Future research should evaluate larger multicenter experiences and assess if pharmacist-supported workflows are associated with treatment persistence, safety monitoring adherence, and clinical outcomes.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by the presence of macrovesicular steatosis in the setting of cardiometabolic risk factors.1 The more severe and progressive form of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), is characterized by lobular inflammation and hepatocellular injury or ballooning with or without fibrosis.2
MASH represents a growing source of liver-related morbidity and mortality in the United States. Prior to 2024, treatment options for MASH were limited to lifestyle modifications, such as diet and weight loss, with no pharmacologic therapies approved by the FDA.3 Off-label use of agents targeting cardiometabolic comorbidities, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), was common, but none were specifically indicated for MASH. In March 2024, resmetirom (Rezdiffra; Madrigal) became the first FDA-approved therapy for noncirrhotic MASH with moderate-to-advanced fibrosis following results from the MAESTRO-NASH trial (NCT3900429).4,5
Following approval, the American Association for the Study of Liver Diseases (AASLD) published practice guidance recommending serial liver function monitoring at 3, 6, and 12 months during the first year of therapy.6 However, implementation of this therapy in routine clinical practice presents several operational challenges, particularly surrounding laboratory monitoring and longitudinal follow-up. Although these recommendations provide a framework for safety monitoring, little real-world data exists regarding the implementation of these workflows or the operational burden associated with maintaining monitoring adherence.
At the University of North Carolina (UNC) Liver Center, an embedded clinical pharmacist practitioner (CPP), a pharmacist with delegated authority to manage medications and monitor under collaborative practice, supports resmetirom management through patient education, laboratory coordination, and longitudinal monitoring. This retrospective study evaluated real-world resmetirom monitoring practices before and after the publication of AASLD guidance.
A retrospective chart review was conducted among adult patients prescribed resmetirom within the UNC hepatology clinic between March 14, 2024, and August 1, 2025. The study was designed to evaluate laboratory monitoring practices and safety outcomes associated with resmetirom initiation before and after publication of AASLD guidance.
Patients were divided into 2 cohorts based on the timing of resmetirom initiation relative to the publication of AASLD guidance for monitoring. Cohort 1 (pre-guidance cohort) included patients who initiated resmetirom between March 14, 2024, and October 18, 2024. Cohort 2 (post-guidance) included patients who initiated resmetirom between October 19, 2024, and August 1, 2025.
The primary outcome evaluated time to the first liver function test (LFT) following resmetirom initiation. Secondary outcomes included completion of recommended LFT monitoring at 3, 6, and 12 months, documentation of laboratory reminder outreach, hepatotoxicity events, and treatment discontinuation.
A total of 98 patients met study inclusion criteria, including 28 in the pre-guidance cohort and 70 in the post-guidance cohort (Table 1). Median time to first LFT was numerically shorter in the post-publication of AASLD guidance group but did not significantly differ between groups (102.5 days vs 90 days; p = 0.12). Completion of recommended laboratory monitoring was numerically higher following publication of guidance, with 3-month, 6-month, and 12-month LFT completion rates increasing from 71.4% to 81.7%, 50.0% to 73.7%, and 42.9% to 53.6%, respectively.
Documentation of laboratory reminder outreach increased substantially in the post-guidance cohort (3.6% vs 43.7%; p < 0.001), reflecting increased workflow coordination required to maintain longitudinal monitoring. Hepatotoxicity events were uncommon overall (0% vs 4.3%) and no patients experienced documented liver failure or hepatic decompensation during the study period. Lower treatment discontinuation rates were observed in the post-guidance cohort (42.9% vs 18.6%; p=0.013). Gastrointestinal adverse effects represent the most common reason for discontinuation.
These findings demonstrate that implementation of resmetirom monitoring recommendations requires substantially more than simply prescribing therapy. Maintaining adherence to AASLD monitoring recommendations introduced meaningful operational workload involving laboratory ordering, patient outreach, reminder documentation, result review, and follow-up coordination. In busy hepatology practices, these responsibilities can become burdensome when managed solely by providers, particularly as the use of novel MASH therapies expands.
The embedded hepatology CPP played a central role in facilitating these processes through longitudinal patient follow-up and structured monitoring support. Under collaborative practice agreements, the hepatology CPP provides longitudinal medication management, patient education, laboratory ordering and review, adverse effect assessment, and coordination of follow-up. This model allows physicians and advanced practice providers to share the operational and clinical responsibilities associated with long-term monitoring while providing additional touchpoints for patients receiving novel therapies. Although patients received counseling regarding recommended monitoring at therapy initiation, a substantial proportion still required additional outreach to complete laboratory testing. The marked increase in documented reminders following the publication of AASLD guidance likely reflects the additional coordination required to maintain adherence to monitoring recommendations. Despite multiple reminders, some patients still did not complete recommended labs. Implementation of AASLD monitoring recommendations required substantially more than laboratory ordering alone, necessitating coordination of patient outreach, reminder documentation, laboratory completion, and longitudinal follow-up.
Although hepatotoxicity events were uncommon, the occurrence of laboratory abnormalities in a small proportion of patients supports continued surveillance during therapy. Lower discontinuation rates were observed in the post-guidance cohort; however, because the study was not designed to evaluate treatment persistence, the relationship between structured monitoring workflows and discontinuation remains uncertain. This finding represents an important area for future investigation.
Madison Owen, PharmD, is a clinical pharmacist at the UNC Medical Center in Chapel Hill.
Brianna Wagoner is a PharmD Candidate at the UNC Eshelman School of Pharmacy in Chapel Hill.
Jane Giang, PharmD, BCPS, BCGP, CPP, is a clinical pharmacist at the UNC Medical Center in Chapel Hill.
As additional therapies enter the MASH treatment landscape, pharmacists will likely play an increasingly important role in coordinating monitoring strategies, improving adherence to guidance recommendations, and supporting longitudinal disease management.
Future research should evaluate larger multi-center experiences with implementation of AASLD monitoring recommendations for resmetirom and explore whether pharmacist-supported workflows are associated with treatment persistence, safety monitoring adherence, and clinical outcomes. Additional investigation is also needed to better understand the relationship between structured follow-up processes and MASH treatment discontinuation, as well as the optimal integration of GLP-1 and GLP-1/glucose-dependent insulinotropic polypeptide therapies alongside resmetirom in patients with MASH and cardiometabolic disease.
