• “中国科技期刊卓越行动计划”中文领军期刊
  • 百种中国杰出学术期刊
  • 中国百强报刊
  • RCCSE中国核心学术期刊(A+)
  • 中国自然科学类核心期刊
  • 中国高校百佳科技期刊
  • 中国精品科技期刊
  • 中国科技论文统计源期刊
  • 中华医学会优秀期刊
  • 中国精品科技期刊顶尖学术论文(5000)项目来源期刊
  • 入选中国高质量科技期刊分级目录(消化病学)T1级
  • 入选《中国学术期刊影响因子年报(自然科学与工程技术)》Q1区
  • 入选《科技期刊世界影响力指数(WJCI)报告(2022)》
  • “中国科技期刊卓越行动计划”中文领军期刊
  • 百种中国杰出学术期刊
  • 中国百强报刊
  • RCCSE中国核心学术期刊(A+)
  • 中国自然科学类核心期刊
  • 中国高校百佳科技期刊
  • 中国精品科技期刊
  • 中国科技论文统计源期刊
  • 中华医学会优秀期刊
  • 中国精品科技期刊顶尖学术论文(5000)项目来源期刊
  • 入选中国高质量科技期刊分级目录(消化病学)T1级
  • 入选《中国学术期刊影响因子年报(自然科学与工程技术)》Q1区
  • 入选《科技期刊世界影响力指数(WJCI)报告(2022)》

肌肉减少症:肝移植的新挑战

徐骁, 陈昊, 鲁迪, 林祖源

徐骁, 陈昊, 鲁迪, 等. 肌肉减少症:肝移植的新挑战[J]. 中华消化外科杂志, 2021, 20(10): 1025-1030. DOI: 10.3760/cma.j.cn115610-20210909-00449
引用本文: 徐骁, 陈昊, 鲁迪, 等. 肌肉减少症:肝移植的新挑战[J]. 中华消化外科杂志, 2021, 20(10): 1025-1030. DOI: 10.3760/cma.j.cn115610-20210909-00449
Xu Xiao, Chen Hao, Lu Di, et al. Sarcopenia: a new challenge in liver transplantation[J]. Chinese Journal of Digestive Surgery, 2021, 20(10): 1025-1030. DOI: 10.3760/cma.j.cn115610-20210909-00449
Citation: Xu Xiao, Chen Hao, Lu Di, et al. Sarcopenia: a new challenge in liver transplantation[J]. Chinese Journal of Digestive Surgery, 2021, 20(10): 1025-1030. DOI: 10.3760/cma.j.cn115610-20210909-00449

肌肉减少症:肝移植的新挑战

基金项目: 

国家自然科学基金 81930016

国家杰出青年科学基金 81625003

详细信息
    通讯作者:

    徐骁,Email:zjxu@zju.edu.cn

Sarcopenia: a new challenge in liver transplantation

Funds: 

National Natural Science Foundation of China 81930016

National Science Foundation for Distinguished Young Scholars 81625003

More Information
  • 摘要:

    肝移植是终末期肝病病人的首选治疗手段。肌肉减少症是一种以肌肉量减低和肌肉功能减退为特征的骨骼肌疾病。在移植术前肝硬化、肝癌病人中,肌肉减少症是常见但易被忽视的并发症,其直接影响病人肝移植等待期间死亡及转归。针对肌肉减少症进行科学评判、精细化分层有望实现精准干预并改善肝移植受者的预后。在肝移植受者围手术期及中长期管理中,肌肉减少症的重要性日益突显,应纳入规范化临床诊断与治疗体系。笔者回溯国内外研究成果,全面阐述肝移植中肌肉减少症的研究进展,旨在提高我国对肝移植受者肌肉减少症的认知和重视。

    Abstract:

    Liver transplantation remains as the first choice treatment for patients with end stage liver diseases. Sarcopenia is a skeletal muscle disease characterized by loss of muscle mass and muscle function. As a common but easily overlooked complication, sarcopenia significantly influences the death and prognosis of recipients with cirrhosis and liver cancer waiting liver trans-plantation, which significantly influences the death and prognosis of those patients. Scientific evalua-tion and fine stratification of sarcopenia are expected to achieve precision intervention and improve prognosis of liver transplantation recipients.As sarcopenia is increasingly important in perioperative as well as medium and long‑term management of liver transplantation recipients, it should be incorporated into normalized clinical diagnosis and treatment system. The authors review the research results at home and abroad, and comprehensively expound the research progress of sarcopenia in liver transplantation, in order to improve the cognition of sarcopenia in liver transplan-tation recipients in China.

  • 1989年Rosenberg提出肌肉减少症的概念,其定义为与年龄增长相关的肌肉量减少,即原发性肌肉减少症[1]。随着对肌肉减少症研究的不断深入,肿瘤、肝硬化、糖尿病、尿毒症等慢性疾病导致的继发性肌肉减少症也逐渐受到关注。目前认为:肌肉减少症是一组多种病因导致的以肌肉量减低和肌肉功能减退为特征的全身性、进行性骨骼肌疾病[2]。预计到2050年,全世界受肌肉减少症影响的人数将从2010年的>5 000万人增加至≥2亿人,成为一个日益严重的公共卫生问题,将严重危害民众健康[3]。近年来,肝移植技术不断成熟,肝移植长期疗效逐步提升。受原发病、营养不良、持续炎症状态、高代谢状态的影响,40%~51%的肝移植等候者合并肌肉减少症[46]。同时,肌肉减少症已被证实是肝移植不良转归的有效预测指标[7]。然而,肝移植中肌肉减少症尚有诸多未解决的问题,包括肌肉减少症的临床评估方式、诊断的最佳临界值以及干预措施等。为此,北美肝移植肌肉减少症工作组于2019年制订有关肝移植肌肉减少症的专家共识[7]。肌肉减少症作为肝移植中不容忽视的新问题,需得到更多重视和研究。笔者回溯国内外研究成果,全面阐述肝移植中肌肉减少症的研究进展,旨在提高我国对肝移植受者肌肉减少症的认知和重视。

    尽管肌肉减少症的定义和诊断标准屡有更新,但尚无统一的国际标准。目前,较公认的是2010年欧洲老年肌肉减少症工作组(EWGSOP)的定义,即肌肉量减低,且肌肉功能减退[3]。近年的研究结果显示:与肌肉量比较,肌肉力量的降低更能有效预测病人预后。2019年EWGSOP提出肌肉力量而非肌肉量是肌肉减少症的主要决定因素,并基于体力程度对肌肉减少症的严重程度进行分类[2]

    根据EWGSOP的定义,肌肉减少症的评估包含肌肉量、肌肉力量、体力3个方面,目前评估肌肉量的方法包括CT检查、MRI检查、双能X射线吸收法、超声检查、生物电阻抗分析、人体测量法等;评估肌肉力量的指标包括非惯用手握力、屈膝和(或)伸膝肌肉力量、呼气流量峰值等;评估体力的方法包括简易体能状况量表、日常步速评估法、计时起立行走试验、爬楼试验、6 min步行距离试验、定时端坐起立试验等。

    在临床实践中,肝移植中心通常采用CT或MRI筛查肝癌并评估血管和胆道解剖结构以制订手术方案。与MRI检查比较,CT检查时间短、成本低,在临床实践中应用更广泛。目前发表有关肝移植中肌肉减少症的研究多采用CT检查,通过测量特定腰椎平面的骨骼肌面积与身高平方的比值,得到骨骼肌指数(skeletal musde index,SMI),或测量腰大肌面积与身高平方的比值,得到腰大肌指数(psoas muscle index,PMI)以诊断肌肉减少症。CT检查作为一种方便、快捷、应用广泛的影像学手段,能分辨身体各层面的组织成分,清晰显示肌肉边界,精确测量肌肉面积,被认为是量化移植候选者肌肉量的金标准和最佳手段[79]

    北美一项大型多中心研究采用CT检查测量第三腰椎平面的SMI,根据SMI与肝移植等候者等待期间生存时间的受试者工作特征曲线(receiver operating characteristic,ROC)确定男性SMI<50 cm2/m2,女性SMI<39 cm2/m2为肌肉减少症诊断标准。该标准与年龄以及终末期肝病模型(model for end stage liver disease,MELD)评分无关,与移植前病死率密切相关[10]

    基于此,2019年北美肝移植肌肉减少症工作组制订的专家共识将CT检查作为评估肝硬化病人肌肉减少症的最佳手段,将CT检查测定的SMI作为评估肌肉减少症的最佳指标,并将男性SMI<50 cm2/m2,女性SMI<39 cm2/m2作为等待肝移植终末期肝病病人肌肉减少症的诊断临界值[7]。笔者团队根据临床实践中病人的CT检查影像学特征,通过影像组学深度学习构建肝癌肝移植受者的预后预测模型,实现对受者生存情况个体化预测,从而指导临床治疗。

    除性别外,不同年龄、种族、基础疾病受者的肌肉状态也存在差异[11]。笔者推测:通过蛋白质组学、代谢组学等方法挖掘肌肉减少症生物标志物,结合影像组学,探索多因子智能诊断标准是实现病人预后精准分层的未来方向。

    移植前肌肉减少症是肝移植临床相关不良结局的良好预测指标。已有的研究结果显示:与未合并肌肉减少症的肝硬化病人比较,合并肌肉减少症病人的生命质量更差,肝功能失代偿风险更高[1213]。肌肉减少症病人在等待移植期间的病死率也更高[1318]。Meza‑Junco等[17]对116例肝癌肝移植受者持续评估的研究结果显示:肌肉减少症病人和非肌肉减少症病人的1年总体生存率分别为52%和82%。与非肌肉减少症病人比较,肌肉减少症病人ICU住院时间[(12±2)d比(6±1)d,P<0.05]和肝移植后住院总时间[(40±4)d比(25±3)d,P<0.05]更长,两者住院期间总医疗费用差异>17 000欧元[1920]。此外,合并肌肉减少症的移植受者并发症发生率亦显著升高。Valero等[21]的研究结果显示:40.4%的肌肉减少症病人在移植后发生并发症,而非肌肉减少症病人移植后并发症发生率仅为18.4%。肌肉减少症对移植后感染性并发症的影响尤为显著,受者移植后感染的风险增加4.6倍[22]。van Vugt等[18]纳入11项研究的Meta分析结果显示:合并肌肉减少症的肝移植受者生存率明显降低。上述研究结果显示:移植前肌肉减少症对移植受者的预后有显著影响。

    不仅是移植前,移植后肌肉减少症对受者转归也有显著影响。Chae等[23]观察围手术期肌肉量变化对受者预后的影响,该研究团队基于473例活体肝移植受者术后肌肉量的变化将其分为高肌肉损失组和低肌肉损失组,其中高肌肉损失定义为术后第7天PMI较术前降低>11.7%;尽管两组基线PMI比较,差异无统计学意义,但多元回归分析结果显示:高肌肉损失与随访期间肝移植受者总体死亡率增高显著相关。Jeon等[24]的研究结果显示:移植后新发肌肉减少症是受者死亡的独立预测因素。由此可见,肝移植围手术期肌肉减少症的转归是一个动态过程,在移植后同样需应用CT检查等评估手段,密切关注肌肉减少症的发生与发展,进而及早识别高风险病人并进行有效干预。

    肝移植是治疗肝癌的有效手段之一。近年来,肝移植适应证中原发性肝癌的比例逐渐上升,占比>1/3[2526]。然而,移植后肿瘤复发严重危害受者生存[27]。虽然部分研究者认为肌肉量减低与移植后肿瘤复发风险无关,但仍有多项研究结果显示:肌肉减少症是肝移植后肿瘤复发的危险因素[2831]。目前,肌肉减少症受者肿瘤复发风险增高的机制尚不清楚。笔者团队通过临床样本的多维组学分析,结合小鼠肿瘤相关肌肉减少症模型及体外实验,探索性实践发现:在肿瘤引起的全身炎症刺激条件下,肌肉细胞分泌的CHI3L1能够通过诱导脂质过氧化促进肿瘤进展,为降低肌肉减少症相关肿瘤复发提供关键的治疗靶点。

    在全世界供肝短缺的严峻形势下,迫切需要确立一种科学评估系统实现供肝分配最优化。MELD评分是一种根据肝硬化病人预期生存发展而来的统计模型,包含血清胆红素、Cr、PT的国际标准化比值(international normalized ratio,INR),其有助于预测移植后的病死率并优先将供肝分配给最可能获得最佳预后的病人[32]。目前,多数移植中心供肝的分配基于MELD评分,但其仍具有局限性,并非所有终末期肝病病人行肝移植的优先级都能通过MELD评分得到合理评估[33]。多项研究结果显示:肌肉减少症与MELD评分无关[6,14,3435]。这说明MELD评分缺乏对移植等待者肌肉状况的评价,具有局限性。

    当前基于MELD评分的供肝分配系统并不会优先将供肝分配给肌肉减少症病人,同时也未将肌肉减少症列为肝移植的禁忌证。由于肌肉减少症会增加肝硬化病人等待移植期间及移植后病死率,在供肝分配过程中,对于肌肉减少症病人应该增加其移植优先权,以降低等待期间的病死率,还是将肌肉减少症作为移植禁忌证,避免移植后病死率过高,造成供肝资源浪费,值得进一步商榷。

    法国一项研究将脐水平的腰大肌厚度纳入MELD评分中,构建MELD‑腰大肌评分[16]。Masuda等[35]将肌肉减少症纳入MELD评分中,构建MELD‑ 肌肉减少症模型,其研究结果显示:合并肌肉减少症与MELD评分增加10分相当。这在低MELD评分病人中的预测性能更佳[14]。该模型在van Vugt等[36]的研究中得到验证。MELD‑肌肉减少症模型对肝硬化病人病死率的预测能力优于MELD评分,这提示在供肝分配过程中应考虑应用MELD‑肌肉减少症评分或为肌肉减少症病人提供额外分值,以增加其优先级。笔者团队的研究结果显示:在杭州标准基础上联合肌肉减少症可以更精准地对肝癌肝移植受者的总体生存率和疾病无复发生存率进行评估,证实了肌肉减少症的预后预测价值[29]

    发生严重肌肉减少前,对肌肉减少症病人优先行肝移植可能降低等待移植期间的病死率,且对术后生存没有负面影响[8]。此外,早期进行移植可能会减少受者移植后的并发症、总住院时间及医疗费用,改善生存预后[6,20,22,35]。但对于晚期肌肉减少症病人,需要警惕围手术期的风险可能高于获益。在此情况下,移植后早期病死率可能过高[37]。Lai等[38]结合肌肉减少症和MELD⁃Na评分创建Sarco模型,其研究结果显示:MELD⁃Na评分<20分的肌肉减少症病人应优先列入移植名单,而MELD⁃Na评分为35~40分的肌肉减少症病人移植后死亡风险高,不宜进行移植。该模型能准确预测移植等候者中途退出名单的风险,同时明确了无效移植的合适阈值,充分考虑了肌肉减少症的“双刃剑”作用,从而为肌肉减少症受者的供肝分配提供新视角。笔者推测:开展高质量的多中心临床研究,将肌肉减少症科学地纳入肝移植术前评估体系及供肝分配的临床决策中将是重要的研究方向。

    终末期肝病病人肌肉减少症的发病机制复杂,涉及营养、代谢、内分泌等多种因素,诸如肌肉中蛋白合成减少以及分解代谢增加、能量摄入不足、肠道菌群失调、肌肉生长抑制素过度表达、高血氨、睾酮水平降低等[3948]

    改善肌肉减少症有望提高肝移植受者预后,这在围手术期治疗中至关重要[49]。然而,目前针对肌肉减少症并无特效疗法。随着对肌肉减少症发病机制认识的不断深入,一些有望改善肌肉减少症的干预措施开始涌现。有研究结果显示:夜间加餐、补充富含亮氨酸的支链氨基酸、降低血氨、运动疗法、降低门静脉压力、进行肌肉生长抑制素阻断剂等分子靶向治疗、补充睾酮等措施有助于逆转肝硬化病人的肌肉减少症,改善病人预后[45,5055]。肝移植本身对移植后肌肉减少症转归情况的影响仍有争议,还需进一步探索[6,5657]

    作为肝移植临床不良转归的重要危险因素,肌肉减少症的评估方法及干预策略已成为新挑战,迫切需要将其纳入肝移植精准诊断与治疗体系中。笔者认为:在精准医学时代背景下,包含肌肉量、肌肉功能和生物学指标在内的,适用于不同病人的肌肉减少症诊断标准和供肝分配优先权的评估策略亟待建立。这些重要临床体系的构建需依托于多中心、大样本量临床研究。此外,高通量测序、多组学整合分析等新技术的应用也有望进一步挖掘肌肉减少症的发病机制和关键治疗靶点,为提升肝移植疗效提供有力保障。

    所有作者均声明不存在利益冲突
    徐骁, 陈昊, 鲁迪, 等. 肌肉减少症:肝移植的新挑战[J]. 中华消化外科杂志, 2021, 20(10): 1025-1030. DOI: 10.3760/cma.j.cn115610-20210909-00449.

    http://journal.yiigle.com/LinkIn.do?linkin_type=cma&DOI=10.3760/cma.j.cn115610-20210909-00449

  • [1]

    RosenbergIH. Sarcopenia: origins and clinical relevance[J]. J Nutr,1997,127(5Suppl):990s-991s. DOI: 10.1093/jn/127.5.990S.

    [2]

    Cruz‑JentoftAJ, BahatG, BauerJ, et al. Sarcopenia: revised European consensus on definition and diagnosis[J]. Age Ageing,2019,48(1):16‑31. DOI: 10.1093/ageing/afy169.

    [3]

    Cruz‑JentoftAJ, BaeyensJP, BauerJM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in older people[J]. Age Ageing,2010,39(4):412‑423. DOI: 10.1093/ageing/afq034.

    [4]

    MontgomeryJ, EnglesbeM. Sarcopenia in liver transplan-tation[J]. Curr Transplant Rep,2019,6(1):7‑15. DOI:10.10 07/s40472-019-0223-3.

    [5]

    Montano‑LozaAJ. Clinical relevance of sarcopenia in patients with cirrhosis[J]. World J Gastroenterol,2014,20(25):8061‑8071. DOI: 10.3748/wjg.v20.i25.8061.

    [6]

    TandonP, NeyM, IrwinI, et al. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value[J]. Liver Transpl,2012, 18(10):1209‑1216. DOI: 10.1002/lt.23495.

    [7]

    CareyEJ, LaiJC, SonnendayC, et al. A North American expert opinion statement on sarcopenia in liver transplan-tation[J]. Hepatology,2019,70(5):1816‑1829. DOI: 10.1002/hep.30828.

    [8]

    StirnimannG, EbadiM, TandonP, et al. Should sarcopenia increase priority for transplant or is it a contraindication?[J]. Curr Gastroenterol Rep,2018,20(11):50. DOI: 10.1007/s11894-018-0656-3.

    [9]

    HeymsfieldSB. Development of imaging methods to assess adiposity and metabolism[J]. Int J Obes (Lond),2008,32(Suppl 7):S76‑S82. DOI: 10.1038/ijo.2008.242.

    [10]

    CareyEJ, LaiJC, WangCW, et al. A multicenter study to define sarcopenia in patients with end‑stage liver disease[J]. Liver Transpl,2017,23(5):625‑633. DOI:10.1002/lt. 24750.

    [11]

    ChenLK, WooJ, AssantachaiP, et al. Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia dia-gnosis and treatment[J]. J Am Med Dir Assoc,2020,21(3):300‑307.e2. DOI: 10.1016/j.jamda.2019.12.012.

    [12]

    NormanK, KirchnerH, LochsH, et al. Malnutrition affects quality of life in gastroenterology patients[J]. World J Gastroenterol,2006,12(21):3380‑3385. DOI: 10.3748/wjg.v12.i21.3385.

    [13]

    Alvares‑da‑SilvaMR, Reverbel da SilveiraT. Comparison between handgrip strength, subjective global assessment, and prognostic nutritional index in assessing malnutri-tion and predicting clinical outcome in cirrhotic out-patients[J]. Nutrition,2005,21(2):113‑117. DOI: 10.1016/j.nut.2004.02.002.

    [14]

    Montano‑LozaAJ, Duarte‑RojoA, Meza‑JuncoJ, et al. Inclu-sion of sarcopenia within MELD (MELD‑Sarcopenia) and the prediction of mortality in patients with cirrhosis[J]. Clin Transl Gastroenterol,2015,6(7):e102. DOI: 10.1038/ctg.2015.31.

    [15]

    DiMartiniA, CruzRJ, DewMA, et al. Muscle mass predicts outcomes following liver transplantation[J]. Liver Transpl,2013,19(11):1172‑1180. DOI: 10.1002/lt.23724.

    [16]

    DurandF, BuyseS, FrancozC, et al. Prognostic value of muscle atrophy in cirrhosis using psoas muscle thickness on computed tomography[J]. J Hepatol,2014,60(6):1151-1157. DOI: 10.1016/j.jhep.2014.02.026.

    [17]

    Meza‑JuncoJ, Montano‑LozaAJ, BaracosVE, et al. Sarco-penia as a prognostic index of nutritional status in con-current cirrhosis and hepatocellular carcinoma[J]. J Clin Gastroenterol,2013,47(10):861‑870. DOI:10.1097/MCG. 0b013e318293a825.

    [18]

    van VugtJL, LevolgerS, de BruinRW, et al. Systematic review and meta‑analysis of the impact of computed tomography‑assessed skeletal muscle mass on outcome in patients awaiting or undergoing liver transplantation[J]. Am J Transplant,2016,16(8):2277‑2292. DOI: 10.1111/ajt.13732.

    [19]

    Montano‑LozaAJ, Meza‑JuncoJ, BaracosVE, et al. Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplanta-tion[J]. Liver Transpl,2014,20(6):640‑648. DOI: 10.1002/lt.23863.

    [20]

    van VugtJ, BuettnerS, AlferinkL, et al. Low skeletal muscle mass is associated with increased hospital costs in patients with cirrhosis listed for liver transplantation-a retrospective study[J]. Transpl Int,2018,31(2):165‑174. DOI: 10.1111/tri.13048.

    [21]

    ValeroV, AminiN, SpolveratoG, et al. Sarcopenia adver-sely impacts postoperative complications following resec-tion or transplantation in patients with primary liver tumors[J]. J Gastrointest Surg,2015,19(2):272‑281. DOI: 10.1007/s11605-014-2680-4.

    [22]

    KrellRW, KaulDR, MartinAR, et al. Association between sarcopenia and the risk of serious infection among adults undergoing liver transplantation[J]. Liver Transpl,2013,19(12):1396‑1402. DOI: 10.1002/lt.23752.

    [23]

    ChaeMS, MoonKU, JungJY, et al. Perioperative loss of psoas muscle is associated with patient survival in living donor liver transplantation[J]. Liver Transpl,2018,24(5):623‑633. DOI: 10.1002/lt.25022.

    [24]

    JeonJY, WangHJ, OckSY, et al. Newly Developed sarco-penia as a prognostic factor for survival in patients who underwent liver transplantation[J]. PLoS One,2015,10(11):e0143966. DOI: 10.1371/journal.pone.0143966.

    [25]

    StepanovaM, WaiH, SaabS, et al. The portrait of an adult liver transplant recipient in the United States from 1987 to 2013[J]. JAMA Intern Med,2014,174(8):1407‑1409. DOI: 10.1001/jamainternmed.2014.2903.

    [26]

    XuX, ChenJ, WeiQ, et al. Clinical practice guidelines on liver transplantation for hepatocellular carcinoma in China (2018 edition)[J]. Hepatobiliary Pancreat Dis Int,2019,18(4):307‑312. DOI: 10.1016/j.hbpd.2019.06.010.

    [27]

    ClavienPA, LesurtelM, BossuytPM, et al. Recommenda-tions for liver transplantation for hepatocellular carcinoma: an international consensus conference report[J]. Lancet Oncol,2012,13(1):e11‑e22. DOI: 10.1016/S1470-2045(11)70175-9.

    [28]

    GrątK, PachoR, GrątM, et al. Impact of body composition on the risk of hepatocellular carcinoma recurrence after liver transplantation[J]. J Clin Med,2019,8(10):1672. DOI: 10.3390/jcm8101672.

    [29] 陈樽.肌肉减少症和炎症细胞因子CHI3L1对肝移植受者肝癌复发的预警价值及其机制研究[C].杭州:浙江大学,2020.
    [30]

    KimYR, ParkS, HanS, et al. Sarcopenia as a predictor of post‑transplant tumor recurrence after living donor liver transplantation for hepatocellular carcinoma beyond the Milan criteria[J]. Sci Rep,2018,8(1):7157. DOI: 10.1038/s41598-018-25628-w.

    [31]

    ItohS, YoshizumiT, KimuraK, et al. Effect of sarcopenic obesity on outcomes of living‑donor liver transplantation for hepatocellular carcinoma[J]. Anticancer Res,2016,36(6):3029‑3034.

    [32]

    KimHY, JangJW. Sarcopenia in the prognosis of cirrhosis: going beyond the MELD score[J]. World J Gastroenterol,2015,21(25):7637‑7647. DOI: 10.3748/wjg.v21.i25.7637.

    [33]

    GotthardtD, WeissKH, BaumgärtnerM, et al. Limitations of the MELD score in predicting mortality or need for removal from waiting list in patients awaiting liver trans-plantation[J]. BMC Gastroenterol,2009,9:72. DOI: 10.1186/1471-230X-9-72.

    [34]

    KalafateliM, MantzoukisK, Choi YauY, et al. Malnutrition and sarcopenia predict post‑liver transplantation out-comes independently of the model for end‑stage liver disease score[J]. J Cachexia Sarcopenia Muscle,2017,8(1):113‑121. DOI: 10.1002/jcsm.12095.

    [35]

    MasudaT, ShirabeK, IkegamiT, et al. Sarcopenia is a prognostic factor in living donor liver transplantation[J]. Liver Transpl,2014,20(4):401‑407. DOI: 10.1002/lt.23811.

    [36]

    van VugtJ, AlferinkL, BuettnerS, et al. A model including sarcopenia surpasses the MELD score in predicting wai-ting list mortality in cirrhotic liver transplant candidates: a competing risk analysis in a national cohort[J]. J Hepatol,2018,68(4):707‑714. DOI: 10.1016/j.jhep.2017.11.030.

    [37]

    UnderwoodPW, CronDC, TerjimanianMN, et al. Sarco-penia and failure to rescue following liver transplantation[J]. Clin Transplant,2015,29(12):1076‑1080. DOI:10.1111/ ctr.12629.

    [38]

    LaiQ, MagistriP, LionettiR, et al. Sarco‑model:a score to predict the dropout risk in the perspective of organ allocation in patients awaiting liver transplantation[J]. Liver Int,2021, 41(7):1629‑1640. DOI: 10.1111/liv.14889.

    [39]

    MorrisonWL, BouchierIA, GibsonJN, et al. Skeletal muscle and whole‑body protein turnover in cirrhosis[J]. Clin Sci (Lond),1990,78(6):613‑619. DOI:10.1042/cs078 0613.

    [40]

    ZoliM, MarchesiniG, DondiC, et al. Myofibrillar protein catabolic rates in cirrhotic patients with and without muscle wasting[J]. Clin Sci (Lond),1982,62(6):683‑686. DOI: 10.1042/cs0620683.

    [41]

    KohnoM, FujiiT, HirayamaC. [15N]glycine metabolism in normal and cirrhotic subjects[J]. Biochem Med Metab Biol,1990,43(3):201‑213. DOI: 10.1016/0885-4505(90)90026-w.

    [42]

    DavidsonHI, RichardsonR, SutherlandD, et al. Macronu-trient preference, dietary intake, and substrate oxidation among stable cirrhotic patients[J]. Hepatology,1999,29(5):1380‑1386. DOI: 10.1002/hep.510290531.

    [43]

    MangnerN, LinkeA, OberbachA, et al. Exercise training prevents TNF‑α induced loss of force in the diaphragm of mice[J]. PLoS One,2013,8(1):e52274. DOI:10.1371/journal. pone.0052274.

    [44]

    GarcíaPS, CabbabeA, KambadurR, et al. Brief‑reports: elevated myostatin levels in patients with liver disease: a potential contributor to skeletal muscle wasting[J]. Anesth Analg,2010,111(3):707‑709. DOI: 10.1213/ANE.0b013e3181eac1c9.

    [45]

    TsienC, DavuluriG, SinghD, et al. Metabolic and mole-cular responses to leucine‑enriched branched chain amino acid supplementation in the skeletal muscle of alcoholic cirrhosis[J]. Hepatology,2015,61(6):2018‑2029. DOI:10. 1002/hep.27717.

    [46]

    GandaOP, RudermanNB. Muscle nitrogen metabolism in chronic hepatic insufficiency[J]. Metabolism,1976,25(4):427-435. DOI: 10.1016/0026-0495(76)90075-5.

    [47]

    LockwoodAH, McDonaldJM, ReimanRE, et al. The dyna-mics of ammonia metabolism in man. Effects of liver disease and hyperammonemia[J]. J Clin Invest,1979,63(3):449‑460. DOI: 10.1172/JCI109322.

    [48]

    SinclairM, GrossmannM, AngusPW, et al. Low testos-terone as a better predictor of mortality than sarcopenia in men with advanced liver disease[J]. J Gastroenterol Hepatol,2016,31(3):661‑667. DOI: 10.1111/jgh.13182.

    [49]

    KaidoT, OgawaK, FujimotoY, et al. Impact of sarcopenia on survival in patients undergoing living donor liver trans-plantation[J]. Am J Transplant,2013,13(6):1549‑1556. DOI: 10.1111/ajt.12221.

    [50]

    SinclairM, GrossmannM, HoermannR, et al. Testosterone therapy increases muscle mass in men with cirrhosis and low testosterone: a randomised controlled trial[J]. J Hepatol,2016,65(5):906‑913. DOI:10.1016/j.jhep.2016.06. 007.

    [51]

    TsienC, ShahSN, McCulloughAJ, et al. Reversal of sarco-penia predicts survival after a transjugular intrahepatic portosystemic stent[J]. Eur J Gastroenterol Hepatol,2013, 25(1):85‑93. DOI: 10.1097/MEG.0b013e328359a759.

    [52]

    HanHQ, ZhouX, MitchWE, et al. Myostatin/activin path-way antagonism: molecular basis and therapeutic poten-tial[J]. Int J Biochem Cell Biol,2013,45(10):2333‑2347. DOI: 10.1016/j.biocel.2013.05.019.

    [53]

    TsienCD, McCulloughAJ, DasarathyS. Late evening snack: exploiting a period of anabolic opportunity in cirrhosis[J]. J Gastroenterol Hepatol,2012,27(3):430‑441. DOI:10.11 11/j.1440-1746.2011.06951.x.

    [54]

    LocklearCT, GolabiP, GerberL, et al. Exercise as an inter-vention for patients with end‑stage liver disease: systema-tic review[J]. Medicine (Baltimore),2018,97(42):e12774. DOI: 10.1097/MD.0000000000012774.

    [55]

    KumarA, DavuluriG, SilvaR, et al. Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis[J]. Hepatology,2017,65(6):2045-2058. DOI: 10.1002/hep.29107.

    [56]

    MerliM, GiustoM, GentiliF, et al. Nutritional status: its influence on the outcome of patients undergoing liver transplantation[J]. Liver Int,2010,30(2):208‑214. DOI: 10.1111/j.1478-3231.2009.02135.x.

    [57]

    EnglesbeMJ, PatelSP, HeK, et al. Sarcopenia and morta-lity after liver transplantation[J]. J Am Coll Surg,2010,211(2):271‑278. DOI: 10.1016/j.jamcollsurg.2010.03.039.

计量
  • 文章访问数:  2016
  • HTML全文浏览量:  0
  • PDF下载量:  0
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-09-08
  • 网络出版日期:  2024-07-18
  • 刊出日期:  2021-10-19

目录

/

返回文章
返回