A systematic review and meta-analysis has identified fibrosis progression and systemic metabolic dysfunction as the main factors driving mortality in metabolic dysfunction–associated steatotic liver disease (MASLD). The findings were presented by Syed Muhammad Hassan Bukhari, MBBS, of Darlington Memorial Hospital NHS England, and colleagues at the British Association for the Study of the Liver (BASL) Annual Meeting 2026, with the abstract published in Gut, according to DocWireNews.
The team set out to examine which factors predict death and poor outcomes in MASLD, focusing on high-risk patient profiles, cardiometabolic burden, fibrosis stage and noninvasive markers. They also looked at predictors tied to liver-related and non-liver complications.
Why it matters
MASLD is a common chronic liver condition, and knowing which patients face the greatest risk of death could help clinicians decide who needs closer monitoring and earlier intervention. The review's central message is that fibrosis stage and overall metabolic health, rather than any single measure, carry the most weight in determining outcomes. The authors concluded that early identification of high-risk patients is essential to reduce future disease burden.
How the review was conducted
The researchers drew on studies indexed in PubMed and PubMed Central published between 2010 and 2026, following PRISMA guidelines for systematic reviews. Eligible studies reported mortality outcomes for patients with MASLD or nonalcoholic fatty liver disease (NAFLD), the condition's former name.
All studies were screened against predefined inclusion criteria. The team extracted data on fibrosis stage, liver stiffness, lean phenotype, cardiometabolic risk, type 2 diabetes (T2D), chronic kidney disease (CKD) and Fibrosis-4 (FIB-4) scores for qualitative analysis and pooled estimates. In total, 131 studies were included.
Fibrosis as the strongest signal
Among the measures examined, fibrosis stage stood out as the strongest predictor of mortality, according to the review. More advanced fibrosis was linked to a significant rise in both all-cause and liver-related deaths.
Noninvasive tools also showed predictive value. FIB-4 scores and other biomarkers were associated with unfavorable outcomes, suggesting these accessible tests may help flag patients at higher risk without requiring a biopsy.
Across the study populations, cardiovascular mortality was more prominent than mortality from liver-related causes, the investigators reported.
Metabolic conditions amplify risk
The analysis identified several factors that heighten risk, including cardiometabolic burden, chronic kidney disease and type 2 diabetes. The reviewers also noted that lean MASLD was associated with increased mortality despite a lower body mass index, a finding that challenges the assumption that risk tracks with weight alone.
Taken together, the results point to fibrosis progression and systemic metabolic dysfunction as the primary drivers of death in MASLD. The authors suggested that future risk stratification in MASLD care should incorporate assessments of both fibrosis and cardiometabolic burden.
The abstract's conclusions rest on pooled data from observational studies rather than a single trial, and the findings were presented in summary form at a conference. Even so, the review adds to a growing body of work urging clinicians to treat MASLD as a condition with consequences beyond the liver.
What to watch: whether these predictors are folded into routine risk-scoring tools and clinical guidance for MASLD, and how upcoming research tests whether earlier identification of high-risk patients translates into fewer deaths.
