Assessment of sarcopenia, hepatic function and clinical outcomes in liver transplantation

Abstract

Cirrhosis is a significant cause of morbidity and mortality in our community and liver transplantation is a well-established treatment for patients with decompensated cirrhosis and hepatocellular carcinoma. However, there remains a proportion of patients who have adverse transplant outcomes. As such, there is an ongoing interest in strategies to identify patients at risk of life-threatening complications, as well as developing strategies to reduce the risk of these complications occurring.Prior evidence suggests patients with reduced skeletal muscle mass have increased morbidity and mortality both pre- and post-transplant [Chapter 1]. A large proportion of these studies have used computed tomography (CT) skeletal muscle area measured on a single transverse image to estimate overall body muscle stores. However, the thresholds used to define low muscle mass were derived from obese patients with malignancy. There is limited reported data on the healthy distribution of skeletal muscle and adipose tissue area on CT to confirm these cut-offs are appropriate for all patient cohorts. Chapter 3 provides important normative CT data on skeletal muscle area, visceral adipose tissue area and subcutaneous adipose tissue area in a cohort of Australian Caucasians.Bedside methods used to assess skeletal muscle mass such as anthropometrics and bioelectrical impedance analysis (BIA) are considered inaccurate in patients with cirrhosis due to assumptions about the hydration fraction of fat-free mass which are not applicable to this patient cohort. Thus, there is a need to identify novel non-invasive, accurate and clinically significant methods of estimating muscle mass in patients with cirrhosis. Chapter 4 evaluated the relationship of several muscle mass assessment methods to a body cell mass reference estimate in patients with cirrhosis. Advances in prior bedside methods, such as multifrequency bioelectrical impedance spectroscopy (BIS), and novel muscle mass estimates using ultrasound (US), were among the methods evaluated. Of the bedside muscle mass estimates, the BIS results had the strongest relationship to the body cell mass reference measurement. However, BIS resulted in misdiagnosis of skeletal muscle mass depletion when compared to dual-energy X-ray absorptiometry (DXA) skeletal muscle index criteria. Of the radiological methods, DXA appendicular lean mass (ALM) had the strongest relationship to the body cell mass reference estimate. CT skeletal muscle area results were consistently inferior to DXA ALM results.Expert panels on sarcopenia have highlighted the importance of measuring muscle strength and physical performance in addition to muscle mass when assessing for sarcopenia. In Chapter 5, comprehensive sarcopenia assessment was performed on a cohort of patients with cirrhosis undergoing liver transplant. Several relationships were identified with pre- and post-transplant complications. In male patients, lower DXA skeletal muscle index had a trend towards an association with delayed extubation and sepsis post-liver transplant. A lower sit-to-stand test score in men was independently associated with pre-transplant sepsis and encephalopathy related admission. In addition, impaired Short Physical Performance Battery was associated with post-transplant sepsis and impaired six-minute walk distance was a predictor of prolonged hospital length of stay.Cardiovascular disease post-liver transplantation is a significant problem and one of the strongest risk factors is post-transplant metabolic syndrome. Chapter 6 evaluates the pre-transplant variables associated with the early onset of post-transplant metabolic syndrome and found that CT visceral adipose tissue is an independent risk factor on multivariate analysis.In Chapter 7, the change in body composition, muscle strength and physical performance from baseline assessment to six months post-transplantation was evaluated. Similar to previous studies, there was a significant increase in DXA fat mass and decline in DXA skeletal muscle mass. This corresponded to a high prevalence of ‘Sarcopenic obesity’. Despite an overall significant improvement in physical performance measures by six months, sarcopenic obesity patients were associated with inferior performance than the non-sarcopenic patients. No association was found with sarcopenic obesity and cardiometabolic risk.In conclusion, this thesis significantly contributes to the literature in several areas. Firstly, it provides important body composition data, both in health and a population with cirrhosis. It also provided evidence of the clinical utility of a comprehensive body composition assessment in patients with cirrhosis undergoing liver transplantation. Furthermore, a sarcopenia evaluation incorporating assessment of skeletal muscle mass, muscle strength and physical performance provides the optimal risk assessment for pre- and post-transplant adverse events. Finally, this research identified that pre-transplant CT visceral adipose tissue is an independent risk factor for post-transplant metabolic syndrome. Identification of high-risk patients using the above techniques could assist risk stratification and/or used to target patients for intervention.