W30 Viral hepatitis (GN) Flashcards
Hepatitis overview:
What is hepatitis?
How many types?
What is the duration of acute/chronic hepatitis?
Hepatitis → inflammation of the liver tissue and may be caused by alcohol, drugs, autoimmune/metabolic diseases or viral infections (over 50%)
* 5
▪ Hepatitis A virus (HAV)
▪ Hepatitis B virus (HBV)
▪ Hepatitis C virus (HCV)
▪ Hepatitis D virus (HDV)
▪ Hepatitis E virus (HEV)
▪ Occasionally, other viruses (e.g. Cytomegalovirus, Epstein-Barr virus)
* Acute= <6 months
* Chronic >6 months
Hepatitis A virus (HAV) – overview (sharing similarities with HEV)
How is it transmitted?
How is it treated?
HAV (sharing similarities with HEV)
* ONLY acute infections → NO CHRONIC HEPATITIS
▪ 30% is asymptomatic/subclinical,
▪ 70% symptomatic after 2-4 weeks of incubation
Transmission
* Orofecal transmission from ingestion of contaminated water or food (mussels, oysters)
Pathogenesis
* Infects intestinal cells → viremia → spread to liver, kidneys, spleens
Treatment/prevention
* No antiviral drug available. The treatment is mainly supportive (self-limiting)
* HAV Vaccine is available and offered to risk groups → BNF LINK
Hepatitis B virus (HBV) - distribution (for info)
- 1/3 of the global population have encountered HBV in their life
- HBV can cause asymptomatic, acute or chronic infections
- 350 million people are chronically HBV-infected, with 1 million deaths annually
-180,000 people with chronic infection in the UK
Hepatitis B virus (HBV) - transmission?
How is it transmitted? (3)
➢Perinatally - At birth (endemic countries)
o Vertical transmission (mother to baby)
▪ Prevented by passive immunisation and vaccines to the new-borns immediately after birth
➢Sexually - STI
o The virus is present in blood and body fluids
➢Parentally - Though blood (most common)
o Unsterilised contaminated medical equipment
o Sharing toothbrush/razors or needles for drugs/tattoos/piercings
o Direct exposure to infected blood - blood transfusion (in the past)
All routes can be prevented:
HBV remains infectious for >5 days on surfaces → inc risk in scenarios with poor hygienic conditions
What are the HBV high risk groups?
- People from endemic regions or travellers
- Babies born from mothers with chronic infections
- Intravenous drug abusers
- Multiple sex partners
- Healthcare personnel (without preventive measures)
- Patients requiring haemodialysis or frequent transfusions
- Immunocompromised patients
Hepatitis B virus (HBV) - Virus Structure
Do Not Learn
- Partially double-stranded DNA
- Enveloped virus
- 10 HBV genotypes (A–J)
- Oncovirus
Viral antigens
1. HBsAG (surface antigen)
Hallmark of infection:
▪ Early phase of acute infection
▪ Persist in chronic infections
- HBeAG (E antigen)
Indicates active replication:
▪ High infectivity and high viral load
▪ Risk factor for chronic hepatitis
HBV life cycle - simplified
What are the steps?
- HBV interacts with receptors of hepatocytes
- HBV enters the cells (endocytosis) and the
genome is released in the nucleus - Cell enzymes repair gaps in the viral DNA
forming cccDNA (full double-stranded DNA) that is transcribed and translated in viral proteins -
HBV reverse transcriptase uses RNA to
replicate viral genome - Some viral DNA integrates into the chromosomes
- Virion assembly inserting the HBV genome
- Virions are released by budding acquiring the
envelope
Pathogenesis - acute phase Hepatitis B
Asymptomatic phase – incubation period (4-12 weeks)
* HBV enters and replicates in hepatocytes without causing symptoms
Acute phase:
* HBV (DNA & HBsAg) is detected in plasma (VIREMIA), preceding symptoms
* T-cell response is activated for viral clearance, but it is also responsible for hepatocellular necrotic damage. HBV itself does not cause hepatotoxicity.
➢ Early response - Cytokines release (IFNγ and TNF) with no cytolytic effect
➢ Late response - Cytotoxic CD8+ T lymphocytes are primed by CD4+ helper T cells
in killing infected cells by releasing granzymes → liver damage & inflammation
* Acute hepatitis can resolve on its own (within 6 months)
Clinical manifestations of acute viral hepatitis (A, B & C)
What are the 3 phases?
- Prodromal (pre-icteric) phase:
▪ Fever, nausea, joint pain, malaise
▪ serum ALT levels rise (severity) - Icteric phase (after 3-10 days):
▪ Jaundice, dark urine, pale faeces
▪ Systemic symptoms often regress
▪ The liver is enlarged and tender - Resolution phase:
▪ Icteric symptoms resolves
▪ fatigue and malaise may last
HBV - 1% fulminant hepatitis→ sudden and extensive liver damage requiring urgent liver transplant
Pathophysiology Hepatitis B chronic infection
What is the Chronic phase defined as?
➢when the immune system fails to clear the virus within six months
- CD8 T cell response that cannot clear the virus causes extensive liver necrosis and
inflammation, leading to clinical complications (cirrhosis and hepatocellular carcinoma) - HBV DNA integrates into hepatocytes’ chromosomes. Viral clearance is very rare
- HBV is an oncovirus:
HBV induces inactivation of tumour suppressor genes, leading to apoptosis inhibition →cancer transformation →hepatocellular carcinoma - HDV superinfection accelerated the hepatitis B clinical progression
Hepatitis B chronic infection progression:
Stages of Chronic liver disease= accelerated by alcohol coinfections (HCV, HIV, HDV), fatty liver diseases
Chronic Hepatitis– Liver Cirrhosis (Compensated/Decompensated)- Hepatocellular Carcinoma
- Cirrhosis is a result of extensive hepatic necrosis that leads to **form fibrous tissue leading to permanent scarring that gradually replace the normal liver tissue, disrupting its functions
- Cirrhosis induce compensatory hepatocyte cell proliferation → liver nodularity
- Uncontrolled hepatocyte hyperproliferation → hepatocellular carcinoma (HCC)
Hepatitis B virus (HBV) – Antiviral therapy:
Nucleoside analogues:
What are some examples? (3)
- Reverse transcriptase is the main target of anti-HBV drugs
Nucleoside analogues:
Lamivudine
Entecavir (ETV)
Telbivudine (LdT)
Nucleoside monophosphate:
* Tenofovir disoproxil fumarate (TDF)
* Tenofovir alafenamide (Vemlidy)
▪ They resemble natural nucleosides and compete with them for incorporation into viral DNA.
▪ Once incorporated, they terminate DNA chain elongation, preventing viral genome replication.
- Peg-IFNα-2a - pegylated derivatives of interferon α
▪ Interferon boosts the immune system to fight viral infection
▪ Pegylation to inc half-life in blood
▪ Associated to many side effects → requiring careful monitoring
Hepatitis B virus (HBV) – Antiviral therapy:
* Chronic HBV infections: How long should patients be monitored?
What are the desired outcomes?
How long is the treatment?
- Patients should be monitored every six months for viral load and renal function
▪ Reducing HBV DNA to undetectable levels
▪ Prevent complications/disease progression/mortality
o Treatment is usually lifelong → complete cure of the HBV chronic is elusive due to viral DNA integration in the chromosomes of the infected hepatocytes
HBV pre-exposure prophylaxis:
What treatment is given?
Who to vaccinate?
3 HBV vaccines available
Within the routine NHS childhood vaccination schedule:
▪ Babies at 8 weeks → part of the 6-in-1 vaccine (with diphtheria, Haemophilus influenzae type
b, tetanus, poliovirus, pertussis (whooping cough). Boosts required at 12 and 16 weeks.
* Babies at birth from infected mothers (with immunoglobulins and following boosts)
* Unvaccinated individuals at risk with no previous HBV exposure (HBsAg negative)
Which one of the following is true about hepatitis B virus?
A) HBV is transmitted primarily through contaminated food and water
B) HBV infection always leads to chronic liver disease
C) Chronic HBV infection is managed by nucleoside/nucleotide inhibitors of the viral reverse transcriptase
D) No vaccines are available to prevent HBV infections
E) HBV infection is always symptomatic
= C
Chronic HBV infection is managed by nucleoside/nucleotide inhibitors of the viral reverse transcriptase
