HCV Background

Epidemiology
 ~3.5 million HCV infected persons in US
o only ~50% of those infected are aware
 How HCV is spread:
o Through exposure to infected blood, usually through percutaneous
exposure
 IV Drug Use (60% of acute HCV infections)
 Intranasal illicit drug use
 Mother  baby
 Recipient of blood products before 1992
 Recipient of clotting factors before 1987
 Long-term hemodialysis
 Needle-stick in healthcare workers
 Patient-patient in poor infection control areas
 Sexual transmission (usually in HIV + MSM)
 Who to test?:
o Baby boomers (1945-1965):
 CDC recommends screening ALL people of this generation with
a one-time test due to risk-based assessment missing 50% of
diagnoses
 Age group accounts for nearly 75% of all HCV infections
o High-risk populations:
 Incarcerated (29% of incarcerated persons + HCV Antibody
 IVDU
 HIV + MSM
 Including those to start PreP
 Unexplained chronic liver disease
 Solid organ donors
 Test IVDU and HIV+MSM at least annually
 Frequency of testing these people with ongoing
exposure is lacking
 Co-morbidities that complicate HCV:
o Diabetes
o Obesity
o HBV
o HIV
 Risk reduction strategies:
o Avoid sharing toothbrushes, dental products, razors
o Stop IVDU
 If continued:
 Avoid sharing syringes, needles, water, cotton,
tunicates, spoons, etc.
 Use new syringes, filters, disinfectants
 Alcohol swab injection site
  Dispose after 1 use.
o Don’t donate blood
o HIV and multiple sexual partners: Barrier method
o Blood spills cleaned up with 1 part bleach 1 part water
 Linkage to care:
o Only 13-18% of HCV infected individuals had been linked to care by
2013
o Barriers to care:
 Contraindications to treatment
 Competing priorities
 Loss to follow up
 Adverse effects
 Lack of access to treatment
o Co-localization of care can help reduce this burden
o ECHO: Extension for Community Healthcare Outcomes
 Videoconferencing to enhance PCP capacity

Pathophysiology
 Hep C Virus:
o Enveloped RNA virus
o Genus: Hepacivirus
o Family: Falvivirde
o 6 genotypes
 120 subtypes
 most common: 1a, 1b, 2, 3, 4, 5, 6
 vary in genotype but similar in transmission, persistence, ad
disease burden
o Structural proteins: core, envelope, E1 and E2
o Non-structural: NS1, Ns2, NS3NS4A, NSA4B, Ns5B
 NS5B variable region and codes for RNA dependent RNA
polymerase
 From the blood  enters the liver cell via bloodstream  replication and cell
necrosis
o Entry into the liver 4 host-derived factors
 Acute
o Either self-limiting or progresses to chronic infection
 Chronic
 How people clear

Testing/Pre-Treatment Lab Work:

 Quantatative
HCV RNA
HCV RNA +
Genotype
HCV Ab +

No active
HCB RNA -
infection

 Liver labs:
o AST
o ALT
o Bilirubin
o INR
o Serum fibrosis marker panels
 Other tests:
o HIV
o Hepatitis B
o Hepatitis A

 Liver biopsy
 Imaging (FibroScan)
 FibroSure®

Who to treat?
 Goal of treatment: reduce all-cause mortality and iver-realted health adverse
consequences
o HCC and ESLD
o Obtained by SVR
 TREAT EVERYONE
o Except those with short life expectancy, Liver transplant, or another
directed therapy
 Benefit of cure:
o Goal = SVR 12 weeks after treatment
  Durable > 5 years in > 99% of patients
 Detection limit on RNA PCR = 25
 HCV Ab will remain + but RNA –
o Decrease of liver inflammation, improved LFT’s
o Reduction in rate of liver fibrosis progression
o SVR associated with a > 70% reduction in HCC and 90% reduction in
liver-related mortality
o Reduces extrahepatic manifestations
 Benefit of treatment <F2:
o Increased survival rate
o Decreased progression
o Waiting till F3 or F4  2-5x higher rate of liver-related mortality

Monitoring
 Drug:
o Drug-Drug interactions
o Proper administration
o Importance of adherence
 Labs within 12 weeks PRIOR to starting:
o CBC
o INR
o Albumin
o Total/Direct bilirubin
o ALT
o AST
o Alkaline phosphatase
o eGFR
o At anytime before starting:
 Genotype and substype
 HCV RNA (viral load)
 During:
o Clinic vists
o After 4 weeks:
 CBC
 SCr
 eGFR
 Hepatic function panel
 10 fold increase ALT – prompt d/c
 < 10 fold but weakness, nausea, vomiting, jaundice,
raised INR/Alk phos  d/c
 Asymptomatic < 10  repeat testing
 Adverse effects
 HCV RNA
 If detectable  repeat 2 weeks after
o If > 10 fold higher  d/c
 o If lower  ?? on what to do with treatment
o 12 weeks after:
 HCV RNA
 Those who achieve SVR:
o No fibrosis: normal follow up
o Assessment for recurrence or re-infection is recommended onl if
ongoing risk factors or unexplained hepatic dysfunction
o F3/F4: twice yearly check for HCC
o Endoscopy in those with varices