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

Abstract

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 advanced from biopsy-confirmed steatosis to decompensated cirrhosis within 11 months and developed recurrent graft steatosis eight 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 showed progressive steatosis with bridging fibrosis before transplant and severe recurrence in the graft, highlighting that transplantation does not remove 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.

Keywords

metabolic dysfunction-associated fatty liver disease / cirrhosis / liver transplantation / PNPLA3 / TM6SF2 / MBOAT7 / GCKR

Rights & permissions

Higher Education Press 2026

Just Accepted

This article has successfully passed peer review and final editorial review, and will soon enter typesetting, proofreading and other publishing processes. The currently displayed version is the accepted final manuscript. The officially published version will be updated with format, DOI and citation information upon launch. We recommend that you pay attention to subsequent journal notifications and preferentially cite the officially published version. Thank you for your support and cooperation.