Hepatitis Flashcards
1
Q
All hepatitis viruses are RNA except which?
A
Hepatitis B is a DNA virus
2
Q
Why do some patients with chronic hepatitis not recall the acute infection?
A
Many acute infections are asymptomatic.
3
Q
Symptoms of acute hepatitis.
A
Fever, malaise, nausea, vomiting, anorexia
4
Q
Where do pts with acute hepatitis have pain?
A
RUQ: location of liver
5
Q
Why does hepatitis cause jaundice?
A
There is excess billirubin in the blood because liver cannot do its job (excrete billirubin).
6
Q
Jaundice causes itching due to
A
bile salts in skin
7
Q
Why does jaundice cause dark urine?
A
When billirubin levels in the plasma are too high they spill into urine, making it dark.
8
Q
Clay-colored stools are due to
A
lack of billirubin excretion
9
Q
How do stools become dark brown?
A
- Liver conjugates billirubin and excretes it into bile
- Once it gets to the GI tract, it is converted into urobilinogen by bacteria.
- Urobilinogen is converted to stercobilin to make stools dark brown.
10
Q
What enzymes spill into the blood when there is liver inflammation?
A
AST/ALT
11
Q
Which enzyme is higher in viral hepatitis?
A
ALT
12
Q
Which enzyme is higher in alcoholic hepatitis?
A
AST
13
Q
Why is there increased direct billirubin in acute hepatitis?
A
During acute hepatitis, liver can still conjugate/synthesize billirubin but cannot transport it into bile. Level becomes high in plasma.
14
Q
Hepatitis can cause a false positive in a screening test for what?
A
Syphillis
VDRL elevation
15
Q
Which hepatitis viruses are non-enveloped and transported via fecal-oral route?
A
A and E
16
Q
What is the prognosis for Hep A and E?
A
Death or Life-long immunity
17
Q
Why is Hep D always associated with Hep B?
A
Hep B must provide certain viral components for replication of Hep D
18
Q
Which hepatitis viruses are blood-sourced and transmitted via percutaneous/permucsoal routes
A
B, C, D
19
Q
What does chronic mean for hepatitis?
A
Infection lasting greater than 6 months
20
Q
Which virus has the highest chance of becoming a chronic infection?
A
Hepatitis C
21
Q
How do you prevent Hepatitis C?
A
Screen blood
22
Q
Vaccine for Hep B also protects you from?
A
Hep D
23
Q
Hepatitis A is a member of which family?
A
Picornaviridae: small RNA virus family
24
Q
Enterovirus 72 =
A
HAV
25
HAV replication occurs
Exclusively in cytoplasm
26
What are the members of the Picorna Virus family?
```
PERCH:
Polio
Echo
Rhino
Coxsackie
Hep A
```
27
Picornaviridae
```
Non-enveloped
(+) ssRNA
linear
icosahedral
Synthesize a large polypeptide that is cleaved into viral proteins
Transmitted fecal-orally
```
28
Hep A Diagnosis
Acute: Anti-HAV IgM antibodies plus symptoms
| Prior disease: Anti-HAV IgG antibodies
29
Hep A Incubation Period
30 days
30
Hep A Transmission
Close personal contact
Contaminated food/water
Blood exposure (rare)
31
Can Hep A cause chronic disease?
No. Acute only.
32
Hep A vaccine is
inactivated virus
33
Hep E is the single member of family
Herpeviridae
34
Hep E
Non-enveloped
(+) ssRNA
linear
Icosahedral
35
Is Hep E transmitted person-to-person
rarely
36
Can Hep E cause chronic disease?
No. Acute only.
37
Diagnosis
HEV in serum or feces (PCR)
| IgM antibodies to HEV
38
Hep E has a higher mortality rate in
pregnant women
39
Is there a Hep E vaccine?
Yes. In China.
40
Which Hep C genotypes are most common in the U.S.?
1, 2 and 3
41
Hep C
1. Hep C is taken up by receptor-mediated endocytosis
2. Capsid is released into cytoplasm
3. (+) RNA is translated on the rough ER to a polyprotein that is cleaved
4. NS5A and NS5B components are involved in (-) intermediates which can become (+) intermediates to continue cycle
5. Maturation in Golgi Complex
42
HBsAg
Hep B Surface Antigen = Envelope glycoprotein
| Antibodies to surface antigen
43
HBcAg
Hep B Core Antigen = Nucleocapsid proten
44
HBeAg
Hep B Early Antigen = Active infection
45
Which protein has been linked to the pathogenesis of HCC?
X protein: Promiscuous transactivator of transcription of cellular and viral genes
46
Hepadnavirus
Hep B
47
Which hepatitis is a DNA rather than RNA virus
Hep B
48
Hep B structure
Enveloped, circular, icosahedral capsid
49
What are the 3 unique properties of Hep B?
1. Genome enters hepatocytes and goes to nucleus
Once it gets into nucleus, DNA becomes fully double stranded
At that point, it will synthesize RNA and RNA will go to cytoplasm
2. Reverse transcriptase synthesized
Viral mRNA is synthesized to viral DNA
Packaged in capsid
3. Envelope comes from ER
50
anti-HBsAg
Antibody of surface antigen. Marker of immunity.
51
anti-HBcAg
Marker of past or current infection
52
IgM Anti-HBc
Recent HBV infection (4-6 months)
53
IgG Anti-HBc
Old HBV infection
54
Anti-HBe
Present in immune or infected person so not helpful
55
HBsAg (-)
Anti-HBc (-)
Anti-HBs (-)
Susceptible to HBV infection
56
HBsAg (-)
Anti-HBc (+)
Anti-HBs (+)
Immune due to natural infection
57
HBsAg (-)
Anti-HBc (-)
Anti-HBs (+)
Immune due to vaccine
58
HBsAg (+)
Anti-HBc (+)
Anti-HBs (-)
IgM Anti-HBc (+)
Acutely infected
59
HBsAg (+)
Anti-HBc (+)
Anti-HBs (-)
IgM Anti-HBc (-)
Chronically infected
60
Anti-HBc Positive
1. Resolved HBV infection (most common)
2. May be susceptible with a false positive anti-HBc
3. May have low level chronic infection
4. May be resolving an acute infection
61
Hep B Incubation
1-4 months
62
Hep B Icteric Hepatitis
30%
63
Chronic Hep B
```
Risk of progression to:
Cirrhosis
Liver failure
HCC (viral DNA integrates into host)
Reactivation (acute hepatitis)
```
64
Immune Reconstitution
If HIV treated w/o treating Hep B severe liver damage results.
Hep B testing usually done prior to HIV therapy.
65
Polyarteritis Nodosa
```
Caused by Hep B
Fevers, fatigue, arthralgias
Abdominal pain, melena
Neuropathy
Rash
```
66
Glomerular Disease
Caused by Hep B
Most common is membranous nephropathy
Presents as proteinuria, nephrotic syndrome
67
Rise in acute disease. Fall as infection resolves.
Antigens
68
Rise as acute infection resolves
Antibodies
69
Hep B Vaccine
Contains recombinant HBsAg
70
Can Hep B Core Antigen be detected in serum?
No. HBcAg is NOT detectable in serum.
71
Window Period
HBsAg undetectable
Anti-HBsAg not yet detectable
Can give false appearance of infection
SOLE marker of infection can is anti-HBc (IgM)
72
HBeAg indicates
Viral replication
73
anti-HBeAg indicates
Fall in viral replication
74
Acute Hep B Treatment
Supportive care
75
Chronic Hep B Treatment
Interferon
Lamivudine (NRTI)
Other antiviral drugs
76
Pegylated Interferon alpha-2a
```
Evaluate pt for liver disease
HBsAg in blood for greater than 6 months
HBeAg in blood (ongoing replication)
Elevated serum aminotransferases
Liver biopsy (examine for decompensated liver disease)
```
77
3TC Lamivudine
Nucleoside analog, inhibitor of reverse transcription
78
Adefovir dipivoxil
Nucleoside analog, also inhibitor of reverse transcription
79
Entecavir
Guanosine analog, also an inhibitor of reverse transcription
80
Telbivudine
Thymidine analog, inhibitor of reverse transcription
81
Tenofovir
Analog of adenine, inhibitor of reverse transcription
82
Hep C
Flavivirus (mostly mosquito illnesses)
Enveloped, (+) ssRNA, linear, icosahedral
High degree of antigenic variation
Difficult for immune system to eradicate effectively
High rate of chronic disease
83
Hep C envelope proteins
Contain a hypervariable region
High mutation rate in genome
Lack of proofreading by viral RNA polymerase
Result: Prone to frequent mutations
84
Hep B can cause HCC through
1. Inflammation
2. Integration through genome
3. Viral proteins
85
HCV has proteins that can lead to
ROS, genomic instability and HCC
86
What is the average incubation period and the incidence of developing a chronic HBV infections?
60-90 days; 9-10%.
87
A patient comes to the Infectious Diseases clinic at KUMC complaining of fever, fatigue, upper abdominal discomfort, and dark colored urine. The patient was a 40-year -old man that had returned from central Mexico approximately 4 weeks ago. He was a large animal veterinarian who was visiting a local veterinary school to present lectures on infectious diseases of swine, which included face time with live animals and inspections of raw pig meat. He had no history of intravenous drug use, unprotected sex, drinking contaminated water or eating raw shellfish. His laboratory results revealed elevated serum liver enzymes with a total bilirubin level of 6 mg/dL, direct bilirubin level was 3.9 mg/dL, serum aspartate aminotransferase (AST) concentration was 1458 U/L, alanine aminotransferase (ALT) was 2232 U/L, and alkaline phosphatase (AP) was 196 U/L. The peak of liver enzymes was observed on the tenth day after the start of the clinical manifestations and returned to normal values on day 25. Which of the following viruses was most likely the cause of this patient’s disease?
Answer: Hepatitis E virus
HEV is a zoonotic disease that occurs in swine. Certain genotypes of HEV are prevalent in swine but can be transmitted to humans. Hep A is unlikely, as he claims to have not eating raw shellfish or drank contaminated water. Hep B, C, and D are not correct, as he had no risk factors associated with the transmission of these viruses.
88
The patient was started on a 2-month course of treatment with pegylated interferon-alpha-2α. Two months later no significant decrease of HBV DNA levels was observed and HDV RNA remained detectable. Which of the following drugs could be added to the therapy to enhance the virologic response against HBV/HDV?
Tenofovir
