Resmetirom Therapy for Metabolic Dysfunction-Associated Steatotic Liver Disease
Publication Date: October 17, 2024
Last Updated: October 22, 2024
Summary of Practice Recommendations
Patient Selection
- Resmetirom can be considered for treatment of adults with MASH and moderate to advanced liver fibrosis (consistent with F2-F3). Criteria for treatment eligibility include:
- Noninvasive liver disease assessment—preferably imaging-based test results—consistent with MASH with F2-F3, or
- Historical liver biopsy demonstrating MASH with F2-F3 (and without evidence of concomitant, histologically active autoimmune liver disease).
- The recommended dosage of resmetirom is 100 mg/d for persons who weigh 100 kg or more, or 80 mg/d for persons who weigh less than 100 kg.
- If resmetirom is used concurrently with a moderate cytochrome P450 2C8 inhibitor (eg, clopidogrel), the recommended dosage is 80 mg/d for persons who weigh 100 kg or more or 60 mg/d for persons who weigh less than 100 kg.
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Pretreatment Considerations
- Resmetirom is not recommended for persons with compensated or decompensated cirrhosis, concomitant uncontrolled active liver diseases (such as autoimmune hepatitis and primary biliary cholangitis), or ongoing alcohol consumption greater than 20 g/d for women or greater than 30 g/d for men.
- Thyroid function assessment is recommended before initiating resmetirom treatment. For persons with untreated hyperthyroidism or hypothyroidism, resmetirom initiation is not recommended until thyroid function is optimized.
- Resmetirom initiation is not recommended for patients with symptomatic gallstone-related conditions such as acute cholecystitis.
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On-treatment Monitoring
- Hepatic function panel testing should be obtained at baseline and at periodic intervals (eg, 3, 6, and 12 months) to determine response and adverse events while on resmetirom therapy. Resmetirom should be discontinued if hepatotoxicity develops, as defined by the AASLD drug-induced liver injury practice guidance.32 There are insufficient data to make a recommendation on monitoring after 12 months of resmetirom treatment but continued monitoring with hepatic function panel testing every 6 months is suggested.
- Among persons with known thyroid disease, standard laboratory monitoring (eg, TSH and free T4) per established guidelines is recommended while receiving resmetirom therapy.
- Resmetirom can be used concurrently with statins; however, practitioners should be aware of the maximum recommended daily dosages, including atorvastatin 40 mg/d, pravastatin 40 mg/d, rosuvastatin 20 mg/d, and simvastatin 20 mg/d. Continued attention to comorbidity management including hyperlipidemia is recommended, particularly if the statin dose is modified at the outset of resmetirom therapy.
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Determination of Efficacy and Futility*
- In persons whose treatment candidacy was determined by liver stiffness measurements (VCTE or MRE), a repeat measurement at 12 months of therapy is recommended to assess for treatment response. In the absence of resmetirom-specific data, the writing group suggests that improvement (or worsening) of VCTE of at least 25% or MRE of at least 20% from baseline represents a significant (ie, clinically meaningful) change beyond intraindividual measurement variability.
- Continuation of resmetirom treatment in persons with significant fibrosis improvement is recommended.
- Among persons with evidence of worsening liver disease at 12 months of treatment, discontinuation of resmetirom should be considered. These individuals can be identified by clinical data suggestive of worsening liver disease including consistent increase in ALT or fibrosis progression as assessed by NILDA.
- Among persons without clear evidence of liver disease improvement or worsening, the decision to continue therapy (pending longer-term data from ongoing studies) should be based on holistic assessment. Clinicians and patients should consider: the baseline fibrosis status and the potential benefit of slowing or stabilizing liver fibrosis even if no regression is noted; the individual comorbidity profile associated with progressive liver disease; concomitant therapy including adherence and response to lifestyle interventions; changes in liver biochemical and NILDA parameters; and adverse effects (if any) during resmetirom therapy.
*These recommendations are based on data at 52 weeks after resmetirom treatment initiation. Since the MAESTRO-NASH trial is ongoing, these recommendations may change when longer-term data become available. The decision to continue treatment beyond 12 months should be based on assessing whether a patient has evidence of improvement, worsening or treatment failure, or disease stabilization.
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Recommendation Grading
Disclaimer
The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.
Overview
Title
Resmetirom Therapy for Metabolic Dysfunction-Associated Steatotic Liver Disease
Authoring Organization
American Association for the Study of Liver Diseases
Publication Month/Year
October 17, 2024
Last Updated Month/Year
October 29, 2024
Supplemental Implementation Tools
Document Type
Guideline
Country of Publication
US
Document Objectives
This article serves as an update to the 2023 AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease.
Inclusion Criteria
Male, Female, Adolescent, Older adult
Health Care Settings
Ambulatory, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Treatment, Management
Diseases/Conditions (MeSH)
D065626 - Non-alcoholic Fatty Liver Disease
Keywords
nonalcoholic fatty liver disease, NAFLD, Resmetirom therapy, Resmetirom, steatotic liver disease
Source Citation
Chen VL, Morgan TR, Rotman Y, Patton HM, Cusi K, Kanwal F, Kim WR. Resmetirom therapy for metabolic dysfunction-associated steatotic liver disease: October 2024 updates to AASLD Practice Guidance. Hepatology. 2024 Oct 18. doi: 10.1097/HEP.0000000000001112. Epub ahead of print. PMID: 39422487.