Chronic Hepatitis C (HCV)

POLICY NUMBER

L.5.01.411

Epclusa (sofosbuvir/velpatasvir)

Harvoni (ledipasvir/sofosbuvir)

Mavyret (glecaprevir/pibrentasvir)

Pegasys (peginterferon alfa-2a)

Ribavirin

Sovaldi (sofosbuvir)

Vosevi (sofosbuvir/velpatasvir/voxilaprevir)

Zepatier (elbasvir/grazoprevir)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Hepatitis C virus (HCV) can cause both acute and chronic hepatitis. The acute process is self-limited, rarely causes hepatic failure, and usually leads to chronic infection. Chronic HCV infection often follows a progressive course over many years and can ultimately result in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation.

HCV antiviral therapy is the cornerstone of treatment of chronic HCV infection. Other general measures in the management of patients with chronic HCV include psychologic counseling, symptom management, dose adjustment of medications, and screening for complications of cirrhosis. Treatment is recommended for all patients with acute or chronic HCV infection, except those with a short life expectancy that cannot be remediated by HCV therapy, liver transplantation, or another directed therapy. Patients with a short life expectancy owing to liver disease should be managed in consultation with an expert. The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences, including end-stage liver disease and hepatocellular carcinoma, by the achievement of virologic cure as evidenced by a sustained virologic response (SVR). SVR (defined as the absence of detectable RNA for at least 12 weeks after completion of therapy) is associated with 97 to 100% chance of being HCV RNA negative during long-term follow-up and can, therefore, be considered a cure of the HCV infection. Attaining an SVR has been associated with decreases in all-cause mortality, liver-related death, need for liver transplantation, hepatocellular carcinoma rates, and liver-related complications, even among those patients with advanced liver fibrosis.

The decisions on when to treat a patient with chronic HCV infection and which regimen to use is based upon several factors, including the infecting genotype, the natural history and stage of the disease, the expected efficacy of therapy, prior treatment history, potential side effects of and ability to tolerate the appropriate treatment regimen. Evaluation prior to management decisions should focus on these factors.

FDA Approved Indications

Direct Acting Antivirals (DAAs):

• Epclusa (sofosbuvir/velpatasvir) is indicated for the treatment of adult patients and pediatric patients 3 years of age and older with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis and with decompensated cirrhosis for use in combination with ribavirin.

• Harvoni (ledipasvir/sofosbuvir) is indicated for the treatment of adults and pediatric patients 3 years of age and older with chronic HCV genotype 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis, genotype 1 infection with decompensated cirrhosis for use in combination with ribavirin, and genotype 1 or 4 infection who are liver transplant recipients without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.

• Mavyret (glecaprevir/pibrentasvir) is indicated for the treatment of adult and pediatric patients 3 years and older with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) and for the treatment of adult and pediatric patients 3 years and older with HCV genotype 1 infection who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor (PI), but not both.

• Sovaldi (sofosbuvir) is indicated for the treatment of genotype 1, 2, 3 or 4 chronic HCV infection without cirrhosis or with compensated cirrhosis as a component of a combination antiviral treatment regimen and for the treatment of genotype 2 or 3 in pediatric patients 3 years of age and older without cirrhosis or with compensated cirrhosis for use in combination with ribavirin.

• Vosevi (sofosbuvir/velpatasvir/voxilaprevir) is indicated for the treatment of adult patients with chronic HCV infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor or genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.

• Zepatier (elbasvir/grazoprevir) is indicated for the treatment of chronic HCV genotype 1 or 4 infection in adult and pediatric patients 12 years of age and older or weighing at least 30kg.

Pegylated interferon:

• Pegasys (peginterferon alfa-2a), as part of a combination regimen with other HCV antiviral drugs, is indicated for the treatment of adults with chronic HCV and compensated liver disease. Pegasys, in combination with ribavirin, is indicated for treatment of pediatric patients 5 years of age and older with chronic HCV and compensated liver disease. Pegasys monotherapy is only indicated for the treatment of patients with chronic HCV and compensated liver disease if there are contraindications or significant intolerance to other HCV antiviral drugs. Pegasys alone or in combination with ribavirin without additional HCV antiviral drugs is not recommended for treatment of patients with chronic HCV who previously failed therapy with an interferon-alfa. Pegasys is not recommended for treatment of patients with chronic HCV who have had solid organ transplantation.

Ribavirin:

• Ribavirin capsules in combination with interferon alfa-2b (pegylated and nonpegylated) are indicated for the treatment of patients 3 years of age and older with chronic HCV infection with compensated liver disease.

• Ribavirin tablets in combination with peginterferon alfa-2a are indicated for the treatment of patients 5 years of age and older with chronic hepatitis HCV infection who have compensated liver disease and have not been previously treated with interferon alpha.

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. 

Initial Evaluation

The requested formulary agent may be considered medically necessary when ALL of the following criteria are met:

1. ONE of the following:

   1. The individual has a documented FDA-labeled indication for treatment with the requested agent and documentation of ALL of the following has been submitted for review:

      1. HCV RNA level;

      2. Infecting genotype for those in whom it may alter treatment recommendations;

      3. Complete blood count (CBC);

      4. Hepatic function panel (i.e. albumin, total and direct bilirubin, ALT, AST);

      5. Estimated glomerular filtration rate (eGFR);

      6. International normalized ratio (INR);

      7. Cirrhosis assessment (i.e. ultrasound, FIB-4 score, FibroScan, FibroSure, or liver biopsy); AND

      8. Prior treatment history; OR

   2. The individual is the recipient of an organ from an HCV-viremic donor and the request is for glecaprevir/pibrentasvir or sofosbuvir/velpatasvir;

2. The individual has been evaluated for HIV and hepatitis B virus ([i.e., hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and total hepatitis B core antibody (anti-HBc)], and the results have been discussed with member/treatment offered when appropriate;

3. If the screening for HBV was positive for current or prior HBV infection, the prescriber will monitor the individual for HBV flare-up or reactivation during and after treatment with the requested agent;

4. The individual has received counseling regarding ALL of the following:

   1. Abstinence of alcohol and substance use;

   2. Vaccination against hepatitis A, hepatitis B, and/or pneumococcal, as appropriate;

   3. Measures to prevent HCV transmission; AND

   4. Medication adherence, potential drug-drug interactions, and adverse events;

5. The requested agent is being prescribed by, or in consultation with, a Board Certified Gastroenterologist, Board Certified Infectious Disease Specialist, or a Transplant Hepatologist or by a Nurse Practitioner collaborating with a Board Certified Gastroenterologist, Board Certified Infectious Disease Specialist, or Transplant Hepatologist;

6. Surveillance for hepatocellular carcinoma and esophageal varices will be performed for individuals with cirrhosis;

7. The individual does not have any contraindication(s) to therapy with the requested agent; AND

8. The prescribed dosage is within the program quantity limits based on the individual’s age and FDA-approved labeled dosage.

Length of Approval: 8 – 48 weeks

POLICY EXCEPTIONS

State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B. appropriate with regard to standards of good medical practice; and

C. not solely for the convenience of the Member, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

POLICY HISTORY

11/19/2003: Approved by external gastroenterology consultants.

12/18/2003: Code Reference section completed.

11/02/2005: Description section updated, Off Label Uses and Renal carcinoma deleted. Policy section updated; changed preferred provider to CuraScript. 

11/4/2005: Code Reference section updated, HCPCS codes J8499, J9213, J9214 moved from the CPT4 code section in the table to the HCPCS code section, a deletion date of 6/30/2005 was added to codes J9213 and J9214; HCPCS codes S0145 and S0146 added with an effective date of 7/1/2005; the Non-Covered Codes table was deleted from the policy.

11/2005: Approved by Pharmacy & Therapeutic (P&T) Committee.

6/29/2006: CuraScript fax number changed from 1-877-462-6234 to 1-866-239-5502.

5/5/2008: Ribavirin dosing information updated.

01/01/2009: CuraScript preferred provider information removed. BCBSMS information added.

12/29/2008: Code Reference section updated per 2009 CPT/HCPCS revisions.

4/14/2009: Policy statement updated to reflect retreatment guidelines.

8/18/2009: Policy updated: Policy statement updated to include statement Peg-Intron® may be considered medically necessary only after failed treatment (nonresponder or relapser) with Pegasys®. Dosing Genotype 1, 2 and 3 deleted.

10/21/2010: Policy description unchanged. Policy statement updated regarding Infergen dosing.

09/15/2011: Policy revised to add Incivek® and Victrelis® and criteria for treatment with triple therapy.

04/01/2014: Policy statement updated regarding treatment with Sovaldi®. Removed deleted HCPCS codes J9213 and J9214 from the Code Reference section.

03/06/2015: Effective 03/15/2015. Policy extensively re-written. Policy description updated regarding HCV prevalence, transmission, and treatments. Policy statement updated with the following: 1) Before an antiviral therapeutic regimen will be approved, patients seeking treatment for Hepatitis C must be evaluated and treated by a Board Certified Gastroenterologist, Board Certified Infectious Disease Specialist, or a Transplant Hepatologist or by a Nurse Practitioner-Board Certified whose collaborating physician is a Board Certified Gastroenterologist, Board Certified Infectious Disease Specialist, or Transplant Hepatologist. This evaluation will be for 6 months, unless the patient meets the criteria for immediate treatment. 2) Antiviral therapeutic regimen must be ordered by a Board Certified Gastroenterologist, Board Certified Infectious Disease Specialist, or a Transplant Hepatologist or by a Nurse Practitioner-Board Certified whose collaborating physician is a Board Certified Gastroenterologist, Board Certified Infectious Disease Specialist, or Transplant Hepatologist. 3) Medical management requirements added. 4) Criteria added to state when immediate treatment with antiviral medication may be considered medically necessary. 5) Added requirements for a SVR 12 weeks after completion of therapy. 6) Added not medically necessary policy statement for terminally ill patients. 7) Added statement that Harvoni® and Sovaldi® are the formulary treatment regimens for HCV infection. 8) Added table of Antiviral Medication Treatment Regimens by genotype. Definition of "medically necessary" and "investigative" updated in the policy guidelines. Added HCPCS codes J9213, J9214, and S0148 to the Code Reference section and removed J9212 and S0146.

06/18/2015: Policy statement regarding direct or indirect assessment of natural history and stage of the liver disease clarified. Fibrosis stage can be assessed directly or indirectly through history, physical exam, medically necessary laboratory tests, or medically necessary imaging studies (eg, ultrasound, magnetic resonance imaging, computed tomography scan). Multianalyte assays with algorithmic analyses (eg, FibroSURE™ FibroSpect) are considered investigational for the evaluation or monitoring of patients with chronic liver disease. The use of non-invasive imaging, including but not limited to transient elastography (eg, FibroScan), magnetic resonance elastography, acoustic radiation force impulse imaging (ARFI; eg, Acuson S2000), or real-time tissue elastography, is considered investigational for the evaluation or monitoring of patients with chronic liver disease. Added link to the Non-invasive Techniques for the Evaluation and Monitoring of Patients With Chronic Liver Disease medical policy.

08/21/2015: Code Reference section updated for ICD-10.

05/26/2016: Policy number L.5.01.411 added.

07/11/2016: Policy updated to include Olysio®, Viekira Pak™, Daklinza™, Technivie™, and Zepatier™. Policy description updated regarding FDA approved Anti-HCV agents. Policy statement regarding medical management of Chronic Hepatitis C was revised to make the following changes: 1) to state that fibrosis stage can be assessed directly or indirectly 2) to remove the statement regarding multianalyte assays with algorithmic analyses, and 3) to change "Diet" to "Alcohol and substance use counseling." Policy section regarding Antiviral Medication Treatment Regimens revised to remove table and list treatment by Drug, Genotype, and Patient Population. Sources section updated.

08/09/2016: Approved by Pharmacy & Therapeutics (P&T) Committee.

11/01/2016: Policy description updated to add Epclusa® as an FDA approved anti-HCV agent. Section D of the policy section updated to remove information regarding Sovaldi and Daklinza and add Epclusa information. Sources section updated.

01/23/2017: Section D of policy section updated to add indications for Harvoni Genotype 1. Effective 11/01/2016.

08/15/2017: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

11/15/2017: Policy description updated to add indications for Viekira Pak™, Viekira XR™, Mavyret™, and Vosevi™. Section D of policy section revised regarding treatment regimens for Epclusa and Harvoni. Added treatment regimens for Mavyret and Vosevi. Sources updated.

05/30/2018: Deleted outdated reference in Sources section.

01/22/2019: Added drug names to the top of the policy. Code Reference section updated to remove HCPCS code J9213.

06/30/2020: Added statement to perform a formulary drug search on the patient's member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member's benefit plan. Policy description updated to add that glecaprevir/pibrentasvir (MAVYRET™) is indicated for treatment in pediatric patients 12 years and older or weighing at least 45 kg. Policy section updated regarding Mavyret treatment regimens for patients 12 years of age and older or weighing > 45kg. Sources updated.

11/01/2020: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding FDA approved indications. Policy section extensively revised. Added the following statements: 1) Prior authorization is required; 2) The use of samples by a Member will not be considered current or stable therapy for purposes of Medical Policy review. Initial evaluation criteria updated. Added treatment regimens for Sovaldi, Viekira, and Zepatier. Added statement that treatment with antiviral medications is considered not medically necessary for terminally ill patients (life expectancy less than 12 months) due to other co-morbid conditions. Policy Exceptions updated regarding State Health Plan members. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders." Sources updated.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

01/14/2025: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy updated to remove the following drugs: Copegus (ribavirin), PEG-Intron® (peginterferon alfa-2b), Rebetol (ribavirin), Ribapak (ribavirin), Ribasphere (ribavirin), and Viekira Pak (ombitasvir/paritaprevir/ritonavir/dasabuvir). Policy description updated regarding treatment of HCV-infected persons. Revised list and updated indications of direct acting antivirals. Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necessary policy statement criteria extensively revised. Added length of approval for requested formulary agent. Policy Guidelines updated to add Child-Turcotte-Pugh (CTP) Classification of the Severity of Cirrhosis. Removed investigative definition. Sources updated. Code Reference section updated to remove HCPCS code S0148. Effective 03/15/2025.

12/02/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated with minor changes. Policy statement criteria updated regarding hepatitis B virus. Sources updated.

SOURCE(S)

1. Chopra S, Pockros P. Overview of the management of chronic hepatitis c virus infection. UpToDate, Conner RF (Ed), Wolters Kluwer. (Accessed on November 11, 2024).

2. Eplcusa prescribing information. Gilead Sciences, Inc. June 2024. Last accessed September 2025.

3. Harvoni prescribing information. Gilead Sciences, Inc. December 2024. Last accessed September 2025.

4. Mavyret prescribing information. AbbVie Inc. June 2025. Last accessed September 2025.

5. Pegasys prescribing information. pharmaand GmbH. August 2025. Last accessed September 2025.

6. Ribavirin tablet prescribing information. Aurobindo Pharma Limited. February 2024. Last accessed September 2025.

7. Ribavirin capsule prescribing information. Aurobindo Pharma Limited. February 2024. Last accessed September 2025.

8. Sovaldi prescribing information. Gilead Sciences, Inc. December 2024. Last accessed September 2025.

9. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Joint panel from the American Association of the Study of Liver Diseases and the Infectious Diseases Society of America. http://www.hcvguidelines.org/ (Accessed on November 11, 2024).

10. Vosevi prescribing information. Gilead Sciences, Inc. July 2025. Last accessed September 2025.

11. Zepatier prescribing information. Merck Sharpe and Dohme LLC. July 2024. Last accessed September 2025.

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document. 

Covered Codes

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