Although some “disease modifiers” (Figure 3), including clinical (i.e., presence and clustering of the metabolic traits) [71], biological (transaminases levels) [92] and genetic (PNPLA3, TM6SF2, HSD17B13) [93,94] factors allow for a “general” estimation of the HCC risk, these approaches are not accurate enough to justify the implementation of the screening strategies in the absence of cirrhosis. This evidence concerns the gene TM6SF2 and Cirrhosis.