treatment duration is shortening (some regimens now only 8 weeks) * Cure of Hepatitis C is achieved in 95% * There is no vaccine available for hepatitis C due to rapid emergence of genetic variants

Question 29

Life-cycle of Hepatitis C diagram (in picture)

Answer 29

Question 30

What type of virus is hepatitis D? When can you contract Hep D? What countries does it affect? What is it transmitted? What is transmission associated with? How do we distinguish between Hep B and D?

Answer 30

* Hep D is an RNA virus * Only possible to be infected with hep D if you already have hepatitis B * Seen in Amazonian basin, Central Africa and Middle east * Hep D is a blood borne virus * Transmission associated with IV drug use * We cannot distinguish between hepatitis B and D in terms of clinical presentation

Question 31

Hep D serology. What do certain antibodies tell us about Hep D infection?

Answer 31

* Hepatitis D IgM antibody detected – acute infection * Hepatitis D IgG detected – indicates immunity

Question 32

What are the effects of co-infection with Hep B and Hep D? What is the only treatment option for Hep D?

Answer 32

* Co-infection with hepatitis B and D represents the most severe form of hepatitis due to the rapid progression of the disease and development of hepatocellular carcinoma * Antivirals used for treatment of hepatitis B do not work against hepatitis D * Pegylated Interferons are the only treatment options, but we don’t know how well they actually work

Question 33

What type of virus is Hep E? What kind of disease does it cause? What is it associated with? How is Hep E spread? What group of people is Hep E associated with? What countries have epidemics of Hep E?

Answer 33

* Hep E is an RNA virus * Hep E causes a zoonotic disease, which is an infectious disease that is transmitted between species from animals to humans * Associated with pig farming/consumption of pork * Hep E is spread via faeco-oral route * Hep E is More common in middle aged men * Epidemics of Hep E have occurred in Asia and India

Question 34

What % of Hep E cases are asymptomatic? What groups of people typically are most severely affected? What are 4 symptoms of Hep E in those who are symptomatic?

Answer 34

* 95% of people infected with Hep E are asymptomatic * Typically, males over the age of 50 are most severely affected * 4 symptoms of Hep E in those who are symptomatic: 1) Diarrhoea 2) Vomiting 3) Fevers 4) Neurological symptoms –10%

Question 35

How is Hep E treated? What is Hep E the most common cause of in the UK? What % of pregnant women affected with Hep E die? Is there a vaccine for Hep E?

Answer 35

* Hep E is usually a self-limiting disease that is only treated using supportive care * Hep E is the most common cause of acute hepatitis in the UK * 25% of pregnant women infected with Hep E die * A vaccine for Hepatitis E is available but only licensed for use in China

Question 36

Summary

Answer 36

* Summary * Hepatitis A & E usually present with acute hepatitis * Both are usually self-limiting but fulminant disease can occur * Hepatitis E is dangerous for pregnant women * Hepatitis B & C can present as acute or chronic hepatitis * Hepatitis A & B are vaccine preventable * New anti-viral drugs raise the prospect of effective cure and maybe eradication of hepatitis C

Question 37

Summary of hepatitis

Answer 37

Question 38

Summary of hepatitis serology

Answer 38