11 Hepatitis C Park Flashcards

1
Q

What type of Virus is Hepatitis C?

A

An enveloped, single stranded, positive sense RNA virus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the incubation period for Acute Hepatitis C?

A

Averages 6-10 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the most characteristic feature of Acute Hepatitis C?

A

Elevations in serum ALT levels, often in a fluctuating pattern

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens after the Acute Hepatitis C infection?

A

15-25% of persons resolve their infection without sequelae. As many as 70-90% of infected people fail to clear the virus during the acute phase of the disease and become chronic carriers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What can Chronic Hepatitis C be defined as?

A

A continuing disease without improvement for at least 6 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How many people with Chronic Hepatitis C have symptoms?

A

Most persons (60-80%) have no symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is Chronic Hepatitis C’s rate of progression to cirrhosis?

A

Usually slow, with 20 or more years elapsing between infection and the development of serious complications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the signs and symptoms of Chronic Hepatitis C infection?

A

Unexplained fatigue. Malaise. Jaundice. Anorexia. Fluid retention. GI bleeding, discomfort. Hepatomegaly. Splenomegaly. Unexplained signs of portal hypertension. Extrahepatic manifestations of HCV infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is diagnosing HCV Infection like?

A

Some persons may not test positive for 6-9 months after the onset of illness. A correct diagnosis can only be made by testing patient’s sera for the presence of specific anti-viral antibodies. Diagnosis is not based solely on elevated transaminases (NON-SPECIFIC). The diagnosis of acute and chronic hepatitis C is based on both anti-HCV detecting using enzyme immunoassays (EIA) and HCV RNA detection using a sensitive molecular biology-based technique

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What do HCV Positive persons have?

A

Antibodies to Hepatitis C virus (anti-HCV) in their blood (generally not detectable before 8-12 weeks following exposure). AND/OR. HCV RNA or HCV core antigen detected in their blood (identified as early as 1-2 weeks following exposure). HCV RNA, as detected by PCR or HCV core antigen detection, becomes positive within days of inoculation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What has become the method of choice for early diagnosis of Hepatitis C infection?

A

PCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which genotypes of HCV tend to respond the best to treatment?

A

Genotype 2 (favorable genotype). Genotype 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which genotype of HCV is “less favorable”?

A

Genotype 1. Most resistant to treatment. Requires higher doses of RBV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the definition of treatment response?

A

Treatment responses are defined by a surrogate virological parameter rather than a clinical endpoint. Several virological responses may occur

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the goal of treatment for HCV?

A

Sustained Virological Response (SVR): HCV RNA negative 24 weeks AFTER cessation of treatment. Prevent complications and death from HCV infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is Rapid Virological Response (RVR)?

A

HCV RNA negative at treatment week 4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What percentage of people achieve SVR with Genotype 1, 2, and 3?

A

1 ~ 40-50%. 2,3 ~ 80%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the three medication classes for HCV?

A

Interferon (IFN). Nucleoside Analog (Ribavirin). Protease Inhibitors (Boceprevir, Telaprevir)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Which HCV medication can only be used for Genotype 1?

A

Protease Inhibitors (in combination with IFN + RBV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the dosing of Pegylated IFN alfa-2a (Pegasys) like?

A

180 micrograms injected SQ once per week

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the dosing of Ribavirin (Copegus) like?

A

1,200mg = > 75kg in genotype 1. 1,000mg = < 75kg in genotype 1. 800mg for genotypes 2,3 regardless of weight

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the dosing of Boceprevir (Victrelis) like?

A

800mg TID Q7-9 hours with food (start on week 5 of HCV treatment)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the dosing of Telaprevir (Incivek) like?

A

750mg TID Q7-9 hours with food

24
Q

Which medication class is indicated for both HIV and HCV treatment?

A

Protease Inhibitors

25
Q

Boceprevir is started at which week relative to the initiation of peg-IFN + RBV?

A

Week 5

26
Q

What do Interferons do?

A

IFNs are named after their ability to “interfere” with viral replication within host cells. Activate immune cells, such as natural killer cells and macrophages. Increase recognition of infection or tumor cells by up-regulating antigen presentation to T lymphocytes. Increase the ability of uninfected host cells to resist new infection by the virus

27
Q

What are the contraindications to using IFN-alfa?

A

Known hypersensitivity (urticaria, angioedema, bronchoconstriction, anaphylaxis, SJS). Autoimmune hepatitis. Hepatic decompensation (Child-Pugh score > 6). Neonates and infants

28
Q

What are the ADRs related to IFN-alfa?

A

Severe acute hypersensitivity reactions. Fatigue. Influenza-like illness. Cytopenias (neutropenia, thrombocytopenia). Psychiatric side effects (depression, suicidal thinking, irritability, sleep disturbance). Rash, pruritus. Insulin resistance. Hypo- and hyperthyroidism

29
Q

What needs to be monitored with IFN use?

A

Complete blood cell count with differential (Hemoglobin, WBC, neutrophils, platelets). Complete metabolic panel. Thyroid function tests (baseline needed). Psychiatric ADRs

30
Q

What are the psychiatric ADRs associated with IFN?

A

Mood changes/mood labiality. Irritability. Poor impulse control. Crying spells. Hopelessness, helplessness. Major depressive disorder. Bipolar disorder, manic episode. Psychosis. Anxiety. Sleep disturbances. Can be managed with appropriate psychotropics and careful, more frequent monitoring

31
Q

What is Ribavirin?

A

A NucleoSIDE analog with antiviral activity. Has direct antiviral activity in tissue culture against many RNA viruses (increases the mutation frequency in the genomes of several RNA viruses, inhibits HCV polymerase in a biochemical reaction). Should NOT be used monotherapy (high rate of and risk of resistance)

32
Q

What are the warnings of Ribavirin use?

A

Monotherapy is NOT effective for the treatment of chronic Hepatitis C virus infection and should not be used alone for this indication. Primary clinical toxicity is hemolytic anemia. Patients with a history of significant or unstable cardiac disease should not be treated with Ribavirin. Contraindicated in women who are pregnant and in the male partners of women who are pregnant

33
Q

What is the dosing of Ribavirin like?

A

Ribavirin tablets should be taken with food. Usually administered in two divided doses (i.e., every 10-12 hrs). Ribavirin tablets should not be used in patients with creatinine clearance < 50

34
Q

What are the ADRs of RBV?

A

N/V. Dry mouth. Dry eyes. Dry cough. Anemia. Teratogenicity

35
Q

What are the monitoring parameters for RBV?

A

Hemoglobin/Hematocrit. Red blood cell count. Renal function

36
Q

What are the general characteristics of Protease Inhibitors?

A

NS3/4A serine protease inhibitors. Indicated for Chronic HCV Genotype 1 in combination with IFN and RBV. Demonstrated markedly improved SVR rates. Not to be used as monotherapy

37
Q

What is the MOA of Protease Inhibitors?

A

A direct-acting antiviral agent with activity against HCV. NS3/4A protease inhibitors inhibit HCV NS3/4A protease. Contains an alfa-ketoamide functional group that selectively, covalently, and reversible binds the active serine site of HCV NS3 protease (NS3 protease is an enzyme essential for viral replication)

38
Q

What are the common ADRs associated with Boceprevir?

A

Fatigue. Anemia. Nausea. HA. Dysguesia

39
Q

What are the common ADRs associated with Telaprevir?

A

Rash. Fatigue. Itching. Nausea. Anemia. Hemorrhoids. Anal pruritus

40
Q

What are the DDIs with Protease Inhibitors?

A

CYP3A4 substrates and potent inhibitors. p-glycoprotein substrates and inhibitors. Avoid using concomitantly with: Sildenafil and Tadalafil

41
Q

What is Response-Guided Therapy (RGT)?

A

Treatment can be tailored based upon the virologic response at specific time points throughout treatment

42
Q

What is the discontinuation of dosing for Boceprevir?

A

Discontinuation of therapy is recommended in all patients with: HCV-RNA levels > 1,000 at treatment week 12. OR. Confirmed detectable HCV-RNA levels at treatment week 24. This is considered “treatment futility”

43
Q

What is the discontinuation of dosing for Telaprevir?

A

Discontinuation of therapy is recommended in all patients with: HCV-RNA levels > 1,000 at treatment week 4 or 12. OR. Confirmed detectable HCV-RNA levels at treatment week 24. This is considered “treatment futility”

44
Q

What are the Anorectal signs and symptoms with Telaprevir?

A

Events such as: Hemorrhoids, anorectal discomfort, anal pruritus, rectal burning. Mild to moderate in severity. Reversible ADR upon d/c of agent

45
Q

What is the affect from food with Telaprevir?

A

Food that is taken with this agent should be ingested within 30 minutes prior to each Telaprevir dose. The fat content of the meal or snack is critical for the absorption of Telaprevir. Food should contain approximately 20 grams of fat

46
Q

What are Erythropoiesis-Stimulating Agents used for?

A

Used to manage anemia associated with RBV. May use when Hgb < 10 after a RBV dose reduction has been attempted x2 weeks. Monitor Hgb every 2 weeks: target < 11

47
Q

What are Erythropoiesis-Stimulating Agents doses?

A

Epoeitin alfa (Epogen or Procrit): 40,000 units SQ every week. Darbepoetin alfa (Aranesp): 200mcg SQ every 2 weeks

48
Q

What are the ADRs associated with Erythropoiesis-Stimulating Agents?

A

HTN. Dyspnea. Peripheral edema. Cough. Anaphylaxis. Abdominal pain. Thrombovascular events (MI, PE, cerebrovascular accidents, CNS hemorrhage)

49
Q

What are the contraindications to Erythropoiesis-Stimulating Agent use?

A

Uncontrolled HTN. Risk of thrombosis. Albumin hypersensitivity (or else use Aranesp, albumin-free)

50
Q

What are Granulocyte Colony-Stimulating Factors?

A

Used to manage neutropenia associated with IFN (i.e., chemotherapy). May use after IFN dose reduction has been attempted x2 weeks and when: ANC < 250 OR < 500 with cirrhosis, liver transplant, HIV/HCV co-infection. Monitor ANC every 1-2 weeks until stable

51
Q

How are the Granulocyte Colony-Stimulating Factors dosed?

A

Filgrastim (Neupogen) 300mcg SQ once/twice per week

52
Q

What are the ADRs associated with Granulocyte Colony-Stimulating Factors?

A

Mild to moderate musculoskeletal symptoms. Nausea. Abdominal pain. Fever

53
Q

What are the contraindications to Granulocyte Colony-Stimulating Factor use?

A

Known hypersensitivity to E. coli-derived proteins

54
Q

What is IL28B?

A

A genetic variant (C to T) near the gene encoding interferon-lambda-3 is a strong predictor of response to pegylated IFN + RBV. SVR rates tended to be higher in C/C genotypes

55
Q

What is HCV treatment like for pregnancy?

A

Protease Inhibitors for HCV treatment currently listed as pregnancy category B. Ribavirin is pregnancy category X. PIs should only be taken in combinatino therapy with peg-IFN + RBV so they are pretty much contraindicated

56
Q

What is the storage of HCV medications like?

A

Pegasys and PegIntron Redipen are stored in the refrigerator by the patient (do not freeze). Boceprevir is stored in the refrigerator until dispensed (can be stored in room temperature for 3 months by the patient)

57
Q

What are some counseling tips for HCV positive persons?

A

Do not donate blood, body organs, tissue, or semen. Don’t share toothbrushes or razors. Keep cuts and skin lesions covered