Hepatitis Viruses

Question 1

What is hepatitis?

Answer 1

• The wound-healing response of the liver to many causes of chronic injury.
• Various risk factors can lead to inflammation of the liver (hepatitis).
• This can be either self-limiting or can progress to chronic fibrosis (scarring).
• Most types of liver insult damage epithelial cells which causes release of inflammatory mediators. This is the main cause of fibrosis in liver injury.

Question 2

What is viral hepatitis?

What are the causes?

Answer 2

• Viral infection of the liver which causes hepatitis.
• Causes:
  
  • ​Viral hepatitis viruses (hepatitis A, B, C, D, E, F and G).
  • Cytomegalovirus
  • Epstein-Barr virus
  • Herpes viruses (mostly in immunocompromised patients)
  • Others (yellow fever virus, dengue virus)

Question 3

Describe the natural history of liver damage.

Answer 3

• Fibrosis normally does not cause much of a problem.
• It becomes clinically relevant and important when dysregulation and excessive scarring occurs in response to persistent injury.
• This leads to tissue dysfunction.
• There is a backward resolution and regression of fibrosis; this is when the underlying cause is eliminated.

Question 4

Discuss the global disease burden of viral hepatitis.

Answer 4

• ~1.5 million deaths per year (death toll comparable to that of HIV, TB and malaria).
• Estimated that 240 million people live with chronic hepatitis B.
• Estimated that 150 million people live with chronic hepatitis C.
• Hepatitis B and C are distributed worldwide, but Africa and Asia have the highest prevalence.
  *

Question 5

What are the clinical features of most viral hepatitisis?

Answer 5

• Prodromal symptoms are generally systemic and variable.
• Constitutional symptoms may precede symptoms and signs of liver disease:
  
  • Anorexia
  • Flu-like symptoms
  • Fatigue
  • Malaise
  • Myalgia
  • Headache
  • Low-grade fever
• Liver dysfunction:
  
  • ​Jaundice
  • Dark urine
  • Abdominal pain
  • Enlarged and tender liver

Question 6

How is the diagnosis of viral hepatitis made?

Answer 6

• Most diagnoses can be made with careful history taking:
  
  • Clinical details
  • Incubation period
  • Epidemiological risk factors
    
    • Travel
    • Drug use
    • Unprotected sex
  • Vaccination history
  • Examination and LFT pattern
    
    • Can tell if acute or chronic

Question 7

CASE STUDY 1

• 30 year old male
• Returning traveller from Thailand
• Presents to GP with abdominal pain
• Generally not feeling well (last 2-3 days)
• Girlfriend has noticed that eyes have become yellow

What are the initial differential diagnoses?

What do you need to obtain from the history?

Answer 7

• Differentials
  
  • ​Hepatitis A
    
    • Patient travelled to high endemic area
  • Hepatitis B
    
    • Don’t know patient’s risk factors
  • Hepatitis C
  • Cholangitis / cholecystitis
  • Medication / other drugs
  • Other infections that could cause abdominal pain (typhoid / dengue)

Question 8

CASE STUDY 1 Continued

• Blood results:
  
  • ALT 1000 (normal range <40)
  • Bilirubin 65 (normal range <12)
  • INR 2.5 (normal range <1)
  • Albumin 34 (normal range >35)
  • Lactate 1.5 (normal range <1)
• Confirms no use of recreational drugs.
• After previous denial, now admits to unprotected sex (heterosexual) 1 month into his travels (~3 months ago).

Now what are the differentials?

Answer 8

• Hepatitis A incubation period ~28 days (15-50 days). Can rule out.
• Hepatitis B incubation period ~3 months - stratify risk.
• Hepatitis C incubation period ~45 days - stratify risk.
• Hepatitis E incubation period ~40 days (but generally present much earlier (15-60 days). Patient has been in an endemic area. Can rule out.
• Cholangitis - unlikely given that he did not present with fever. Can rule out.
• Drugs - denies use but cannot rule out.
• Other infections that could cause abdominal pain (typhoid, dengue) - no history of fever so not likely. Can rule out.

Question 9

What is the incubation period of HBV?

How is it transmitted?

What percentage of babies and children under 6 become chronically infected?

Answer 9

• Incubation period - up to 6 months.
• Infection becomes chronic in 5% of patients.
• 90% of babies and 30-50% of children under the age of 6 will develop chronic infection.

Question 10

What is the incubation period of HCV?

How is it transmitted?

What percentage of patients spontaneously clear the infection?

What percentage of patients become chronically infected?

Answer 10

• Incubation period - up to 6 months, but most patients present after ~45 days.
• Approximately 30% spontaneously clear the infection.
• 70% become chronically infected.

Question 11

CASE STUDY 1

What is the top differential?

Answer 11

• Top differential is HVB.
• Still need to exclude HCV and HIV (returning traveller, unprotected sex).
• Given that he presented with very high LFTs - suggests acute infection.

Question 12

What are the viral serology tests which can be carried out for HBV?

Answer 12

• HBV surface antigen (HBsAg) - active or current infection.
• HBV anti-surface antibody (Anti-HBsAb) - vaccine / natural immunisation.
• HBV core IgG antibody (IgG Anti-HBcAb) - chronic HBV or past infection.
• HBV core IgM antibody (IgM Anti-HbcAb) - diagnostic for acute infection
• HBV e antigen / antibody (HBeAg/Ab)
• HBV DNA (PCR) - not a screening test.

Question 13

What are the viral serology tests which can be carried out for HCV?

Answer 13

• Anti-HCV antibody - past or chronic infection
• HCV antigen - active / current infection
• HCV RNA (PCR) - not a screening test

Question 14

Describe the management of acute HBV.

Answer 14

• Acute hepatitis B does not usually require specific treatment, but may require treatment to relieve the symptoms.
• Likely to will spontaneously clear HBV.
• No need to carry out HBV DNA as it will certainly be high; not useful.
• Repeat bloods in 3-4 weeks to ensure he develops antibodies.
• Advise to use protection.
• Vaccination of household contacts and partner.

Question 15

Describe the properties of chronic HBV infection.

What follow-up do these patients need?

Answer 15

• HBsAg positive > 6 months.
• IgG anti-HBc - positive.
• Anti-HBsAg - negative.
• HDV caused superinfection with HBV.
• Referral to an infectious diseases specialist or gastroenterologist is required.
• These patients will require regular (minimum 6 monthly) LFTs, HBV markers and fibroscan due to increased risk of HCC, and some patients require treatment.

Question 16

Describe the management of chronic HBV.

Outline the current treatment options.

Answer 16

• The goal of treatment is to improve survival and quality of life by preventing disease progression, and consequently HCC development.
• Current treatment options are:
  
  • Pegylated interferon (PegIFNa): subcutaneous for 48 weeks.
  • Nucleos(t)ide analogue (NA) therapy: oral treatment, long-term until HBsAg loss.
    
    • Iamivudine (LAM), adefovir dipivoxil (ADV), entecavir (ETV), telbivudine (TBV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF).

Question 17

What is meant by ‘functional cure’ of HBV?

Answer 17

The loss of HBsAg is regarded as the optimal treatment end-point and is termed ‘functional cure’.

Question 18

What are the goals of treatment of chronic HCV?

Answer 18

• Prevent the complications of HCV-related liver and extra-hepatic diseases, including hepatic necroinflammation, fibrosis, cirrhosis, decompensation of cirrhosis, HCC, severe extra-hepatic manifestations and death.
• Improve quality of life and remove stigma.
• Prevent onward transmission of HCV.

Question 19

Describe the management of chronic HCV.

Answer 19

• Current treatment includes oral direct acting antivirals achieving sustained virological response / clearance (cure).
• Current treatment has >95% efficacy.

Question 20

Describe the aetiology of hepatitis A.

Answer 20

• Transmission - faecal-oral route.
• Person-to-person contact, or contaminated food or drink.
• Foodborne outbreaks have been reported following ingestion of certain shellfish (mussels, oysters and clams that feed by filtering large volumes of sewage-polluted waters) and salad vegetables.

Question 21

How does hepatitis A infection present in most children?

And in most adults?

Answer 21

• Asymptomatic disease is common in children; jaundice may occur in 70-80% of those infected as adults.
• Causes acute infection. Does not cause chronic infection.

Question 22

What are the risk factors for HAV related outbreaks?

Answer 22

• Among MSM
• IVDU
• Consumption of contaminated frozen berries

Question 23

Describe the aetiology of hepatitis E.

Answer 23

• Transmission: feacal-oral route.
• Can also become infected from contaminated drinking water, uncooked / undercooked pork or deer meat, person-to-person transmission, contaminated blood / organ.
• Endemic to EU/EEA countries.

Question 24

Describe how hepatitis E presents.

Answer 24

• Infection may be asymptomatic or cause an acute self-limiting hepatitis.
• HEV infection can also cause extrahepatic manifestations, neurological, renal and haematological disorders.
• Persistent chronic HEV infection has been reported particularly among those who are immunosuppressed or who have pre-existing liver disease.

Question 25

What are the available tests for HAV and what do they tell you?

Answer 25

• Anti-HAV IgM - recent infection.
• Anti-HAV IgG - past infection / vaccination.
• HAV RNA (PCR) - not widely available, not a screening test.

Question 26

What are the available tests for HEV and what do they tell you?

Answer 26

• Anti-HEV IgM - recent infection.
• HEV RNA (PCR) - not a screening test.

Question 27

Describe the management of acute HAV.

Answer 27

• Advice on good hygiene practice.
• Exclude from work until 7 days post-onset of jaundice or in absence of jaundice, from the onset of compatible symptoms.
• Identify possible source of infection.
• Undertake risk assessment.
• Infectious period is taken from 2 weeks before the onset of first symptoms and until one week after the onset of jaundice.
• Management of close contacts.
• Inform public health.