Overview
Initial treatment of HCV infection includes patients with chronic hepatitis C who have not been previously treated with interferon, peginterferon, ribavirin, or any HCV direct-acting antiviral (DAA) agent, whether investigational, or US Food and Drug Administration (FDA) approved.
Simplification of the treatment regimen may expand the number of healthcare professionals who prescribe antiviral therapy and increase the number of persons treated. This would align with the National Academies of Science, Engineering, and Medicine strategy to reduce cases of chronic HCV infection by 90% by 2030 (NAS, 2017).
Simplified HCV Treatment
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Simplified HCV Treatment Algorithm for Treatment-Naive Adults With Compensated Cirrhosis
Who Is NOT Eligible for Simplified Treatment (With Cirrhosis) Patients who have any of the following characteristics: Current or prior…
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Simplified HCV Treatment* for Treatment-Naive Adults Without Cirrhosis
Who Is NOT Eligible for Simplified Treatment (Without Cirrhosis) Patients who have any of the following characteristics: Prior hepatitis C…
The level of evidence available to inform the best regimen for each patient and the strength of the recommendation vary and are rated accordingly (see Methods Table 2). In addition, specific recommendations are given when treatment differs for a particular group (eg, those infected with different genotypes). Recommended regimens are those that are favored for most patients in a given group, based on optimal efficacy, favorable tolerability and toxicity profiles, and treatment duration. Alternative regimens are those that are effective but, relative to recommended regimens, have potential disadvantages, limitations for use in certain patient populations, or less supporting data than recommended regimens. In certain situations, an alternative regimen may be an optimal regimen for an individual patient or clinical setting. Specific considerations for pediatric patients and persons with HIV/HCV coinfection, decompensated cirrhosis (moderate or severe hepatic impairment; Child-Turcotte- Pugh [CTP] class B or C), HCV infection post liver transplant, and severe renal impairment, end-stage renal disease (ESRD), or post kidney transplant are addressed in other sections of the guidance.
Recommended and alternative regimens are listed by pan-genotypic activity and in order of level of evidence. When several regimens are at the same recommendation level, they are listed in alphabetical order. Regimen choice should be determined based on patient-specific data, including drug-drug interactions. Patients receiving antiviral therapy require careful pretreatment assessment for comorbidities that may influence treatment response or regimen selection. All patients should have access to an HCV care provider during treatment, although preset clinic visits and/or blood tests depend on the treatment regimen and may not be required for all regimens/patients. Patients receiving ribavirin require additional monitoring for anemia during treatment (see Monitoring section).
The following pages include guidance for management of treatment-naive patients by genotype (although most patients will fall into the simplified treatment algorithms above).
Decompensated Cirrhosis
Genotype 1
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Peginterferon/Ribavirin-Experienced, Genotype 1a Patients With Compensated Cirrhosis
Page Retired 1/21/2021 Recommended and alternative regimens listed by evidence level and alphabetically for: Peginterferon/Ribavirin-Experienced, Genotype 1a Patients With Compensated Cirrhosisa…
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Peginterferon/Ribavirin-Experienced, Genotype 1a Patients Without Cirrhosis
Page Retired 1/21/2021 Recommended regimens listed by evidence level and alphabetically for: Peginterferon/Ribavirin-Experienced, Genotype 1a Patients Without Cirrhosis RECOMMENDED DURATION RATING…
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Peginterferon/Ribavirin-Experienced, Genotype 1b Patients With Compensated Cirrhosis
Page Retired 1/21/2021 Recommended and alternative regimens listed by evidence level and alphabetically for: Peginterferon/Ribavirin-Experienced, Genotype 1b Patients With Compensated Cirrhosisa…
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Peginterferon/Ribavirin-Experienced, Genotype 1b Patients Without Cirrhosis
Page Retired 1/21/2021 Recommended regimens listed by evidence level and alphabetically for: Peginterferon/Ribavirin-Experienced, Genotype 1b Patients Without Cirrhosis RECOMMENDED DURATION…
Genotype 2
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DAA-Experienced (Including NS5A Inhibitors Except Glecaprevir/Pibrentasvir Failures), Genotype 2 Patients, With or Without Compensated Cirrhosis
Page Retired 1/21/2021 (For glecaprevir/pibrentasvir treatment failures, please see that topic.) Recommended regimens listed by evidence level for: Sofosbuvir +…
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Peginterferon/Ribavirin-Experienced, Genotype 2 Patients With Compensated Cirrhosis
Page Retired 1/21/2021 Recommended regimens listed by evidence level and alphabetically for: Peginterferon/Ribavirin-Experienced, Genotype 2 Patients With Compensated Cirrhosisa RECOMMENDED DURATION…
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Peginterferon/Ribavirin-Experienced, Genotype 2 Patients Without Cirrhosis
Page Retired 1/21/2021 Recommended regimens listed by evidence level and alphabetically for: Peginterferon/Ribavirin-Experienced, Genotype 2 Patients Without Cirrhosis RECOMMENDED DURATION RATING…
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Treatment-Experienced Genotype 2
Page Retired 1/21/2021 The following pages include guidance for management of treatment-experienced patients with genotype 2. Peginterferon/Ribavirin-Experienced, Genotype 2…
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Treatment-Naive Genotype 2
The following pages include guidance for management of treatment-naive patients with genotype 2 infection. Treatment-Naive Genotype 2 Without Cirrhosis Treatment-Naive…
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Treatment-Naive Genotype 2 With Compensated Cirrhosis
Recommended and alternative regimens listed by pangenotypic, evidence level and alphabetically for: Treatment-Naive Genotype 2 Patients With Compensated Cirrhosisa RECOMMENDED…
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Treatment-Naive Genotype 2 Without Cirrhosis
Recommended and alternative regimens listed by pangenotypic, evidence level and alphabetically for: Treatment-Naive Genotype 2 Patients Without Cirrhosis RECOMMENDED DURATION…
Genotype 3
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DAA-Experienced (Including NS5A Inhibitors Except Glecaprevir/Pibrentasvir Failures), Genotype 3 Patients, With or Without Compensated Cirrhosis
Page Retired 1/21/2021 (For glecaprevir/pibrentasvir treatment failures, please see that topic.) Recommended regimens by evidence level for: Sofosbuvir +…
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Peginterferon/Ribavirin-Experienced, Genotype 3 Patients With Compensated Cirrhosis
Page Retired 1/21/2021 Recommended and alternative regimens listed by evidence level and alphabetically for: Peginterferon/Ribavirin-Experienced, Genotype 3 Patients With Compensated Cirrhosisa…
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Peginterferon/Ribavirin-Experienced, Genotype 3 Patients Without Cirrhosis
Page Retired 1/21/2021 Recommended and alternative regimens listed by evidence level and alphabetically for: Peginterferon/Ribavirin-Experienced, Genotype 3 Patients Without Cirrhosis RECOMMENDED…
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Treatment-Experienced Genotype 3
Page Retired 1/21/2021 The following pages include guidance for management of treatment-experienced patients with genotype 3 infection. Peginterferon/Ribavirin-Experienced, Genotype…
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Treatment-Naive Genotype 3
The following pages include guidance for management of treatment-naive patients with genotype 3 infection. Treatment-Naive Genotype 3 Without Cirrhosis Treatment-Naive…
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Treatment-Naive Genotype 3 With Compensated Cirrhosis
Recommended and alternative regimens listed by pangenotypic, evidence level and alphabetically for: Treatment-Naive Genotype 3 Patients With Compensated Cirrhosisa RECOMMENDED DURATION…
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Treatment-Naive Genotype 3 Without Cirrhosis
Recommended and alternative regimens listed by pangenotypic, evidence level and alphabetically for: Treatment-Naive Genotype 3 Patients Without Cirrhosis RECOMMENDED DURATION…
Genotype 4
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DAA-Experienced (Including NS5A Inhibitors Except Glecaprevir/Pibrentasvir Failures), Genotype 4 Patients, With or Without Compensated Cirrhosis
Page Retired 1/21/2021 (For glecaprevir/pibrentasvir treatment failures, please see that topic.) Recommended regimen for: DAA-Experienced (Including NS5A Inhibitors Except…
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Peginterferon/Ribavirin-Experienced, Genotype 4 Patients With Compensated Cirrhosis
Page Retired 1/21/2021 Recommended and alternative regimens listed by evidence level and alphabetically for: Peginterferon/Ribavirin-Experienced, Genotype 4 Patients With Compensated Cirrhosisa…
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Peginterferon/Ribavirin-Experienced, Genotype 4 Patients Without Cirrhosis
Page Retired 1/21/2021 Recommended regimens listed by evidence level and alphabetically for: Peginterferon/Ribavirin-Experienced, Genotype 4 Patients Without Cirrhosis RECOMMENDED DURATION RATING…
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Treatment-Experienced Genotype 4
Page Retired 1/21/2021 The following pages include guidance for management of treatment-experienced patients with genotype 4 infection. Peginterferon/Ribavirin-Experienced, Genotype…
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Treatment-Naive Genotype 4
The following pages include guidance for management of treatment-naive patients with genotype 4 infection. Treatment-Naive Genotype 4 Without Cirrhosis Treatment-Naive…
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Treatment-Naive Genotype 4 With Compensated Cirrhosis
Recommended and alternative regimens listed by pangenotypic, evidence level and alphabetically for: Treatment-Naive Genotype 4 Patients With Compensated Cirrhosisa RECOMMENDED…
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Treatment-Naive Genotype 4 Without Cirrhosis
Recommended and alternative regimens listed by pangenotypic, evidence level and alphabetically for: Treatment-Naive Genotype 4 Patients Without Cirrhosis RECOMMENDED DURATION…
Genotype 5 or 6
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DAA-Experienced (Including NS5A Inhibitors Except Glecaprevir/Pibrentasvir Failures), Genotype 5 or 6 Patients, With or Without Compensated Cirrhosis
Page Retired 1/21/2021 (For glecaprevir/pibrentasvir treatment failures, please see that topic.) Recommended regimen for: DAA-Experienced (Including NS5A Inhibitors Except…
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Peginterferon/Ribavirin-Experienced, Genotype 5 or 6 Patients With or Without Compensated Cirrhosis
Page Retired 1/21/2021 Recommended regimens listed by evidence level and alphabetically for: Peginterferon/Ribavirin-Experienced, Genotype 5 or 6 Patients, With or Without…
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Treatment-Experienced Genotype 5 or 6
Page Retired 1/21/2021 The following pages include guidance for management of treatment-experienced patients with genotype 5 or 6 infection.…
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Treatment-Naive Genotype 5 or 6
Recommended and alternative regimens listed by pangenotypic, evidence level and alphabetically for: Treatment-Naive Genotype 5 or 6 Patients With and…
Mixed Genotypes
Rarely, genotyping assays may indicate the presence of a mixed infection (eg, genotypes 1a and 2). Treatment data for mixed genotypes with DAAs are sparse but utilization of a pangenotypic regimen is recommended in this circumstance (Chiu, 2020). When the correct combination or duration of treatment is unclear, expert consultation should be sought.

