Oral intake is frequently reduced in patients with chronic liver disease for a variety of reasons. Their appetite can be impaired due to early satiety, side effects of medications and psychological and neurological impairment. Zinc deficiency can be associated with anosmia (lack of smell), dysguesia (altered taste) and appetite suppression. ¹¹ Proinflammatory cytokines (TNF) and leptin, which are increased in chronic liver disease, may impose an anorexic effect. ^{12.13. and 14.} It is not uncommon to have intermittent anorexia for episodes of gastrointestinal bleeding and portosystemic encephalopathy. The concern for precipitating encephalopathy and worsening fluid retention often leads to excessive restriction of protein and fluid intake, exacerbating general illness and negative nitrogen balance.

Malabsorption may occur with liver disease in the presence of cholestasis. Fat, fat-soluble vitamins and mineral stores may be depleted. Medications used to treat encephalopathy, such as lactulose and neomycin, can also affect absorption. Pancreatic insufficiency with alcoholic liver disease will play a role with poor absorption of vitamins and nutrients. Thiamin and magnesium deficiency are common in the setting of alcoholic liver disease.

Patients with ascites requiring large-volume paracentesis (LVP) will experience losses of protein and electrolytes, exacerbating negative nitrogen balance. The impact of frequent LVP on nutritional status is so far undefined.

Abnormal fuel metabolism is associated with chronic liver disease. As the liver is responsible for metabolism of most nutrients, liver disease alters the metabolic processes, causing changes in energy, carbohydrate, protein and lipid. These changes are similar to those seen in states of starvation. ¹⁵ The respiratory quotient (RQ) of cirrhotic patients is lower than controls after an overnight fast, indicating utilisation of fat as fuel. ¹⁶

The metabolic rate in patients with chronic liver disease has been studied using indirect calorimetry, and compared with the Harris–Benedict equation to determine basal energy expenditure (BEE) and found to be quite variable. In a recent study of 476 patients, high metabolic rate was found in 33.8%. ¹⁷ These patients could not be identified by clinical or biochemical measures of liver disease, such as Child–Pugh class or aetiology of disease. Variability based on an earlier study, in which 18% were hypermetabolic and 31% were hypometabolic, did not consistently correlate with the cause, duration or severity of cirrhosis. ¹⁶ However, BEE was found to closely relate to fat-free mass, age, gender and increased beta-adrenergic activity. Hypermetabolism has been found to be associated with decreased survival in patients with cirrhosis undergoing OLT, regardless of the aetiology. ¹⁸ In the same study it was shown that presence of ascites was not associated with changes in metabolic rate; that is, it did not contribute to hypermetabolism.

It is also important to differentiate between total body mass and body cell mass. Body cell mass is directly responsible for basal energy expenditure. Energy expenditure relative to body cell mass is more reflective of true BEE and patient physiology. Irrespective of the degree of ascites or Child–Pugh score, low body cell mass and hypermetabolism correlated with a poorer prognosis after OLT. In fact, hypermetabolism appears to persist after transplantation. This suggests that hypermetabolism may be an extrahepatic manifestation of liver disease.

Glucose intolerance, insulin resistance and hyperinsulinemia are found in a majority of liver disease patients. Glucose intolerance can occur in over 70% of cirrhotic patients with diabetes mellitus developing in up to 37% of patients. ¹⁹ Fortunately, they do not appear to be at higher risk for cardiovascular disease. ²⁰ These patients have decreased hepatic circulation and extraction of insulin, decreased hepatic sensitivity to insulin and decreased production and storage of glycogen in muscles. Because of the decreased glycogen stores, fat is utilised as their main substrate for energy. ^15,21,22 This leads to an ‘accelerated starvation’, in which patients with overnight fasting have biochemical evidence of increased gluconeogenesis, lipid oxidation and protein catabolism. Increased gluconeogenesis eventually leads to loss of subcutaneous fat tissue and muscle wasting.

Alterations in lipoproteins and essential fatty acid profile occur in liver disease. Hypertriglyceridemia (250–500 mg/dL) is found frequently in both alcoholic and viral liver disease and tends to resolve when the liver disease improves. Polyunsaturated and essential fatty acid levels are reduced, which may correlate for both malnutrition and liver dysfunction. ²³ Arachidonic acid is necessary for prostaglandin and leukotriene synthesis, as well as cell membrane function. Supplementation with arachidonic acid in cirrhotic patients may improve platelet aggregation. ²⁴

Protein stores in liver disease are altered due to decreased absorption, decreased synthesis of body protein and increased degradation of body protein. Increased protein catabolism can be present in early cirrhosis. In a study of 268 patients with cirrhosis, 51% were found to have significant protein depletion. ²⁵ Even in patients with mild liver disease (Child–Pugh A), malnutrition was observed in > 40%. ²⁵ The group with the greatest depletion was with alcoholic liver disease. In general protein deficiency worsens as liver disease progresses. Abnormal amino acid metabolism is common, including decreased leucine oxidation. Increased proteolysis may be present, which is not suppressed with active feeding. Furthermore, patients with compensated liver disease can retain nitrogen when fed for long periods of time without developing portosystemic encephalopathy. ^26,27 Protein intakes of up to 1.8 g/kg/day were well tolerated. These data indicate that protein-deficient patients with compensated liver disease have the capacity to retain nitrogen, provided that enough protein is present to reverse net protein loss. Therefore patients with chronic liver disease should avoid protein restriction, and avoid a fasting state, include frequent meals to balance protein synthesis and degradation. Hepatic encephalopathy should be aggressively managed with other treatment modalities before protein restriction is considered. Acute exacerbation of liver disease such as infections (urinary tract infections, spontaneous bacterial peritonitis and pneumonia), tense ascites, gastrointestinal bleeding and encephalopathic episodes may increase the protein requirement and affect nutritional status rapidly.

Nonalcoholic fatty liver disease (NAFLD) encompasses simple fatty liver and nonalcoholic steatohepatitis (NASH), which can lead to cirrhosis. In the general population, the estimated prevalence of NAFLD is 20% (range 15–39%) and the prevalence of NASH is 2–3%, making NAFLD the most common form of liver disease in the USA. ²⁸ The causes of NAFLD are listed in Box 13.3. Obesity is most-often associated with NAFLD. In a study of 210 healthy obese patients, 80% had fatty liver. Insulin resistance is a major risk factors predicting NAFLD. ²⁹ Type 2 diabetes and glucose intolerance with or without obesity is also associated with NAFLD. Hyperlipidemia is also found in this population, and there is growing evidence that there is higher overall mortality and increased risk from cardiovascular disease. ³⁰ NASH was found in 88% of patients with metabolic syndrome in a study by Marchesini and colleagues, ³¹ and should now be considered a component of metabolic syndrome.