Emerging awareness on the importance of skeletal muscle in liver diseases: time to dig deeper into mechanisms!

Abstract

Skeletal muscle is a tissue that represents 30–40% of total body mass in healthy humans and contains up to 75% of total body proteins. It is thus the largest organ in non-obese subjects. The past few years have seen increasing awareness of the prognostic value of appreciating changes in skeletal muscle compartment in various chronic diseases. Hence, a low muscle mass, a low muscle function and muscle fatty infiltration are linked with poor outcomes in many pathological conditions. In particular, an affluent body of evidence links the severity, the complications and mortality of chronic liver disease (CLD) with skeletal muscle depletion. Yet it is still not clear whether low muscle mass is a cause, an aggravating factor, a consequence of the ongoing disease, or an epiphenomenon reflecting general alteration in the critically ill patient. The mechanisms by which the muscle compartment influences disease prognosis are still largely unknown. In addition, whether muscle alterations contribute to liver disease progression is an unanswered question. Here, we first review basic knowledge about muscle compartment to draw a conceptual framework for interpreting skeletal muscle alteration in CLD. We next describe recent literature on muscle wasting in cirrhosis and liver transplantation. We then discuss the implication of skeletal muscle compartment in non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), focusing on plausible metabolic disruption in muscle compartment that might participate in NAFLD progression. Finally, we discuss shortcomings and challenges we need to address in the near future prior to designate the muscle compartment as a therapeutic target in CLD.

Myosteatosis to predict inferior perioperative outcome in patients undergoing orthotopic liver transplantation

“…In our cohort, patients with myosteatosis had significantly more major complications over the first 3 months and low muscle density was additionally associated with increased rates of EAD, higher CCI scores, and an increased need for intraoperative blood transfusions. 19,37,38 The association of myosteatosis with the abovementioned parameters of perioperative outcome is further supported by the correlation and quartile analyses, demonstrating that gradually decreasing muscle density leads to more perioperative complications, longer in-hospital stay, and higher estimated costs. The estimated mean procedural costs were more than 20 TEur higher in patients with myosteatosis compared to the rest of our cohort.…”

“…19,40 While myosteatosis is also seen in normal weight or underweight patients, 41 it is reasonable to assume that the skeletal muscle does not only act as a plain ectopic storage of energy surplus, and as such mechanisms other than excessive fat intake may play an important role in the development of pathological muscle fat deposition. 19,40 While myosteatosis is also seen in normal weight or underweight patients, 41 it is reasonable to assume that the skeletal muscle does not only act as a plain ectopic storage of energy surplus, and as such mechanisms other than excessive fat intake may play an important role in the development of pathological muscle fat deposition.…”

“…19,40 While myosteatosis is also seen in normal weight or underweight patients, 41 it is reasonable to assume that the skeletal muscle does not only act as a plain ectopic storage of energy surplus, and as such mechanisms other than excessive fat intake may play an important role in the development of pathological muscle fat deposition. 19 Several clinical risk-assessment tools have been developed for assessing outcome following OLT. 19 Several clinical risk-assessment tools have been developed for assessing outcome following OLT.…”

“…[8][9][10][11][12][13] While some of these models are helpful in predicting posttransplant outcomes, none of these scores include information on the recipient's BC. While some studies have recently reported an association of sarcopenia with clinical outcome in cirrhosis and orthotopic liver transplantation (OLT), 15,[19][20][21][22][23] the prognostic value of muscle quality (skeletal muscle density and myosteatosis) compared to muscle quantity (skeletal muscle mass-SMM, as the morphological aspect of sarcopenia) remains to be determined. 2,15 The importance of nutritional status and its assessment in patients with chronic liver disease are further highlighted by the recent European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD) guidelines on nutrition in chronic liver disease.…”

“…14 Cross-sectional computed tomography (CT) imaging studies are validated and widely available, and as such, BC could be easily integrated in the process of risk-stratification and routine clinical workup of transplant recipients. 2,[19][20][21][22] The goal of the present study was to comprehensively assess the role of different CT-based recipient BC profiles and compare the value and limitations of reduced muscle mass and myosteatosis in predicting perioperative outcomes in adult patients undergoing deceased donor OLT. [16][17][18] Patients with terminal liver disease are frequently burdened by malnutrition and muscle wasting.…”