Fig. 2: SHGS tracks with MASLD progression, regression, and clinical outcomes.

A Deconvolution analysis in bulk liver RNA-seq data of the Duke MASLD human cohort (GSE213623, n = 368) demonstrated that SHGS is enriched in MASLD patients versus healthy controls. B SHGS enrichment scores correlate negatively with albumin levels, but positively with serum AST and Fib4 score in MASLD patients. C SHGS enrichment scores progressively increase with steatosis, hepatocyte ballooning, portal inflammation, and fibrosis severity during MASLD progression (GSE213623, n = 368). D SHGS was also applied to deconvolute liver transcriptomic data sets of MASLD patient cohorts from Germany (GSE33814, n = 44), Japan (GSE167523, n = 98) (H), USA (GSE49541, n = 72), and Europe (GSE135251, n = 216). In all cohorts, SHGS is more enriched in patients with MASH, and in patients with advanced liver fibrosis (F3F4) versus mild fibrosis (F0F1). E SHGS enrichment scores correlate with a high risk for primary MASLD-HCC (GSE193066, n = 106) and recurrent MASLD-HCC (GSE193080, n = 59). HCC risk was pre-determined using an etiology-agnostic prognostic liver signature (PLS) developed by Dr. Yujin Hoshida’s group. SHGS enrichment scores were reduced in (F) subsequent follow-ups after bariatric surgery (GSE83452, n = 25) and (G) statin treatment (GSE130991, n = 157) interventions that improve MASLD. Boxplots show the upper quantile (75%), median (50%), and lower quantile (25%) of overall data distribution (A, C, D, E, G). p-values were calculated using two-sided Wilcoxon’s rank-sum test in (A, C, D, E, G), Pearson’s correlation test in (B), and paired t-test in (F).