Medicine (Austin & Northern Health) - Theses
Permanent URI for this collection
Search Results
1 - 3 of 3
-
ItemTargeting malnutrition to improve patient and clinical outcomes in liver tranpslantation( 2023-12)Background: Malnutrition and sarcopenia are highly prevalent in decompensated cirrhosis and are independently associated with increased morbidity and mortality before and after liver transplantation. Broadly defined, malnutrition in liver disease is characterised by dry weight loss, muscle wasting, fatigue, and weakness; occurring when the diet does not provide sufficient calories and protein to maintain nutritional status, or the body is unable to fully absorb or utilise food consumed secondary to liver disease. Sarcopenia encompasses the complete spectrum of reduced muscle mass, muscle strength and muscle function. Despite the established interplay of malnutrition, sarcopenia and poor patient outcome, effective therapies to improve nutritional status and muscle function in the pre-transplant period have mostly remained elusive, and any subsequent impact on post-transplant outcomes have not been described. The ability to accurately define and subsequently achieve energy requirements in cirrhosis is poorly described in the current literature and may contribute to the outcomes described thus far, which are conflicting and fail to demonstrate consistent improvement in muscle and nutrition parameters. Aims: This research aims to discover nutritional interventions that prevent nutritional decline and improve functional status in patients awaiting liver transplantation, and to accurately characterise energy requirements in cirrhosis. We hypothesise that targeted enteral feeding in the pre-transplant period will be superior to standard high-energy, high-protein oral diet in delivering improved nutritional, functional and clinical outcomes in patients before and after liver transplantation. Methods: A retrospective analysis of 373 patients consecutively transplanted at a single centre was conducted to assess the impact of pre-transplant nutritional status and muscle function on post-transplant clinical outcomes and healthcare costs. A prospective observational study then followed 110 candidates under assessment for liver transplant and compared their measured energy expenditure (via indirect calorimetry) with estimated energy requirements (via predictive equations). Patient and clinical factors predictive of measured energy expenditure were also explored. An additional observational study of patients treated with continuous terlipressin infusion for management of portal hypertension, evaluated the impact of terlipressin therapy on dietary intake and muscle strength in a small cohort of patients awaiting liver transplant. Finally, a prospective randomised controlled trial comparing pre-transplant enteral feeding with standard high-energy high-protein diet in 50 malnourished and sarcopenic patients, evaluated the effect of enteral feeding on patients’ nutrition, muscle and immune function both before and after transplant. Results: In patients undergoing liver transplant surgery, severe malnutrition and low grip strength were independent predictors of adverse post-transplant outcomes including ICU length of stay, hospital length of stay, and post-transplant infection (p all < 0.05). Additionally, hospital costs were 30% higher in severely malnourished compared to well-nourished recipients (p = 0.012). When prospectively analysing predicted versus measured energy requirements in cirrhotic patients, there was poor correlation between the two methods, and hypermetabolism was common. Treatment of portal hypertension with continuous terlipressin infusion was associated with significantly increased dietary energy and protein intake, by 54% and 56%, respectively (both p < 0.001); which translated to a 3.13 kg (SD 3.55), or 12% increase in HGS (p < 0.001). The randomised controlled trial demonstrated that nasogastric feeding for a median 84.5 days (IQR 40.25 - 130.5) resulted in a median increase in HGS of 3.90kg (2.02 - 5.05), compared to a decrease of 0.35kg (-3.02 to 0.63) in controls (p < 0.001). Dry body weight, mid upper-arm circumference, triceps skinfold and immune function all increased significantly for the nasogastric feed group compared to no change in controls. Post-transplant clinical outcomes were similar between groups. Conclusion: Malnutrition and reduced muscle strength are highly prevalent in cirrhotic patients and are independent predictors of poor outcomes after LT which significantly increases healthcare costs. Nutritional interventions in this cohort should involve measurement of individual energy requirements, as relying on predictive equations in this patient population may result in significant under or over feeding. Effective treatment of portal hypertension with terlipressin infusion appears to improve nutritional and muscle parameters not previously described and warrants further investigation. Finally, targeted enteral feeding before liver transplant improves grip strength, anthropometric markers, and immune function in severely malnourished patients. Larger-scale studies are required to assess the effect of enteral feeding on clinically meaningful endpoints such as infection prevalence, post-transplant length of stay and survival.
-
ItemClinical studies and interventions for sarcopenia in cirrhosis( 2023-09)Sarcopenia, defined as reduced muscle mass and impaired muscle function, is associated with higher morbidity and mortality in patients with advanced liver disease. Despite its recognised prognostic importance, radiological tools recommended for the measurement of muscle mass are either not widely validated in cirrhotic cohorts or poorly accessible amongst clinicians. As such, uptake of sarcopenia assessment in the clinical setting is greatly limited. The mechanisms underlying sarcopenia associated with cirrhosis are complex. The pathophysiology of muscle loss in this population differs from sarcopenia associated with aging and other chronic diseases as it is driven by different metabolic, hormonal and physiological changes that are specific to advanced liver disease. In particular, the development of portal hypertension and its sequelae such as ascites may contribute to reduced nutritional intake, impaired nutrient absorption, increased heat loss and systemic inflammation. Branched-chain amino acids (BCAAs) are an integral part of muscle homeostasis and promote muscle protein synthesis and anabolism. BCAA levels are reduced in cirrhosis due to protein malnutrition and utilisation in extra-hepatic ammonia clearance. These mechanisms provide several targets for interventional clinical trials. Yet there is a lack of prospective studies examining therapies to prevent or ameliorate sarcopenia in cirrhosis. It is also uncertain whether addressing the drivers of muscle loss in cirrhosis will improve outcomes. This thesis sought to address current deficiencies in the cirrhotic literature surrounding diagnostic tools and interventions for sarcopenia. The first study validated the use of an open access web-based program for the measurement of muscle mass using CT scans amongst clinicians in a cohort of cirrhotic patients. This was compared to a widely used dedicated software program. The new program showed excellent inter-rater and between-program agreement for the measurement of muscle mass and provided an accurate and accessible platform for clinicians to assess sarcopenia in patients with cirrhosis undergoing CT scans. The second diagnostic study aimed to assess the use of dual-energy x-ray absorptiometry (DEXA) in predicting post-transplant outcomes in patients with cirrhosis undergoing liver transplantation. We identified reduced upper limb lean mass as a novel predictor of adverse post-transplant outcomes including sepsis and length and stay in men undergoing liver transplantation. Two prospective studies were conducted aiming to evaluate different interventions on sarcopenia, frailty and physical performance in patients with cirrhosis. The first was a cohort study of 12 patients who were referred for transjugular-intrahepatic portosystemic shunt (TIPS) insertion. This is a radiological procedure used to treat complications of portal hypertension, a major driver of sarcopenia in cirrhosis. Compared to baseline, at 6-months post TIPS insertion, patients demonstrated a significant increase in muscle mass and subcutaneous fat mass. There however was no improvement in muscle quality or function or physical frailty. TIPS insertion was associated with improvements in immune function as measured by a novel global immune function assay. Finally, we conducted a double-blinded randomised controlled trial of 150 patients to assess the effect of oral BCAAs supplementation on sarcopenia and clinical outcomes. Compared to a standard protein control, BCAAs did not improve measures of muscle strength, mass, performance or quality of life.
-
ItemClinical risk stratification in patients with advanced liver disease and portal hypertension( 2021)Liver cirrhosis, an advanced stage of progressive hepatic fibrosis resulting from any chronic insult to the liver, is a serious medical condition that adversely affects both quality of life and life expectancy. Risk stratification represents a systematic predictive modelling process to identify patients who are at risk of poorer health outcomes and who are expected to benefit most from a particular intervention. Risk stratification in liver disease was first developed in the 1960's and has experienced a resurgence of interest with the development of new therapies for cirrhosis and the increasing accessibility of liver transplantation. The aim of this thesis is to advance the knowledge of risk stratification in patients with cirrhosis to guide clinical decision making and ultimately improve patient care. In the lifecycle of a typical patient with cirrhosis, clinical settings were identified where a paucity of literature currently exists in relation to risk stratification. These include acute variceal bleeding, the development of hepatic encephalopathy, pre-transplantation stratification of cardiac risk and post-transplantation clinical deterioration and unplanned intensive care unit readmission.