Hepatitis Flashcards
Herpesviridae family- where do they hide?
Herpes simplex 1 (cold sores) and 2 (genital warts)
Lay dormant in the dorsal root ganglia
Varicella Zoster virus (chicken pox and shingles)- where does it hide?
Hides in dorsal root ganglia
Epstein Barr virus (glandular fever)- where does it hide?
Hides in lymphocytes
Symptoms for these viruses
T cell action in the cell mediated response
Antigens are presented to T cells by antigen presenting cells (APCs) eg. a dendritic cell.
Antigens are processed by the APC and the resulting peptides are displayed on the major histone compatibility complexes (MHC) type 1 and 2.
T cells only respond to an antigen when displayed by an MHC, helping to reduce autoimmune complications.
Therefore, different types of T cells are activated based on whether the antigen is bound to MHC class 1 or 2.
If antigen is bound to MHC class 1 = CD8 cell will be activated, this will then cause apoptosis via cytotoxic killing.
If the antigen is bound to an MHC class 2 = naïve CD4 cell will differentiate into a B cell, then differentiate into a plasma cell which will produce antibodies.
Key things to remember is that MHC class 1 are present on all nucleated cells whereas MHC class 2 are only present on APCs. (dendritic, macrophages)
CD4+ vs CD8+ T cells
CD4+ helper T cells: recognise antigens (peptides) displayed by MHC class II
CD8+ cytotoxic T cells: recognise antigens (peptides) displayed by MHC class I
What do naive T cells need to be activated?
For a naïve T cell to be activated it needs two signals:
- One from the MHC class 2
- One co-stimulatory in this diagram it is B7
This combination gives the green light for naive T helper cellsto differentiate. The next step is for them to differentiate into eitherTH1 cells, which promote cytotoxic T cells and cell-mediated immunity, orTH2 cells, which promote B cells and humoral immunity, via antibodies.
Differences in action, cell surface markers and cytokines between Th1, Th2 and CTL cells?
Define hepatitis and clinical presentation
inflammation of the liver. Which can vary from chronic low level, to acute and severe.
CLINICAL PRESENTATION: Hepatitis may be asymptomatic or could present with non-specific symptoms: Abdominal pain Fatigue Pruritis (itching) Muscle and joint aches Nausea and vomiting Jaundice Fever (viral hepatitis)
Causes of hepatitis
Viral hepatitis Alcoholic hepatitis Non-alcoholic fatty liver disease Autoimmune hepatitis Drug induced hepatitis (e.g., paracetamol overdose)
What causes aplastic anaemia in a sickle cell patient?
Parvovirus
Indications for LFTs
ALT is found in high concentrations within hepatocytes and enters the blood following hepatocellular injury. It is, therefore, a useful marker of hepatocellular injury and inflammation.
ALP is particularly concentrated in the liver, bile duct and bone tissues, therefore is less specific to the liver. However, ALP is a useful indirect marker of cholestasis (obstructive picture).
Hepatitis pathophysiology- how does infection occur
Hepatocyte becomes infected with virus
Hepatocyte expresses MHC 1 and presents abnormal viral proteins on surface
→ circulating CD8 T cell detects abnormal proteins → binds → cytotoxic killing → cell apoptosis (Councilman bodies on biopsy)
Hepatocyte death → inflammation + accumulation of more immune cells → hepatomegaly and pain
→ loss of hepatocytes → less ability to conjugate bilirubin → jaundice + leakage of conjugative bilirubin bc liver damage
What if ALT and ALP are both raised?
Often ALT and ALP are both raised. It is the ratio between them that you need to be observing.
If ALT is raised markedly compared to the ALP, this is primarily a hepatocellular (inflammation) pattern of injury.
If ALP is raised markedly compared to ALT, this is primarily a cholestatic (obstructive) pattern of injury.
Why would deranged LFTs mean you are more likely to bruise?
The liver synthesising clotting factors, thus with liver damage the prothrombin time (PT) is deranged, therefore clotting will take longer, more likely to bleeding/bruise.
What LFT is often raised in alcoholic liver disease?
A good way to remember that GGT is often raised in alcoholic liver disease is Gamma Gin and Tonic
LFT markers of hepatitis
high transaminases (AST/ALT) Proportionally less ALP
Raised bilirubin due to inflammation- mix of conjugated and unconjugated
Investigations for hepatitis
LFTs
Hepatitis serology
FBC, U&E’s, clotting screen
consider: Fibroscan (cirrhosis), liver ultrasound (HCC), liver biopsy, CT/MRI, testing for co-infection
Hepatitis types overview
Hepatitis A:
Faecal oral transmitted
Is acute and self resolves
Hepatitis B:
The only virus containing DNA
Is transmitted through the 3 B’s: blood, baby, birth
Can be acute or chronic
Hepatitis C:
Is the type most likely to cause hepatocellular carcinoma
The 2C’s: chronic, cancer
Hepatitis D:
This type of hepatitis can only be contracted in the presence of hepatitis B (the person has to already have a current Hep B infection)
Can also be acute or chronic
Hepatitis E:
Faecal oral transmission
Hep E is predominantly acute, usually self resolves via supportive management (rest, get adequate nutrition and fluids, avoid alcohol, stop drugs impacting on liver function)
Which hepatitis viruses are transmitted faecal-orally?
A and E lol
Which hepatitis viruses are transmitted through blood/percutaneous routes, sexual or perinatal/pregnancy?
B and C
Risk factors for hepatitis
Men who have sex with men
Unprotected anal sex
Sex with IVDU
Active STI infection
Perinatal transmission
Transmission from mother’s blood to baby via mucus membranes during birth
Key components of Hep B virus: 3 antigens
Surface antigen – proteins in the outer lipid envelope, can test the serum (blood) for presence of it. The Hep B vaccine contains the HbsAg, however, it can also be a sign of active infection.
E antigen – is a marker of how fast the virus is replicating and therefore how infectious the person is, and is positive in the acute phase
Core antigen – is inside the capsid, not detectable in serum because covered by envelope therefore you won’t detect it
Key components of Hep B virus: 3 antibodies
Surface antibodies – are present when you have immunity to HepB, either through a past infection or a vaccination
E antibody - this is not always present, but may be observed in the chronic phase or after someone has cleared the infection
Core antibodies – are produced in response to infection. IgM antibodies are predominant in the acute phase and IgG are the predominant antibody in the chronic phase, due to class switching (assisted by T Helper Cells and their cytokines)
Serology result for successful Hep B immunisation
Only Anti-HBs should be positive, everything else negative
When is Hep B vaccine offered?
Hepatitis B vaccination is
routinely available as part of the NHS
vaccination schedule. It’s offered to all
babies at 8, 12 and 16 weeks of age.
Hep B treatment
pegylated interferon and/or antiviral agent or interferon free treatments.
- Antiviral agents – examples Entecavir and Tenofovir disporoxil
- May treat those with dual infection e.g. HIV and HBV
- Treatment strategy depends on hep B virus infection status - viral load – coinfection with hep C or HIV and liver cirrhosis
Hep C diagnosis
• Infected and recovered
– HCV RNA -ve
– IgG antibodies +ve
• Chronic infection
– HCV RNA +ve
– IgG antibodies +ve
For patients with chronic infection, genotyping will be performed in pre-treatment assessment.
Prevention of Hep C
No vaccine yet
• Prevention based on avoidance of exposure
– Education of IVDUs and MSMs
– Needle exchange programmes
– Caesarean Section for pregnant patients with HCV
– Avoidance of inoculation injuries by Health Care Workers
– Screening of blood/organ donors (also true for HBV)
– Screening of HCWs performing Exposure prone procedures
– Infection prevention and control in hospitals
Hep C treatment
- Treatment with pegylated interferon and ribavirin, but
* Rapidly advancing field with specific antivirals allowing interferon free treatments
Hep D diagnosis
Patient must have HBV infection
- detection of HDV RNA and serology
Viral infections causing abnormal LFTs
Epstein Barr
Cytomegalovirus
Hep B infection serology
Hep B ACUTE infection serology
Hep A infection serology
no treatment
vaccine available
many asymptomatic infections
Stages of viral hepatitis
Clinical signs of viral hepatitis
