Tsien Cynthia, Garber Ari, Narayanan Arvind, Shah Shetal N, Barnes David, Eghtesad Bijan, Fung John, McCullough Arthur J, Dasarathy Srinivasan
Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA.
J Gastroenterol Hepatol. 2014 Jun;29(6):1250-7. doi: 10.1111/jgh.12524.
Pre-transplant sarcopenia (reduced skeletal muscle mass) predicts poor outcome in cirrhosis. In contrast, whether muscle mass increases post-orthotopic liver transplantation (OLT) is not known and was studied prospectively.
Consecutive patients who underwent a comprehensive nutritional evaluation in a liver transplant nutrition clinic were included. Core abdominal muscle area was measured on abdominal computed tomography obtained pre- and post-OLT. Age- and gender-based controls were used to define sarcopenia. Measures of body composition pre-transplant were correlated with computed tomography measurements. Predictors and clinical impact of post-OLT change in muscle area were examined. In three subjects post-OLT and three controls, expression of genes regulating skeletal muscle mass were quantified.
During the study period, 53 patients (M:F 41:12; age 56.9 ± 7.5 years) were followed up after OLT for 19.3 ± 9 months. Five patients died and another five had acute graft rejection. Pre-OLT sarcopenia was present in 33 (66.2%). Pre-transplant clinical characteristics including Child's score, MELD score, and nutritional status or post-transplantation immunosuppression regimen did not predict post-transplant change in muscle mass. New onset post-OLT sarcopenia developed in 14 patients. Loss of muscle mass post-OLT increased risk of diabetes mellitus and a trend toward higher mortality. Skeletal muscle expression of myostatin was higher and that of ubiquitin proteasome proteolytic components lower post-OLT than in controls.
Post-transplantation sarcopenia is common and could not be attributed to pre-transplant characteristics or the type or duration of post-OLT immunosuppression. Post-transplant sarcopenia contributes to adverse consequences and strategies targeting myostatin may be beneficial.
移植前肌肉减少症(骨骼肌质量降低)预示着肝硬化患者预后不良。相比之下,原位肝移植(OLT)后肌肉质量是否增加尚不清楚,因此进行了前瞻性研究。
纳入在肝移植营养门诊接受全面营养评估的连续患者。在OLT前后获得的腹部计算机断层扫描上测量核心腹部肌肉面积。使用基于年龄和性别的对照来定义肌肉减少症。将移植前的身体成分测量值与计算机断层扫描测量值进行相关性分析。研究了OLT后肌肉面积变化的预测因素和临床影响。对3名OLT后患者和3名对照者的骨骼肌质量调节基因表达进行了定量分析。
在研究期间,53例患者(男:女为41:12;年龄56.9±7.5岁)在OLT后接受了19.3±9个月的随访。5例患者死亡,另有5例发生急性移植物排斥反应。33例(66.2%)患者存在OLT前肌肉减少症。移植前的临床特征,包括Child评分、终末期肝病模型(MELD)评分和营养状况,或移植后的免疫抑制方案,均不能预测移植后肌肉质量的变化。14例患者出现OLT后新发肌肉减少症。OLT后肌肉质量的丧失增加了患糖尿病的风险,并呈现出死亡率升高的趋势。与对照组相比,OLT后肌肉生长抑制素的骨骼肌表达较高,而泛素蛋白酶体蛋白水解成分的表达较低。
移植后肌肉减少症很常见,且不能归因于移植前特征或OLT后免疫抑制的类型及持续时间。移植后肌肉减少症会导致不良后果,针对肌肉生长抑制素的策略可能有益。