Medicine (Austin & Northern Health) - Theses
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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.