Studies of Prognosis and Nutritional Intervention in Liver Cirrhosis and Liver Transplantation

Abstract

In patients with chronic liver disease protein-energy malnutrition (PEM) is a common finding. These patients are predisposed to higher rates of in-hospital mortality, hepatic encephalopathy and infectious complications. In cirrhotic patients awaiting orthotopic liver transplantation (OLT), a strong correlation is noted between worsening PEM and higher post-transplant complications and reduced survival. Some gaps in the literature exist with regard to PEM in cirrhosis. This thesis aimed to address some of these issues: the prognostic utility of markers of PEM; the therapeutic benefit of a specialised immunonutritional supplementation in the peri-OLT setting; and whether PEM returns to normal in the long term, following successful OLT. To assist with these aims, accurate assessment of PEM is required. The body composition laboratory (BCL) offers state of the art methods to assess nutritional status. Dual-energy x-ray absorptiometry (DXA) and in vivo neutron activation analysis (INAA) allow for accurate assessment of body weight, fat, protein and water content, all of which are deranged in cirrhotic patients. In a longitudinal analysis of cirrhotic patients’ serum sodium, hydration state and resting energy expenditure (REE) independently predicted transplant-free survival (TFS) when compared to the Child-Pugh and MELD scores, which are the established prognostic tools in liver cirrhosis. Impact (Nestle), a form of immunonutrition (IN) containing omega-3 fatty acids, arginine and nucleotides, was provided to cirrhotic patients awaiting liver transplantation in a double-blind randomised controlled trial (RCT). When compared to an isocaloric isonitrogenous control feed, pre-OLT body protein gain, post-OLT body composition changes and clinical outcomes were similar. A sub-group of patients also underwent whole-body protein turnover measurements to establish any underlying mechanism of action for IN. Patients were catabolic, which did not improve significantly after fourteen days of IN. Finally, in a cohort of patients followed for three or more years after OLT, body composition had returned to normal, although quality of life (QOL) was reduced when compared to the normal population. In conclusion, the studies from this thesis have shown serum sodium, hydration and REE to be significant predictors of TFS in cirrhotic patients. IN was not superior to an iso-caloric iso-nitrogenous control feed in the peri-OLT setting, and long-term survivors after OLT were restored to normal nutritional status.