Hepatitis – A/B/C/D/E/autoimmune Flashcards
Define hepatitis.
Hepatitis describes inflammation in the liver. This can vary from a chronic low level inflammation to acute and severe inflammation that leads to large areas of necrosis and liver failure.
How long does hepatitis persist for to be deemed chronic?
6 months.
Give 5 general causes of hepatitis.
- Alcoholic hepatitis
- Non alcoholic fatty liver disease
- Viral hepatitis
- Autoimmune hepatitis
- Drug-induced hepatitis (e.g. paracetamol overdose)
Give 3 infective causes of acute hepatitis.
Viral -
1. Hepatitis A and E infection.
2. Herpes viruses e.g. EBV, CMV, VZV
Non-viral -
3. Leptospirosis
4. Toxoplasmosis
5. Coxiella (Q fever)
Give 3 infective causes of chronic hepatitis.
- Hepatitis B (+/-D).
- Hepatits C.
- Hepatitis E.
Give 3 non-infective causes of acute and chronic hepatitis.
- Alcohol.
- Drugs.
- Toxins.
- Autoimmune.
- Hereditary metabolic.
Give 3 symptoms of acute hepatitis.
- General malaise.
- Myalgia.
- GI upset.
- Abdominal pain.
- Raised AST, ALT.
- +/- jaundice.
- Tender hepatomegaly.
Give 4 symptoms of chronic liver disease that can be seen in chronic hepatitis.
+/- signs of chronic liver disease:
- Clubbing
- Palmar erythema
- Dupuytren’s contracture (one or more fingers bending into palm of hand)
- Spider naevi
What are the potential complications of chronic hepatitis?
Uncontrolled inflammation -> fibrosis -> cirrhosis -> HCC.
Is HAV a RNA or DNA virus?
HAV is a RNA virus.
Is HAV acute or chronic?
Acute! There is 100% immunity after infection.
How is HAV transmitted?
Faeco-oral transmission. E.g. contaminated food/water; shellfish.
Who could be at risk of HAV infection?
Travellers and food handlers.
What are the risk factors for HAV?
Poor sanitation, overcrowding, contaminated food/water. (fish in sewage water)
Give 3 symptoms of HAV.
Give 2 later signs of HAV.
Symptoms: fever, malaise, anorexia, nausea, vomiting, arthralgia (joint pain).
Later signs - jaundice, moderate hepatosplenomegaly, lymphadenopathy.
Can cause cholestasis (slowing of bile flow through the biliary system) with dark urine, pale stools and moderate hepatomegaly.
How might you diagnose someone with HAV infection?
Viral serology:
Initially anti-HAV IgM (acute);
And then anti-HAV IgG (raised for life - carrier)
Blood test:
LFTs - AST/ALT are raised
Describe the management of HAV infection.
- Supportive.
- Monitor liver function to ensure no fulminant hepatic failure.
- Manage close contacts.
Describe the prevention of HAV.
Passive and active immunisation (inactivated protein).
Good hygiene.
Is HAV a notifiable disease or not?
YES!!
Is HEV a RNA or DNA virus?
HEV is a small RNA virus.
Is HEV acute or chronic?
Usually acute, but there is a risk of chronic disease in the immunocompromised.
Once you’ve had HEV, then you cannot get infected again - 100% immunity
What infection is HEV similar to?
HAV.
How is HEV transmitted?
Faeco-oral transmission.
Usually spread by contaminated water, rodents, dogs and pigs.
How might you diagnose someone with HEV infection?
Viral serology: Initially anti-HEV IgM and then anti-HEV IgG.
What can you detect in blood and stools to confirm a diagnosis of chronic HEV infection?
Use HEV RNA to detect chronic infection
Describe the primary prevention of HEV.
- Good food hygiene and sanitation.
- A vaccine is in development.
Is HEV a notifiable disease or not?
YES!!
Is HBV a RNA or DNA virus?
HBV is a DNA virus! It replicates in hepatocytes.
How is HBV transmitted?
Blood-borne transmission
e.g. blood products, IVDU, needle-stick, tattoos, sexual
HBV is found in saliva and semen
Vertical transmission:
Mother-to-child transmission (MTCT)
Horizontal transmission - particularly in children
* Through minor abrasions or close contact with other children
* HBV can survive on household articles such as toys or toothbrushes for
prolonged periods of time
HBV is highly infectious!
Name 3 at-risk groups for HBV.
- Healthcare personnel + their sexual partners and carers
- Emergency + rescue teams and morticians = exposure to blood
- CKD/haemodialysis patients
- Travellers
- Homosexual men
- IV drug users
- Babies of HBV+ mothers
- Haemophiliacs
Describe the natural history of HBV in 4 phases.
- Immune tolerance phase: unimpeded viral replication -> high HBV DNA levels.
- Immune clearance phase: the immune system ‘wakes up’. There is liver inflammation and high ALT.
- Inactive HBV carrier phase: HBV DNA levels are low. ALT levels are normal. There is no liver inflammation.
- Reactivation phase: ALT and HBV DNA levels are intermittent and inflammation is seen on the liver -> fibrosis.
What HBV protein triggers the initial immune response?
The core proteins.
What are the different viral markers for HBV?
Surface antigen (HBsAg) – active infection
E antigen (HBeAg) – marker of viral replication and implies high infectivity
Core antibodies (HBcAb) – implies past or current infection
Surface antibody (HBsAb) – implies vaccination or past or current infection
Hepatitis B virus DNA (HBV DNA) – this is a direct count of the viral load
Explain the pathophysiology of HBV.
- HBV = DNA virus
- Structure of HBV:
- Inner core or nucleocapsid
- Surrounded by an outer envelope of surface protein (Hepatitis B surface antigen = HBsAg) - HBsAg made in excess by infected hepatocytes and can exist separately from the whole vision in serum and body fluid.
- After penetration into hepatocyte, the virus loses its coat and the virus core is transported to the nucleus without processing.
- Following infection, which may be subclinical (I.E. little symptoms), around
1-10% of patients will not clear the virus and will develop chronic Hep B - Not clearing virus = chronic infection -> cirrhosis -> decompensated cirrhosis -> liver failure
- Both cirrhosis and chronic infection can lead to HEPATOCELLULAR CARCINOMA - VERY BAD!!
What percentage of people with acute HBV infection will progress onto chronic infection?
Approximately 5%.
What are the clinical features of HBV?
In many: the infection can be subclinical I.E. little symptoms.
Resembles HAV:
- Fever, malaise, nauseas, anorexia.
- Arthralgia (joint pain) and urticaria (hives).
What are the potential consequences of chronic HBV infection?
- Cirrhosis.
- HCC.
- Decompensated cirrhosis.
How might you diagnose someone with HBV?
Viral serology - HBV ‘assay’:
- HBs-Ag is present 1-6 months after exposure
- HBs-Ag presence for more than 6 months implies carrier status
- HBe-Ag
- Anti-HBs
- Anti-HBc IgM after 3 months
How would you know if someone had acute or chronic HBV infection?
You would do a follow up appointment at 6 months to see if HBV surface Ag (HBs-Ag) had cleared.
If it was still present, then the person would have chronic hepatitis.
Describe the management of HBV infection.
- Supportive.
- Monitor liver function.
- Manage contacts.
- Follow up at 6 months to see if HBV surface Ag has cleared. If present -> chronic hepatitis.
Describe 2 treatment options for chronic HBV infection.
- SC Pegylated Interferon-alpha 2A
(boosts immune system.) - Antivirals e.g. oral tenofovir, oral entecavir
(They inhibit viral replications.)
HBV treatment: give 3 side effects of alpha interferon treatment.
- Myalgia.
- Malaise.
- Lethargy.
- Thyroiditis.
- Mental health problems.
How can HBV infection be prevented?
Vaccination - injecting a small amount of inactivated HbsAg.
Passive immunisation is given to non-immune contacts after high-risk exposure.
Hep B vaccine given (UK) to children born to +ve mothers, chronic liver patients, haemophilia patients, offered as a travel vaccine, and to healthcare workers.
List 2 possible complications of HBV.
Cirrhosis, HCC, fulminant hepatic failure, cholangiocarcinoma, cryoglobulinaemia
Is HBV a notifiable disease or not?
YES!!
Is HDV a RNA or DNA virus?
It is a defective RNA virus. It required HBsAG to protect it.
Infection with what virus is needed for HDV to survive?
HDV can’t exist without HBV infection!
HDV = an incomplete RNA that needs Hep B for assembly
It needs HBsAg to protect it.
How is HDV transmitted?
Blood-borne transmission (same as HBV), particularly IVDU.
How can you test for HDV?
Test for:
HDV- RNA
Anti- HDV antibody
Same as HBV.
What would confirm co-infection of HBV and HDV?
Serum IgM anti-HDV in the presence of IgM anti-HBV confirms co-infection
What can HDV cause as a result of co-infection with HBV?
- Secondary acute hepatitis
- Worsening liver fibrosis
- Increase risk of fulminant hepatitis
- Chronic hepatitis
- Hepatocellular carcinoma (HCC)
How can you treat HDV infection?
- SC Pegylated Interferon-alpha 2A
(boosts immune system.) - May need liver transplant as interferon alpha has limited success.
How can HDV be prevented?
Hep B vaccination
Is HDV a notifiable disease or not?
YES!!
Is HCV a RNA or DNA virus?
HCV is a RNA flavivirus.
How is HCV transmitted?
Blood borne (blood products + bodily fluids)
Give 4 risk factors for developing HBV/HCV infection.
- IVDU.
- People who have required blood products e.g. blood transfusion.
- Needle-stick injuries.
- Unprotected sexual intercourse.
- Materno-foetal transmission.
What haematological disorder is associated with HCV?
Non-Hodgkin’s lymphoma
How might you diagnose someone with current HCV infection?
Viral serology:
HCV antibody:
* Present within 4-6 weeks
* False negative in immunosuppressed (no antibodies produced) and in
acute infection (I.E. before 4 weeks)
HCV RNA:
* Indicates current infection
* Diagnoses acute infection
You want to find out if someone has previously been infected with HCV. How could you do this?
Viral serology - anti-HCV IgM/IgG indicates that someone has either a current infection or a previous infection.
What viral markers would you look for in HCV at 8 weeks?
HCV RNA at 8 weeks.
If you took a liver biopsy of a HCV patient, what might you see?
Lymphoid follicles in portal tracts and fatty change
Describe the treatment for HCV.
If HCV RNA does not decline:
= SC PEGYLATED INTERFERON-ALPHA 2A/B + ORAL RIBAVIRIN
Triple therapy with direct acting antivirals (DAA) are currently in use e.g. NS5A and NS5B:
- NS5A (initiates viral replication) inhibitor end in ASVIR e.g. ledipasvir,
ombitasvir, ritonasvir - NS5B (needed for viral replication) inhibitors end in BUVIR e.g.
sofosbuvir, dasabuvir
What is the disease course of HCV? How many recover? How many develop a chronic infection?
- 1 in 4 fights off the virus and makes a full recovery
- 3 in 4 it becomes chronic
Give 2 possible complications of chronic HCV infection.
Liver cirrhosis and associated complications
Hepatocellular carcinoma (HCC)
How can HCV infection be prevented?
- Screen blood products.
- Lifestyle modification.
- Needle exchange.
- Precaution when handling body fluid.
There is currently no vaccination and previous infection does not confer immunity.
What types of viral hepatitis are capable of causing chronic infection?
Hepatitis B (+/-D); C and E in the immunosuppressed.
Is HCV a notifiable disease or not?
YES!!
VIRAL HEPATITIS SUMMARY:
- A is Acquired by mouth from Anus, is Always cleared Acutely and only ever Appears once
- E is Even in England and can be Eaten (found in pigs), if not always beaten
- B is Blood-Borne and if not Beaten can be Bad
- B and D is DastarDly
- C is usually Chronic but Can be Cured - at a Cost
What is autoimmune hepatitis?
Autoimmune hepatitis is a rare cause of chronic hepatitis.
Not sure of the exact cause, however it could be associated with a genetic predisposition and triggered by environmental factors such as a viral infection that causes a T cell-mediated response against the liver cells.
This is where the T cells of the immune system recognise the liver cells as being harmful and alert the rest of the immune system to attack these cells.
There are 2 types of AI hepatitis. Describe them.
2 types that have different ages of onset and autoantibodies:
Type 1: occurs in adults
Type 2: occurs in children
Type 1 typically affects women in their late 40s/50s. It presents around or after the menopause with fatigue and features of liver disease on examination. It takes a less acute course than type 2.
In type 2, patients in their teenage or early 20s present with acute hepatitis with high transaminases and jaundice.
What are the type 1 autoimmune antibodies for AI hepatitis?
Type 1 Autoantibodies:
Anti-nuclear antibodies (ANA)
Anti-smooth muscle antibodies (anti-actin)
Anti-soluble liver antigen (anti-SLA/LP)
What are the type 2 autoimmune antibodies for AI hepatitis?
Type 2 Autoantibodies:
Anti-liver kidney microsomes-1 (anti-LKM1)
Anti-liver cytosol antigen type 1 (anti-LC1)
What investigation is used to confirm AI hepatitis?
Liver biopsy
Management of AI hepatitis.
- High dose steroids e.g. prednisolone
- Taken alongside immunosuppressants - Immunosuppressants e.g. azathioprine
- Immunosuppressant treatment is usually successful in inducing remission
- Usually required life long. - Liver transplant may be required in end stage liver disease, however the autoimmune hepatitis can recur in transplanted livers.
