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Robbins Liver & Biliary > Viral hepatitis > Flashcards

Viral hepatitis Flashcards

1
Q

What are some viruses that cause hepatitis?

A

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

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2
Q

What are the potential outcomes of hepatitis virus infection?

A

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

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3
Q

Do HAV or HEV cause chronic hepatitis?

A

No, they are acute only (but do not have to be symptomatic)

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4
Q

Does HCV cause acute hepatitis?

A

Mainly chronic

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5
Q

Which hepatotropic virus is most associated with fulminant hepatitis?

A

HBV

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6
Q

How are asymptomatic hepatotropic virus infected individuals diagnosed?

A

Incidental findings in serology

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7
Q

What hepatotropic viral infections are most commonly associated with asymptomatic infections?

A

HAV and HBV when infection occurs in childhood (only diagnosed in adulthood by antibodies)

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8
Q

What are the four phases of an acute hepatotropic viral infection?

A

Incubation

Symptomatic preicteric phase

Symptomatic icteric phase

Convalescence

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9
Q

When are hepatitis viruses most infectious during the infection?

A

The last part of the asymptomatic phase, and the first few days of symptoms

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10
Q

What is the definition of chronic hepatitis virus infection?

A

Symptomatic, biochemical or serological evidence of an ongoing or relapsing hepatitis infection over more than 6 months

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11
Q

Do the clinical features of chronic hepatotropic viral infection predict the prognosis?

A

No, unless they are bad signs such as cirrhosis or hepatocellular carcinoma

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12
Q

What are common symptoms of chronic hepatitis virus infection?

A

Fatigue (most common)

Malaise

Loss of appetite

Mild jaundice

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13
Q

What are common signs of chronic hepatitis virus infection?

A

Spider erythemas

Mild hepatosplenomegaly and tenderness

palmar erythema

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14
Q

What are some common laboratory findings in chronic hepatitis virus infection?

A

^ prothrombin time

Hyperglobulinaemia

Hyperbilirubinaemia

^ Alkaline phosphatase

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15
Q

What is an occasional complication of antibodies circulating in chronic hepatitis virus infection?

A

Immune complex disease secondary to the presence of circulating antibody-antigen complexes

Includes vasculitis and glomerulonephritis

Cryoglobulinaemia (35% of HCV infected)

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16
Q

HBV can be chronic – what predicts how chronic it will be?

A

Age at time of infection (much more chronic earlier in life)

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17
Q

What is a problem with reducing chronic HBV in endemic areas?

A

More chronic when infected earlier, but perinatal transmission is high

Difficult to cure as well

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18
Q

What are the treatment goals with chronic HBV?

A

Slow disease progression

Reduce liver damage

Prevent liver cirrhosis or cancer

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19
Q

What are the major problems with current HBV treatment regimens?

A

Viral resistance and side effects

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20
Q

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?

A

They are a carrier

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21
Q

How common is the carrier state with HBV?

A

<1% of cases in non-endemic areas

~90% of cases in endemic areas (because infected early in life)

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22
Q

Is there any evidence that HIV and HBV/HCV coinfect?

A

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

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23
Q

What are the main consequences of liver cirrhosis?

A

Liver failure

Hepatic encephalopathy

Massive haematemesis from varices

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24
Q

What is the definition of fulminant hepatic failure?

A

Hepatic insufficiency that progresses from the onset of symptoms to hepatic encephalopathy within 2-3 weeks

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25
What is the mortality of fulminant hepatic failure?
80% without transplantation 35% with transplantation
26
Which hepatitis viruses are transmitted through the faecal-oral route?
HAV and HEV
27
Which hepatitis virus has an incubation period of 1-6 months?
HBV
28
What fatality rate is associated with HAV?
0.1% Only rarely progresses to serious disease
29
What are the symptoms of acute hepatitis virus infection?
Malaise/nausea Fever Jaundice Hepatosplenomegaly in some cases
30
T/F HAV replicates in both intestinal epithelia and hepatocytes
True
31
What treatments are available for HAV infection?
Supportive (rehydration and nutrition)
32
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
33
When is an HAV infected individual excreting virions?
2 weeks before and 1 week after onset of jaundice (symptoms)
34
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
35
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
36
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)
37
How many people in the world have been infected with HBV?
2 billion
38
How many people in the world have chronic HBV infection?
400 million
39
How is HBV transmitted in high prevalence areas?
Perinatally (90% of cases)
40
How is HBV transmitted in moderate prevalence areas?
Horizontally (via wounds etc)
41
How is HBV transmitted in low prevalence areas?
Unprotected intercourse IV drug use
42
Which hepatitis virus has an incubation period of 2-6 weeks?
HAV
43
What percentage of HBV acute infections show no symptoms?
~70%
44
How many HBV serotypes are there?
8
45
Describe the structure of HBV
Spherical double layered 'Dane particle' Partially dsDNA genome
46
What does the HBV genome code for
HBcAg (hepatitis B core protein) HBeAG (precore) BHsAg (surface antigen) Pol (DNA polymerase) HBx
47
What is the distribution of HBeAg and HBcAg?
HBeAg is secreted into the blood HBcAg remains in hepatocytes for virion assembly
48
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)
49
What is special about HBV polymerase?
Can act as both a DNA polymerase and a reverse transcriptase
50
What is the function of HBxAg?
Transcriptional activator Implicated in the progression to hepatocellular carcinoma
51
Which antigens are present shortly after the incubation period?
HBeAg HBV-DNA HBsAg
52
What is the best indicator of active HBV replication?
HBeAg
53
What is the serological consequence of hepatocyte destruction?
Presence of HBcAg Rising anti-HBcAg
54
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
55
Does Anti-HBcAg or Anti-HBeAg rise earlier in disease progression?
Anti-HBcAg
56
What does the presence of Anti-HBsAg in serology alone mean?
Vaccinated
57
What does the presence of Anti-HBsAg and Anti-HBcAg in serology mean?
Previous infection with HBV
58
Is Anti-HBsAg present during a HBV infection?
No
59
Is HBsAg present during HBV infection?
Yes -- rises before onset of symptoms and peaks during acute symptoms
60
Does the HBV virus cause hepatocyte damage?
No -- CD8+ T cells cause the damage
61
How is HBV vaccinated against?
Purified HBsAg Produces protective Anti-HBsAg in 95%
62
What are the risk groups for HBV infection?
IV drug users Health workers Sexually promiscuous
63
What are the symptoms of HBV infection?
Like HAV but arthralgia, urticaria as well
64
What are some complications of HBV infection?
Fulminant hepatic failure Relapse Cholestasis Cirrhosis Hepatocellular carcinoma (more likely if HBsAg and HBeAg +ve) Glomerulonephritis Cryoglobulinaemia
65
Is HVC a chronic or an acute infection?
Almost always chronic
66
How often does HCV progress to cirrhosis?
20-30% of cases
67
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
68
What is the most common paediatric route of transmission for HCV?
Perinatal But much lower perinatal transmission than HBV
69
Describe the structure of HCV
Enveloped ssRNA
70
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
71
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
72
What is the most variable part of the HCV genome?
E2 Because of the two HVR (hypervariable) regions
73
T/F E2 of the HCV genome is a target for anti-HCV antibodies
True
74
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
75
What is the incubation period of HCV?
6-12 weeks
76
Is the percentage of acute phase HCV infection that are asymptomatic, 75% or 85%?
85%
77
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
78
How do serum transaminase levels fluctuate in chronic HCV infection?
Rise and fall with the cyclical presentation of symptoms
79
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
80
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)
81
What are the limitations of using enzyme immunoassay (EIA) in HCV infection?
Cannot distinguish acute from chronic infection Does have 97% specificity though
82
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
83
What is the standard HCV treatment?
PED-IFN, ribavirin and protease inhibitors (simprevir)
84
Why are interferons given in HCV treatment?
Immunomodulatory cytokine that enhances phagocytic activity of macrophages and cytotoxic activity of lymphocytes
85
Can HDV exist without HBV?
No Needs HBV surface antigen
86
What are the three types of HDV infection?
Acute coinfection Superinfection Helper-independant latent infection
87
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
88
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
89
Describe helper-independent latent HCV infection
Observed in liver transplant settings HDV detectable in hepatocytes Can be reactivated
90
In the case of HDV, is co-infection or superinfection worse for prognosis?
Superinfection Leads to chronic liver disease in 70-80% of patients
91
What are the symptoms of HDV infection?
Jaundice Abdominal pain Nausea and vomiting Dark urine Anorexia
92
How many HDV patients are asymptomatic?
90% (medscape)
93
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)
94
How does HDV infection complicate HBV diagnosis?
Active HDV replication almost completely removes HBsAg from serum
95
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
96
How is HEV transmitted?
Faecal-oral route Contaminated water (water-borne virus)
97
Is HEV infection in children common?
Very rarely Occurs mostly in young to middle-aged adults
98
Does HEV have animal reservoirs?
Yes -- commonly found and spread through animals Monjeys, cats, pigs and dogs
99
What is the mortality rate of HEV in pregnant women?
20% Mortality increases in second and third trimesters
100
How does HEV cause death in pregnant women?
Encephalopathy DIC (disseminated intravascular coagulation) Fulminant hepatic failure rates high
101
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
102
What is the fatality rate of HEV infections?
4% Though much higher in pregnant women and liver transplant patients
103
How is HEV infection diagnosed?
The presence of anti-HEV IgM HEV-RNA can be detected before onset of symptoms but not long after
104
What is the incubation period of HEV?
15-60 days
105
With what history will HEV patients present?
Anorexia Nausea/vomiting Right upper quadrant pain that increases with activity Jaundice Dark urine Pale stools Pruritus
106
How is HEV infection treated?
Self-limiting, hence supportive therapy including rehydration In severe cases, or in immunocompromised, may consider ribavirin
107
How long do symptoms last in HEV?
2-4 weeks
108
Is Hepatitis G virus (HGV; GB virus C) hepatotropic?
No Causes no increase in aminotransferase levels
109
Where does HGV (GBV-C) replicate?
Bone marrow Spleen
110
What are the symptoms of HGV (GBV-C) infection?
GBV-C does not cause human disease
111
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
112
How often does cholestasis occur in HEV infection?
50%

Robbins Liver & Biliary (6 decks)

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