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PHRM 865 > Viral Hepatitis > Flashcards

Viral Hepatitis Flashcards

1
Q

What is hepatitis? What is viral hepatitis?

A

Hepatitis: Inflammation of the liver
Viral hepatitis: Hepatitis caused by one of at least five distinct viruses - hepatitis A, B, C, E, or delta virus

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2
Q

What are the characterisitics of viral hepatitis?

A

Hepatotrophic – systemic infections that primarily affect the liver
RNA viruses – except HBV (which is a DNA virus)
All can produce an acute illness
* Nausea, anorexia, fever, malaise, and abdominal pain
* Jaundice or elevated liver transaminases

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3
Q

What are the modes of transmission of hepatitis A?

A

main transmission: fecal-oral; Close personal contact or sexual contact with an infected
person; Ingestion of contaminated food or water
perinatal transmission: no

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4
Q

What is the pathogenesis of hepatitis A?

A
  • Classified as a picornavirus
  • Replicates in the liver, excreted in the bile, and is shed in the stool
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5
Q

What are the symptoms of hepatitis A?

A

Can be asymptomatic or symptomatic (varies based on age)
Abrupt onset, usually lasts less than 2 months
* Abdominal pain, nausea, and/or vomiting
* Dark urine or clay-colored stools
* Diarrhea
* Fatigue
* Fever
* Jaundice
* Joint pain
* Loss of appetite

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6
Q

What is the diagnosis and serologic testing of hepatitis A?

A

Diagnosis of acute HAV requires the detection of either:
* IgM anti-HAV in serum (usually becomes detectable within 5-10 days of symptom onset) OR
* HAV RNA in serum or stool
IgG anti-HAV appears early in the infection, remains
detectable providing lifelong immunity
Total anti-HAV (measuring both IgG and IgM) is used to assess immunity

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7
Q

What is the management of hepatitis A?

A
  • Supportive care
  • No role of antiviral agents for treatment
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8
Q

What are the modes of transmission of hepatitis B?

A

main transmission: blood, sexual
percutaneous or mucosal contact: sexual contact, injecting drug use, mother-to-child transmission, contact with blood or open sores, needle sticks, sharing razors or toothbrushes
perinatal transmission: yes

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9
Q

What is the pathogenesis of hepatitis B?

A
  • Classified as a hepadnavirus
  • The virus enters the liver through the bloodstream, replicates in the liver
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10
Q

What are the symptoms of hepatitis B?

A
  • Acute symptoms: same as HAV infection (except no diarrhea)
  • Chronic infection is typically asymptomatic until onset of cirrhosis, end-stage liver disease or hepatocellular carcinoma (HCC)
  • 15-25% of people with chronic HBV infection are at risk for premature death from cirrhosis and HCC
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11
Q

What are the screening recommendations for hepatitis B?

A
  • Screen all adults aged 18 years and older at least once in their lifetime using a triple panel test
  • Screen for HBsAg during each pregnancy regardless of vaccination status and history of testing
  • People who are at ongoing risk for exposure should be tested periodically
  • Test anyone who requests HBV testing regardless of disclosure of risk
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12
Q

What are the modes of transmission of hepatitis C?

A

main transmission: blood; spread through large or repeated percutaneous exposures to infected blood
perinatal transmission: yes

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13
Q

What are the risk factors of hepatitis A?

A

Direct contact with someone with HAV; International travelers; Men who have sex with men; People who use or inject drugs; People with occupational risk for exposure; People who anticipate close personal contact with an international adoptee; People experiencing homelessness

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14
Q

What are the risk factors of hepatitis B?

A

Born to infected mother
* People born in certain countries where hepatitis B is common
* People born in the United States who were not vaccinated as infants
and whose parents were born in countries with high rates of hepatitis B
* People who have hepatitis C.
* People who have sexually transmitted infections, such as HIV
* People who are on dialysis
* People who have liver damage or inflammation
* People who have been in jail or prison
* People who inject drugs or share needles, syringes, and other types of
drug equipment
* Sex partners of people who have hepatitis B
* Men who have sex with men
* People who live with someone who has hepatitis B
* Health care and public safety workers who are exposed to blood on the
job

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15
Q

What are the risk factors of hepatitis C?

A

Injection drug use

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16
Q

What are the methods of prevention of heptatitis A?

A

HAV vaccine:
* Two dose series given at 0 and 6-12 months
* Inactivated vaccine – safe in pregnancy
* Pre- and post-vaccination serologic screening is typically not recommended
* Post-exposure prophylaxis should be given ASAP after exposure (within 2 weeks): Vaccine for people >12 months of age; IM immune globulin if <12 months; Give both if >40 years with increased risk of severe disease

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17
Q

What are the methods of prevention of heptatitis B?

A

HBV vaccine

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18
Q

What are the methods of prevention of heptatitis C?

A

Counsel infected patients how to avoid transmission
Post-exposure prophylaxis for health-care personnel

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19
Q

What’s the potential for chronic infection of hepatitis A?

A

none
Acute, then resolved

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20
Q

What’s the potential for chronic infection of hepatitis B?

A

can produce a chronic infection; 90% of infants, 25-50% of children ages 1-5, 5% of adults; Symptoms ranges from subclinical to cirrhosis or hepatocellular carcinoma (HCC)
treatment is curative

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21
Q

What’s the potential for chronic infection of hepatitis C?

A

can produce a chronic infection; >50% develop
chronic infection; Symptoms ranges from subclinical to cirrhosis or hepatocellular carcinoma (HCC)
treatment is curative

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22
Q

How do you interpret hepatitis B serologic test results? - Hepatitis B surface antigen

A

Hepatitis B surface antigen (HBsAg) - Marker of presence of ongoing infection; answers the question “Is the patient infectious?”

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23
Q

How do you interpret hepatitis B serologic test results? - Antibody to hepatitis B surface antigen

A

Antibody to hepatitis B surface antigen (anti-HBs) - Marker of immunity (indistinguishable whether acquired from disease or vaccination); answers the question “is the patient immune?”

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24
Q

How do you interpret hepatitis B serologic test results? - Antibody to hepatitis B core antigen

A

Antibody to hepatitis B core antigen (total anti-HBc) - Marker of exposure to the infection (persists for life, does not account for time since infection); answers the question “Has the patient been exposed to the virus?”

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25
How do you interpret hepatitis B serologic test results? - Immunoglobulin M class of antibody to hepatitis B core antigen
Immunoglobulin M class of antibody to hepatitis B core antigen (IgM anti-HBc) - Marker of acute or recently acquired HBV infection (can give false positives); answers the question "Has the patient been recently exposed to the virus?"
26
HBsAg, anti-HBs, and anti-HBc all negative
clinical state: Susceptible, never infected action: Offer HepB vaccine per ACIP recommendations
27
HBsAg - negative; anti-HBs - positive; anti-HBc - positive
clinical state: Resolved infection action: Counsel about HBV infection reactivation risk
28
HBsAg - negative; anti-HBs - positive; anti-HBc - negative
clinical state: Immune from receipt of prior vaccination (if documented complete series) action: If not vaccinated, then complete vaccine series
29
HBsAg - positive; anti-HBs - negative; anti-HBc - positive; IgM anti-HBc - positive
clinical state: Acute infection action: Link to hepatitis B care
30
HBsAg - positive; anti-HBs - negative; anti-HBc - positive; IgM anti-HBc - negative
clinical state: Chronic infection action: Link to hepatitis B care
31
What is the management of hepatitis B?
* Acute infection: No treatment; Supportive care * Chronic infection: Goals of therapy 1. Achieve sustained suppression of HBV replication 2. Remission of liver disease 3. Prevent cirrhosis, hepatic failure, and HCC 4. functional cure – HBsAg loss with or without anti-HBe gain – is attainable 5. virological cure – eradication of cccDNA from hepatocyte nuclei – is not yet attainable
32
What is the management of chronic infection hepatitis B?
Initial evaluation: * History (risk factors) and physical exam * CBC, liver panel, INR, HBeAg, anti-HBe, HBV DNA PCR * Test for coinfection with HCV, HDV, HIV, anti-HAV * Baseline alfa fetoprotein assay (AFP), abdominal US, and fibrosis staging (via elastography or fibrosis panel) to assess for evidence of HCC * Liver biopsy (diagnostic gold standard) is becoming rare
33
What are the phases of chronic HBV?
based on HBeAg, ALT, HBV DNA, and presence of cirrhosis e+ immune-tolerant, e+ immune-active, e+ cirrhosis e- inactive (carrier), e- immune reactivation, e- cirrhosis
34
e+ immune-tolerant
normal ALT elevated HBV DNA monitor
35
e+ immune-active
elevated ALT elevated HBV DNA treat if ALT > 2xULN, HBV DNA >20,000 IU/mL, otherwise monitor
36
e+ cirrhosis
elevated ALT elevated HBV DNA low albumin, low platelets treat indefinitely if HBV DNA > 2,000 IU/mL, otherwise monitor
37
e- inactive
normal ALT low/undetectable HBV DNA monitor
38
e- immune reactivation
elevated ALT elevated HBV DNA treat indefinitely if ALT >2xULN, HBV DNA >2,000 IU/mL, otherwise monitor
39
e- cirrhosis
elevated ALT elevated HBV DNA low albumin, low platelets treat indefinitely if HBV DNA >2,000 IU/mL, otherwise monitor
40
What is the upper limit of normal for alanine aminotransferase (ALT) for females?
25 U/L
41
What is the upper limit of normal for alanine aminotransferase (ALT) for males?
35 U/L
42
What is the treatment eligibility for HBV?
HBV DNA > 2,000 IU/mL (most important predictor) PLUS ALT > 2xULN or cirrhosis
43
What is the MOA of first line nucleoside analogs?
* Inhibit HBV replication through incorporation into viral DNA by the HBV reverse transcriptase * Results in DNA chain-termination
44
What are examples of nucleoside analogs?
1st line: tenofovir, tenofovir alafenamide, entecavir non 1st line: lamivudine, adefovir, telbivudine
45
What is the MOA of cytokines? What is an example?
Cytokine with antiviral, antiproliferative, and immunomodulatory effects Ex. peginterferon alfa 2a
46
Cytokines are contraindicated in what patients?
current psychosis, severe depression, neutropenia, thrombocytopenia, symptomatic heart disease, decompensated liver disease!!, and uncontrolled seizures
47
What do you monitor in HBV?
ALT, HBV DNA levels, HCC surveillance
48
HBV in pregnancy
To minimize risk of perinatal transmission, beginning at week 28-32 of gestation, treat pregnant women with HBV DNA > 200,000 IU/mL with tenofovir DF Infants should receive HBV vaccination + immunoglobulin
49
HBV vaccine - use in pregnancy?
All are inactivated – safe in pregnancy administered at 0, 1, and 6 mo
50
What is the diagnosis and serologic testing for HCV?
anti-HCV only indicates past exposue to HCV HCV RNA is diagnostic of current HCV infection
51
All direct acting antivirals carry a warning for what?
risk of Hepatitis B Virus reactivation
52
What are the therapeutic agents of HCV?
Direct Acting Antivirals (DAAs) * NS3/4A protease inhibitors * NS5B polymerase inhibitors: Nucleoside/Nucleotide and Nonnucleoside * NS5A replication complex inhibitors ribavirin interferons
53
What are NS3/4A protease inhibitors?
NS3/4A serine protease cleaves the HCV RNA- encoded polyprotein into its functional units - NS3/4A protease inhibitors block this process ex. boceprevir, telaprevir, simeprevir, peritaprevir, grazoprevir; glecaprevir; voxilaprevir
54
What are the NS5B polymerase inhibitors?
Inhibit the RNA NS5B polymerase responsible for replication of HCV two different MOAs: Nucleotide analog competes for the enzyme active site and Nonnucleoside agent binds to an allosteric site inhibiting polymerase activity Ex. sofosbuvir (nucleotide analog) - avoid amiodarone coadmin due to bradycardia; dasabuvir (nonnucleoside analog)
55
What are NS5A replication complex inhibitors?
Inhibit the protein NS5A, needed for HCV RNA replication and assembly ex. ledipasvir - need to space apart acid reducing agents; ombitasvir; daclatasvir - metabolized by CYP3A4; elbasvir; velpatasvir; pibrentasvir
56
What special pre-treatment testing is considered prior to initiation of elbasvir?
Prior to use in patients with genotype 1a, an NS5a genotype must be performed to screen for presence of resistance-associated substitutions (RASs) at baseline Presence of any subsitutions at codons 28, 30, 31, or 93 (12% prevalence) requires an extended 16-week course + ribavirin
57
What special pre-treatment testing is considered prior to initiation of velpatasvir?
Prior to use in compensated cirrhotic patients with genotype 3, an NS5A genotype must be performed to screen for presence of the Y93H substitution (9% prevalence); presence requires added ribavirin or voxilaprevir
58
What is the special on-treatment monitoring parameter for grazoprevir?
monitor ALT, d/c if >5xULN
59
Notes on ribavirin
Adverse effects: hemolytic anemia (10%), pancreatitis, pulmonary dysfunction (dyspnea, pulmonary infiltrate, pneumonitis), insomnia, pruritis Teratogenic – category X Contraindicated in patients with creatinine clearance <50 mL/min Monitor CBC: decrease dose if Hgb <10 g/dL; d/c if Hgb <8.5 g/dL
60
How long to treat for all regimens?
12 weeks
61
Treatment duration for elbasvir/gasoprevir?
if 1b: 8 week course considered for pts with mild fibrosis
62
Treatment duration for pibrentasvir/glecprevir?
8 weeks
63
Treatment duration for vepatasvir/sofosbuvir/voxilaprevir?
64
Treatment duration for ledipasvir/sofosbuvir?
65
Treatment duration for velpatasvir/sofosbuvir?

PHRM 865 (61 decks)

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