Subgroups of Steatotic Liver Disease Have Distinct Clinical Phenotypes.

Steatotic liver disease (SLD) describes a spectrum of liver disease caused by cardiometabolic risk factors (CMRF) and/or alcohol. We aimed to describe the effect of cumulative CMRF and alcohol in subgroups of SLD and compare clinical outcomes. Patients from a single centre with biopsy proven SLD were retrospectively included. Patients were classified according to consensus definitions into three subgroups of SLD. The risk of liver-related death or liver transplantation during follow-up was analysed considering competing risks. Outcomes were tabulated for ordinal groups of CMRF and alcohol intake. 726 patients were included: 516 (71%) had metabolic dysfunction-associated steatotic liver disease (MASLD), 85 (12%) MASLD with increased alcohol intake (MetALD), and 125 (17%) had ALD. Patients were followed up for a median of 60.5 months (IQR 29-84.5), during which time 64 (8.8%) patients died, including 23 liver-related deaths. Competing risk regression analysis showed that ALD was associated with higher risk of liver-related death sHR 8.47 (95% CI, 2.26-31.8, P = 0.002) compared to MASLD. The risk of major adverse liver outcomes or liver-related death increased with the number of CMRF and with alcohol, showing a synergistic effect of these factors on patient outcomes. Amongst patients with SLD, patients with ALD have the greatest risk of adverse liver outcomes. Conversely, liver-related outcomes are less common in MASLD in the short to medium-term. This emphasises the need to identify and treat alcohol misuse as an important risk factor for adverse outcomes.