CLINICAL BURDEN OF COMPENSATED METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS (MASH) CIRRHOSIS: A SYSTEMATIC LITERATURE REVIEW
Author(s)
Yestle Kim, MSc, PharmD1, latashree Goswami, MPH2, Atish De, MS2, Nipun Atreja, MS, PhD1, Karen Phillips, PharmD, BCPS1, Danielle Zielinski, PharmD1, Nandini Hadker, MA2.
1Madrigal Pharmaceuticals, West Conshohocken, PA, USA, 2Trinity Life Sciences, Waltham, MA, USA.
1Madrigal Pharmaceuticals, West Conshohocken, PA, USA, 2Trinity Life Sciences, Waltham, MA, USA.
OBJECTIVES: Compensated Metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis (MASH F4c) represents a substantial increase in clinical risk vs. earlier stages, yet data on this population have not been comprehensively synthesized. This systematic literature review was conducted to characterize MASH F4c clinical progression, highlighting progression from compensated to decompensated cirrhosis, hepatocellular carcinoma (HCC), liver transplant (LT), and mortality, identification of risk factors for progression, and predictors of fibrosis regression.
METHODS: Protocol and PRISMA-driven searches were conducted in Embase and PubMed (2017-February 2026 for articles; 2021-February 2026 for conference abstracts). Studies with adults with MASH F4c in the US, UK, France, Germany, Italy and Spain were included if they reported epidemiological, clinical, economic, or humanistic outcomes. Title/abstract and full text screening were performed in duplicate, and all extractions were conducted by one reviewer and independently validated by another. Study findings were synthesized narratively across natural history cohorts and interventional trials.
RESULTS: A total of 123 studies reporting aforementioned outcomes were identified. Across real-world and trial cohorts, MASH F4c showed rapid, predictable progression from compensated to decompensated cirrhosis, HCC, and LT (11% in Year 1 to 37% in Year 5 across all outcomes). Long-term mortality (72.2% over 20 years) was driven by both liver (37%) and non-liver (27%) causes (e.g., cardiovascular disease). Progression risk was consistently associated with greater fibrosis burden, portal hypertension, alongside age, frailty, and cardiometabolic comorbidities; presence of metabolic factors alone were insufficient in contributing to these risks. Across interventional studies, no pharmacotherapy demonstrated consistent cirrhosis reversal; however, fibrosis regression, when achieved, was strongly associated with fewer liver-related events and lower likelihood of progression to LT.
CONCLUSIONS: Evidence demonstrates rapid progression, high mortality and sustained risk due to LT, underscoring an urgency to manage/stabilize disease, and ultimately prevent progression and/or outcomes in MASH F4c. Additional studies are needed to understand the burden of disease.
METHODS: Protocol and PRISMA-driven searches were conducted in Embase and PubMed (2017-February 2026 for articles; 2021-February 2026 for conference abstracts). Studies with adults with MASH F4c in the US, UK, France, Germany, Italy and Spain were included if they reported epidemiological, clinical, economic, or humanistic outcomes. Title/abstract and full text screening were performed in duplicate, and all extractions were conducted by one reviewer and independently validated by another. Study findings were synthesized narratively across natural history cohorts and interventional trials.
RESULTS: A total of 123 studies reporting aforementioned outcomes were identified. Across real-world and trial cohorts, MASH F4c showed rapid, predictable progression from compensated to decompensated cirrhosis, HCC, and LT (11% in Year 1 to 37% in Year 5 across all outcomes). Long-term mortality (72.2% over 20 years) was driven by both liver (37%) and non-liver (27%) causes (e.g., cardiovascular disease). Progression risk was consistently associated with greater fibrosis burden, portal hypertension, alongside age, frailty, and cardiometabolic comorbidities; presence of metabolic factors alone were insufficient in contributing to these risks. Across interventional studies, no pharmacotherapy demonstrated consistent cirrhosis reversal; however, fibrosis regression, when achieved, was strongly associated with fewer liver-related events and lower likelihood of progression to LT.
CONCLUSIONS: Evidence demonstrates rapid progression, high mortality and sustained risk due to LT, underscoring an urgency to manage/stabilize disease, and ultimately prevent progression and/or outcomes in MASH F4c. Additional studies are needed to understand the burden of disease.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO148
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy, Relating Intermediate to Long-term Outcomes
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity)