Nutrition Assessment and Management in Advanced Liver Disease

INTRODUCTION

- Malnutrition is one of the most common complications occurring in patients with advanced liver disease, regardless of the etiology, and has important prognostic implications.

- It is estimated that malnutrition is present in at least 50% and up to 90% of patients with cirrhosis

- Malnutrition appears to be more common in those patients hospitalized with alcoholic liver disease than nonalcoholic liver disease.

- Malnutrition, when present in cirrhotics, is associated with an increased risk for morbidity, mortality, compromised immune function, respiratory function, decreased muscle mass, increased recovery time, and delayed wound healing

- The presence of ascites and hepatorenal syndrome is significantly greater among those patients with concurrent protein-calorie malnutrition (PCM)

The progress from compensated to decompensated cirrhosis

- Advanced liver disease, although typically progressive, may present with a long initial period of well-compensated cirrhosis.

- Compensated cirrhosis occurs when the liver is heavily scarred but is still able to perform many of its important functions.

- Individuals with compensated cirrhosis often have few or no symptoms; however, liver decompensation may occur rapidly and dramatically.

- Decompensated cirrhosis occurs when the liver is extensively scarred and unable to function properly and is often accompanied by complications (eg, ascites, variceal bleeding, encephalopathy) that can be life-threatening

- With the high prevalence of malnutrition and its associated poor outcomes in patients with advanced liver disease, it is crucial to identify malnutrition early and initiate aggressive nutrition interventions to prevent further complications and decrease hospital length of stay

CAUSES OF MALNUTRITION

- The clinical conditions and pathophysiological mechanisms that drive cirrhotic patients to a disruptive metabolic state are multiple and interrelated.

-Major contributors to malnutrition include inadequate oral intake, metabolic disturbances, malabsorption, and decreased capacity of the liver to store nutrients.

- Table 1 provides a list of potential causes of the malnutrition seen in advanced liver disease

NUTRITION ASSESSMENT

- All patients with advanced liver disease should undergo nutrition screening to assess risk of developing malnutrition.

- Nutrition screening is the initial step in the documentation of nutrition care, and it can be performed by any healthcare professional in either an inpatient or an outpatient setting

- Nutrition assessment is more comprehensive than screening and is defined by the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) as “a comprehensive approach to define nutrition status that uses medical, nutrition, and social histories; physical examination; anthropometric measurements; and laboratory data”.

- A properly conducted nutrition assessment provides a global assessment of both nutrition status and the severity of underlying illness—both important considerations given the fundamental relationship between the two.

1) Assessment of Nutrition History and Energy Intake

- Review nutrition history to assess intake of energy, protein, macro- and micronutrients, and overall understanding of and compliance with the prescribed diet

- Note factors contributing to diet history such as past dietary restrictions, appetite, satiety levels, taste changes, socioeconomic status, fad diets, supplement use, ethnic or religious preferences, and food intolerances or allergies.

- Although all have limitations, oral intake history may be obtained using the 24-hour diet recall, food frequency questionnaire, calorie counts, or food diary

- Nutrition risk can be predicted using the Subjective Global Assessment (SGA) scale, which is a score based on medical diagnoses, weight changes, intake, gastrointestinal (GI) symptoms, and function capacity and physical signs of malnutrition.

- Table 2 lists available nutrition assessment tools and their respective advantages and limitations

2) Assessment of Body Composition

- Individuals with cirrhosis have been shown to have increased extracellular and decreased intracellular fluid compared with healthy individuals

- A decrease in muscle mass and adipose tissue is often present but not always apparent as it may be masked by fluid retention

- Peng et al: men lost an average of 20% of their body protein stores compared with only 11% in women; patients with higher protein depletion also had significantly decreased bone density, hand grip strength, and respiratory muscle strength.

- Changes in body composition have been shown to progress with the course of the liver disease and correlate well with the Child-Pugh score, a commonly used method for assessing the severity and prognosis of liver disease

- The Child-Pugh score is calculated using lab values such as serum albumin and bilirubin, as well as factors such as the presence of ascites and encephalopathy.

- Child-Pugh score A has the best prognosis of survival of 100% at 1 year, whereas a B or C score carries a prognosis of 81% and 45% at 1 year, respectively

- Physical examination should include an assessment of musculature, adipose tissue, body habitus, oral cavity, skin, hair, nails, and temperature

- In the cirrhotic patient, special attention should be paid to the presence of muscle atrophy, ascites, and peripheral edema

- It is often difficult to accurately identify malnutrition and body composition changes in cirrhotic patients who have ascites and edema, as fluid weight gains mask muscle and adipose tissue losses

- The visualization of muscle wasting may be more evident in the temporal, clavicular, and scapular regions, as they are typically less affected by fluid retention

- Tools available to aid in the assessment of body composition include skin-fold measurement, dual-energy X-ray absorptiometry scan (DEXA), handgrip strength (HGS), body cell mass (BCM), and bioelectrical impedance (BIA); however, some of these tools may not be readily available to the clinician, and their accuracy may be limited in the presence of fluid retention.

- Table 3 reviews available tools for assessing body composition in the cirrhotic patient, including their strengths and limitations.

3) Biochemical Assessment

- Prealbumin (transthyretin) and serum albumin are produced in the liver and are commonly, yet erroneously, considered indicators of nutrition status.

- Due to the location of their synthesis and response to inflammation, the value of prealbumin and serum albumin as indicators of nutrition status is poor, particularly in patients with advanced liver disease.

- Although prealbumin and serum albumin may not be accurate nutrition indicators, they appear to have use as markers of prognosis, morbidity, and mortality

- As liver disease progresses, the synthesis of prealbumin and serum albumin is reduced, a property that has historically made them useful as markers of liver disease severity

- Therefore, prealbumin, serum albumin, and transferrin reflect the severity of underlying illness and inflammation and not the individual’s nutrition status.

MICRONUTRIENTS

- Micronutrient deficiencies are common in end-stage liver disease.

- Therefore, periodic assessment of serum vitamin levels is important to allow for appropriate supplementation to prevent complications related to deficiencies.

- Table 4 summarizes the more common micronutrient deficiencies that may occur in liver disease, the role these micronutrients play in liver disease, the signs of micronutrient deficiency, and recommended supplementation.

1) Fat-soluble vitamins

- Deficiencies in fat-soluble vitamins (A, D, E, and K) are likely to develop in liver disease due to reduced oral intake, malabsorption, and/or hepatic effects involving reduced synthesis of carrier and transfer proteins.

- It has been demonstrated that as the severity of liver disease progresses, fat-soluble vitamins tend to become deficient

- Vitamin A deficiency may cause nyctalopia (ie, night blindness) and dry corneas and is associated with increased risk for the development or cirrhotic progression to hepatocellular cancer in patients with end-stage liver disease.

- Retinol is typically normal in Child-Pugh score A patients and decreased in Child-Pugh score B and C

- Suboptimal vitamin D stores can be associated with both cholestatic and noncholestatic liver disease

- More than 90% of those with advanced liver disease are vitamin D deficient. Patients who have progressed to cirrhosis have twice the incidence of deficiency as their noncirrhotic counterparts.

- Depending on the etiology of liver disease, deficiency may be attributed to low vitamin D intake, fat malabsorption, bile acid deficiency, and impaired liver function

- Vitamin D deficiency in adults contributes to the development of osteopenia and osteoporosis and may cause osteomalacia, bone pain, and muscle weakness.

- Vitamin D supplementation is recommended in all patients with chronic liver disease in combination with calcium.

- Oral replacement with vitamin D2 or vitamin D3 (2000 IU) daily is generally adequate along with 1200–1500 mg/d of calcium.

- Vitamin E levels are low in nearly half of cirrhotic patients.

- Clinical manifestations of vitamin E deficiency may include increased platelet aggregation, decreased red blood cell survival, hemolytic anemia, decreased serum creatinine with creatinuria, and neuronal degeneration

- It has been theorized that administration of vitamin E may ameliorate oxidative stress. Oxidative stress may initiate cellular injury, leading to a chronic inflammatory response. Vitamin E may act as a chain-breaking antioxidant that neutralizes free radicals.

- Low vitamin E levels have also been linked to high triglyceride levels, and it has been suggested that deficiency of this vitamin may lead to enhanced progression of fatty liver to steatohepatitis

- A dosage ranging from 400-1200 IU daily in nonalcoholic steatohepatitis (NASH) was shown to improve serum aminotransferase levels and fibrosis scores

- Also, steatosis was also improved with vitamin E supplementation ranging from 300 to 1000 IU daily for 6 months to 3 years

- Vitamin K is an important clotting factor but also plays a role in skeletal development and bone health

- The most common sign of deficiency is bleeding.

- Patients with vitamin K deficiency tended to have elevated serum alkaline phosphatase and bilirubin levels and more advanced histological staging compared with patients with normal vitamin K levels.

- For patients with impaired prothrombin time (and/or international normalization ratio [INR]), vitamin K supplementation should be considered

2) Water-soluble vitamins

- Symptoms of a neuropsychiatric nature seen in patients with chronic liver disease may be the consequence of water-soluble vitamin deficiencies

- Deficiency in pyridoxine, thiamine, or vitamin B12 may result in peripheral neuropathy and other neurologic disturbances

- Due to diminished hepatic storage, deficiencies in thiamine and folic acid may develop more rapidly in cirrhotic patients than those without liver disease.

- In addition to liver disease causing pyridoxine deficiency, inadequate diet, alcoholism, medications, and chronic renal failure can also contribute to deficiency

- Serum B12 level tends to be falsely elevated in patients with cirrhosis because the laboratory value includes endogenous metabolically inactive cobalamin analogues (transcobalamins I and III), despite vitamin B12 tissue levels being depleted

- Ocular disturbances, confusion, and ataxia are classical signs of thiamine deficiency and have been reported in patients with alcohol-related and chronic hepatitis C-related cirrhosis

- Individuals with chronic alcohol-related liver disease, particularly when accompanied by mental status changes, should receive thiamine supplementation due to the high risk of Wernicke encephalopathy (WE).

3) Trace elements

- Zn deficiency in cirrhotic patients may lead to anorexia, altered taste and smell, immune dysfunction, and altered protein metabolism. Other manifestations of Zn deficiency may include skin rash, depressed mental function, hypogonadism, poor wound healing, and altered immune function

- Serum Zn is bound to serum albumin, which is typically decreased in advanced liver disease; therefore, caution is needed regarding overinterpretation of serum Zn levels. Zinc deficiency in liver disease may be related to increased losses in the gastrointestinal system due to diarrhea or intestinal malabsorption, increased urinary losses and reluctance regarding protein intake

- Despite conflicting data on oral Zn supplementation and its effects on hepatic encephalopathy, improved Zn status has been associated with improvement in liver function. Zinc may be used long-term or at least until the serum zinc level has normalized. A once-daily dose of 50 mg elemental zinc (220 mg zinc sulfate) is recommended which does not inhibit copper absorption

- If malabsorption is the cause of malnutrition in alcoholic and cholestatic liver disease, consider the use of medium-chain triglycerides (MCT) and pancreatic enzymes

- Concentrations of homocysteine, cysteine, copper (Cu), and the Cu:Zn ratio in cirrhotic patients were found to be significantly higher compared with healthy individuals

- Furthermore, the Cu:Zn ratio was shown to be significantly lower as liver disease severity progressed according to the Child-Pugh score.

- Copper and manganese are both excreted in the bile, and it is recommended that both of these be decreased or omitted from parenteral nutrition (PN) formulations in patients with cirrhosis and/or cholestasis

NUTRITION MANAGEMENT

- Goal: to meet estimated energy needs and to prevent further protein catabolism.

- This may be accomplished via oral, enteral, parenteral, or a combination of these routes.

Estimating Protein and Energy Requirements

- Experts in the field agree that compensated, stable patients have energy requirements near normal, with more critically ill patients having higher requirements.

- For well-compensated patients, 25-35 kcal/kg/d of energy is appropriate.

- Malnourished patients may require 30-40 kcal/kg/d to promote anabolism

- Historically, protein restriction was recommended in advanced liver disease to prevent an increase in serum ammonia level and reduce the risk of hepatic encephalopathy

- Recent studies, however, have shown that high-protein diets are more beneficial in cirrhosis with respect to prognosis due to improvement in overall nutrition status without exacerbating hepatic encephalopathy

- Cordoba et al in a RCT showed that restriction of protein actually worsens hepatic encephalopathy due to increased protein catabolism, and a protein intake of 0.5 g/kg/d led to increased muscle breakdown compared with an intake of 1.2 g/kg of protein per day

- It is now recommended that patients with cirrhosis consume 1.0-1.5 g/kg of protein per day to prevent muscle catabolism and promote gluconeogenesis.

- A temporary protein restriction (0.6-0.8 g/kg/d) may still be appropriate in patients with acute exacerbations of encephalopathy until the cause is determined and eliminated, at which time a high protein intake can be resumed.

- Table 5 lists methods for determining energy and protein requirements relevant to the patient with advanced liver disease.

- Note that a dry weight or estimated dry weight should be used when calculating energy and protein needs

Carbohydrate and Fat Requirements

- Many patients with cirrhosis have glucose intolerance or frank diabetes. Glucose intolerance has been found to correlate with poor prognosis of patients with cirrhosis.

- Glucose should not be given in doses larger than 5-6 g/kg/d, and serum glucose should be monitored closely

- Impaired fat metabolism is present in cirrhosis with incomplete metabolism of long-chain triglycerides.

- Overfeeding, regardless of the energy source, should be avoided because excess calories can contribute to fat synthesis and accumulation in the liver.

- A range of 25%-30% of the calories from fat is generally recommended.

- If steatorrhea is present, medium-chain triglycerides may be useful to supplement a low-fat diet

Fluid needs

- Fluid intake of 30-40 mL/kg/d maintains fluid balance in the average adult

- An alternate method of determining fluid requirements is to provide 1 mL/kcal/d.

- In general, fluid gains (intake) should be in balance with fluid losses (output).

- Excess fluid administration and/or decreased urine output contribute to fluid overload

- Fluid losses can be influenced by diarrhea, wounds, surgical drains, nasogastric tube drainage, chest tubes, ostomy output, pancreatic secretions, and urine output, which can increase fluid requirements

- In advanced liver disease, fluid requirements vary greatly depending on the patient’s volume status.

- Fluid restriction of 1.5 L/d may be indicated if there is coexistence of ascites and significant hyponatremia, typically <120-125 mEq/L.

- Fluid restriction in cirrhosis is controversial and is not recommended for those patients with ascites who are hypovolemic or have only mild to moderate hyponatremia.

NUTRITION CHALLENGES IN THE CIRRHOTIC PATIENT

- Goals of nutrition interventions in advanced liver disease are to improve overall nutrition status, maintain lean body mass, minimize fluid retention, and reduce morbidity and mortality associated with malnutrition

Optimizing Intake to Meet Nutrient Needs

- Meal frequency and timing is of upmost importance in maintaining nutrition status in the cirrhotic patient

- After a single night fast, calorie requirements in patients with liver disease remain the same as those with a healthy liver. However, due to the reduced storage capacity for glycogen, the fuel sources being used by cirrhotic patients after a 10-hour fast are the same as what would be used after a 3-day fast in a patient with a healthy liver

- The reduction in hepatic glycogen stores causes an increase in use of muscle glycogen, free fatty acid oxidation, and hepatic production of ketone bodies. The cascading effects of these metabolic alterations coupled with poor nutrition intake lead to rapid loss of lean body mass and wasting.

- The prevention of long periods of fasting may lessen the muscle loss seen in the cirrhotic patient

- The intake of 4-6 small portion-sized meals daily is generally recommended to promote protein-calorie intake, prevent longer periods of fasting, and have a muscle-sparing effect.

- The addition of a bedtime or late evening nutrient-dense snack or nutrition supplement

has been shown to increase total body protein levels in both decompensated and well-compensated cirrhosis

- Importantly, in the hospital setting, patients are often kept fasting for testing and may be away from the floor during mealtimes. Infusion of intravenous (IV) fluids containing dextrose at the rate of 2-3 g/kg/d may be beneficial in preventing hypoglycaemia and overuse of muscle glycogen stores if the patient will be fasting for >10 hours

Protein Supplementation and Hepatic Encephalopathy

- The use of serum ammonia levels as an indicator to initiate protein restriction is discouraged because of a lack of correlation between ammonia and encephalopathy and the high protein needs of the cirrhotic patient previously described

- The role of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) in liver disease has long been studied and debated

- Amino acid metabolism is altered in hepatic failure and leads to an increase in circulating levels of AAAs (phenylalanine, tyrosine, and tryptophan) and a decrease in levels of BCAAs (isoleucine, leucine, and valine)

- It was hypothesized that the increase in AAAs is a contributing factor in hepatic encephalopathy (HE) as AAAs can cross the blood-brain barrier and act as false neurotransmitters

- On this basis, it was speculated that a modification of the ratio of dietary AAA to BCAA would help in the management of HE while allowing sufficient protein intake

- Subsequent studies, however, have not supported this approach, finding that BCAA supplementation, although reducing plasma concentrations of AAA, does not consistently improve encephalopathy

- Nevertheless, recent studies suggest that the use of BCAAs in advanced cirrhosis may have other benefits

- Although no significant improvement in encephalopathy, but improvements in overall nutrition status, including increased serum albumin and improved energy metabolism, were noted in the BCAA group compared with the control group

- Other potential benefits of BCAA supplementation reported include a decrease in frequency of hospitalizations, improved Child-Pugh score, and improved overall quality of life.

- When used as a bedtime snack, BCAA supplements were found to be more beneficial than regular food at improving serum albumin and preventing muscle catabolism.

- Compliance with long-term use of BCAA may be problematic due to poor palatability. BCAAs in the form of granules may be better accepted.

- Glutamine may promotes muscles development. However, it is metabolized into ammonia and may increase plasms ammonia levels in cirrhotic patients. Therefore, despite the unclear significance of an elevated ammonia level, it may be advisable for cirrhotic patients to avoid glutamine supplements until more information is available

- Prebiotic, probiotic, and synbiotic (combination of prebiotic and probiotic agents) agents are currently being evaluated in the treatment of nonsevere HE.

- Two recent RCTs involving patients with HE showed a reduction in serum ammonia levels plus an improvement in protein tolerance and neurological symptoms in the symbiotic/probiotic group [Study 1: Bifidobacterium species + fructo-oligosaccharide (FOS); Study 2: probiotic yogurt without FOS]

- Although additional investigation is needed, these studies showed improvements with the probiotic supplements plus FOS that were equal to those of lactulose therapy, the general standard of care treatment of HE, with fewer side effects, better patient compliance, and beneficial effects that lasted even when there was an interruption in treatment

- The use of pre- and probiotics in this setting may, therefore, offer a more tolerable treatment to lactulose and a less expensive, lower risk alternative to antibiotic therapy. Further studies on this subject are clearly warranted.

- Among liver transplant recipients, prebiotics and probiotics may also offer protection from infection.

- A significant reduction in postoperative infection rates was seen in the group who received synbiotic-containing formula than group with standard fiber-free formula, in a recent study of liver transplant recipients with early EN.

Nutrition Support

- The long-term benefits of nutrition support in liver cirrhosis remain controversial

- If nutrition support is initiated early, improvement in mortality may be seen.

- However, since malnutrition is often diagnosed later in the course of the disease, it may be difficult to demonstrate improvements in overall morbidity and mortality

- Conversely, other studies show that continuous or cyclical nutrition support may be considered to supplement the oral diet as early and aggressive nutrition interventions have been shown to improve morbidity and mortality if oral intake is insufficient

Enteral Nutrition (EN)

- EN is the preferred route for nutrition support when the GI tract is functional.

- The European Society for Parenteral and Enteral Nutrition (ESPEN) guidelines recommend initiating EN if energy intake does not meet estimated energy needs to improve nutrition status or slow the rate of decline.

- EN may be initiated via a fine-bore nasoenteral tube, even in patients with nonbleeding esophageal varices.

- The placement of a percutaneous gastrostomy tube (either endoscopically or radiologically placed) is generally not recommended in patients with ascites or gastric varices given the potential for ascitic fluid leakage, infection, and bleeding.

- Aspiration precautions should be taken when the feeding is into the stomach due to an increased presence of gastroparesis in the cirrhotic patient.

- An alternative is to advance the tube beyond the pylorus and feed into the small bowel

- Routine use of a BCAA-enriched “hepatic” enteral formula is not necessary in advanced liver disease

- The use of immune-enhancing formulas remains controversial, and further well-designed clinical trials are needed

- A concentrated, high-energy formula (≥1.5 kcal/mL) is preferred in patients with hyponatremia and ascites to regulate fluid balance

- In addition, a calorie-dense formula may be better tolerated because it can be delivered at a low rate and still allow for adequate provision of nutrients.

- In hepatorenal syndrome, a renal (low-electrolyte) formula may be indicated when persistent hyperkalemia and/or hyperphosphatemia are present

Parenteral Nutrition (PN)

- PN should be reserved for those patients who do not tolerate EN.

- EN may not be tolerated in advanced cirrhosis because of the presence of severe ascites or other factors such as nausea, bloating, abdominal distension, and discomfort.

- Occasionally, EN may not be possible in patients with advanced cirrhosis due to hemodynamic instability from a decrease in systemic vascular resistance that may require vasopressors

- When PN is used, glucose levels should be monitored carefully due to an increased likelihood of glycemic imbalance. If hyperglycemia develops, the amount of dextrose should be reduced to 2-3 g/kg/d.

- PN may need to be concentrated to prevent fluid overload

- In patients with cholestasis, reductions in manganese and copper should be considered due to impaired biliary excretion of these trace elements.

- The composition of dextrose and fat should generally be balanced to decrease the incidence of steatosis.

- In patients receiving long-term PN, parenteral lipid emulsion should not provide >1 g/kg/d to reduce any further risk of worsening the liver disease

- A cyclic PN infusion regimen allows a period of time off PN and has a favorable effect on serum liver enzymes compared with continuous PN infusion

- Liver tests and electrolytes should be monitored regularly in patients receiving long-term PN, especially those with preexisting liver disease.

- PN may lead to hepatic steatosis, cholestasis, and eventually fibrosis and cirrhosis.

- When liver tests are elevated in the parenterally fed patient, and it is not due to medication or disease process, adjustments to the PN regimen should be made, including a reduction in dextrose, fat, and overall calories (as appropriate), cycling the infusion and/or maximizing use of EN.

Fluid Imbalance

- Sodium levels are often abnormal in the cirrhotic patient due to complex fluid abnormalities.

- In well-compensated patients, sodium levels are usually normal.

- As liver disease progresses, the presence of portal hypertension leads to the development of peripheral edema and ascites.

- The movement of fluids into the extremities and peritoneal cavity leads to decreased renal blood flow

- This change triggers a decrease in renal sodium and fluid excretion with an increase in renal reabsorption to maintain vascular blood volume and blood pressure.

- The overall effect is greater free water accumulation than sodium retention, leading to dilutional hyponatremia

- Body sodium levels may be further depleted due to urinary losses from high-dose diuretics, GI tract losses, and/or decreased energy intake.

- Increased fluid intake due to polydipsia can further exacerbate hyponatremia

Ascites

- Ascites is the accumulation of fluid in the peritoneal cavity and typically occurs in patients with advanced cirrhosis.

- The presence of ascites has been correlated with a decline in nutrition status, and those with tense ascites typically have the lowest protein-energy intake as well as the most compromised nutrition status.

- Aqel et al evaluated gastric function and symptoms in cirrhotic patients with ascites both before and after large-volume paracentesis. After paracentesis, patients reported an improvement in early satiety and were able to consume larger meals. These changes were found to correlate with enhanced gastric accommodation.

- An important nutrition goal is to reduce the amount of ascites when present and promote protein-energy intake

- Ascites is generally managed initially with sodium restriction, usually ≤2 g sodium per day, and diuretics.

- This strategy has been shown to be effective in more than 90% of patients in achieving a reduction in the volume of ascites to acceptable levels.

- Fluid restriction (1-1.5 L) is not necessary in treating patients with ascites unless the serum sodium is <120-125 mEq/L.

- Fluid restrictions should be recommended with care due to frequency of plasma hypovolemia seen in conjunction with ascites.

- Refractory ascites is defined as ascites that is either unresponsive to diuretics and a low-sodium diet or is resistant to the use of diuretics due to the development of severe electrolyte or renal impairment

- Refractory ascites often requires repeated large-volume paracentesis; however, paracentesis removes not only fluid from the peritoneal space but also a large amount of calories in the form of carbohydrates, proteins, and fats.

- As a consequence, the frequent need for large volume paracentesis can further advance the catabolic state already seen in advanced cirrhosis

- This calorie loss needs to be replaced to prevent further decline in nutrition status.

- It is a common practice to administer a serum albumin infusion after paracentesis when >5 L of fluid is removed to promote plasma expansion and to prevent hyponatremia and renal insults.

- Importantly, the use of serum albumin in this setting has no effect on nutrition status.

- A late evening snack or post-paracentesis PN was demonstrated to improve morbidity and mortality compared with a control group receiving a low-sodium diet that provided 30-35 kcal/kg daily.

- Even so, the administration of PN is not recommended after large-volume paracentesis to replete nutrition losses

Hepatorenal Syndrome

- Hepatorenal syndrome (HRS) is an oftentimes fatal complication occurring in acute and chronic liver failure.

- It is characterized by functional renal failure due to renal vasoconstriction in the absence of underlying kidney pathology.

-There are 2 types of HRS: type 1 progresses rapidly and generally has poor prognosis, whereas type 2 has a slower onset and progression.

- In appropriate candidates, liver transplantation will typically correct the renal failure without the need for a concomitant renal transplant.

- Nutrition therapy for HRS generally consists of a low-salt diet along with fluid restriction in those with hyponatremia.

- In some instances, HRS may lead to chronic kidney damage and may require renal replacement therapy.In these cases, a renal diet may be warranted if potassium and phosphorus levels become elevated.

Obesity

- There has been much debate regarding assessing energy needs in the obese patient.

- In patients with nonalcoholic fatty liver disease (NAFLD) who are clinically well compensated but have advanced fibrosis, weight reduction becomes an urgent issue.

- Obese patients with NAFLD-related decompensated cirrhosis are often significantly malnourished with protein deficits due to the catabolic nature of cirrhosis. In these patients, weight loss remains beneficial; however, it is important to ensure adequate protein needs are being met

Insulin Resistance and Diabetes

- Chronic liver disease patients have a high prevalence of glucose intolerance and overt diabetes due to the presence of insulin resistance and β-cell dysfunction.

- Liver disease may somehow be the initiating factor in the development of diabetes if the cirrhotic patient presents with 1 or more of the following conditions: the diagnosis of cirrhosis was established at least 5 years before the onset of diabetes; there is no family history of diabetes; the patient lacks any factors known to adversely affect glucose metabolism such as obesity, excessive energy intakes, or medication side effects; and the patient has no history of hemochromatosis or exocrine pancreatic dysfunction

- Interestingly, there is a positive association between ferritin concentrations and insulin resistance. A recent study demonstrated that phlebotomy led to a decrease in both ferritin level and insulin resistance

- Type 2 diabetes mellitus (T2DM) is strongly associated with NAFLD

- Both hepatic fat and visceral obesity correlate with insulin resistance, an important precursor in the development of T2DM.

- Metabolic changes are seen not only in fatty liver disease but also in many other diseases of the liver, including chronic hepatitis C (HCV) and cryptogenic cirrhosis. The prevalence of diabetes in HCV is 2-3 times higher than the general population

- Due to the high prevalence of impaired glucose metabolism and the important role of the liver in carbohydrate metabolism, it is generally assumed that impaired hepatic metabolism plays a major role in the cause of impaired glucose tolerance in liver disease. However, it has been demonstrated that insulin resistance also resides in the muscle, which makes the role of the liver less clear

- Dietary and lifestyle interventions to promote weight reduction can help improve glycemic control, insulin resistance, and the lipid profile while reversing histological changes seen in liver disease

- Gradual weight reduction is recommended in patients with diabetes with a BMI >25 kg/m2, with a goal weight loss of at least 5%-10% to improve insulin sensitivity

- Creating a calorie deficit of 500-1000 kcal/d should result in a modest rate of weight loss

- The maintenance of high caloric intake is advocated especially during periods of hospitalization or illness; promoting weight loss during these times may not be warranted.

- The use of bariatric surgery or weight loss medications may be useful but should be used with caution as in even the well-compensated cirrhotic, rapid weight loss may cause decompensation

CONCLUSION

- The relationship between malnutrition and survival in patients with advanced liver disease is complex and multifactorial

- Malnutrition is a common complication of cirrhosis, and its presence carries with it important prognostic implications. In addition, a direct correlation exists between the progression of liver disease and the severity of malnutrition

- Due to the prevalence of malnutrition and the potential for serious consequences in the setting of advanced liver disease, nutrition screening, assessment, and intervention are critical facets in improving clinical outcomes in these patients.

Johnson et al. Nutr Clin Pract 2013 28(1): 15-29. DOI: 10.1177/0884533612469027