Viral Hepatitis Flashcards
Define hepatitis?
6 viruses known to infect humans- A, ,C,D,E nd G other viruses that inect liver= CMV, EBV, yellow fever, herpes
what are the six different viruses known to infect
what is the typical presentation for hepatitis?
fever, jaundice, raised ALT, AST
what is the typical presentation for hep A?
Travel, faecal-oral (contaminated water is a major source/ poor hygiene), acute, usually asymptomatic, supportive management , 2 weeks incubation - Asia and Africa
what is the typical presentation for hep B?
acute, MSM, unprotected sex, blood transfusion/ IVDU, causes high ALP as well, most clear the infection, 4-12wks, health care workers, likely in children, Africa
what is the typical presentation for Hep C?
chronic, rf for hepatocellular carcinoma, TRANSFUSIONS, blood to blood transmission/IVDU, 2wks-6mnths, Eastern Mediterranean
what is the typical presentation for Hep D?
only with Hep B
what is the typical presentation for Hep E?
Enteric, faecal oral (water), Pregnancy, immunocompromised, supportive management, acute
Define hepatitis A and E?
hepatitis caused by infection with RNA viruses, hepatitis A or hepatitis E that follow an acute course with progression to chronic carriage
go to A and E with Hep A and E
what type of viruses are Hep A and E?
small non-enveloped single stranded linear RNA viruses of roughly 7500 nucleotides-> with transmission via faeco-oral route
HAV- picornavirus
HEV - calcivirus
describe the aetiology of hepatitis A and E?
HAV = picornavirus HEV = calicivirus
Transmission = faecal-oral route
Both viruses replicate within hepatocytes and are secreted into bile
Liver inflammation and hepatocyte necrosis is caused by the immune response
Infected cells are targeted by CD8+ T cells and NK cells
What is the transmission of hepatitis A and E?
faecal -oral route
describe the histological features of hepatitis A and E
Inflammatory cell infiltration of portal tracts (neutrophils, macrophages, eosinophils, lymphocytes)
Zone 3 necrosis
Bile duct proliferation
what are the risk factors for hepatits A and E?
endemic region with poor sanitation
homosexual men
close contact with infected person
think went on hols and had some shellfish
summarise the epidemiology of viral hepatitis?
Hep A – more common than Hep E
HAV is endemic in the developing world
Infection often occurs sub-clinically (no clinical findings)
Better sanitation in the developed world means that it is less common, age of exposure is higher and, hence, patients are more likely to be symptomatic
Annual UK incidence: 5000
HEV is endemic in Asia, Africa and Central America
what is the incubation period of HAV and HEV?
3-6 weeks
what are the prodromal period symptoms ( early symptoms) of Hepatitis A and Hep E?
malaise
anorexia- distaste in cigarettes in smokers
fever
nausea and vomiting
RUQ pain
what are the symptoms of hepatitis?
dark urine
pale stools
jaundice lasting around 3 weeks
ocassionally, itching and jaundice may last several weeks in HAV infection
what are the signs of hep A and Hep E?
pyrexia
jaundice
tender hepatomegaly
spleen may be palpable
ABSENCE of stigmata of chronic liver disease (although some spider naevi may appear transiently)
what are the appropriate investigations for Hep A and Hep E and interpret the results?
Bloods
- LFTs - high AST, ALT, ALP and bilirubin
- High ESR
- Low albumin + high platelets (if severe)
Vital Serology
- Hep B and C serology must be done to rule them out
- Hepatitis A:
- Anti-HAV IgM (during acute illness, disappears after 3-5 months)
- Anti- HAV IgG (recovery phase and lifelong persistence)
- Hepatitis E:
- Anti-HEV IgM (raised 1-4 weeks after onset)
- Anti-HEV IgG
Urinalysis
- Positive for bilirubin
- Raised urobilinogen
outline the management plan for viral hepatitis?
There is no specific management other than bed rest and symptomatic treatment (e.g. antipyretics, antiemetics or cholestyramine (for severe pruritus))
Prevention and Control
- Public Health - safe water, sanitation and food hygiene
- These are notifiable diseases
- When travelling, personal hygiene and dietary precautions
- Immunisation is available for HAV only
Passive immunisation with IM human immunoglobulin (effective for a short time)
Active immunisation with attenuated HAV vaccine offers safe and effective immunity for those travelling to endemic areas and high-risk individuals
what are the possible complications of Hep A and Hep E?
Fulminant hepatic failure (in a very small proportion of patients but is more common in pregnant women)
Cholestatic hepatitis with prolonged jaundice and pruritus can develop after HAV infection
Post-hepatitis syndrome: continued malaise for weeks to months
summarise the prognosis of viral hepatitis?
Recovery is usually within 3-6 weeks
Occasionally patients may relapse during recovery
There are no chronic sequelae
Fulminant hepatic failure has a mortality of 80%
Define Hep B?
Hepatitis caused by infection with hepatitis B virus (HBV), which may follow an acute or chronic course
Chronic is defined as viraemia and hepatic inflammation continuing for > 6 months
what
Define Hep D?
a defective virus, that may only co-infect with HBV or superinfect people who are already carriers of HBV – D is Dependent
describe the transmission of hep B and hep D?
sexual contact, blood and vertical transmission (from mother to baby)
what are the risk factors for Hep B and Hep D?:
IV drug use
Unscreened blood and blood products inc haemodialysis
Infants of HBeAg/HBsAg-positive mothers
Sexual contact with HBV carriers
Younger individuals (particularly babies) are more likely to become chronic carriers
Genetic factors are associated with varying rates of viral clearance
what type of virus is HBV?
enveloped, partially double stranded DNA virus
What type of virus if HDV
HDV is a single-stranded RNA virus coated with HBsAg
What are the various viral proteins produced by Hep B?
Core antigen (HBcAg)
Surface antigen (HBsAg)
e antigen (HBeAg)
describe the histology of Hep B?
mild to severe inflammation and changes to cirrhosis
outline the aetiology of Hep B and Hep D?
HBV is an enveloped, partially double-stranded DNA virus
Transmission: sexual contact, blood and vertical transmission (from mother to baby)
Various viral proteins are produced such as:
Core antigen (HBcAg)
Surface antigen (HBsAg)
e antigen (HBeAg)
This is a marker of high infectivity
HDV is a single-stranded RNA virus coated with HBsAg
Antibody and cell-mediated immune response to viral replication leads to liver inflammation and hepatocyte necrosis
what are the risk factors for Hep B and Hep D?
IV drug use
Unscreened blood and blood products inc haemodialysis
Infants of HBeAg/HBsAg-positive mothers
Sexual contact with HBV carriers
Younger individuals (particularly babies) are more likely to become chronic carriers
Genetic factors are associated with varying rates of viral clearance
summarise the epidemiology of viral hepatitis?
Common
1-2 million deaths annually
Common in Southeast Asia, Africa and Mediterranean countries
HDV is also found worldwide
what is the incubation period of viral hepatitis?
3-6 months
6 months in chronic carriers
what are the presenting symptoms of Hep B and Hep D?
Most children have an asymptomatic acute infection and 50% of adults have an asymptomatic acute infection (esp if they have HIV)
1-2 week prodrome consisting of:
- Malaise
- Headache
- Anorexia
- Nausea and vomiting
- Diarrhoea
- RUQ pain
- Serum-sickness type illness may develop (e.g. fever, arthralgia, polyarthritis, urticaria, maculopapular rash)
Jaundice then develops with dark urine and pale stools
Recovery usually within 4-8 weeks
1% develop fulminant liver failure
Chronic carriage may be diagnosed after routine LFT testing or if cirrhosis or decompensation develops
what are the signs of chronic Hep B infection?
Jaundice
Pyrexia
Tender hepatomegaly
Splenomegaly
Cervical lymphadneopathy (in 10-20% of patients)
Occasionally: urticaria and maculopapular rash
what are the signs of chronic Hep B?
May be no findings
May have signs of chronic liver disease or decompensation
describe the viral serology?
describe the viral serology of acute HBV?
HBsAg positive
IgM anti-HBcAg
+/- HbEAg - if this is negative it reduces the likelyhood of transmission from mum to baby
what is the viral serology for chronic Hep B?
HBsAg positive
IgG anti-HBcAg
+/- HBeAg (correlates with severity)
describe serology for HBV cleared?
Anti-HBsAg antibody positive
IgG anti-HBcAg
describe the serology of HBV that has been vaccinated against?
Anti-HBsAg antibody positive
Describe the serology of HDV infection?
Detected by IgM or IgG against HDV
PCR is used for detection of HDV
summarise serology for Hep B infection?
what are the appropriate investigations for Hep B and what are the results?
viral serology
LFTs
- High: AST, ALT, ALP, bilirubin
- Also do a coag screen with baseline liver USS
FBC
- Microcytic anaemia (indicative of portal HT)
- Thrombocytopenia (indicative of portal HT)
Clotting
- High PT (in severe disease)
TO CONSIDER: Liver Biopsy – percutaneous or transjugular if clotting is deranged or ascites peresent
describe the prevention of Hep B?
blood screening, safe sex, instrument sterilisation
what are the possible complications of Hep B?
1% get fulminant hepatic failure
Chronic HBV infection (10% of adults, much higher in neonates)
Cirrhosis
HCC
Extrahepatic immune complex disorders (e.g. glomerulonephritis, polyarteritis nodosa)
Superinfection with HDV may lead to acute liver failure or more rapidly progressive disease
summarise the prognosis of Hep B?
describe the management of acute hep B?
Symptomatic treatment (antipyretics, antiemetics and cholestyramine) and bed rest
Nucleoside/nucleotide analogues (entecavir OR tenofovir)
Notifiable disease - trace sexual and needle sharing contacts and offer a vaccination against HBV
outline the management of chronic Hep B?
1st Line: Nucleoside/nucleotide analogues (entecavir OR tenofovir)
2nd Line OR + if coninfected by HepD: Interferon alpha (standard or pegylated – pegylated has inc half life)
- Cytokine which augments natural antiviral mechanisms
- Side-effects: flu-like symptoms such as fever, chills, myalgia, headaches, bone marrow suppression and depression – 5-10% discontinue
- Signs of good response to interferon: high serum transminases, low HBV DNA, active histological changes, absence of complicating disease
- Usually on these for life
describe the passive immunisation of Hep B?
Hepatitis B immunoglobulin following acute exposure and to neonates born to HBeAg-positive mothers (in addition to active immunisation)
Describe the active immunisation of Hep B?
Recombinant HBsAg vaccine for individuals at risk and neonates born to HBV +ve mothers
Immunisation against HBV protects against HDV
define Hep C?
Hepatitis caused by infection with hepatitis C virus (HCV), often following a chronic course (in 80% of cases)
describe the transmission of HCV?
PARENTERAL
Sexual transmission
Vertical transmission
What type of virus of Hep C?
HCV is a small, enveloped, single-stranded RNA virus
RNA viruses have poor fidelity of replication and mutation rates are high - so, there are lots of HCV genotypes
what are the risk factors for Hep C?
Recipients of blood and blood products
IV drug users
Non-sterile acupuncture
Tattooing
Haemodialysis
Health care workers
describe the pathogenesis of Hep C?
The virus is not thought to be directly hepatotoxic
It is the humoral and cell-mediated responses to the viral infection that leads to hepatic inflammation and necrosis
describe liver biospy of hep C?
Chronic hepatitis
Lymphoid follicles in portal tracts
Fatty change
Cirrhosis may be present
Summarise the epidemiology of Hep C?
COMMON
Different genotypes of HCV have different geographical prevalence
what are the presenting symptoms of Hep C?
90% of acute infections are ASYMPTOMATIC
10% become jaundiced with mild flu-like illness
May be diagnosed after incidental abnormal LFT or in older patients with complications of cirrhosis
what are the signs of Hep C on physical examination?
May be NO SIGNS
There may be signs of chronic liver disease (if long-standing HCV infection) e.g. jaundice, ascites
May be signs of hepatic encephalopathy if advanced CLD
Extra-hepatic manifestations (rare) include:
- Skin rash
- Renal dysfunction (due to glomerulonephritis)
what are the appropriate investigations for Hep C and describe the results?
HCV Serology
- Anti-HCV antibodies - IgM (acute) or IgG (past exposure or chronic)
Reverse-transcriptase PCR
- Allows detection and genotyping of HCV
- Used to confirm antibody testing or if suspected in pt but serology negative
LFT
- Acute infection: High ALT, AST and bilirubin
- Chronic infection: 2-8 x elevation of AST + ALT (often fluctuates over time)
what investigations would you consider for Hep C?
Liver Biopsy
- Assess the degree of inflammation and liver damage (NOT for diagnosis)
- NOTE: transaminase (AST and ALT) levels bear little correlation to histological changes
- Useful for diagnosing cirrhosis – as these pts require monitoring for HCC
describe the prevention management for Hep C?
Screen blood, blood products and organ donors
Needle exchange schemes for IV drug users
Instrument sterilisation
NO VACCINE AVAILABLE
describe the medical management for Hep C?
Acute - mainly supportive (antipyretics, antiemetics, cholestyramine)
Chronic
- Antivirals are now curative: NS5A inhibitors
- Pegylated interferon-a
- AND
- Ribavarin
Monitor HCV viral load after 12 weeks to determine treatment efficacy
HCV RNA level measured by polymerase chain reaction on EDTA blood sample is used to monitor response to treatment. Undetectable HCV RNA at 48 weeks after completion of treatment defines cure (known as ‘sustained virological response’ or SVR)
Regular US of the liver may be needed if the patient has cirrhosis
There is no post exposure prophylaxis available for hepatitis C, unlike HIV.
what are the possible complications of Hep C?
Fulminant hepatic failure
Chronic carriage of HCV
Hepatocellular carcinoma
Less common: porphyria cutanea tarda, cryoglobulinaemia, glomerulonephritis
summarise the prognosis of Hep C?
80% of exposed will progress to chronic carriage
Of these, 20-30% will develop cirrhosis over 10-20 years
