Nutritional issues in adult patients with cirrhosis

INTRODUCTION — Protein-calorie malnutrition is common in patients with cirrhosis, and it has been associated with complications including variceal bleeding, ascites, increased surgical morbidity and mortality, reduced survival, and possibly worsening liver function. Recognizing malnutrition is important because nutrition intervention has been associated with improved outcomes.

This topic will discuss evaluating nutritional status in ambulatory adult patients with cirrhosis and dietary management. The diagnosis and management of cirrhosis are discussed separately:

●(See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis".)

●(See "Cirrhosis in adults: Overview of complications, general management, and prognosis".)

Nutrition support for patients who are acutely ill is discussed separately. (See "Nutrition support in intubated critically ill adult patients: Initial evaluation and prescription".)

Nutrition support for patients with alcohol-associated hepatitis is discussed separately. (See "Management and prognosis of alcoholic hepatitis", section on 'Nutrition'.)

Nutritional status in patients with sustained heavy alcohol use is discussed separately. (See "Nutritional status in patients with sustained heavy alcohol use".)

TERMINOLOGY — The definition of malnutrition and related terms (frailty, sarcopenia) has varied across published studies in hepatology and other specialties. To promote consistency across studies, nutrition-related terminology for patients with cirrhosis was developed by expert consensus as part of society practice guidance [1-4]:

●Malnutrition – Malnutrition refers to imbalance (deficiency or excess) of nutrients that causes measurable adverse effects on tissue/body form (ie, body shape, size, composition), function, and/or clinical outcome. Malnutrition is often used as a synonym for undernutrition [2].

The term "disease-related malnutrition" is used to describe a syndrome of wasting caused by systemic illness that is unrelated and unresponsive to nutrition support. Patients with disease-related malnutrition are probably more likely to develop problems with oral intake, and this is discussed separately. (See "Nutrition support in intubated critically ill adult patients: Initial evaluation and prescription".)

●Frailty – For patients with cirrhosis, frailty describes limited physical function due to impaired muscle contraction and muscle weakness [1].

●Sarcopenia – Sarcopenia is the generalized loss of muscle mass and function [1].

EPIDEMIOLOGY AND RISK FACTORS

Prevalence — Disease-related malnutrition has been reported in 50 to 100 percent of patients with decompensated cirrhosis and in approximately 20 percent of patients with compensated cirrhosis [5,6].

Contributing factors — Factors that contribute to malnutrition in patients with cirrhosis can be broadly categorized as the following, although some factors are interrelated [1,5]:

●Impaired intake – Reduced dietary intake may be related to symptoms such as anorexia, nausea, cognitive changes related to hepatic encephalopathy, and abdominal distension from ascites. A sodium-restricted diet and alcohol use may also contribute to reduced dietary intake.

●Impaired uptake – Malabsorption and maldigestion of nutrients can result from altered bile salt regulation, bacterial overgrowth, altered intestinal motility, intestinal inflammation, and increased intestinal permeability.

●Cirrhosis-related factors – Cirrhosis represents an accelerated state of wasting, and fuels other than glucose (ie, protein, lipids) are used [7]. There is an overall loss of protein from reduced synthesis of urea and liver proteins, reduced intestinal protein absorption, and increased urinary nitrogen excretion.

●Physical inactivity – Physical inactivity may contribute to reduced muscle mass [8]. Hepatic encephalopathy is associated with reduced physical activity [9].

●Other factors – For some patients with cirrhosis, metabolic status contributes to the imbalance between calorie requirements and dietary intake [10,11]. Some liver diseases have been associated with a chronic inflammatory state that may lead to reduced muscle protein synthesis [12]. For older patients with cirrhosis, age-related factors contribute to sarcopenia [13]. (See "Normal aging", section on 'Muscle'.)

NUTRITION SCREENING — For patients with cirrhosis who do not meet criteria for nutrition assessment, nutrition risk screening tools are a rapid strategy to identify at-risk patients who may benefit from a comprehensive nutritional assessment. (See 'Nutrition assessment' below.)

We use nutrition screening tools in the inpatient and outpatient settings. Small studies have evaluated the Liver Disease Undernutrition Screening Tool [14], the Nutritional Risk Screening-2002 [15], the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) [16], and the Patient Generated Subjective Global Assessment [17]. Although further validation is required, the use of RFH-NPT is supported by society guidelines [1,2]. The RFH-NPT score is based on several factors, including fluid retention, body mass index (BMI), weight loss, and dietary intake (figure 1) [16]. Patients are classified into three nutritional risk categories (low, moderate, and high risk). Patients with selected conditions such as acute alcohol-associated hepatitis or who require enteral tube feeding are deemed as high risk. The RFH-NPT has been correlated with outcomes such as patient survival and quality of life [16]. From a practical perspective, two questions that can be used at every clinical encounter and may alert the clinician to risk for malnutrition are "Are you eating less than normal?" and "Have you lost weight without trying?" [18].

NUTRITION ASSESSMENT — Nutrition assessment is required for all patients with cirrhosis who score at-risk on a nutrition screen or who have the following characteristics [2,5,6,19]:

●Body mass index (BMI) <18.5 kg/m²

●Decompensated cirrhosis (or Child-Pugh class C disease) (see "Cirrhosis in adults: Overview of complications, general management, and prognosis", section on 'Prognosis')

●Patients being evaluated for liver transplantation

Diagnosis of malnutrition — The diagnosis of malnutrition is typically based on clinical assessment after reviewing the following data (see 'Assessment tools' below):

●Clinical history (eg, weight loss, activity level, disease-specific symptoms such as early satiety related to ascites)

●Physical examination (focusing on loss of muscle mass)

●Body mass index (BMI) (eg, <18.5 kg/m²)

●Dietary intake (eg, intake of solids and liquids)

●Laboratory studies (table 1)

●Global assessment tool (eg, subjective global assessment [SGA] (form 1), Royal Free Hospital-Subjective Global Assessment [RFH-SGA]) (algorithm 1)

Identifying patients with malnutrition is important because nutritional status influences morbidity and mortality [20,21]. The assessment for malnutrition in patients with cirrhosis typically includes a focused history, physical examination, and laboratory studies. Some clinicians also use an assessment tool (eg, the SGA, or the RFH-SGA, which is specific to cirrhosis) [22]. Use of specialized testing (eg, cross-sectional imaging [CT scan], bioelectrical impedance analysis [BIA]) is mainly limited to research settings because of factors such as availability, need for radiation/contrast exposure and/or special equipment, and cost (see 'Specialized methods' below). However, there is no gold standard for evaluating nutritional status in patients with cirrhosis, and clinical practice varies.

Assessment tools

History — Historical elements of the evaluation include:

●Weight – Serial measurements of body weight offer a simple assessment for nutritional adequacy and change in nutritional status. Patients are questioned about their usual weight, recent weight loss (ie, during the previous two weeks), and weight loss over six months. Unintentional weight loss of >10 percent over six months is considered clinically significant. However, weight history may be less useful for assessing patients with decompensated cirrhosis because of weight fluctuations related to fluid retention and diuretic therapy. If fluid retention is a concern, we estimate dry weight by using post-paracentesis weight or by subtracting a percentage of weight based on the amount of fluid retention (mild, 5 percent; moderate, 10 percent; severe, 15 percent; an additional 5 percent is subtracted in patients with bilateral pedal edema to the knees) [1].

●Dietary assessment – Food intake can be assessed by 24-hour dietary recall. The patient recounts the frequency and types of meals and snacks on a typical day, intake of food from each of the food groups, and the use of nutritional supplements. Although specific food choices are not documented in the patient's chart, the dietary recall process assists with an overall appraisal for balanced dietary intake. In clinical practice, a registered dietitian often performs the dietary assessment. (See "Dietary assessment in adults".)

●Evaluating for food insecurity and other issues – We inquire as to social issues such as access and affordability of food, ability to prepare meals, and the role of family members in food preparation [23]. We also question patients about appetite, symptoms that can impact dietary intake (eg, nausea, early satiety, anxiety, depression), and alcohol consumption. The evaluation of common gastrointestinal symptoms that often impact dietary intake (eg, nausea, diarrhea) is discussed separately. (See "Approach to the adult with nausea and vomiting" and "Approach to the adult with chronic diarrhea in resource-abundant settings".)

Nutritional issues related to sustained heavy alcohol use are discussed separately. (See "Nutritional status in patients with sustained heavy alcohol use".)

●Symptoms of nutritional deficiency – We assess for clinical features of micronutrient deficiency. These include dermatitis (zinc, vitamin A, niacin) , night blindness or photophobia (vitamin A), burning of the mouth or tongue (vitamin B12, folate), easy bruising (vitamin C, vitamin K), and paresthesia (thiamine, pyridoxine) (table 2).

Physical examination — Physical examination is focused on the following:

●We measure patient height and weight and use it to determine BMI (calculator 1). Physical findings such as pedal edema and ascites are noted with weight measurement because weight fluctuates with fluid retention. However, there is no validated method to adjust for volume overload in patients with cirrhosis.

●We assess for ankle or sacral edema, ascites, muscle wasting (as determined in the temporalis muscle, quadriceps, and deltoids), and loss of subcutaneous fat (as determined in the triceps, chest, and eye sockets).

Laboratory studies — The approach to laboratory testing is informed by severity of cirrhosis and etiology of liver disease as outlined in the table (table 1) [24].

For all patients with cirrhosis, we obtain complete blood count, serum albumin, serum creatinine, international normalized ratio (INR), serum 25-hydroxyvitamin D, and C-reactive protein (CRP). CRP may be useful in assessing degree of catabolism and interpreting measures of other nutrients. For example, serum 25-hydroxyvitamin D and albumin levels may decrease in inflammatory states and thus, a low vitamin D level in patients with inflammation may not represent deficiency. (See "Acute phase reactants", section on 'C-reactive protein'.)

For selected patients with cirrhosis (ie, those with decompensated cirrhosis, alcohol-associated cirrhosis, or cirrhosis related to cholestatic liver disease), we obtain additional laboratory tests as outlined in the table (table 1).

Limitations of laboratory assessment in patients with cirrhosis include:

●Vitamin B12 – Patients with cirrhosis may have elevated serum vitamin B12 levels [25]. Vitamin B12 is stored in the liver and may be released with hepatocellular injury. In addition, decreased vitamin B12 clearance may contribute to elevated levels. However, other causes of an elevated serum B12 level should be evaluated before attributing it to cirrhosis, and this is discussed separately. (See "Causes and pathophysiology of vitamin B12 and folate deficiencies", section on 'Elevated levels of vitamin B12 or folate'.)

●Liver-synthesized proteins – The liver is the major site where serum proteins (albumin and coagulation factors) are synthesized. Albumin levels are influenced by acute changes such as catabolism, hepatic inflammation, decreased production, capillary leak, and sequestration. Thus, the use of these tests may be limited in patients with decompensated cirrhosis and synthetic dysfunction. Tests of the liver's biosynthetic capacity are discussed in more detail separately. (See "Tests of the liver's biosynthetic capacity (eg, albumin, coagulation factors, prothrombin time)".)

Testosterone levels may also help guide therapy in male patients who are malnourished [26]. Symptoms of hypogonadism may overlap with those of chronic liver disease, and the evaluation of male patients with suspected hypogonadism is discussed separately. (See "Clinical features and diagnosis of male hypogonadism".)

Assessment questionnaires — Standardized questionnaires can be used as part of nutritional assessment to identify patients who have malnutrition [16,27-29]:

●Subjective global assessment – The SGA can be administered at the bedside and includes a focused history and physical examination (form 1) [30-32]. The historical components of the SGA include weight loss, change in dietary intake, gastrointestinal symptoms, functional capacity, and metabolic demand associated with the disease state. Physical examination components include edema, ascites, muscle wasting, and loss of subcutaneous fat. The components are combined to obtain an SGA rating that ranges from well-nourished to severely malnourished.

While the SGA is accessible and easy to administer, the sensitivity of the SGA in patients with cirrhosis has been questioned in several studies [33-35]. In addition, although SGA correlates with postoperative outcomes in patients without cirrhosis [30-32], there is growing evidence that other assessments (eg, muscle mass measurement) may be more useful for predicting clinical outcomes [33-38]. In a study of 315 patients with cirrhosis who were evaluated with skeletal muscle index (SMI) using cross-sectional imaging and with the SGA, there was weak concordance between sarcopenia (as determined by SMI) and the SGA [35]. In a study of 79 patients with cirrhosis, malnutrition was detected by the SGA in 25 patients (32 percent), while body composition analysis identified 48 patients with malnutrition (60 percent) [34].

●Royal Free Hospital-Subjective Global Assessment – Because of the limitations of the SGA in patients with cirrhosis, the RFH-SGA was developed (algorithm 1). This assessment incorporates subjective and objective variables (BMI, midarm muscle circumference, and dietary intake) [39]. Although the RFH-SGA requires more time than the SGA, it has shown promise as a predictor of mortality and of post-transplantation outcomes [37,40]. Studies that validate the RFH-SGA are awaited.

●Assess for frailty – Selecting an assessment for frailty is individualized and guided by equipment availability, center experience, and the patient's ability to participate in testing. Global tests of frailty include the clinical frailty scale and the frailty index [41]. Short, survey-based instruments that do not involve patient participation include those that assess activities of daily living and performance status (ie, measure of patient's functional capacity) (table 3). (See "Survival estimates in advanced terminal cancer", section on 'Performance status'.)

Measures of physical frailty that require patient participation include the Liver Frailty Index (ie, hand grip strength, balance testing, chair sit-to-stand), the Short Physical Performance Battery (ie, hand grip strength, balance testing, short gait speed), and the six-minute walk test [19,33,41-47]. (See "Frailty", section on 'Concepts and definitions'.)

For patients with cirrhosis, studies suggest that a diagnosis of frailty has been associated with an increased risk of mortality [48].

Specialized methods

Body composition testing — Assessment of muscle mass and bone mass can contribute to better understanding of nutritional status in patients with cirrhosis. However, use of specialized body composition assessment methods in clinical practice is limited by factors such as availability and cost. Thus, specialized methods are typically reserved for research settings.

Methods to assess body composition include (see "Determining body composition in adults"):

●Computed tomography – Computed tomography (CT) may be used to assess for sarcopenia (loss of muscle mass) in patients with cirrhosis if abdominal CT is being performed for other indications (eg, liver transplantation evaluation). Otherwise, cross-sectional imaging for assessing body composition is mainly used in research settings due to limited availability of specialized equipment required for data analysis, radiation and contrast exposure, and cost. Strategies to increase access to methods for analyzing body composition remain in development [49]. Despite these limitations, evaluating for sarcopenia with abdominal CT has demonstrated good correlation with pretransplant morbidity and mortality across studies [2,19,20,48].

●Bioelectrical impedance analysis – BIA is performed by applying electrodes to one arm and one leg or by standing on a specialized scale. BIA measures impedance or resistance to the flow of an electrical current within the body, which is used to determine total body water and can distinguish muscle mass from fat. However, the patient's volume status may impact the results because BIA uses estimated water content to calculate muscle mass [50-52]. In a study of 136 patients with cirrhosis, BIA phase angle was moderately correlated with CT scan-based muscle mass using the SMI, irrespective of the presence of ascites [51]. In addition, BIA phase angle was an independent predictor of mortality.

●Anthropometry – Anthropometry is a tool used to assess body fat and lean tissue stores that is largely unaffected by fluid overload. Commonly used measurements include midarm muscle circumference, which estimates muscle mass at the midarm level, and skinfold thickness, which may be used to estimate total body fat percentage [53,54]. Limitations to anthropometry include interobserver variability and accuracy in adults; thus, more advanced measures of body composition (eg, CT scan) have replaced anthropometry in some centers where body composition in adults is assessed [55].

●Dual energy X-ray absorptiometry – Dual energy X-ray absorptiometry (DEXA) accurately estimates fat mass in patients with liver disease but does not provide as accurate an assessment of lean body mass [56-58]. This inaccuracy is most likely related to the increase in extracellular water in patients with decompensated cirrhosis. However, the use of appendicular skeletal muscle measurements may improve testing accuracy [57,58].

DEXA is commonly used in the diagnosis of low bone mass in patients with cholestatic liver disease (eg, primary biliary cholangitis). (See "Evaluation and treatment of low bone mass in primary biliary cholangitis (primary biliary cirrhosis)".)

MANAGEMENT PRINCIPLES

General measures — General measures for patients with cirrhosis include [2,59]:

●Nutrition education – We provide patient education resources including nutrition handouts and digital resources for patients with cirrhosis.

●Referral to registered dietitian – We routinely refer patients with malnutrition to a registered dietitian for an individualized nutritional plan that incorporates the patient's nutritional habits and food preferences [1]. This includes tailored calorie and protein intake recommendations based on the patient's nutritional status, current dietary intake, and body mass index (BMI).

●Avoid prolonged fasting – Patients are advised to eat at regular intervals (eg, every four hours) while awake, and to eat breakfast as well as a late evening snack. Oral intake at regular intervals has been associated with improved nutritional status for patients with cirrhosis. In a trial including 103 patients with cirrhosis, night-time oral nutrition supplements resulted in greater improvement in total body protein after 12 months compared with daytime oral supplements [60].

●Avoid raw or undercooked foods – Patients are advised to avoid eating raw or undercooked shellfish, fish, meat, and unpasteurized dairy products [61]. (See "Vibrio vulnificus infection".)

In the United States, foodsafety.gov provides detailed advice on food safety for patients who are immunocompromised, including those with liver disease [62].

●Vitamin supplementation – We advise patients to take a daily multivitamin, and we provide additional micronutrient repletion based on specific deficiencies (table 4).

●Lifestyle intervention – We encourage patients to increase physical activity because data have suggested that physical activity (in combination with nutritional counseling) was associated with improved muscle function and muscle mass [8,63]. (See "Exercise prescription and guidance for adults".)

●Manage underlying liver disease – Measures to reduce liver inflammation (eg, alcohol abstinence, treatment for chronic viral hepatitis) are implemented as part of a comprehensive nutritional plan.

●Multidisciplinary care – Nutrition management typically involves a multidisciplinary team including specialists from primary care, gastroenterology/hepatology, and physical and exercise therapy.

Target daily intake — Target daily intake is determined by estimating the patient's total calorie and protein needs, and this is often done with the assistance of a registered dietitian. (See 'Total calorie intake' below and 'Protein intake' below.)

Total calorie intake — Total calorie intake is based on resting energy expenditure (REE) and can be assessed using indirect calorimetry to inform personalized nutrition prescriptions.

If indirect calorimetry measurement is not available, alternative methods for estimating total calorie intake include using a predictive equation or a weight-based equation [59]:

●Predictive equations – In the absence of indirect calorimetry, we typically use predictive equations such as the Harris-Benedict equation, recognizing that they can underestimate the REE [10,64]. The accuracy of the Harris-Benedict equation in determining REE is subject to individual variability based upon the factors included in the equation (weight, height, age, sex).

The Harris-Benedict equations for males and for females are presented separately. (See "Nutritional demands and enteral formulas for adult surgical patients", section on 'Predictive equation: Harris-Benedict'.)

●Weight-based equations – An alternative method for estimating calorie needs is use of a weight-based equation. Whether ideal body weight should be used in weight-based calculations is uncertain, and society guidelines differ in their approach [2,48]. Until further data are available, we support the following options:

•For patients without obesity – Target daily minimum energy intake is 35 kcal/kg

•For patients with obesity – Target daily minimum energy intake may be either a tailored, moderately hypocaloric diet (ie, 500 to 800 kcal/day) or a BMI-stratified intake target:

-For patients with BMI <30 kg/m², the target daily minimum energy intake is 35 kcal/kg

-For patients with BMI 30 to 40 kg/m², the target daily minimum energy intake is 25 to 35 kcal/kg

-For patients with BMI ≥40 kg/m², the target daily minimum intake is 20 to 25 kcal/kg

An online tool for calculating the patient's nutrition prescription that uses the BMI-stratified intake and estimated dry weight can be found here [65].

Protein intake — The target daily protein intake is 1.2 to 1.5 g/kg, based on ideal body weight (calculator 2). In adults with cirrhosis who are critically ill, the target daily protein intake is 1.2 to 2.0 g/kg, based on ideal body weight [1]. We consult with a dietician to help determine protein requirements for patients with cirrhosis and Class II or III obesity. Additional studies are needed to determine true protein requirements in this patient population to ensure they are not being underdosed.

We advise patients to consume a diverse range of protein sources (eg, vegetable, chicken, fish, dairy-based proteins), and advise them to consume protein at each meal and with each snack.

Monitoring — Monitoring patients with cirrhosis who are following a nutrition prescription typically includes reassessing weight, physical examination, and laboratory tests every 6 to 12 months (table 1). Patients with decompensated cirrhosis are monitored with more frequent laboratory testing (every two to three months) because such patients are at risk for electrolyte imbalances and refeeding syndrome. (See "Anorexia nervosa in adults and adolescents: The refeeding syndrome".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Healthy diet in adults".)

SUMMARY AND RECOMMENDATIONS

●Terminology – Nutrition-related terminology for patients with cirrhosis has been developed by expert consensus (see 'Terminology' above):

•Malnutrition – Malnutrition refers to an imbalance (deficiency or excess) of nutrients that causes altered body form (body shape, size, composition), function, and/or clinical outcome. Malnutrition is often used as a synonym for undernutrition.

•Frailty – Frailty describes limited physical function due to impaired muscle contraction and muscle weakness.

•Sarcopenia – Sarcopenia is the generalized loss of muscle mass and function.

●Nutritional screening – We use nutrition risk screening tools for patients with cirrhosis who do not meet criteria for a comprehensive nutrition assessment. Nutrition screening may identify additional at-risk patients who may benefit from a nutritional assessment (figure 1). (See 'Nutrition screening' above.)

●Nutritional assessment

•Indications – Comprehensive nutrition assessment by a skilled professional (bypassing the need for nutrition screening) is indicated for patients who are at increased risk for malnutrition (see 'Nutrition assessment' above):

-Patients with body mass index (BMI) <18.5 kg/m²

-Patients with decompensated cirrhosis (or Child-Pugh class C disease)

-Patients who are being evaluated for liver transplantation

•Diagnosis of malnutrition – The diagnosis of malnutrition is based on clinical assessment after reviewing the following data (see 'Diagnosis of malnutrition' above):

-Clinical history (eg, weight loss, activity level, disease-specific symptoms such as early satiety related to ascites)

-Physical examination (focusing on loss of muscle mass)

-BMI

-Dietary intake (eg, intake of solids and liquids)

-Laboratory studies (table 1)

-A global assessment tool (eg, subjective global assessment (form 1), the Royal Free Hospital-Subjective Global Assessment (algorithm 1))

●Management

•General measures – General measures for patients with cirrhosis include (see 'General measures' above):

-For patients with malnutrition, referral to a registered dietitian for dietary counseling

-Avoid prolonged fasting (ie, eating at regular intervals while awake and including a late evening snack)

-Avoid raw or undercooked shellfish, fish, meat, and avoid unpasteurized dairy products

-Manage underlying liver disease to control inflammation (eg, treatment for chronic viral hepatitis, alcohol abstinence)

-Vitamin supplementation consisting of a daily multivitamin and additional micronutrient repletion based on specific deficiencies (table 4)

-Encourage increased physical activity

•Estimate target daily intake – Target daily intake is based on resting energy expenditure (REE) that can be assessed using indirect calorimetry if such testing available. Alternatives to indirect calorimetry for estimating total calorie and protein needs include (see 'Target daily intake' above):

-A predictive equation such as the Harris-Benedict equation. (See "Nutritional demands and enteral formulas for adult surgical patients", section on 'Predictive equation: Harris-Benedict'.)

-A weight-based equation with target daily intake stratified by BMI. An online tool for calculating the patient's nutrition prescription that uses the BMI-stratified intake can be found here.

Target daily protein intake is 1.2 to 1.5 g/kg, based on ideal body weight (calculator 2).