Clinical Practice Guidelines

Nutrition in chronic
liver disease
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
About these slides

• Definitions of all abbreviations shown in these slides are provided

within the slide notes

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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
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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)
Outline

Methods • Grading evidence and recommendations

Background • Present knowledge

Guidelines • Key recommendations

The future • Unresolved issues

 Methods
Grading evidence and recommendations
 Grading evidence and recommendations

• Grading is adapted from the GRADE system1

Grade of evidence
I Randomized, controlled trials
II-1 Controlled trials without randomization
II-2 Cohort or case-control analytical studies
II-3 Multiple time series, dramatic uncontrolled experiments
III Opinions of respected authorities, descriptive epidemiology
Evidence quality
A High
B Moderate
C Low
Grade of recommendation
1 Strong recommendation: Factors influencing the strength of the recommendation included the
quality of the evidence, presumed patient-important outcomes, and cost
2 Weaker recommendation: Variability in preferences and values, or more uncertainty: more
likely a weak recommendation is warranted
Recommendation is made with less certainty: higher cost or resource consumption

1. Guyatt GH, et al. BMJ 2008:336:924–6

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

Deconditioning Deterioration of muscle functional capacity related to immobility and chronic

debilitating disease
Frailty Loss of functional, cognitive, and physiological reserve leading to a
vulnerable state. Frailty may be considered a form of nutrition-related
disorder
Immunonutrition Use of specific nutrients in an attempt to modulate the immune system (not
necessarily in the presence of malnutrition) and function to improve health
state. Examples include enteral nutritional formulas enriched with ω-3 fatty
acids, arginine, glutamine and nucleotides
Malnutrition A nutrition-related disorder resulting from lack of intake or uptake of nutrition
that leads to altered body composition (decreased fat-free mass) and body
cell mass leading to diminished physical and mental function and impaired
clinical outcome from disease. In the present CPG, we have used
“malnutrition” as a synonym of “undernutrition”
Muscle wasting The active, progressive loss of muscle mass due to an underlying disease,
ultimately leading to muscle atrophy. Most inflammatory diseases induce
muscle wasting
Sarcopenia Reduction in muscle mass and function due to ageing (primary sarcopenia),
acute or chronic illness (secondary sarcopenia), including chronic liver
disease
Undernutrition Synonym of malnutrition (see above)
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
 Guidelines
Key recommendations
Topics

1. Screening and assessment for malnutrition and obesity in liver

cirrhosis: who, when and how
2. Nutritional management principles in patients with liver cirrhosis
3. Micronutrients
4. Nutritional treatment options for hepatic encephalopathy
5. Nutritional treatment options in cirrhotic patients with bone diseases
6. Malnutrition in patients undergoing liver surgery and liver
transplantation
7. Malnutrition in critically ill cirrhotic patients
8. The future for nutrition in chronic liver disease
Screening and assessment for malnutrition and
obesity in liver cirrhosis: who, when and how

Recommendations Grade of evidence Grade of recommendation

Perform rapid nutritional screen in all patients with cirrhosis and complete a
detailed assessment in those at risk of malnutrition to confirm the presence II-2 B 1
and severity of malnutrition
Assume risk for malnutrition to be high if BMI <18.5 kg/m2 or Child–Pugh C.
In all other instances, utilize nutritional screening tools to assess the risk of II-2 B 1
malnutrition
In the diagnosis of obesity (BMI >30 kg/m 2) take care of the confounding
II-2 B 1
effect of fluid retention. Estimate dry body weight, although accuracy is low
Screening and assessment for malnutrition and
obesity in liver cirrhosis: who, when and how

Recommendations Grade of evidence Grade of recommendation

Always include an assessment of sarcopenia within the nutritional
assessment II-2 B 1
Assess muscle mass by CT imaging, where this is available (having been
performed for other purposes). Anthropometry, DEXA or BIA are possible II-2 B 1
alternatives, which also allow serial measurements
Assess muscle function, in the clinical setting, with the most appropriate tool
such as handgrip strength (HGS) and the Short Physical Performance II-2 B 1
Battery (SPPB)
Assess dietary intake by trained personnel (ideally a dietician with
knowledge of managing patients with liver disease) working as part of a
team with the hepatologist. Assessment should include: quality and quantity II-2 B 1
of food and supplements, fluids, sodium in diet, number and timing of meals
during the day and barriers for eating
 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
body weight 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
Nutritional management principles in patients with
liver cirrhosis

Recommendations Grade of evidence Grade of recommendation

Start nutritional counselling by a multidisciplinary team supporting the patient
for adequate calories and protein intake in patients with malnutrition and II-2 C 1
cirrhosis
Optimal daily energy intake should not be lower than the recommended
II-2 B
35 kcal/kg actual body weight
 
  1
 
Optimal daily protein intake should not be lower than the recommended
II-2 B
1.5 g/kg actual body weight
Include late evening oral nutritional supplementation (ONS) and breakfast
containing some proteins in malnourished decompensated cirrhotic patients II-1 B 1
BCAA supplements and leucine enriched amino acid supplements should be
considered in decompensated cirrhotic patients II-1 B 1
In patients with malnutrition and cirrhosis who are unable to achieve
adequate dietary intake with the oral diet (even with oral supplements), a II-1 B 1
period of enteral nutrition is recommended
Nutritional management principles in patients with
liver cirrhosis

Recommendations Grade of evidence Grade of recommendation

Avoid hypomobility in cirrhotic patients and propose a personalized physical
activity program even in decompensated patients whenever possible III C 1
Implement a nutritional and lifestyle program to achieve a progressive
weight loss (> 5–10%) in obese cirrhotic patients (BMI >30 kg/m 2 corrected II-2 C 1
for water retention)
Adopt a tailored, moderately hypocaloric (-500–800 kcal/day) diet, including
an adequate amount of protein (>1.5 g protein/kg BW/day) to achieve weight III C 2
loss without compromising protein stores in obese cirrhotic patients
Micronutrients

Recommendations Grade of evidence Grade of recommendation

In cirrhotic patients, administer micronutrients and vitamins to treat
confirmed or clinically suspected deficiency III C 1
Assess vitamin D levels in cirrhotic patients as deficiency is highly prevalent
and adversely affects clinical outcomes II-3 B 1
Supplement vitamin D orally in cirrhotic patients with vitamin D levels
<20 ng/ml, to reach serum vitamin D (25(OH)D) >30 ng/ml III B 1
In cirrhotic patients with ascites following sodium restriction (recommended
intake of sodium ~80 mmol day = 2 g of sodium corresponding to 5 g of salt
II-2 B 1
added daily to the diet according to EASL guidelines) take care to improve
diet palatability as this regime may cause a reduction in calorie intake
Nutritional treatment options for hepatic
encephalopathy

Recommendations Grade of evidence Grade of recommendation

Always evaluate nutritional status and sarcopenia in patients with hepatic
III C 1
encephalopathy (HE)
Avoid protein restriction in patients with HE II-1 A 1
Optimal daily protein and energy intake should not be lower than the general
II-1 A 1
recommendations for cirrhotic patients
Encourage the consumption of vegetables and dairy protein III-B B 1
BCAA supplementation can be considered to improve neuropsychiatric
II-2 B 1
performance and to reach the recommended nitrogen intake
In patients who can tolerate oral intake prefer dietary intake by mouth In
patients with grade III–IV encephalopathy, who are unable to eat, provide
III B 1
nutrition by naso-gastric tube (in patients with protected airways) or
parenterally
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
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
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
 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
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
Nutritional treatment options for patients with bone
diseases

Recommendations Grade of evidence Grade of recommendation

Evaluate BMD in cirrhotic patients and in patients with cholestatic liver
III A 1
diseases, long-term corticosteroid treatment, and before liver transplantation
Utilize lumbar and femoral densitometry (DEXA) for diagnosing osteoporosis
and osteopenia. Lateral X-rays of dorsal and lumbar spine for diagnosing II-3 A 1
vertebral fractures
Repeat DEXA after 2–3 years in patients within normal BMD, and within
III B 1
1 year when rapid bone loss is expected
Include supplements of calcium (1,000–1,500 mg/day) and 25-hydroxy-
vitamin D (400–800 IU/day or 260 µg every 2 weeks) in patients with CLD II-3 A 1
and a T-score below -1.5
Utilize bisphosphonates in cirrhotic patients with osteoporosis and in those
IA 1
waiting for liver transplantation
Consider testosterone supplementation and venesection in males with
II-2 B 1
haemochromatosis and hypogonadism
Malnutrition in patients undergoing liver surgery and
liver transplantation – preoperative nutrition

Recommendations Grade of evidence Grade of recommendation

Screen for malnutrition liver cirrhosis patients listed for transplantation or
scheduled for elective surgery. Treat sarcopenia prior to elective surgery, as III B 1
this will allow improvement in body protein status and clinical outcomes
Screen for sarcopenic obesity with body composition analysis in obese
cirrhotic patients considered for surgery in order to identify those at higher III C 1
risk for morbidity and mortality
Preoperatively, if the treatment goal is maintenance of nutritional status, plan
a total energy intake of 30 kcalkg-1d-1 and a protein intake of
II-3 B 1
1.2 gkg-1d-1. If improvement of nutritional status is the goal, plan a total
energy intake of 35 kcalkg-1d-1 and a protein intake of 1.5 gkg-1d-1
For preoperative nutrition, utilize standard nutrition regimens since
specialized regimens (e.g. BCAA-enriched, immune-enhancing diets) have II-1 B 1
not been shown to improve morbidity or mortality
Malnutrition in patients undergoing liver surgery and
liver transplantation – postoperative nutrition

Recommendations Grade of evidence Grade of recommendation

After liver transplantation initiate normal food and/or enteral tube feeding
preferably within 12–24 hours postoperatively, or as soon as possible, to II-2 B 1
reduce infection rates
When oral or enteral nutrition are not possible or impracticable, prefer
parenteral nutrition to no feeding in order to reduce complication rates, time II-2 B 1
on mechanical ventilation and ICU stay
After the acute postoperative phase, provide an energy intake of
II-2 C 1
35 kcalkg-1d-1 and a protein intake of 1.5 gkg-1d-1
After other surgical procedures, manage patients with chronic liver disease
III C 1
according to the ERAS protocol
Consider PN in patients with unprotected airways and hepatic
encephalopathy (HE) when cough and swallow reflexes are compromised, II-2 C 1
or enteral nutrition is contraindicated or impractical
Utilize enteral tube feeding and/or PN with a reduced target energy intake
(25 kcalkg-1d-1) and an increased target protein intake (2.0 gkg-1d-1) in III C 1
obese patients
Malnutrition in critically ill cirrhotic patients

Recommendations Grade of evidence Grade of recommendation

Consider nutritional status and presence of sarcopenia in all critically ill
cirrhotic patients and institute nutritional care while treating other II-3 C 1
manifestations of severe decompensation
Supplement dietary intake by enteral nutrition in critically ill cirrhotic patients
who are unable to achieve adequate diet by mouth. If oral diet or enteral III A 1
nutrition are not tolerated or contra-indicated, consider parenteral nutrition
Naso-gastroenteric tubes are not contraindicated in patients with
II-2 A 1
non-bleeding oesophageal varices
Avoid PEG insertion in cirrhotic patients due to risk of bleeding III B 2
Malnutrition in critically ill cirrhotic patients

Recommendations Grade of evidence Grade of recommendation

Take care that daily energy intake in critically ill cirrhotic patients is not lower
than the recommended 35–40 kcalkg-1d-1 or 1.3 times measured resting II-2 B 1
energy expenditure
Take care that daily protein intake in critically ill cirrhotic patients is not lower
II-2 B 1
than the recommended 1.2-1.3 gkg-1d-1
Utilize standard nutrition regimens since no advantage has been shown for
specialized regimens (e.g. BCAA-enriched, immune-enhancing diets) in II-1 B 2
terms of morbidity or mortality
In patients with hepatic encephalopathy, consider BCAA-enriched solutions
IA 1
to improve its resolution
In cirrhosis and severe/acute alcoholic hepatitis, consider nutritional support
as it may accelerate resolution of hepatic encephalopathy and improve II-1 A 1
survival in patients with low calorie intake
The future for nutrition in
chronic liver disease
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
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
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?