Cause-specific mortality across ICD10 chapters in steatotic liver disease stratified by subtypes and fibrosis status

Background and aimsTo examine the associations between Steatotic liver disease (SLD), its subtypes (MASLD, MetALD, ALD), fibrosis stages and mortality from a broad spectrum of diseases. MethodsWe analysed 486156 UK Biobank participants. We summarised the causes of death during follow-up, by SLD status and subtypes. Multivariable Cox models estimated associations between SLD, SLD subtypes, FIB4 score, and cause-specific mortality outcomes across ICD10 disease categories. ResultsAmong 178336 participants with SLD, 20766 died over a median follow up of 13.8 years. The leading causes of deaths were neoplasm (46.4%), circulatory disease (24.2%), respiratory disease (7.0%), and digestive disease (4.8%). Compared to participants without SLD (n=307820), those with SLD had significantly higher mortality from neoplasm (HR 1.24 (1.20, 1.28)), circulatory (1.57 (1.50, 1.64)), and digestive disease (1.85 (1.67, 2.05)), as well as from metabolic, and genitourinary diseases, across all FIB4 score levels. Elevated risks were also observed for mortality from diabetes (3.40 (2.59, 4.46))), Covid-19 (1.97 (1.76, 2.21)), myocardial infarction (1.69 (1.53, 1.86)), stroke (1.24 (1.04, 1.48)), and several cancers, such as breast (1.50 (1.35, 1.68)), colorectal (1.22 (1.11, 1.34)), and prostate cancer (1.22 (1.09, 1.37)). SLD subtypes exhibited distinct patterns of cause-specific mortality. ConclusionSLD is associated with increased mortality across a wide range of disease categories, with extrahepatic cancers and circulatory diseases being the primary contributors. These findings underscore the importance of multidisciplinary management strategies targeting liver fibrosis, cardiometabolic burden, and cancer prevention in individuals with SLD. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/25342903v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1ee89c0org.highwire.dtl.DTLVardef@195a679org.highwire.dtl.DTLVardef@1e45af3org.highwire.dtl.DTLVardef@10f4503_HPS_FORMAT_FIGEXP M_FIG C_FIG