ModifiedPremera Blue Cross of WashingtonPolicy 5.01.636

Chronic Hepatitis B and D Antiviral Therapy

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This policy governs medical-necessity and prior-authorization criteria for selected antiviral drugs used to treat chronic hepatitis B virus and hepatitis D virus infection.

Policy Summary

PayerPremera Blue Cross of Washington

PolicyChronic Hepatitis B and D Antiviral Therapy

Policy CodePolicy 5.01.636

Change TypeModified

Effective DateNov 1, 2026

Last ReviewNov 1, 2026

Next Review DateN/A

Key ActionSubmit documentation showing that product-specific medical-necessity criteria are met for prior authorization.

SourceLink

POLICY UPDATE CHANGES

The policy title was changed from Chronic Hepatitis B Antiviral Therapy to Chronic Hepatitis B and D Antiviral Therapy.

Coverage criteria were added for Hepcludex (bulevirtide-gmod) for treatment of chronic hepatitis delta virus.

Coverage criteria for Pegasys (peginterferon alfa-2a) were moved from policy 5.01.636 to policy 5.01.664.

3Antiviral products with coverage criteria

Up to 12 monthsMaximum initial authorization period

Up to 12 monthsMaximum reauthorization period

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ModifiedPremera Blue Cross of WashingtonPolicy 5.01.636

Chronic Hepatitis B and D Antiviral Therapy

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Sign up for premerabluecrossofwashington Policy 5.01.636 alerts

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This policy governs medical-necessity and prior-authorization criteria for selected antiviral drugs used to treat chronic hepatitis B virus and hepatitis D virus infection.

Policy Summary

PayerPremera Blue Cross of Washington

PolicyChronic Hepatitis B and D Antiviral Therapy

Policy CodePolicy 5.01.636

Change TypeModified

Effective DateNov 1, 2026

Last ReviewNov 1, 2026

Next Review DateN/A

Key ActionSubmit documentation showing that product-specific medical-necessity criteria are met for prior authorization.

SourceLink

POLICY UPDATE CHANGES

The policy title was changed from Chronic Hepatitis B Antiviral Therapy to Chronic Hepatitis B and D Antiviral Therapy.

Coverage criteria were added for Hepcludex (bulevirtide-gmod) for treatment of chronic hepatitis delta virus.

Coverage criteria for Pegasys (peginterferon alfa-2a) were moved from policy 5.01.636 to policy 5.01.664.

3Antiviral products with coverage criteria

Up to 12 monthsMaximum initial authorization period

Up to 12 monthsMaximum reauthorization period

Minimum age for Baraclude coverage

Age 18+Minimum age for Hepcludex coverage

Pharmacy benefitBenefit application

Coverage Criteria Overview

Baraclude (entecavir) — Initial Therapy

Baraclude (entecavir) may be considered medically necessary when ALL of the following criteria are met:

ALL of the following

The individual is aged 2 years or older.
Has a confirmed diagnosis of chronic hepatitis B virus (HBV) infection.
ONE of the following
- Is aged 18 years or older with compensated or decompensated liver disease.
- Is aged 2 to 17 years with compensated liver disease.
ONE of the following
- Does not have a co-infection with human immunodeficiency virus (HIV).
- Has a co-infection with HIV and is receiving highly active antiretroviral therapy (HAART).
Has tried and had an inadequate response or intolerance to generic entecavir.

Hepcludex (bulevirtide-gmod) — Initial Therapy

Hepcludex (bulevirtide-gmod) may be considered medically necessary when ALL of the following criteria are met:

ALL of the following

The individual is aged 18 years or older.
Has a confirmed diagnosis of chronic hepatitis D virus (HDV) infection with a current positive HDV RNA test.
ONE of the following
- Is without cirrhosis.
- Has compensated cirrhosis (Child-Pugh A).

Vemlidy (tenofovir alafenamide) — Initial Therapy

Vemlidy (tenofovir alafenamide) may be considered medically necessary when ALL of the following criteria are met:

ALL of the following

The individual is aged 6 years or older.
Has a confirmed diagnosis of chronic hepatitis B virus (HBV) infection.
Has compensated liver disease.
ONE of the following
- Does not have a co-infection with human immunodeficiency virus (HIV).
- Has a co-infection with HIV and is receiving highly active antiretroviral therapy (HAART).

Continuation Therapy — Reauthorization

Continuation or reauthorization may be approved when ALL of the following criteria are met. All reviews for drugs listed in this policy may be approved for up to 12 months.

ALL of the following

The applicable medical necessity criteria for the requested drug continue to be met.
The individual continues to show a positive clinical response to therapy, such as a reduction in hepatitis B or D virus DNA levels.
Medical records submitted for review document that the medical necessity criteria are met.
The drug is prescribed and administered in accordance with the product's U.S. Food and Drug Administration (FDA) dosage and administration prescribing information.
The medications listed in this policy are subject to the product's FDA dosage and administration prescribing information.

Coding and Clinical Thresholds

HCPCSHCPCS

S0145

Injection, PEGylated interferon alfa-2A (Pegasys), 180 mcg per ml (code terminated 11/01/26)

Chronic hepatitis B duration

ThresholdHBsAg positive for at least 6 months

MarkerHepatitis B surface antigen (HBsAg)

ConditionChronic hepatitis B (CHB)

Immune-active CHB, HBeAg-positive

HBV DNA threshold>20,000 IU/mL

Serologic statusHBeAg-positive

Disease phaseImmune-active chronic hepatitis B

Prior Authorization and Submission Requirements

Prior Authorization

Drug-Specific Prior Authorization Required

Prior authorization is required for each listed medication. Requests are reviewed against the product-specific medical-necessity criteria and the product’s U.S. Food and Drug Administration (FDA) dosage and administration prescribing information.

Baraclude (entecavir)
Hepcludex (bulevirtide-gmod)
Vemlidy (tenofovir alafenamide)

Step Therapy

Generic Entecavir Trial Required Before Baraclude

Before Baraclude authorization, the individual must have tried generic entecavir and had an inadequate response or intolerance. Submit the trial history and the reason it was unsuccessful or not tolerated.

Applies to requests for Baraclude (entecavir).
Document the generic entecavir trial, inadequate response, or intolerance.

Clinical Background

Chronic hepatitis B (HBV) is a vaccine-preventable liver infection. Although most individuals recover, some develop chronic hepatitis B (CHB), which may initially be asymptomatic or cause nonspecific symptoms such as fatigue. Over time, chronic infection can progress to liver scarring (cirrhosis) and hepatocellular carcinoma. Antiviral therapies, including entecavir and tenofovir alafenamide, are used in appropriate individuals to suppress HBV replication and manage chronic disease.

Hepatitis D virus (HDV) cannot survive or spread independently and requires concurrent HBV infection for replication. Chronic HDV infection can accelerate liver damage, progression to cirrhosis, hepatocellular carcinoma, and mortality compared with HBV infection alone. This policy addresses medical-necessity and prior-authorization criteria for selected antiviral therapies used to treat chronic HBV and chronic HDV infection.

Clinical Definitions

Chronic hepatitis B (CHB)

HBsAg durationHBsAg positive for at least 6 months

HBV DNAVaries from undetectable to several billion IU/mL

HBeAg statusMay be positive or negative

ALT and/or ASTMay be normal or elevated

Liver findingsChronic hepatitis with variable necroinflammation and/or fibrosis on biopsy

Immune-tolerant chronic hepatitis B

HBsAg durationPresent for at least 6 months

Initial Therapy by Product

Baraclude Initial Therapy

Baraclude may be considered medically necessary when all criteria are met.

Baraclude criteria

The individual is aged 2 years or older and has a confirmed diagnosis of chronic hepatitis B virus (HBV) infection.Age >=2 years
Liver disease
- The individual is aged 18 years or older with compensated or decompensated liver disease.
- The individual is aged 2 to 17 years with compensated liver disease.
HIV status

Reauthorization

All reviews for drugs listed in this policy may be approved up to 12 months when the medical-necessity criteria are met and there is evidence the individual continues to show a positive clinical response to therapy.

Reauthorization criteria

The applicable medical-necessity criteria remain met.
The individual continues to show a positive clinical response to therapy, such as a reduction in hepatitis B or D virus DNA levels.

Required Prerequisite Therapy

Step	Required prior therapy	Medication requested	Required outcome
1	Try generic entecavir	Baraclude (entecavir)	Inadequate response or intolerance

Step	Required prior therapy	Medication requested	Applicable individuals and required outcome
1	Try generic tenofovir disoproxil fumarate	Vemlidy (tenofovir alafenamide)	Adults and pediatric individuals weighing at least 35 kg; inadequate response or intolerance

Policy Summary

PayerPremera Blue Cross of Washington

PolicyChronic Hepatitis B and D Antiviral Therapy

Policy CodePolicy 5.01.636

Change TypeModified

Effective DateNov 1, 2026

Last ReviewNov 1, 2026

Next Review DateN/A

Key ActionSubmit documentation showing that product-specific medical-necessity criteria are met for prior authorization.

SourceLink

On This Page

For adults and pediatric individuals who weigh at least 35 kg, has tried and had an inadequate response or intolerance to generic tenofovir disoproxil fumarate.>= 35 kg

Immune-active CHB, HBeAg-negative

HBV DNA threshold>2,000 IU/mL

Serologic statusHBeAg-negative

Disease phaseImmune-active chronic hepatitis B

Immune-tolerant CHB

HBV DNA thresholdTypically >1 million IU/mL

Serologic statusHBeAg positive

Disease phaseImmune-tolerant chronic hepatitis B

Inactive CHB

HBV DNA threshold<2,000 IU/mL

Serologic statusHBeAg negative and anti-HBe positive

Disease phaseInactive chronic hepatitis B

Step Therapy

Generic Tenofovir Disoproxil Fumarate Trial Required

For Vemlidy, adults and pediatric individuals who weigh at least 35 kg must have tried generic tenofovir disoproxil fumarate and had an inadequate response or intolerance before coverage can be considered.

Applies to adults and pediatric individuals weighing at least 35 kg.
Document the generic tenofovir disoproxil fumarate trial, inadequate response, or intolerance.

Documentation Required

Required Clinical Records

Submit medical records establishing the diagnosis, relevant treatment history, clinical findings, laboratory results, and medical necessity for the requested product.

Office visit notes containing the diagnosis, relevant history, physical evaluation, laboratory tests, and medication history.
Records must demonstrate that the applicable product-specific medical-necessity criteria are met.

Denial Risk

Failure to Meet Medical-Necessity Criteria May Result in Denial

Requests may be denied when the individual does not meet the product-specific age, diagnosis, liver-disease, HIV-management, laboratory, or prerequisite-therapy requirements.

Baraclude: individual must be at least 2 years old with confirmed chronic HBV; adults must have compensated or decompensated liver disease, while individuals ages 2–17 must have compensated liver disease; HIV co-infection requires highly active antiretroviral therapy (HAART), and generic entecavir must have produced an inadequate response or intolerance.
Hepcludex: individual must be at least 18 years old with confirmed chronic HDV and a current positive HDV RNA test, and must be without cirrhosis or have compensated cirrhosis (Child-Pugh A).
Vemlidy: individual must be at least 6 years old with chronic HBV and compensated liver disease; HIV co-infection requires HAART, and applicable adults and pediatric individuals weighing at least 35 kg must have failed or not tolerated generic tenofovir disoproxil fumarate.

Denial Risk

Positive Clinical Response Required for Reauthorization

Reauthorization may be approved for up to 12 months only when the applicable medical-necessity criteria continue to be met and records show a positive clinical response to therapy.

Document continued clinical benefit, such as a reduction in hepatitis B or D virus DNA levels.
Insufficient or undocumented response may result in denial of renewal.

HBV DNATypically >1 million IU/mL

ALT and/or ASTNormal or minimally elevated

Liver findingsNo fibrosis and minimal inflammation on biopsy or noninvasive testing

Immune-active CHB

HBsAg durationPresent for at least 6 months

HBV DNA, HBeAg-positive>20,000 IU/mL

HBV DNA, HBeAg-negative>2,000 IU/mL

ALT and/or ASTIntermittently or persistently elevated

Liver findingsModerate or severe necroinflammation, with or without fibrosis

Inactive CHB

HBsAg durationPresent for at least 6 months

SerologyHBeAg negative and anti-HBe positive

HBV DNA<2,000 IU/mL

ALT and/or ASTPersistently normal

Liver findingsNo significant necroinflammation; variable fibrosis may be present

Hepatitis B surface antigen (HBsAg)

LocationFound on the virus surface

MeaningHepatitis B surface antigen

InfectiousnessAll persons with HBsAg are infectious

HBV DNA

StructurePartially double-stranded DNA molecule

LocationFound in the inner core of the virus

InfectiousnessPersons with elevated HBV DNA are most infectious

HBeAg seroconversion

DefinitionLoss of HBeAg and detection of anti-HBe

Prior HBeAg statusPreviously HBeAg positive

Prior anti-HBe statusPreviously anti-HBe negative

Undetectable HDV RNA

DefinitionHDV RNA below the lower limit of quantification

LLOQ50 IU/mL

Target statusTarget not detected

Combined response

HDV RNA responseUndetectable HDV RNA or at least a 2-log10 IU/mL decline from baseline

ALT requirementALT normalization

Response typeCombined virologic and biochemical response

Virologic response

Undetectable HDV RNAQualifies as a virologic response

Alternative criterionAt least a 2-log10 IU/mL decline from baseline

ALT requirementALT normalization is not required for this definition

LLOQ

AbbreviationLLOQ

MeaningLower limit of quantification

Use in HDV RNA testingThe threshold used to define undetectable HDV RNA

The individual does not have a co-infection with human immunodeficiency virus (HIV).

The individual has HIV co-infection and is receiving highly active antiretroviral therapy.

The individual has tried and had an inadequate response or intolerance to generic entecavir.

Hepcludex Initial Therapy

Hepcludex may be considered medically necessary when all criteria are met.

Hepcludex criteria

The individual is aged 18 years or older.Age >=18 years
The individual has a confirmed diagnosis of chronic hepatitis D virus (HDV) infection with a current positive HDV RNA test.Current positive HDV RNA test
Cirrhosis status
- The individual is without cirrhosis.
- The individual has compensated cirrhosis (Child-Pugh A).Child-Pugh A

Vemlidy Initial Therapy

Vemlidy may be considered medically necessary when all criteria are met.

Vemlidy criteria

The individual is aged 6 years or older and has a confirmed diagnosis of chronic hepatitis B virus (HBV) infection.Age >=6 years
The individual has compensated liver disease.
HIV status
- The individual does not have a co-infection with human immunodeficiency virus (HIV).
- The individual has HIV co-infection and is receiving highly active antiretroviral therapy (HAART).
For adults and pediatric individuals who weigh at least 35 kg, the individual has tried and had an inadequate response or intolerance to generic tenofovir disoproxil fumarate.Weight >=35 kg for the applicable prior-treatment requirement