Week 6 - D - Viral Hepatitis - Hepatitis A, E, D - Hepaitits B, C (serology and management more complicated)

Question 1

Viral hepatitis may cause acute liver injury, acute liver failure or chronic liver disease / cirrhosis Name the common viral hepatitis causes List other viral hepaitits causes

Answer 1

Common causes of viral hepatitis * Hepatitis A * Hepatitis B * Hepatitis C * Hepatitis E Rare causes of viral hepaitis Hepatitis D (delta agent), EBV, CMV, HSV, Yellow fever virus

Question 2

Hepatitis A, B, C, D, E State which typically cause acute liver injury and which typically cause chronic liver injury

Answer 2

Hepatitis A, B and E are associated with acute liver injury (hepatitis D also if patient has hep B infection already) Hepatitis B and C are associated with chronic liver injury

Question 3

What is the difference in presenting features of * Acute hepatitis and * Acute liver failure?

Answer 3

Acute hepatitis - patients typically develop a flu like syndrome Anorexia, malaise, tender RUQ, nausea and vomiting, hepatomegaly Acute hepatitis in severe causes causes an acute liver failure type picture. Characterized by * Jaundice * Coagulopathy, * Encephalopathy

Question 4

What type of virus causes * Hepatitis A * Hepatitis B * Hepatitis C * Hepatitis D * Hepatitis E

Answer 4

Hepatitis A - RNA virus Hepatitis B - DNA virus Hepatitis C - RNA flavivirus Hepatitis D - Incomplete RNA virus (needs hepatitis B for its assembly) Hepatitis E - RNA virus

Question 5

Hepatitis A Hepatitis A is typically a benign, self-limiting disease, with a serious outcome being very rare. What is the route of transmission of hepatitis A? - when is transmission more likely Stae the type of virus it is again? Does it cause acute or chronic liver disease?

Answer 5

Hepatitis A is transmitted through faecal-oral spread It is more likely to be transmitted in areas of poor hygiene / overcrowding It is an RNA virus and it causes acute hepatitis and rarely fulminant hepatitis (acute liver failure)

Question 6

What is the incubation period of a hepatitis A infection? What are the presenting features of a hepatitis A infection?

Answer 6

Incubation period around 2-6 weeks Usually a mild/flu like illness with full recovery Malaise, fever, anorexia, nausea Then jaundice and hepatosplenomegaly

Question 7

Hepatitis A is confirmed by laboratory confirmation of acute infection What is tests for in the blood? What marker will be positive for life? What happens to the LFTs in hepatitis A infection?

Answer 7

Blood serology for Hepatitis A IgM is usually detectable by the onset of illness Hepatitis A IgG will remain positive for life LFTs - big rise in AST and ALT usually a month after exposure

Question 8

How is hepatitis A managed? A vaccination is available to prevent hepatitis A infection Who receives this vaccination?

Answer 8

Hepatitis A is generally managed with supportive care * hygiene * alcohol avoidance * paracetamol if no evidence of severe liver disease for pain/fever There is a hepatitis A vaccination * Given as prophylaxis to people travelling to high risk areas eg africa/south america /asia * People who inject drugs * People with chronic liver disease

Question 9

Which other viral type of hepatitis is clinically similar to hepatitis A? Which is commoner in the UK?

Answer 9

Hepatitis E is clinically similar to hepatitis A and is also become more common than Hep A in the UK

Question 10

Heptatitis E What is the route of transmission of hepatitis A?Which animal is it associated with? State the type of virus it is again? Does it cause acute or chronic liver disease?

Answer 10

Hepatitis E is spread via faecal oral spread It s associated with pigs as a spread of infection Like hep A, it is caused by an RNA virus It causes acute liver disease, not chronic

Question 11

What is the clinical presentation of hepatitis E? What is the incubation period? When does the mortality rate of this infection increase? - ie what type of people are associated with severe disease

Answer 11

Usually a mild/flu like illness with full recovery Malaise, fever, anorexia, nausea Then jaundice and hepatosplenomegaly Incubation period is about 3- 8 weeks Hepatitis E is associated with severe disease in pregnant women and immunocompromised patients

Question 12

How is hepatitis E diagnosed? What is the management?

Answer 12

Hepatitis E diagnosed by serology - same as hep A Hep E IgM (IgM anti-hep E) shows positive if current or recent infection Hep E IgG is positive for life after infection Management is mainly via supportive care

Question 13

Hepatitis D When are hepatitis D infections found?

Answer 13

Hepatitis D infections are only found in people with hepatitis B virus * Hep D is an incomplete RNA virus and needs hep B for its assembly Either a co-infection or super-infection Co-infection: Hepatitis B and Hepatitis D infection at the same time. Superinfection: A hepatitis B surface antigen positive patient subsequently develops a hepatitis D infection.

Question 14

What is the clinical significance of a hepatitis D infection? What is the route of transmission? When do you actually test for this?

Answer 14

The clinical significance is that it exacerbates hepatitis B infections It is transmitted in a similar fashion to hepatitis B (exchange of bodily fluids (specifically blood)) It is only tests for in patients with hepatitis B surface antigen positive disease

Question 15

What are the complications of hepatitis D infection? How is it managed?

Answer 15

Superinfection is associated with high risk of fulminant hepatitis, chronic hepatitis status and cirrhosis. It is managed with interferon alfa although this has limited success Liver transplant may be required

Question 16

Hepatitis B What is the route of transmission of hepatitis B? If the first exposure to infection is in childhood/at birth, what does this increase the risk of?

Answer 16

Route of transmission of hepatitis B is via * Blood * Blood products * Sexually * Vertically Chronic infection and complications are much more likely to result if first exposure is in childhood

Question 17

What increases the risk of the different routes of transmission in the UK?

Answer 17

People at higher than average risk in the UK * Blood - PWIDs, tattoos * Blood products - unscreened transfusion * Sexually - increased risk with more sexual partners * Vertically - in utero - children of infected mothers

Question 18

What is the progression of the disease in a patient who is infected with hepatitis B? How does increasing age of first exposure to hep B correlate to risk of chronic infection occuring?

Answer 18

* Asymptomatic -> resolution * Acute liver failure -> death * Acute hepatitis -> resolution or chronic infection -> cirrhosis * Cirrhosis to cancer or chronic liver failure -> both to death Increasing age of infection decreases likelihood of chronic infection

Question 19

What is the incubation period of hepatitis B? What are the common complications of a hepatitis B infection?

Answer 19

INcubation period of a hepatitis B infection is apprx 1-6 months Complications include * Fulminant hepatic failure * Cirrhosis * Hepatocellular carcinoma * Also cholangiocarcinoma * Membranous nephropathy * Polryarteritis nodosa * Cryoglobulinaemia

Question 20

Lab confirmation of hepatitis B is actually quite complicated * What is the first marker to appear and is present in the blood of all infected individuals? - this stimulates the formation of the anti-Hep B antibodies (anti-HBs) * Which marker is present in the blood of highly infectious individuals?

Answer 20

First marker to appear and is present in the blood of all infected individuals - Hepatitis B surface antigen (HBsAG) Marker that is is present in the blood of highly infectious individuals - Hepatitis B e antigen (HBeAg)

Question 21

HBsAg normally implies acute disease How long does it have to be present for to imply chronic disease? What happens to HBeAg in chronic disease?

Answer 21

if HBsAg is present for > 6 months then this implies chronic disease HBeAG is only positive in acute infection and implies high infectivity, not measurable in chronic phase

Question 22

What does anti-HBs implies? When is it negative? When is anti-HBe positive?

Answer 22

Anti-HBs implies immunity (present in exposure or immunization related immunity) * It is negative in patients who are acute/chronic disease Anti-HBe may be positive in chronic disease

Question 23

Anti-hepatitis B core (Anti-HBc) implies previous or current infection What markers are measured for anti-HBc? * Which implies acute infection? * Which implies chronic? (also known as a carrier)

Answer 23

IgM anti-HBc appears during acute or recent hepatitis infection IgG anti-HBc also appears at this time and persists lifelong showing patients had the infection

Question 24

What is the more sensitive predictor of prognosis and infectivity than HBeAG that can be measured?

Answer 24

Hep B virus DNA always also present in high titre (amount) in highly infectious individuals - more sensitive than HBeAG for prognosis and degree of infectivity Hep B DNA tests also used to predict risk of chronic liver disease and monitor therapy

Question 25

Lets summarise the serology State when each of the following is positive or negative * HBsAg * HBeAg * Anti-HBs * Anti-HBe * HBV DNA * IgM anti-HBc * IgG anti-HBc

Answer 25

* HBsAG - positive in active infection, if >6 months implies chronic disease (aka carrier of disease) * HBeAG - positive in acute disease showing high degree of infectivity * Anti-HBs - positive if immunity (exposure or immunisation mediated) * Anti-HBe - positive in chronic disease * HBV DNA - always present in high titre in highly infectious indivudal IgM and IgG anti-HBc - show active and active/chronic infection respectively

Question 26

Here is an example * What would be positive in a patient who has previously been immunised against hepatitis B? * What would should in patient who has had hepatitis B>6month ago, and is not a carrier for chronic infection? (ie they had an acute episode of hepatitis B) * What would show in a patient who has had hepatitis B and now is a carrier for chronic infection?

Answer 26

* Previously been immunised - anti-HBs positive, all others negative * Patient who had an acute episode >6months ago and has now recovered -> IgG anti-HBc positive, anti-HBs positive, all others negative * Patient who had an acute episode and is now a carrier for chronic infection -> IgG anti-HBc positive, HBsAG positive, HBV DNA & anti-HBe may be positive

Question 27

HBeAg is positive acutely in highly infectious individuals HBV DNA is always (acute and chronic) positive in highly infectious individuals State which are positive and which are negative from HBsAG, anti-HBs and anti-HBc (IgM and IgG) when patient is * Suscpetible * Vaccinated * Past infection * Acute infection * Chronic infection

Answer 27

Susceptible = all negative Vaccinated = Anti-HBs posititve Past infection = Anti-HBs and IgG anti-HBc positive Acute infection = HBsAG and IgM anti-HBc positive Chronic infection = HBsAG and IgG anti-HBc positive

Question 28

We will discuss the management of hepatitis B infection later in this deck of cards when we discuss hepatitis C infection For now, lets discuss how to minimize exposure * Who is the hepatitis B vaccination available to? when is it given? * What is given as post-exposure prophylaxis eg to babies whom mothers are chornically infected or have had an acute infection during pregnancy?

Answer 28

Hepatitis B vaccination is given to children at 8 weeks, 12 weeks and 16 weeks as part of the 6in1 vaccintion It is also given to olde children/adults who are at high risk - eg healthcare workers or IV drug users Post exposure prophylaxis Give vaccination plus hyperimmune hep B immunoglobulin

Question 29

Hepatitis C What is the route of transmission of hepatitis C? What type of virus is it? Does it normally result in acute or chronic infection?

Answer 29

Hepatitis C is transferred similarly to hepatitis B * Blood * Blood products * Sexually - less commonly than hepatitis B * Vertically in utero Natural history is that, irrespective or age, the majority become chronically infected

Question 30

Six months of infection defines chronic liver infection Is spontaneous cure common in hepatitis B or C after chronic infection? Which type usually presents as asymptomatic for many years before progressing to chronic infection?

Answer 30

Spontaneous cure is not uncommon in hepatitis B even after many years of infection Spontaneous cure is not seen once chronic infection is established in hepatitis C infection - most patients will be asymptomatic for decades, until they develop signs of chronic liver disease.

Question 31

What is the incubation period in hepatitis C infections? What are the complications of this condition? What skin condition is it linked to?

Answer 31

Incubation period is around 6-9 weeks Complications include * Cirrhosis * Hepatocellular carcinoma * Membranous glomeruloonephritis * Polyarteritis nodsa * Cryoglobulinaema Porphyria cutanea tarda is a recognized complication with people with HepC infection

Question 32

State the different incubation periods for each of the viral hepatitis (dont need to do for hep D)

Answer 32

Hepatitis A - 2-6 weeks Hepatitis B - 1-6 months Hepatitis C - 6-9 weeks Hepatitis E - 3-8 weeks Parenteral transmission refers to the passage or transfer of potentially dangerous pathogens via a way other than through the digestive system

Question 33

Is there a vaccination available for hepatitis C?

Answer 33

No vaccination available

Question 34

If a patient is at risk of hepatitis C or has signs of chronic liver disease What initial test is carried out to test for hepatitis C? What is then the test of choice to confirm active infection?

Answer 34

Initially test is to test IgG antibodies to hepatitis C - if positive this means positive or past infection HCV RNA is the investigation of choice to diagnose acute infection IgG anti-Hep C pos, RNA neg = past infection (may still get re-infected if still injecting), will not get liver disease due to HCV unless they get re-infected IgG pos, RNA pos = active infection (usually chronic)

Question 35

Treatment of hep B and C infection What is the treatment strategy for hepatitis B?

Answer 35

Option 1 - more widely used Suppressive antiviral drug eg entacavir or tenofovir Option 2 Peginteferon alfa2a alone

Question 36

What is the different advnatages of both options to treat hepatitis B infection?

Answer 36

Option 1 - suppressed antiviral drug (aentacavir or tenofovir) * Much safer and increasing range available * However not cure and resistance can develop Option 2 - Peginterferon alfa-2a alone * Sustained cure possible * However side effects and only minority gain benefit

Question 37

What are the side effects of peginterferon?

Answer 37

Common side effects are management - flu like symptoms of chills, sore muscles and malaise Less common but more severe * Thyroid disease * Autoimmune disease * Psychiatric disease - psychosis, depression

Question 38

What is the aim of treatment of chronic hepatitis? (with regards to serology)

Answer 38

reduction in HBV DNA (suppression) loss of HBeAg (more enduring suppression) loss of HBsAg (cure)

Question 39

What is the treatment of hepatitis C infection?

Answer 39

Combination of direct acting antivirals are given for hep C infection eg sofosbuvir, ledipasivir, daclatasivir Interferon-based treatment regimens are no longer recommended for HCV infection as direct-acting antivirals (DAAs) are now considered first-line treatment. DAAs target different stages in the HCV lifecycle and are successful for over 90% of people with HCV infection -

Question 40

What are the aims of treatments in patients with chronic hepatitis C?

Answer 40

Response defined by loss of HCV RNA in blood sustained to 6 months after end of therapy -> virological cure known as Sustained Virological Response or SVR relapse after SVR is rare