Type II fibre atrophy and nuclear disruption in decompensated cirrhosis

Abstract

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).

Methods

Rectus abdominis 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.

Results

At LT, 39 patients (68.4%) had decompensated cirrhosis. Decompensated cirrhosis was associated with reduced skeletal muscle index (females: 37.5 ± 4.5 vs. 44.4 ± 5.7 cm²/m², p = 0.008; males: 44.6 ± 8.1 vs. 51.8 ± 7.4 cm²/m², p = 0.029) and higher sarcopenia prevalence (59% vs. 22%, p = 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 vs. 5,295 ± 2,612 μm², p = 0.003), the percentage of centralized nuclei was higher (11.6 ± 7.4 vs. 5.3 ± 3.0%, p <0.001), and total tissue triglyceride content was lower (19.0 ± 12.37 vs. 31.6 ± 12.77 μg/mg, p <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.

Conclusions

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.

Impact and implications

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.