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PHRM 865: Theraputics V > Lecture 25: Viral Hepatitis > Flashcards

Lecture 25: Viral Hepatitis Flashcards

1
Q

What is the difference between Hepatitis and Viral Hepatitis?

A
  • Hepatitis: Inflammation of the liver
  • Viral Hepatits: caused by one of five viruses
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2
Q

What are the five Viral Hepatitises?

A
  • Hepatitis A [HAV]
  • Hepatitis B [HBV]
  • Hepatitis C [HCV]
  • Hepatitis Delta [HDV]
  • Hepatitis E [HEV]

A, B, C are the most common

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3
Q

What are some the characterisitcs of Viral Hepatitis?

A
  • Hepatotrophic: Mainly affecting the liver
  • RNA [except HBV (DNA virus)]
  • HBV and HCV –> Chonic Infections
  • Common AE: Nausea, Anorexia, Fever, Malaise…
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4
Q

What is the Virology and Pathogensis of Hepatitis A?

A
  • Picornavirus [non-eveloped]
  • Replicates in LIVER and excreated in bile
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5
Q

What is the Tranmission and some of the risk groups associated with Hepatitis A?

A
  • Fecal-to-Oral
  • Groups: International Travelers, Gay Sex, Using illegal drugs, Occupational expsoure, homelessness
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6
Q

What are some of the symptoms that are assoicated with Hepatitis A?

A
  • Asymptomatic or Symptomatic
  • Fever, Fatigue, Loss of Appetite, N/V/D, Joint Pain, Jaundice [Abrupt Onset]

Rarley Fatal

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7
Q

What are some of the diagnositc and serlogic testing for Hepatitis A?

A
  • Acute HAV needs detections; IgM anti-HAV in serum [see for ~6m] & HAV RNA in serum or stool
  • Total Anti-HAV assesses immunity
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8
Q

What is some fo the managment for Hepatitis A?

A
  • Supportive Care
  • NO role for antivirals
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9
Q

Who are some of the people that should get Vaccinated [Prevention] for Hepatitis A?

Same as the risk groups

A
  • Anyone under 18 years old
  • International Travlers
  • Men having sex with other men
  • Using illegal drugs
  • Occupational Exposure
  • Homelessness
  • Pregnant Woman at risk of HAV
  • ANYONE that asks for it
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10
Q

What is the HAV vaccine?

A
  • Two dose series given at 0 and 6-12 months
  • Inactivated = safe in pregnancy
  • NO need for Pre- & Post- serology
  • Post-exposure prophylaxis is ASAP
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11
Q

What is the Virology and Pathogensis of Hepatitis B?

A
  • Hepednavirus
  • Enters the LIVER through the blood, then replicates there
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12
Q

What is the transmission for Hepatitis B?

A
  • Precutaneuos or Muscosal: Sexual contact, injections, Mother-to-Child[Most Common], Contact with blood, Needle Sticks, sharing toothbrushes or razors
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13
Q

What are some of the ways that Hepatitis B cannot be spread?

A
  • Food
  • Water
  • Sharing Utensils
  • Kissing
  • Coughing
  • Holding Hands
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14
Q

What are some of the risk groups assoicated with Hepatitis B?

Some the same as Hep A

A
  • Infants born to HBsAg + people
  • Hx of HIV
  • Hx of HCV
  • Men having sex with Men
  • Needle Sharing
  • Hx of STIs
  • In Jail

q

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15
Q

What are some of the symptoms assoicated with Hepatitis B?

A
  • Acute: Same as HAV [Fever, Fatigue, Loss of Appetite, N/V, Joint Pain, Jaundice [Abrupt Onset]]
  • Chronic: Cirrhosis, End-stage Liver disease, Hepatocellular carcinoma
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16
Q

What are some of the HBV serologic markers used and what is the importance of each?

A
  • HBsAg [Are they Infectious?]
  • Anti-HBs [Are they Immune?]
  • Total anti-HBc [Have they been Exposed?]
  • IgM anti-HBc [Acute/recent exposure]
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17
Q

What is the acute managment of Hepatitis B?

A
  • No treatment
  • Supportive care
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18
Q

What is teh chronic managment of Hepatitis B?

GOALS OF THERAPY? What is Functional and Virological care?

A
  • Achieve suppression of HBV replication
  • Remission of Liver Disease
  • Prevent Cirrhosis, heaptic failure, HCC
  • Functional Cure: HBsAg loss +/- anti-HBe gain [Attainable]
  • Virological Cure: eradication of cccDNA [NOT attainable]\
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19
Q

For Chronic infection Managment of Hepatits B, what is the initail evaluation?

A
  • History and Physical Exam
  • CBC, Liver Panel, INR, HBeAg, anti-HBe, HBV DNA PCR
  • Liver Biopsy is gold standard BUT rare todo
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20
Q

What are the Phase of Chronic HBV?

A

Based on HBeAg, HBV DNA, & Cirrhosis

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21
Q

What are the priniples of treatment for Hepatitis B?

HBV DNA & ALT levels?

A
  • HBV DNA > 2000 IU/ml
  • ALT ULN: Men = 35 UL/ml & Women = 25 IU/ml
  • Combo is not any better than mono
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22
Q

What is the treatment eligibility for Hepatitis B?

A
  • e+ Immune-Tolernet: MONITOR [because tolerating]
  • e+ Immune-active: TREAT if ALT >2xULN, HBV DNA >20,000 IU/ml
  • e+ cirrhosis: TREAT INDEFINITELY
  • e- Inactive: MONITOR [liver tolerating]
  • e- Immune Reactivation: TREAT INDEFINITELY
  • e- cirrhosis: TREAT INDEFINITELY
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23
Q

What is the First Line Nucleoside Analogs that is used in Hepatitis B, and its Mechanism of Action?

A
  • Tenofovir 300mg PO QD
  • MOA: inhibits HBV replication by inserting into viral DNA by HBV RT - Chain Termination

Can cause a LOT of NEPHROPATHY

24
Q

What is the alternative First Line Nucleoside Analog that is used instead of Tenofovir fo Hepatitis B?

MOA?

A
  • Tenofovir Alafenamide 25mg PO QD
  • Imporved Safety
  • Absorbed from GI to blood then into target to activate Tenofovir
25
Q

What is the First Line Cytokine that is used for Hepatitis B, and what is it mechanism of action?

A
  • Peginterferon Alfa 2a 180mcg SUBQ for 48 weeks
  • MOA: Cytokine with antiviral, antiproliferative, and immunomodulatory effects
26
Q

s

What are some of the things that Peginterferon Alfa is contraindicated in during Hepatitis B treatment?

A
  • Current psychosis, severe depression, neutropenia, thrombocytopenia, heart disease, Decompensated Liver Disease, seizures

ALOT OF SIDE EFFECTS

27
Q

What are some of the monitoring that should be done during Hepatitis B treatment?

A
  • Immune Tolerance: ALT 3-6m & eAg 6-12m
  • HBV DNA every 3m unitl undetectable
  • Stopped?: every 3m for at least 1 year
  • ALL HBsAg+ people with cirrhosis
28
Q

Who are the speical populations for using Hepatitis B treatment, and what should you do?

A
  • Renal Issues: dose adjust Nuc
  • Pregnancy: Start at 28-32w; treat with HBV DNA > 200,000 with TDF
  • HIV Coinfection
29
Q

Who should be vaccinated for Hepatitis B?

A
  • REALLY ANYONE
  • Infants
  • Unvaccinated kids <19 years old
  • Adults 19-59
  • Adults >60
30
Q

What are the Two Types of HBV vaccines?

A
  • Single Agent: ENGERIX-B, RECOMBIVAX HB, PREHEVBRIO,HEPLISAV-B
  • Combo: PEDIARIX, VAXELIS, TWINRIX

ALL are safe in pregnancy
3 injection starting a 0,1, 6 months
NO need to restart

31
Q

What is the Virology and Pathogensis of Hepatitis C?

A
  • Flavivirus
  • 7 major genotypes [1a & 1b most common and 2 & 3 second most common]
  • Relplicates in liver [duh]
32
Q

What is the Transmission and some of the risk groups of Hepatitis C?

Risk Groups are the same as Hep A & B

A
  • Percutaneous exposure to infected blood
  • Groups: People with HIV, Injecitons, Hemo patients, Occupational exposure, Mother-to-Child, Men having sex with Men, Sharing toothbrushes/razors
33
Q

What are some of the Acute and Chroinc Hepatitis C infection symptoms?

A
  • Acute: Asymptomatic, 1/3 have same as HBV
  • Chronic: Few symptoms but; Fatigue, depression, RUQ pain, Nausea, Poor Appetite, Hepatomegaly

CHRONIC = detectable HCV RNA > 6m

34
Q

What are some of the Diagosis & Serologic Testing for Hepatitis C?

A
  • Anti-HCV: detectable after 8-11w
  • HCV RNA: shows current infections; detectable after 1-2w
35
Q

What is the managment that we should do for Hepatitis C?

Guidelines? Goals of therapy?

A
  • www.hcvguideline.org is a good reference
  • Goals: sustained virological response - undectectable for 12w & prevent cirrhosis, HCC, or death
36
Q

What are some of the fundamental principles of treatment for Hepatitis C?

A
  • SUBQ interferon + PO Ribavirn –> ALL ORAL REGIMENS
  • Combo decreases resistance
  • Treatment for all Chronic HCV [except for those with <12m life expectanices]
  • ALL DAAs increase HBV reactiviation
37
Q

What are some of the HCV therapeutics classes used?

Direct Acting Antivirals

A
  • NS3/4A Protease Inhibitors
  • NS5B Polymerase Inhibitors
  • NS5A Replication Complex Inhibitors
38
Q

What is the MOA for the NS3/4A Protease Inhibitors for Hepatitis C?

A
  • Block the NS3/4A protease from cleaving HCV RNA into its funcional units
  • ALL are potent 3A4 Inhibitors

7 approved BUT 4 withdrawen and 3 remain

39
Q

What are the 4 NS3/4A Protease Inhibitors that were withdrawn for Hepatitis C treatment?

A
  • Boceprevir
  • Telaprevir
  • Simeprevir
  • Peritaprevir
40
Q

What are the NS3/4A Protease Inhibitors that are used for Hepatitis C?

A
  • Grazoprevir
  • Glecaprevir
  • Voxilaprevir
41
Q

What is important to know about Grazoprevir in Hepatits C treatment?

A
  • 100mg po qd with or without food
  • AE: Fatigue, Headache, Nausea, Anemia, Increase ALT
  • Patient should have ALT checked at 8w; D/C if >5xULN
  • Contraindicated: Child-Pugh B or C

Child-Pugh = Cirrhosis mortality

42
Q

What is important to know about Glecaprevir in Hepatits C treatment?

A
  • 300mg PO QD with food
  • AE: Fatigue, Headache
  • 8w course for non-cirrhotics
  • NOT recommended for Child-Pugh B; Contriandicated in Child-Pugh C
43
Q

What is important to know about Voxilaprevir in Hepatits C treatment?

A
  • 100mg po qd with food
  • AE: Fatigue. Headache, Diarrhea, Nausea
  • Approved from those treatmetn by NS5A before
  • NOT recommened in Child-Pugh B or C
44
Q

What is the MOA for the NS5B Polymerase Inhibitors in Hepatits C treatment??

A
  • Inhibits NS5B Polymerase causing HCV repliaction
  • Nucleotide: competes for active site
  • Non-Nucleotide: Binds to allosteric site
45
Q

What the NS5B Polymerase Inhibitors that were withdrawn for the treatment of Hepatitis C?

46
Q

What is the NS5B Polymerase Inhibitors that is approved for Hepatitis C treatment?

A
  • Sofosbuvir
47
Q

What is important to know about Sofosbuvir in Hepatits C treatment?

A
  • 400mg po qd with ot without food
  • AE: Fatigue, Headache
  • AVOID with Amiodarone = bradycardia
  • NO dose adjustment
48
Q

What is the MOA for the NS5A Replication Complex Inhibitors in the treatmnet of Hepatitis C?

A
  • Inhibits NS5A which is needed for HCV RNA Replication and Assembly
49
Q

What are the NS5A Replication Complex Inhibitors that were withdrawn for Hepatitis C treatment?

A
  • Ombitasvir
  • Daclatavir
50
Q

What are the NS5A Repilcation Complex Inhibitors that are used for Hepatitis C?

A
  • Ledipasvir
  • Elbasvir
  • Velapatasvir
  • Pibrentasvir [used a little]
51
Q

What is important to know about Ledipasvir in Hepatits C treatment?

A
  • 90mg po qd with or without food
  • AE: Fatigue, Headache
  • Increased pH decreases solubility = Give H2RA or PPI
  • NO dose adjustment
52
Q

What is important to know about Elbasvir in Hepatits C treatment?

A
  • 100mg po qd with or without food
  • With genotype 1a, a NS5A genotyping MUST be preformed - looking for substituation in codon 28, 30, 31, 93 = 16w therapy + Ribavirn
53
Q

What is important to know about Velpatasvir in Hepatits C treatment?

A
  • 100mg po qd with or without food
  • AE: Fatigue, Headache
  • For ALL Genotypes
  • Compenstated cirrhotic patients with GENOTYPE 3, a NS5A genotype MUST be done - if Y93H present = + Ribavirn or Voxilaprevir
  • NO dose adjustment
54
Q

What are some things to note about Ribavirn in Hepatitis C treatment?

Dosing? Adverse Effects? Is it teratogenic? Contraindications? Monitoring?

A
  • Weight-based dosing
  • AE: Hemolytic Anemia, Pancreatitis, Pulmonary Dysfunction, Insomia Pruritis
  • Teratogenic Cat X [MUST HAVE PREGNANCY TEST MONTHLY]
  • Contraindicated in CrCl <50
  • Monitor CBCs
55
Q

What is some of the prevention for Hepatitis C?

A
  • Avoid sharing toothbrushes, stop reusing or sharing needles, DO NOT donate blood

PHRM 865: Theraputics V (42 decks)

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