Clinical Practice GuidelinesEASL Clinical Practice Guidelines on nutrition in chronic liver disease
Introduction
Malnutrition is frequently a burden in patients with liver cirrhosis, occurring in 20–50% of patients. The progression of malnutrition is associated with that of liver failure. While malnutrition may be less evident in patients with compensated cirrhosis it is easily recognisable in those with decompensated cirrhosis. Malnutrition has been reported in 20% of patients with compensated cirrhosis and in more than 50% of patients with decompensated liver disease.1 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.[2], [1]
As detailed in these clinical practice guidelines (CPGs), malnutrition and muscle mass loss (sarcopenia), which has often been used as an equivalent of severe malnutrition,3 are associated with a higher rate of complications4 such as susceptibility to infections,5 hepatic encephalopathy (HE)6 and ascites, 4 as well as being independent predictors of lower survival in cirrhosis[7], [8] and in patients undergoing liver transplantation.9 Given these observations, malnutrition and sarcopenia should be recognised as complications of cirrhosis, which in turn worsen the prognosis of cirrhotic patients.
Whether malnutrition can be reversed in cirrhotic patients is controversial. Although there is general agreement about the need to improve the dietary intake of these patients, by avoiding limitations and restrictions that are not evidence based, amelioration of the nutritional status and muscle mass is not always achievable.[10], [11], [12]
Although the term “malnutrition” refers both to deficiencies and to excesses in nutritional status, in the present CPGs “malnutrition” refers to “undernutrition”. More recently, in addition to undernutrition, overweight or obesity are increasingly observed in cirrhotic patients because of the increasing number of cirrhosis cases related to non-alcoholic steatohepatitis (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], [14], [15], [3]
No previous guidelines released by the European Association for the Study of Liver Disease (EASL) have dealt with nutrition in advanced liver disease and/or have evaluated the relationship between nutritional status and the clinical outcome of patients. Therefore, the EASL Governing Board has asked a panel of experts in the field of nutrition and hepatology to produce the present CPGs.
Section snippets
Methodology
The panel initially established the most relevant questions to answer, considering relevance, urgency and completeness of the topics to be covered. The main questions addressed were: How can nutritional problems be recognised? In which conditions are nutritional assessments recommended? What are the available methods of evaluation? What are the consequences of malnutrition and its correction? Different clinical scenarios have been considered with special attention paid to nutrition in HE and
Screening and assessment for malnutrition and obesity in liver cirrhosis: Who, when and how
Given the worse prognosis associated with malnutrition, all patients with advanced chronic liver disease, and in particular patients with decompensated cirrhosis are advised to undergo a rapid nutritional screen. Those at risk of malnutrition should complete a more detailed nutritional assessment to confirm the presence and severity of malnutrition,[17], [18], [19] in order to actively manage this complication.
Nutritional management principles in patients with liver cirrhosis
Since malnutrition and sarcopenia are independent predictors of adverse clinical outcomes including survival[57], [58], [59], [17], [60] any nutritional approach in cirrhotic patients needs to be guided by some general principles of nutritional management.
Factors related with sarcopenia in patients with cirrhosis
Skeletal muscle mass is the largest protein store in the body. A balance between skeletal muscle protein synthesis and breakdown is responsible for protein homeostasis (or proteostasis) that maintains skeletal muscle mass.[66], [87], [88] In the past, whole body protein turnover studies have yielded conflicting results with unaltered, increased or decreased protein synthesis and breakdown in cirrhosis.[3], [89] Skeletal muscle mass depends on a number of physiological factors including age,
Nutritional approach and management of obesity in patients with liver cirrhosis
Two studies have shown that obesity is at least as frequent in compensated cirrhosis as it is in the general population, ranging from 20 to 35%,[13], [125] regardless of the origin of liver disease. In NASH-related cirrhosis obesity is present in most cases. Moreover, a sedentary lifestyle is highly prevalent in patients with cirrhosis and might be seen as a cofactor, leading to an increase in BW in this population. In the HALT-C trial125 the risk of histological progression or decompensation
Micronutrients
In general, vitamin deficiencies in liver disease are related to hepatic dysfunction, diminished reserves and, with increasing disease severity, inadequate dietary intake and malabsorption.
Fat-soluble vitamin deficiencies are common. A retrospective study reported that the majority of liver disease patients being considered for transplantation presented with vitamin A and D deficiencies.127
The prevalence of vitamin D deficiency in the general population ranges from 20 to 100% when referring to
Nutritional treatment options for hepatic encephalopathy
The relationship between malnutrition and HE has been known since the seminal observation that decreased energy intake determines weight loss and coma in Eck’s fistula dogs.148 Human studies also support this association. HE occurs more frequently in malnourished patients with cirrhosis, and there is an inverse relationship between muscle mass and blood ammonia levels.[149], [150] Sarcopenia, as assessed by the skeletal muscle index, is an independent risk factor for the development of HE after
Nutritional treatment options in cirrhotic patients with bone diseases
‘Hepatic osteodystrophy’, including osteoporosis and osteomalacia, has been used for years to describe the bone disease of patients with liver damage. Osteoporosis, characterised by loss of bone mass and quality that leads to fragility fractures, is common in patients with chronic liver disease.173 Osteomalacia resulting from poor bone mineralisation is uncommon and only present when associated with persistent vitamin D deficiency in individuals with severe and long-lasting cholestasis and
Preoperative nutrition
Both severe under nutrition (BMI <18.5 kg/m2) and severe obesity (BMI >40 kg/m2) prior to liver transplantation are associated with increased mortality and morbidity.[224], [225], [226], [227] Severe obesity prior to liver transplantation is associated with a higher prevalence of comorbidities (diabetes, hypertension), cryptogenic cirrhosis and increased mortality from infectious complications, cardiovascular disease and cancer.[226], [227] Some investigators found that severe obesity was
Conclusion
Nutrition in chronic liver disease is a rapidly evolving field and the object of growing clinical interest. These Clinical Practice Guidelines have been produced with the aim of summarising current knowledge in this field. Nutritional impairment and sarcopenia have been recognised as crucial complications of chronic liver disease, which severely impact on prognosis. Undernutrition and sarcopenia are also interconnected with other complications of cirrhosis such as HE, ascites and the
Conflict of interest
S.D. reports grant/research support from the National Institutes of Health, RO1 DK113196; RO1 GM 119174; R21 AR071045; P50 AA024333; UO1 AA021890; UO1061732 and the Mikati Foundation Research Grant. A.P. reports grants, personal fees and other from Intercept Pharmaceuticals, other from Novartis, personal fees from Cymabay Therapeutics, Inc., outside the submitted work. M.M. reports personal fees from Kedrion. All other authors report no conflicts of interest.
Please refer to the accompanying
Acknowledgements
We would like to thank the reviewers of this Clinical Practice Guideline for their time and critical reviewing; EASL Governing Board, Dominique Valla, Stephan Bischoff, Puneeta Tandon.
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