Hepatitis Flashcards
Hepatitis A - type of virus?
Picorna (RNA) virus
What is a picornavirus?
group of related nonenveloped RNA viruses
small, positive-sense, single-stranded
Where is hepatitis A infection most common?
Sanitation is poor (developing countries)
What is the route of transmission for hepatitis A?
Faeco-oral (food, water, close-contact)
What factors related to sex appears to increase risk of hepatitis A in MSM?
oro-anal sex Digital-rectal sex Multiple sexual partners Anonymous partners Sex in public places Group sex
What difference may occur in HIV positive people with hep A infection?
More infectious
not at increased risk
What situations have hep A outbreaks been reported in?
MSM
PWID
institutions for people with learning difficulties
contaminated batches factor VIII
How is a person infectious for with hep A?
2 weeks before and 1 week after JAUNDICE
HIV +ve >90 days
Describe the hep A outback in UK and Europe 2016-17?
3 strains/clusters
Spanish strain
Europride (Amsterdam) strain
Berlin strain
What number of hep A cases in England were linked to this outbreak?
266
What proportion of the UK outbreak with hep A were in MSM?
74%
Hepatitis A - incubation period?
15-45 days
What are the symptoms of hep A?
Most children and half adults ASYMPTOMATIC
Prodromal (3-10 days) - Flu-like illness + Right upper abdominal pain
Icteric (1-3 weeks) - jaundice + anorexia, nausea and fatigue
What is the typical hepatic dysfunction picture?
Mixed hepatic and cholestatic jaundice
What proportion of hepatitis A infection develops acute liver failure?
0.4%
What is overall mortality with hep A?
<0.1%
What is the mortality associated with hep A infection AND acute liver failure?
40%
What impact does hepatitis A have on pregnancy?
Increased miscarriage
Premature labour
Possible vertical transmission
Hepatitis A infection - diagnosis?
HAV-IgM positive
HAV IgG does not distinguish between current or past infection
How long does HAV IgM remain positive?
45-60 days although can be >6 months
Describe the LFT derangement in hep A?
Transaminases (AST/ALT) 500 - 10000
Bilirubin 500
What other blood test suggests severe hep A infection?
PT prolongation >5 secs
Acute liver failure typically PT > 50
What general advice should be given to people with acute hepatitis A infection?
Avoid food handling and unprotected sex until non-infectious
If a person is hep A positive what else should be screened for?
hepatits B, C and E
HIV and other STIs
How should acute icteric hepatitis be managed in hep A infection?
Mild/moderate - outpatient, rest, oral hydration
Severe - vomiting, diarrhoea, altered conscious level - admit to hospital
What contact tracing needs to take place following hepatitis A infection?
Recent partners 2 weeks before and 1 week after jaundice onset
Household contacts
At risk of food/water contamination
Notifiable disease
When can hepatitis A vaccine be given post exposure?
Within 14 days of contact with source if source was within infectious period
When should human normal immunoglobulin (HNIG) be considered?
If higher risk of complications
- co-infection HBV/HCV or HIV
- chronic liver disease
- > 50 yrs
When should HNIG be administered post exposure to hepatitis A?
best within first few days of first contact
< 2weeks
HNIG may reduce disease severity even if administered after 2 week period. How long may it be useful for?
up to 28 days
How effective is HNIG and reducing risk of acquiring hepatitis A after contact?
90% effective if given within first few days
How should hepatitis A vaccine typically be dosed? What is the BASHH guidance?
0 and 6 months; all MSM SINGLE dose
What protection does hep A vaccine offer?
95% up to 10 years
Does hep A vaccine need repeated at 10 yrs?
increasing evidence that vaccine- induced immunity may be >20 years and possibly lifelong
if immunocompetent no boost/repeat course
What follow up should a person with acute hepatitis A have?
2 weekly LFTs until normal
Why does the BASHH guidance on hep A vaccination differ from the typical schedule?
International shortage of vaccine; however once sully restored offer full vaccination
Is it reasonable to screen for past hep A exposure/immunity prior to vaccination?
Yes
When might you opt to give vaccination prior to waiting for hep A antibody test result?
During outbreak situation
MSM will not return
What alternative vaccines can be used for hep A if monovalent or combined A+B are not available?
For emergency situation:
paediatric monovalent
hepatitis A/typhoid
Who else other that MSM should be vaccinated against hep A?
PWID with HBV or HCV infection
Travellers to developing countries
Hepatitis B - type of virus?
hepadna (DNA) virus
What is a hepadnavirus?
group of DNA viruses that infect hepatocyte
Hepatitis B virus in UK - seroprevalence?
0.01-0.04%
What is the zero-prevalence of HBV in PWID and MSM in UK?
> 1%
How many distinct genotypes are there for HBV?
8
genotype A-H
What sexual behaviours are associated with HBV infection and MSM?
multiple partners
unprotected anal sex
oro-anal sex
How likely is HBV sexual transmission between heterosexual regular partners?
18% infection rate; higher for sex workers
Other than sexual how is HBV acquired?
Vertical
Parenteral (PWID, blood products, occupational needlestick, non-sterile acupuncture/tattoos)
Hepatitis B - incubation period?
40-160days
In HBV the prodromal and icteric phases are very similar to hepatitis A, but may be more severe and prolonged. How common is acute liver failure?
<1%; but carries a worse outcome than HAV
How many phases of chronic HBV infection or carriage?
5 phases
Describe phase 1 of chronic HBV infection.
HB eAg +ve
HIGH levels DNA
NORMAL AST/ALT
little/no liver inflammation on biopsy
Describe phase TWO of chronic HBV infection.
HB eAg +ve
FALLING levels DNA
RAISED AST/ALT
liver inflammation on biopsy AND progressive FIBROSIS
Describe phase THREE of chronic HBV infection.
HB eAg -ve
LOW levels DNA
normal AST/ALT
Describe phase FOUR of chronic HBV infection.
HB eAg -ve
FLUCTUATING levels DNA - possible mutations
normal AST/ALT
INFLAMMATION and progressive FIBROSIS on biopsy
Describe phase FIVE of chronic HBV infection.
HB surfaceAg NEGATIVE HB coreAb POSITIVE possible HB sAb +ve undetectable DNA normal ALT
In which phases of HBV chronic infection does progression to cirrhosis occur?
2 and 4
What causes reactivation of hepatitis B infection?
Immunosuppression including Advanced HIV
Treatment of HBV and stopping treatment
chronic renal failure
Co-infection with which infections leads to increased risk of HBV complications?
hepatitis C
HIV
delta virus infection
What proportion of chronic HBV carriers will develop cirrhosis?
10-50%
What proportion of HBV associated cirrhosis will lead to premature death?
50%
What proportion of HBV associated cirrhosis will lead to liver cancer?
10%
If hepatitis B surface antigen positive what advice should be given to patient?
No unprotected sex including oral-anal and oral-genital
Regular partners and close household contacts should be vaccinated
No organ/semen/blood donation until surface antigen negative
When should a patient with HBV be referred to specialist in viral hepatitis?
surface antigen positive
What considerations are made before hepatitis B treatment?
HBV DNA level
Liver inflammation/fibrosis
When is treatment for chronic HBV typically offered?
HBV DNA >2000
evidence of liver necro-inflammation +/I fibrosis
What treatment options are available for HBV alone?
tenofovir disoproxil and alfenamide (TDF or TAF)
Entecavir
Pegylated interferon
Which ARVs can be used for both HBV and HIV infection?
Lamivudine or emtricitabine with TDF or TAF
Why must a dual NRTI regimen be used when treating both HBV and HIV?
significant risk of ART HIV resistance if used as monotherapy
Why should entecavir NOT be used for HBV treatment in HIV positive patients?
If HIV VL not suppressed entecavir can lead to M184V (3TC/FTC) resistant mutation
What is the benefit of treatment or HBV?
reduced liver damage and decreased risk of liver cancer
How frequently should a person with significant fibrosis/cirrhosis have follow up? What is the follow up?
6-12 monthly
Hepatology review
liver US and alpha-feta protein (AFP)
Which patient groups are at highest risk of HCC developing without cirrhosis in HBV infection?
African >20 yrs old
Asian males >40 yrs old
Asian females>50 yrs old
Family history of HCC
How common is vertical transmission with HBV infection?
HB eAg +ve 90% risk of transmission
HB sAg +ve, eAg -ve 10%
Children infected with HBV through vertical transmission, what proportion are chronic carriers?
90%
How can vertical transmission of HBV be reduced? How effective is it?
Tenofovir to mother third trimester
Hepatitis B specific immunoglobulin to baby
Vaccination at birth
Reduces vertical transmission 90%
How soon after exposure to HBV infection should specific hepatitis B immunoglobulin (HBIG) be administered?
Works best within 12 hours
Ideally by 48 hours
No good after 7 days
Who should be offered Hepatitis B vaccine in relation to a known source of infection?
All given HBIG
All regular sexual and household contacts
Give within 6 weeks
Ultra rapid or rapid accelerated course
If a person has been vaccinated in the past and is then exposed to HBV infection, what should they be offered>
Single booster dose of hepatitis B vaccine
What is the antibody response with ultra-rapid vaccination for HBV?
80% response within 4-12 weeks of third dose
Offer booster if no detectable antibody at 4-12 weeks
What proportion will have an antibody response by 12 months following primary course of hepatitis B vaccination?
95%
What proportion of HBV infection develop natural immunity lifelong after recovery from infection (sAg -ve)?
90%
HB cAb +ve, sAg -ve with HB sAb and HB eAb negative, what might this suggest?
HB cAb false positive
How can the possibility of HB cAb false positive be established?
Single hepatitis B vaccine dose will induce HBsAb +ve 4 weeks after vaccine if previous natural exposure to HBV
What test should be used for hepatitis B screening?
HB cAb
or
HB sAg
Who should be offered hepatic B vaccination as primary prevention?
MSM Sex workers PWID HIV +ve Sexual assault victims People from high prevalence HBV - Western Europe, North America, Australasia Needlestick Heterosexual with >10 partners/year Sexual partners of positive or high risk of HBV
What impact does HIV have on response to hepatitis B vaccine?
Reduced response
Better if CD4 cell count >500 and VL undetectable
Become HBsAb NEGATIVE more quickly
If double dose hepatitis B vaccine is used for PWLH, what effect does it have?
increases response by 13%
Hepatitis D (delta virus) - describe what it is?
Small incomplete RNA virus
Only infects people with HB sAg +ve infection
Who is at risk of hepatitis D?
acquired the infection abroad
PWID and their sexual partners
sex workers
When should hepatitis D be suspected?
Acute hepatitis severe
or
further attack in HBV infection
What is the clinical implication of co-infection with HBV and HDV?
High rate of fulminant hepatitis and cirrhosis
Rapidly progressive liver disease
How is hepatitis D diagnosed?
Should be tested in all HBV positive
positive anti-HDV antibody
What is hepatitis D response to antivirals?
Poor
Hepatitis C - type of virus?
RNA virus in flaviviridae family
What is a flaviviridae?
positive, single-stranded, enveloped RNA viruses
How many people in UK are infected wit HCV?
215 000
What are the most common genotypes of HCV?
1 and 3
What proportion of HCV in UK are genotype 1 or 3?
90%
What is the most common route of transmission of HCV in UK?
Parenteral spread
What is the rate of sexual transmission of HCV in heterosexual couples?
<0.1% in 10 years
What is the steadily increasing incidence of HCV in MSM linked to?
HIV co-infectionn
What other factors increase the risk of sexually acquired CV?
MSM -Co-infection syphilis or LGV -traumatic anal sex -fisting -sharing sex toys -communal lubricant -group sex -sero-sorting -recreational drug use Sex workers
What is the rate of vertical transmission of HCV?
5%
7% if HIV co-infection
Hepatitis C - incubation period?
4 to 20 weeks
What proportion of HCV infection is serology positive at 3 months?
90%
What proportion of HCV infection is asymptomatic?
Majority >60%
How likely is acute fulminant hepatitis in HCV infection?
Rare <1%
What proportion of HCV infection become chronic carriers?
50-85%
What makes spontaneous clearance of HCV more likely?
favourable polymorphisms around IL28B gene
What proportion of significant liver disease from HCV can occur with normal transaminases?
35%
30% chronic carriers HCV will progress to severe liver disease, after what period of time?
14-30 years
How soon after initial infection will HCV-RNA be detectable?
2 weeks
Define acute hepatitis C infection.
Recent exposure to HCV
HCV-RNA positive
likely HCV antibody negative
What is a surrogate marker of HCV replication? What is its limitation?
HCV core antigen
Less sensitive than HCV RNA
What general advice should be given to those will HCV infection?
Curable or spontaneously clear
Should not donate blood, semen or organs
Refer to specialist
In addition to STI tests and LFTs what other investigation may be considered?
Fibroscan
Liver US
What is the goal of HCV treatment?
CURE HCV infection
REDUCE liver fibrosis, cirrhosis, HCC and extrahepatic manifestations
Define HCV cure.
Negative CV RNA in blood 12 weeks after completion treatment
Define HCV spontaneous resolution
loss of HCV RNA in first 6 months
When is treatment for HCV indicated?
acute HCV with <2 log10 decline in RNA by week 4
or
HCV RNA remains positive by week 12
How long should HCV monitoring continue if treatment not indicated?
48 weeks
What classes of direct-acting antiviral agents (DAAs) are used?
NS3/4 protease inhibitors
NS5A
NS5B
What considerations are made when deciding on DAA of HCV infection?
HCV genotype and viral load liver disease stage prior HCV treatment co-morbidity Drug-drug interactions
Can treatment be offered in pregnancy?
No
Small risk vertical transmission
Who should contact tracing include for HCV infection?
Sexual partner if patient or partner HIV +ve
PWID sharing needles
What follow up is required for chronic untreated HCV?
6-12 monthly fibroscans
HCV + advanced fibrosis/cirrhosis require what follow up?
6 monthly HCC screening
- liver US
- AFP
Does past HCV infection protect a person from further acute infection?
NO
Neither past cleared or treated or chronic infection
Dual/super infection well documented
What group of patients may be at risk of HCV especially pre1990?
Haemophiliacs
or
people who received blood or blood products
If untested - TEST
When did screening of blood products for HCV start in the UK?
September 1991
