Natural killer cell activity in alcoholic cirrhosis: influence of nutrition

Forty-five patients with alcoholic cirrhosis, 20 chronic alcoholics with normal liver function tests and 36 healthy subjects were investigated. A combined index of nine anthropometric and biochemical parameters (triceps skinfold, arm muscle circumference, mid-arm muscle area, body fat percentage, creatinine-height index, serum albumin, plasma transferrin, prealbumin and retinol-binding protein levels) was used to evaluate nutritional status, allowing a distinction to be made between those patients with adequate nutrition (group I: 40 per cent of cirrhotics and 55 per cent of alcoholics), those with slight malnutrition (group II: 37.7 per cent of cirrhotics and 45 per cent of alcoholics) and those with severe malnutrition (group III: 22.2 per cent of cirrhotics and none alcoholic). Natural Killer (NK) cell activity of peripheral blood lymphocytes was determined using a 51Cr releasing cytotoxicity assay against K562 target cells. This was significantly lower in the cirrhotics than in the controls and chronic alcoholics (P less than 0.001 and P less than 0.01 respectively), but there was no difference between the latter two groups. Natural Killer activity was significantly lower in samples obtained from cirrhotics with severe malnutrition than in those with adequate nutrition, suggesting that malnutrition may play a role in the onset of the immunological disorder. No relationship could be established between nutritional status, NK activity and the clinical activity of the disease using Orrego's index on the liver function tests.     

Nutritional assessment in various stages of liver cirrhosis

OBJECTIVES: The aims of this study were to determine the prevalence of protein-calorie malnutrition, characteristics, and clinical importance of nutrition disorders in patients with liver cirrhosis according to severity of disease. METHODS: Nutrition assessments such as subjective global assessment, anthropometric and biochemical measurements, immunocompentency, thiamin and riboflavin status in 60 patients with cirrhosis (33 male and 27 female) were recorded between June 1999 and December 1999 at an outpatient clinic at Ramathibodi Hospital, Bangkok, Thailand. The origin of liver disease was alcohol related in 50% of patients. Child-Pugh criteria were used to establish the severity of liver disease. RESULTS: In terms of energy malnutrition, 13.3% of patients had ideal body weights below 90% and 11.7% had body mass indexes below 18.5 kg/m(2). Protein malnutrition (low albumin) and immunoincompetence (abnormal response to skin tests) were found much more frequently (45% and 22%) than energy malnutrition. Patients with alcoholic cirrhosis had ascites (P < 0.05) and hepatic encephalopathy (P < 0.001) more frequently and less triceps skinfold thickness than those with non-alcoholic cirrhosis. Subjective global assessment and serum proteins correlated with the degree of liver-function impairment, but immunologic tests correlated inversely in cirrhosis patients. Mean values for creatinine-height index, hemoglobin, cholesterol, and complement C4 showed significant decreases in severe liver failure (Child-Pugh class C) only in patients with alcoholic cirrhosis (P < 0.05). Malnutrition was correlated with the clinical severity of liver disease. CONCLUSIONS: The study showed that protein-energy malnutrition is a common complication of liver cirrhosis. Nutritional disorders appeared to be related to the degree of liver injury and the etiology of nutritional disorders. Nutritional disorders were more severe with alcoholic cirrhosis than with non-alcoholic cirrhosis.     

酒精性肝硬化和病毒性肝硬化病人营养状况调查和分析

目的:对比分析酒精性肝硬化和病毒性肝硬化病人的营养状况,为营养支持提供针对性依据。方法:选择酒精性肝硬化病人95例,病毒性肝硬化病人260例,入院后48 h内采用欧洲营养风险筛查2002(NRS2002)和主观整体评估(SGA)法对病人进行评估,记录病人的性别、年龄、肝功能Child-Pugh分级、血清清蛋白(ALB)、前清蛋白(PA)和血红蛋白(Hb)指标,测量病人身高、体重,计算体重指数(BMI)。结果:酒精性肝硬化和病毒性肝硬化病人的NRS 2002营养风险发生率分别为76.80%和65.00%,SGA评估的营养不良发生率分别为67.40%和61.90%。两组病人的性别、Child-Pugh A级、ALB、PA、Hb、NRS 2002筛查等结果差异均有显著性统计学意义。而年龄、Child-Pugh B级、Child-Pugh C级、BMI、SGA评估等结果则无显著性差异。结论:两种类型肝硬化病人普遍存在营养问题,酒精性肝硬化病人的营养风险发生率、贫血程度显著高于病毒性肝硬化病人。     

Osteopenia assessed by body composition analysis is related to malnutrition in alcoholic patients.

Osteopenia is frequent among alcoholics. Its pathogenesis seems to be multifactorial, including ethanol intake, hormonal changes, liver cirrhosis, and malnutrition. Our objective is to determine the relative role of malnutrition on bone loss. One hundred and eighty-one male alcoholic patients, drinkers of more than 80 g ethanol/day, were included, recording data on the intensity of alcoholism, liver cirrhosis, nutritional assessment based on feeding habits, body mass index (BMI), midarm anthropometrics, subjective nutritional assessment, lean and fat mass by dual energy X-ray absorptiometry (DEXA), serum proteins and insulin growth factor Type I (IGF-I), calcitropic hormones, parathyroid hormone (PTH), osteocalcin 25OHD3, and bone mass assessed by DEXA, which was also performed in 43 healthy controls. Alcoholics showed decreased serum osteocalcin, PTH, 25OHD3, IGF-I, and bone mass. Alcoholics were frequently malnourished with decreased BMI, lean, and fat mass. The loss of bone mass was not related to the alteration of calcitropic hormones, to the intensity of alcoholism, or to the existence of liver cirrhosis, but to malnutrition. For a similar BMI, bone loss was more intense in alcoholics than in controls, especially in those with irregular feeding habits. Although cross-sectional ones, our data suggest that alcoholic osteopenia may be interpreted as a form of nutritional osteoporosis, notwithstanding the influence of other factors.     

Nutrition and alcoholic liver disease

While the rate of malnutrition is relatively modest in alcoholic patients without alcoholic liver disease, the rate of malnutrition is virtually 100% in patients with alcoholic hepatitis and/or alcoholic cirrhosis. The reasons for malnutrition in the alcoholic hepatitis patient include various factors such as anorexia, poor diet, malabsorption, and altered metabolic state. When the patient is hospitalized, the malnutrition frequently worsens because of fasting for tests, continued anorexia, and complications such as gastrointestinal bleeding. Patients with severe acute hepatitis appear to be both hypermetabolic and hypercatabolic, whereas data are much more conflicting concerning patients with more stable liver disease. Most studies suggest that patients with alcoholic liver disease require at least 60 g of protein per day to maintain positive nitrogen balance. Consistent alterations in plasma amino acid profiles occur in alcoholic liver disease, and specialized nutritional formulations have been devised to correct this amino acid profile with the intent of improving overall nutritional status, hepatic encephalopathy, and mortality. The effects of nutritional support (including use of specialized products) on outcome, on acute hepatic encephalopathy, and on chronic or latent portal systemic encephalopathy are reviewed.     

慢性重症肝炎患者营养支持及疗效评价

目的: 评价慢性重症肝炎患者营养状况、营养支持及疗效。方法: 143例慢性重症肝炎患者,入院后进行SGA评估,明确营养状况。分三组,肝病综合治疗和肠内营养+肠外营养;综合治疗+肠外营养;综合治疗+肠内营养。监测0~6 w肝功能及营养指标变化,最后评价临床疗效。结果: 90%以上患者存在中重度营养不良。综合治疗+肠内和肠外营养方案改善肝功能(ALT、Tbil)及营养指标(TP、TC)效果最好,显效率明显高于另两组(P<0.05)。肠内营养略好于肠外营养方案。结论: 慢性重症肝炎患者多数存在营养不良。综合治疗的同时肠内+肠外营养支持疗效最好,应鼓励患者适量进食。     

Nutritional status of alcoholic patients: it's possible relationship to alcoholic liver damage

This study was performed to look for a possible relationship between the nutritional status and the presence of liver damage in alcoholic patients. One hundred chronic alcoholics admitted for treatment to the Alcoholism Ward, without clinical signs of liver failure, were studied. In 84, anthropometric nutritional indexes, liver function tests, and a liver biopsy were performed; in 69 patients a dietary survey was obtained. A dietary imbalance was observed in the total group; 65% of ingested calories were derived from ethanol. The intake of proteins, vitamins, and minerals was below the RDA, NAS/USA, and no differences were found between patients with and without liver damage. Neither were significant differences in daily alcohol calories or total ethanol dose found between both groups of patients. Mean anthropometric values were within 80 to 100% of commonly used standards. However, patients with alcoholic hepatitis and/or cirrhosis had a significantly higher percentage of ideal body weight, compared to alcoholics with normal livers or less severe histological alterations (109.7 +/- 20.3 versus 95.6 +/- 12.5, SD, p less than 0.005). A similar difference was observed in arm muscle areas. These findings show that overweight is associated with liver alterations in the alcoholic and should be investigated as a risk factor to develop liver damage.     

Maladies alcooliques du foie et dénutrition

The aim of this study is to try to answer to four questions from a literature review.

1) What is the prevalence of malnutrition in alcoholic patients with and without liver disease?

2) Is nutritional status independently correlated with survival in patients with alcoholic cirrhosis?

3) Is nutritional supplementation useful in patients with severe liver disease?

4) What energy substrate and nitrogen sources should be used for intravenous nutrition in patients with cirrhosis?

The answers to these questions are:

1) The prevalence of malnutrition in alcoholic patients depends on definition of the studied population. The objective assessment of nutritional status by quantitative clinical and biological parameters is difficult.

2) It has not been demonstrated that nutritional status has an independent prognostic value in patients with alcoholic cirrhosis.

3) The effectiveness of supplementary parenteral nutrition on survival and nutritional status of patients with severe alcoholic liver disease has not been proved.

4) Neither fat emulsions nor conventional amino acids solutions are contraindicated in patients with cirrhosis when parenteral nutrition is necessary.

RELATIONSHIP BETWEEN ETHANOL-RELATED DISEASES AND NUTRITIONAL STATUS IN CHRONICALLY ALCOHOLIC MEN

Two-hundred and fifty chronically alcoholic men (mean age, 41± 11 years) entering an alcoholism treatment programwere studied. Detailed clinical history, nutritional assessmentand measurement of muscle strength by electronic myometer wereperformed in each case. In addition, hepatic ultrasonographyand liver biopsy, echocardiography and radionuclide cardiacscanning, and electrophysiological testing of peripheral nerveswere performed when there was clinical evidence of liver disease,cardiomyopathy or neuropathy, respectively. Alcoholic cirrhosiswas diagnosed in 20 cases, skeletal myopathy in 117, dilatedcardiomyopathy in 20 and peripheral neuropathy in 41 cases.No patients with chronic myopathy or cardiomyopathy showed eitherclinical or laboratory evidence of malnutrition. Patients withcirrhosis showed a significantly lower lean body mass than controls(P = 0.03) and significantly lower nutritional protein levelsthan those alcoholics without cirrhosis. Alcoholics with peripheralneuropathy had significantly lower anthropometric parametersand nutrition protein levels than their counter parts (P <0.001). However, in the multivariate analysis, the only independentfactor for developing these complications of alcoholism wasthe total lifetime dose of ethanol (P < 0.001). We concludethat alcohol-related diseases are common in asymptomatic alcoholicmen and these diseases appear to be due to an accumulative toxiceffect of ethanol. Age and nutritional status do not seem toplay a part in the development of such diseases.     

Nutrition and survival in patients with liver cirrhosis

Although the effect of malnutrition on survival has been demonstrated by a number of studies, it is not clear whether malnutrition represents an independent risk factor in patients with liver disease. We studied 212 hospitalized patients with liver cirrhosis who were followed clinically for 2 y or until death. Body fat and muscle mass were evaluated by triceps skinfold thickness (TSF) and midarm muscle circumference (MAMC), respectively. Multivariate analysis according to Cox's model assessed the predictive power of nutritional parameters on survival. Thirty-four percent of patients had severe malnutrition as determined by MAMC and/or TSF below the 5th percentile and 20% had moderate malnutrition (MAMC and/or TSF < 10th percentile). Twenty-six percent of patients were overnourished (MAMC and/or TSF > 75th percentile). Severely and moderately malnourished patients had lower survival rates than normal and overnourished patients. When analyzed with Cox's regression analysis, severe depletion of muscle mass and body fat were found to be independent predictors of survival. The inclusion of MAMC and TSF in the Child-Pugh score, the prognostic score used most with liver disease, improved its prognostic accuracy. The prognostic power of MAMC was higher than that of TSF. These data demonstrate that malnutrition is an independent predictor of survival in patients with liver cirrhosis. The inclusion of anthropometric measures in the assessment of these patients might provide better prognostic information.     

Usefulness of the Mini Nutritional Assessment in Predicting the Nutritional Status of Patients With Liver Cancer in Taiwan

Liver cancer patients are confronted with the additional risk of malnutrition because the disease is often associated with hepatitis, liver cirrhosis, and metabolic disturbances. Nutritional intervention can improve treatment outcome, but early detection is important. This study aimed to determine whether the Mini Nutritional Assessment (MNA) could effectively rate the nutritional status of patients with liver cancer in Taiwan. A total of 300 patients were evaluated for nutritional status with two modified versions of the MNA in short and long forms. MNA-Taiwan Version 1 adopted population-specific anthropometric cutpoints, whereas Version 2 replaced mid-arm and calf circumferences in place of body mass index. Predicted statuses were compared to results predicted by the Council on Nutrition Appetite Questionnaire (CNAQ) and analyzed for correlations with biochemical or cancer status parameters. Results showed that both versions of the MNA were effective in predicting nutritional status, and predictions by the short forms agreed well with those by the long forms. The nutritional scores correlated well with hemoglobin, serum albumin, C-reactive protein, r-glutamyl transpeptidase, TNM (tumor, node, metastasis) staging, and severity of cirrhosis. These results suggest that the MNA can be an effective tool for assessing the nutritional status of patients with liver cancer.     

Usefulness of the mini nutritional assessment in predicting the nutritional status of patients with liver cancer in Taiwan

Liver cancer patients are confronted with the additional risk of malnutrition because the disease is often associated with hepatitis, liver cirrhosis, and metabolic disturbances. Nutritional intervention can improve treatment outcome, but early detection is important. This study aimed to determine whether the Mini Nutritional Assessment (MNA) could effectively rate the nutritional status of patients with liver cancer in Taiwan. A total of 300 patients were evaluated for nutritional status with two modified versions of the MNA in short and long forms. MNA-Taiwan Version 1 adopted population-specific anthropometric cutpoints, whereas Version 2 replaced mid-arm and calf circumferences in place of body mass index. Predicted statuses were compared to results predicted by the Council on Nutrition Appetite Questionnaire (CNAQ) and analyzed for correlations with biochemical or cancer status parameters. Results showed that both versions of the MNA were effective in predicting nutritional status, and predictions by the short forms agreed well with those by the long forms. The nutritional scores correlated well with hemoglobin, serum albumin, C-reactive protein, r-glutamyl transpeptidase, TNM (tumor, node, metastasis) staging, and severity of cirrhosis. These results suggest that the MNA can be an effective tool for assessing the nutritional status of patients with liver cancer.     

Évaluation de l’état nutritionnel au cours de la cirrhose : méthodes,limites et implications

Liver plays a key-role in the metabolism of nutrients. Therefore, liver failure is often associated with malnutrition. It is well established that malnutrition stands as a pejorative factor for prognosis in cirrhotic patients with liver failure. But nutritional assessment is difficult in cirrhotic patients since standard anthropometric and biological indexes are linked with liver dysfunction. We detail here the various causes and mechanisms leading to malnutrition in cirrhosis. We also describe the reliable methods used to assess nutritional state of cirrhotic patients. Finally, we put emphasis on the involvement of nutritional care in cirrhosis and liver dysfunction, describing its specific characteristics and indications.     

NUTRITIONAL STATUS IN CHRONICALLY ALCOHOLIC MEN FROM THE MIDDLE SOCIOECONOMIC CLASS AND ITS RELATION TO ETHANOL INTAKE

Two-hundred and fifty chronically alcoholic men (mean age, 41± 11 years) entering an alcoholism treatment programwere studied. Detailed clinical history, nutritional assessmentand measurement of muscle strength by electronic myometer wereperformed in each case. In addition, hepatic ultrasonographyand liver biopsy, echocardiography and radionuclide cardiacscanning, and electrophysiological testing of peripheral nerveswere performed when there was clinical evidence of liver disease,cardiomyopathy or neuropathy, respectively. Alcoholic cirrhosiswas diagnosed in 20 cases, skeletal myopathy in 117, dilatedcardiomyopathy in 20 and peripheral neuropathy in 41 cases.No patients with chronic myopathy or cardiomyopathy showed eitherclinical or laboratory evidence of malnutrition. Patients withcirrhosis showed a significantly lower lean body mass than controls(P = 0.03) and significantly lower nutritional protein levelsthan those alcoholics without cirrhosis. Alcoholics with peripheralneuropathy had significantly lower anthropometric parametersand nutrition protein levels than their counter parts (P <0.001). However, in the multivariate analysis, the only independentfactor for developing these complications of alcoholism wasthe total lifetime dose of ethanol (P < 0.001). We concludethat alcohol-related diseases are common in asymptomatic alcoholicmen and these diseases appear to be due to an accumulative toxiceffect of ethanol. Age and nutritional status do not seem toplay a part in the development of such diseases     

VA Cooperative Study on Alcoholic Hepatitis. III: Changes in protein-calorie malnutrition associated with 30 days of hospitalization with and without enteral nutritional therapy

Patients with moderate to severe alcoholic hepatitis and features of protein-calorie malnutrition were studied with respect to changes in their nutritional status during 30 days of hospitalization. Thirty-four patients served as controls, were given a 2500 kcal hospital diet and allowed to eat ad libitum. Twenty-three patients were given, in addition to the hospital diet, a nutrition supplement high in calories, protein, and branched-chain amino acids (Hepatic Aid). Because of anorexia, the controls consumed lesser amounts of both calories and protein while those given the nutritional therapy exceeded their estimated energy requirements (116.1%) and consumed a mean of 98.3 g of protein per day. This was well tolerated despite the fact that portal systemic encephalopathy was present in 72% of the patients. Mortality associated with the liver disease was comparable in both groups, 16.7% in the treated vs 20.6% in the controls. In those patients that survived the 30 days of hospitalization, clinical and biochemical tests of liver injury improved in both groups. With respect to their nutritional status, those given nutritional therapy showed significant improvement in six of the nine parameters (67%) used to assess nutrition. In the controls significant improvement was observed in only two nutritional parameters (22%) while three parameters (33%) deteriorated further. These three were all associated with calorie deprivation (marasmus). This study suggests that patients with acute alcoholic hepatitis require additional nutritional therapy to maintain and improve their nutrition parameters, especially those related to marasmus; and that Hepatic Aid is well tolerated for this purpose.     

早期肠内营养对急性重症胰腺炎炎症介质及营养指标的影响简

目的：探讨早期肠内营养对急性重症胰腺炎患者炎症介质、营养指标及临床恢复的影响。方法2006年1月至2010年3月收治的急性重症胰腺炎患者患者59例,随机分成早期肠内营养组31例,肠外营养组28例,观察上述两组治疗后1、3、7天血清中TNF-α、IL-1β、前白蛋白、清蛋白的水平;外周血淋巴细胞数;并观察两组血清淀粉酶恢复时间,全身炎性反应综合征（ Systemic infammactery response syndrome ,SIRS）、腹腔脓肿及肝功能异常例数,治疗费用等指标的差异。结果早期肠内营养组治疗后3、7天血清TN F-α、IL-1β浓度明显低于肠外营养组（ P＜0．05）,前白蛋白、清蛋白的水平、外周血淋巴细胞数明显高于肠外营养组（P＜0．05）,治疗费用低于肠外营养组（P＜0．05）,两组血清淀粉酶恢复时间,SIRS、腹腔脓肿及肝功能异常例数无明显差异（P＞0．05）。结论早期肠内营养在改善急性重症胰腺炎患者营养状态方面明显优于肠外营养,有利于提高机体的抗感染能力和各系统机能的恢复,是可靠、安全、经济的营养支持手段。     

Contrasts in interleukin-1 and interleukin-2 activity in alcoholic hepatitis and cirrhosis

To investigate whether disordered immune function, as shown by abnormalities in lymphokine production, is present in alcoholic liver disease, interleukin-1 and interleukin-2 activity were assayed in a group of patients with acute alcoholic hepatitis in the absence of underlying cirrhosis, and a group of patients with inactive alcoholic cirrhosis. Activities of both IL-1 and IL-2 in alcoholic hepatitis were similar to those of normal individuals, although in abstinent patients with alcoholic cirrhosis, IL-1 activity was increased and IL-2 activity decreased. Lymphocyte transformation in response to PHA in patients with alcoholic hepatitis was significantly impaired when compared with normal controls, and addition of exogenous IL-2 did not correct this impaired response over a wide range of concentrations of both PHA and IL-2. These observations suggest the underlying defects in cell mediated immunity in acute alcoholic hepatitis, as assessed by blast transformation, could be fundamentally different from those of alcoholic cirrhosis and could be secondary to the metabolic effects of acetaldehyde or altered redox potentials on the behaviour of proliferating cells.     

Effects of an appropriate oral diet on the nutritional status of patients with HCV-related liver cirrhosis: a prospective study

BACKGROUND AND AIMS: In patients with liver cirrhosis, protein-energy malnutrition is a frequent finding and a risk factor influencing survival. The aim was to estimate the effects of an adequate diet on malnutrition and clinical outcome in patients with Child A or B HCV-related liver cirrhosis. METHODS: We enrolled 90 consecutive outpatients (M/F=52/38) with liver cirrhosis, 30 in Child class A and 60 in class B. Patients were evaluated by anamnesis, clinical examination, estimation of daily caloric intake and measurement of anthropometrical and biochemical indexes. Patients were randomized into two groups: group 1 with a 3-month oral controlled diet started one week after the first examination and this was followed by a 3-month of spontaneous dietary intake, and group 2 which started a 3-month spontaneous dietary intake followed by a 3-month of controlled diet. The follow-up was performed every month. RESULTS: During the period of controlled diet in patients of both groups, protein malnutrition assessed by midarm muscle circumference, creatinine-height index and serum albumin significantly improved independently of the Child class. Lipid malnutrition, assessed by triceps skin fold thickness values, did not improve during the course of the study. The compliance to the prescribed diet was very high in both groups, and no carry over effect of the previous dietary intake was observed during the follow-up period. CONCLUSIONS: The results emphasize the importance of both nutritional status evaluation and improvement in the Child A and B cirrhotic patients with HCV-related disease. The proposed nutritional approach was able to influence their protein malnutrition positively.     

Portacaval shunt,nutritional status and immunocompetence in the cirrhotic patient: Results of a prospective study

Twenty-four patients with cirrhosis were investigated. A nutritional study and an assessment of cellular immunity were performed prior to portacaval shunt and 2 months, 6 months and 12 months following this procedure. Serum bilirubin concentration and coagulation factors II and V were also measured. Following portacaval shunting, there was a progressive and significant increase of arm muscle circumference (P < 0.001) and serum albumin concentration (P < 0.001) as well as an improvement in delayed hypersensitivity and an increase of peripheral T lymphocytes. Serum bilirubin concentration significantly increased and coagulation factors significantly decreased. Among the 20 patients with alcoholic cirrhosis, 19 stopped drinking: 17 of them markedly improved their nutritional and immunological parameters whereas two remained unchanged. One patient pursued a heavy alcohol intake and his parameters deteriorated. The four patients with non alcoholic cirrhosis had mild malnutrition prior to portal systemic shunt which was not significantly altered by this procedure. These results suggest that: a) portacaval shunt does not aggravate the pre-existing malnutrition in cirrhotic patients; b) there is no relationship between the variations of nutritional status and that of liver function; c) improvement of the nutritional status observed in alcoholics following portal diversion is most likely related to alcohol abstinence.