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Nutrition in Patients With Cirrhosis
Fernando Calmet, MD, Paul Martin, MD, and Michelle Pearlman, MD
Dr Calmet is a fellow, Dr Martin is a Abstract: Malnutrition is a common complication of cirrhosis,
professor and the division chief, and increases in frequency with Child-Turcotte-Pugh (CTP) score, and
Dr Pearlman is an assistant professor in is associated with an increased morbidity and mortality. Although
the Division of Gastroenterology and malnutrition is easily recognized in chronically ill patients with
Hepatology at the University of Miami CTP class C cirrhosis, it is present but often unrecognized in up to
Miller School of Medicine in Miami,
Florida. 50% of patients with CTP class A cirrhosis; thus, all patients with
cirrhosis, regardless of etiology or severity, should be screened for
malnutrition. A nutritional screening should be incorporated into
Address correspondence to: the routine clinical care of patients with cirrhosis, with a more
Dr Paul Martin extensive nutritional assessment that includes a detailed history,
Division of Gastroenterology and dietary recall, baseline nutrition laboratory tests, and evaluation
Hepatology
University of Miami Miller School of sarcopenia using imaging modalities or strength testing to
of Medicine determine the degree of frailty. A thorough assessment will allow
1120 NW 14th Street for a personalized treatment plan that provides the patient with
Miami, FL 33136 total daily caloric intake goals with an emphasis on quality protein,
Tel: 305-243-2147 education on timing of oral intake with a reduction in periods of
Fax: 305-243-7545 fasting, identification and treatment of micronutrient deficiencies,
E-mail: pmartin2@med.miami.edu
and recommendation of safe and realistic exercise programs to
help prevent and/or reduce sarcopenia and improve frailty.
alnutrition is a common complication of cirrhosis,
although the definition of malnutrition is quite variable in
Madults and is even more nebulous in patients with hepatic
dysfunction. In adults, malnutrition in cirrhosis is typically defined
as loss of skeletal muscle mass and strength (sarcopenia) in addi-
tion to diminished subcutaneous and visceral fat mass (adipopenia)
from reduced protein and energy consumption. Hepatic cachexia is
another term used to describe the loss of skeletal muscle in patients
with cirrhosis. Lack of consensus in regard to the precise definition
of malnutrition in this patient population makes outcome-based
studies difficult to perform and interpret.1 Protein-calorie malnutri-
tion is associated with low body mass index (BMI), sarcopenia, and
2
immune incompetence. Sarcopenia is one of the major components
Keywords of frailty; however, frailty not only involves loss of skeletal mass but
Cirrhosis, malnutrition, sarcopenia, frailty, also requires loss of performance.3 The prevalence of malnutrition
nutritional assessment in patients with cirrhosis ranges from 50% to 90%, increases in
248 Gastroenterology & Hepatology Volume 15, Issue 5 May 2019
NUTRITION IN PATIENTS WITH CIRRHOSIS
patients with higher Child-Turcotte-Pugh (CTP) scores, aromatic amino acids (AAAs) and branched-chain
and is associated with an increased morbidity and mor- amino acids (BCAAs), which are released from skeletal
4,5
tality. Although malnutrition is obvious in chronically muscle via proteolysis. BCAAs are catabolized in skeletal
ill patients with CTP class C cirrhosis, it is present in muscle, which leads to low serum levels. Conversely,
approximately 50% of patients with CTP class A cir- AAAs are catabolized in the liver, and serum levels are
5
rhosis and is often underrecognized. Malnutrition has elevated because of decreased hepatic uptake due to
been most commonly associated with chronic viral and/ portosystemic shunting and hepatocellular dysfunction.
or alcoholic liver disease attributed to inadequate protein- A decrease in circulating BCAAs, particularly leucine,
calorie consumption; however, with the increasing preva- subsequently causes decreased protein synthesis and
11,12
lence of nonalcoholic fatty liver disease and nonalcoholic increased protein catabolism. Other disturbances
steatohepatitis (NASH), there is now a distinct phenotype that promote proteolysis and protein synthesis inhibition
of overweight and obese patients with cirrhosis who also include increased skeletal muscle ammonia production,
6 8,11,12
meet criteria for malnutrition and/or sarcopenia. endotoxemia, and low testosterone levels.
Pathophysiology of Malnutrition in Chronic Impact of Malnutrition on Clinical Outcomes
Liver Disease
Malnutrition is prevalent in the cirrhotic population
The pathogenesis of malnutrition in cirrhosis is multi- and is associated with increased morbidity and mortal-
factorial. Factors include decreased oral intake and both ity. One systematic review reported that sarcopenia is
maldigestion and malabsorption, particularly in patients associated with a hazard ratio (HR) of 1.84 (95% CI,
with cholestasis.4,7 Decreased oral intake occurs for 1.11-3.05; P=.02) for posttransplantation mortality and
several reasons, including anorexia, dysgeusia owing to an HR of 1.72 (95% CI, 0.99-3.00; P=.05) for patients
13
zinc deficiency, and/or unpalatable diets due to sodium on the transplant waiting list. Sarcopenia has also been
restriction and inappropriate protein restriction for associated with increased risk for bacterial infections
patients who have hepatic encephalopathy or chronic both before and after transplantation, as well as a reduced
12
renal insufficiency. Additionally, patients with decom- quality of life. In regard to loss of performance, research
pensated cirrhosis and ascites experience early satiety has demonstrated that frailty leads to worse outcomes
because of extrinsic compression of the gastrointestinal independent of the Model for End-Stage Liver Disease
7
tract from peritoneal fluid. Poor oral intake also occurs (MELD) score. In one study, waitlist mortality or delist-
frequently during hospitalization because of procedures ing because of critical illness was 9% for nonfrail patients
and/or hepatic encephalopathy.8 Cirrhotic patients also with MELD scores less than 18, and increased to 16%
experience fat malabsorption because of diminished for patients with MELD scores of at least 18. However,
luminal bile acids resulting from decreased synthesis in frail patients, this rate was 23% irrespective of the
14
and portosystemic shunting as well as coexisting chronic MELD score.
pancreatitis in patients with chronic alcohol consump-
tion.4 Malabsorption may also occur in patients with Nutritional Evaluation
portal hypertensive gastropathy and/or enteropathy,
intestinal dysbiosis, and chronic lactulose use.7 In addi- Obtaining an accurate and reliable nutritional assessment
tion to decreased oral intake and malabsorption, patients in cirrhotic patients presents unique challenges. Typical
with cirrhosis have alterations in metabolism because nutrition biomarkers are skewed in cirrhosis because of
of decreased hepatocyte mass, which results in a shift decreased protein synthesis (albumin) and volume over-
from glycogenolysis to gluconeogenesis as a source of load leading to alterations in body weight. Currently,
energy. Gluconeogenesis subsequently leads to lipopenia there are sparse validated screening tools as well as a lack
and sarcopenia.4 Hypermetabolism is also seen in 15% of consensus of the definition of malnutrition in this
to 34% of patients with cirrhosis and may be related to patient population. An assessment typically starts with
sympathetic overactivity, gastrointestinal bacterial trans- a nutritional screening questionnaire to identify patients
9,10
location, and a proinflammatory phenotype. at risk of malnutrition. If this initial screening raises
Sarcopenia is a major consequence of malnutrition concern, it should be followed by a more extensive nutri-
7
and correlates with frailty. Sarcopenia occurs as a tional assessment by a registered dietitian with expertise
7
consequence of increased proteolysis and a reduction in in liver disease.
protein synthesis. Glycogen store depletion in cirrhosis Any patient with cirrhosis should undergo a
leads to an increased reliance on gluconeogenesis as a nutritional assessment; however, particular attention
source of glucose. Gluconeogenesis primarily utilizes should be made to patients with a BMI of less than 18.5
Gastroenterology & Hepatology Volume 15, Issue 5 May 2019 249
CALMET ET AL
Step 1
Does this patient have acute alcoholic hepatitis or is
he or she being tube fed?
No (score 0) Yes (score 6)
Step 2
Does this patient have fluid overload
(ie, peripheral edema/ascites)?
No (score 0) Yes (score 1)
BMI Score Does the fluid overload interfere
>20.0 0 with the patient's ability to eat? Score
18.5-20.0 1 No 0
<18.5 2 Occasionally 1
Yes 2
Did the patient have unplanned Has the patient lost weight in the
weight loss in the past 3-6 months? Score past 3-6 months? Score
<5% 0 No 0
5%-10% 1 Difficult to assess due to diuretic use 1
>10% 2 Yes 2
Is the patient acutely ill and has there been, Has the patient's dietary intake
or is there likely to be, no nutritional reduced by 50% or more over the
intake for >5 days? Score last 5 days? Score
No 0 No 0
Yes 2 Yes 2
Step 3
Add the scores together to calculate the
overall risk of malnutrition.
Management Guidelines
Score 0 Score 1 Score 2-7
Low Risk Moderate Risk High Risk
Perform routine clinical Perform routine Discuss referral with
care. clinical care. dietitian.
Repeat screening weekly. Monitor food charts. Monitor food charts.
Encourage eating and Encourage eating and
offer snacks. offer snacks.
Repeat screening Repeat screening
weekly. weekly.
Figure. A flow chart showing the Royal Free Hospital–Nutritional Prioritizing Tool to determine a patient’s risk of malnutrition.
BMI, body mass index.
16
Reproduced from Amodio et al with permission by Wiley.
250 Gastroenterology & Hepatology Volume 15, Issue 5 May 2019
NUTRITION IN PATIENTS WITH CIRRHOSIS
or with CTP class C cirrhosis, as these patients are at Sarcopenia and lipopenia may be underestimated
highest risk of malnutrition, frailty, and sarcopenia.7,15 in patients with volume overload. The presence of sarco-
Two screening tools have been developed for patients penia is easily overlooked in obese patients, particularly
7
with liver disease, the Royal Free Hospital–Nutritional in those with NASH cirrhosis. Specific definitions for
Prioritizing Tool (RFH-NPT) and the Liver Disease sarcopenia in cirrhosis have recently been proposed. The
2
Undernutrition Screening Tool (LDUST). skeletal muscle area (SMA) is calculated (in cm ) as the
The RFH-NPT helps estimate a patient’s risk of cross-sectional area of the abdominal muscles on com-
malnutrition and is an independent predictor of hepatic puted tomography at the top of the L3 vertebral level
16
decompensation and transplant-free survival (Figure). (notably including the psoas, paraspinal, and abdominal
Patients who demonstrate an improvement in their wall muscles). The skeletal muscle index (SMI) is calcu-
RFH-NPT score have an improved survival. The score is lated by dividing the SMA by height squared (in m2). An
2 2 2 2
based on several factors, including fluid overload, BMI, SMI less than 50 cm /m for men or less than 39 cm /m
recent weight loss, and decreased oral intake. Patients are for women suggests sarcopenia and is associated with an
then categorized as being at low, moderate, or high risk increased mortality risk in patients with end-stage liver
23
for malnutrition. Of note, patients with acute alcoholic disease. Dual-energy x-ray absorptiometry scans can
hepatitis or who are receiving enteral tube feeding are also be used to assess sarcopenia and have the capability
17 24
automatically considered high risk. to measure bone, fat, and lean muscle mass content.
The LDUST is a 6-item questionnaire that incor- Patients with cirrhosis may also develop myosteatosis, an
porates oral intake, weight loss, loss of subcutaneous fat increased accumulation of intramuscular and intermus-
18,19
or muscle mass, fluid retention, and functional status. cular fat. Importantly, sarcopenia, sarcopenic obesity,
25
The questionnaire has a positive predictive value of 93.0% and myosteatosis correlate with increased mortality.
for malnutrition and a negative predictive value of 37.5%, In addition to sarcopenia, assessment of muscle func-
indicating that a negative test does not reliably exclude tion correlates with mortality and can be easily evaluated
18 14,26,27
malnutrition. by measuring handgrip strength (HS). Overall func-
tional status and frailty may also be assessed with the Short
Nutritional Assessment Physical Performance Battery (SPPB), the 6-minute walk
test, or the Clinical Frailty Scale (CFS).14,27-29 HS can be
A comprehensive nutritional assessment should include assessed in less than 1 minute with a Jamar dynamometer
a detailed evaluation of a patient’s dietary intake, body with the mean of 3 readings taken with the dominant
composition, and functional assessment as well as evalu- hand. In men, HS of less than 29 kg (BMI ≤24), less than
7,20
ation for micronutrient deficiencies. 30 kg (BMI 24.1-28), and less than 32 kg (BMI >28) is
Assessment of dietary intake should include the considered weak, whereas in women, HS of less than 17 kg
composition and timing of food and liquid consumption, (BMI ≤23), less than 17.3 kg (BMI 23.1-26), less than 18
with particular attention to periods of fasting, which kg (BMI 26.1-29), and less than 21 kg (BMI >29) is con-
may be especially detrimental in cirrhosis. Twenty-four– sidered weak and is associated with increased waitlist mor-
hour dietary recalls, food frequency questionnaires, and tality. The SPPB consists of timed repeated chair stands,
calorie counts should be utilized to determine whether balance testing, and a timed 13-foot walk. The SPPB takes
20
or not patients are meeting their daily caloric needs. up to 3 minutes to complete, and patients are given up to
Barriers to adequate oral intake, including anorexia, 4 points for each task with a maximum score of 12. Scores
dysgeusia, nausea, ascites, hepatic encephalopathy, and of 9 or lower were associated with increased waitlist mortal-
dietary restrictions, are also important to identify and ity.14,27 A 6-minute walking distance of less than 250 m was
7,20 28
address. also associated with an increased mortality risk. The CFS
Assessment of body composition includes calcula- is a 10-point descriptive scale that assesses overall perfor-
tion of BMI and identification of volume overload, mance status. A CFS score of 5 or greater was associated
29
sarcopenia, and lipopenia. There is no validated method with an increased risk of hospitalization and death.
to adjust the BMI calculation in cirrhotic patients, which
is often inaccurate in volume overload. Prior research has Micronutrient Deficiencies
utilized postparacentesis weight or calculated dry weight
7
empirically based on the severity of ascites. One such Deficiencies in fat-soluble vitamins are common in
method estimates dry weight by subtracting 5%, 10%, patients with advanced cirrhosis due to malabsorption,
and 15% of the actual weight in the presence of mild, decreased intake, and reduced production of carrier
moderate, or severe ascites, respectively, with an addi- proteins, and are especially prevalent in patients with
21,22 20,30
tional 5% subtracted for pedal edema. cholestatic liver disease. Vitamin A deficiency can
Gastroenterology & Hepatology Volume 15, Issue 5 May 2019 251
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