What is the treatment for acute hep B?
- Conservative, OP
- Liver function, PT, HBV status (HbsAg, eAg, anti-Hbe and anti HBs) monitored
- Advice: do not drink alcohol and avoid hepatotoxic drugs until hepatitis resolved.
Who needs to be tested for HBV? And what needs else to be done to them
- Sexual and close household contacts: tested for evidence of current of past HBV infection
- Give first dose of hep B vaccine to all sexual partners whilst awaiting results.
- If NO evidence of either give active immunisation with hep B vaccine
- If infected or already immune to HBV discontinue immunisation.
- Give HBIG to recent susceptible sexual contacts. Close household contacts do not need HBIG, just the vaccine.
What does the patient with HBV infection need to be warned about infectivity?
Warn patient: infectivity of his blood: sharing razors, toothbrushes, needles. Do not donate blood for at least 2 years. Condom until no longer infectious and blood no longer contains HbsAg.
What are the indications for hepatitis B vaccine?
- 1. injecting drug users
- 2. multiple sexual partners – prostitutes, homosexual and bisexual men
- 3. household and sexual contacts of HBV infected persion
- 4. baby born to HBV infected mother
- 5. patients receiving lots of blood transfusion eg thalassaemic or blood products eg haemophiliacs
- 6. relatives responsible for administration of blood products to eg haemophiliacs
- 7. health care and lab workers who have contact with blood or blood contaminated body fluids
- 8. chronic renal failure: need double dose of vaccine
- 9. staff and patients in residential accommodation for mentally handicapped
what is the HBV vaccine used in this country?
- Recombinant HbsAg
- Expressed in yeast cells
If anti-HCV antibodies are absent, does that exclude an acute HCV infection?
No because anti-HCV seroconversion may be delayed up to 1 month after an acute HCV infection.
How is diagnosis of HCV made?
Detection of serum HCV RNA or HCV Ag
What are the ways HCV can be transmitted?
- Needle stick
- Blood products
- Mother to child
What are the pathological features of Hepatitis?
- Liver cell necrosis
- Inflammatory cell infiltrate
What are clinical features of viral hepatitis?
- Liver enlarged and tender
- AST:ALT ratio <1 (compared to alcoholic where it is >1)
Which drugs can cause hepatitis?
- Anti TB eg isoniazid
- Paracetamol OD
Acute heptatitis pathology
- Ballooning degeneration
- Councilman bodies (acidophils)
- Inflam lymphocytes
Which drugs can cause chronic active hepatitis?
what are the symptoms of acute hepatitis?
- Non-specific, pro-dromal symptoms eg fever, malaise, N+V, anorexia, diarrhoea, abdo pain, headache, myalgia, arthlagia
- Jaundice follows a few days-2weeks later
What examination findings of acute hepatitis?
- Tender hepatomegaly
- Cervical lymphadenopathy
- Skin rash
What is the most common type of acute hepatitis?
How is hep A spread, who?
- Travellers tropics
- Raw or poorly cooked shellfish
What is the incubation time for hep A? and what type of virus?
when is the virus present in the infected person’s faeces?
- 2 weeks before onset of jaundice
- But only a few days after symptoms! So spread before you know you've got it!
How is hep A diagnosed?
showing IgM anti-HAV in the patient's blood. This antibody is present within 10 days of onset of viraemia and therefore detectable at presentation in almost all cases.
What is the treatment of hep A?
- Supportive, no alcohol
- If fulminant then give interferon alpha
Who needs hep A prophylaxis?
- 1. pre-exposure: active immunisation eg Havrix monodose, an inactivated protein derived from HAV
- a. traveller
- b. severe CLD
- c. job risk
- d. haemophiliac
- e. homosexual
2. post exposure
a. passive immunisation HNIG (human normal Ig) to contacts and household, remember faeco-oral!
What is the natural progression of hepatitis A?
- Usually self-limiting
- Over in 3-6 weeks
Which kind of people are at risk of hep A?
- 1. travellers
- 2. vagrants
- 3. sanitation workers
- 4. workers in child care centres and institutions for the destitute
- 5. homosexual men
- 6. recipients of clotting factors
- 7. community wide outbreaks
what type of virus is hep B?
what is the incubation period for hep B?
What are the modes of transmisison of hep B?
- Vertical: mother to infant
- Needle stick injury
- Needle sharing IVDU
- Blood and blood products
Where can expression of HbcAg be seen in the cell?
Where can expression of HbsAg and HbeAg be seen in the cell?
When is the eAg made and what does high levels indicate?
- Made in active viral replication
- High levels indicates high degree of infectivity
What do the cells look like in acute hep b?
Ground glass hepatocytes
What is the mortality assocaietd with acute hep b infection?
Less than 1%
What % of adults will become HBV carriers?
Which age group/type of people are most likely to become HBV carriers?
HBV infections in neonates and immunosuppressed
What may HBV carriers develop?
- Extra-hepatic disease: GN in childern, PAN, cryoglobulinaemia
What makes a carrier have high infectivity and what are they referred to and why?
- When their serum contains lots of sAg and eAg
- Referred to as supercarriers as are principal reservoir of infection
How do carriers become less infective? Describe blood results and what are these people referred to as?
- After time the infection becomes partially suppressed
- The sAg remains in serum but eAg is replaced by anti-HBe and virions disappear from circulation
- These carriers are less infectious and referred to as SIMPLE carriers
What defines chronic hep B?
Presence of surface antigen for over 6 months = carrier status: chronic
If a patient had anti-HbsAg alone, what would that indicate?
In HBV, what is the method of monitoring the response to treatment?
HBC PCR – see the viral load
What is the prognosis of an acute HBV infection which presents with jaundice?
Virtually NEVER leads to CHRONIC carriage
What is the treatment of acute hep B?
- No alcohol
What is the treatment of chronic hep B, which group of patients are treated and why?
- Treat supercarriers (eAg+) in order to seroconvert them to simple carriers who have anti-HBe
- Use interferon-a and lamivudine (nucleoside analogue. Nucleoside reverse transcriptase inhibitor (NRTI)
What needs to be given to non-immune contacts after high risk exposure? Give example of who
- Passive immunisation with HBIG
- Eg newborn baby of HBsAG positive mother
Which staff cannot do EPPs?
If HBeAg carriers
Which parts of the world is HBV common in?
How do you know if an acute hep B infection has recovered completely?
Disappearance of HBsAg frin serum (and will have anti-HBs)
What are the SE of lamivudine?
- Lactic acidosis
- Loss of subcut fat
- Nausea, dyspnoea
What are SE of pegINF?
- Flu like symptoms
What are the adv of pegINF over normal INF?
- Increased half life
- Reduced clearance
- Only need once weekly dosing
- Better response rates with peg
What are the complications of HBV infection?
- Chronic hepatitis
- Fulminant hep failure
Where has a national HBV vaccine been introduced and what has this led to?
reduction in incidence of HCC particularly in countries such as Taiwan, which has high prevalence of hepatitis B
What type of virus is HCV?
what is the incubation period of HCV?
Before screening of blood donoation, what was the most important cause of post-transfusion NANB hep?
What is the MAIN mode of transmission of HCV?
- IVDU and needlestick
- Mother to child and sexually is seen but not as much
How many different genotypes of HCV are there?
What are the clinical features of most acute infecitons?
Subclinical! If there are symptoms they are usually MILD. Jaundice is uncommon, only in about 10%
What proportions of acute infections develop into chronic?
What can chronic HCV infection act as a trigger factor for developing…?
- Mixed essential cryoglobulinaemia
- Porphyria cutanea tarda
- Autoimmune liver disease
What is Porphyria cutanea tarda?
- Blistering of the skin in areas receiving high levels of sunlight exposure. Heals with scars
- It is due to enzyme deficiency is the last step of haem synthesis
How is ACUTE HCV infection diagnosed?
- Detection of HCV RNA by RT-PCR
- Serology cannot be used for HCV infection as seroconversion may be delayed for several months
How is chronic HCV infection diagnosed?
Serology: antibody detection (as takes several months for antibodies to form after acute infection)
What is the treatment of HCV? And how many get viral eradication?
Infereon and ribavirin. 40% eradication
How does the treatment of HCV depend on its genotype?
- Genotype 1, 4: treat for 1 year (40% sustained response)
- Genotype: 2, 3: treat for 6 months (80% sustained response)
How is HCV treatment monitored?
Quanititative real time RT PCR to measure viral load
What is the prophylaxis for HCV infection?
There is none at the moment! No vaccine yet
What type of virus is hep D? what does it need to replicate?
- Delta virus
- Defective RNA virus
- Dependent on Hep B for its own replication
What are the 2 patterns of replication of Hep D? which is more likely to become chronic?
- Co-infection: HDV simultaneously with HBV infection
- Superinfection: infection of HDV into a person with acute or chronic HBV. Superinfection usually develops into chronic HDV infection and high risk of CLD, cirrhosis, hepatoma
What happens to the total anti-HDV levels in co-infection? Also what happens to ALT?
- Become undetectable fast, even though it’s a severe infection, it is ACUTE
- ALT goes high first then low quickly
What happens to the total anti-HDV levels and ALT in superinfection?
Total anti-HDV remains high and ALT remains high
What is the MAIN mode of transmission of HDV?
Parenteral – IVDU (can sexually)
How is prophylaxis of HDV achieved?
By preventing HBV infection
What type of virus is Hep E?
how is Hep E transmitted? And what is it assoc with?
- Faeco-oral route
- Assoc with large water-borne outbreaks eg sewage overflow into water reservoirs
What is the spread of HEV like in household contacts
LOW as its not spread by close contact
What is the natural progression of HEV and what makes its prognosis bad?
- Usually self-limiting, like HAV.
- In pregnancy: very high mortality of 20%
How is the diagnosis of HEV made?
- Serology: anti-HEV antibodies
- Can use HEV RT-PCR to confirm infection
What is the treatment of HEV?
Supportive with complete resolution in most cases.
What is the prophylaxis for HEV?
None but ENSURE CLEAN WATER SUPPLY (no uncooked or shellfish)
What are the features of Hep GBV-c?
What is spread of Hep GBV and who gets it?
- Spread: parenteral
- post-transfusion hepatitis
what is the progression of HGV?
- Infections resolve spontaneously
- But persistent infections are common with a prevalence of 2% in UK
When there is jaundice, what level of bilirubin is likely to be in the blood?
When you think a patient has Gilberts but want to clarify, which simple blood test can be done?
Split bilirubin and the unconjugated will be higher than the conjugated
Which clotting factor does the liver NOT make?
Give 2 situations when there is a raised unconjugated bilirubin?
- Haemolysis: acquired/inherited…
- Failure of conjugation: Gilberts, neonate
If there is a raised conjugated bilirubin, what does that indicate?
Haemolysis or failure of conjugation
Give 2 reasons why urinary urobilinogen would be absent?
When would you see a raised urobilinogen?
- Hepatocellular dysfunction
Which protein is an important marker of acute liver damage and why not another one?
- Clotting factors as short half life.
- Not albumin as long half life of 20 days
What is the deficiency in Wilsons?
What are the values for iron, ferritin and TIBC in haemochromatosis?
Iron up, ferritin up, TIBC down or normal (as transferrin is fully saturated)
Which Ig is raised in PBC?
Which Ig is raised in micronodule cirrhosis?
If there is a raised ALP, which simple test can you do to confirm the ALP is coming from liver?
GGT as it follows ALP pattern
What type of liver disease do you see a raise in GGT?
Alcoholic liver disease
What are the causes of pre-hepatic jaundice?
- Ineffective erythropoeisis: pernicious anaemia
- Excess RBC destruction: immune anaemia, sickle cell
- Breast feeding
- Crigler Najjar
what are the causes of intrahepatic jaundice?
- Drugs: chlorpromazine
- Infiltration: tumour, sarcoid,
- Rotor syndrome
- Dubin Johnson
What are causes of extrahepatic jaundice?
- Head of pancreas ca
- Stones in CBD
- Biliary atresia
Why do you get excess urobilinogen in hepatic jaundice?
Failure of liver to take it up after gut absorption therefore more excreted via kidneys
If you suspect tumour and detect noradrenaline which tumour is it?
If you suspect tumour and detect 5HIAA which tumour is it?
in carcinoid tumours
If you suspect tumour and detect Calcitonin which tumour is it?
in Medullary Ca Thyroid
If you suspect tumour and detect HCG which tumour is it?
in Choriocarcinoma / Teratoma
If you suspect tumour and detect Prolactin which tumour is it?
If you suspect tumour and detect paraprotein which tumour is it?
If you suspect tumour and detect PSA which tumour is it?
If you suspect tumour and detect AFP which tumour is it?
in hepatoma / testicular teratoma
If you suspect tumour and detect CEA which tumour is it?
in colorectal carcinoma
If you suspect tumour and detect CA125 which tumour is it?
in ovarian carcinoma
If you suspect tumour and detect CA15-3 which tumour is it?
in carcinoma of breast
If you suspect tumour and detect CA19-9 which tumour is it?
in adenocarcinoma of pancreas
if you suspect ca pancreas, which Ix would u do?
If you suspect cholangitis which Ix would u do and what are u looking for?
Ultrasound to look for GS and thickened GB wall
What is the most likely cause of a swinging temperature and a cystic liver mass in an international aid worker?
Amoebic liver abscess
What type of liver damage does paracetamol do?
What type of liver damage does methotrexate do?
What type of liver damage does octreotide do?
Gallstones as it alters fat absorption and reduces GB motility
What type of liver damage does chlorpromazine do?
By eating mouldy food, what is the potential liver damage?
Neoplasm – aflatoxins made by fungi increase risk of HCC
What is Dubin-Johnson syndrome? symptoms
- Autosomal recessive cause of intrahepatic cholestatic jaundice
- Defective hepatocyte excretion of conjugated bilirubin
- Intermittent jaundice and pain in R hypochondrium
What is Rotor syndrome?
Defective excretion of conjugated bilirubin producing cholestatic jaundice
If a lady of age 44 had high ALT and AST and was feeling malaise and fatigue, what liver problem is it and what further test?
- Autoimmune hepatitis
- Do antiSMA (not LKM1 as children get type 2)