tbl 6: viral hepatitis Flashcards
Hepatitis A virus (HAV) – small (27 nm) RNA virus belonging to the ______________ group
- Hepatitis A occurs in places with poor water sanitation – spreads via the faecal-oral route mainly through water supply that is contaminated by the sewage
- Short incubation period of _________________ (compared to hepatitis B which has an incubation period of 2 to 6 months)
- Hepatitis A virus infection is often subclinical – only a minority becomes jaundiced)
- In patients with underlying liver disease – hepatitis A vaccine will be recommended to prevent a serious complication
- Notifiable in the UK (report to public health authorities) – dangerous if the patient is a chef and handles food
o Main occupational risks – people who work in sewage plants
o Genitourinary medicine (GUM) clinics also see hepatitis A patients as their patients are typically men who engage in sexual intercourse with other men
- Cases of hepatitis A outbreaks –
o Shanghai 1998 – 310000 people were infected with hepatitis A due to consumption of blood clams (clams filter 40l of water/day and even in 2004, 5-10% of these clams are still hepatitis A positive)
§ Hence, people with jaundice will be asked on their diet (especially with respect to shellfish)
o New Zealand – consumption of Waikato blueberries from December 2001 to January 2002 led to 17 cases of hepatitis A – shows that hepatitis A virus is not killed by freezing
picornavirus;
2 to 6 weeks;
Characteristics of hepatitis A viral infection – incubation period of 2 to 6 weeks,
- One-off infection (does not cause chronic infection) – 2 to 6 weeks after infection, there is a rise in ALT and it then settles down
- Diagnostic test – anti-hepatitis A antibody, IgM
o IgM antibodies suggests recent infection whereas IgG antibodies come on more gradually to give protection against future infections
o IgM suggests recent infection and Ig G suggests previous infection
o Raised antibodies could also indicate the patient has just undergone a vaccine for hepatitis A
- Hepatitis A vaccine is safe and can be combined with other vaccines such as __________ for frequent travellers, or _____________ for people at high risk (gay men)
typhoid;
hepatitis B
Hepatitis B
- Occurs in high prevalence in places such as sub Saharan Africa, areas of South America, North America and Southeast Asia
- In countries such as Taiwan, before a widespread vaccine was introduced, about 20% of the population had hepatitis B
o There are different genotypes of hepatitis B – _____________ is usually seen in northern Europe whereas B and C are usually seen in Asia
- Hepatitis B virus is the most common cause of chronic viral liver disease in Singapore and is endemic
o HBsAg prevalence is 5.7% for males and 3.4% for females, with the highest rate among the Chinese
o Liver cirrhosis is observed in 20% of hepatitis B patients
o Estimated total annual cost of chronic hepatitis B virus infection and associated complications e.g. cirrhosis and hepatocellular carcinoma in Singapore is about US $279 million – represents a sizable economic burden
genotype A;
Hepatitis B virus – DNA hepadnavirus (heap – liver + DNA) which is structurally and immunologically complex
- Electron microscopy of HBV reveals three distinct particles – double-layered circles (__________________) that churn out excess surface antigens in 2 forms, spheres (in white) and tubules
- Overlapping reading frames in the genome – if there is a mutation in the polymerase gene, the mutation may also affect the ________________
o _________ indicates current HBV infection while __________ is an indicator of active viral replication – can likely transmit the virus on to another person
Dane particles;
surface antigen;
HBsAg;
HBeAg
Course of hepatitis B infection
- Hepatitis B has an incubation period of 2 to 6 months – transmission routes are sexual, vertical (mother to baby) and through blood
o Hepatitis B can cause both acute and chronic (> 6 months) infections
o HBV can be a silent killer – patients with no symptoms or previous medical problems can suddenly develop cirrhosis (late stage) and screening is advised
- 2 to 6 months after infection, there is an increase in ALT levels – these patients would also be antigen positive for hepatitis B as well as containing hepatitis B virus DNA in their blood
o Develop ________________ quickly – diagnosis test for acute hepatitis B infection
o If patients only have _______________ and not antihepatitis B core antibodies – only exposed to the surface antigen of the virus (vaccination)
o Cirrhotic patients often have normal LFTs – only clinical signs (e.g. palmar erythema) should be considered in the diagnosis of HBV and cirrhosis
anti-hepatitis B core antibodies (IgM) ;
anti-hepatitis B surface antibodies
Presence of HBsAg indicates infection of Hep B – if ____________ show that it is positive, it means that the infection is chronic
o Within the scope of chronic infection, LFT e.g. ALT determines if it is an active chronic infection or an inactive carrier state
o Recovery refers to the resolution of the acute infection of Hepatitis B indicated by an undetectable HBsAg after 6 months
Chronic hepatitis B infection – about 90% of babies exposed to hepatitis B develop chronic infection, whereas only 5% of adults develop chronic infections
- Risk is increased in chronic infections such as _____________________
- In chronic infection, an acute infection causes ________________ and over time, results in cirrhosis
o A cirrhotic liver has a 4% risk/year of developing liver cancer (hepatocellular carcinoma)
o HCC – multifocal, occurring usually in a background of a diseased liver
repeat test 6 months away;
renal failure and low CD4 count in HIV;
inflammation which then leads to scarring
Disease stages and recovery from hepatitis B infection
- Hepatitis B cannot be completely eradicated from the body – in a patient with an HBV infection, resolution may mean that ________________ is lost but core antibodies still remain
o In vaccinated individuals – antibodies to HBsAg is positive and core antibodies are negative
- In hepatitis B infection, _________________ persists after an infection
o May lead to reactivation of hepatitis B after the patient is immunocompromised after recovery – e.g. immunosuppressive therapy commenced in chemotherapy for patients who have recovered or are carriers
o Risk of reactivation varies – patients with chronic infection are more likely to experience a flare compared to carriers and recovered patients - HBsAg: Indicates __________________
- Anti HBc: Indicates _________________________)
- Anti HBs: Immunised against Hep B either through vaccination or previous infection (antisurface)
- __________: Difference between chronic and acute Hep B infection
- HBeAg: Indicates infectivity (envelope antigen)
- ___________: Indicates lowered infectivity during infection
HBsAg (surface antigen);
covalently closed circular DNA (cccDNA)
infection or recent vaccination (surface antigen);
infection or history of infection (anti-core antigen antibody;
IgM Anti HBc;
Anti HBe
HBsAg, Anti HBs and Anti HBc in someone preciously immunised with vaccine?
Anti HBs +ve
HBsAg, Anti HBs and Anti HBc in someone with early infection/ recent vaccination ?
HBsAg +ve
HBsAg, Anti HBs and Anti HBc in someone during window period in acute infection?
Anti HBc +ve
HBsAg, Anti HBs and Anti HBc in someone after resolution of acute infection?
Anti HBs +ve. anti HBC +ve
HBsAg, Anti HBs and Anti HBc in someone with chronic infection?
HBsAg +ve. anti HBc +ve
Disease stages of hepatitis B – immune tolerant, immune reactive, inactive carrier state, HBeAg negative chronic HBV and HBsAg negative phase
o _________________ – hepatitis B carrier, high viral load but normal LFT and immunology, highly contagious
o _____________ – HBeAg positive, body attempts to clear the virus. Immune response is mounted, jaundice may develop, but sometimes it may be asymptomatic
§ HBeAg becomes negative from positive (eAg negative hepatitis B)
o ______________ – HBeAg negative, viral load falls, ALT normal and liver biopsy show minimal activity
Immune tolerant;
Immune active;
Inactive carrier
Studies of hepatitis B
- REVEAL study – natural history studies, measurement of baseline ___________ in patients and following up for complications
o Shows that 11-year incidence of cirrhosis increases with increasing ______________ (viral load)
- Also shows that incidence of HCC (13-year) increases with increasing HBV DNA baseline viral level
Treatment of hepatitis B – _____________ is used to determine the patient’s condition and there are many guidelines in the treatment of hepatitis B
- Hepatitis B is not curable – treatment is long term suppressive treatment
o Treatment includes interferon-α, lamivudine, adefovir, tenofovir, entecavir and emtricitabine
- Interferon-α should be given to patients who already have an _______________ (high liver function test – high level of ALT)
o Should not be given to patients who are immunocompromised such as HIV patients and renal failure patients
o Large number of side effects – causing flu-like symptoms, depression and toxic to platelet/white cell count - Reverse transcriptase inhibitors (NRTIs) – used to manage HIV patients as well
o Lamivudine, Adefovir, Tenofovir, Entecavir, Emtricitabine
o HIV and hepatitis B virus infection – combination of ______________ is usually given (Truvada)
o Long term suppressive therapy – ___________ are usually given as monotherapies for hepatitis B patients with higher risk for life-threatening complications
o _______________ has a quick development of resistance towards it and ___________ has nephrotoxic side effects
HBsAg and DNA;
baseline serum HBV DNA level;
viral load in the blood;
immune response mounted against the virus;
tenofovir and emtricitabine;
tenofovir and entecavir ;
Lamivudine monotherapy;
adefovir
Liver transplantation in hepatitis B
- Patients with untreated hepatitis B can also develop liver failure in the severe end of the spectrum – prior to the development of the drugs, liver transplantation resulted in ___________________ quickly
o Limited treatment options – interferon-α cannot be used in immunocompromised settings
o Newer developments – nucleoside analogues, ________________ (good titres against HBV)
- If patient develops decompensated liver disease – anti-viral drugs sometimes sufficient in the recovery of these patients (do not require a liver transplant)
Prevention of hepatitis B
- Safer sex recommended
- Hepatitis B vaccines – healthcare workers, liver disease patients and gay men etc.
- New vaccines are being developed for people who do not respond to current vaccines
graft reinfection;
specific HBV immunoglobins;
