What is the life expectancy of someone with MASLD (Multisystem Autoimmune Syndrome with Lipodystrophy)?

Life Expectancy in MASLD

Individuals with MASLD in the general population have an increased all-cause mortality of 17.05 per 1,000 person-years compared to matched controls, though the majority of deaths are from cardiovascular disease rather than liver-related causes. 1

Mortality Risk Stratification by Disease Stage

Simple Steatosis Without Fibrosis

• MASLD without significant fibrosis does not substantially reduce life expectancy in the general population 1
• The condition may remain benign in 70-75% of cases without progression to inflammation or fibrosis 2
• However, MASLD is associated with a 34% increased risk of extrahepatic outcomes (HR 1.34), primarily cardiovascular events 1

MASH (Metabolic Dysfunction-Associated Steatohepatitis)

• Liver-related mortality in biopsy-proven MASH reaches 25.6 per 1,000 person-years (range 6.3-103.8) 1
• Both MAFLD and MASLD definitions show an 18-19% increased risk of all-cause mortality (aHR 1.18-1.19) 3
• This mortality risk is primarily driven by cardiovascular disease, which remains the leading cause of death even in MASH patients 4

Advanced Fibrosis and Cirrhosis

• Fibrosis stage is the strongest predictor of mortality in MASLD 1
• Progression to cirrhosis occurs in only 3-5% of MASLD patients but typically takes more than 20 years 5
• Patients with advanced fibrosis (F3-F4) show a 71-81% increased risk of all-cause mortality (aHR 1.71-1.81) across all three nomenclature systems (NAFLD, MAFLD, MASLD) 3

Compensated Advanced Chronic Liver Disease (cACLD)

• The 5-year cumulative incidence of first decompensation in MASLD-related cACLD is 3.5% 6
• First decompensation increases the cause-specific hazard of liver-related death by 18.9-fold 6
• Among those experiencing first decompensation, the 5-year cumulative incidence of further decompensation is 43.9%, which further increases liver-related death risk by an additional 1.52-fold 6

Key Modifiers of Life Expectancy

Cardiometabolic Risk Factors

• Type 2 diabetes and obesity have the greatest impact on MASLD natural history and mortality 1
• Hypertension increases all-cause mortality risk by 42% (aHR 1.42) 7
• Pre-diabetes or diabetes increases mortality by 28% (aHR 1.28) 7
• Hypertriglyceridemia adds a 19% increased mortality risk (aHR 1.19) 7
• The mortality risk increases proportionally with the number of cardiometabolic risk factors present 1

Age and Sex Considerations

• Males aged >50 years and postmenopausal women face increased risk of progressive fibrosis and cirrhosis complications 1
• Higher mortality risk for MASLD is particularly observed among older adults (≥65 years) and non-Hispanic whites 3
• Younger adults with MASLD show increasing cardiometabolic burden, necessitating early intervention 7

Hepatocellular Carcinoma (HCC)

• HCC independently increases the cause-specific hazard of liver-related death by 2.95-fold in the overall MASLD cohort 6
• Even after first decompensation, HCC further increases liver-related death risk by 1.43-fold 6
• MASLD has become the top indication for liver transplant in the United States for those with HCC and women 4

Extrahepatic Mortality Burden

Cardiovascular Disease

• Cardiovascular disease remains the most common cause of death in MASLD patients, not liver disease 4
• MASLD increases the risk of non-fatal cardiovascular disease by 40% (HR 1.40) 1
• Coronary heart disease risk increases by 33% (OR 1.33) 1
• Heart failure risk increases by 50% (OR 1.5) 1

Other Extrahepatic Complications

• Chronic kidney disease risk increases by 43% (HR 1.43) 1
• Type 2 diabetes risk increases by 119% (HR 2.19) 1
• Diabetes-related peripheral polyneuropathy risk increases by 148% (HR 2.48) 1
• Increased risk of extrahepatic cancers, particularly thyroid and gastrointestinal malignancies 1

Post-Liver Transplant Outcomes

• Obesity after liver transplantation is independently associated with a 2-fold higher mortality risk 1
• Recurrence rates at 5 years post-transplant for MASLD patients: metabolic syndrome (86%), steatosis (80%), steatohepatitis (60%), and advanced fibrosis (20%) 1
• Cardiovascular complications are the second most common cause of non-hepatic mortality in liver transplant recipients 1

Clinical Implications for Prognosis

The projected MASLD prevalence in adults will increase to over 55% by 2040, emphasizing the growing public health burden 4. Without aggressive management of cardiometabolic risk factors—particularly diabetes, hypertension, and obesity—life expectancy will be most significantly impacted by cardiovascular events rather than liver failure in the majority of MASLD patients 1, 4. However, the subset progressing to advanced fibrosis and cirrhosis faces substantially reduced survival, with decompensation events serving as critical inflection points that dramatically worsen prognosis 6.