HCV (Exam 2 Cut Off)

Question 1

HCV

Answer 1

• RNA virus with 6 major genotypes
• Commonality: GT1 > GT3 > GT2 (NM specific)
• 85% infected develop cirrhosis
• Can further develop ESLD, liver cancer, transplant need
• HIV and continued alcohol use can severely affect progression
• Infections tend to be asymptomatic

Question 2

Extrahepatic HCV Manifestations

Answer 2

• HCV causing disease outside of the liver

- Diabetes, joint pain, neuropathy, Parkinson’s

Question 3

Testing Recommendation

Answer 3

-Anyone >=18 y.o. should be tested for HCV antibody at least once

Question 4

HCV Transmission

Answer 4

• Blood contact
• IDU major driver of current HCV infections
• Non-professional tattoos
• Comorbidities associated with higher HCV prevalence
• Children born to HCV positive mother
• Occupational exposure
• HCV+ sexual partners
• MSM

Question 5

HCV Diagnosis

Answer 5

• HCV antibody test to identify exposure

- HCV RNA necessary to determine if chronic infection

Question 6

Anti-HCV Caveats

Answer 6

• Those who spontaneously clear or undergo HCV therapy will continue to test anti-HCV positive
• HCV Ab positive doesn’t confer immunity against HCV

Question 7

HCV Treatments Goals

Answer 7

• Goal: Cure
• Viral eradication defined as sustained virologic response
• Preventing complications like fibrosis, cirrhosis, ESLD, HCC
• Improving QoL
• Reducing symptoms
• Resolve extrahepatic manifestations

Question 8

Interferon Based Therapy

Answer 8

• Low SVR rates, long treatment courses (up to a year)
• Major toxicities, lab abnormalities
• Causes fear in older patients since many new an interferon patient and they now fear the SE

Question 9

DAA Based Therapy

Answer 9

• Current standard of care, preferably pan-genotypic therapy
• Specific DAAs act on 1 of 3 targets on the HCV virion to inhibit viral replication
• Current therapies are combination of 2 or more drugs

Question 10

Suffix + Drug Targets

Answer 10

• Previr = PI
• asvir = NS5A inhibitor
• buvir = NS5B inhibitor

Question 11

DAA Concerns/Limitations

Answer 11

• Concerns to resistance especially in regards to interrupted regimens
• HBV reactivation is a warning for all these drugs, can result in liver failure and death (watch for LFT increase and serologies)
• PI can’t be used in patients with decompensated cirrhosis, precipitates liver failure

Question 12

Mavyret

Answer 12

• Glecaprevir/Pibrentasvir
• Pan-genotypic
• Approved for 12 y.o.+
• Take with food
• Can be used in all renal insufficiency but not in decompensated cirrhosis
• Avoid ethinyl estradiol products while on medication, raises ALT

Question 13

Epclusa

Answer 13

• Sofosbuvir/Velparasvir
• Pan-genotypic
• Approved for 6 y.o.+
• Safe in all levels of renal and hepatic disease
• Test for resistance before treating GT3, add ribavirin if resistance found
• Avoid PPIs
• Take H2 blockers at the same time or 12 hours apart
• Antacids should be take 4 hours after last dose and 8 hours before the next

Question 14

Vosevi

Answer 14

• Sofosbuvir/Velpatasvir/Voxilaprevir
• Pan-genotypic
• Used for previously failed DAA therapy, including previously failed NS5A inhibitor
• With or without food
• SE: diarrhea
• Can be used in all renal insufficiency but not in decompensated cirrhosis

Question 15

Harvoni

Answer 15

• Ledipasvir/Sofosbuvir
• GT1 and 4
• Approved for 3 y.o.+
• Safe in all levels of renal and hepatic disease
• Ledipasvir requires similar acidic environment to velpatasvir

Question 16

Zepatier

Answer 16

• Elbasvir/Grazoprevir
• No longer used due to resistance testing needed before GT1 use
• Used for GT1 and 4

Question 17

Ribavirin

Answer 17

• Inhibits viral replication in synergistic effect
• Exact mechanism isn’t understood
• Not effective as monotherapy but can be used to augment existing DAA therapies
• Weight based dosing that is titrated based on expected anemia effect

Question 18

Ribavirin SE

Answer 18

• Nausea (split into BID dosing to minimize)
• Hemolytic anemia: monitor until steady state is achieved (worse in renal impaired)
• Teratogen, avoid in pregnancy (recommend 2 forms of birth control during and for 6 mo after), Category X

Question 19

DAAs + Lab Abnormalities

Answer 19

• Very few lab abnormalities unless specified

- Few SE, HA is most common

Question 20

DDI for DAAs

Answer 20

• Amiodarone: concerns for symptomatic bradycardia
• Serious, symptomatic bradycardia noted in sofosbuvir patients
• Acid suppression: problem for LDV and VEL
• Avoid ethinyl estradiol in GLE/PIB patients
• Avoid herbals due to limited data
• Avoid major CYP inducers like rifampin and AEDs
• Hold statins while on therapy, interactions vary but holding will have minimal lipid panel effects and is the safest option overall

Question 21

Minimizing Further Liver Damage

Answer 21

• Vaccinate for HAV, HBV, flu, and pneumonia
• Avoid/decrease alcohol
• Avoid/minimize smoking
• Weight loss in overweight/obese

Question 22

HCV + Cirrhotic Patients

Answer 22

• Screen for hepatocellular carcinoma every 6 months with AFP and abdominal US
• Evaluate for varices with endoscopy
• Avoid NSAIDs and aspirin due to increase bleed risk, renal toxicity potential, and impaired response to diuretics