Viral hepatitis Flashcards
What are some viruses that cause hepatitis?
Hep A, B, C, D, and E
Epstein-Barr virus (EBV; infectious mononucleosis; acute phase)
Cytomegalovirus (CMV; in newborn or immunocompromised)
Yellow fever virus (tropical areas
What are the potential outcomes of hepatitis virus infection?
Acute asymptomatic infection with recovery
Acute symptomatic hepatitis with recovery, anicteric or icteric
Chronic hepatitis, with or without progression to cirrhosis
Fulminant hepatitis with massive to submassive hepatic necrosis
Do HAV or HEV cause chronic hepatitis?
No, they are acute only (but do not have to be symptomatic)
Does HCV cause acute hepatitis?
Mainly chronic
Which hepatotropic virus is most associated with fulminant hepatitis?
HBV
How are asymptomatic hepatotropic virus infected individuals diagnosed?
Incidental findings in serology
What hepatotropic viral infections are most commonly associated with asymptomatic infections?
HAV and HBV when infection occurs in childhood (only diagnosed in adulthood by antibodies)
What are the four phases of an acute hepatotropic viral infection?
Incubation
Symptomatic preicteric phase
Symptomatic icteric phase
Convalescence
When are hepatitis viruses most infectious during the infection?
The last part of the asymptomatic phase, and the first few days of symptoms
What is the definition of chronic hepatitis virus infection?
Symptomatic, biochemical or serological evidence of an ongoing or relapsing hepatitis infection over more than 6 months
Do the clinical features of chronic hepatotropic viral infection predict the prognosis?
No, unless they are bad signs such as cirrhosis or hepatocellular carcinoma
What are common symptoms of chronic hepatitis virus infection?
Fatigue (most common)
Malaise
Loss of appetite
Mild jaundice
What are common signs of chronic hepatitis virus infection?
Spider erythemas
Mild hepatosplenomegaly and tenderness
palmar erythema
What are some common laboratory findings in chronic hepatitis virus infection?
^ prothrombin time
Hyperglobulinaemia
Hyperbilirubinaemia
^ Alkaline phosphatase
What is an occasional complication of antibodies circulating in chronic hepatitis virus infection?
Immune complex disease secondary to the presence of circulating antibody-antigen complexes
Includes vasculitis and glomerulonephritis
Cryoglobulinaemia (35% of HCV infected)
HBV can be chronic – what predicts how chronic it will be?
Age at time of infection (much more chronic earlier in life)
What is a problem with reducing chronic HBV in endemic areas?
More chronic when infected earlier, but perinatal transmission is high
Difficult to cure as well
What are the treatment goals with chronic HBV?
Slow disease progression
Reduce liver damage
Prevent liver cirrhosis or cancer
What are the major problems with current HBV treatment regimens?
Viral resistance and side effects
How would you classify a patient who is infected with a hepatitis virus, but has either no liver damage or the liver damage is not progressing?
They are a carrier
How common is the carrier state with HBV?
<1% of cases in non-endemic areas
~90% of cases in endemic areas (because infected early in life)
Is there any evidence that HIV and HBV/HCV coinfect?
Yes – of HIV patients, 10% have HBV and 30% have HCV
Chronic HBV and HCV infection is now a leading cause of morbidity and mortality for HIV patients
What are the main consequences of liver cirrhosis?
Liver failure
Hepatic encephalopathy
Massive haematemesis from varices
What is the definition of fulminant hepatic failure?
Hepatic insufficiency that progresses from the onset of symptoms to hepatic encephalopathy within 2-3 weeks
What is the mortality of fulminant hepatic failure?
80% without transplantation
35% with transplantation
Which hepatitis viruses are transmitted through the faecal-oral route?
HAV and HEV
Which hepatitis virus has an incubation period of 1-6 months?
HBV
What fatality rate is associated with HAV?
0.1%
Only rarely progresses to serious disease
What are the symptoms of acute hepatitis virus infection?
Malaise/nausea
Fever
Jaundice
Hepatosplenomegaly in some cases
T/F HAV replicates in both intestinal epithelia and hepatocytes
True
What treatments are available for HAV infection?
Supportive (rehydration and nutrition)
Describe the HAV vaccine
Inactivated virions pre-expose
Requires more than one vaccination
Expensive process (diploid cells required)
Requires good testing to ensure virions are inactivated
When is an HAV infected individual excreting virions?
2 weeks before and 1 week after onset of jaundice (symptoms)
What does serum IgM anti-HAV in a patient tell you?
IgM correlates with loss of faecal shedding of virus
Reliable indicator of current active infection
IgM anti-HAV reduces after a few months – what is it replaced by?
Probably IgG, but there are no specific tests for IgG anti-HAV
What are the 5 possible outcomes of HBV infection? (percentages in low prevalence areas)
Acute hepatitis with clearance (90%)
Fulminant hepatitis with massive hepatic necrosis (30% of chronic)
How many people in the world have been infected with HBV?
2 billion
How many people in the world have chronic HBV infection?
400 million
How is HBV transmitted in high prevalence areas?
Perinatally (90% of cases)
How is HBV transmitted in moderate prevalence areas?
Horizontally (via wounds etc)
How is HBV transmitted in low prevalence areas?
Unprotected intercourse
IV drug use
Which hepatitis virus has an incubation period of 2-6 weeks?
HAV
What percentage of HBV acute infections show no symptoms?
~70%
How many HBV serotypes are there?
8
Describe the structure of HBV
Spherical double layered ‘Dane particle’
Partially dsDNA genome
What does the HBV genome code for
HBcAg (hepatitis B core protein)
HBeAG (precore)
BHsAg (surface antigen)
Pol (DNA polymerase)
HBx
What is the distribution of HBeAg and HBcAg?
HBeAg is secreted into the blood
HBcAg remains in hepatocytes for virion assembly
What are the three types of HBsAg
Large HBsAg (containing Pre-S1, Pre-S2 and S transcripts)
Middle HBsAg (Pre-S2 and S)
Small HBsAg (S only)
What is special about HBV polymerase?
Can act as both a DNA polymerase and a reverse transcriptase
What is the function of HBxAg?
Transcriptional activator
Implicated in the progression to hepatocellular carcinoma
Which antigens are present shortly after the incubation period?
HBeAg
HBV-DNA
HBsAg
What is the best indicator of active HBV replication?
HBeAg
What is the serological consequence of hepatocyte destruction?
Presence of HBcAg
Rising anti-HBcAg
How do you know that an infection is a new infection, and not the result of a vaccination or past infection?
IgM titre
Rising IgG titre
Does Anti-HBcAg or Anti-HBeAg rise earlier in disease progression?
Anti-HBcAg
What does the presence of Anti-HBsAg in serology alone mean?
Vaccinated
What does the presence of Anti-HBsAg and Anti-HBcAg in serology mean?
Previous infection with HBV
Is Anti-HBsAg present during a HBV infection?
No
Is HBsAg present during HBV infection?
Yes – rises before onset of symptoms and peaks during acute symptoms
Does the HBV virus cause hepatocyte damage?
No – CD8+ T cells cause the damage
How is HBV vaccinated against?
Purified HBsAg
Produces protective Anti-HBsAg in 95%
What are the risk groups for HBV infection?
IV drug users
Health workers
Sexually promiscuous
What are the symptoms of HBV infection?
Like HAV but arthralgia, urticaria as well
What are some complications of HBV infection?
Fulminant hepatic failure
Relapse
Cholestasis
Cirrhosis
Hepatocellular carcinoma (more likely if HBsAg and HBeAg +ve)
Glomerulonephritis
Cryoglobulinaemia
Is HVC a chronic or an acute infection?
Almost always chronic
How often does HCV progress to cirrhosis?
20-30% of cases
What are the common risk factors for HCV? (descending order)
IV drug use (80% of cases)
Promiscuity
Surgery within past 6 months
Needle stick injury
Health worker
What is the most common paediatric route of transmission for HCV?
Perinatal
But much lower perinatal transmission than HBV
Describe the structure of HCV
Enveloped
ssRNA
Describe the genome of HCV
RNA that codes a single polyprotein
Nucleocapsid core protein
Envelope proteins E1 and E2
E2 has two hypervariable regions (HVR1 and 2)
NS2, NS3, NS4A and B, NS5A and B (NS = non-structural)
NS5B is the RNA dependant RNA polymerase
How would you describe the NS5B (RNA polymerase) protein of HCV?
Poor fidelity
Leads to transcriptional errors, leading to multiple ‘quasispecies’ within one infected individual
What is the most variable part of the HCV genome?
E2
Because of the two HVR (hypervariable) regions
T/F E2 of the HCV genome is a target for anti-HCV antibodies
True
HCV being highly variable presents which problems?
Anti-HCV antibodies do not always confer any protection
This means that HCV becomes chronic because it mutates and evades the immune system’s current response leading to renewed hepatic damage
What is the incubation period of HCV?
6-12 weeks
Is the percentage of acute phase HCV infection that are asymptomatic, 75% or 85%?
85%
When is HCV-RNA detectable in the blood in a HCV infection?
After the incubation period (only in 50-70% of patients though, the rest of which have it later)
When symptoms are present
And when serum transaminases are present
How do serum transaminase levels fluctuate in chronic HCV infection?
Rise and fall with the cyclical presentation of symptoms
What are some methods by which HCV is able to evade the immune system in chronic infection?
NS5A is an IFN resistance factor which prevents IFN mediated cellular anti-viral responses
Inhibits TLR signalling in responset o viral RNA recognition
What tests should you do in suspected HCV infection?
LFT (AST:ALT <1:1 until cirrhosis)
Anti-HCV antibodies
Liver biopsy to determine extent of damage and need for treatment/transplant
Screening tests for substance abuse and/or depression
Complete blood cell count (CBC) (thrombocytopaenia in 10% of patients)
What are the limitations of using enzyme immunoassay (EIA) in HCV infection?
Cannot distinguish acute from chronic infection
Does have 97% specificity though
How do you approach a health professional who has suffered a needlestick injury in the context of possible HCV infection?
Immediate PCR for HCV
Repeat every 2 months until 6 months since infection
What is the standard HCV treatment?
PED-IFN, ribavirin and protease inhibitors (simprevir)
Why are interferons given in HCV treatment?
Immunomodulatory cytokine that enhances phagocytic activity of macrophages and cytotoxic activity of lymphocytes
Can HDV exist without HBV?
No
Needs HBV surface antigen
What are the three types of HDV infection?
Acute coinfection
Superinfection
Helper-independant latent infection
Describe acute coinfection of HDV
Follows exposure to serum containing HDV and HBV
HBV must become established to provide the HBsAg necessary for HDV assembly
Clinically presents as Hepatitis B+D
Describe HDV superinfection
Occurs when a chronic HBV carrier is exposed to a new inoculate of HDV
Presents as clinical HDV symptoms with no HBV symptoms
Results in disease 30-50 days later
Describe helper-independent latent HCV infection
Observed in liver transplant settings
HDV detectable in hepatocytes
Can be reactivated
In the case of HDV, is co-infection or superinfection worse for prognosis?
Superinfection
Leads to chronic liver disease in 70-80% of patients
What are the symptoms of HDV infection?
Jaundice
Abdominal pain
Nausea and vomiting
Dark urine
Anorexia
How many HDV patients are asymptomatic?
90% (medscape)
What lab tests can be performed to diagnose HDV infection?
HDV-RNA (90% specific)
Anti-HBcore IgM are positive only in co-infection
LFT (INR>1.5, Prothrombin time > 15s)
How does HDV infection complicate HBV diagnosis?
Active HDV replication almost completely removes HBsAg from serum
How do you treat a HDV/HBV co-infection?
Treating the HBV will limit HDV effectiveness
IFN-alpha-2a has shown effectiveness at directly treating the HDV
How is HEV transmitted?
Faecal-oral route
Contaminated water (water-borne virus)
Is HEV infection in children common?
Very rarely
Occurs mostly in young to middle-aged adults
Does HEV have animal reservoirs?
Yes – commonly found and spread through animals
Monjeys, cats, pigs and dogs
What is the mortality rate of HEV in pregnant women?
20%
Mortality increases in second and third trimesters
How does HEV cause death in pregnant women?
Encephalopathy
DIC (disseminated intravascular coagulation)
Fulminant hepatic failure rates high
What is the most common route of transmission of HEV in non-epidemic areas?
Contaminated food (eg undercooked pork)
Results from HEV making reservoirs in animals, such as pork
What is the fatality rate of HEV infections?
4%
Though much higher in pregnant women and liver transplant patients
How is HEV infection diagnosed?
The presence of anti-HEV IgM
HEV-RNA can be detected before onset of symptoms but not long after
What is the incubation period of HEV?
15-60 days
With what history will HEV patients present?
Anorexia
Nausea/vomiting
Right upper quadrant pain that increases with activity
Jaundice
Dark urine
Pale stools
Pruritus
How is HEV infection treated?
Self-limiting, hence supportive therapy including rehydration
In severe cases, or in immunocompromised, may consider ribavirin
How long do symptoms last in HEV?
2-4 weeks
Is Hepatitis G virus (HGV; GB virus C) hepatotropic?
No
Causes no increase in aminotransferase levels
Where does HGV (GBV-C) replicate?
Bone marrow
Spleen
What are the symptoms of HGV (GBV-C) infection?
GBV-C does not cause human disease
What is the relationship between HGV (GBV-C) and HIV?
Co-infection occurs in 35% of HIV cases
Co-infection is thought to be protective
How often does cholestasis occur in HEV infection?
50%
