Nutrition Support of Patients with Cirrhosis

Component

Purpose

Specific elements

Physical assessment

Determine general nutrition condition including fat and muscle stores and fluid retention

Is the patient of appropriate weight for stature?

Does the patient have noticeable ascites, edema, or other fluid retention?

Is muscle wasting apparent?

What are the patient’s fat stores and where is the adipose tissue distributed?

Is the patient jaundiced?

Is the patient alert?

Does the patient require oxygen, wheelchair, or other assistive device?

Assess the degree and distribution of nutrient deficiencies

Evaluate degree and distribution of fat and/or muscle loss and fluid retention.

Examine skin for color, texture, ecchymoses, etc.

Examine nail beds and hair for symptoms of nutrient deficiencies.

Assess the oral cavity for dental problems or signs of vitamin deficiencies.

History

Determine cause, degree, and duration of nutrient deficiencies

Obtain medical history of the type, degree, duration, and treatment of liver disease and associated complications.

Inquire about patient’s physical function.

Obtain diet history to determine adequacy of intake.

Note gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, early satiety) and other factors affecting appetite or intake.

Question patient or caregiver about the use of nutrition supplements, vitamin or mineral supplements, and herbal or complementary products.

Assess psychosocial and economic conditions to determine patient’s ability to obtain food and comply with prescribed diet recommendation.

Anthropometric measurements

Provide objective measurements to evaluate and monitor progress

Fluid retention may have least effect on upper arm measurements.

Anthropometric measurements are unlikely to be useful in the critical care setting.

Anthropometric measurements have limitations in sensitivity and reliability but may be useful if monitored serially over time.

Reliability is improved if all serial measruements are made by a single observer.

Functional status tests

Indirect measure of muscle function

Functional measurements such as hand-grip strength, sit-to-stand test, and 6-min walk are not useful in an acute setting.

These tests may be useful in a chronic setting over a period of time to monitor muscle strength and function.

Laboratory tests

Provide detailed information; must be used selectively to avoid tests confounded by nonnutritional factors

Serum protein concentrations are not considered measures of nutrition status but of inflammation as they are acute phase reactants.

Vitamin and mineral levels may be helpful to determine when micronutrients need to be supplemented or restricted.

Body composition measures

Give more accurate detail on lean vs. fat mass

CT and MRI scans of abdomen can be analyzed to determine fat and muscle content; typically measured at L3 level; tests are expensive and CT scan involves radiation.

Full body dual energy X-ray absorptiometry (DXA) scans can provide accurate assessment of fat mass; not portable and can’t be used at bedside.

Bioelectrical impedance analysis (BIA) requires special equipment and can be used at bedside but standard BIA devices are not accurate when patients have fluid shifts; bioimpedance spectroscopy has not been validated in patients with cirrhosis.

Adapted with permission from Hasse [52]

Leading Causes of Malnutrition in Cirrhosis

As part of the evaluation of nutrition status, it is important to determine the cause of malnutrition so that interventions not only provide adequate nutrients but also address the root causes of malnutrition. The cause of malnutrition in this group of chronically ill patients is due to many factors that influence nutrient intake, metabolism, and expenditure (Table 6.2).

Table 6.2

Factors contributing to malnutrition in patients with chronic liver disease

Inadequate nutrient intake

↑ levels of tumor necrosis factor-α & leptin → loss of appetite

Ascites → impaired gastric expansion → early satiety, delayed gastric emptying, bloating, abdominal distention

Hepatic encephalopathy → altered consciousness with decreased oral intake

Alcohol intake replaces nutrition

Nausea and vomiting

Restrictive diets (low-sodium, low-protein, fluid restriction)

Altered taste perception (zinc deficiency)

Socioeconomic constraints

Metabolic Alterations

Altered glucose, lipid, and protein metabolism

Altered pattern of energy consumption

Decreased glycogen levels and reduced ability to store nutrients

Insulin resistance

Malabsorption

Bile salt deficiency in cholestatic liver disease and cholestasis

Small bowel bacterial overgrowth

Portal hypertensive enteropathy

Reprinted with permission from Hasse and DiCecco [19]

Nutrient Metabolism

Because the liver is involved in numerous metabolic processes, cirrhosis can lead to metabolic alterations including increased protein catabolism, reduced hepatic and skeletal muscle glycogen synthesis, and a state of increased lipolysis [3].

Protein Alterations

Protein catabolism can be increased in patients with liver failure; therefore, protein should typically not be restricted even in the face of hepatic encephalopathy. Cordoba et al. randomized patients admitted to an intensive care unit to receive tube feeding with either protein at 1.2 g/kg body weight from the outset vs. 0 g protein initially gradually increasing up to 1.2 g/kg over a period of 2 weeks [4]. There was no difference in encephalopathy between the groups but there was increased protein breakdown in the low-protein group. Many factors such as infections, GI bleeds, electrolyte abnormalities, constipation, diuretic overdosing, medications, and hypoglycemia are most often associated with precipitation of hepatic encephalopathy rather than excessive dietary protein intake [24, 47].

Controversy exists with regards to benefit of branched-chain amino acid (BCAA) supplementation for hepatic encephalopathy. In a recent Cochrane Review, BCAAs were shown to have some beneficial effects on hepatic encephalopathy but results were not different between groups treated with BCAA or lactulose or rifaximin therapy [14]. In addition, BCAAs have not been found to improve nutrition or quality of life outcomes [14, 28, 50]. It has been suggested to utilize BCAA supplements when patients don’t respond to other treatments for hepatic encephalopathy [24] and North American and Japanese consensus guidelines recommend use of BCAAs when other treatments fail [13, 47].

Glutamine is an amino acid involved in one of the proposed mechanisms of hepatic encephalopathy [20]. Ammonia can be converted to glutamine in muscle, brain, and lungs. However, glutamine released from muscle and brain is catabolized back to ammonia by enterocytes and kidneys leading to increased circulation of ammonia in the blood because the liver is unable to convert ammonia to urea (Fig. 6.1). Adverse effects of increased glutamine production include swelling of astrocytes and altered transmission in brain and catabolism of BCAAs in skeletal muscle [20].

Fig. 6.1

The role of glutamine (GLN) in ammonia detoxification in liver failure. In liver failure, ammonia escapes the urea cycle and is detoxified to GLN in the brain, skeletal muscle, and lungs. Enhanced GLN availability leads to enhanced GLN catabolism to ammonia in enterocytes and the kidneys. Thus GLN-ammonia cycling among tissues is activated. PSS Portal-systemic shunts (Used with permission from Holecek [20])

Leucine has been singled out as a potential essential amino acid to aid in treating muscle wasting in patients with cirrhosis [30]. The mechanism is thought to be through activation of anabolic signaling via mammalian target of rapamycin (mTOR) [10, 11, 45]. The effect of specific amino acid supplementation other than BCAAs on nutrition status and patient outcomes has not been studied in the cirrhosis population.

Glucose Alterations

Hyperglycemia is common in the early stages of cirrhosis. Glucose transport and peripheral glucose utilization are reduced in the early stages of cirrhosis. The rate of gluconeogenesis is increased leading to elevated blood glucose levels in the early stages of liver failure. Hyperglycemia may also occur due to impaired insulin sensitivity (especially common with NAFLD and hepatitis C) in spite of adequate or even elevated insulin levels. Insulin secretion worsens with increasing severity of liver disease, suggesting a detrimental effect of liver failure on pancreatic islets on its own [16]. In late stages of liver disease, hypoglycemia becomes more common due to depleting glycogen stores and decreasing gluconeogenic capacity.

Lipid Alterations

The liver is central in the processing of lipoproteins. Steatosis occurs in nonalcoholic fatty liver disease (NAFLD) due to increased delivery of free fatty acids from adipose tissue to the liver, accelerated hepatic lipogenesis, reduced fatty acid oxidation in hepatocytes, and altered triglyceride export from the liver in the form of very-low-density lipoprotein (VLDL) cholesterol [5]. Insulin resistance is a contributing factor to these lipid alterations [5]. Alcoholic steatosis is caused by impaired ß-oxidation of fatty acids by mitochondria, increased de novo hepatic lipogenesis, and enhanced fatty acid uptake. VLDL secretion is also reduced [5]. On the other hand, hepatitis C is associated with hypolipidemia – reduced levels of total and low-density lipoprotein (LDL) cholesterol. Cholestatic liver disease leads to elevated total cholesterol levels but mainly in the form of lipoprotein-X. In patients with cirrhosis, lipoprotein metabolism usually reflects the degree of impairment in the liver [5].

With regards to digestion and absorption of dietary fat, steatorrhea can occur in patients with cholestatic liver disease due to a deficiency of bile salts in the intestine that aid in absorption. Steatorrhea can also contribute to fat-soluble vitamin deficiencies.

Other Metabolic Derangements

Other metabolic derangements including electrolyte abnormalities may occur in liver failure. Hypervolemic hyponatremia is a common complication of advanced cirrhosis. It arises in part due to inappropriate secretion of antidiuretic hormone resulting in free water retention and is treated with a free water restriction (not supplementation of sodium). Severe hyponatremia can precipitate hepatic encephalopathy in patients with advanced liver disease. Functional renal dysfunction can occur in patients with cirrhosis of liver due to changes in renin-angiotensin system and sympathetic nervous system. This further exacerbates the electrolyte disturbances seen in patients with cirrhosis. Decreased pyruvate dehydrogenase activity is also noted with hepatic dysfunction [40]. This leads to impaired lactate utilization predisposing patients with cirrhosis to lactic acidosis.

Refeeding syndrome has been reported in malnourished patients who are treated with aggressive nutrition correction. Refeeding syndrome is characterized by onset usually within 5 days of feeding patients who are undernourished or have had impaired intake for at least 48 h [41]. Hypophosphatemia occurs in nearly all patients with about half of the patients also having low serum levels of magnesium or potassium [41]. Some patients can display low serum levels of all three electrolytes. Hypophosphatemia can contribute to hemolysis, rhabdomyolysis, paresthesias, tremors, and ATP depletion resulting in cardiac or respiratory failure [41]. This can further exacerbate the deficiency of potassium, phosphorus, magnesium, and vitamins often seen in patients with cirrhosis. Thiamine deficiency is already common in patients with cirrhosis (especially with chronic alcoholism, malabsorptive states, and malnutrition) and reintroduction of carbohydrate can exacerbate a further reduction in thiamine stores [34]. If a patient is at risk of refeeding syndrome, electrolyte levels should be checked and treated. Nutrition support should “start low and advance slow” while monitoring electrolyte levels and supplementing them as needed [7].

Nutrient Needs

Nutrient requirements in a patient with end-stage liver disease are influenced by disease state, nutrition status, and other complicating factors. For example, patients with cholestatic liver diseases are more likely than patients with noncholestatic disease to have fat and fat-soluble vitamin malabsorption. Those who are malnourished have an increased caloric need compared with patients who are of normal or overweight status. Patients who have undergone surgery or those with fever and infection are likely to be hypermetabolic and have greater calorie and protein needs than those who are stable and without complicating factors. Patients with ascites can undergo large-volume paracentesis; protein needs can be increased as protein is lost with the ascitic fluid. Table 6.3 highlights general macronutrient recommendations.

Table 6.3

General macronutrient considerations for individuals with cirrhosis

Nutrient	Estimated Needs	Comments
Protein	1–1.5 g/kg Up to 2 g/kg for critical illness	Dependent upon nutrition status and comorbidities Protein needs would be increased with surgery Consider using dry weight or ideal body weight if patient is fluid-overloaded Protein restriction is not recommended as it leads to muscle loss and does not improve outcomes Protein can be lost with paracentesis
Calories	Usually 20–50% above basal	Dependent on nutrition status and losses Indirect calorimetry is the most accurate way to determine actual calorie needs Caloric restriction may be required for weight loss in face of obesity
Fat	As needed to provide adequate calories	Patients with cholestatic liver disease may experience fat malabsorption
Carbohydrate	Controlled carbohydrate intake if patient has diabetes mellitus or insulin resistance is present Frequent meals and/or late evening snack to prevent hypoglycemia	Patients with liver disease or obesity may have insulin resistance and hyperglycemia In severe or acute liver failure, hypoglycemia may ensue due to inability of the liver to store glycogen or undergo gluconeogenesis
Sodium	2 g/day	If patient has fluid retention
Fluid	Restrict to 1000–1500 mL/day	If patient has hyponatremia

Patients with chronic liver disease develop deficiencies of various micronutrients including magnesium, zinc, selenium, and vitamins. Possible mechanisms include poor appetite and dietary restrictions, altered metabolism, and poor absorption. Cholestatic liver diseases lead to malabsorption of fat-soluble vitamins (A, D, E, and K). Patients with alcoholic liver disease are at risk of poor absorption of potassium and magnesium and low levels of B vitamins. Zinc is mainly metabolized in the liver leading to its deficiency in chronic liver disease. Its deficiency can cause loss of appetite causing further malnutrition. Poor intake of potassium, zinc, calcium and vitamin C has been noted in patients with chronic hepatitis C in the absence of cirrhosis [15]. Iron stores could be depleted as a result of GI bleeds or anemia of chronic illness; on the other hand, iron supplementation should be avoided if the patient has hemosiderosis or hemochromatosis.

Nutrition Support Indications

Because patients with cirrhosis are at high risk of malnutrition and heightened nutrient needs, inadequate oral intake should precipitate early consideration of nutrition support. Oral intake could be limited due to anorexia, nausea, vomiting, dysgeusia, or early satiety (commonly seen with tense ascites). When oral intake is inadequate, nutrition guidelines recommend prompt initiation of nutrition support for patients who are at high nutrition risk [26, 27]. In addition to cirrhotic patients having a poor appetite or early satiety, oral intake can be interrupted by complications such as hepatic encephalopathy and variceal bleeding. Patients with exacerbations of encephalopathy may not be alert enough to eat. In extreme cases, patients may require intubation to protect their airways in which case nutrition support would be required. Variceal bleeding can also cause an interruption in oral intake. Active bleeding is a contraindication for enteral feeding; if variceal banding is performed or a transjugular intrahepatic portosytemic shunt (TIPS) is placed, oral or enteral nutrition usually can be considered 48 h or longer after the procedure and if the bleeding has stopped. Other complications such as respiratory failure requiring mechanical ventilation warrant consideration of nutrition support. When nutrition support is indicted, EN is preferred over parenteral nutrition (PN). The benefits derived from early enteral nutrition (Table 6.4) outweigh the potential detrimental effects of parenteral nutrition on worsening liver function in patients with cirrhosis. Figure 6.2 from the American Society for Parenteral and Enteral Nutrition (ASPEN) outlines who is a candidate for EN vs. PN. The goal for nutrition support should be clearly defined before it is initiated – is it mainly to support a patient during an acute event or surgery or is it to improve a patient’s condition to allow for repletion and eventual liver transplant [19].

Table 6.4

Benefits of early enteral nutrition