Incidence of Cardiovascular Events and Extrahepatic Malignancies in Steatotic Liver Disease Subgroups

People with metabolic dysfunction-associated steatotic liver disease (MASLD) or alcohol-related liver disease (ALD) are at increased risk of cardiovascular (CV) events and extrahepatic cancers. However, data on MASLD with increased alcohol intake (MetALD) are limited. We investigated the incidence of CV events and extrahepatic cancers across SLD subgroups.

Patients with histologically confirmed SLD were included. Incident CV events (heart failure, ischemic heart disease (IHD), cerebrovascular disease, peripheral vascular disease) and extrahepatic cancers were recorded. Five-year cumulative incidence and sHR were estimated using competing risk regression with death and transplantation as competing events.

739 patients were included: 525 (71%) MASLD, 88 (12%) MetALD and 126 (17%) ALD. Mean age was 51 ± 13 years and 63% were male. Advanced fibrosis (F ≥ 3) was present in 39%. Over a median follow-up of 6.3 (IQR 3.8-8.3) years, 75 (10.1%) patients died, and 60 incident CV events occurred, most commonly IHD (46.6%). Estimated five-year cumulative incidence of CV events was 5.3% in MASLD, 7.4% in MetALD and 3.2% in ALD. Extrahepatic cancers occurred in 55 patients, most frequently skin and prostate. Estimated five-year cumulative incidence of extrahepatic cancers was 3.4% in MASLD, 4.9% in MetALD and 4.3% in ALD. The SLD subgroup was not independently associated with CV events, but MetALD (sHR 2.43, p = 0.021) and ALD (sHR 1.96, p = 0.040) were independently associated with extrahepatic cancer risk.

In this cohort of biopsy-proven SLD, the risk of extrahepatic cancer was higher in patients with MetALD. These findings may reflect synergistic effects of metabolic risk and alcohol exposure.