Lecture 25: Viral Hepatitis Flashcards
(55 cards)
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
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
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…
4
Q
What is the Virology and Pathogensis of Hepatitis A?
A
- Picornavirus [non-eveloped]
- Replicates in LIVER and excreated in bile
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
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
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
8
Q
What is some fo the managment for Hepatitis A?
A
- Supportive Care
- NO role for antivirals
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
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
11
Q
What is the Virology and Pathogensis of Hepatitis B?
A
- Hepednavirus
- Enters the LIVER through the blood, then replicates there
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
13
Q
What are some of the ways that Hepatitis B cannot be spread?
A
- Food
- Water
- Sharing Utensils
- Kissing
- Coughing
- Holding Hands
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
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
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]
17
Q
What is the acute managment of Hepatitis B?
A
- No treatment
- Supportive care
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]\
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
20
Q
What are the Phase of Chronic HBV?
A
Based on HBeAg, HBV DNA, & Cirrhosis
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
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
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
What is the **First Line Cytokine** that is used for **Hepatitis B**, and what is it mechanism of action?
- **Peginterferon Alfa 2a** 180mcg SUBQ for 48 weeks
- MOA: Cytokine with antiviral, antiproliferative, and immunomodulatory effects
26
# s
What are some of the things that **Peginterferon Alfa** is contraindicated in during **Hepatitis B** treatment?
- Current psychosis, severe depression, neutropenia, thrombocytopenia, heart disease, **Decompensated Liver Disease**, seizures
## Footnote
**ALOT OF SIDE EFFECTS**
27
What are some of the monitoring that should be done during **Hepatitis B** treatment?
- 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
Who are the speical populations for using **Hepatitis B** treatment, and what should you do?
- Renal Issues: dose adjust Nuc
- Pregnancy: Start at 28-32w; treat with HBV DNA > 200,000 with TDF
- HIV Coinfection
29
Who should be vaccinated for **Hepatitis B**?
- **REALLY ANYONE**
- Infants
- Unvaccinated kids <19 years old
- Adults 19-59
- Adults >60
30
What are the Two Types of **HBV** vaccines?
- Single Agent: ENGERIX-B, RECOMBIVAX HB, PREHEVBRIO,HEPLISAV-B
- Combo: PEDIARIX, VAXELIS, TWINRIX
## Footnote
ALL are safe in pregnancy
3 injection starting a 0,1, 6 months
NO need to restart
31
What is the Virology and Pathogensis of **Hepatitis C**?
- Flavivirus
- 7 major genotypes [**1a & 1b most common** and 2 & 3 second most common]
- Relplicates in liver [duh]
32
What is the Transmission and some of the risk groups of **Hepatitis C**?
## Footnote
Risk Groups are the same as Hep A & B
- 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
What are some of the Acute and Chroinc **Hepatitis C** infection symptoms?
- Acute: Asymptomatic, 1/3 have same as HBV
- Chronic: Few symptoms but; Fatigue, depression, RUQ pain, Nausea, Poor Appetite, Hepatomegaly
## Footnote
CHRONIC = detectable HCV RNA > 6m
34
What are some of the Diagosis & Serologic Testing for **Hepatitis C**?
- Anti-HCV: detectable after 8-11w
- HCV RNA: **shows current infections**; detectable after 1-2w
35
What is the managment that we should do for **Hepatitis C**?
## Footnote
Guidelines? Goals of therapy?
- **www.hcvguideline.org** is a good reference
- Goals: **sustained virological response - undectectable for 12w** & **prevent cirrhosis, HCC, or death**
36
What are some of the fundamental principles of treatment for **Hepatitis C**?
- 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
What are some of the **HCV** therapeutics classes used?
## Footnote
Direct Acting Antivirals
- NS3/4A Protease Inhibitors
- NS5B Polymerase Inhibitors
- NS5A Replication Complex Inhibitors
38
What is the MOA for the **NS3/4A Protease Inhibitors** for **Hepatitis C**?
- Block the NS3/4A protease from cleaving HCV RNA into its funcional units
- ALL are potent 3A4 Inhibitors
## Footnote
7 approved BUT 4 withdrawen and 3 remain
39
What are the 4 **NS3/4A Protease Inhibitors** that were withdrawn for **Hepatitis C** treatment?
- Boceprevir
- Telaprevir
- Simeprevir
- Peritaprevir
40
What are the **NS3/4A Protease Inhibitors** that are used for **Hepatitis C**?
- Grazoprevir
- Glecaprevir
- Voxilaprevir
41
What is important to know about **Grazoprevir** in **Hepatits C** treatment?
- 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**
## Footnote
Child-Pugh = Cirrhosis mortality
42
What is important to know about **Glecaprevir** in **Hepatits C** treatment?
- 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
What is important to know about **Voxilaprevir** in **Hepatits C** treatment?
- 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
What is the MOA for the **NS5B Polymerase Inhibitors** in **Hepatits C** treatment??
- Inhibits NS5B Polymerase causing HCV repliaction
- Nucleotide: competes for active site
- Non-Nucleotide: Binds to allosteric site
45
What the **NS5B Polymerase Inhibitors** that were withdrawn for the treatment of **Hepatitis C**?
- Dasabuvir
46
What is the **NS5B Polymerase Inhibitors** that is approved for **Hepatitis C** treatment?
- Sofosbuvir
47
What is important to know about **Sofosbuvir** in **Hepatits C** treatment?
- 400mg po qd with ot without food
- AE: **Fatigue, Headache**
- AVOID with Amiodarone = bradycardia
- NO dose adjustment
48
What is the MOA for the **NS5A Replication Complex Inhibitors** in the treatmnet of **Hepatitis C**?
- Inhibits NS5A which is needed for HCV RNA Replication and Assembly
49
What are the **NS5A Replication Complex Inhibitors** that were withdrawn for **Hepatitis C** treatment?
- Ombitasvir
- Daclatavir
50
What are the **NS5A Repilcation Complex Inhibitors** that are used for **Hepatitis C**?
- Ledipasvir
- Elbasvir
- Velapatasvir
- Pibrentasvir [used a little]
51
What is important to know about **Ledipasvir** in **Hepatits C** treatment?
- 90mg po qd with or without food
- AE: **Fatigue, Headache**
- Increased pH decreases solubility = Give H2RA or PPI
- NO dose adjustment
52
What is important to know about **Elbasvir** in **Hepatits C** treatment?
- 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
What is important to know about **Velpatasvir** in **Hepatits C** treatment?
- 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
What are some things to note about Ribavirn in **Hepatitis C** treatment?
## Footnote
Dosing? Adverse Effects? Is it teratogenic? Contraindications? Monitoring?
- 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
What is some of the prevention for **Hepatitis C**?
- Avoid sharing toothbrushes, stop reusing or sharing needles, DO NOT donate blood
