Assessment and prognostic importance of nutritional status and body composition in liver transplantation

Sammanfattning: Chronic liver disease and liver cirrhosis are progressive diseases closely linked to metabolism and nutritional status. Weight loss is a result of negative energy balance and is therefore a good measure of risk of malnutrition. Screening and assessment of malnutrition in patients with liver cirrhosis is difficult because ascites and oedema are prevalent in late stages of liver cirrhosis. Accumulated fluid could make weight loss as an indicator of malnutrition inappropriate and malnourishment in obese patients can be challenging to identify. Knowledge about body composition, especially the presence of sarcopenia or sarcopenic obesity, is of great clinical value in the liver transplant setting. The scientific and clinical field is hampered by a lack of consensus on how to assess nutritional status in patients with liver cirrhosis. More research is needed to clarify the first part of the nutrition care process: nutritional assessment. The aims of this thesis were to extend knowledge about nutritional assessment for patients with chronic liver disease before and after liver transplantation. The different parts of the nutritional assessment that are studied in my thesis are body composition methods, nutrition impact symptoms (NIS) and estimation of energy needs. Study I and Study II were retrospective cohort studies based on patients that underwent liver transplantation between 2009-2012. Study III was a prospective cross-sectional study of patients undergoing evaluation for liver transplantation between 2016-2018. Study IV was based on a retrospective analysis of the early phase post liver transplantation for patients who underwent a liver transplanta- tion between 2011-2018. Information on body composition was retrieved from dual-energy x-ray absorptiometry (DXA) scans and computed tomography (CT) scans together with anthropometric data, as well as data from questionnaires and information from indirect calorimetry. Additionally, information was obtained from medical charts and the local liver transplant register. In study I, the influence of nutritional status on outcome after liver transplantation was studied. The prevalence of malnutrition was 2-20 % during the pre-transplant evaluation. The prevalence differed between genders and assessment methods. When measured with DXA, 20 % of the men and 5 % of the women were mal- nourished. An association was found between fat-free mass index and occurrence of infections within 30 days after the liver transplantation. In study II we performed inter-method comparisons between muscle mass depletion measured with DXA and CT. Muscle mass depletion was found in 30-40% of the entire population, in women it varied between 13-69% with the different methods and in men between 27-40%. Muscles in arms and legs measured with DXA had a strong correlation with muscles at the third lumbar vertebrae (L3) measured with CT but whole-body fat-free mass measured with DXA did not. In study III the aim was to assess the prevalence and severity of NIS and to explore associations with malnutrition and health-related quality of life (HRQOL). The prevalence of malnutrition was 32%. NIS were prevalent with 90% of the population presenting with one symptom or more and 51% of the population with four or more symptoms. A higher frequency of NIS was associated with malnutrition and worse HRQOL. Energy require- ment early after liver transplantation was studied in study IV, and we found that the Harris & Benedict equation for predicting resting energy expenditure (REE), as well as the fixed factors 25, 30, 35 kcal/kg suggested in European guidelines, provided estimates of energy requirement that were too inaccurate to be of clinical value. There is a risk of both under- and overfeeding individual patients if fixed factors are used to estimate energy requirement early after liver transplantation. Measured REE was significantly associated (p < 0.05) with age, gender, Model for End-Stage Liver Disease score before liver transplantation, surgery time and graft cold ischemia time. Together, the results from this thesis contributes to an understanding of the impor- tance of a structured nutritional assessment as well as body composition assess- ment in patients undergoing liver transplantation. The proportion of individuals who are malnourished or muscle mass depleted varies depending on the method used, NIS are prevalent and associated with malnutrition and worse health-related quality of life. Energy requirements should be measured and not estimated after liver transplantation.