Disease-Modifying Therapies for Metabolic Dysfunction–Associated Steatohepatitis

Key Messages

What Is the Issue?

• Metabolic dysfunction–associated steatohepatitis (MASH), an advanced stage of metabolic dysfunction–associated steatotic liver disease (MASLD), is emerging as a leading cause of liver cancer and transplant in Canada, with prevalence projected to rise.
• Management of MASH traditionally relies on lifestyle modifications, including diet and exercise. New disease-modifying therapies (DMTs) may target underlying disease mechanisms and promote fibrosis (liver scarring) regression from moderate disease stages.
• In Canada, the first DMT for MASH — a glucagon-like peptide-1 receptor agonist — received conditional regulatory approval in December 2025. In other countries, a glucagon-like peptide-1 receptor agonist and/or a thyroid hormone receptor–beta agonist (liver-directed thyroid hormone receptor therapy) have received conditional regulatory approval.
• In 2020, the annual cost of managing MASH and MASLD in Canada was an estimated $3.76 billion, largely driven by other medical conditions such as diabetes and cardiovascular disease.

What Did We Do?

• Canada’s Drug Agency sought to assess the readiness of health care systems in Canada for the potential introduction of DMTs for MASH. We summarized evidence and experiences along the current patient pathway for MASH, including specific system-level challenges and opportunities to improve care.
• We applied a mixed-evidence approach, combining targeted literature searches on health system readiness and diagnostic accuracy of noninvasive tests. Evidence was supplemented through consultations with clinical experts and engagement with patients, carers, and Indigenous people to capture contextual insights on care pathways, equity, and cultural considerations in anticipation of the potential introduction of DMTs in Canada.

What Did Canada’s Drug Agency Find?

The introduction of DMTs into clinical care for MASH in Canada may increase pressure on existing health care systems. Evidence and insights shared from clinical providers and patients on the MASH care pathway highlight areas that may constrain care integration and the uptake of DMTs.

• MASH is a progressive, multisystem disease that often involves complex care needs and interconnected comorbidities.
• As awareness and treatment options for MASH expand, there may be a need to strengthen diagnostic capacity and improve access to specialists who typically treat advanced MASH across jurisdictions.
• Clinical guidance is evolving to support earlier risk identification and management across the disease spectrum, reflecting a shift from a historical focus on late-stage disease toward earlier intervention.
• People with low-risk MASH may be monitored. Earlier and more proactive care may help prevent or slow MASH progression.
• Emerging MASH care pathways emphasize coordinated, multidisciplinary care to support patients with complex needs across specialties.

What Does This Mean?

The report highlights system-level opportunities to improve how MASH is identified and managed in Canada as new DMTs emerge. Strengthening MASH care would require greater coordination. Processes could be standardized and consolidated to prepare for rising demand. Evidence and engagement feedback point to a few high-level priorities, including:

• strengthening awareness and education about MASH and its multisystemic nature to support early identification and reduce stigma
• increasing diagnostic testing capacity to enable earlier and timely identification
• expanding and standardizing multidisciplinary care models to improve coordination and continuity and to support patients with complex metabolic and liver needs
• embedding equity considerations across the care pathway.