Assessing Nutrition Through Observation (A.N.T.O. Study).

ACKNOWLEDGEMENTS:

I would like to express my sincere thanks to the Florence Nightingale Foundation led by Professor Elizabeth Robb and collaborators, in particular NHS Professionals to grant a second research scholarship to support this course of studies. They have greatly believed in my potentials and the value of this project, without their precious support I would have not been here writing this progress report. My sincere respects and thanks go to the Nottingham University Charitable Trust, they have assessed my application for funding and granted a prime priming award to support the clinical direct costs linked to this project. I would also like to express my gratitude to my line manager, the NIHR NDD BRU Department and the University of Nottingham. Last but certainly not least, I would like to thank my academic and clinical supervisors for their continuous support and encouragement.

INTRODUCTION and BACKGROUND

Several studies demonstrate that malnutrition in patients suffering with cirrhosis of the liver is a major problem and in spite of the known effect on morbidity and mortality, it remains underdiagnosed and undertreated. There is a lack of research on early nutritional interventions in people suffering with early stage cirrhosis of the liver; the combination of methods for nutritional assessment are various and often used inappropriately in this particular population. For the purpose of nutritional assessment various tools are available and currently used in clinical practice. As the assessment of nutritional status in patients suffering with early cirrhosis of the liver is a challenge, a review of previous work was necessary. The aim of one of my previous work was to highlight targeted nutritional interventions and methods of assessment and to highlight the most appropriate tools to assess malnutrition in early cirrhosis of the liver.

As many as one in ten people in England have some form of liver disease(1).Currently is the fifth most common cause of mortality in the UK and the trend of mortality is rising when compared to other major causes of deaths(1). Rates for males from all types of liver disease increased by 85% from 1996 to 2006 and the corresponding rate for females showed a 65% increase for the same decade(2). Estimates suggest that liver disease mortality may double in the next decade(3) with cirrhosis of the liver and cancer of the liver accounting for one in every 40 deaths worldwide. The UK has historically experienced low rate of liver disease compared to mainland Europe however since the 1970s the number of deaths increased while the corresponding European figures decreased(1). Cirrhosis is the major cause of death(4), about 4-5000 deaths in the UK each year(5,6). A growing number of reports(7,8) have shown that cirrhosis is occurring in younger groups and individuals in their twenties have been reported to suffer with the disease.

Main causes of cirrhosis are alcoholism, hepatitis C and B and fatty liver disease. Cirrhosis can be divided in 2 categories: compensated stage and decompensated stage. In compensated cirrhosis the liver is heavily scarred but can still perform many important functions (Child Pugh class A). In decompensated cirrhosis the liver is extensively scarred and unable to function properly (Child Pugh class B and C). People in this latter stage will eventually develop a variety of symptoms such as fatigue, loss of appetite, aches and pains and more serious complications, some can be life threatening such as ascites (accumulation of fluids in the abdominal cavity), portal hypertension (scar tissue in the liver can restrict the flow of blood), formation of varices (veins in the stomach and oesophagus become stretched and dilated with high risk of bleeding).

Several studies demonstrate that malnutrition (i.e. where there is inadequate calorie or protein intake), in patients suffering with cirrhosis of the liver is a major problem and in spite of the well-known effect on morbidity and mortality of malnutrition in liver disease, it remains underdiagnosed and undertreated in clinical practice(9). There is a lack of research on early nutritional interventions in people suffering with early stage cirrhosis Child-Pugh class A. Many chronic liver diseases are associated with malnutrition; one of the most common is cirrhosis. The prevalence of Protein-Calories-Malnutrition (PCM) ranges from 10% to 100% in patients suffering with liver disease, it is higher in liver cirrhosis(10,11) People suffering with cirrhosis often experience loss of appetite, nausea, vomiting and weight loss. When there is liver disease, nutritional status is severely affected, signs of PCM are found in most patients with cirrhosis, however this is still underdiagnosed and undertreated. Once established, PCM damages hepatocytes and worsen prognosis leading to liver transplantation which is found to increase by 40% in malnourished patients(12). Changing the diet by increasing or decreasing proteins, carbohydrates, fats, and vitamins may further affect the function of the diseased liver, especially its protein and vitamin production and therefore dietary interventions need to be implemented carefully and after an in-depth assessment by specialist clinicians(9). Therefore appropriate nutritional assessment for this group of patients is becoming mandatory in order to identify those who require nutritional interventions. A combination of handgrip strength <30 kg/F and MAMC <23 cm had previously been shown to have a 94% sensitivity and 97% negative predictive value in identifying malnourished patients(13). 21 patients will be identified (as part of my study) who meet the above cut off measurements from an existing cohort. Dexa scanning will be used to assess bone mineral content as well as body fat and FFM (fat-free mass).The Dexa scanner uses x-ray absorption to determine total body calcium and measures total body fat and total fat-free soft tissue and provides an estimate of body water and body protein compartments.

At present the vast majority of research studies have attempted to assess and quantify malnutrition in end of stage liver disease and although current literature confirms that liver patients are at risk of malnutrition from the very early stage of the disease, there are currently no implemented interventions. This study aims to identify, assess and follow 21 malnourished compensated cirrhosis patients for 6 months by using very simple and economic screening tools such as anthropometry, simple blood tests, subjective global assessment (SGA) and Dual-energy X-ray absorptiometry (DEXA) scanning. The primary objective is to quantify changes in body composition through DEXA scanning. We will also be able to highlight bone density defects (if any at this stage of the disease) due to impaired liver functions. This test is reasonably economical but at the moment it is not routinely prescribed in this population to assess malnutrition. The second objective is to assess quality of life and to assess dietary compliance. A targeted dietary plan will be formulated by a specialist gastroenterology dietician and a 60 minutes consultation will be delivered by the dietician to the volunteer on a one to one basis. Volunteers will be followed up from Baseline, at week 2 via telephone consultation, at Month 2 via clinical assessment, at Month 4 via telephone consultation. Month 6 will mark the end of the study. A final DEXA scan, biomarkers and anthropometry assessment will be undertaken at month 6. A quality of life questionnaire/interview will also be completed at Baseline, Month 2 and Month 6.

PROGRESS REPORT

The study is currently in progress and hosted within the NIHR Nottingham Digestive Diseases Biomedical Research Unit in Nottingham. The total target number of patients to be recruited is 21. I have currently received consent form 10 patients, 2 patients have completed the full study, the remaining 8 patients are due to attend follow up visits in the New Year. It is my aim to send further invitation letters during the month of January 2016 and February 2016 and hopefully complete the recruitment phase by the end of spring 2016. I hope to be able to recruit participant 21 by the end of May 2016. The forecast is to complete the final visit by the end of December 2016.

A database has been created to collect the data. The database is securely stored within the NIHR NDDBRU on a secured, password protected NHS IT system. Only authorised and trained personnel have been granted the permission to access this data. It is my aim to complete data entry and data analysis by the end of spring 2017. The final thesis will be submitted by the end of December 2017 and at the same time it is my aim to submit the final report to the Florence Nightingale Foundation including results which will have to be kept strictly confidential until the date of publication.

As part of the doctoral degree I have also recently been involved in a service evaluation. The service evaluation will support this main study project and will give new perspectives into non-alcoholic fatty liver disease (NAFLD). Prevalence of NAFLD has risen throughout the world and it is now the most common cause of liver disease both in the UK and India(14).  The disease is highly associated with the development of cirrhosis and diabetes. The Indian population develop NAFLD and diabetes more readily and at a lower BMI (Body Mass Index), yet when comparing BMI measurements, the level of mortality in India is surprisingly lower than that of western countries(15).

The service evaluation concentrates on a main question: to what extent is the prevalence of NAFLD in India and the UK linked to environmental factors, lifestyle and dietary habits and why is the level of mortality lower in the Indian population when compared to western countries? The primary objective was to gain an in-depth understanding and appreciation of local customs and practices. Secondary objectives was be to develop a sustainable network of health professionals with expertise, skills and experience in the prevention and treatment of NAFLD through dietary and lifestyle interventions and to better understand disease dynamics and outcomes.

The results of the service evaluation and the main study will be submitted as part of my final report.

As part of my course of studies (Doctor of Health and Social Care Practice) I have successfully passed the first Module at Level 7: ENGAGING WITH STUDY AND PROFESSIONAL PRACTICE AT DOCTORAL LEVEL. This module was designed to enable doctoral students to understand and engage with doctoral level education and access a wide literature review to underpin their studies and to gain knowledge of their specialist field. Students were encouraged to develop interdependent relationships with relevant professional associations, special interest research groups, and societies, and to contribute their work to conferences and publications, with the intention of disseminating their work to a wider audience. It included 300 hours student learning effort in total, 50 hours lectures/workshops, 10 hours tutorials, 200 hours of person/directed/online and independent study, 40 hours of professional development and networking. We also had to attend  8 full teaching days over the academic course year (excluding induction sessions). Assessment included a systematic or critical literature review of published work and grey literature in the appropriate field of study that was written to the guidelines of a peer reviewed journal of national or international standing from within our own field and a critically reflective paper justifying the area for the proposed research that includes a dissemination strategy.

I am currently due to complete the following Module at Level 8: PROPOSAL SERVICE AND PRACTICE DEVELOPMENT. Submission date is the 7th of January 2016. This module will examine two synergistic areas. Firstly the nature of research and notions of evidence in the students own field in order to prepare us for the final independent research stage. This will lead to an understanding of fundamental epistemological concepts in and contemporary debates about the validity of alternative approaches to research appropriate methodologies and statistical approaches will be examined in relation to the requirements of students’ individual research projects. The second part of this module requires the completion of a small service or practice development project from within the student’s professional field (as described previously). This must be disseminated through the production of an article for a professional peer reviewed journal agreed as suitable with the module leader. Students must also give an oral presentation of 15-20 minutes and a poster presentation at a student led conference (presentation slide included with this progress report).

I will be submitting the proposal by the 7th of January 2016. The service evaluation will be submitted to the University of Derby by the end of March 2016. As previously mentioned, the service evaluation is based on a project run in collaboration with colleagues. The project involved travelling to India from the 1st to the 12th of December 2015. I have collected data which will be analysed in the next few weeks. I will then be able to comply with workload and submission requirements for this last Module.

LESSONS TO BE LEARNED

Throughout the first phase of this study I have developed excellent networking and organisational skills. It is of paramount importance to be able to open and maintain collaborations with colleagues and the wider multidisciplinary team. At the moment I am closely liaising with the dietetic and nutrition team, the School of Physiology (dexa scans) and my academic and professional supervisors.

I have established good working relationships with colleagues although I tend to work solo on this project due to concomitant managerial and departmental commitments. One big lesson to be learned is to build a team of competent and reliable individuals with the capacity, ability and enthusiasm needed to run a research project in the absence of the Principal Investigator. As this is a pilot/feasibility study, I have managed to run this study single handed at a very good standard. However, contingency plans must be in place in the future when I will be designing and hopefully run a randomised controlled trial (RCT) based on the findings of this initial study. The RCT will require additional staff, resources and logistical plans to successfully achieve stated targets.

REFLECTIONS AND CONCLUSIONS

My work based on previous studies shows that for the purpose of nutritional assessment anthropometric parameters, serum albumin concentration, subjective global assessment (SGA), body composition analysis and other tools are available and although relationships between nutritional status and clinical outcome in patients with cirrhosis have been investigated (mainly in class B and C) many studies reported significant relationships that are based on “inappropriate” nutritional variables such as albumin concentration. The assessment of nutritional status in patients suffering with cirrhosis is considered to be inaccurate and most methods have considerable limitations(16). Body weight and BMI are inaccurate because of water retention and other abnormalities such as lymphocyte count and plasma visceral proteins are depleted as the liver is impaired irrespectively of malnutrition.

Hand grip strength (HG) reflects changes that occur in muscle groups even in the early protein calories malnutrition phase and is not directly influenced by liver disease(17.18) . HG was also used to assess muscle mass to assess protein depletion in cirrhotics (19,20,21) although Watters et al(22) found it to be a controversial measurement. Alvares da Silva(23) correlated nutritional status with clinical outcome using SGA, PNI and HG. The reliability of SGA measurements is also supported by Baker et al(24), Barbosa-Silva et al(25) and Stephenson et al(26) for the assessment of malnutrition. Hirsch et al(27) validated SGA in 175 gastroenterology patients in 1990. That study found significant differences between well-nourished and moderately or severely undernourished patients in serum albumin, weight, midarm muscle circumference (MAMC), and triceps skinfold measurements. Based on reviews, HG can be classified as one of the simplest and effective method to detect PCM or risks associated to poor dietary intake.  Anthropometric parameters are a safe and reliable method to assess malnutrition and although most published studies evaluated hospitalised patients and in general at the end of stage liver disease(28,29,30,31), there is enough published evidence to support their reliability(32,33) in clinical practice in the early stage of the disease as discussed in my previous work.

In conclusion, anthropometric measurements are preferred for the assessment of malnutrition: these are triceps skin fold thickness (TSF), mid upper arm circumference (MAC), mid arm muscle circumference (MAMC) and hand grip strength (HG).

There is a lack of studies addressing malnutrition in early cirrhosis. Various methods adopted for the assessment of nutritional status in patients with cirrhosis have been identified and discussed. It is preferable to intervene nutritionally at an earlier time and studies are required to demonstrate that nutritional interventions are vitally important for this group of patients at an early stage of the disease. Dietary/health promotion interventions are essential in the early stage of the disease.