Hepatitis C Virus

Hepatitis C

What is the MOST common bloodborne pathogen in the US?

A. HIV

B. Hepatitis B

C. Syphilis

D. Hepatitis C

Syphilis

What is the LEAST commonly treated bloodborne pathogen in the US?

A. HIV

B. Hepatitis B

C. Syphilis

D. Hepatitis C

Hepatitis C

-is an inflammation of the liver caused by the hepatitis C virus

-The virus can cause both acute and chronic hepatitis, ranging in severity from a mild illness to a serious, lifelong illness including liver cirrhosis and cancer

-is a blood borne virus, and most infections occur through exposure to blood from unsafe injection practices, unsafe health care, unscreened blood transfusions, injection drug use and sexual practices that lead to exposure to blood

no

Is there a vaccine for Hep C?

HCV

is though to be responsible for about 40% of primary liver cancer/cirrhosis deaths in the US and is a common cause of liver transplantation

no fibrosis

Stage 0 HCV disease

portal fibrosis - no septa

Stage 1 HCV disease

few septa

Stage 2 HCV disease

numerous septa

Stage 3 HCV disease

cirrhosis

Stage 4 HCV disease

HCV testing

– ALL individuals 18 years and older (one-time)

– Individuals involved in one or more increased risk activity:

▪ Injection drug use (previously or currently)

▪ Intranasal illicit drug use

▪ Use of glass crack pipes

▪ Male engagement in sex with men (MSM)

▪ Engagement in chem sex (intentional combination of sex with the particular use of nonprescription drugs in order to facilitate or enhance the sexual encounter)

– Individuals with known risk exposures

▪ Long-term hemodialysis (previously or currently)

▪ Percutaneous/parenteral exposures in an unregulated setting

▪ Healthcare workers following needlestick, sharps, or mucosal exposure to HCV-infected blood

▪ Children born to HCV-infected women

▪ Historical recipients of blood transfusion/organ transplant

▪ Individuals who have ever been incarcerated

– All pregnant persons as part of routine prenatal care

with each pregnancy

– Annual testing populations:

▪ Individuals with HIV

▪ Persons who inject drugs

▪ MSM who are currently on pre-exposure prophylaxis (PrEP)

s/s of HCV

• Fatigue

• Myalgia

• Low-grade fever

• Dark urine

• Nausea

• Vomiting

• Jaundice

• Right upper quadrant pain

• Hepatic failure is RARE in acute HCV

initial

• Fibrosis staging

• Genotype

• Drug-drug interaction assessment - especially non-traditional treatments like herbals and vitamins

• Patient education regarding the important of communication of med changes, adherence, and proper administration

• Screen for HIV coinfection

• Screen for HBV coinfection - treat if criteria are met

• Safety of DAAs in pregnancy not yet assessed, so discuss avoidance of pregnancy during therapy

• Possible HCV RAS screening

within 6 months of therapy initiation

• CBC

• INR

• Hepatic function panel

• eGFR

Also labs we've already discussed for initial diagnosis plus a HCV genotype if needed

monitoring during therapy

• Warn about changes in glucose for diabetic patients with cirrhosis since hypoglycemia is a concern with DAA therapy

• Clinic visits or telephone follow-ups to encourage adherence & screen for DDIs

• INR changes can occur for patients on warfarin

• Other lab and HBV monitoring per guidelines

• Quantitative HCV testing

• Viral load testing is important to be certain the patient has responded to therapy.

• The guidelines recommended testing 12 weeks or more after the completion of therapy with DAAs. This is to verify SVR.

An undetectable HCV RNA level 12 weeks after completing therapy generally translates into along-term cure of HCV infection

What defines HCV cure?

clinical improvement of HCV

- Reduce all-cause mortality

- Reduce liver-related health adverse consequences, including end-stage liver disease and hepatocellular carcinoma

Sofosbuvir/Velpatasvir (Epclusa)

• NS5A/NS5B Inhibitor (400mg / 100mg)

• Adverse effects: Headache, fatigue, nausea, insomnia, rash

• Contraindications/Precautions: hepatitis B reactivation

• Pearls:

‒ Majority of patients using this drug take 1 tablet once daily and have a treatment course of 12 weeks.

‒ Some patients (genotype 3) in uncommon situations require baseline NS5A resistance-associated substitution (RAS) testing.

‒ Pangenotypic, approved for cirrhosis and compensated cirrhosis

‒ When used in combination with ribavirin, it is also used for cases with decompensated cirrhosis.

4 hrs

Separate Antacids and SOF/VEL by _______

H2 receptor antagonists with SOF/VEL

-Administer simultaneously with or 12 hours apart from SOF/VEL.

-Do not exceed doses comparable to famotidine 40 mg twice

daily.

PPI with SOF/VEL

Coadministration not recommended. If required, SOF/VEL should be administered with food and taken 4 hours before omeprazole 20 mg. Use with other proton pump inhibitors has not been studied.

Antiarrhythmic: amiodarone with SOF/VEL

Significant bradycardia expected with concurrent use. Coadministrationnot recommended. If concurrent use required, cardiac monitoring is recommended, see package insert for additional information

Anticoagulant: warfarin with SOF/VEL

frequent INR monitoring drug coadministration and after stopping therapy recommended

Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin with SOF/VEL

Significant decrease in SOF/VEL levels expected. Coadministration not recommended

Antimycobacterials: rifampin,rifabutin, rifapentine with SOF/VEL

Significant decrease in SOF/VEL levels expected. Coadministration not recommended

Digoxin with SOF/VEL

increase in digoxin levels possible. Monitor digoxin levels

Herbal products: St John's wort with SOF/VEL

Significant decrease in SOF/VEL levels expected. Coadministration not recommended

HMG Co-A reductase inhibitors: atorvastatin, rosuvastatin with SOF/VEL

▪ Increase in atorvastatin likely with SOF/VEL; monitor for signs of

myopathy and rhabdomyolysis

▪ Significant increase in rosuvastatin levels when used with SOF/VEL leading to increased risk of myopathy, including rhabdomyolysis. Rosuvastatin may be used at dose that does not exceed 10 mg

Glecapravir/Pibrentsavir (Mavyret)

• NS3/4A protease inhibitor-NS5A inhibitor

• Adverse effects: Headache, fatigue, nausea, diarrhea, pruritus

(in renal failure)

• Contraindications/Precautions: hepatitis B reactivation,

contraindicated in moderate or severe renal impairment (Child-

Pugh B or C), contraindicated co-administration with atazanavir

& rifampin

• Pearls:

‒ Majority of patients using this drug take 3 tablets once daily with food and have a treatment course of 8 weeks.

‒ Best absorption with food

‒ Pangenotypic, approved for cirrhosis and compensated cirrhosis

‒ When used in combination with ribavirin, it is also used for cases with decompensated cirrhosis.

Atazanavir, rifampin with GLE/PIB

CI

Carbamazepine, efavirenz,phenytoin, St. John's wort with GLE/PIB

Significant decrease in GLE/PIB levels expected. Coadministration not recommended

Cyclosporine, darunavir, lopinavir,ritonavi with GLE/PIB

Significant increase in GLE/PIB levels expected. Coadministration not recommended

HMG Co-A reductase inhibitors with GLE/PIB

▪ Significant increase in co-administered drug (atorvastatin, lovastatin, simvastatin). Coadministration not recommended.

▪ Significant increase in fluvastatin or pitavastatin concentration when coadminstered. Use the lowest approved dose.

▪ Significant increase in pravastatin concentration when coadminstered. Reduce dose by 50%.

▪ Significant increase in rosuvastatin concentration when coadminstered. Do not exceed rosuvastatin 10 mg/day

Digoxin with GLE/PIB

Increase in digoxin levels possible. Monitor digoxin levels

Ethinyl estradiol-containing medications (i.e. oral contraceptives) with GLE/PIB

Significant decrease in GLE/PIB levels expected. Coadministration not recommended

Dabigatran etexilate with GLE/PIB

Refer to dabigatran etexilate PI for dose modifications in combination with P-gp inhibitors in the setting of renal impairment.

GLE/PIB

-protease inhibitor/NSSA inhibitor

-3 pills qd

-8 weeks

-food required

-DDIS: anticonvulsants, statins, st johns wort, warfarin

-CI: severe hepatic impairment (CP C) concurrent ATV or rifampin use

-HBV reactivation risk

SOF/VEL

-NS5B inhibitor/NS5A inhibitor

-1 pill qd

-12 weeks

-no food

-DDIs: anticonvulsants, PPI, rifampin, st john's wort, warfarin

-CIs: do not use RBV in pts with RBV CI

-HBV reactivation risk bradycardia with amiodarone coadmin

Ledipasvir/Sofosbuvir (Harvoni)

• NS5A inhibitor-nucleotide analog/NS5B inhibitor

• Adverse effects: Headache, fatigue, nausea, diarrhea, insomnia

‒ Rare: depression, angioedema, blisters

• Contraindications/Precautions: Bradycardia with amiodarone coadministration, use with P-gp Inducers (Ex. St. John's Wort and rifampin) is also not recommended

• Pearls:

‒ Majority of patients using this drug take 1 tablet once daily and have a treatment course of 12 weeks. This dosing varies in more complicated patients.

‒ Used in treatment of genotypes 1, 4, 5, & 6 naïve or experienced with or without compensated cirrhosis.

‒ When used in combination with ribavirin, it is also used for genotype 1 cases with decompensated cirrhosis.

‒ Comes in oral pellet dosing form, which utilizes weight based dosing

LDV/SOF with Carbamazepine, Phenytoin, and Phenobarbital

may decrease efficacy of LDV/SOF

HMG Co-A reductase inhibitors with LDV/SOF

Statin concentrations (rosuvastatin, atorvastatin) are increased. Coadministration not recommended.

Tipranavir and Ritonavir with LDV/SOF

May decrease efficacy of LDV/SOF

Ritonavir + TDF with LDV/SOF

Avoid coadministration due to increased exposure to TDF

antacids with LDV/SOF

Separate LDV/SOF by 4 hours

H2 receptor antagonists with LDV/SOF

H2-receptor antagonists may be administered simultaneously with or 12 hours apart from LDV/SOF at a dose that does not exceed doses comparable to famotidine 40 mg BID

PPI with LDV/SOF

Proton-pump inhibitor doses comparable to omeprazole20 mg or lower can be administered simultaneously with LDV/SOF under fasted conditions.

Sofosbuvir-velpatasvir-voxilaprevir (Vosevi)

• NS5A inhibitor/NS5B inhibitor/NS3/4A protease Inhibitor

• Adverse effects: Headache, fatigue, nausea, diarrhea, insomnia, astheniam bilirubin increases, asymptomatic lipase and CK elevations

‒ Less common: Rash, mild-moderate depression, angioedema, rashes with blistering

• Contraindications/Precautions: Hepatitis B reactivation, advanced liver disease, bradycardia with amiodarone, concurrent treatment with inducers of P -GP and/or strong inhibitors of CYP 2B6, 3A4, or 2C8, contraindicated with rifampin

• Pearls:

‒ Pangenotypic in non-cirrhotic or CTP Class A (NOT B or C) patients with previous DAA failure

‒ Should be taken with food to boost voxilaprevir absorption

Sofosbuvir/Velpatasvir (Epclusa) for 12 weeks

Glecaprevir/Pibrentasvir (Mavyret) for 8 weeks

Tx for tx naive pts with Hep C:

- Choice in drug depends on what initial treatment option was.

- If a patient failed therapy with ANY sofosbuvir-based regimen (Epclusa and

Harvoni):

▪ Sofosbuvir/velpatasvir/voxilaprevir (Vosevi) for 12 weeks

▪ Alternative regimen: glecaprevir/pibrentasvir (Mavyret) for 16 weeks

▪ The main exception is patients with genotype 3 and cirrhosis, in which case we will add ribavirin for 12 weeks.

- If a patient failed therapy with glecaprevir/pibrentasvir (Mayvret):

▪ Glecaprevir/pibrentasvir (Mavyret) PLUS daily sofosbuvir 400mg (Sovaldi) and weight-based ribavirin for 16 weeks

▪ Alternative regimen: sofosbuvir/velpatasvir/voxilaprevir (Vosevi) for 12 weeks.

Tx for tx experienced pts with Hep C:P