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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.
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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.
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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.
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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
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what is the HBV vaccine used in this country?
- Recombinant HbsAg
- Expressed in yeast cells
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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.
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How is diagnosis of HCV made?
Detection of serum HCV RNA or HCV Ag
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What are the ways HCV can be transmitted?
- Needle stick
- Blood products
- Sexual
- Mother to child
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What are the pathological features of Hepatitis?
- Liver cell necrosis
- Inflammatory cell infiltrate
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What are clinical features of viral hepatitis?
- Liver enlarged and tender
- Jaundice
- AST:ALT ratio <1 (compared to alcoholic where it is >1)
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Which drugs can cause hepatitis?
- Anti TB eg isoniazid
- Paracetamol OD
- Halothane
- NSAIDs
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Acute heptatitis pathology
- Ballooning degeneration
- Councilman bodies (acidophils)
- Inflam lymphocytes
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Which drugs can cause chronic active hepatitis?
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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
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What examination findings of acute hepatitis?
- Tender hepatomegaly
- Splenomegaly
- Cervical lymphadenopathy
- Skin rash
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What is the most common type of acute hepatitis?
Hep A
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How is hep A spread, who?
- Travellers tropics
- Faeco-oral
- Raw or poorly cooked shellfish
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What is the incubation time for hep A? and what type of virus?
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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!
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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.
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What is the treatment of hep A?
- Supportive, no alcohol
- If fulminant then give interferon alpha
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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
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2. post exposure
a. passive immunisation HNIG (human normal Ig) to contacts and household, remember faeco-oral!
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What is the natural progression of hepatitis A?
- Usually self-limiting
- Over in 3-6 weeks
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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
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what type of virus is hep B?
dsDNA virus
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what is the incubation period for hep B?
2-6 months
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What are the modes of transmisison of hep B?
- Vertical: mother to infant
- Needle stick injury
- Needle sharing IVDU
- Tattoos
- Piercings
- Sexual
- Blood and blood products
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Where can expression of HbcAg be seen in the cell?
Hepatocyte nuclei
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Where can expression of HbsAg and HbeAg be seen in the cell?
Cytoplasm
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When is the eAg made and what does high levels indicate?
- Made in active viral replication
- High levels indicates high degree of infectivity
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What do the cells look like in acute hep b?
Ground glass hepatocytes
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What is the mortality assocaietd with acute hep b infection?
Less than 1%
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What % of adults will become HBV carriers?
5-10%
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Which age group/type of people are most likely to become HBV carriers?
HBV infections in neonates and immunosuppressed
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What may HBV carriers develop?
- CLD
- Cirrhosis
- HCC
- Extra-hepatic disease: GN in childern, PAN, cryoglobulinaemia
- Cholestasis
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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
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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
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What defines chronic hep B?
Presence of surface antigen for over 6 months = carrier status: chronic
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If a patient had anti-HbsAg alone, what would that indicate?
Vaccination
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In HBV, what is the method of monitoring the response to treatment?
HBC PCR – see the viral load
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What is the prognosis of an acute HBV infection which presents with jaundice?
Virtually NEVER leads to CHRONIC carriage
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What is the treatment of acute hep B?
- Conservative
- Supportive
- No alcohol
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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)
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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
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Which staff cannot do EPPs?
If HBeAg carriers
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Which parts of the world is HBV common in?
China
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How do you know if an acute hep B infection has recovered completely?
Disappearance of HBsAg frin serum (and will have anti-HBs)
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What are the SE of lamivudine?
- Lactic acidosis
- Loss of subcut fat
- Nausea, dyspnoea
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What are SE of pegINF?
- Neutropenia
- Insomnia
- Flu like symptoms
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What are the adv of pegINF over normal INF?
- Increased half life
- Reduced clearance
- Only need once weekly dosing
- Better response rates with peg
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What are the complications of HBV infection?
- Chronic hepatitis
- CLD
- Cirrhosis
- HCC
- Cholestasis
- GN
- Cryoglobulinaemia
- Fulminant hep failure
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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
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What type of virus is HCV?
ssRNA
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what is the incubation period of HCV?
2-3 months
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Before screening of blood donoation, what was the most important cause of post-transfusion NANB hep?
HCV
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What is the MAIN mode of transmission of HCV?
- IVDU and needlestick
- Mother to child and sexually is seen but not as much
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How many different genotypes of HCV are there?
6
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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%
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What proportions of acute infections develop into chronic?
Majority! 70%
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What can chronic HCV infection act as a trigger factor for developing…?
- GN
- Mixed essential cryoglobulinaemia
- Porphyria cutanea tarda
- GN
- Autoimmune liver disease
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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
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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
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How is chronic HCV infection diagnosed?
Serology: antibody detection (as takes several months for antibodies to form after acute infection)
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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)
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How is HCV treatment monitored?
Quanititative real time RT PCR to measure viral load
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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
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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
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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
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What happens to the total anti-HDV levels and ALT in superinfection?
Total anti-HDV remains high and ALT remains high
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What is the MAIN mode of transmission of HDV?
Parenteral – IVDU (can sexually)
-
How is prophylaxis of HDV achieved?
By preventing HBV infection
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What type of virus is Hep E?
ssRNA
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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
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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
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What is the treatment of HEV?
Supportive with complete resolution in most cases.
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What is the prophylaxis for HEV?
None but ENSURE CLEAN WATER SUPPLY (no uncooked or shellfish)
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What are the features of Hep GBV-c?
Asymptomatic
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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
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When there is jaundice, what level of bilirubin is likely to be in the blood?
Over 50umol/l
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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
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Which clotting factor does the liver NOT make?
Factor 8
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Give 2 situations when there is a raised unconjugated bilirubin?
- Haemolysis: acquired/inherited…
- Failure of conjugation: Gilberts, neonate
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If there is a raised conjugated bilirubin, what does that indicate?
Haemolysis or failure of conjugation
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Give 2 reasons why urinary urobilinogen would be absent?
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When would you see a raised urobilinogen?
- Haemolysis
- 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
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What is the deficiency in Wilsons?
Caeruloplasmin
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What are the values for iron, ferritin and TIBC in haemochromatosis?
Iron up, ferritin up, TIBC down or normal (as transferrin is fully saturated)
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Which Ig is raised in PBC?
IgM
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Which Ig is raised in micronodule cirrhosis?
IgA
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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
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What type of liver disease do you see a raise in GGT?
Alcoholic liver disease
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What are the causes of pre-hepatic jaundice?
- Ineffective erythropoeisis: pernicious anaemia
- Excess RBC destruction: immune anaemia, sickle cell
- Breast feeding
- Novobiocin
- Gilbert’s
- Crigler Najjar
- prematurity
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what are the causes of intrahepatic jaundice?
- Drugs: chlorpromazine
- Hepatitis
- CLD
- Infiltration: tumour, sarcoid,
- Rotor syndrome
- Dubin Johnson
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What are causes of extrahepatic jaundice?
- Head of pancreas ca
- Stones in CBD
- PSC
- Biliary atresia
- Cholangiocarcinoma
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Why do you get excess urobilinogen in hepatic jaundice?
Failure of liver to take it up after gut absorption therefore more excreted via kidneys
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If you suspect tumour and detect noradrenaline which tumour is it?
in phaeochromocytoma
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If you suspect tumour and detect 5HIAA which tumour is it?
in carcinoid tumours
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If you suspect tumour and detect Calcitonin which tumour is it?
in Medullary Ca Thyroid
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If you suspect tumour and detect HCG which tumour is it?
in Choriocarcinoma / Teratoma
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If you suspect tumour and detect Prolactin which tumour is it?
in prolactinoma
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If you suspect tumour and detect paraprotein which tumour is it?
in myeloma
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If you suspect tumour and detect PSA which tumour is it?
in prostate
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If you suspect tumour and detect AFP which tumour is it?
in hepatoma / testicular teratoma
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If you suspect tumour and detect CEA which tumour is it?
in colorectal carcinoma
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If you suspect tumour and detect CA125 which tumour is it?
in ovarian carcinoma
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If you suspect tumour and detect CA15-3 which tumour is it?
in carcinoma of breast
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If you suspect tumour and detect CA19-9 which tumour is it?
in adenocarcinoma of pancreas
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if you suspect ca pancreas, which Ix would u do?
ERCP
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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?
Acute hepatitis
-
What type of liver damage does methotrexate do?
Fibrosis
-
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?
Acute cholestatic
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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
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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)
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