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<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive condition linked to obesity and insulin resistance, potentially leading to cirrhosis. While lifestyle intervention is a primary treatment, the molecular mechanisms driving the regression of advanced fibrosis remain poorly understood. We report a man in his 30&#xa0;s with severe obesity (BMI 35.2&#xa0;kg/m<sup>2</sup>) and advanced fibrosis (liver stiffness measurement [LSM] 18&#xa0;kPa) who underwent a 12-month caloric restriction and resistance training program. He achieved 33.8% weight loss while preserving skeletal muscle, resulting in normalized liver enzymes and an 80.6% reduction in LSM. Comparative serum proteomic analysis revealed that the “Neutrophil extracellular traps (NETs) formation” pathway was the most significantly upregulated, contrasting with downregulated metabolic pathways. Detailed mapping confirmed increased expression of NETosis-essential proteins, including peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), myeloperoxidase (MPO), and citrullinated histone H3 (citH3), alongside upstream signaling such as ROS, Akt/mTOR, and NADPH oxidase components. This case demonstrates that intensive lifestyle intervention can induce rapid regression of advanced fibrosis in MASLD. The transition from metabolic stress to NETosis activation indicates that neutrophil-mediated immune regulation may be a key driver in the systemic and hepatic remodeling process.</p>

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Rapid regression of advanced hepatic fibrosis in a patient with metabolic dysfunction-associated steatotic liver disease and severe obesity: a case report highlighting lifestyle-induced NETosis activation through serum proteomic analysis

  • 期刊论文

  • 发表日期：

    2026年5月6日

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  • Toru Nakamura,
  • Shigemune Bekki,
  • Dan Nakano,
  • Atsutaka Masuda,
  • Keisuke Amano,
  • Masahito Nakano,
  • Takumi Kawaguchi

摘要

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive condition linked to obesity and insulin resistance, potentially leading to cirrhosis. While lifestyle intervention is a primary treatment, the molecular mechanisms driving the regression of advanced fibrosis remain poorly understood. We report a man in his 30 s with severe obesity (BMI 35.2 kg/m2) and advanced fibrosis (liver stiffness measurement [LSM] 18 kPa) who underwent a 12-month caloric restriction and resistance training program. He achieved 33.8% weight loss while preserving skeletal muscle, resulting in normalized liver enzymes and an 80.6% reduction in LSM. Comparative serum proteomic analysis revealed that the “Neutrophil extracellular traps (NETs) formation” pathway was the most significantly upregulated, contrasting with downregulated metabolic pathways. Detailed mapping confirmed increased expression of NETosis-essential proteins, including peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), myeloperoxidase (MPO), and citrullinated histone H3 (citH3), alongside upstream signaling such as ROS, Akt/mTOR, and NADPH oxidase components. This case demonstrates that intensive lifestyle intervention can induce rapid regression of advanced fibrosis in MASLD. The transition from metabolic stress to NETosis activation indicates that neutrophil-mediated immune regulation may be a key driver in the systemic and hepatic remodeling process.