Viral hepatitis Flashcards
What is hepatitis?
inflammation of the liver
What changes are seen in acute hepatitis?
o Inflammation of the liver
o Raised ALT / AST
o Jaundice
o Clotting Derangement
What changes have been seen in chronic hepatitis
o Hepatitis virus present for more than 6 months
o Jaundice has normally settled by this point
o Variable changes in Liver Function
What can cause acute hepatitis?
- infections
- toxins
- drugs
- alcohol
- autoimmune
- Wilsons
- Haemochromatosis
What infections can lead to acute hepatitis?
o Hep A, B, C, D, E o EBV, CMV, Toxoplasmosis o Leptospirosis o Q Fever o Syphilis o Malaria o viral haemorrhagic fever
Describe the transmission of the hepatitis A virus
o Faeco-oral transmission
o Contaminated water and food
o Person-person
o Humans are the only reservoir
Virus shed via biliary tree into gut and faeces
Virus can survive for months in contaminated water
No chronic carriage
Describe the epidemiology of hepatitis A
Highly prevalent in areas of poor public health
infrastructure
o Poor water and sanitation
In UK, mostly seen in travellers
What is the incubation period for hepatitis A?
~30 days
What symptoms are associated with hepatitis A infection?
Fever, abdominal pain, diarrhoea, jaundice, itch,
muscle pains
o Flu-like symptoms + jaundice
What is the outcome of hepatitis A infection?
Usually self-limiting illness
o Very low death rates
Age is main determinant of severity
o Mostly asymptomatic in children 50 year – but rare in this age group
How is hepatitis A managed?
No specific treatments
Maintain hydration, avoid alcohol
No role for vaccine or IgG
o Preventative vaccine exists but no vaccine for treatment
What are the test results of hepatitis A patients
Acute Hep A: IgM Positive or RNA in blood or stool (using PCR – tests for the viral nucleic acid)
What are the test results of a patient who has been vaccinated against hepatitis A
IgG Positive
IgM suggests a new infection, whereas IgG (mature antibody) suggests secondary response/immunity
Describe the hepatitis A vaccine
- inactivated virus
- protection 4 weeks after dose
- 2nd dose gives life protection
When is the hepatitis A vaccine given?
Pre-exposure:
- travellers
- homosexual men
- IVDU
- chronic liver disease patients
Post-exposure:
- outbreak control
What is the hepatitis A immune globulin and when is it given?
- pooled immunoglobulin
- confers 3-6 months immunity
Pre-exposure:
- if vaccine allergic
- <4weeks to travel
post-exposure:
- outbreak control
Summarise hepatitis A
RNA virus Faeco-oral spread 1 month incubation Diagnosed by IgM to Hep A, and deranged Liver Tests Very low death rate No specific treatment No chronic carriage Travel related, rare in UK Excellent vaccine
Describe the hepatitis E virus
RNA virus
More common now than Hep A in the UK
Incubation period 40 days
4 Genotypes
How is hepatitis E transmitted?
o Faeco-oral
o Pork products
o Minimal person-to- person transmission
What is the epidemiology of hepatitis E
Much more common now in the UK than it used to be
o Appears to be related to contact with contaminated pork
o More common than Hepatitis A
Between 1996 and 2003, only 9% of cases were acquired in the UK
71% of 2012 cases were acquired in the UK
Chronic Hep E is seen in very immunosuppressed patients, e.g. bone marrow transplants.
o Hazard for the patient and the wards they visit (lots of immunosuppressed patients)
What are the clinical symptoms of hepatitis E
Fever, abdominal pain, diarrhoea, jaundice, itch,
muscle pains
o Flu-like symptoms + jaundice
(Similar to Hepatitis A plus rare reports of neurological effects)
What is the neurological manifestation of hepatitis E
May be genotype (GT) 3 associated 5% patients affected in one series o Guillaine Barre syndrome o Encephalitis o Ataxia o Myopathy
What is the fatality rate of Hepatitis E
Case-fatality rate: 1 - 3%
o Fatality rate is higher in Pregnant women for some genotypes (especially GT 1)
How is hepatitis E managed?
Treatment: Supportive
No Vaccine
Treatment with ribavirin
Summarise Hep E
High mortality, esp. in Pregnancy with GT 1
No Vaccine
No Immunity
Increasingly recognised as a cause of hepatitis in UK
Neurological complications described
Chronic carriage in some
What is the link between hepatitis B and mortality?
o Causes chronic liver inflammation, ALT remains elevated
o Results in liver scarring and eventual cirrhosis
o Liver decompensation/upper GI haemorrhage (due to varices) can result
o High risk of hepatocellular carcinoma
How is hepatitis B transmitted?
- transfusion (blood, blood products)
- fluids (blood, semen)
- organs and tissue transplant
- child to child
- mother to child (vertical transmission at birth)
- contaminated needles and syringes
What are the common modes of transmission in the tropics?
Majority of infections occur vertically or during childhood by horizontal transmission between children
and infected persons
o Child to child transmission – children fighting/playing
Contact with open sores, scarification, circumcision, bedbugs
Not transmitted by Mosquitoes
Sexual
Iatrogenic
What are the common modes of transmission in the UK?
95% of new diagnoses in the UK are immigrants infected elsewhere moving to the UK
Many are picked up on antenatal screening of pregnant women
New sexual infections in UK are rare
Describe acute hep B infection
Incubation: 2 - 6 months
Fever, fatigue, jaundice, myalgia, joint pains
Acute case-fatality rate: 0.5% - 1%
Age at the time of infection determines:
1. Severity of acute illness
2. Risk of Chronic HBV Infection (CHB)
How can age affect the chronicity of hep B?
Infection at birth / young child is usually asymptomatic but leads to chronic infection
o Baby has very little independent immune system and cannot fight the infection becomes
chronically established
o Lack of symptoms (clinical illness) is also because of the lack of immune response
o Newborn babies should be vaccinated to prevent lifelong infection
Infection as an adult is usually symptomatic but cleared
What symptoms are associated with Hep B infection?
Weight loss, abdominal pain, fever Cachexia Mass in abdomen s Bloody ascites (malignant ascites) o Suggests hepatoma HB sAg +ve
What are the complications associated with chronic hepatitis B infection?
Development of chronic liver disease in 25%, particularly those infected as babies o Cirrhosis o Decompensation o Hepatocellular Carcinoma (HCC) o Death
How do we test for Hepatitis B Serology?
sAg - Surface antigen sAb – Surface antibody cAb – Core antibody eAg – e antigen eAb – e antibody HBV DNA
What is the surface antigen?
marker of infection
o blood test to check for infection
o sAg present = infected
what is the surface antibody?
marker of immunity
o Only seen in people who have been infected in the past
but have cleared the virus
o Seen in vaccinated individuals
What is the core antibody?
o Definitely been infected (currently or in the past)
o Check surface antigen to determine if infection is active
What is the significance of the e antigen?
suggests high infectivity
What is the significance of the e antibody?
– suggests low infectivity
What is the purpose of testing for HBV DNA?
Measures how much of the virus is in the blood
How is hepatitis B diagnosed?
HBV infection is diagnosed if sAg or DNA are detectable
HBV cAb + only, means past infection but now cleared
What should you test for alongside hepatitis B and C?
always test patient for HIV (also with Hep C) because they have the same transmission route
How does liver damage occur in hepatitis b
Liver damage occurs when the body tries to fight the virus
The damage increase the risk of liver cirrhosis and hepatocellular cancer
How are chronic hepatitis B patients classified?
sAg detectable for >6/12
- eAg +ve (early disease)
- eAg –ve (late disease)
What are the features of chronic hep b (early disease)?
o High Viral Load
o High risk of chronic liver disease and hepatocellular carcinoma
o Highly infectious
What are the features of chronic hep b (late disease)?
o Low viral load
o Lower risk of CLD and HCC
o Less infectious
How is acute HBV treated?
o No treatments
How is chronic hbv treated?
Chronic HBV
o Treat those with liver inflammation (LFT and Biopsy)
o Small number, <5%, will clear sAg spontaneously
o Aim of treatment is NOT to cure, but to suppress viral replication +/- to convert from eAg+ to eAb+
What two types of therapy can be used in chronic Hep b?
- immunological (Pegylated interferon alpha)
- antiviral (Tenofovir/Entecavir)
Describe the use of immunological therapies in chronic hep b
Pegylated interferon alpha
Increases cellular immune responses, boosts immune system to prevent further damage
Lots of side-effects – flu-like symptoms for entire duration of treatment
Injection in the stomach once a week
1 year course of medication
Describe the use of antiviral therapies in chronic hep b
(nucleoside/tides) to suppress viral replication
o Tenofovir
o Entecavir
o NB: no major side effects, but once started, treatment continues for life
How can hep b be prevented?
Education (safe sex, injecting etc.) Screening of pregnancy women / doctors Protect blood supply & hospital supplies Immunisation: o Active (HBV sAg Vaccine) High risk groups in UK All in USA, most African / Asian countries o Passive (HBIG) Babies born to some HBV+ mothers Post exposure in non-immune
What is the risk of hbv transmission from mother to baby dependent on
depends on mother’s viral load
What interventions are in place to prevent hbv transmission from mother to baby
- HBV vaccination
=> given to all newborns - HBV Immunoglobulin
=> given if mother is eAg+ or has high viral load - Tenofovir
=> given during the last trimester if high VL (>10 6 IU/mL)
- Aims to reduce mother’s viral load to try and prevent transmission
Describe hepatitis D
ss RNA virus
Requires HBV to replicate (unable to replicate on its own)
o Can only be present with Hepatitis B
How is hepatitis D transmitted?
Transmission same as Hep B, but vertical transmission is rare
Acquired by:
o Co-infection with HBV
Infection at the same time
o Super-infection of chronic HBV carriers
Patient is infected with hep B and then catches Hep D
What complications are associated with hepatitis d
Increases risk of chronic liver disease
How is hep d treated?
Peg IFN only
Summarise hep B and D
Blood / Sex / Needle Transmission
Hep D requires Hep B to survive
Chronic Carriers have risk of Cirrhosis and Cancer
Hep B is most common Hepatitis Virus worldwide
Preventable by excellent vaccine
Vaccine used only in high risk groups in UK
Treatments for Hep B are not curative, but reduce risk of complications and reduce infectivity
How is hepatitis c transmitted?
Transmission:
o Injecting drugs
o Transfusion + Transplant
o Sexual/vertical transmission are rare
How is hep c prevented?
No vaccine, no post exposure prophylaxis
Describe hepatitis c in scotland
Most common hepatitis virus in Glasgow (0.7% Scottish population)
Most commonly seen in drug users (> 50% of Injecting Drug Users are
hep C infected)
What is the incubation period for hepatitis c
Incubation period average 6-7 weeks
How does hepatitis c present?
Mostly asymptomatic
Most diagnosed by screening of high risk groups
How is hepatitis c diagnosed?
Test for antibodies (IgG) first
o Anti HCV IgG positive = chronic infection or cleared infection
Then test for virus itself (antigen test or PCR test)
o PCR or Antigen positive = current infection / viraemia
What is the aim of hep c treatment?
“Sustained Virological Response”
= Cure
= PCR negative 12 weeks after
treatment
How is hep c treated?
Direct Acting Antivirals (DAAs) have substantially increased the chance of cure
Sofosbuvir
Simeprevir
Ledipasvir
Highly effective but very expensive SMC approved drugs for HCV
Different drugs target
different aspects - Can be used in combination
How is Direct-Acting Antivirals regimen decided?
according to Genotype and degree of fibrosis / cirrhosis
Summarise hep c
Hep C is most common Hepatitis Virus in UK
Needle / Blood Transmission
Infection is usually asymptomatic and not noticed
70% develop Chronic infection and at risk of cirrhosis
Treatment aim is to cure
Newer antiviral drugs cure nearly all
No Vaccine and no reliable immunity after infection
