Dental Aspects of Hepatitis

• Viral hepatitis:

  • Parental transmission (not via the GI tract):
  • Hepatitis B
  • Hepatitis C
  • Hepatitis D
  • Enteral transmission (likely to begin with the oral cavity):
  • Hepatitis A
  • Hepatitis E
• Modes of liver damage in hepatitis:

  • ACUTE: infection of the hepatocytes with direct killing by effector lymphocytes
  • Most hepatitis infections are acute and self-limiting - experience typical viral aches but the occurrence of jaundice will indicate liver problems
  • CHRONIC: low level chronic immune damage with additional direct cytopathic effects and the sequelae of chronic damage, fibrosis and repair (cirrhosis)
• Viral hepatitis - Hepatitis A:

  • Acute: self-limiting illness; hospitalisation may not be needed. Can be (rarely) fatal.
  • Chronic: nil
  • Carrier: nil
  • Prevention: vaccination
  • Reduced herd immunity
  • Super-added infection
  • Most common type of viral hepatitis - variant of food poisoning (sea food can act as a vector)
  • 'Carriers' can be infected but will experience no liver damage - there are no carriers for hepatitis A
• Viral hepatitis - Hepatitis E:

  • Acute: self-limiting illness; hospitalisation may not be needed. Can be (rarely) fatal (particular problem in pregnancy)
  • Chronic: immuno-suppressed patients (can't clear the infection from their body), CLD (chronic liver disease)
  • Carrier: nil
  • Prevention: no vaccination at present, therefore main way to tackle it is good food hygiene
  • Another variant of food poisoning - comes from uncooked pork - can produce worse symptoms than hepatitis A
• Viral hepatitis - Hepatitis B:

  • DNA virus - therefore little evolution of the virus
  • Integrates into the human genome
  • Infection gives rise to significantly different outcomes in different patients
  • The differing outcome seen following infection with hepatitis B is entirely a result of differences in the host response
  • There is a wide spectrum of outcomes following exposure to virus. This spectrum entirely reflects the immune response to the virus
• Viral hepatitis - Hepatitis B:

  • Acute: self-limiting illness; hospitalisation may not be needed
• Viral hepatitis - Hepatitis B:

  • Acute: self-limiting illness; hospitalisation may not be needed
  • Chronic: sAg+ve (+/- eAg), DNA+ve with ongoing liver damage and abnormal LFTs (liver function tests. Liver cancer risk ++
  • Carrier: vertical transmission (contract it in utero or at delivery from mother to child); low risk high infectivity
• Viral hepatitis - Hepatitis B:

  • Carrier: vertical transmission (contract it in utero or at delivery from mother to child); low risk high infectivity
  • No immune response to the virus at all - liver function is normal and people live in this state all throughout their life
  • Vaccination has been used to overcome the immune tolerance that comes about because you will encounter the virus early in life
  • Carriers in a population where there is a low level of natural immunity are bad though; viral levels are high since there's no immune system control over the virus
• Viral hepatitis - Hepatitis B:

  • Infection in adult life (after 6 months of age)
  • 95% of people will clear the virus normally
  • 5% will fail to clear the virus and develop chronic hepatitis (predisposing to cirrhosis)
  • 0.1% will develop fulminant liver failure
  • Acute clearance of the virus is so effective it clears the liver hepatocytes
  • Only treatment is liver transplant
• Viral hepatitis - Hepatitis B:

  • Adult infection - risk factors:
  • Sexual transmission (risk relatively high)
  • IV drug abuse
  • Blood transfusion
  • "Soft" blood contact - eg helping a carrier of the virus on the street who is bleeding
  • Professional exposure - shouldn't really be an issue now though; everyone who could be exposed at work will have been vaccinated and the vaccine is highly effective
• Viral hepatitis - Hepatitis B:

  • Adult infection - clinical course:
  • "Incubated period" up to 6 weeks
  • "Flu-like" symptoms 1-2 weeks
  • Jaundice (other symptoms resolve) 2-4 weeks
  • Resolution (or continuation)
  • There is no way of knowing, during the acute illness, who will go on to develop chronic disease. Disease is defined as chronic at 6 months. Pts with chronic hepatitis are at risk of developing cirrhosis and hepato-cellular carcinoma.
• Viral hepatitis - Hepatitis B:

  • Adult infection - clinical features of acute infection:
  • Lethargy
  • Joint pain
  • Flu-like illness
  • Jaundice & dark urine
  • Liver pain
• Viral hepatitis - Hepatitis B:

  • Adult infection - clinical features of chronic infection:
  • General features of Chronic Liver Disease - the features of the metabolic state caused by poor liver function and chronic liver damage
  • Skin thinning
  • Weight loss
  • Variceal bleeding because of a rise in portal venous pressure
  • Can be totally asymptomatic
  • If someone has hepatitis B and has developed cirrhosis it's still important to treat the hepatitis B because that will preserve the remaining liver function and reduce the potential for that person to affect others
• Viral hepatitis - Hepatitis B:

  • Adult infection - diagnosis = liver function tests (LFTs):
  • ALT raised
  • Alkaline phosphatase (released by bile ducts) raised
  • Bilirubin raised (because liver is not clearing it)
  • Degree of elevation of ALT and bilirubin don't predict disease severity, just indicates liver damage
  • Albumin (produced by liver and released into circulation) decreased
  • PT (prothrombin time) raised - risk factor for bleeding too
  • Abnormality in albumin or PT predicts severity of disease
  • These markers suggest presence of liver injury, but don't tell you aetiology (needs testing)
• Viral hepatitis - Hepatitis B:

  • Adult infection - "Hepatitis B markers" 1: Antigens & DNA
  • HepBsAg (surface antigen)
  • Marker of viral presence - indicates there's virus in the body which is shedding this protein into the circulation where we can measure it
  • Present in acute and chronic disease
  • Disease and carrier state
  • Its presencetells you nothing about the nature of the disease, only that hepatitis B is there
• Viral hepatitis - Hepatitis B:

  • Adult infection - "Hepatitis B markers" 1: Antigens & DNA
  • HepBeAg (e antigen)
  • E antigen comes from the core of the virus - present in some patients with hepatitis B, particularly if there's a v high degree of viral load or if the virus is replicating a lot; there are no replication states of hepatitis B that are e antigen negative
  • Marker of degree of viral load
  • In chronic disease and carrier state
  • Not to be used to identify the presence of the virus; it can be negative in people with hepatitis B infection - just used to measure severity
• Viral hepatitis - Hepatitis B:

  • Adult infection - "Hepatitis B markers" 1: Antigens & DNA
  • HepB DNA
  • Measurement of nucleic acid
  • Marker of degree of replication
• Viral hepatitis - Hepatitis B:

  • Adult infection - "Hepatitis B markers" 1: Antigens & DNA
  • HepBsAg (surface antigen)
  • HepBeAg (e antigen)
  • HepB DNA
• Viral hepatitis - Hepatitis B:

  • Adult infection - "Hepatitis B markers" 2: Antibodies
  • HepBsAb (surface antibody)
  • HepBeAb (e antibody) & HepBcAb (core antibody)
• Hepatitis B surface antibody is the antibody produced in response to hepatitis B surface antigen. In hepatitis B, you are either surface antigen positive or surface antibody positive - you can't have both; when you mount an immune response to the surface antigen, the antibody will clear the antigen and it'll no longer be present - this is a marker of immunity.
• Viral hepatitis - Hepatitis B:

  • Adult infection - "Hepatitis B markers" 2: Antibodies
  • HepBsAb (surface antibody)
  • Marker of immunity
  • If you are surface antibody positive then you are immune to hepatitis B and have cleared the virus
  • People who are vaccinated against hep B will be surface antibody positive though - marker of vaccination too
• Viral hepatitis - Hepatitis B:

  • Adult infection - "Hepatitis B markers" 2: Antibodies
  • HepBeAb (e antibody) & HepBcAb (core antibody)
  • Markers of low risk in chronic hepatitis patients
  • E antibody is the reverse of e antigen - again you can either be e antigen positive or e antibody positive, you can't be both
  • If you are e antigen positive you'll have high replication rates
  • If you are e antibody positive - indicates a lower level of viral infection, but can in fact give more in the way of chronic injury
• Viral hepatitis - Hepatitis B:

  • Adult infection - "Hepatitis B markers" 2: Antibodies
  • HepBeAb (e antibody) & HepBcAb (core antibody)
  • Markers of low risk in chronic hepatitis patients
  • There is no core antigen that we can measure, but there is a core antibody - core antibody is the earliest immune response that we see to hepatitis B
  • This is important; there's a v small group of people who have a mutant form of hepatitis B that means the surface antigen test can't identify them, so measuring for core antibody as well as antigens helps to pick these people up
• Viral hepatitis - Hepatitis B:

  • Adult infection
  • All pts with acute HepB will be surface antigen (sAg) and e antigen (eAg) positive. They will then develop eAb (e antibody) and sAb (surface antibody), at which point the disease has resolved. They are now "immune".
  • After 6 months, when patients are defined as having chronic hepatitis they will remain sAg +ve and sAb -ve (with one important exception, cAb +ve).
  • Screen pts by sAg+ cAb. If -ve, they do not have Hep B. If +ve do full markers to assess risk.
• Viral hepatitis - Hepatitis B:

  • Perinatal infection
  • Around 50% of children born by vaginal delivery will be infected and become chronic carriers
  • NOTE: these children will not develop liver disease (they have no immune response to the virus), but will be infectious (very) and might be at risk of liver cancer
  • They are able to be vaccinated though
• Viral hepatitis - Hepatitis B:

  • Therapy: the aim of therapy is to clear HBV (hepatitis B virus) in patients with chronic hepatitis thereby reducing the risk of, cirrhosis (and HCC [hepato-cellular carcinoma])
  • Antiviral drugs
  • Interferon, Lamivudine, Adefovir etc.
  • Immuno-stimulatory therapies:
  • Inferferon
  • Therapies against hep B can control the virus but not eliminate it permanently
  • Transplantation: effective but high re-infection risk (because virus is present at time of transplant), so we use prophylaxis
  • Prevention: vaccination
• Viral hepatitis - Hepatitis C:

  • RNA virus - therefore has led to viral variation (different viral types) over time
  • Does not integrate into the human genome
  • Although it does still give rise to cancers - likely because of the degree of chronic inflammation it gives rise to
  • Infection gives rise to a single clinical pattern (chronic disease)
  • The majority of  patients exposed to hepatitis C will end up getting a chronic infection
• Viral hepatitis - Hepatitis C:

  • Excessive host response
  • Does not occur
  • Normal host response
  • Viral clearance with clinical resolution (no acute illness) occurs in less than 20% of infected individuals
  • Inadequate host response
  • Chronic hepatitis (viraemic ++)
  • No host response
  • No equivalent carrier state
• Viral hepatitis - Hepatitis C:

  • Causes chronic insidious damage to the liver with a very high risk of chronic liver damage and HCC (hepato-cellular carcinoma)
  • 3 risk groups:
  • IV drug abusers
  • Receivers of blood products
  • Factor X (those who don't use IV drugs or receive blood products - ie unknown cause)
  • Hep C seems to be harder to contract than Hep B - mostly via blood contact
• Viral hepatitis - Hepatitis C:

  • Presentation
  • Abnormal LFT (liver function test)
  • IV drug abusers for screening
  • Blood donors
  • Screening of recipients of blood products
  • People who are Hep C +ve don't normally present with clinical features of liver disease/damage
• Viral hepatitis - Hepatitis C:

  • Investigation
  • ALT 50-100
  • ELISA antibody test - everybody with Hep C will have the antibody to it - good screening test
  • PCR - can look at RNA virus
  • Biopsy - see degree of injury to the liver
• Viral hepatitis - Hepatitis C:

  • Prevention:
  • Risk modulation NOT vaccination; there is no vaccination against Hep C
  • Challenging because don't know all transmission paths and sufferers don't typically show signs of liver disease - therefore hard to diagnose
• Viral hepatitis - Hepatitis C:

  • Advice to families:
  • "Casual" transmission is rare
  • Treatment:
  • (Peg-Interferon 180 mcg weekly + Ribavirin)
  • Novel protease and polymerase inhibitors
  • Results:
  • 30-50% originally. 90%+ control and clearance of the virus now.
  • Unlike Hep B or HIV therapy, Hep C therapy now cures people of the disease - therefore no reason not to diagnose Hep C; can really transform people's lives.
  • Earlier diagnosis and treatment is much more likely to be effective; more difficult to treat people as cirrhosis has developed.
• Viral hepatitis - Hepatitis C:

  • Combination therapy is the norm to avoid the development of resistance (use protease + polymerase inhibitor)
  • Hepatitis C treatment pros and cons:
  • Pros:
  • Potential cure
  • Reduced progression to cirrhosis even if virus not cleared
  • Reduced risk of HCC (hepato-cell carcinoma - ie cancer) even if virus not cleared
  • Cons:
  • Sustained response rate less than 50% until recently
  • Length and nature of old treatment
  • Side effects of old treatment
  • Costs (+++ in case of new generation therapies)
• "Risk"  in viral hepatitis for dentists:

  • To the pt
  • Bleeding in the patients with chronic liver disease (platelet aspects and clotting factor aspects)
  • Infection in a non-infected pt
  • To the dentist
  • Infection by an infected pt
  • Therapy is not a reality