Therapeutics Iv Exam 2- Viral Hepatitis

Front 1

historical classification of viral hepatitis-->types and their modes of infection (5)

Back 1

infectious-->Hep A
Serum --> B, D

Parenteral-->C
Enteric-->E

Front 2

% incidence of Hep a, b, c in the US in the 80-90s

Back 2

47%- hepA
16%- hep C
34%- hep B

Front 3

acute hepatitis phases and brief description (4)

Back 3

incubation- asymptomatic
preicteric (prodromal)- symptoms- weight loss, nausea, flu like, febrile
icteric- evidence if high bilirubin (GI sx, hepatomegaly pain)
convalescent- after hepatitis has resolved

Front 4

fulminant hepatitis

Back 4

rapidly deteriorating hepatitis- necrosis of liver, coagulopathies...liver is dying/failure/death

high mortality late if not transplanted

Front 5

3 forms of hepatitis

Back 5

acute
fulminant
chronic hepatitis

Front 6

general clinical presentation of hepatitis (3 sx, 2 labs)

Back 6

 Flu‐like illness
 Malaise
 Fatigue
 N/V
 ↑ LFTs
 ↑ total bilirubin

Front 7

increased bilirubin symptoms (4)

Back 7

 Jaundice
 Icteric sclera (yellow eyes)
 Dark urine (tea colored)
 Light stools (clay colored- why??? isn't this pancreas related??)

Front 8

hep A virus- properties (what kind of virus is it? - 3)
size...?

family
survivability

Back 8

 Nonenveloped, single‐stranded, ribonucleic acid (RNA) virus, 27‐32 nm
 Picornaviridae family
 Hardy virus- can live on inanimate objects for a while

Front 9

Hep A- primary site of replication
released where?

Back 9

 Primary site of replication is hepatocyte
 HAV released in biliary system → feces

Front 10

Hep A transmission- (3)

Back 10

transmission: fecal-oral so...
close contact with infected people (sex too)
fecal oral contamination (food/water)
blood borne (rare)- like injecting drug users

Front 11

Hep A- annual cases world wide

countries it is often found (4)

Back 11

 1.4 million cases worldwide annually
mostly underdeveloped countries (third world with shitty water systems, hygiene) like Africa, S. America, Middle east, southeast asia - rec vaccines before visiting

Front 12

risk factors for Hep A in the US (4)

Back 12

 International travelers
 Children and employees of day care centers (and secondary contact)
 Household or sexual contact with infected individuals
 MSM (man sex man)

Front 13

US HAV incidences- where is there higher incidences? (2)

Back 13

out west of US
heavily on reservation areas

Front 14

examples of close personal contact where you might get HAV exposure (2)

Back 14

 Household or sexual contact
 Daycare centers

is this still fecal/oral related?? I assume so...

Front 15

fecal/oral food/water contamination routes for HAV (3)

Back 15

 Food handlers
 Raw shellfish
 Travel to endemic areas

Front 16

HAV Pre-clinical phase (3) sypmtoms, duration, properties

Back 16

 Most infectious, active replication
 Asymptomatic
 10‐50 days (mean 30 days)

Front 17

prodromal phase (pre-icteric)- duration

symptoms (7)

Back 17

 Lasts from days to a week

▪ Flu‐like (fevers, fatigue, nausea, vomiting, diarrhea, with or without dark urine)
▪ Pale stools

Front 18

Icteric phase: adult sx (2) vs. child (age)

PE will show... (3)

Back 18

▪ Jaundice and pruritis (70% adults) from bilirubin
▪ Children < 6 yrs often asymptomatic

Hepatomegaly, splenomegaly, and postcervical lymphadenopathy on physical exam

Front 19

extrahepatic manifestations of HAV icteric phase (3)

Back 19

▪ Arthritic type symptoms
▪ Cryoglobulinemia
▪ Vasculitis

Front 20

death rates of HAV (based on age) (2)

Back 20

▪ < 40 years ‐ 0.2%
▪ > 40 years ‐ 2%

Front 21

convalescent period of HAV (2)

Back 21

 Resolution of the disease
 No chronic liver disease documented (self limiting)

Front 22

Dx of HAV- serum antibodies (2)

Back 22

 IgM HAV antibody (anti‐HAV)
 IgG anti‐HAV

Front 23

IgM HAV Ab- present for how long after exposure?

does it become undetectable? when?

Back 23

 Present in serum ~3 weeks after exposure
 Becomes undetectable within 6 months

Front 24

IgG antiHAV- present when? for how long? (2)

Back 24

 Present at same time as IgM
 Remains for a lifetime

Front 25

treatment of HAV (2)

Back 25

 Supportive care- only thing you can do for active HAV
 Immunoglobulin/vaccine- if they present early enough

Front 26

post exposure ppx for HAV- immunoglobulin dose and when to give

who would you use this on? (age? other characteristics?)

Back 26

▪immunoglobulin 0.02 mL/kg within two weeks of exposure (> 85% protection)
▪ For persons < 12 months or > 40 years OR use Ig in those allergic to the
vaccine who come in contact with a person with acute HAV

Front 27

immunoglobulin for HAV post exposure ppx- route

what to avoid afterwards (and for how long)

Back 27

 IM in deltoid or gluteal muscle
 Avoid concomitant administration of live vaccines (i.e., MMR) for 3 months and live attenuated vaccine for 2 weeks (idk why because immunoglobulin might attack it?)

Front 28

alternative to HAV Immunoglobulin for post exposure ppx

age for this

Back 28

Single dose of vaccine may used in persons aged 12 months – 40 years in lieu of immunoglobulin

Front 29

passive immunization for HAV (prophylactic) (passive is transferring Abs...active is vaccination to have body protect itself)

dose (2 doses that provide protection for different durations)

Back 29

Preexposure prophylaxis with
immunoglobulin (not ideal)

▪ 0.02 mL/kg = passive immunization for < 3 months
▪ 0.06 mL/kg = passive immunization for < 5 months

Front 30

targeted population for HAV ppx with immunoglobulin (2)

Back 30

▪ Persons > 40 years who did not receive Hep A vaccine > 2 weeks prior to travel...maybe just give the vaccine anyway cuz still possibility they will respond to it

▪ Travelers < 12 months of age (young kids)

Front 31

2 Hep A vaccines and their difference/dosing units

Back 31

VAQTA (preservative free)- dosed in units
Havrix- has 2‐phenoxyethanol (preservative) dosed in ELISA units

Front 32

efficacy of HepA vaccines- 1st and 2nd dose (relate in % of population that gets Ab)

Back 32

-Antibodies in 94‐100% of adults and 97‐100% of children with 1st dose

-100% with 2nd dose in all recipients > 2 years

Front 33

adverse effects of HAV vaccine- adults (3), children additional AE

Back 33

Adults ‐ injection site reaction- soreness (56%), headaches (14%), fatigue (7%)

Children ‐ in addition may have feeding disturbances (8%)

Front 34

significant AE of HAV vaccine (but rare i think)...she didn't really go over this (5) idk if these are even AEs

Back 34

brachial plexus neuropathy, encephalopathy, erythema
multiforme, Guillain‐Barré syndrome, multiple sclerosis

Front 35

6 risk factors (again...) for HAV

Back 35

sex (15%)
international travel
MSM (lots)
Injection drug use
child or employee in daycare
food/water

most is unknown though

Front 36

rec who for HAV vaccinations? (7)

Back 36

 All children at 1 year of age
 Persons traveling to or working in highly endemic countries
 MSM
 Illegal drug users
 Occupational risk for infection (working in hospitals)
 Clotting factor disorder (getting blood products)
 Chronic liver disease (don't want to worsen it)

Front 37

HAV vaccine licensed when? result?

Back 37

HAV vaccine licensed in 1995- dramatically declined since then

Front 38

1-18 dose for HAV vaccines is what % of adult dose?

schedule of dosing (Like how many total shots, when to give)

Back 38

dose of age 1-18 is half of adult dose
schedule is 0, then 6-12 months after second dose (total 2 doses)

Front 39

Havrix and VAQTA adult doses

Back 39

Havrix adult dose: 1440 ELISA units
VAQTA: 50 units

Front 40

Travel recommendations for HAV vaccines (give ages for recs- different rec for 3 different age groups)

Back 40

Single dose of the vaccine any time prior to travel in persons aged 12 months – 40 years

Travelers < 12 months or > 40 years are still recommended to receive a dose of immunoglobulin with the vaccine if traveling within 2 weeks

Front 41

hep B family

Back 41

Hepadnaviridae family

Front 42

hep B replication location

Back 42

Replication primarily in hepatocytes, but some extrahepatic reservoirs
exist

Front 43

how does hep B dmg the liver? (2)

Back 43

not cytopathic- doesn't directly hurt liver
what hurt's the liver is the host's response to virus

Front 44

hep B transmission (3)

Back 44

blood or body fluids through perinatal, sexual, or percutaneous exposure

Front 45

worldwide HepB epidemiology stats (3)

Back 45

-2 billion people infected
-360 million are chronically infected
in 2002 600k people died from hep B so...pretty fair amount

Front 46

US Hep B epidemiology stats (2) how many new infections per year

how many carriers

Back 46

 300,000 new infections per year
 1.25 million carriers of HBV

Front 47

% of people with chronic Hep B in NA/Western europe

% is higher where?

Back 47

 1% in North American and
Western Europe
 10‐15% in Southeast Asia

Front 48

risk factors for Hep B (8)

Back 48

 Infants born of mothers who are infected with HBV and are HBeAg +
 Children in endemic area
(South Asia, Africa, China)
 MSM
 Multiple heterosexual partners
 IVDU
 Recipients of blood products
 Household contacts of HBV
 Health care providers with needle sticks

Front 49

Hep B prevalent in what continents (4)

Back 49

africa
southeast asia
native americans in NA
parts of south america

Front 50

HBsAg- what is it? when do you start to see it in serum?
how long is it in the serum? (2)

Back 50

hep B surface antigen

In serum 2‐10 weeks after exposure and before onset of symptoms

In self‐limited acute hepatitis, undetectable after 4‐6 months

Persistence of HBsAg > 6 months implies chronic infection (CHB)

Front 51

Anti‐HBs = ? what is it?

when do you see it?

how long is it in blood?

Back 51

antibody to HBsAg (surface antigen)

Follows disappearance of HBsAg

Persists for life (implies long‐term immunity)

Front 52

HBcAg- what is it

Back 52

hepatitis B core antigen

Front 53

Anti‐HBc = what is it? 2 types of Ig and how long they last

Back 53

Acutantibody to HBcAg

Acute: IgM type; 4‐6 months after acute infection

Means past infection and recovery: IgG type

Front 54

HBeAg = what is it? found when?

what does having this antigen imply about your virus? (3)

Back 54

hepatitis B “e” antigen (core protein)

Soluble viral core protein found in serum early during acute infection- excreted i think (e for excretory) only found during active replication. some strains do not make this and are less virulent (i believe)

Greater infectivity, greater viral replication, need for antiviral therapy

Front 55

if HBeAg persistence is > ____ months? what does this mean?

Back 55

Persistence > 3months = progression to CHB

Front 56

Anti‐HBe = what is it?

what does it mean?

Back 56

antibody to HBeAg

Seroconversion (meaning developing Anti-HBe) is associated with reduction of HBV DNA viral levels and remission of liver disease (marker of recovery)

Front 57

HBV highest in what bodily fluids? (3)

Back 57

• Blood
• Serum
• Wound
exudates

Front 58

HBV moderate in what bodily fluids (3)

Back 58

• Semen
• Vaginal
fluid
• Saliva

Front 59

HBV low in what bodily fluids (5)

Back 59

• Urine
• Feces
• Sweat
• Tears
• Breastmilk

Front 60

HBV most prevalent genotype in NA

what is beneficial about this genotype

Back 60

Type A genotype prevalent in NA...more responsive to interferons

Front 61

HBV hx/progression of disease - 3 possibilities (give incidence rates)

Back 61

Most patients recover and develop anti‐HBs (lifelong immunity)

2% get fulminant hepatitis from acute infection and high risk of death if no liver transplant

15% get CHB being unable to seroconvert

Front 62

% of newborns, young children and healthy adults that will end up with chronic hep B upon acute infection

Back 62

 100% of newborns, 70% of young children, <10% of healthy adults

Front 63

definition of chronic hep B infection (doesn't necessarily mean hepatitis)

can progress to what?

risk for what?

Back 63

 If HBsAg persists for > 6 months
 Progression to cirrhosis (prob 20 years down the road)
 Risk for HCC (hepatocellular carcinoma)

Front 64

"pathway" of chronic HBV infection- 5 steps (though they all kind of intermingle- not sequential)

Back 64

chronic HBV infection (inactive carrier state- can spread) --> chronic hepatitis-->cirrhosis-->HCC

Front 65

3 phases of HBV

Back 65

Acute phase (immunotolerent)
Immunoactive phase
convalescent phase (seroconversion)

Front 66

HBV Acute phase- what will you see in labs? (4)

Back 66

High HBV/DNA leels
HBeAg detectable
Anti-HBc IgM detectable
LFTs may be normal

Front 67

HBV acute phase- sx in adults vs kids

Back 67

Children asymptomatic but more prone to CHB

Adults symptomatic but disease resolves completely Iimmune response causing sx but helps fight off virus)- usually flu like symptoms, n/v with or without pale stools/dark urine

Front 68

HBV incubation period

Back 68

Incubation period 45‐160 days (120 days mean)

Front 69

immunoactive phase of HBV- labs (2)

Back 69

 Decrease in HBV DNA
 Increase in ALT (host immune systems fights off virus)

Front 70

immunoactive phase of HBV- sx (3)

Back 70

 Jaundice, liver tenderness, and pale stools

Front 71

convalescent phase of HBV- sx (2)

Back 71

 Jaundice dissipates
 Fatigue persists for months

mostly resolution of disease

Front 72

convalescent phase of HBV- labs- what becomes detectable? (2)

what takes longer?

Back 72

 Anti‐HBc IgG detectable
 HBeAg seroconverts to anti‐HBe
 HbsAg loss can take 4‐6 months (may take years for anti‐HBs)

Front 73

things that make HBV more virulent, give example

when does this occur?

prognosis

Back 73

Precore and core promoter mutants

HBeAg negative but have high levels of HBV DNA

 Occurs during immunoactive phase when trying to clear
virus
 Poorer long‐term prognosis than HBeAg+

Front 74

chronic vs. acute hep B- what is the difference in immune response?

Back 74

in chronic HebB you never see the increase in anti-HBs (both have increase in anti-HBc though)

Front 75

Immune with vaccination: what will appear on Ab/Ag labs (2)

Back 75

Anti HBs + Anti HBe (these are the ones you want!!)

Front 76

Immune with hx of infection: Ag/Ab labs (3)

Back 76

Anti-HBs, Anti-HBc (infection will have core), Anti-HBe

Front 77

Acute infection: Ag/Ab labs (4)

Back 77

HBsAg (will have antigen present) + AntiHBc, IgM ANtiHBc, HBeAg (antigen)

Front 78

Chronic infection: Ag/Ab labs (3)

Back 78

HBsAg, AntiHBc, +/-HBeAg

Front 79

other tests for HBV replication (2)

Back 79

 HBeAg- this predicts more virulence of virus
 HBV DNA levels

Front 80

tests ordered to Assess liver disease in Hep B (4)

Back 80

 CBC with platelets (platelets drop due to splenic sequestration- not that they're really low, just that spleen is gobbling them up and holding on to them)
Tbili?
 LFTs
 PT/IN

Front 81

2 non-lab stuff you have to do in ppl with Hep B (stuff to evaluate)

Back 81

 Family history of liver disease, HCC
 Rule out co‐infection with HCV/HIV

Front 82

active immunization (vaccines) for Hep B recommended for...

Back 82

pretty much everyone (idk you can look at list if you want)

Front 83

3 Hep B vaccines and their preservatives

Back 83

recombivax HB- no thimerosal
EnergixB- trace thimerosal
twinrix- havrix (hep A) + energixB- Contains thimerosal and 2‐phenoxyethanol

Front 84

amount of thimerosal in adult vs. peds version of energixB

Back 84

▪ Pediatric formulation < 0.5 mcg mercury
▪ Adult formulation < 1 mcg mercury

Front 85

efficacy of hep B vaccine

Back 85

Antibody response is 96% after 3 doses

Front 86

lower response to hep B vaccine in which patients (3)

Back 86

 Lower response in older patients, dialysis, immunosuppressed population

Front 87

longest follow up of hep B vaccine?? wtf

Back 87

 Longest follow‐up is 9 years

Front 88

recombivax dosages (3) indicate for whom

Back 88

 5 mcg/0.5 mL (pediatric- 0-19 yo)
 10 mcg/1 mL (adult- 20+)
 40 mcg/1 mL (dialysis)

Front 89

engerix B dosages (2) indicate for whom

Back 89

 10 mcg/0.5 mL (pediatric 0-19 yo)
 20 mcg/1 mL (adult 20+)

Front 90

recombivax/engerix B dosing schedule (how many doses, when)

Back 90

3 doses
0, 1, 6 months

Front 91

combination hep B vaccines (3)

Back 91

comvax (HBV, Hib)
pediarix (HBV+DTaP + IPV)
Twinrix (HAV + HBV)

Front 92

comvax- what is it

given at what age?
given when/how many doses

Back 92

HBV/Hib
>= 6 weeks age
given at 2,4 6 months

Front 93

twinrix age
what is it
dosing schedule

Back 93

HepA, HBV
 For ≥ 18 years
 Given at 0, 1, and 6 months OR 0, 7, 21‐30 days w/booster at 12 mont

Front 94

postexposure ppx for hep B- use what?

dosing and when to give

Back 94

Hepatitis B immunoglobulin (HBIg)

▪ Give within 14 days
▪ 0.06 mL/kg IM x 1

Front 95

indications for postexposure ppx for hep B (2)

Back 95

▪ Perinatal exposure of infants born to HBsAg+ mother
▪ Exposure to HBsAg+ blood

Front 96

chronic hep B treatment goals (4)

Back 96

 Seroconversion
 Viral suppression
 Halt progression to cirrhosis and HCC
 Minimize liver injury

Front 97

when to initiate hep B therapy (treatment) (based on 4 conditional variables)

Back 97

Moderate/severe necroinflammation and/or significant fibrosis

If HBeAg+ (more virulent strain) ... initiate therapy if HBV DNA (IU/mL) > 20k (because more virulent strain = bigger immune response)

If HBeAg-, then if HBV DNA > 2000

OR if ALT x ULN is > 1 regardless of HBV DNA

Front 98

Special populations to consider for treatment regardless of HBV DNA and ALT (5)

Back 98

 Rapid deterioration of liver function
 Decompensated cirrhosis (interferon contraindicated)
 Recurrent HBV infection after liver transplantation
 HBV carriers undergoing immunosuppressive or cytotoxic chemotherapy
(antiviral prophylaxis)
 Compensated cirrhosis with HBV DNA < 2000 IU/mL regardless of ALT

Front 99

interferon (for hep B therapy) - what is it and what effects does it have? more effective in what?

Back 99

 Cytokine with antiviral, antiproliferative, and immunomodulatory effects
 More effective in genotype A

Front 100

1st line therapy options for hep B (3)

Back 100

Entecavir, tenofovir , peg‐interferon alfa‐2a

Front 101

interferons used to treat hep B (2) indicate the difference between the 2 and which is preferred

Back 101

interferon alpha-2b (conventional interferon)- not preferred because it has lesser response rate than pegylated interferons

peginterferon alpha-2a- pegylated to give longer half life- so once weekly dosing

Front 102

2 pegylated interferons- which one approved for HBV

Back 102

pegasys and pegintron- only pegasys has been approved in HBV

Front 103

Interferon α‐2b dose for how long

Back 103

10 million units sq/IM 3x/week x 16 weeks

Front 104

peginterferon (pegasys) alpha-2a dosing and duration

Back 104

180 mcg qweek x 48 weeks

Front 105

interferon/peginterferon ADR (3)
and monitoring

Back 105

LFT week 2, 4 then monthly
 Flu‐like symptoms (keep up hydration, or take APAP)
 Psychological symptoms- specifically depression- maybe don't use in severely depressed or hx of depression
 Bone marrow suppression- keep eye on wbc/platelets too

Front 106

5 antivirals for HBV (oral options)

is this used WITH interferon?

Back 106

lamivudine
adefovir dipivoxil
entecavir
telbivudine
tenofovir disoproxil fumarate WHAT HTE SHIT

pick one or the other (antiviral or interferon)

Front 107

lamivudin- what is it

Back 107

Nucleoside (cytosine) reverse transcriptase inhibitor (NRTI) for HBV and HIV

Front 108

lamivudin dosing

Back 108

100 mg daily (dose reduce for renal dysfunction)

Front 109

ADR lamivudin (3)

Back 109

fatigue, N/V/D, headache

Front 110

duration of antiviral therapy for HBV (same for all of the reverse transcriptase inhibitors) (2)

Back 110

IF HBeAg positive: continue for 6 months following HBeAg seroconversion (i.e., 18‐36 months)

IF HBeAg negative: > 1 year (indefinitely)

Front 111

lamivudine- is it used much now? why or why not?

Back 111

Fallen out of favor due to YMDD mutant (treatment induced mutant that confers resistance)

by 1 year 25% of people are resistant

then 5 years -->75% so...meh

Front 112

adefovir dipivoxil (hepsera)- what is it?

Back 112

for HPV, Nucleotide reverse transcriptase inhibitor (NRTI) that is ACTIVE against YMDD mutant

Front 113

adefovir dosing

Back 113

 10 mg per day (adjust for renal dysfunction)

Front 114

ADR for adefovir (5 + 1 rare but serious)

Back 114

asthenia, dyspepsia, abdominal pain, n/d headache, nephrotoxicity (rare, but serious)

Front 115

adefovir recommended? why or why not?

Back 115

no, fallen out of favor due to resistance
 None at 1 year
 3% at 2 years
 29% at 5 years

Front 116

entecavir- what is it?

active against what?

Back 116

 Guanosine nucleoside reverse transcriptase inhibitor (NRTI) for HBV

 Active against YMDD mutant and adefovir‐resistant strains

Front 117

dosing for entecavir (2 dosing regimens- what are they and why)

Back 117

 Lamivudine‐resistant: 1 mg daily
 Lamivudine‐naïve: 0.5 mg daily

(also renal...)

Front 118

ADR for entecavir and resistance rates

Back 118

 Black box warning for lactic acidosis
 1% resistance at 5 years

Front 119

telbivudin- what is it?

Back 119

Thymidine nucleoside reverse transcriptase inhibitor (NRTI)

Front 120

telbivudin dosing

Back 120

 600 mg per day (adjust for renal dysfunction)

Front 121

telbivudin AE (2)

Back 121

Black box warning‐ for lactic acidosis and
hepatotoxicity (underlying disease? no one knows)

Front 122

telbivudin resistance

Back 122

17% resistance at 2 years

Front 123

tenofovir- what is it

Back 123

Adenosine nucleotide reverse transcriptase inhibitor (NRTI) for HBV and HIV

Front 124

tenofovir dosing

Back 124

300 mg per day (adjust for renal dysfunction)

Front 125

tenofovir AE (2)

Back 125

Black box warning for lactic acidosis and
hepatotoxicity

Front 126

HBV IgG- WHAT DO YOU GET THIS FROM INFECTION OR VACCINE OR WTF

Back 126

---

Front 127

Hep C family

type of pathogen

Back 127

Flaviviridae family
Blood‐borne pathogen

Front 128

4 genotypes of hep C virus and general location

Back 128

US and Northern Europe
▪ Genotype 1a or 1b – 75%**most
▪ Genotype 2a or 2b – 14%
▪ Genotype 3 – 5%

 Genotype 4 in Africa and Middle East

Front 129

7 risk factors for acute infection of Hep C

Back 129

BLOOD BORNE:

 IVDU
 Sex with multiple sexual
partners
 Inmates in correctional
facilities- has to do with piercings/tattoos
 Body piercing, tattoos
 Accidental needle sticks
in health care workers
 Infants born to HCV+
mothers
 Blood transfusions prior
to 1992

Front 130

Hep C often leads to...

Back 130

HCC

Front 131

progression of hep C disease (5)

how long does it take to get to this point

Back 131

acute hep C-->chronic infection(55-85%)-->chronic hepatitis C (70%) -->cirrhosis (20)-->HCC or decompensation (1-5% chance per year)

time line is like 20-30 years to get to HCC/decompensation point

Front 132

hep C sx (most are what? 6 sx)

Back 132

 Most are asymptomatic
 May have nonspecific symptoms such as weight loss, anorexia, flu‐like symptoms, fatigue, abdominal pain, and arthralgias

Front 133

acute Hep C- labs (2)

resolves after how long?

Back 133

 Elevated LFTs (ALT may be 15x ULN)
 HCV RNA detectable
 Resolves in 6 months (unless chronic)

Front 134

chronic HCV definition

Back 134

if hep C continues for > 6 months

Front 135

chronic HCV sx- are there usually any?

if so what are they? (6)

Back 135

Most are asymptomatic until development of progressive liver fibrosis, cirrhosis, end‐stage liver disease

if there are sx...fatigue, dull RUQ pain, nausea, pruritis, arthralgia, anorexia

Front 136

labs for chronic HCV (2)

Back 136

Elevated LFTs (ALT > 2x ULN)
 HCV RNA detectable

Front 137

if there is cirrhosis present in HCV what would we see on PE? (4)

Back 137

▪ Splenomegaly and/or hepatomegaly on exam
▪ Encephalopathy or ascites

Front 138

past hx of patient that would warrant HCV screening (4)

Back 138

 Current or past use of injection drug use
 Received blood transfusion or organ transplant before
1992
 Received clotting factors before 1987
 Ever on chronic hemodialysis

Front 139

5 current patient factors that would warrant HCV screening

Back 139

 Coinfection with HIV
 Patients with unexplained elevated ALT levels or
evidence of liver disease
 Healthcare and public safety workers after an
occupational exposure
 Children born to HCV+ mothers
 Immigrants from countries with a high prevalence of
HCV infection

Front 140

Screening with serological assay for HCV is effective in detecting virus in....what % of people?

however...?

Back 140

97%

but high false positives

Front 141

confirmation tests for HCV to confirm serological assay (2)

Back 141

 Recombinant immunoblot assay (RIBA)
 Nucleic acid test for HCV RNA

Front 142

3 treatment goals of HCV

Back 142

 Virological response: HCV eradication (i.e.,undetectable HCV RNA)
 Biochemical response: ALT normalization
 Histological response: improving fibrosis score to prevent progression to
cirrhosis , end‐stage liver disease, and HCC

Front 143

Early virological response (EVR)

Back 143

2 log reduction in viral (HCV RNA)
load by the 12th week of therapy

Front 144

End of treatment response (ETR):

Back 144

no detectable viral load at the end of therapy

Front 145

Sustained virological response (SVR):

Back 145

no detectable viral load at the conclusion of therapy and 6 months later**THE CURE- most important

Front 146

3 types of "responders" a patient can be to HCV treatment and define them

Back 146

Relapser: initial response to therapy but detectable viral
load at the end of therapy
 Nonresponder: detectable viral load throughout therapy
 Partial responder: 2 log reduction in viral load but never
achieves undetectable virus

Front 147

treatment algorithm for genotype I HCV

Back 147

genotype HCV if chronic

If genotype I-->get liver biopsy

if no fibrosis, can consider not treating them due to low tolerance and cost

if there is more than portal fibrosis-->start treatment

treat with: peginterferon + ribavirin (weight based dosing)

at 12 weeks, determine quantitative HCV RNA

complete EVR(HCV RNA-)-->continue treatment for 48 weeks and check again for HCV RNA and again at 72

if no EVR stop treatment

if partial EVR< determine qualitative HCV RNA at 24 weeks and reassess- if still positive stop treatment
if negative continue for total of 48 weeks

Front 148

know logarithm shit

Back 148

--

Front 149

genotype I: peginterferon dosing for HCV (2 types) + what? dosing for that too (2)

duration of therapy

Back 149

Peginterferon α‐2a 180 mcg/wk
or
Peginterferon α‐2b 1.5 mcg/kg/wk

ribavirin
< 75 kg = 1,000 mg
≥ 75 kg = 1,200 mg

48 weeks

Front 150

genotype II, III: peginterferon (2) /ribavirin dosing what's different? duration?

Back 150

Peginterferon α‐2a 180 mcg/wk
or
Peginterferon α‐2b 1.5 mcg/kg/wk

800 mg ribavirin

24 week duration

Front 151

Interferon for HCV- usage?

SVR with ribavirin

Back 151

Rarely used now as SVR lower than with peg‐IFN
▪ SVR 12‐16%, 36% with ribavirin combination therapy

Front 152

pegasys- what is it?
PEG structure
distributed where (3)

metabolism and excretion

Back 152

pegasys- alpha-2a
PEG is branched
distributed to liver, spleen kidneys
metabolism liver, excretion renal

Front 153

peg-intron what is it?
PEG structure distributed where
metabolism/excretion

Back 153

a-2b
linear PEG
distributes through body depending on body weight
liver/renal

Front 154

3 main ADRs of interferon for HCV

Back 154

Psychological symptoms
(depression, irritability,
insomnia, suicidal
ideations)
Flu like symptoms
bone marrow suppression (wbc/platelets)

Front 155

how to combat flu sx ADR of interferon (2)

Back 155

 APAP or NSAID prior to
dose
 Hydration 64 oz. fluid/day

Front 156

treatment of psych sx from interferons HCV (2)

Back 156

 Antidepressants (SSRIs)
 Mood stabilizers and
anxiolytics

Front 157

monitoring of peginterferon- what to look for, when, how long

Back 157

 Monitor WBC with
differential at baseline, 2
weeks, and 4 weeks after
initiation of therapy

Front 158

neutropenia resulting from IFN- when would you reduce dose? when would you d/c?

how can you "treat" it?

Back 158

▪ Dose reduce if ANC <
750/mm3
▪ d/c if ANC < 500/mm3
▪ gCSF 300 mcg sq 1‐3 x/week

Front 159

platelets resulting from IFN- when would you reduce dose and when would you d/c (2)

Back 159

▪ Dose reduce if platelets <
50,000/mm3
▪ d/c if platelets < 25,000/mm3

Front 160

ribavirin MoA

Back 160

Guanosine analog which inhibits viral polymerase by
depleting intracellular phosphate

Front 161

ribavirin dosing- based on what?
avoid in what pt? (contraindication) and why

Back 161

 Based on body weight
 Avoid in patients with CrCl < 50 mL/min due to build up of drug causing hemolytic anemia

Front 162

ADRs for ribavirin (2)

Back 162

 Hemolytic anemia
category x (teratogenicity)

Front 163

ribavirin hemolytic anemia- monitor what, when?

when would you reduce dose?

how would you treat this side effect?

Back 163

▪ Monitor Hgb and Hct at baseline, 2 weeks, and 4 weeks then monthly
▪ Dose reduce if Hgb < 10 mg/dL and d/c if < 8.5 mg/dL
▪ Erythropoietin 40,000 IU sq weekly

Front 164

ribavirin teratogenicity- how to prevent and who would you counsel this in

Back 164

▪ 2 forms of contraception during and 6 months after therapy
▪ Women of childbearing potential and males with female partners

Front 165

patient characteristic risk factors associated with poor response to ribavirin/Peg-IFN (6)

Back 165

 African‐American
 Men
 Older age (> 40 years)
 BMI > 30 kg/m2
 Continued alcohol use
 Non‐adherence

Front 166

pathological factors associated with poor response to ribavirin/Peg-IFN (3)

Back 166

 Cirrhosis or bridging fibrosis
 Genotype 1 or 4

 High viral load

Front 167

hepatitis D -how do you get it? (2) (not exposure, but required conditions to have it)

Back 167

Requires coinfection with HBV
or superinfection (of chronic HBsAg carrier)

Front 168

2 routes of exposure of hep D

Back 168

 Percutaneous exposure- IVDA
 Permucosal exposure- Sex

Front 169

HDV + coinfection with HBV clinical features (2)

Back 169

 Clinically indistinguishable from acute HBV
 Low risk of chronic infection

Front 170

Clinical features of HDV gotten from superinfection in HBsAg carriers (3)

Back 170

 Severe acute hepatitis
 Usually develop chronic HDV infection
 High risk of severe chronic liver disease

Front 171

geographic prevalence of HDV

Back 171

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Front 172

HBV‐HDV coinfection prevention

Back 172

Pre‐ or post‐exposure prophylaxis to prevent HBV infection

Front 173

HBV‐HDV superinfection prevention

Back 173

Educate patients with chronic HBV infection on how to reduce high‐risk behaviors

Front 174

HEV incubation period

Back 174

Incubation period 15‐60 days (mean, 40 days)

Front 175

HEV clinical features- fatality rate (2)

severity of illness vs. age
chronic?

Back 175

low fatality rate (1-3%)

higher in pregnant women

severity of illness increases with age
no chronic sequelae

Front 176

HEV transmission- usually due to what? usually NOT due to what? US cases usually have hx of what?

Back 176

 Outbreaks due to fecally contaminated
drinking water
 Minimal person‐to‐person transmission
 U.S. cases usually have travel history to endemic areas

Front 177

non pharm prevention of HEV

Back 177

 Avoid drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruits and vegetables not peeled/prepared by traveler

Front 178

pharm prevention of HEV (2)

Back 178

 Ig prepared from donors in Western countries does not prevent infection

 Unknown efficacy of Ig prepared from donors in endemic areas

Front 179

HGV- family

2 types

Back 179

 Flavivirus
 Hepatitis G virus (HGV) and hepatitis GV virus
(HGBV‐C) - May represent same virus

Front 180

HGV transmission (2)

Back 180

 Transmitted parenterally and possibly
sexually

Front 181

patients at increased risk of HGV

Back 181

Hemodialysis patients appear to be at
increased risk

Front 182

how to calculate ANC (absolute neutrophil count)

Back 182

take total wbc x the % of neutrophils

Front 183

segs and bands

Back 183

immature neutrophils (add them up)- sometimes wbc is so low that machine does not do autodifferential

Front 184

hard genotypes of HCV to treat

Back 184

genotype 1 and 4

Front 185

combinations for HCV- which is the best for genotype 1? second best (supposedly)? worst?

Back 185

PEG-IFN + ribavirin + telaprevir- best % achieving SVR (80)

Peg-IFN + ribavirin + bocepervir (not head to head comparison, just reports from drug company)

Peg-IFN + ribavirin (40%)

Front 186

2 phase III clinical trials for boceprevir, their study pops, results of both

Back 186

RESPOND II- ppl who had failed HCV treatment prior
SPRINT II- treatment naive

increased SVR at f/u 24 weeks

Front 187

peg-interferon + ribavirin + boceprivir dosing

Back 187

Peg‐interferon alfa and ribavirin x 4 weeks, then add boceprevir 800 mg (200 mg x 4) po q8h w/meals

just based on clinical trials

Front 188

boceprivir regimen duration is dosed differently based on what condition?

Back 188

with or without compensated cirrhosis (wtf is compensated)

Front 189

boceprivir regimen with and without compensated cirrhosis (duration)

Back 189

Without cirrhosis: response‐guided therapy based on HCV RNA levels determines duration

With compensated cirrhosis: continue boceprevir x 44 weeks

Front 190

when would you d/c boceprevir?

Back 190

Discontinue if HCV RNA ≥ 100 IU/mL at week 12 or any HCV RNA detectable at week 24 (would stop all 3 treatments at this point anyway due to treatment failure)

Front 191

boceprevir- CYPs (2) and what they do to those CYPs

Back 191

Strong inhibitor of and partially metabolized by CYP450 3A4/5

Front 192

teleprevir- CYPs (and what they do to CYP) and other interaction

Back 192

glycoprotein P in gut- teleprevir
strong inhibitor of and partially metabolized by CYP3A4

Front 193

boceprevir AE (2)

Back 193

More anemia and neutropenia compared with peginterferon alfa and ribavirin therapy alone

Dysgeusia

Front 194

monitoring for boceprevir/teleprevir- what to monitor and how frequently (they differ in one spot)

Back 194

CBC at tx initiation; weeks 4, 8, and 12; then prn

telprevir monitors once at 2 weeks too

Front 195

teleprevir- 3 clinical trials and what they displayed

based on results, what is the new std of HCV genotype 1 treatment?

Back 195

whether treatment naive or not, pt did better when teleprevir was added
ADVANCE
ILLUMINATE
REALIZE trials

new std of HCV genotype 1 is to add boceprevir/teleprevir (3 drug regimen now)

Front 196

teleprevir not recommended in what pt pop?

Back 196

Not recommended in Child‐Pugh class B or C cirrhosis (severe)

Front 197

dosing for teleprevir (note how it is different from borceprevir)

peg-INF/ribavirin duration dependent on what?

Back 197

750 mg (375 mg x 2) po q8h w/non‐low‐fat food x 12 weeks w/standard peginterferon alfa and ribavirin- no 4 week lead in period

 Peginterferon alfa and ribavirin duration dependent on HCV RNA levels

Front 198

AE of teleprevir (3)

Back 198

More anemia compared with peginterferon alfa and ribavirin therapy alone

Rash in 56% – up to Stevens‐Johnson syndrome

Hyperuricemia

Front 199

geographic locations of HDV (3) risk in US?

Back 199

risk in US pretty low
south america
central asia
parts of africa

Front 200

HEV locations

Back 200

mexico
africa
asia

Front 201

hep E vaccine? efficacy?
schedule/dosing?

Back 201

hep E vaccine being made- pretty effective (100% at month 12) in asia
months 0, 1, 6

Front 202

summary of hep viruses (see slide too)
which is the only hep virus that is DNA virus?

which 2 aren't enveloped?

which 2 are fecal-oral? how are they other types transmitted?

Back 202

only HepB is a DNA virus

HepA/E aren't enveloped

HepA/E fecal-oral

other types are primarily blood/bodily fluid