Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia, USA.
Division of Gastroenterology and Hepatology, Hunter-Holmes McGuire VA, Richmond, Virginia, USA.
Liver Int. 2022 Jun;42(6):1401-1409. doi: 10.1111/liv.15178. Epub 2022 Feb 24.
Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT).
Patients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation).
The two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p < .001), indicative of impaired FA utilization. In subgroup analysis of the NASH cohort, body mass index but not liver fat content (MRI-PDFF) was an independent predictor of fasting RQ. In NASH, fasting RQ inversely correlated with fat-free muscle volume and directly with visceral adipose tissue.
Reduced metabolic flexibility in patients transplanted for NASH cirrhosis may precede the development of non-alcoholic fatty liver disease after LT.
评估肝移植(LT)后代谢灵活性的变化。
纳入因非酒精性脂肪性肝炎(NASH)(n=35)和非 NASH(n=10)而接受 LT 的患者。选择 NASH 是因为这些患者发生代谢并发症的风险最高。使用全身量热法测量代谢灵活性,并以呼吸商(RQ)表示,RQ 的范围为 0.7(纯脂肪酸氧化)至 1.0 是(碳水化合物氧化)。
两组除 NASH 组肥胖和糖尿病的患病率较高外,其他特征相似。进餐后,两组的 RQ 均增加(即碳水化合物利用率增加),但 NASH 组的峰值 RQ 和达到峰值 RQ 的时间更高。NASH 患者的空腹 RQ 明显更高(0.845 比 0.772,p<0.001),表明脂肪酸利用受损。在 NASH 亚组分析中,体重指数而不是肝脂肪含量(MRI-PDFF)是空腹 RQ 的独立预测因子。在 NASH 中,空腹 RQ 与去脂肌肉量呈负相关,与内脏脂肪组织呈正相关。
NASH 肝硬化患者移植后代谢灵活性降低可能先于 LT 后发生非酒精性脂肪性肝病。