Cause-specific mortality in 13,099 patients with metabolic dysfunction-associated steatotic liver disease in Sweden

BACKGROUND & AIMS: Data on cause-specific mortality in metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. We aimed to determine the rate and risk of death from different causes in patients with MASLD compared to the general population in Sweden. METHODS: In this population-based cohort study, we identified individuals with an ICD-10 code for MASLD in inpatient or specialized outpatient care using Swedish healthcare registers from 2002-2020 (n = 13,099) and matched them with up to 10 controls (median 9) from the general population for age, sex, municipality, and calendar year (n = 118,884). We used Cox regression to estimate adjusted hazard ratios (HRs) and 95% CIs for 11 different primary causes of death. 15-year cumulative incidences of death were calculated while accounting for competing risks. RESULTS: In total, 1,628 (12.4%) deaths occurred in patients with MASLD and 9,119 (7.7%) in controls during a median follow-up of 4.7 (IQR 2.0-9.2) and 5.8 years (IQR 2.7-10.5), respectively. MASLD was associated with higher all-cause mortality (HR 1.85, 95% CI 1.74-1.96) and higher rates of all specific causes of death except mental health disorder. The strongest associations were observed for non-hepatocellular carcinoma (HCC) liver-related (HR 26.9, 95% CI 19.4-37.3) and HCC-related (HR 35.0, 95% CI 17.0-72.1) mortality. However, the highest estimated 15-year cumulative incidences of death in patients with MASLD were for non-HCC cancer (7.3%) and cardiovascular disease (7.2%). CONCLUSIONS: MASLD was strongly associated with liver- and HCC-related mortality, but the absolute risks of death were highest for non-HCC cancer and cardiovascular disease. Mortality was increased for nearly all causes in patients with MASLD, suggesting that earlier multidisciplinary care is needed to reduce excess mortality. IMPACT AND IMPLICATIONS: Previous studies on mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) were either small, restricted to liver-related mortality, relied on liver biopsy to identify patients (thus inducing selection bias), or mainly used data from old cohorts. In a nationwide cohort study of all patients diagnosed with MASLD in inpatient or specialized outpatient care in Sweden between 2002 and 2020, we found a nearly doubled all-cause mortality rate and higher mortality than the general population from a wide range of causes, indicating that earlier multidisciplinary care may be needed to reduce premature mortality in patients with MASLD. The absolute risk estimates of death in our study may be useful for clinicians and policymakers to inform patients about their prognosis and potentially implement clinical or public health strategies to reduce premature mortality.