22/23 - Hep C Flashcards
HCV Basics
- *SS-RNA** Virus
- *WITHOUT proofreading polymerase**
6 HCV Genotypes w/ treatment recommendations
+ 67 subtypes (a/b/c….)
Genotype 1 = MOST COMMON in US: 75%
(1a>>1b)
Genotypes 2 & 3 = ~20-25%
Decline in ACUTE HCV Cases from 1992-2005
Caused by WHAT?
2nd generation of Antibody tests
We know how to Diagnose & PREVENT it
WHY are Acute HCV Cases on the RISE in the US?
2010-now
INCREASE IN
IV DRUG USE
Symptoms of ACUTE HCV
& When do they appear
FATIGUE
but MOST Patients are ASYMPTOMATIC
Symptoms would appear in
4-12 Weeks after infection
Does NOT just Affect the liver:
ExtraHepatic Manifestations, even in the absence of cirrhosis
Arthralgia / diabetes / cryogloulinemia / dermatologic
Fever / loss of appetite / NV
Ab Pain / Jaundice / Choluria / Joint Pain
Clay-Colored Stool
When are Antibodies / RNA Detectable in the blood
for HCV?
Incubation of Acute HCV = 2wks - 6mo
AntiBodies
4-10 weeks after infection
takes time to be detectable
- *RNA**
- *2-3 weeks** after infection
symptoms CAN appear in 4-12 weeks
HIGH RISK
for HCV Transmission
IV Drug use
Blood Transfusion / Solid Organ Xplants
PRIOR to 1992
Clotting Factors
PRIOR to 1987
Lower Risk
for HCV Transmission
PeriNATAL Transmission / SEXUAL Transmission
Hemodialysis
IntraNASAL Drug Use
Occupational Exposure
TATTOOS / Accupuncture / Bodypiercing
Prevention for HCV
COUNSEL Patients to AVOID Risk factors
NO VACCINE
due to MANY mutations/strains & variation in genotypes/subtypes
NO Pre/Post-Prophylaxis Recommended
HCV SCREENING
Recommendations
3 Focus
All Patients W/ Risk Factors
- *EVERYONE** Born between 1945 - 1965
- regardless of risk factors*, due to IV Drug Use
ANNUAL testing of pts with ONGOING Risk Factors
IV Drug users
HIV+ men who have MM sex
Recommendations for HCV Screening
- Anyone born between 1945 and 1965
- Current or past use of injection drug use
- Coinfection with HIV
- blood transfusions or organ transplantations before 1992
- Received clotting factors before 1987
- Patients who have ever been on hemodialysis
- unexplained elevated ALT levels or evidence of liver disease
- needle-stick or mucosal exposure to HCV-positive blood
- Children born to HCV-positive mothers
- Sexual partners of HCV-positive patients
Which Chronic Infection has the
HIGHEST MORTALITY RATE
in the US
HCV
Used to be HBV but in 2006 –> HCV
due to baby boomers –> Cirrhosis developing
Diagnosing Proceedure for
HCV
“ARG”
HCV AntiBody
Prior or current exposure to HCV, requires further evaluation
if positive test….
HCV RNA level
Prior HCV infection may indicate prior resolution or prior successful treatment
if detectable then….
HCV GENOTYPE
helps determine the treatment options
What does this Indicate?
HCV Antibody = +Positive
HCV RNA Quantitative = +/-
- *Detectable HCV RNA**
- *Acute or Chronic HCV Infection**
- NOT* detected HCV RNA
- Spontaneous resolution** of HCV Infection = *RARE ~15%
- *or successful treatment**
What does this Indicate?
HCV Antibody = -negative-
HCV RNA Quantitative = +/-
DETECTABLE HCV RNA
EARLY Acute infection
or Chronic HCV infection in an immunocompromised patient
- NOT detectable*
- double negative = NO HCV infection*
HCV Antibody Test
OraQuick HCV
FDA Approved Rapid AB Test 2011
1uL BLOOD sample –> 20 min
98% accurate in detecting HCV AB
still requires confirmatory testing
HCV Progression
15% can Resolve ON THEIR OWN
85% –> CHRONIC –> 20% develop Cirrhosis
3-6% / year –> decompensation -> ESLD/Transplant
1-4% / year –> HCC = CANCER
Stages of LIVER FIBROSIS
METAVIR Scoring
(no fibrosis) F0 -> F4 (worst)
F4 = CIRRHOSIS / Advanced Liver Fibrosis
Determination of FIBROSIS STAGE
- *NON-Invasive Labs**
- *APRI** = AST to PLATELET Ratio Index
- *FIB-4** = Calculation
- *Fibrosure** = Biochemical Marker Index
- *Non-invasive PROCEDURES**
- *FIBROSCAN** = Transient Elastrography
- *MRE** = Magnetic Resonance Elastrography
Liver Biopsy = Invasive
FIBROSCAN
Transient Elastrography
Non-Invasive Procedure for determining Fibrosis Stage
Uses VIBRATION** to measure the liver’s **STIFFNESS
kPa of >12.5 = F4
Fibrosis / excessive scarring
Goal of HCV Treatment
Eradication of Infection
SVR = CURE
Sustained virological response, undetectable viral load
12 weeks AFTER treatment completion
We wait 12 weeks and test again to make sure that the
HCV does NOT come back
- *PREVENTION** of Complication & Death from:
- *Cirrhosis / ESLD + Liver Transplant / HCC**
Why do we SCREEN if we do NOT or can NOT Treat?
KNOWLEDGE IS POWER
LIFESTYLE CHANGES
&
Monitor for HCC
if F3 or F4
RIBAVIRIN
RBV
Indication / ADR / Warnings
Antiviral for HCV GT’s 1-6
- *NOT effective as MONOTHERAPY**
- *ALWAYS** used with Other DAA
weight based dosing + renally adjusted
Anemia -> fatigue
pregnancy cat X = teratogenic
MUST USE 2 Forms of contraception & 6mo’s after D/C
HCV RNA Components
Structural Proteins = Core + E1 + E2
Non-Structural Proteins
NS3 / NS4A / NS5A+B
are ALL TARGETS
- we do NOT have targets for:*
- *NS4B / NS2**
-PREVIR
HCV Medication Class Suffixes
DAA (direct acting antivirals)
_NS3/4A
Protease Inhibitors_ (PIs)
P = Protease Inhibitor
-previr
sime / parita / grazo / voxilla / gleca
-ASVIR
HCV Medication Class Suffixes
DAA (direct acting antivirals)
_NS5A
Replication Complex Inhibitors_
NS5A =-Asvir
ledip / ombit / daclat / elb / pibrent
-BUVIR
HCV Medication Class Suffixes
DAA (direct acting antivirals)
- *NS5B**
- *Polymerase Inhibitors**
NS5B = -Buvir
sofos / dasa
Sime-previr
SMV
NS3/4A Protease Inhibitor
used with RBV (Ribavirin)
RARELY USED IN THERAPY
2- copays & fewer FDC regimens
Child-Pugh Class B/C = Not Used
hepatic issues / decompensated
Sofos-buvir
SOF
NS5B Polymerase Inhibitor
HUGE BACKBONE used with many other DAA’s:
Good for ALL Genotypes = GT: 1-6 W/ other agent
DI: P-GP transporters, active metabolite
NOT USED FOR RENAL IMPAIRMENT
CrCl < 30 ml/min or ESRD/hemodialysis
no adjustments for HEPATIC
Ledi-Pasvir / Sofos-Buvir
LDV / SOF
NS5A / NS5B
- *1 pill combo** for GT’s 1/4/5/6 ,but NOT for all GT’s no 2/3
- *8-12 Week** treatment
DI: requires acidic environment / discuss antacid use
P-gp substrate
NOT USED FOR RENAL IMPAIRMENT
CrCl < 30 ml/min or ESRD/hemodialysis
no adjustments for HEPATIC
PrOD or PrO
NS3/4A PI / Ritonavir / NS5A +/- NS5B
RARELY USED DUE TO DRUG INTERACTIONS
due to RITONAVIR = booster that makes everythign WORSE
inhibitor of CYP3A4 / BCRP / P-gp
3A4 & 2D6 substrate
CI w/ hepatic impairment
Not defined for <15ml/min CrCl
Daclat-Asvir
DCV
NS5A Replication Complex Inhibitor
- *NOT USED DUE TO PRICE**
- *2 copays** = 2 drugs & newer FDC regimens
Elb-Asvir / Grazo-Previr
EBR / GZR
NS5A RCInhibitor / NS3 PI
1 Tab +/- RBV
for GT 1/2
GT1A:
Must check NS5A RESISTANCE @ Baseline & LFTs wk8/12
no adjustment for RENAL
NOT recommended for HEPATIC CP-B/C
Sofos-Buvir / Velpat-Asvir
SOF / VEL
NS5B Polymerase Inhibitor / NS5A RCInhibitor
1 Tab = Approved for All GT’s 1-6
VEL needs acidic absorption + discuss antiacids
NOT used for RENAL impairment
CrCl < 30 ml/min or ESRD/hemodialysis
no adjustments for HEPATIC
Sofos-Buvir / Velpat-Asvir / Voxila-Previr
SOF / VEL / VOX
NS5B PI / NS5A RCI / NS3/4A PI
1 Tab = ALL GT’s 1-6
for people who have FAILED PREVIOUS TREATMENT
DAA Failures
NOT used for RENAL IMPAIRMENT
CrCl < 30 ml/min or ESRD/hemodialysis
VOX ONLY:
NOT recommended for HEPATIC CP-B/C
Gleca-Previr / Pibrent-Asvir
G / P
NS3/4A PI / NS5A RCI
- *3 TABS** QD –> All GT’s 1-6
- *8 week treatment** & CHEAP (1 copay)
Used for NAIVE PTs & DAA Failures
(NS5A OR NS3, NOT both)
no adjustment for RENAL
NOT recommended for HEPATIC CP-B/C
What DAA Treatments are indicated for
ALL GENOTYPES?
SOF / VEL
SOF / VEL / VOX
- *G/P**
- *Gleca-Pravir / Pibrent-Asvir**
What DAA treatments are an
8 week treament?
most treatments are 12 weeks!
GT1 / Naive / Non-cirrhotic:
G/P
GlecaPrevir / PibrentAsvir = ONLY 8 week & CHEAP
LDV / SOF = 8-12 weeks
What DAAs / HCV Treatments are
okay for RENAL IMPAIRMENT
use in CKD / ESRD > 30 mL/min:
All are okay
Safe for DIALYSIS:
PrOD & EBR / GZR & G/P
if SOF
NOT USED FOR DIALYSIS
What DAAs / HCV Treatments are
safe for use in HEPATIC Impairment
- *Cirrhosis / Child-Pughs B+C**
- generally SOF backbones are safe, except VOX*
LDV / SOF
DCV + SOF
- *SOF / VEL**
- (not w/ VOX)*
What DAAs / HCV Treatments
need to be taken WITH FOOD?
G / P
SOF / VEL / VOX
(VOX requires the food, only VEL does not need food)
PrOD
SMV / SOF
What DAAs / HCV Treatments are
1 Pill ONLY
SOF / VEL +/- VOX
EBR / GZR
LDV / SOF
What DAAs / HCV Treatments are
the CHEAPEST
1 Copay
G / P
EBR / GZR
What DAAs / HCV Treatments are
- *used for NS5A or NS3 Failures**
- NOT BOTH*
- *used for NS5A or NS3 Failures**
- NOT BOTH*
G / P
SOF / VEL / VOX
What LABS are monitored for HCV
HCV Genotype / Subtype / RNA
HBsAg + HBcAb Total
CBC / INR
Creatinine / GFR
PREGNANCY Test
due to RBV, if indicated
Hapatic Liver Fxn Panel
albumin / bilirubin / ALT / AST / Alkaline Phosphatase
Why is HEP B Tested for before HCV Treatment?
HBV Surface Antigen + Core Ab total
due to B+C
CO-INFECTION** & **REACTIVATION
29 cases of B being reactivated once C is treated
have to check HP B before treating hep C,
monitor DURING treatment
What Labs are Monitored at
Week 4 & 12 Weeks of treatment
HCV RNA
for 12 weeks & 4 weeks
12 to see if HCV comes BACK
- *CBC / Creatinine / GFR / Hepatic FXN Panel**
- NOT INR*
HBV DNA
throughout if they were HBsAg +POS
What do you need to know to
SELECT an HCV Treatment
GENOTYPE
Previous Treatment History
Presence/Absence of Cirrhosis
Child-Pughs Assessment
Renal Impairment / Post-Transplant
Concomitant medications
Recommended HCV Regimens for
- *Naive / Non Cirrhotics**
- *GT 1A / 1B**
- *G / P**
- (8 week Treatment)*
LDV / SOF
8 weeks if: VL <6mil / not AA / no HIV
if NOT, 12 week treatment along with:
EBR / GZR
SOF / VEL
Recommended HCV Regimens for
Naive / COMPENSATED Cirrhotics
GT 1a / 1b
ALL ARE 12 WEEKS
G / P
EBR / GZR
LDV / SOF
SOF / VEL
Special Populations
in HCV
ELDERLY
there is NO “MAX” AGE,
treat if life expectancy is >12 months
do not treat if expected to die soon
- *Pediatrics**
- do not focus on, only 2 clinical trials*
Pregnancy
NO clinical trials for DAAs in pregnancy
LOW chance of vertical transmission, 12 week therapy dont give in pregnancy
HCV / HIV CO-Infection
NO CHANGES!
Just have to manage the DDIs
data shows that there is STILL A GOOD RESULT
SVR > 95%
Renal Impairment in HCV Treatment
If CrCl > 30mL/min; then there are NO CHANGES
general rule is if there is SOF, we do not use in renal impairment or Dialysis
<3 Options in ESRD / Dialysis
EBR / GZR —- PrOD —- G / P
RBV requires DOSAGE CHANGES
CrCl > 50 ml/min = no changes
CrCl 30 - 50 ml/min = 200mg - 400mg QD
CrCl <30 mL/min = 200 mg QD
Recommended HCV Regimens in
SEVERE Renal Impairment
<30 mL/min or ESRD
- *EBR / GZR**
- *12 weeks** for GT 1A/B + 4
- *G / P**
- treat based on treatment history & stage*
- *8-16 weeks** for ALL GTs
Hepatic Impairment in HCV Treatment
- *3** recommended regimens GT1
- *generally if it does NOT have SOF, then it is okay**
- exception is SOF/VEL/VOX + G/P*
- *DCV + SOF —- LDV / SOF —– SOF / VEL**
RBV is generally added
if not we can extend the length of treatment
HCV Treatment for
DECOMPENSATED Cirrhosis
- *F4** or (F3 + HCC & Post Transplant)
- *REFER TO TRANSPLANT CENTER**
If then we can treat with agents that HAVE SOF
exception is those wiith VOX / SMV**, can’t use these
LDV + SOF —- SOF + VEL —– DCV + SOF
all are 12 weeks
but if we can NOT use RBV = >24 weeks
Which HCV Regimen for DECOMPENSATED Cirrhotics
require a WEIGHT BASED RBV?
VEL / SOF
requires weight-based RBV or a low dose RBV like the other regimens
12 week regimen for ALL GT 1,4 / 5,6 / 2,3
but if no RBV = >24 weeks
Which HCV Regimens for DECOMpensated Cirrhotics
Treat GT 1/4
ALL 3 REGIMENS
12 weeks / >24 weeks without RBV
LDV / SOF
SOF / VEL
- *DCV / SOF**
- expensive as hell*
Which HCV Regimens for DECOMpensated Cirrhotics
Treat GT 5/6
LDV / SOF
SOF / VEL
(treats ALL, but needs weight based RBV)
DCV / SOF
does not treat GT 5/6
Which HCV Regimens for DECOMpensated Cirrhotics
Treat GT 2/3
LDV / SOF
does not treat 2/3
SOF / VEL
works for all 3 but needs a weight-based RBV
DCV + SOF
HCV Treatment for
POST-Liver Transplant
Some regimens need RBV
Watch DDIs w/ immunosupression
Varies on CTP (Child-Pughs) Score
MOST have SOF
Recommended HCV Treatment for
POST LIVER Transplant & CTP A
For GT 1,4 / 5,6
LDV / SOF
(weight based)
- *G / P**
- non-cirrhotic*
For GT 2,3
DCV + SOF
Recommended HCV Treatment for
POST LIVER Transplant & CTP B/C
NO G/P because cirrhotic, CTP B/C
for GT 1,2 / 5,6
LDV / SOF
ONLY
for GT 2,3
DCV + SOF
SOF / VEL
Drug Interactions of DAAs & TACROLIMUS
Which ones are generally OKAY to take together
Tacrolimus = immunosupressive for TRANSPLANT
DCV
LDV / SOF
SOF / VEL
G/P and others have potential drug interactions
need to adjust dose
Ribovirin
RBV Dosing / Considerations
- *MONITOR HEMOGLOBIN**
- -> hemolytic anemia
Weight-based dosing
≤75mg: 1000mg
>75kg: 1200mg/day
Renally adjusted
–If CrCl > 50mL/min: no changes
–If CrCl 30 – 50 mL/min: 200mg – 400mg daily
–If CrCl <30 mL/min: 200mg daily
