A Randomized, Controlled Trial of Treatment of Alcoholic Hepatitis with Parenteral Nutrition and Oxandrolone. II. Short-Term Effects on Nitrogen Metabolism, Metabolic Balance, and Nutrition

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 3.5% crystalline amino acids in 5% 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 weekly; blood studies included white blood cell counts and differentials, serum prealbumin, transferrin, and total protein and plasma aminograms. Four-days complete balance studies and measures of 15N,1-13C-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,1-13C-leucine was normal and was not affected significantly by treatment. Therapy with PPN and/or oxandrolone was tolerated well. We conclude that PPN has favorable effects on energy and protein metabolism 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.     

Accelerated improvement of alcoholic liver disease with enteral nutrition.

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.     

Stimulation of oxidative drug metabolism by parenteral refeeding of nutritionally depleted patients

To determine whether intravenous nutritional repletion can influence oxidative drug metabolizing capacity, antipyrine metabolism was studied in 6 malnourished patients on the second day of a 2-day baseline period and on the last day of two sequential, 8-day intravenous nutritional repletion periods. During the baseline period they received 5% dextrose, 440 kcal per day, intravenously. During the repletion periods they received 20 mg of nitrogen per kilocalorie of baseline resting energy expenditure and, in random order, dextrose to provide a total caloric intake of either 0.95 or 1.75 times baseline resting energy expenditure. There were no statistically significant differences between the high- and low-dextrose repletion regimens in their effects on antipyrine metabolism. Seven days of nutritional repletion resulted in a 42% decrease in mean half-life (range 12%-52%) and an 87% increase in mean metabolic clearance rate (range 29%-155%) for antipyrine. An additional 8 days of nutritional repletion resulted in no further change in these pharmacokinetic parameters.     

Corticosteroid therapy of alcoholic hepatitis.

Fifty-five patients with alcoholic hepatitis were studied in a 28- to 32-day randomized double blind treatment trial comparing prednisolone (40 mg per day) with placebo therapy. Of 31 placebo-treated patients, 4 died during the study interval and 2 more died within 5 days of study completion. Only 1 of 24 prednisolone-treated patients died during the same interval (Fisher exact test; P = 0.10). Stepwise discriminant analysis of laboratory factors associated with death revealed independently significant associations with prolongation of prothrombin time and height of serum bilirubin at the initiation of the study. When treatment was included as a variable in this discriminant analysis, it was found that corticosteroid therapy significantly decreased mortality (P less than 0.05). The corrected wedged hepatic venous presure decreased to a similar extent in the two groups. These studies suggest that corticosteroid therapy does decrease early mortality in patients with severe alcoholic hepatitis, but has no short term effect on the development of portal hypertension.     

How reversible is hepatic functional impairment in autoimmune hepatitis?

BACKGROUND AND AIMS: We quantifed the short-term effects of immunosuppressive therapy on hepatic metabolic function in autoimmune hepatitis to establish how long it takes to achieve maximum functional improvement. METHODS: We studied 14 newly diagnosed patients with autoimmune hepatitis (12 type 1, two type 2) by antipyrine clearance and conventional liver tests, then repeated studies at 3-6 month intervals during the first 18 months of immunosuppressive therapy. RESULTS: Low values for antipyrine clearance were found in 13 of 14 cases; serum albumin concentration was low in four, bilirubin raised in eight and prothrombin time prolonged in four. Following immunosuppressive treatment for 3 months, antipyrine clearance improved by 98% (standard error of the mean 24%), which was proportionally greater than for serum albumin, bilirubin or prothrombin time. Antipyrine clearance and serum albumin continued to improve after 6-12 months of immunosuppressive treatment in several cases, whereas there were no further improvements in alanine aminotransferase (ALT), bilirubin and prothrombin time. CONCLUSIONS: In the short term, immunosuppressive therapy for autoimmune hepatitis markedly improves hepatic metabolic function, which is particularly striking for the sensitive metabolic test antipyrine clearance, but may also be seen with serum albumin. However, it may take up to 12 months to achieve maximal functional recovery. Management guidelines on autoimmune hepatitis should be extended to emphasize that changes in hepatic metabolic function, as well as ALT and gamma-globulin levels, be taken into consideration in the definition of remission.     

Protein-calorie malnutrition associated with alcoholic hepatitis. Veterans Administration Cooperative Study Group on Alcoholic Hepatitis

Three hundred sixty-three alcoholic patients with alcoholic hepatitis were studied in six Veterans Administration medical centers. By history, alcohol consumption was 227.9 g per day, with a mean duration of 23.8 years. Cirrhosis accompanied the alcoholic hepatitis in 58.7 percent of the patients who underwent biopsy or autopsy. Complete nutritional assessment was performed in 284 patients, and observed nutritional changes were classified into those associated with marasmus or those characterizing kwashiorkor. A smaller comparison group of 21 alcoholic patients matched for age and alcohol consumption but without clinically evident liver disease was also studied in an identical manner. None of the patients with liver disease was completely free from malnutrition, whereas 62 percent of the alcoholic patients without liver disease showed abnormalities. In patients with alcoholic hepatitis, some findings associated with marasmus were seen in 86 percent, and some features of kwashiorkor were observed in 100 percent. When present together, the complete picture of kwashiorkor and marasmus correlated closely with the clinical severity of the liver disease (p less than 0.005). The nearly constant association of either complete or partial kwashiorkor or marasmus suggests that the separation of these two entities is artificial in alcoholic patients with liver disease. Although, experimentally, malnutrition may not be essential for the development of alcoholic hepatitis, clinically, it appears to precede the development of the liver injury, which suggests an interaction. Recognition is important so that appropriate nutritional therapy can be provided.     

Nutritional management of patients with chronic liver disease

The focus of the nutritional management in liver disease has swung from micronutrients with the supplementation of vitamins back to the problems of the macronutrients and especially the importance of protein metabolism. Whether the considerable activity in this area in the last few years, particularly in patients with acute alcoholic hepatitis, will result in significant improvements not only in the overall medical management and consequently the quality of life, but also on life itself, still remains to be seen.     

Metabolomics Discloses a New Non-invasive Method for the Diagnosis and Prognosis of Patients with Alcoholic Hepatitis

Introduction and aims. Alcoholic hepatitis is the most severe manifestation of alcoholic liver disease. Unfortunately, there are still some unresolved issues in the diagnosis and management of this disease, such as the need of histological diagnosis, an accurate prognostic stratification, and the development of novel targeted therapies. The present study aimed at addressing these issues by means of metabolomics, a novel high-throughput approach useful in other liver diseases.Material and methods. 64 patients with biopsy-proven alcoholic hepatitis were included and compared with 26 patients with decompensated alcoholic cirrhosis without superimposed alcoholic hepatitis, which was ruled out by liver biopsy.Results. The comparison of the metabolic profiles of patients with alcoholic hepatitis and decompensated cirrhosis showed marked differences between both groups. Importantly, metabolic differences were found among alcoholic hepatitis patients when subjects were stratified according to 90-day survival. Based on these findings, two non-invasive signatures were developed. The first one allowed an accurate non-invasive diagnosis of alcoholic hepatitis (AUROC 0.932; 95% CI 0.901-0.963). The second signature showed a good performance in the prognostic stratification of patients with alcoholic hepatitis (AUROC 0.963; 95% CI 0.895-1.000).Conclusions. Signatures based on metabolomics allowed an accurate non-invasive diagnosis and prognostic stratification of alcoholic hepatitis. The differences observed in the metabolic profile of the patients according to the presence and severity of alcoholic hepatitis are related with different mechanisms involved in the pathophysiology of alcoholic hepatitis such as peroxisomal activity, synthesis of inflammatory mediators or oxidation. This information could be useful for the development of novel targeted therapies.     

Normal antipyrine metabolism in patients with cholesterol cholelithiasis

Plasma antipyrine half-lives and metabolic clearances were measured after a single oral dose of antipyrine in 10 control subjects, 12 patients with gallstones, and 9 patients having undergone cholecystectomy for cholesterol cholelithiasis, to determine whether impairment of hepatic antipyrine metabolism occurs in patients with cholesterol cholelithiasis. The plasma antipyrine half-life and metabolic clearances in the control subjects were 11.7±1.0 hours and 42.5±3.3 ml/min, respectively; in patients with gallstones, 12.3±1.3 hours and 36.0±3.2 ml/min, respectively; and in patients having undergone cholecystectomy, 13.2±1.8 hours and 33.8±4.2 ml/min, respectively. Values for antipyrine half-life and metabolic clearance were not statistically different in these three groups. This study suggests the presence of normal hepatic antipyrine metabolism in patients with cholesterol cholelithiasis.     

Vitamin A and iron supplementation is as efficient as hormonal therapy in constitutionally delayed children

OBJECTIVE: To assess the effect of nutritional supplementation on growth and puberty in constitutionally delayed children. PATIENTS: One hundred and two boys, 13.6-15.5 years of age, who were referred because of short stature and delayed puberty. METHODS: The boys were randomly allocated to one of the following treatment groups: oxandrolone therapy, 5 mg/day for 6 months (n = 15), testosterone depot, 100 mg monthly for 3 months (n = 15) or for 6 months (n = 20), nutritional programme (n = 17), oxandrolone and nutritional programme (n = 15) or passive observation (n = 20). Boys in the nutritional programmes received 12 mg/day iron and 6000 IU/week of vitamin A. Outcome measurements were of height, weight, pubertal signs, dietary intake, serum vitamin A, iron, GH and IGF-1. RESULTS: Six months of vitamin A supplementation induced growth acceleration similar to that seen in the oxandrolone- and testosterone-treated children, and significantly greater than in the observation group (9.3 +/- 2.9 vs. 4.0 +/- 0.9 crn/yr, P < 0.001). Whereas in the vitamin A-supplemented group, puberty (increase in testicular volume >/= 12 ml) was induced within 12 months. In all testosterone-treated patients, pubic hair was noted within 3 months and a testicular volume of >/= 12 ml was observed 9-12 months after the initiation of therapy. No pubertal signs were noted in the observation group during this time. CONCLUSIONS: Subnormal vitamin A intake is one of the aetiological factors in delayed pubertal maturation. Supplementation of both vitamin A and iron to normal constitutionally delayed children with subnormal vitamin A intake is as efficacious as hormonal therapy in the induction of growth and puberty.     

Predictive value of whole blood chemiluminescence in patients with alcoholic hepatitis

Recent reports suggest that ethanol metabolism leads to reactive oxygen intermediates that may be responsible for the lesions observed in alcoholic hepatitis. This study investigated the production of reactive oxygen intermediates in peripheral blood phagocytes of patients with alcoholic hepatitis and attempts to evaluate its predictive value. Using a luminol-dependent chemiluminescence method, reactive oxygen intermediate production was measured directly within microamounts of whole blood, both in the absence (basal chemiluminescence production) and in the presence of phagocyte-stimulating agents including latex, zymosan, phorbol myristate acetate and N-formyl-methionyl-leucyl-phenylalanine. Thirty patients with well-documented and histologically proven alcoholic hepatitis were studied. Pugh's and Child's classification, Orrego's composite clinical and laboratory index and Maddrey's discriminant function were used to assess the prognosis of the liver disease. Patients were followed up monthly for 6 mo. Results were compared with those obtained in 17 patients with nonalcoholic liver disease and in 78 normal control subjects. Basal chemiluminescence production was significantly higher in patients with alcoholic hepatitis than in those with nonalcoholic liver disease and in normal subjects (p less than 0.001). Chemiluminescence responses to latex, zymosan and phorbol myristate acetate were significantly lower in alcoholic hepatitis patients than in normal subjects (p less than 0.001); however, when compared with nonalcoholic liver disease patients, these responses were significantly decreased only in the presence of zymosan (p less than 0.05). Both basal chemiluminescence production (p less than 0.001) and zymosan-induced chemiluminescence responses (p less than 0.02) were closely related to alcoholic hepatitis prognosis indices (i.e., Pugh's and Child's classification, Orrego's composite clinical and laboratory index and Maddrey's discriminant function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of prolonged oral nutritional support in malnourished cirrhotic patients: results of a pilot study

OBJECTIVES: The aim of this prospective study was to evaluate the acceptance and the effects of nutritional supplementation in malnourished ambulatory patients with liver cirrhosis. METHODS: From June 1999 through June 2000, alcoholic cirrhotic patients with moderate to severe malnutrition as assessed with the Detsky index were included in the study. Patients were instructed to consume, in addition to their regular diet, a commercial solution that provided 500 kcal/day. Physical examination, dietary recalls and laboratory tests were performed at 1, 2 and 3 Month. RESULTS: Twenty-nine patients with a mean age of 52 Years were included. The Child-Pugh grade was A in 6 patients, B in 14 and C in 8. Eighteen patients (62%) completed the 3 Month study protocol. Mean non-alcohol calorie intake increased significantly by 31% at 1 Month and by 48% at 3 Months. At the same time alcohol calorie intake decreased significantly by 68% and 77%, respectively. Subjective improvement in nutritional status was associated with significant improvement of mean Child-Pugh score (P=0.0007) and triceps skinfold thickness (P=0.005). The increase of mid-arm circumference was not significant. CONCLUSION: This study showed that oral supplementation in ambulatory patients with liver cirrhosis is feasible and associated with a significant improvement of nutritional status and biological parameters including the Child-Pugh score. This benefit was associated with a concomitant reduction of alcohol intake.     

Diagnosis and management of alcoholic liver disease

Alcohol is the most commonly used hepatotoxin worldwide. About 90% of heavy drinkers (more than 60 g/day of alcohol) show evidence of fatty livers, while only 10-35% develop alcoholic hepatitis and 5-15% developed cirrhosis. The daily intake of alcohol that results in liver injury varies and depends on a number of risk factors. Alcoholic disease developes at lower doses in females, Hispanic, obese objects, and patients with hepatitis C. Insights into the pathogenesis of alcohol-induced liver injury has improved significantly but the translation into clinical benefit has been slow. The importance of continued abstinence and correction of nutritional deficiencies are major components in the long-term management of liver disease. Alcohol hepatitis has a variable mortality and the prognosis is determined most commonly by the modified discriminant function. The mocel of end-stage liver disease (MELD) is being increasingly used to predict outcome in alcoholic hepatitis even though standard cut offs are not available. Anti-inflammatory therapy with corticosteroids and anticytokine therapy with corticosteroids and pentoxifylline are effective for patients with severe alcoholic hepatitis. Patients with endstage liver disease should be considered for liver transplantation. Six months of abstinence is considered to be a requirement prior to transplant, but this length of time may be adjusted in individual bases.     

慢性乙型肝炎伴萎缩性胃炎患者幽门螺旋杆菌感染序贯根除的疗效

目的 探讨慢性乙型肝炎伴萎缩性胃炎患者幽门螺旋杆菌的感染率及序贯根除的临床效果。方法300例慢性乙型肝炎患者通过胃镜进行组织活检,病理证实为慢性萎缩性胃炎,均通过组织WS染色及14C．尿素呼气试验（UBT）检测幽门螺旋杆菌,其中195例阳性者随机分为治疗组105例和对照组90例,治疗组先给予雷贝拉唑＋阿莫西林5d,随后给予雷贝拉唑＋克拉霉素＋甲硝唑5d,进行10d序贯治疗,对照组给予传统三联既雷贝拉唑＋克拉霉素＋阿莫西林7d疗法,治疗结束4周后予14C—UBT复查。结果慢性乙型肝炎患者伴萎缩性胃炎幽门螺旋杆菌的感染率为65．0％,传统方法幽门螺旋杆菌的根除率约为70．0％,治疗组幽门螺旋杆菌的根除率达92．3％,两者比较,10d序贯疗法明显优于7d疗法（P〈0．05）,两组副作用发生率无明显差异。结论慢性乙型肝炎伴萎缩性胃炎患者幽门螺旋杆菌的感染率较高,序贯治疗有较好的根除效果。     

Ascorbic acid deficiency in liver disease.

Leucocyte ascorbic acid (LAA) levels were measured in 138 patients with liver disease. Significantly reduced levels were found in 37 patients with alcoholic liver disease (P less than 0-01) and 25 patients with primary biliary cirrhosis (P less than 0-05). In the primary biliary cirrhosis patients, cholestyramine therapy was associated with significantly lower levels of the vitamin (P less than 0-05). Liver ascorbic acid measured in Menghini needle biopsies in 20 patients was significantly correlated with LAA (r=0-807, P less than 0-001). No significant correlation was found between LAA and haematological indices, conventional liver function tests, or cholesterol levels in any group of patients. Patients with LAA levels below 100 nM/10(8) WBC had significantly higher antipyrine half-lives (mean=28-3 h) than patients with LAA levels above this level (mean=18-6 h) (P less than 0-05). Delayed drug metabolism related to low LAA should be considered when drugs metabolised by the liver are prescribed for patients with alcoholic liver disease or primary biliary cirrhosis.     

Alcoholic liver disease: Treatment

The excess consumption of alcohol is associated with alcoholic liver diseases(ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol in-take, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psycho-therapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation.     

Pathogenesis and management of alcoholic hepatitis

Alcoholic hepatitis is a potentially life-threatening complication of alcoholic abuse, typically presenting with symptoms and signs of hepatitis in the presence of an alcohol use disorder. The definitive diagnosis requires liver biopsy, but this is not generally required. The pathogenesis is uncertain, but relevant factors include metabolism of alcohol to toxic products, oxidant stress, acetaldehyde adducts, the action of endotoxin on Kupffer cells, and impaired hepatic regeneration. Mild alcoholic hepatitis recovers with abstinence and the long-term prognosis is determined by the underlying disorder of alcohol use. Severe alcoholic hepatitis is recognized by a Maddrey discriminant function >32 and is associated with a short-term mortality rate of almost 50%. Primary therapy is abstinence from alcohol and supportive care. Corticosteroids have been shown to be beneficial in a subset of severely ill patients with concomitant hepatic encephalopathy, but their use remains controversial. Pentoxifylline has been shown in one study to improve short-term survival rates. Other pharmacological interventions, including colchicine, propylthiouracil, calcium channel antagonists, and insulin with glucagon infusions, have not been proven to be beneficial. Nutritional supplementation with available high-calorie, high-protein diets is beneficial, but does not improve mortality. Orthotopic liver transplantation is not indicated for patients presenting with alcoholic hepatitis who have been drinking until the time of admission, but may be considered in those who achieve stable abstinence if liver function fails to recover.     

Granulocytapheresis (GCAP) for severe alcoholic hepatitis-A preliminary report.

AIM: To evaluate the efficacy of granulocytapheresis therapy in alcoholic hepatitis. METHODS: We attempted to trap leukocytes in the peripheral circulation using the granulocytapheresis (GCAP) technique in patients with severe alcoholic hepatitis who showed a marked elevation of peripheral leukocytes. Corticosteroids were co-administered. RESULTS: The Maddrey's indices for these patients varied between 42 and 117 and MELD scores for alcoholic hepatitis (Mayo) ranged from 20 to 44. Survival rate was 50% (3/6), which is better than the results reported recently for similar patients in a national survey (29%). The effect of GCAP was reflected in decreases in interleukin-6 and interleukin-8 levels as well as in serum concentrations of soluble intercellular adhesion molecule. White blood cell counts were not affected. In the surviving patients, the Maddrey's indices and MELD scores for alcoholic hepatitis varied between 49 and 67, and 20 and 22, respectively, showing that GCAP is effective in patients with disease of moderate severity. Hemolytic anemia occurred in one patient after GCAP therapy. Other events such as pancreatitis, pneumonia, and cerebral hemorrhage were considered to be related to the alcoholic hepatitis itself. CONCLUSION: GCAP therapy deserves further evaluation as a new therapeutic modality for a moderately severe alcoholic hepatitis.     

Treatment of alcoholic liver disease

Alcoholic Liver Disease (ALD) is a major cause of morbidity and mortality both in the United States and worldwide. In the United States, it is projected that over 2,000,000 persons have ALD, and the mortality for cirrhosis with superimposed alcoholic hepatitis is much worse than that of many common types of cancer. Unfortunately, there is no FDA approved therapy for ALD. We have made major strides in the last decade in identifying mechanisms for the development of liver injury in ALD, and therapies are evolving directed at specific mechanisms. It is clear that life style modification with abstinence, cessation of smoking and weight loss (if overweight) are beneficial. It is also clear that most patients with advanced liver disease have some form of malnutrition, and nutritional supplementation is of benefit. Patients with alcoholic hepatitis that is relatively severe in nature, but not complicated by issues such as infection or GI bleeding, appear to benefit from steroids. A drop in bilirubin should be monitored in steroid treated patients. Pentoxifylline appears to be beneficial in patients with alcoholic hepatitis, especially those with early hepatorenal syndrome. A variety of other agents such as PTU, lecithin, colchicine, and anabolic steroids are probably not effective. Complementary and alternative medicine agents such as zinc, milk thistle, and SAM have great therapeutic rationale. Results of ongoing NIH studies evaluating agents such as specific anti-TNF's, SAM and Milk Thistle are eagerly awaited. Transplantation is clearly an option for end stage ALD in patients who are abstinent.     

Hyperalimentation in Alcoholic Hepatitis

Enteral hyperalimentation in four patients with severe alcoholic hepatitis and anorexia increased spontaneous food intake, increased their nitrogen balance and the patients improved clinically. Seven patients with alcoholic hepatitis, who were clinically ill and able to eat only 410-1,100 calories per day, were given a 900 mosM/l. parenteral "hyperalimentation" solution by a peripheral vein (P-900). The intravenous nutrition provided daily 51.6-77.4 gm. amino acids in addition to oral intake. All patients improved. None developed detectable encephalopathy after 16-42 days of P-900 therapy. Five additional patients had ascites and alcoholic hepatitis. The daily infusion of 2,000 ml. P-900 was not associated with hyponatremia, renal failure or encephalopathy in four of these five patients who improved and continued their diuresis. P-900 therapy was discontinued in one because of progressive hyponatremia. The observations indicate that over and above the maximum tolerable oral nutrition, intravenous nutrition can be effectively utilized by clinically ill, jaundiced patients with alcoholic hepatitis without precipitating encephalopathy or interference with standard therapy of ascites.