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71 Cards in this Set
- Front
- Back
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***what are common routes of transmission of HCV
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IV drug users
multiple sex partners |
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what is the #1 cause of liver transplant
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HCV
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what is the main source of new HCV infections
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injection drug use
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what are the genotypes of HCV
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type 1 and 4
type 2 and 3 |
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what genotype of of HCV is the most difficult to treat
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type 1
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what is needed to clear out acute hepatitis infection
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high immune response
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why do the majority of pts infected with acute HCV become chronic
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most don't mount a strong enough immune response
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what can chronic hepatitis lead to
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cirrhosis > hepatocellular carcinoma
cirrhosis > decompensation |
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what are some things that can speed up the normal course (10-20 years) of HCV infection
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alcohol
HIV infection |
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what is the primary serological factor we follow in Acute HCV infection
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HCV RNA
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does Anti-HCV correlate with immune status/immunity
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no
ALMOST ALL PTS DEVELOP ANTI HCV ANTIBODIES |
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how long does it take for HCV RNA to be detectable in Acute HCV
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2 weeks
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what is the Acute HCV presentation
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rarely seen in clinical practice
SSx: fatigue, anorexia, jaundice, abdominal pain, dark urine |
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what is the definitive classification of Chronic HCV infection
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HCV RNA > 6 months
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what is commonly seen in the physical exam of someone with Chronic HCV
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hepatomegaly
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what factors decrease risk of acute infection becoming chronic
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non african american
age < 40 symptomatic acute HCV not immunosuppressed |
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what are the HCV-RNA and ALT levels of a pt with chronic HCV
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they flutuate
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what are somethings you would see in a pt with decompensated cirrhosis
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clubbing
edema jaundice spider angiomata ascites palmar erythema gynecomastia splenomegally small firm liver caput medusea |
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what are some complications of decompensated cirrhosis
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esophageal variceal bleeding
encephalopathy bleeding disorders ascites hepatocellular carcinoma spontaneous bacterial peritonitis |
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what are the diagnostic tests for HCV
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anti-HCV
qualitative and quantitive HCV-RNA genotype test |
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what does Anti HCV test tell us
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persists in all pts
once you are infected you will always be positive |
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what does quantititave HCV-RNA test tell us
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useful in seeing how pt is responding to therapy
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what does qualitative HCV-RNA tell us
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whether the pt has HCV or not
more useful in diagnosis |
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what does the genotype test tell us
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helps us determine what tx to use
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what is the most important predictor of prognosis in HCV
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degree of fibrosis in the liver (advanced cirrhosis = decrease response to tx)
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what are the treatment goals in HCV
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viral clearance (can't get 100% clearance b/c always have chance of reactivation)
delay decompensation prevent hepatocellular carcinoma prevent reccurence of HCV infection after transplant |
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if someone is HCV-RNA negative in 4 WEEKS this is
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rapid virological response (RVR)
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if there is a decrease in HCV-RNA > 2 log 10 after 12 WEEKS
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early virological response (EVR)
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if HCV -RNA is undetectable at the end of treatment this is
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End of Treatment Response (ETR)
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HCV-RNA undetectable 6 months after completion of trreatment
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Sustained virological response (SVR)
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what are the non pharmacological treatment options for HCV
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hep A/B vaccination
Alcohol cessation (alcohol can progress disease) lifestyle modification (obesity and smoking can progress disease) |
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what are contraindications of combination therapy
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pregnancy (ribavirin is teratogenic)
autoimmune hepatitis (IFN worsens autoimmune disease) decompensated liver disease (IFN worsens this) ischemic cardio or cerebrovascular disease hemoglobinopathies CrCl < 50 or hemodialysis |
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what are predictors of good treatment response
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age <40
HCV-DNA < 400000 ALT > 3x ULN non cirrhotic (not a lot of fibrosis in liver) white, non hispanic NOT GENOTYPE 1 PATIENTS WITH EVR (>2 log decrease in HCV-DNA in 12 weeks) |
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WHAT IS THE LARGEST PREDICTOR OF GOOD TREATMENT RESPONSE
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NOT BEING GENOTYPE 1
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why do patients with HEP B and C respond better to PEG-IFN vs IFN
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longer t1/2
higher AUC |
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what are IFN AE
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flu like illness
mood sing, depression bone marrow suppression thyroid dysfunction neutropenia thrombocytopenia excacerbation of autoimmune disease |
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what is the mOA of Ribavirin
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interferes with viral replication
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how is RIbavirin administered to treat HCV
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orally
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for Genotype 1 and 4 what is the dosing for Ribavirin
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<75kg 1000 mg PO in divided doses
>75kg 1200 mg PO in divided doses |
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for Genotype 2 and 3 what is the dosing for Ribavirin
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800 mg PO in divided doses
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how do you dose a pt with HIV coinfection using Ribavirin
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same as genotype 1 and 4
<75kg 1000 mg PO in divided doses >75kg 1200 mg PO in divided doses |
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what are the AE of Ribavirin
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hemolytic anemia
teratogenic |
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when would you adjust the dose of Ribavirin
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Hgb < 10 g/dl
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when can you get pregnant after Ribavirin
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must wait till 6 months after tx
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what are the protease inhibitors and what genotype do they treat
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telaprevir
boceprevir ONLY GIVEN AS COMBO THERAPY (w/ PEG-IFN and Ribavirin) TO TX GENOTYPE ONE |
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what is the dosing of Telapravir and how is it taken
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750 mg PO TID
take with non-low fat meal (must contain 20 g of fat) |
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what strength does Telapravir come in
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375 mg tabs
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what are the major AE of telapravir
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rash
pruritis (anemia) |
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what is the dosing of Boceprevir and how is it taken
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800 mg PO TID
take with light meal/snack |
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what strength does Boceprevir come in
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200 mg capsule
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what are the major AE of Boceprevir
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anemia
dysguesia |
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what substrate are Telaprevir and Boceprevir and what drugs must you watch out for
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CYP3A4 substrate
watch out for CYP3A4 inducers (rifampin, phenytoin, phenobarbital) |
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why must you be careful when doing combo therapy with P,R, boceprivir in a pt with anemia
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Ribavirin and Bociprivir will both cause anemia
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how do you tx a Genotype 1 pt with Boceprivir
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4 week lead in w/ PEG-IFN and Ribavirin only
start boceprevir, continue with PEG-IFN and Ribavirin for 24-44 more weeks |
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when treating with Boceprevir how soon can you stop tx if:
HCV RNA UNDETECTABLE AT WEEK 8 AND 24 |
28 weeks
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when treating with Boceprevir how soon can you stop tx if:
HCV-RNA > 100 at week 12 |
stop all 3 drugs
-week 12 is EVR mark so if no decrease in HCV-RNA by week 12 then treatment is uneffective and pt unlikely to have SVR |
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what is the min and max of tx with Boceprevir
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28 weeks min
48 weeks max |
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how do you tx genotype 1 pt with Teleprevir
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12 weeks of Teleprevir with PEG-IFN and Robivarin
after week 12 stop Teleprevir and continue PEG-IFN and Robavirin for 12 - 36 more weeks |
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when treating with Teleprevir how soon can you stop tx if:
HCV-RNA UNDETECTABLE AT WEEK 4 (RVR) THROUGH 12 (EVR) |
stop tx after 24 weeks
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when treating with Teleprevir how soon can you stop tx if:
HCV-RNA > 1000 AT WEEKS 4 (RVR) THROUGH 12 (EVR) |
stop all 3 drugs
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what regimen is prefered in genotype 1 pt that were previous non responders
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teleprevir + ribavirn + PEG-IFN
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what is the treatment regimen for genotype 2 and 3
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800 mg (divided doses) Ribavirin + PEG-IFN
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what is the treatment process in pts with genotype 2 and 3
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quantitative HCV-RNA and genotype test
at week 4 (RVR) check quantitative HCV-RNA did it decrease > 2 logs IF YES: if detectable complete 24 week therapy if undetectable can D/C therapy IF NO recheck at 12 weeks (EVR) and if no response stop tx b/c ineffective if @ 12 week recheck and see decrease then complete 24 week tx |
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what is the earliest you can D/C therapy for genotype 2 and 3 pts
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4 weeks if HCV-RNA has decreased > 2logs and is undetectable
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what are the special populations you must consider when treating HCV
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normal ALT
decompensated Cirrhosis Relapsed following tx Non responders |
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what is the treatment consideration for pt with normal ALT
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may decrease fatigue
but go over risk/benefit with pt |
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what ALT response corresponds with good therapy
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increase ALT
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what is the treatment consideration for pt with decompensated cirrhosis
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tx for HCV requires combo therapy which contains PEG-IFN which will excacerbate decompensated cirrhosis and is therefore contraindicated for these pts
THEREFORE THESE PTS CAN ONLY GET LIVER TRANSPLANT |
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what is the treatment consideration for pt that relapsed following tx
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tx with 3 drug regimen (these pt most likely only received PEG-IFN + Ribavirin)
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what is the treatment consideration for pt with Non responders
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use teleprevir + ribavirin + PEG IFN
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what is the treatment consideration for pt with cirrhosis
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treat for 48 weeks with triple regimen regardless of response (even if you don't see EVR continue to treat till complete 48 week tx)
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