Virus 6 (DNA/RNA): Hepatitis

Question 1

What are the different hepatitis viruses and which ones have vaccines?

Answer 1

• Globally 350 million are living with chronic hepatitis B and C
• WHO: Viral hepatitis kills more people then malaria or HIV but gets less attention
• All RNA viruses except Hep-B which is DNA virus
• Incubation period 2-6 weeks. Hep-B is an outlier with up to 6 month incubation.
• All can cause chronic infection except Hep A.
• There are vaccinations against Hep A, Hep B [some Hep E in China only]

Hep A vaccination is only relevant to travellers: x2 doses = lifelong immunity

• A & E – faeco-oral. E can also be through eating undercooked shellfish/pork.
• B & C – blood/needles/sexual/mother-to-child [C > blood; B > sex].
• D – only those with Hep-B.
• There is no effective acute treatment for any of the hepatitis viruses.

Question 2

What are important features in the history and on clinical examination?

Answer 2

• Clinical Hx for hepatitis
  
  • Jaundice
  • Country of birth
  • Alcohol, drugs
  • Injecting drug use
  • Tattoos, piercing
  • Travel and treatments abroad
  • Blood products
• O/E
  
  • Icterus – jaundice
  • HSM
  • Loss of body hair
  • Small Testes
  • Gynaecomastia
  • Liver palms
  • Easy bruising
  • Ascites
  • Encephalopathy
  • Asterixis

Question 3

Hep A and E important facts

Answer 3

Hep A & E

• Faeco-oral, typically acute and mild; rarely fulminant except E in pregnancy.
• Hep A common throughout LMIC. Infection leads to immunity.
• Hep E seems to be endemic worldwide; can cause cholestasis No immunity from prior infection and no vaccine available.
• Hep A – can give immunoglobulin. Hep E – can Rx with Ribavarin

Hepatitis A Immunity

• Most adults in LMIC will have Hep A immunity from previous infection, so an outbreak across age groups is more likely to be Hep E than Hep A.

Havrix is the vaccine

Hep E immunity

Vaccine only available in China

Question 4

Where is HBV found, how common is it and how does it progress?

Answer 4

• Quite common worldwide [less so Americas]: Africa, China, Indonesia
• 350 million worldwide (10x HIV)
• It is the leading cause of HCC worldwide.
• Incubation 6 weeks to 6 months
• One big difference to Hep C is that in Hep B you can develop liver cancer without first developing carcinoma
• Peri-natal transmission: chronic in 95%
• Adult transmission: chronic in 5%

Question 5

How is HBV transmitted?

Answer 5

• Needle-stick transmission risk:
  
  • HIV 0.3%
  • HCV 3%
  • HBV 30%
• In sub Saharan Africa and in the absence of effective prophylaxis endemic and chronic hepatitis B infection is established in early childhood

Question 6

What are the different antigens & antibodies involved in HBV?

Answer 6

• If you have a detectable antigen in the blood then it means you have the virus because the antigen comes directly from the virus
• However, if you have the antibody, then it means you have been previously exposed or that you have been vaccinated
• If you have been vaccinated then you have a positive surface antibody with a negative surface antigen; you will not have a core antibody/antigen as the core antigen is part of the virus itself
• eAg is associated with when the virus is rapidly multiplying and means a high viral load and high likelihood of liver damage – it is not commonly used anymore as an infective marker – viral load is preferred

Question 7

How do we interpret Hep B serology?

Answer 7

• The Hep-B antibodies generally indicates recovery and immunity or vaccination. Vaccination will give + HepB surface-antibody (HBsAb) only but NO antigens.
• Hepatitis B antigen (HBsAg) is detected during acute or chronic infection. If present for >6 months = chronic infection. It is absent in recovery/immunity.
• Total hepatitis B core antibody (anti-HBc): Appears at the onset of symptoms in acute hepatitis B and persists for life, indicating current or past infection. If pt has HBsAb+ but HBcAb- then they have been vaccinated not infected. All people infected with HBV should have HBV core antibody.
• Hep B e-antigen+ = high infectivity rates, [core mutations will give false neg]
• HBV DNA is the most sensitive marker of active infection/viral load – it cannot be deceptively negative with core-mutant disease either

Question 8

What is the HBV vaccine?

Answer 8

• Recombinant HBVsAg grown in Saccharomyces cervisiae

Question 9

What is the management algorithm for HBV +ve patients?

Answer 9

• HBV treatment criteria
  
  • Histological - evidence of cirrhosis (fibroscan)
  • Biochemical - abnormal ALT > 2x ULN
  • Virological HBV-DNA >20,000 iu/ml
  • Co-infection - with HIV (HBV active HIV therapy)

Question 10

Wha vaccine do we use for HBV?

Answer 10

• Recurrent preparation is a recombinant DNA vaccine, and this has displaced the previous HBsAg vaccine that was harvested from the plasma of hepatitis B carriers.
• Early immunization against hepatitis B gives excellent results, even in infants. After three doses the majority of people seroconvert to an anti-HBs antibody level >10 mIU/L, which is sufficient to provide protection.

Question 11

What drugs do we use to treat HBV infection?

Answer 11

WHO choice are NRTI Entecavir [children] or Tenofovir.

• In HIV co-infection: Tenofovir + Lamivudine – useful combination. IRIS is common in co-infected pts started on ART and HBV Rx should continue.
• Surveillance 6 monthly monitoring ALT, USS, AFP, DNA for Hep B & C.
• Note: co-infection or super-infection with HbsAg+ pts with Hep-D causes flare of Hep B. Diagnosed with IgM anti-delta.
• Complications: fulminant liver failure, Hep D, cirrhosis, HCC, glomerulonephritis
• In pregnancy if viral level >200,000 pts may receive Tenofovir in 3rd trimester. HBV vaccination should be given to infant at delivery. Breastfeeding fine.

NICE guidelines below:

Question 12

Why does HDV not exist without HBV?

Answer 12

• Hep D does not exist without Hep B because the surface antigen of B is required for the surface of D
• Superinfection (getting D after having already acquired B) and this is associated with fulminant hepatitis

Question 13

Where is HCV found, how common is it and how does it progress?

Answer 13

• 71 Million worldwide [less so Americas]: Africa, China, Indonesia. Iatrogenic infection of 1/3 adult population in Yemen and Egypt (re-use of needles).
• Curable – unlike Hep B. Aim is sustained virological response at 12 weeks after completing treatment [SVR12]. Virtually no side-effects and cheap.
• No vaccine – 6 genotypes of 1-6 with a and b as well – 8 with subtypes.
• Prognosis: 80% chronic of whom 20% become cirrhotic of whom 33% HCC. Estimated that 50% are unaware that they are infected
• Ix: definitive diagnosis HCV RNA or HCV core Antigen

Question 14

How is HCV transmitted?

Answer 14

Question 15

How do we test for HCV infection?

Answer 15

• 1 in 5 clear spontaneously
• HCV antibody - Hep C previous exposure
• HCV-RNA or core Ag = current infection

Question 16

What is the treatment algorithm for HCV?

Answer 16

hcvguidelines. org for up-to-date info
* 8 different genotypes of HCV, all slightly different responsiveness to treatment

Question 17

Answer 17

Answer Hep C – Hep B unlikely as not HBVcAb and sAB probably due to vaccine so ALT rise most likely due to Hep C. Also, this is clearly a blood borne transmission.

Question 18

Answer 18

• HCC secondary to hep B infection seems very likely as it is very prevalent in this region

Question 19

Answer 19

• The most likely answers here are either Hep A or Hep E. Once you have been exposed to Hep A once in your life (and a 65 year old lady from Bangladesh will have been), you have lifelong protection

Question 20

Answer 20

• Interferons can be ruled out because of toxicity (not longer recommended). Tenfofvir used in B but not C. Ledipasvir not very effective in genotype 3.

Question 21

Answer 21

• Anyone with viral load over 20000, with HIV and cirrhosis needs to be treated. That leaves you with option C