Nutritional Therapy for Alcoholic Hepatitis: Are We There Yet?
Authors: Morgan Timothy R. , Mendenhall Charles L. 
Published: March 2007

This prospective study compared the effects of tube–fed nutrition with those of a regular diet in alcoholic liver disease. The high prevalence of malnutrition in patients with alcoholic liver disease requires clarification of the benefits of aggressive nutritional support. Patients were randomly assigned a regular diet without or with tube–fed supplementation, delivering 1.5 g/kg protein and 167 kJ/kg daily. Comparisons of encephalopathy, antipyrine clearance, metabolic rate, and biochemical parameters were performed weekly for 4 weeks. Sixteen patients receiving enteral supplementation had antipyrine half–life (50% vs. 3% reduction), serum bilirubin (25% vs. 0% reduction), and median encephalopathy scores that improved more rapidly than those of controls. Initially, 15 controls did not consume adequate calories to meet measured resting energy expenditure. Aggressive nutritional intervention accelerated improvement in alcoholic liver disease. Adverse effects did not offset the demonstrated benefits of a 2–cal/mL, casein–based tube–fed supplement. These findings support the use of standard, casein–based solutions in the treatment of alcoholic liver disease and as the control condition for future studies.

The present studies were designed to provide careful measures of effects of oxandrolone, an anabolic steroid, intravenous nutritional supplementation, and the combination of these two treatments on liver functions, metabolic balances, nitrogen metabolism, and nutritional status in patients with moderate to severe alcoholic hepatitis. Of 43 patients originally recruited, 39 (19 men, 20 women) with typical clinical and laboratory features of alcoholic hepatitis (11 Child's–Pugh class B; 28 class C) were admitted to a metabolic unit and completed a 35–day three–phase protocol. Phase I was a 10–day baseline period of observation, during which routine and special quantitative tests of liver function (galactose and antipyrine metabolism), a 7–day elemental balance study, and a 15N, 13C–leucine metabolism study were done. Phase II was a 21–day treatment period during which patients were randomly assigned to receive one of four regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation consisting of 2 L daily of 3.5% crystalline amino acids (in 6% dextrose), given by peripheral vein; or 4) a combination of oxandrolone and nutritional supplementation, along with standard therapy. Metabolic balances were repeated during phase 11. Phase III was 2 or 3 days posttreatment, during which special studies of liver functions and volumes and leucine metabolism were repeated. All patients who completed phase I of study and were randomly allocated to one of the four treatment groups completed the subsequent two phases. Overall, with time, patients showed highly significant improvements in most clinical and laboratory features. For most standard laboratory tests (e.g., serum albumin, transferrin, prothrombin time) improvements were more marked in patients treated with nutritional supplementation and/or oxandrolone than in those given standard therapy alone. Liver volumes fell in all treatment groups, with greater improvement in those treated with nutritional supplementation. Improvements in galactose and antipyrine metabolism rates were significant only in those treated with nutritional supplementation or oxandrolone. Effects of treatments on metabolic balances, nitrogen metabolism, and measures of nutrition are described in this issue in a companion paper. We conclude that the addition of nutritional supplementation and oxandrolone to standard therapy of moderately severe or severe alcoholic hepatitis is well tolerated, and leads to more rapid improvement in the laboratory parameters measured.

Patients with moderately severe or severe alcoholic hepatitis, described in a companion paper in this issue, had serial studies of energy and protein metabolism and elemental balances before and during treatment for 21 days with one of four randomly assigned regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2 ) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 liters of 3.6% crystalline amino acids in 6% dextrose given by peripheral vein (PPN) plus standard therapy; and 4) a combination of the other three treatments. Dietary and intravenous intakes and weights were recorded daily, and weekly averages were calculated. Anthropometric measurements and blood studies were done weeus blood studies included white blood cell counts and differentials, serum prealbumin, transferrin, and total protein and plasma aminograms. Four–day complete balance studies and measures of 15N,1–12C–leucine metabolism also were performed at baseline and after the treatment period. Major findings were as follows: a) Intakes of total calories and protein were significantly higher in PPN–treated than in other groups. b) All patients had positive elemental balances, both at baseline and at the end of the treatment period. However, those treated with PPN (with or without oxandrolone) had higher positive balances of nitrogen, potassium, phosphorus, and magnesium, indicating improvement in lean body mass. c) Anthropometric measurements showed no significant changes, but measures of the visceral protein compartment (serum prealbumin, transferrin, total protein, total lymphocyte count) improved significantly with time. For most of these variables, increases were significantly greater in those treated with PPN with or without oxandrolone than in the other groups. However, for prealbumin, the increase was greatest in the oxandrolone–treated group. d) PPN treatment produced dramatic increases in levels of branched–chain amino acids and improvement in the ratio of plasma branched chain to aromatic amino acids. Other treatments had no effect on plasma aminograms. e) Metabolism of 15N,13C–leucine was normal and was not affected signiftcantly by treatment. Therapy with PPN and/or oxandrolone was tolerated well. We conclude that PPN has favorable effects on energy and protein metaboliem in florid alcoholic hepatitis; oxandrolone has lesser effects, although it may exert some additional action and particularly increases serum prealbumin levels. The results support the use of nutritional supplementation in therapy of moderately severe or severe alcoholic hepatitis.