Clinical Practice Guidelines

1. Clinical Practice Guidelines Nutrition in chronic liver disease

2. About these slides These slides give a comprehensive overview of the EASL clinical practice guidelines on nutrition in chronic liver disease The guidelines were first presented at the International Liver Congress 2018 and will be published soon in the Journal of Hepatology • The full publication will be downloadable from the Clinical Practice Guidelines section of the EASL website once available Please feel free to use, adapt, and share these slides for your own personal use; however, please acknowledge EASL as the source

3. About these slides • Definitions of all abbreviations shown in these slides are provided within the slide notes • When you see a home symbol like this one: , you can click onthis to return to the outline or topics pages, depending on whichsection you are in • Please send any feedback to: slidedeck_feedback@easloffice.eu These slides are intended for use as an educational resource and should not be used in isolation to make patient management decisions. All information included should be verified before treating patients or using any therapies described in these materials

4. Guideline panel • Chair • Manuela Merli • Panel members • Shira Zelber-Sagi, Srinivasan Dasarathy, Sara Montagnese, Laurence Genton, Mathias Plauth, Albert Parés, Annalisa Berzigotti(EASL Governing Board Representative)

5. Outline

6. Methods Grading evidence and recommendations

7. Grading evidence and recommendations • Grading is adapted from the GRADE system1 1. Guyatt GH, et al. BMJ 2008:336:924–6

8. Methods • Questions to address were first established, taking into account relevance, urgency and completeness of each • Key questions addressed: • How to recognize nutritional problems. In which conditions is nutritional assessment recommended? • What are the available methods of evaluation? • What are the consequences of malnutrition and its correction in different clinical scenarios • Nutrition in chronic liver disease • Nutrition in hepatic encephalopathy • Nutrition before and after liver transplantation • Bone metabolism in chronic liver disease • A literature search was performed in different databases to identify references. Pertinent key words were defined for each specific topic of the Guideline • Reference selection was based on appropriateness of study design, number of patients, and publication in peer-reviewed journals. Original data were prioritised

9. Background The burden of malnutrition in liver cirrhosis Malnutrition definition Mechanisms and potential targets for sarcopenia

10. Prevalence and implications of malnutrition and sarcopenia in cirrhosis • Malnutrition is a frequent burden in liver cirrhosis; reported in 20% of patients with compensated cirrhosis and in more than 50% of patients with decompensated liver disease • The progression of malnutrition is associated with the progression of liver failure, and while malnutrition may be less evident in compensated cirrhosis, it is easily recognizable in decompensated patients • Both adipose tissue and muscle tissue can be depleted; female patients more frequently develop a depletion in fat deposits while males more rapidly lose muscle tissue

11. Prevalence and implications of malnutrition and sarcopenia in cirrhosis • Malnutrition and muscle mass loss (sarcopenia), which has been often used as an equivalent of severe malnutrition, are associated with a higher rate of complications • Susceptibility to infections • Hepatic encephalopathy • Ascites • Independent predictors of lower survival in cirrhosis and in patients undergoing liver transplantation • Given these observations, malnutrition and sarcopenia should be recognized as a complication of cirrhosis, which in turn further worsens the prognosis of cirrhotic patients  

12. Malnutrition definition • The term “malnutrition” refers both to deficiencies and to excesses in nutritional status. In the present guidelines, we identify “malnutrition” with “undernutrition” • More recently, in addition to undernutrition, cirrhotic patients who are overweight or obese are increasingly being observed due to the increased number of cirrhosis cases related to NASH • Muscle mass depletion may also occur in these patients, but due to the coexistence of obesity, sarcopenia might be overlooked • Obesity and sarcopenic obesity may worsen the prognosis of patients with liver cirrhosis

13. Terminology

14. Mechanisms resulting in sarcopenia and failure to respond to standard supplementation • Anabolic resistance and dysregulated proteostasis result in failure to respond to standard supplementation • These mechanisms represent potential therapeutic targets

15. Guidelines Key recommendations

16. Topics • Screening and assessment for malnutrition and obesity in liver cirrhosis: who, when and how • Nutritional management principles in patients with liver cirrhosis • Micronutrients • Nutritional treatment options for hepatic encephalopathy • Nutritional treatment options in cirrhotic patients with bone diseases • Malnutrition in patients undergoing liver surgery and liver transplantation • Malnutrition in critically ill cirrhotic patients • The future for nutrition in chronic liver disease

17. Screening and assessment for malnutrition and obesity in liver cirrhosis: who, when and how Grade of evidence Grade of recommendation

18. Screening and assessment for malnutrition and obesity in liver cirrhosis: who, when and how Grade of evidence Grade of recommendation

19. Nutritional screening and assessment in patients with cirrhosis †In a case of fluid retention, body weight should be corrected by evaluating the patient’s dry weight by post-paracentesis bodyweight or weight recorded before fluid retention if available, or by subtracting a percentage of weight based upon severity of ascites (mild, 5%; moderate, 10%; severe, 15%), with an additional 5% subtracted if bilateral pedal oedema is present

20. Nutritional management principles in patients with liver cirrhosis Grade of evidence Grade of recommendation

21. Nutritional management principles in patients with liver cirrhosis Grade of evidence Grade of recommendation

22. Micronutrients Grade of evidence Grade of recommendation

23. Nutritional treatment options for hepatic encephalopathy Grade of evidence Grade of recommendation

24. Short, practical dietary advice for bedside or outpatient clinic use Dear patient, • Most of what you have heard/read on the relationship between food and the liver has limited scientific evidence to support it. Generally, healthy eating of a variety of foods is advisable to all patients • Virtually no food other than alcohol actually damages the liver and/or is genuinely contraindicated in patients with chronic liver disease • In most patients with chronic liver disease, eating an adequate amount of calories and protein is much more important than avoiding specific types of food, so it is important that you have a good, varied diet that you enjoy

25. Short, practical dietary advice for bedside or outpatient clinic use • You should try to split your food intake into three main meals (breakfast, lunch and dinner) and three snacks (mid-morning, mid-afternoon, late evening). The late-evening snack is the most important, as it covers the long interval between dinner and breakfast • You should try to eat as many fruit and vegetables as you can. If you feel that this makes you feel bloated, and that it makes you eat less, please report to your doctor or dietician • You should try not to add too much salt to your food. It may take some time to adjust, but it usually gets easier with time. However, if you keep feeling that this makes your food unpleasant to eat, and that it makes you eat less, please report to your doctor or dietician

26. Short, practical dietary advice for bedside or outpatient clinic use • Patients with liver disease may have hepatic encephalopathy, which may make them tolerate animal proteins (meat) less well than vegetable proteins (beans, peas etc) and dairy proteins. Before you make any changes to your protein intake, you should always ask your doctor or dietician. Please do not reduce your total protein intake as it is not advisable in cirrhosis • Some patients with liver disease have other diseases, for example diabetes or are overweight/obese, which require dietary adjustments. Please remember to tell your doctor about all your illnesses and about any dietary advice you have already received from other doctors, nurses or dieticians

27. Diagnosis and management of bone disease in patients with chronic liver disease *Calcium (1,000–1,500 mg/d) and 25-hydroxy-vitamin D (400–800 IU/day or 260 μg every 2 weeks) to preserve normal levels; **According to the severity of liver disease and cholestasis, and in patients taking corticosteroids; ***Depending on additional risk factors

28. Risk factors for the development of osteoporosis in chronic liver disease • Alcohol abuse • Smoking • Body mass index <19 kg/m2 • Male hypogonadism • Early menopause • Secondary amenorrhea of more than 6 months • Family history of osteoporotic fracture • Treatment with corticosteroids (≥5 mg/d prednisone for ≥3 months) • Advanced age

29. Nutritional treatment options for patients with bone diseases Grade of evidence Grade of recommendation

30. Malnutrition in patients undergoing liver surgery and liver transplantation – preoperative nutrition Grade of evidence Grade of recommendation

31. Malnutrition in patients undergoing liver surgery and liver transplantation – postoperative nutrition Grade of evidence Grade of recommendation

32. Malnutrition in critically ill cirrhotic patients Grade of evidence Grade of recommendation

33. Malnutrition in critically ill cirrhotic patients Grade of evidence Grade of recommendation

34. The future for nutrition in chronic liver disease

35. New research should answer the following topics • Does the improvement in muscle mass and/or muscle function improve clinical outcomes (reduced risk of first decompensation, ascites, infection and encephalopathy, hospital readmissions or falls, decreased length of hospital stay, improved survival)? • Do ammonia-lowering strategies in decompensated cirrhosis reverse muscle loss and improve clinical outcomes? • Does a gradual increase in physical activity delay or reverse muscle loss and contractile dysfunction? The type of exercise and its duration that are beneficial in cirrhotic patients need to be determined

36. New research should answer the following topics • Is the addition of supplements (leucine, isoleucine, or other nutrient supplements) needed to lower ammonia and increase mitochondrial intermediates during training? • How to implement therapies targeting muscle protein synthesis pathways or dysregulated muscle autophagy • How to overcome anabolic resistance or reverse the underlying causes of anabolic resistance in cirrhotic patients

37. New research should answer the following topics • In the absence of indirect calorimetry, what is the best way to calculate energy needs in critically ill patients with liver disease? • Does increased energy and protein intake improve outcome in critically ill patients with liver diseases? • Should the nutritional recommendations differ according to the nutritional status at baseline?