The role of preoperative optimization of the nutritional status on the improvement of short-term outcomes after liver transplantation? A review of the literature and expert panel recommendations.

BACKGROUND: Malnutrition is a known risk factor for postoperative morbidity and mortality in patients awaiting liver transplantation (LT). Malnutrition is a potentially reversible risk factor, though there are no clear guidelines on the best mechanism for an improvement. It also remains unclear if preoperative nutritional interventions have benefits to post-transplant outcomes for transplant recipients. OBJECTIVES: Primary objective: To identify if preoperative optimization of nutritional status is associated with improved short-term outcomes after LT. SECONDARY OBJECTIVES: To determine if preoperative improvement of malnutrition improves short-term outcomes after LT, as well as if weight loss in obese patients affects short-term outcomes after LT. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. POSPERO Protocol ID: CRD42021237450 RESULTS: 3851 records were identified in searching the databases, 3843 records were excluded by not fulfilling eligibility criteria. Seven full-text articles were included for the final analysis of which three were randomized controlled trials, one was prospective observational studies, and three were retrospective observational studies. No appreciable difference in mortality, post-transplant complication rate was noted across the studies. Length of stay (LOS) was noted to be shorter in two observational studies of Vitamin D deficiency in liver transplant patients. CONCLUSIONS: We have made a weak recommendation supporting pre-transplant nutritional supplementation due to possible benefit in reducing LOS as well as the lack of harm (Quality of Evidence low | Grade of Recommendation; Weak). No effective conclusions were reached for the secondary objectives due to the conflicting evidence.

Home-Based Exercise in Patients Awaiting Liver Transplantation: A Feasibility Study.

Frailty is associated with increased mortality both before and after liver transplantation (LT). There are no standardized exercise programs, in particular home-based exercise programs (HBEPs), for patients awaiting LT. The aim was to investigate the feasibility of such a program in patients awaiting LT. Patients were randomly selected from the Birmingham LT waiting list and provided with a 12-week HBEP, including average daily step (ADS) targets and twice-weekly resistance exercises. Feasibility was based on patient eligibility (≥66% of waiting list), target recruitment (≥90% of n = 20), safety (no related serious adverse events), and adherence (≥66% adherence to 6-week HBEP). Measures of aerobic (incremental shuttle walk test [ISWT], ADS), functional capacity (short physical performance battery test [SPPBT]), and health-related quality of life (EuroQol 5-Dimension 5-Level (EQ-5D-5L) and hospital anxiety and depression score [HADS]) were taken at baseline and at 6 and 12 weeks. 18 patients (50% male; median age, 55 years) were recruited. All domains of the study feasibility criteria were met. ISWT improved after 6 weeks (50 m; P ≤ 0.01) and 12 weeks (210 m; P ≤ 0.01), despite withdrawal of the telephone health calls. Similarly, improvements were seen in ADS (2700/day; P ≤ 0.01) and the SPPBT (2.5; P = 0.02) after 12 weeks. There was no difference in HADS (median difference [MD] -3; P = 0.69), but EQ-5D-5L after 12 weeks (17.5%; P = 0.04). In conclusion, a 12-week HBEP, incorporating both easy-to-apply resistance and aerobic exercises, is safe and feasible in patients awaiting LT. Measures of aerobic and functional capacity demonstrate trends toward improvement that warrant further investigation in a randomized controlled trial.

Duke Activity Status Index and Liver Frailty Index predict mortality in ambulatory patients with advanced chronic liver disease: A prospective, observational study.

BACKGROUND: There remains a lack of consensus on how to assess functional exercise capacity and physical frailty in patients with advanced chronic liver disease (CLD) being assessed for liver transplantation (LT). Aim To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD. AIM: To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD. METHODS: We recruited patients from outpatient clinics at University Hospitals Birmingham, UK (2018-2019). We prospectively collated the DASI and LFI to identify the prevalence of, respectively, functional capacity and physical frailty, and to evaluate their accuracy in predicting overall and pre-LT mortality. RESULTS: We studied 307 patients (57% male; median age 54 years; UKELD 52). Median DASI score was 28.7 (IQR 16.2-50.2), mean LFI was 3.82 (SD = 0.72), and 81% were defined either 'pre-frail' or 'frail'. Female sex and hyponatraemia were significant independent predictors of both DASI and LFI. Age and encephalopathy were significant independent predictors of LFI, while BMI significantly predicted DASI. DASI and LFI were significantly related to overall (HR 0.97, p = 0.001 [DASI], HR 2.04, p = 0.001 [LFI]) and pre-LT mortality (HR 0.96, p = 0.02 [DASI], HR 1.94, p = 0.04 [LFI]). CONCLUSIONS: Poor functional exercise capacity and physical frailty are highly prevalent among ambulatory patients with CLD who are being assessed for LT. The DASI and LFI are simple, low-cost tools that predict overall and pre-LT mortality. Implementation of both should be considered in all outpatients with CLD to highlight those who may benefit from targeted nutritional and exercise interventions.

Quality standards for the management of alcohol-related liver disease: consensus recommendations from the British Association for the Study of the Liver and British Society of Gastroenterology ARLD special interest group.

OBJECTIVE: Alcohol-related liver disease (ALD) is the most common cause of liver-related ill health and liver-related deaths in the UK, and deaths from ALD have doubled in the last decade. The management of ALD requires treatment of both liver disease and alcohol use; this necessitates effective and constructive multidisciplinary working. To support this, we have developed quality standard recommendations for the management of ALD, based on evidence and consensus expert opinion, with the aim of improving patient care. DESIGN: A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology ALD Special Interest Group developed the quality standards, with input from the British Liver Trust and patient representatives. RESULTS: The standards cover three broad themes: the recognition and diagnosis of people with ALD in primary care and the liver outpatient clinic; the management of acutely decompensated ALD including acute alcohol-related hepatitis and the posthospital care of people with advanced liver disease due to ALD. Draft quality standards were initially developed by smaller working groups and then an anonymous modified Delphi voting process was conducted by the entire group to assess the level of agreement with each statement. Statements were included when agreement was 85% or greater. Twenty-four quality standards were produced from this process which support best practice. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice and an audit tool provided. CONCLUSION: It is hoped that services will review their practice against these recommendations and key performance indicators and institute service development where needed to improve the care of patients with ALD.

Protocol for a case-control prospective study to investigate the impact of Hepatic Encephalopathy on Nutritional Intake and Sarcopenia status in patients with end-stage LIVer disease: HENS-LIV study.

INTRODUCTION: Hepatic encephalopathy (HE) is a debilitating symptom of end-stage liver disease (ESLD), but there remains a paucity of evidence regarding its impact on nutritional status, nutritional intake, compliance with nutritional support and resultant muscle health and function. Malnutrition and sarcopenia are associated with increased morbidity and mortality in patients with ESLD. The aim of the current case-control study is to prospectively investigate the impact of HE on nutritional intake and sarcopenia status in patients with ESLD. METHODS AND ANALYSIS: Patients with ESLD, with HE (n=10) and without HE (n=10) will be recruited at the outpatient liver unit, University Hospital Birmingham, UK. All patients will undergo clinical assessment at baseline and again at 6-8 weeks (in-line with their routine clinical follow-up), to assess the impact of HE on reported nutritional intake, nutritional status and sarcopenia/physical functional status. Standard medical, dietetic and home-based exercise physiotherapy care will continue for all participants as determined by their clinical team. Two methods of assessing nutritional intake will include the 24-hour food recall and 3-day food diaries. Assessment of sarcopenia status will be undertaken using anthropometry (mid-arm muscle circumference (MAMC)) and ultrasound imaging of the quadriceps muscle group. Markers of physical function (hand grip strength; chair rise time), frailty (Liver Frailty Index (LFI)), physical activity (accelerometery) and exercise capacity (Duke Activity Status Index (DASI)) will be assessed at both clinic visits. ETHICS AND DISSEMINATION: The study is approved by Wales Research Ethics Committee 2 and Health Research Authority (REC reference: 21/WA/0216). Recruitment into the study commenced November 2021. The findings will be disseminated through peer-reviewed publications and international presentations. TRIAL REGISTRATION NUMBER: RRK7156.

Nutrition in alcohol-related liver disease: Physiopathology and management.

Malnutrition encompassing both macro- and micro-nutrient deficiency, remains one of the most frequent complications of alcohol-related liver disease (ArLD). Protein-energy malnutrition can cause significant complications including sarcopenia, frailty and immunodepression in cirrhotic patients. Malnutrition reduces patient's survival and negatively affects the quality of life of individuals with ArLD. Moreover, nutritional deficit increases the likelihood of hepatic decompensation in cirrhosis. Prompt recognition of at-risk individuals, early diagnosis and treatment of malnutrition remains a key component of ArLD management. In this review, we describe the pathophysiology of malnutrition in ArLD, review the screening tools available for nutritional assessment and discuss nutritional management strategies relevant to the different stages of ArLD, ranging from acute alcoholic hepatitis through to decompensated end stage liver disease.

Home-based exercise therapy in patients awaiting liver transplantation: protocol for an observational feasibility trial.

INTRODUCTION: Liver disease is the third most common cause of premature mortality in the UK. Liver failure accelerates frailty, resulting in skeletal muscle atrophy, functional decline and an associated risk of liver transplant waiting list mortality. However, there is limited research investigating the impact of exercise on patient outcomes pre and post liver transplantation. The waitlist period for patients listed for liver transplantation provides a unique opportunity to provide and assess interventions such as prehabilitation. METHODS AND ANALYSIS: This study is a phase I observational study evaluating the feasibility of conducting a randomised control trial (RCT) investigating the use of a home-based exercise programme (HBEP) in the management of patients awaiting liver transplantation. Twenty eligible patients will be randomly selected from the Queen Elizabeth University Hospital Birmingham liver transplant waiting list. Participants will be provided with an individually tailored 12-week HBEP, including step targets and resistance exercises. Activity trackers and patient diaries will be provided to support data collection. For the initial 6 weeks, telephone support will be given to discuss compliance with the study intervention, achievement of weekly targets, and to address any queries or concerns regarding the intervention. During weeks 6-12, participants will continue the intervention without telephone support to evaluate longer term adherence to the study intervention. On completing the intervention, all participants will be invited to engage in a focus group to discuss their experiences and the feasibility of an RCT. ETHICS AND DISSEMINATION: The protocol is approved by the National Research Ethics Service Committee North West - Greater Manchester East and Health Research Authority (REC reference: 17/NW/0120). Recruitment into the study started in April 2017 and ended in July 2017. Follow-up of participants is ongoing and due to finish by the end of 2017. The findings of this study will be disseminated through peer-reviewed publications and international presentations. In addition, the protocol will be placed on the British Liver Trust website for public access. TRIAL REGISTRATION NUMBER: NCT02949505; Pre-results.