Summary: Patients Who Develop Recurrent HCV Infection Post Liver Transplantation

Post Liver Transplantation: Genotype 1-6​

Recommended regimens listed by evidence level and alphabetically for:

Treatment-Naive and -Experienced Patients With Genotype 1-6 Infection in the Allograft Without Cirrhosis

RECOMMENDED DURATION RATING
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)a 12 weeks I, B
Genotype 1, 4, 5, or 6 only: Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks I, B
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, B
a Dosing is 3 coformulated tablets (glecaprevir [100 mg]/pibrentasvir [40 mg]) taken once daily. Please refer to the prescribing information.

 

Recommended regimens listed by evidence level and alphabetically for:

Treatment-Naive and -Experienced Patients With Genotype 1-6 Infection in the Allograft With Compensated Cirrhosis

RECOMMENDED DURATION RATING
Genotype 1, 4, 5, or 6 only: Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with ribavirin starting at 600 mg and increased as tolerated to weight-based dosea 12 weeks I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)a 12 weeks I, B
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)a,b 12 weeks I, C
a Ribavirin was only studied with ledipasvir/sofosbuvir, however, for patients with multiple negative baseline characteristics, consideration should be given to adding ribavirin. The starting dose of ribavirin should be 600 mg/d and increased or decreased as tolerated. If renal dysfunction is present, a lower starting dose is recommended. Maximum ribavirin dose is 1000 mg/d if <75 kg and 1200 mg/d if ≥75 kg body weight.
b Dosing is 3 coformulated tablets (glecaprevir [100 mg]/pibrentasvir [40 mg]) taken once daily. Please refer to the prescribing information.

 

Recommended regimens listed by evidence level and alphabetically for:

Treatment-Naive and -Experienced Patients With Genotype 1-6 Infection in the Allograft and Decompensated Cirrhosisa

RECOMMENDED DURATION RATING
Genotype 1, 4, 5, or 6 only: Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with low initial dose of ribavirin (600 mg, increase as tolerated)b 12 to 24 weeksc I, B
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) starting at 600 mg and increased as toleratedb 12 to 24 weeksc I, B
a Includes CTP class B and class C patients.
b The starting dose of ribavirin should be 600 mg/d and increased or decreased as tolerated. If renal dysfunction is present, a lower starting dose is recommended. Maximum ribavirin dose is 1000 mg/d if <75 kg and 1200 mg/d if ≥75 kg body weight.
c 24-week treatment duration is recommended if treatment experienced.

 

Recommended regimen for:

DAA-Experienced Patients With Genotype 1-6 Infection in the Allograft, With or Without Compensated Cirrhosisa

RECOMMENDED DURATION RATING
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100 mg)b 12 weeks I, C
a Excludes CTP class B and class C patients.
b For patients with cirrhosis plus multiple negative baseline characteristic, consideration should be given to adding ribavirin. The starting dose of ribavirin should be 600 mg/d and increased or decreased as tolerated. If renal dysfunction is present, a lower starting dose is recommended. Maximum ribavirin dose is 1000 mg/d if <75 kg and 1200 mg/d if ≥75 kg body weight.

 

Recommendations When Considering Use of HCV-RNA-Positive Donor Organs for HCV-Negative Recipients

RECOMMENDED RATING
Informed consent should include the following elements:
  • Risk of transmission from an HCV-viremic donor (and if PHS-defined high risk, the potential risks for other viral infections)
  • Risk of liver disease if HCV treatment is not available or treatment is unsuccessful
  • Benefits, specifically reduced waiting time and possibly lower waiting list mortality
  • Unknown long-term consequences (hepatic and extrahepatic) of HCV exposure (even if cure attained)
  • Risk of graft failure
  • Risk of HCV transmission to partner
I, C
Transplant programs should have a programmatic strategy to:
  • Document informed consent
  • Assure access to HCV treatment and retreatments, as necessary
  • Insure long-term follow-up of recipients (beyond SVR12)
I, C

 

Recommendations for Treatment of Organ Recipients from HCV-RNA-Positive Donors

RECOMMENDED RATING
Timing of DAA Therapy - Considerations for preemptive versus delayed initiation of therapy
  • Oral delivery of DAA therapy is assured.
    • There are limited data on the efficacy of DAAs given crushed via a nasogastric tube.
    • Nothing-by-mouth status may affect the absorption of some DAAs.
  • Preemptive therapy requires a pangenotypic regimen as donor genotyping is not routinely performed.
  • Delayed therapy involves awaiting documentation of viremia post transplantation and tailoring treatment to genotype or using a pangenotypic regimen.
II, B

 

Recommended and alternativea regimens listed by evidence level and alphabetically for:

Treatment of Organ Recipients from HCV-RNA-Positive Donors

RECOMMENDED DURATION RATING
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 12 weeks I, C
Genotype 1, 4, 5, or 6 only: Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks I, C
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, C
ALTERNATIVE DURATION RATING
Genotype 1 and 4 only: Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) for patients without baseline NS5A RASsc for elbasvir 12 weeks I, C
a Other considerations in selection of the DAA regimen:
  • Presence of renal dysfunction in the post-transplant period as sofosbuvir-inclusive regimens are not recommended if creatinine clearance is <30 mL/min
  • Presence of liver dysfunction (eg, elevated bilirubin) as protease inhibitors should be avoided
  • Specific drugs that are contraindicated or not recommended with specific DAA agents, including but not limited to:
    • High-dose antacid therapy (eg, twice daily proton pump inhibitor)
    • Amiodarone (contraindicated with sofosbuvir-inclusive regimens)
    • Specific statins (eg, atorvastatin)
  • Consideration of immunosuppressive drugs and DAA interactions (see below)

b Dosing is 3 coformulated tablets (glecaprevir [100 mg]/pibrentasvir [40 mg]) taken once daily. Please refer to the prescribing information.​
c Includes genotype 1a resistance-associated substitutions at amino acid positions 28, 30, 31, or 93 known to confer antiviral resistance.

 

Table. DAA Interactions With Calcineurin Inhibitors
 

 

Cyclosporine (CSA)

Tacrolimus (TAC)

Sofosbuvir (SOF) 4.5-fold ↑ in SOF AUC, but GS-331007 metabolite unchanged; no a priori dose adjustment No interaction observed; no a priori dose adjustment
Ledipasvir No data; no a priori dose adjustment No data; no a priori dose adjustment
Elbasvir / grazoprevir (EBR/GZR) 15-fold ↑ in GZR AUC and 2-fold ↑ in EBR AUC; combination is not recommended 43% ↑ in TAC; no a priori dose adjustment
Velpatasvir No interaction observed; no a priori dose adjustment No data; no a priori dose adjustment
Glecaprevir / pibrentasvir (GLE/PIB) 5-fold ↑ in GLE AUC with higher doses (400 mg) of CSA; not recommended in patients requiring stable CSA doses >100 mg/day 1.45-fold ↑ in TAC AUC; no a priori dose adjustment; monitor TAC levels and titrate TAC dose as needed
Sofosbuvir / velpatasvir / voxilaprevir (SOF/VEL/VOX) 9.4-fold ↑ in VOX AUC; combination is not recommended No data; no a priori dose adjustment
AUC=area under the curve

 

Last update: 
November 6, 2019
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