CurrentPremera BluecrossPolicy 5.01.615

Pharmacologic Treatment of Chronic Non-Infectious Liver Diseases

Defines medical necessity criteria, prescriber and dosing limits, duration of approval, reauthorization requirements, and investigational exclusions for Iqirvo (elafibranor), Livdelzi (seladelpar), and Rezdiffra (resmetirom) when used to treat primary biliary cholangitis (PBC) and MASH-related fibrosis (F2-F3). Managed through the pharmacy benefit.

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Chronic Non-Infectious Liver Diseases

Policy CodePolicy 5.01.615

Change TypeCoverage removal and criteria updates (2026)

Effective DateMar 1, 2026

Next Review DateMar 1, 2026

Key ActionSubmit office visit notes documenting diagnosis, relevant history, physical evaluation and medication history demonstrating that medical necessity criteria are met.

SourceLink

POLICY UPDATE CHANGES

Ocaliva (obeticholic acid) coverage criteria removed as product withdrawn from market due to liver-related safety risks.

Updated Iqirvo, Livdelzi, and Rezdiffra criteria to remove requirement to exclude combination use with Ocaliva.

Added Livdelzi (seladelpar) coverage criteria for treatment of PBC (2025).

Added Iqirvo (elafibranor) coverage criteria (2024).

Rezdiffra (resmetirom) moved from Policy 5.01.605 to Policy 5.01.615 (2025) with no coverage changes.

3Drugs with covered indications in policy

1Drugs removed from policy (Ocaliva)

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Maximum approval duration (months)

Coverage summary

This policy (effective Mar. 1, 2026; last reviewed Feb. 23, 2026) defines pharmacy-managed coverage for three specific agents and indications: Iqirvo (elafibranor) and Livdelzi (seladelpar) for the treatment of primary biliary cholangitis (PBC), and Rezdiffra (resmetirom) for treatment of MASH with stage F2–F3 fibrosis. The policy specifies prescriber types, dosing limits, documentation and reauthorization requirements, and a maximum approval duration of 12 months when criteria are met. All other uses of Iqirvo, Livdelzi, and Rezdiffra not described in this policy are considered investigational. The policy notes removal of Ocaliva (obeticholic acid) from the policy following market withdrawal for liver-related safety risks.

Key thresholds & quick facts

Minimum age>= 18 years

ALP elevation for PBC diagnosisConsistently elevated for at least 6 months

Rezdiffra fibrosis eligibilityStage F2–F3 (no cirrhosis/F4)

Alcohol use limits for Rezdiffra<=15 drinks/week (male); <=10 drinks/week (female)

A1c requirement (if diabetic) for RezdiffraA1c < 9%

Iqirvo (elafibranor) dose limit80 mg once daily

Livdelzi (seladelpar) dose limit10 mg once daily

Rezdiffra (resmetirom) dose limit100 mg daily

Maximum approval durationUp to 12 months

Iqirvo (elafibranor) — PBC: Initial therapy (Medical necessity)

Iqirvo (elafibranor) — Primary Biliary Cholangitis (PBC) Medical Necessity

Iqirvo may be considered medically necessary in adults with PBC as adjunct to UDCA in inadequate responders or as monotherapy if unable to tolerate UDCA when ALL criteria are met:

ALL of the following

Individual is aged 18 years or older
Cirrhosis status
- Has PBC without cirrhosis
- Has PBC with compensated cirrhosis (Child-Pugh A) and no evidence of portal hypertension
Diagnosis is confirmed by consistently elevated alkaline phosphatase (ALP) for at least 6 months at time of diagnosis and ONE of: positive antimitochondrial (AMA) test; presence of sp100 or gp210 autoantibodies if AMA negative; OR liver biopsy consistent with PBC

Livdelzi (seladelpar) — PBC: Initial therapy (Medical necessity)

Livdelzi (seladelpar) — Primary Biliary Cholangitis (PBC) Medical Necessity

Livdelzi may be considered medically necessary in adults with PBC as adjunct to UDCA in inadequate responders or as monotherapy if unable to tolerate UDCA when ALL criteria are met:

ALL of the following

Individual is aged 18 years or older
Cirrhosis status
- Has PBC without cirrhosis
- Has PBC with compensated cirrhosis (Child-Pugh A) and no evidence of portal hypertension
Diagnosis is confirmed by consistently elevated alkaline phosphatase (ALP) for at least 6 months at time of diagnosis and ONE of: positive antimitochondrial (AMA) test; presence of sp100 or gp210 autoantibodies if AMA negative; OR liver biopsy consistent with PBC

Rezdiffra (resmetirom) — MASH (F2–F3): Initial therapy (Medical necessity)

Rezdiffra (resmetirom) — MASH with F2-F3 fibrosis Medical Necessity

Rezdiffra may be considered medically necessary for treatment of MASH with stage F2 or F3 fibrosis when ALL criteria are met:

ALL of the following

Individual is aged 18 years or older
Diagnosis: Has evidence of hepatic steatohepatitis and stage F2 or F3 fibrosis confirmed by a liver biopsy or a liver testF2 or F3 fibrosis
Additional baseline requirements
- Alcohol use: Consuming ≤15 standard drinks per week if male or ≤10 standard drinks per week if female

Continuation / Reauthorization criteria

For reauthorization, non-formulary exception reviews and other approvals for Iqirvo and Livdelzi may be granted up to 12 months when drug-specific criteria are met and submitted chart/office visit notes document that the individual continues to show a reduction in alkaline phosphatase (ALP) from baseline. For Rezdiffra, reauthorization may be approved up to 12 months when chart notes document a continued positive clinical response to therapy. Office visit notes should include diagnosis, relevant history, physical evaluation, and medication history to demonstrate that medical necessity criteria are met.

Reauthorization operational thresholds

Reauthorization documentation — PBC agents (Iqirvo/Livdelzi)Chart notes must show continued reduction in alkaline phosphatase (ALP) from baseline

Reauthorization documentation — RezdiffraChart notes must demonstrate continued positive clinical response to therapy

Typical reauthorization intervalAuthorizations (initial and reauthorization) may be approved up to 12 months when criteria met

Investigational / Not medically necessary

Investigational / Not Medically Necessary

All other uses not outlined in this policy

All other uses of Iqirvo (elafibranor), Livdelzi (seladelpar), and Rezdiffra (resmetirom) for conditions not outlined in this policy are considered investigational

Denial Risk

Investigational uses not covered

Claims for uses of Iqirvo (elafibranor), Livdelzi (seladelpar), and Rezdiffra (resmetirom) that are not specified in this policy are considered investigational and therefore not medically necessary.

Affected drugs: Iqirvo (elafibranor), Livdelzi (seladelpar), Rezdiffra (resmetirom)

Applicable codes

Codingmixed

No codes listed

Provider actions & operational requirements

Prior Authorization

Pharmacy benefit prior authorization

Drugs in this policy are managed through the pharmacy benefit. Non-formulary exception reviews and other reviews may be approved for up to 12 months when the applicable medical necessity criteria are met.

Documentation Required

Medical record documentation required

Submit office visit notes that document the diagnosis, relevant history, physical evaluation, and medication history to demonstrate that the medical necessity criteria are met.

Clinical evidence and trial summaries

51%Iqirvo ELATIVE primary composite biochemical response vs 4% placebo

15%Iqirvo ALP normalization at 12 months (Iqirvo vs 0% placebo)

61.7%Livdelzi RESPONSE POISE biochemical response vs 20% placebo; ALP normalization 25% vs 0%

36%/28%Rezdiffra Trial 1 Month 12: MASH resolution and fibrosis improvement higher with resmetirom (80/100 mg) vs placebo across pathologist readings

The evidence base includes surrogate and clinical endpoints: Iqirvo received accelerated FDA approval based on a surrogate biochemical composite endpoint driven by ALP reduction (ELATIVE trial showed 51% vs 4% for the composite biochemical response). Livdelzi's pivotal RESPONSE trial met biochemical response by POISE criteria (61.7% seladelpar vs 20% placebo, with ALP normalization 25% vs 0%). Rezdiffra's approval was supported by biopsy-based month-12 trial endpoints showing higher rates of MASH resolution and fibrosis improvement for resmetirom versus placebo. Limitations exist (surrogate endpoints, ongoing confirmatory trials, and variability in biopsy readings), and full trial publications and prescribing information should be consulted for detailed methods and outcomes.

Background and definitions

Background: The policy covers chronic non-infectious liver diseases including Primary Biliary Cholangitis (PBC) and Metabolic Dysfunction-Associated Steatohepatitis (MASH). Ursodeoxycholic acid (UDCA) is the first-line therapy for PBC; targeted agents (such as Iqirvo and Livdelzi) are considered second-line for inadequate UDCA responders or as monotherapy in UDCA-intolerant patients. Rezdiffra (resmetirom) is the FDA-approved therapy for MASH with stage F2–F3 fibrosis. The medications addressed in this policy are managed through the pharmacy benefit.

Term	Definition
PBC
Primary biliary cholangitis
UDCA
Ursodeoxycholic acid (first-line therapy for PBC)
MASH
Metabolic dysfunction-associated steatohepatitis
ALP
Alkaline phosphatase

Revision history

03/10/2020policy_created

Policy created (approved March 10, 2020) establishing criteria and adding Ocaliva (obeticholic acid) for PBC.

2021restriction

Ocaliva prescribing guidance restricted in 2021: contraindicated in PBC patients with decompensated cirrhosis, prior decompensation, or compensated cirrhosis with portal hypertension; AASLD warned about risks and recommended monitoring.

2024added

Added Iqirvo (elafibranor) coverage criteria; Ocaliva criteria updated to include a prescriber requirement, exclusion of combination use with Iqirvo, and a quantity limit.

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Chronic Non-Infectious Liver Diseases

Policy CodePolicy 5.01.615

Change TypeCoverage removal and criteria updates (2026)

Effective DateMar 1, 2026

Next Review DateMar 1, 2026

Key ActionSubmit office visit notes documenting diagnosis, relevant history, physical evaluation and medication history demonstrating that medical necessity criteria are met.

SourceLink

On This Page

ALP ≥ elevated for ≥6 months

Two of three AASLD diagnostic criteria also summarized elsewhere in policy

Exclusions: Diagnosis is not associated with a cholestatic drug reaction, complete biliary obstruction, sarcoidosis, or primary sclerosing cholangitis

UDCA trial requirement

Tried ursodeoxycholic acid (UDCA) for at least 1 year and had an inadequate response to UDCA therapy≥1 year trial
Tried UDCA and has documented intolerance to use of UDCA (eligible for monotherapy)

Prescriber: Iqirvo is prescribed by or in consultation with a gastroenterologist or hepatologist

Combination exclusion: Iqirvo will not be used in combination with Livdelzi (seladelpar)

Dose limit: Dose is limited to 80 mg once daily80 mg once daily

ALP ≥ elevated for ≥6 months

Exclusions: Diagnosis is not associated with a cholestatic drug reaction, complete biliary obstruction, sarcoidosis, and primary sclerosing cholangitis

UDCA trial requirement

Tried ursodeoxycholic acid (UDCA) for at least 1 year and had an inadequate response to UDCA therapy≥1 year trial
Tried UDCA and has documented intolerance to use of UDCA (eligible for monotherapy)

Prescriber: Livdelzi is prescribed by or in consultation with a gastroenterologist or hepatologist

Combination exclusion: Livdelzi will not be used in combination with Iqirvo (elafibranor)

Dose limit: Dose is limited to 10 mg once daily10 mg once daily

≤15/wk male; ≤10/wk female

Hep C viral load: Negative or undetectable hepatitis C viral load OR a suppressed hepatitis C viral load for 12 weeks prior to starting Rezdiffra (resmetirom)12 weeks suppressed or negative

Hemochromatosis exclusion: Does not have a diagnosis of hemochromatosis as defined by serum transferrin saturation ≥45% and serum ferritin above the normal rangetransferrin sat ≥45% and ferritin above normal => hemochromatosis

Wilson's disease: If individual is <30 years of age, the individual does not have a diagnosis of Wilson's diseaseage <30: exclude Wilson's disease

Diabetes control: If individual has type 2 diabetes mellitus, the individual has an A1c <9%A1c <9%

Obesity management: If body mass index ≥30, the individual is following diet modification using a dietary plan and has increased physical activity using a fitness planBMI ≥30: diet and fitness plan

No cirrhosis: Does not have cirrhosis (F4 fibrosis)No F4

Concomitant conditions: Is being treated for any concomitant conditions (e.g., cardiovascular disease, diabetes, dyslipidemia, and hypertension)

Prescriber: Rezdiffra is prescribed by or in consultation with an endocrinologist, gastroenterologist or hepatologist

Dose limit: Dose is limited to 100 mg daily100 mg daily

Step Therapy

UDCA trial requirement for PBC

For members with PBC, prior trial of ursodeoxycholic acid (UDCA) for at least 1 year with an inadequate response, or documented intolerance to UDCA, is required to qualify for Iqirvo or Livdelzi (eligible as adjunct to UDCA or as monotherapy if UDCA intolerant).

Billing Rule

Dose limits enforced

Authorization is contingent on adherence to the policy dose limits listed below.

Iqirvo (elafibranor): 80 mg once daily
Livdelzi (seladelpar): 10 mg once daily
Rezdiffra (resmetirom): 100 mg daily

Denial Risk

Investigational uses not covered

Uses of Iqirvo, Livdelzi, or Rezdiffra that are not described in this policy are considered investigational and therefore not medically necessary.

Documentation Required

Re-authorization documentation

For reauthorization: chart notes must document continued benefit — for Iqirvo and Livdelzi demonstrate continued reduction in alkaline phosphatase (ALP) from baseline; for Rezdiffra demonstrate continued positive clinical response to therapy.

2025added

Added Livdelzi (seladelpar) coverage criteria for treatment of PBC; updated Iqirvo and Ocaliva criteria to exclude combination use with Livdelzi; Rezdiffra (resmetirom) moved into this policy (Policy 5.01.615) from Policy 5.01.605.

2025revised

Updated Rezdiffra criteria to allow prescription by or in consultation with an endocrinologist, removed statin requirements, and clarified treatment of concomitant conditions.

2026removedLatest

Ocaliva (obeticholic acid) coverage criteria removed as the product was withdrawn from the market due to liver-related safety risks; material change flagged.

2026revisedLatest

Updated Iqirvo, Livdelzi, and Rezdiffra criteria to remove the requirement to exclude combination use with Ocaliva (reflecting Ocaliva withdrawal).