PNPLA3 and metabolic dysfunction-associated steatotic liver disease: To illustrate the potential clinical relevance of this finding, when the multivariate analysis was repeated subdividing the NAFLD cohort into those with mild fibrosis (F0–1) and advanced fibrosis (F2–4), carriage of each copy of the TM6SF2 rs58542926 C>T minor allele was associated consistently with a significant increased risk of advanced fibrosis, independent of gender, age at biopsy, BMI, T2DM and PNPLA3 rs738409 genotype across each cohort studied (Table 1).