Hepatitis C Treatment Options: 5 Direct Questions

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This month’s quiz focuses on HCV guidelines for treatment, including options for patients with decompensated cirrhosis or severe renal impairment, management of persons who report injection drug use, resistance testing before starting therapy, and more. Ready to get started?

1. According to treatment guidelines, how long should treatment with the combination of ledipasvir and sofosbuvir be continued in a noncirrhotic patient with HCV genotype 1 and a baseline HCV RNA of less than 1 million IU/mL who has not previously received direct acting antiviral (DAA) therapy?

A. 8 weeks
B. 12 weeks
C. 24 weeks
D. 8, 12, or 24 weeks

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Answer: A. 8 weeks

The combination of ledipasvir and sofosbuvir for 12 weeks is approved for treatment of patients with HCV genotype 1; however, treatment guidelines state that HCV genotype 1 patients who are noncirrhotic, naive to treatment, and have a baseline HCV RNA less than 6 million IU/mL can be treated for 8 weeks. That recommendation was based on post-hoc analysis of the ION-3 study showing very high sustained virologic response (SVR) rates in HCV genotype 1 patients without cirrhosis, which investigators said supported shorter trials of the regimen in selected patients

2. Which two DAA regimens would be recommended (in addition to ribavirin) for a patient with HCV genotype 3 infection and decompensated cirrhosis?

A. Sofosbuvir/velpatasvir or glecaprevir/pibrentasvir
B. Sofosbuvir/velpatasvir or elbasvir/grazoprevir
C. Sofosbuvir/velpatasvir or daclatasvir/sofosbuvir
D. Sofosbuvir/velpatasvir or ledipasvir/sofosbuvir

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Answer: C. Sofosbuvir/velpatasvir or daclatasvir/sofosbuvir

Current HCV guidelines for decompensated cirrhosis recommend 24 weeks of either a daily fixed-dose combination of sofosbuvir/velpatasvir plus weight-based ribavirin, or daily daclatasvir/sofosbuvir with a low initial ribavirin dose, increased as tolerated. The use of sofosbuvir/velpatasvir in patients with decompensated cirrhosis is supported in part by results of the phase 3 randomized ASTRAL-4 study, as described in the guidelines, while the ALLY-1 study supports using of daclatasvir/sofosbuvir plus ribavirin in patients with genotype 2 or 3 infection who have decompensated cirrhosis.

3. Going by guidelines, what would be the most appropriate next step in the management of a HCV-infected individual who reports ongoing injection drug use but wants to start direct-acting antiviral therapy?

A. Initiate therapy and offer linkage to a treatment program
B. Defer therapy until the patient enters a treatment program
C. Defer therapy until the patient completes a treatment program
D. Therapy is contraindicated; consider alternative therapy

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Answer: A. Initiate therapy and offer linkage to a treatment program

The traditional argument for restricting access to highly active DAA therapy in this situation is that people who inject drugs won’t adhere to therapy and that they have high rates of reinfection. However, experts say there is strong evidence that these individuals demonstrate treatment adherence and actually have lower than expected rates of reinfection.

Studies also suggest that combining HCV treatment with needle exchange and treatment programs has been effective in decreasing HCV burden. Thus, recent or active injection drug use should not be seen as an absolute contraindication to DAA therapy, according to current guidelines, which recommend these individuals be treated in a multidisciplinary setting that includes services to reduce risk of reinfection and to manage common social and psychiatric issues.

4. In a treatment-naive individual with an HCV genotype 1a infection, NS5A resistance-associated substitution (RAS) testing would be recommended when considering which of the following regimens?

A. Ledipasvir/sofosbuvir
B. Glecaprevir/pibrentasvir
C. Sofosbuvir/velpatasvir
D. Elbasvir/grazoprevir

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Answer: D. Elbasvir/grazoprevir

NS5A RAS testing is recommended when elbasvir/grazoprevir is being considered in patients with HCV genotype 1a, and if present, a different regimen should be considered. Testing can be considered, according to guidelines, for cirrhotic patients with an HCV genotype 1a infection who are treatment-experienced and being considered for treatment with ledipasvir/sofosbuvir. Testing would not be recommended for a patients with HCV genotypes 1-6 who are being considered for 12 weeks of sofosbuvir/velpatasvir or for 8, 12, or 16 weeks of glecaprevir/pibrentasvir.

5. Which of the following DAA regimens would be recommended for a patient with severe chronic kidney disease (CKD) who has an HCV genotype 2 infection?

A. Glecaprevir/pibrentasvir
B. Elbasvir/grazoprevir
C. Ledipasvir/sofosbuvir
D. Sofosbuvir/velpatasvir

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Answer: A. Glecaprevir/pibrentasvir

For patients with severe CKD (eGFR 15-29 mL/min), HCV guidelines would recommend a daily fixed-dose combination of glecaprevir/pibrentasvir. The duration of treatment would be 8 to 16 weeks, depending on prior treatment (naive or experienced) and on whether or not cirrhosis is present. Twelve weeks of elbasvir/grazoprevir would be recommended for patients with severe CKD or end-stage renal disease with genotype 1a, 1b, or 4, according to the guidelines.