Motamedrad Maryam, Ebadi Maryam, Sanchez-Fernandez Norberto, Parente Alessandro, Dunichand-Hoedl Abha R, Rider Elora, Kneteman Norman M, Shapiro A M James, Bigam David, Dajani Khaled, Anderson Blaire, Baracos Vickie E, Mazurak Vera, Montano-Loza Aldo J
Division of Gastroenterology and Liver Unit, University of Alberta Hospital, Edmonton, Alberta, Canada.
Division of Human Nutrition, University of Alberta, Edmonton, Alberta, Canada.
JHEP Rep. 2025 May 24;7(9):101455. doi: 10.1016/j.jhepr.2025.101455. eCollection 2025 Sep.
BACKGROUND & AIMS: Loss of skeletal muscle mass is a common complication in cirrhosis that is associated with higher morbidity and mortality. Since the specific pathophysiology of cirrhosis-related muscle loss is unclear, we performed histological evaluation of muscle tissue from patients with cirrhosis undergoing liver transplantation (LT).
muscle was collected at LT from 57 patients. Specimens were analyzed for immunohistochemical determination of fibre size and type, nuclear position and total tissue triglyceride. Computed tomography was used to determine the skeletal muscle index and sarcopenia was defined using previously published cut-offs. The D'Amico cirrhosis classification was used to categorize patients as having decompensated cirrhosis.
At LT, 39 patients (68.4%) had decompensated cirrhosis. Decompensated cirrhosis was associated with reduced skeletal muscle index (females: 37.5 ± 4.5 44.4 ± 5.7 cm/m, = 0.008; males: 44.6 ± 8.1 51.8 ± 7.4 cm/m, = 0.029) and higher sarcopenia prevalence (59% 22%, = 0.01) compared to compensated cirrhosis. In patients with decompensated cirrhosis, the size of type IIA fibres was reduced by 35.7% (3,405 ± 1,894 5,295 ± 2,612 μm, = 0.003), the percentage of centralized nuclei was higher (11.6 ± 7.4 5.3 ± 3.0%, <0.001), and total tissue triglyceride content was lower (19.0 ± 12.37 31.6 ± 12.77 μg/mg, <0.001) than in patients with compensated cirrhosis. In the multivariate logistic regression analysis, size of type IIA fibres and percentage of centralized nuclei were independently associated with decompensated cirrhosis.
Patients with decompensated cirrhosis have myopathy characterized by fibre type II atrophy and disruption of nuclear positioning. Further work is warranted to evaluate the factors related to the development of muscle pathology in cirrhosis and to develop regimens of muscle rehabilitation for this patient population pre- and post-LT.
Our study illustrates the presence of myopathy at the histological level in patients with cirrhosis undergoing liver transplantation. Patients with decompensated cirrhosis, compared with compensated cirrhosis, exhibit type II (glycolytic) muscle fibre atrophy and disruption of nuclear positioning. Patients with decompensated cirrhosis gain an extended survival benefit from liver transplantation but are likely to begin this extension of life enfeebled by loss of muscle mass and function. The involvement of glycolytic muscle fibres may have implications for strength and fatiguability; thus, post-transplant resistance exercise may help with rehabilitation.
骨骼肌质量丢失是肝硬化常见的并发症，与更高的发病率和死亡率相关。由于肝硬化相关肌肉丢失的具体病理生理学尚不清楚，我们对接受肝移植（LT）的肝硬化患者的肌肉组织进行了组织学评估。
从57例患者肝移植时采集肌肉。对标本进行免疫组织化学分析，以确定纤维大小和类型、核位置及总组织甘油三酯。采用计算机断层扫描确定骨骼肌指数，并使用先前公布的临界值定义肌肉减少症。采用达米科肝硬化分类法将患者分类为失代偿期肝硬化。
肝移植时，39例患者（68.4%）为失代偿期肝硬化。与代偿期肝硬化相比，失代偿期肝硬化与骨骼肌指数降低（女性：37.5±4.5对44.4±5.7cm/m²，P=0.008；男性：44.6±8.1对51.8±7.4cm/m²，P=0.029）及更高的肌肉减少症患病率（59%对22%，P=0.01）相关。在失代偿期肝硬化患者中，IIA型纤维大小减少35.7%（3405±1894对5295±2612μm²，P=0.003），中央核百分比更高（11.6±7.4对5.3±3.0%，P<0.001），且总组织甘油三酯含量更低（19.0±12.37对31.6±12.77μg/mg，P<0.001）。在多因素逻辑回归分析中，IIA型纤维大小和中央核百分比与失代偿期肝硬化独立相关。
失代偿期肝硬化患者存在以II型纤维萎缩和核定位破坏为特征的肌病。有必要进一步开展工作，以评估与肝硬化肌肉病理发展相关的因素，并为该患者群体在肝移植前后制定肌肉康复方案。
我们的研究表明，接受肝移植的肝硬化患者在组织学水平存在肌病。与代偿期肝硬化相比，失代偿期肝硬化患者表现出II型（糖酵解型）肌纤维萎缩和核定位破坏。失代偿期肝硬化患者从肝移植中获得了延长生存期的益处，但可能在肌肉质量和功能丧失的情况下开始这种生存期的延长。糖酵解型肌纤维的受累可能对力量和疲劳性有影响；因此，移植后进行抗阻运动可能有助于康复。
