Ultra-rapid progression of MAFLD to cirrhosis and post-transplant steatosis in a patient with a polygenic risk profile.

Metabolic dysfunction-associated fatty liver disease (MAFLD) usually progresses slowly, but some patients experience exceptionally rapid deterioration. We report a 38-year-old woman who progressed from biopsy-confirmed steatosis to decompensated cirrhosis within 11 months and developed recurrent graft steatosis 8 months after liver transplantation. Genetic testing revealed heterozygous variants in PNPLA3, TM6SF2, MBOAT7, and GCKR, indicating a polygenic predisposition to lipid accumulation, inflammation, and fibrogenesis. Histology and imaging analyses showed progressive steatosis with bridging fibrosis before transplantation and severe recurrence within the graft after transplantation, highlighting that transplantation does not eliminate the underlying metabolic-genetic vulnerability. This case suggests that a polygenic background may contribute to ultra-rapid disease trajectories and supports integrating genetic profiling into diagnostic and prognostic evaluation for MAFLD. Awareness of such risk patterns may guide early surveillance and long-term metabolic management even after transplantation.