Viral Hepatitis

Question 1

What is Hepatitis A?

Answer 1

The family Picornaviridae, genus hepatovirus

Single-stranded, positive sense RNA genome

Quasi-enveloped virions

Question 2

How is Hepatitis A transmitted?

Answer 2

Faeco-oral versus blood-borne transmission

Incubation period of 15-50 days

Question 3

What is the epidemiology of Hepatitis A?

Answer 3

Approx. 1.5 millions of cases worldwide annually

Developing countries with poor socio-economic conditions

300-500 cases annually in the UK

Mostly among age 15-34 and non-travellers

Outbreaks among MSM (2016/17) & IVDU (2001 & 2017)

Question 4

What are the signs and symptoms of Hepatitis A?

Answer 4

Wide disease spectrum from asymptomatic to fulminant hepatitis.

Strong correlation with age: <10% symptomatic among children <6 years old versus 70% in adults.

Typical symptoms: Fever, malaise, anorexia/nausea, abdominal discomfort, diarrhoea, jaundice.

Extra-hepatic diseases.

Question 5

Is Hepatitis A acute or chronic?

Answer 5

Acute presentation; 99% resolution

NOT an aetiology for chronic hepatitis

Question 6

What is the timecourse of the immune response to Hepatitis A infection?

Answer 6

Question 7

How is Hepatitis A diagnosed?

Answer 7

Based on serology:

• Acute infection: IgM reactive; unlikely if bilirubin level < 30umol/L
• Past infection: IgM non-reactive, IgG reactive

Question 8

What are the public health implications of Hepatitis A?

Answer 8

Notifiable disease

Pre-exposure immunisation among population at risk

Post-exposure prophylaxis:

Within 14 days of exposure to index case: HAV vaccine +/- HNIG (for 60 years and above, chronic liver diseases inc CHB/CHC, immunocompromised contact)

Over 14 days: HAV vaccine +/- HNIG (for chronic liver diseases inc CHB/CHC, immunocompromised contact)

Question 9

What is Hepatitis B?

Answer 9

The family Hepadnaviridae

Double-strained DNA with reverse transcriptase

Enveloped virions

10 genotypes (A-J) with distinctive geographic distribution

Question 10

How is Hepatitis B transmitted?

Answer 10

Blood-borne transmission: horizontal & vertical

Incubation period of 40-160 days

Question 11

What is the typical presentation of acute Hepatitis B?

Answer 11

Age related presentation & prognosis in acute hepatitis B.

Neonates & children: Mostly asymptomatic or anicteric; 90% HBV-infected neonates develop CHB, and 30% among children age <5 years.

Adult: 30-50% icteric hepatitis; 10% become CHB.

Question 12

What are risks associated with acute Hepatitis B infection?

Answer 12

0.1-0.05% risk of fulminant hepatitis; related to co-infection with HCV/HDV.

Maternal HBeAg/Ab status & HBV viral load.

HBeAg as the most important risk predictor for vertical transmission.

Question 13

What is the definition of chronic Hepatitis B infection?

Answer 13

Persistence of HBsAg for 6 months or more after acute HBV infection.

Question 14

What are risks associated with chronic Hepatitis B infection?

Answer 14

Cirrhosis: 8-20% untreated CHB in 5 years;

Hepatocellular carcinoma: The annual risk of 2-5% among CHB cirrhotic patients; affected by host (e.g. alcohol abuse) and viral factors (e.g. high HBV viral load & qHBsAg).

Question 15

What is the epidemiology of Hepatitis B?

Answer 15

Approximately 296 million people are living with CHB worldwide; CHB-related mortality at roughly 820,000 people per year.

Question 16

What are the public health implications of Hepatitis B infection?

Answer 16

Acute hepatitis B: A notifiable disease

Pre-exposure prophylaxis:

• Routine childhood immunisation in the UK since 2017
• High risk population

Post-exposure prophylaxis:

• Neonate born to mother living with hepatitis B.
• Sexual partner: HBV vaccine +/- HBIG (within one week from the contact).
• Needle stick injury.

Question 17

What is Hepatitis D?

Answer 17

Single-stranded, circular RNA genome.

A defective virus that relies on HBV for propagation.

Question 18

How is Hepatitis D transmitted?

Answer 18

Blood-borne transmission

Incubation period: 3-6 weeks

Question 19

What is the association between Hepatitis B and Hepatitis D?

Answer 19

HBV/HDV simultaneous co-infection: Similar to classic acute hepatitis B; mostly self-limited. <5% chronic infection.

HDV super-infection in CHB: 80% chronic infection. Increased risk of cirrhosis and HCC than CHB alone.

Question 20

How is Hepatitis D diagnosed and treated?

Answer 20

Anti-HDV serology; other HDV investigations rarely used.

PEG-interferon alpha licensed for HDV superinfection in CHB.

Pre-exposure HBV immunisation.

Question 21

WHat are the public health implications for Hepatitis D infection?

Answer 21

Notifiable disease

Question 22

What is Hepatitis C?

Answer 22

The family Flaviviridae, genus Hepacivirus.

Single-stranded, positive sense RNA genome.

Question 23

How is Hepatitis C transmitted?

Answer 23

Blood borne transmission.

Incubation period: 2-6 weeks.

Question 24

What is the epidemiology of Hepatitis C?

Answer 24

58 million people living with chronic hepatitis C worldwide.

1.5 million new cases every year.

Question 25

What is the presentation of Hepatitis C infection?

Answer 25

Acute infection:

• 30% spontaneous clearance
• 70% become chronic hepatitis C (CHC)

Hepatic versus extra-hepatic manifestation.

Cirrhosis (15-30% in 20 years) & HCC as complication of CHC.

Question 26

How is Hepatitis C treated?

Answer 26

Revolutionised the treatment for acute/chronic HCV infection.

Any HCV cases should be considered:

• 8 or 12 weeks
• Sustained virological response (SVR) at week 12
• Pan-genotypic regimen
• Single-tablet regimen
• Drug-drug interaction

Question 27

What are the public health implications of Hepatitis C infection?

Answer 27

Notifiable disease in the UK.

Nil vaccine available.

Nil post-prophylaxis available.

Active HCV screening.

Risk reduction (e.g. safe handling and disposal of sharps, protected sex).

Question 28

What is Hepatitis E?

Answer 28

The family Hepeviridae, genus Orthohepevirus; species A strains (8 genotypoes) infect humans.

Single-stranded, positive sense RNA genome.

Quasi-enveloped HEV.

Question 29

How is Hepatitis E transmitted?

Answer 29

Faeco-oral versus blood-borne transmission

Incubation period: 15-60 days

Question 30

What are the natural reservoirs for the different strains of Hepatitis E?

Answer 30

G1 & G2: Obligate human pathogens

G3 & G4: Zoonotic; pigs & wild boar are natural hosts

Question 31

What is the epidemiology of Hepatitis E?

Answer 31

Approximately 20 million new HEV cases worldwide annually

3.3m symptomatic hepatitis E

44,000 mortality annually

UK is a HEV G3 endemic country

Question 32

What is the clinical manifestation of Hepatitis E?

Answer 32

Mostly self-limited; advised against alcohol during the course

Hepatic and systemic symptoms

Question 33

Which groups are particularly at risk of developing Hepatitis E infection?

Answer 33

Pregnant women: G1; fulminant hepatic failure and obstetric complications (e.g. eclampsia and haemorrhage); 25% maternal mortality & high perinatal infant mortality.

Chronic liver disease patients.

Immunocompromised patients: May develop chronic hepatitis E (G3 & G4)/

Question 34

How is Hepatitis E diagnosed?

Answer 34

Immunocompetent: HEV serology

Immunocompromised: HEV PCR

Question 35

What are the public health implications of Hepatitis E infection?

Answer 35

Notifiable disease

HEV patient should avoid prepping food during the first 2 weeks.

Immunocompromised and chronic liver disease patients should avoid consumption of undercooked meat (pork, wild boar and venison) and shellfish.

HEV vaccination: Only licensed in China.

Question 36

What is the treatment of Hepatitis E?

Answer 36

Only indicated in chronic hepatitis E as most acute HEV infection are self-limited.