Patients with cirrhosis of the liver require an increased amount of protein to achieve N balance. However, the utilization of protein with increased protein intake, i.e. the slope from regression analysis of N balance v. intake, is highly efficient (Nielsen et al. 1995). In the present study, protein requirement and protein utilization were investigated further by measuring protein synthesis and degradation. In two separate studies, five or six patients with cirrhosis of the liver were refed on a balanced diet for an average of 2 or 4 weeks. Protein and energy intakes were doubled in both studies. Initial and final whole-body protein metabolism was measured in the fed state by primed continous [15N]glycine infusion. Refeeding caused a statistically significant increase of about 30% in protein synthesis in both studies while protein degradation was only slightly affected. The increase in protein synthesis was associated with significant increases in plasma concentrations of total amino acids (25%), leucine (58%), isoleucine (82%), valine (72%), proline (48%) and triiodothyronine (27%) while insulin, growth hormone, insulin-like growth factor (IGF)-I and IGF-binding protein-3 were not changed significantly. The results indicate that the efficient protein utilization is due to increased protein synthesis, rather than decreased protein degradation, and suggest that increases in plasma amino acids may be responsible for the increased protein synthesis. A comparison of the patients who had a normal protein requirement with the patients who had an increased protein requirement suggests that the increased protein requirement is due to a primary increase in protein degradation. It is speculated that this is due to low levels of IGF-I secondary to impaired liver function, since initial plasma concentration of IGF-I was about 25% of control values and remained low during refeeding.

A previous study has shown that malnourished, clinically stable patients with liver cirrhosis are in protein and energy balance at their spontaneous dietary intake and that an improvement in nutritional status cannot be anticipated at this intake (Nielsen et al. 1993). In the present study we examined to what extent oral intake could be increased by nutritional support, and to what extent dietary protein would be retained with increased intake. The techniques used for balance studies were also validated since this information is not available for patients with liver cirrhosis. Fifteen malnourished patients with alcoholic liver cirrhosis were given increasing amounts of a balanced ordinary diet for 38 (SE 3) d. Intakes of protein and energy were recorded by weighing servings and leftovers on food trays. Protein intake was calculated from food tables. Total N disposal was calculated after measurement of urinary N excretion, and protein balance was calculated from the N balance. A validation study of protein balance in a subgroup of patients (analysis of N in food by the duplicate portion technique, correction for incomplete recovery of urine by measurement of urinary para-aminobenzoic acid (PABA) after administration of PABA tablets, and measurement of faecal N) did not change protein balance values. Protein intake increased from 1. 0 (SE 0.1) g/kg per d to 1·8 (SE 0·1)g/kg per d. With increasing protein intake, 84 (SE 8)% of the increase in intake was retained. The rate of protein retention was not saturated at the intakes obtained in this study. Protein intolerance was only encountered in one patient. Available evidence indicates that the requirement for achieving N balance is increased in these patients but protein retention is highly efficient with increased intake. Protein retention is dependent on energy balance. Energy intake was calculated from food tables and total energy expenditure was calculated by the factorial method. A validation study was performed in a subgroup of patients. The energy contents of food sampled by the duplicate portion technique, and of urine and faeces were measured by bomb calorimetry. Resting energy expenditure (REE) was measured by indirect calorimetry before and at the end of the study, and O2 uptake during bicycle exercise was measured before and at the end of the study. The measured intake of metabolizable energy was on average 13% lower than the value given in food tables. Calculated energy expenditure was not changed by the validation study. Mean energy intake was 163 (SE 10) kJ/kg per d and mean energy expenditure was 134 (SE 5) kJ/kg per d (P = 0·007), indicating that the protein retention described occurred at a positive energy balance. It is concluded that a substantial retention of dietary protein can be obtained by oral nutrition support over a prolonged period of time in patients with liver cirrhosis. Requirements of protein for maintenance and repletion in these patients are discussed.

The effect of a regular oral diet supplying 167 kJ/kg per d (40 kcal/kg per d) on nutritional state, liver function and serum lipid profile was assessed in thirty severely malnourished alcoholic cirrhotic in-patients. Their diet was monitored by a trained dietitian and they were vigorously encouraged to eat all meals served. One month after their entry into the study, protein and energy intakes were significantly higher (P 0·001) in keeping with an improvement of their nutritional status as evaluated by means of height-creatinine index, muscular mid-arm circumference, tricipital skinfold thickness (P 0·01 for all) and fat mass (P 0·001). Assessment of liver function tests showed that levels of aspartate amino-transferase (EC 2.6.1.1), y-glutamyl transferase (EC 2.3.2.2) and bilirubin decreased (P <0·05, P > 0·02 and P > 0·05 respectively) while prothrombin time values increased (P < 0·05). Similarly, serum albumin increased modestly while transthyretin did not change. Orosomucoid and C-reactive protein decreased (P < 0·001 and P < 0·01 respectively), indicating an improvement of the inflammatory state. Apolipoprotein Al and high-density-lipoprotein (HDL)-cholesterol correlated with several tests of liver function and improved significantly during the study period (P < 0·001 and P < 0·02 respectively). Moreover, changes in cholesterol and HDL-cholesterol correlated with those in transthyretin (P < 0·02 and P < 0·05 respectively). The changes in ApoAl and HDL-cholesterol were greater in patients whose fat mass increased significantly. Our findings show that adequate oral nutrition resulted in a better nutritional status in cirrhotics after 1 month of hospitalization. The serum lipid variables appeared to be more useful indicators of functional liver improvement than the classic liver function tests which rather indicate liver damage.