Bone mineral density, osteoporosis, and fractures among people with eating disorders: a systematic review and meta-analysis.

OBJECTIVE: To provide meta-analytical evidence of bone mineral density (BMD), fractures, and osteoporosis rates in eating disorders (ED) vs. healthy controls (HCs). METHOD: Three independent authors searched major electronic databases from inception till August 2015 for cross-sectional studies reporting BMD in people with ED (anorexia nervosa, (AN); bulimia nervosa, (BN); eating disorders not otherwise specified, (EDNOS)) vs. HCs. Standardized mean differences (SMDs) ±95% and confidence intervals (CIs) were calculated for BMD, and odds ratios (ORs) for osteopenia, osteoporosis, and fractures. RESULTS: Overall, 57 studies were eligible, including 21 607 participants (ED = 6485, HCs = 15 122). Compared to HC, AN subjects had significantly lower BMD values at lumbar spine (SMD = -1.51, 95% CI = -1.75, -1.27, studies = 42), total hip (SMD = -1.56, 95%CI = -1.84, -1.28, studies = 23), intertrochanteric region (SMD = -1.80, 95%CI = -2.46, -1.14, studies = 7), trochanteric region (SMD = -1.05, 95%CI = -1.44, -0.66, studies = 7), and femoral neck (SMD = -0.98, 95%CI = -1.12, -0.77, studies = 20). Reduced BMD was moderated by ED illness duration and amenorrhea (P < 0.05). AN was associated with an increased likelihood of osteoporosis (OR = 12.59, 95%CI = 3.30-47.9, P < 0.001, studies = 4) and fractures (OR = 1.84, 95% CI = 1.17-2.89, I(2) = 56, studies = 6). No difference in BMD was found between BN and EDNOS vs. HC. CONCLUSION: People with AN have reduced BMD, increased odds of osteoporosis and risk of fractures. Proactive monitoring and interventions are required to ameliorate bone loss in AN.

Sugar cane policosanol failed to lower plasma cholesterol in primitive, diet-resistant hypercholesterolaemia: a double blind, controlled study.

Previous clinical studies have shown that oral administration of sugar cane policosanol (SCP) reduces plasma total cholesterol and low-density lipoprotein cholesterol levels. A double blind, randomized, placebo controlled trial was performed in hypercholesterolaemic, diet-resistant patients. Seventy patients meeting the selection criteria were enrolled. Each subject was treated with policosanol 10 mg/d in addition to a dietetic regimen for 8 weeks. At the start and at the end of the study body weight, body mass index (BMI), total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides (TG) plasma levels were measured. Thirty-three subjects in the policosanol and Thirty-one subjects in the control group completed the study. During the study body mass index, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides plasma levels did not change significantly within and between groups. In conclusion, sugar cane policosanol at a dose of 10mg/d showed no lipid lowering effects in subjects with primitive, diet-resistant hypercholesterolaemia.

Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism. Multicentre prospective study by the 'Nutritional Problems in Gastroenterology' Section of the Italian Society of Gastroenterology (SIGE).

BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.

Vegetarian diets in hepatic encephalopathy: facts or fantasies?

Diet treatment characterized by a reduction in or a selection of food proteins is currently suggested in hepatic encephalopathy. This article is a review of the present knowledge about the characteristics and the rationale of vegetarian diets in cirrhotic patients with overt or latent encephalopathy. In addition, evidence relating diet and encephalopathy and the nutritional features and needs of cirrhotic patients is reported. Finally, the rationale of a diet based on vegetable and milk-derived proteins that may overcome the limits and the possible adverse effects of a strict vegetarian diet is presented.

Insulin-like growth factor 1 (IGF-1), a nutritional marker in patients with eating disorders.

BACKGROUND AND AIMS: Though low levels of insulin-like growth factor-1 (IGF-1) have been repeatedly reported in patients with eating disorders, the nutritional significance of IGF-1 has not been evaluated. The study aimed to assess the utility of IGF-1 for screening malnutrition and for monitoring nutrition intervention in patients with eating disorders. METHODS: IGF-1 and nutritional status were evaluated in 82 patients, 59 with anorexia nervosa (AN), and 23 with bulimia nervosa (BN). Nutritional assessment included the evaluation of body mass index (BMI), body fat (FAT) and muscle mass (MM), assessed by skinfold anthropometry, serum albumin, transthyretin and retinol-binding protein, energy and protein intake. IGF-1 and nutritional parameters were reevaluated in the early phase of refeeding (2-4 weeks) in 20 AN patients who entered a refeeding program. RESULTS: Mean IGF-1 z-score was -1.74+/-0.74 in AN, and -0.74+/-0.91 in BN. Serum proteins were reduced in only a minority of patients. IGF-1 correlated with BMI (r=0.64), FAT (r=0.57), MAMC (mid-arm muscle circumference) (r=0.58) and MM (r=0.66) (P<0.001), while it did not correlate with serum proteins. In the early phase of nutritional repletion serum proteins and anthropometric parameters did not vary significantly, while a prompt and marked increase (73.9%) of IGF-1 was observed. CONCLUSIONS: IGF-1 represents a biochemical marker of malnutrition and a sensitive index of nutritional repletion in patients with eating disorders.

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.

Tryptophan levels, excessive exercise, and nutritional status in anorexia nervosa.

OBJECTIVE: It has been hypothesized that reduced dietary availability of tryptophan may be the cause of impaired serotonin activity in underweight anorexics. The study reported here evaluated the relationship between tryptophan availability in the blood and nutritional status in anorexia nervosa. METHODS: The total amount of tryptophan and the ratio between tryptophan and other large neutral amino acids (TRP/LNAA) were assessed in a sample of 16 starving anorexic patients. Body weight and composition and energy intake were evaluated in all patients. All subjects also completed self-reported questionnaires such as the Hopkins Symptom Checklist and Eating Disorders Inventory (EDI). RESULTS: The TRP/LNAA ratio seems to be higher in patients with a more severe catabolic status. It is, in fact, significantly inversely correlated with body mass index, body fat, muscle mass, daily energy intake, and daily tryptophan intake. The TRP/LNAA ratio also correlates with growth hormone and the EDI drive for thinness. Patients who exercise excessively had significantly higher TRP/LNAA ratios. CONCLUSIONS: In starving anorexic patients, the TRP/LNAA ratio does not seem to be determined by the content of tryptophan in the diet, but it correlates with measures of catabolism. The relationship of the TRP/LNAA ratio to excessive exercise and starvation indicates the importance of further investigations exploring the role of tryptophan availability in maintaining anorexia nervosa.

Clinical features and survivial of cirrhotic patients with subclinical cognitive alterations detected by the number connection test and computerized psychometric tests.

The prevalence and the clinical implications of subclinical cognitive alterations in cirrhotic patients have not been well defined as yet. Therefore, we performed a study to assess the clinical features and the survival of cirrhotic patients with cognitive alterations detected by the number connection test (NCT) and a set of computerized psychometric tests (Scan, Choice1, and Choice2) measuring the reaction times and the percentage of errors in performing specific tasks. Ninety-four cirrhotic patients (aged 58 +/- 9 years) without overt hepatic encephalopathy and 80 controls (aged 53 +/- 15 years) were consecutively enrolled. The median follow-up in cirrhotic patients was 426 days (lower quartile = 213 days; upper quartile = 718 days). Results of the NCT, Scan test, and Choice2 test were significantly worse in cirrhotic patients, whereas Choice1 did not differ significantly from the controls. In cirrhotic patients, the prevalence of altered psychometric tests was 21% (CI95% = 14%-31%) by NCT, 23% (CI95% =15%-33%) by Scan test, and 20% (CI95% =16%-30%) by Choice2 test. The alterations of NCT, Scan, and Choice2 were found to be related to the severity of liver disease, independently of its etiology. Increased risk of death was found to be associated with altered Scan test (hazard ratio = 2.4; CI95% =1. 1-5.3), or altered Choice2 test (hazard ratio = 2.8; CI95% = 1.2-6. 3). Multivariate regression showed that Scan and Choice2 tests had prognostic value on survival, in addition to Child-Pugh classes in the first year of follow-up.

Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide.

The aim of the study was to verify the effects of the administration of an inhibitor of the release of endogenous vasodilators together with a vasoconstrictor agent in patients with hepatorenal syndrome (HRS). This new medical perspective was compared with a traditional medical approach for HRS, such as the infusion of nonpressor doses of dopamine to produce renal vasodilation. Thirteen patients with type 1 HRS were enrolled in the study. Five of them were treated with the oral administration of midodrine and the parenteral administration of octreotide. In addition, the patients received 50 to 100 mL of 20% human albumin solution daily for 20 days. Midodrine and octreotide were dosed to obtain a stable increase of at least 15 mm Hg of mean arterial pressure. Eight patients were treated with the intravenous administration of nonpressor doses of dopamine (2-4 micrograms/kg/min) and the same daily amount of albumin. After 20 days of treatment with midodrine and octreotide, an impressive improvement in renal plasma flow (RPF), glomerular filtration rate, and urinary sodium excretion was observed in patients. This was accompanied by a significant reduction in plasma renin activity, plasma vasopressin, and plasma glucagon. No side effects were observed. Three patients were discharged from the hospital. One of them successfully underwent liver transplantation. One of the two remaining patients is still alive after 472 days with a preserved renal function, and the other died from terminal liver failure after 76 days. One of the two patients who were not discharged from the hospital successfully underwent liver transplantation, and the other died from pneumonia after 29 days. Seven out of eight patients who were treated with dopamine experienced a progressive deterioration in renal function and died during the first 12 days. Only one patient recovered renal function and underwent liver transplantation. In conclusion, the long-term administration of midodrine and octreotide seems to be an effective and safe treatment of type 1 HRS in patients with cirrhosis.

[Zinc deficiency in liver cirrhosis: a curiosity or a problem?]. / La carenza di zinco nella cirrosi epatica: curiosità o problema?

This article reviews the literature on the role of zinc in liver cirrhosis and dietary zinc supplementation for cirrhotic patients with hepatic encephalopathy. Zinc is a trace metal found in many proteins and enzymes having catalytical, cocatalytical and structural functions. Zinc deficiency has been demonstrated in cirrhotic patients, and dietary supplementation of this metal could benefit the urea cycle, glucose and protein metabolism, and central nervous system neurotransmission in these subjects. After some brief considerations on normal zinc metabolism, the role zinc plays in the central nervous system, and its conduct in patients with hepatic encephalopathy, possible links between zinc deficiency and the pathophysiology of central nervous system dysfunction in cirrhotic patients are discussed. The article concludes with a critical review of favorable and unfavorable evidence for zinc supplementation in patients with hepatic encephalopathy.

Study on the Sternberg paradigm in cirrhotic patients without overt hepatic encephalopathy.

Memory dysfunction is reported in cirrhotics. The aim of this paper was to increase insight into memory function of cirrhotic patients without overt hepatic encephalopathy. Eighty-six consecutive cirrhotics without overt hepatic encephalopathy (aged 54+/-10 yr., mean+/-s.d.) and 28 controls (52+/-10 yr.) with comparable education level were enrolled. Seventeen patients were class A, 55 class B, 14 class C according to Child-Pugh classification; 29 had alcoholic cirrhosis. The presence of subclinical signs of central nervous system dysfunction were assessed by Number Connection Test (NCT) and quantified EEG analysis. Memory scanning was evaluated by reaction times (RTs) in the Sternberg paradigm. MANOVA analysis showed that RTs were higher (F1,99=11, p<0.01) and time outs (TOs) more frequent (F1,110=10, p<0.01) in cirrhotics than in controls, whereas button press errors (BPEs) did not differ significantly (F1,110=2, p=n.s.). In cirrhotics, an interaction Child-Pugh class x memory set size was found (F2,146=4, p<0.05), showing exceedingly delayed RTs with greater memory set size in class C patients. Patients with altered NCT had significantly prolonged RTs (F1,71=4, p<0.05) and more TOs (F1,82=11, p<0.01) than patients with normal NCT. Cirrhotics with altered EEG had significantly prolonged RTs (F2,70=6, p<0.01). RTs were found to be correlated to alpha relative power (r=-0.4, p<0.01) and theta relative power (r=0.4, p<0.01). In conclusion, cirrhotics without over encephalopathy, but with NCT or EEG alterations, perform a computerized digit recognition task more slowly and with higher TOs than cirrhotic patients with normal NCT or EEG. In severe liver insufficiency (class C cirrhotics) also an impairment of memory scanning was detected. Sternberg test performance correlates with NCT and quantitative EEG parameters.

Visual attention in cirrhotic patients: a study on covert visual attention orienting.

Attentional dysfunction, which influences overall cognitive productivity, is not well characterized in cirrhotic patients. The aim of this study was to clarify the features of covert visual attention orienting in cirrhotics without overt hepatic encephalopathy. One hundred consecutive cirrhotic patients and 40 controls were enrolled. Visual covert attention orienting was assessed by the Posner test, which evaluates the effect of a cue on visual reaction times. Patients were characterized by the number connection test (NCT) and electroencephalographic (EEG) spectral analysis. The severity of liver disease was graded using standard laboratory parameters and the Child-Pugh's classification. Fifty-five psychometric and EEG evaluations were performed in the follow-up of 17 patients to assess the relationship between the variations of psychometric and neurophysiological findings. NCT and quantified-EEG parameters (altered in 19% and 40% of cirrhotic patients, respectively) were linked to each other and to the severity of liver disease. The Posner test showed a delay of visual reaction times in class B-C cirrhotic patients. Reaction times were correlated with ammonia and EEG parameters. The effect of the cue was higher in cirrhotic patients than in controls, particularly in the invalid position. This study suggests that cirrhotic patients have a reduced activity rate and reduced capacity to disengage attention previously focused on a cue. Such alterations are linked to NCT and EEG findings.

Nutritional and prognostic significance of serum hypothyroxinemia in hospitalized patients with liver cirrhosis.

BACKGROUND/AIMS: A variety of severe illnesses can induce changes in thyroid hormone metabolism, leading to findings referred to as "sick euthyroid syndrome". In several groups of patients the reduction of serum thyroxine concentration (T4), characteristic of the low-T4 variant of sick euthyroid syndrome, has been found to be a good predictor of survival. Although the pathophysiology of hormonal alterations has not yet been defined, nutritional deficits have been suggested to play a role. The study aimed to define the prognostic and nutritional significance of serum thyroxine in liver cirrhosis. METHODS: Thyroid hormones and nutritional status were evaluated in a group of 75 consecutive hospitalized patients with cirrhosis, followed-up clinically for 12 months. RESULTS: A low-T4 variant of sick euthyroid syndrome was found in 23 of the 75 enrolled patients with cirrhosis (30.6%). Serum T4, but not serum T3, correlated with mid-arm muscle circumference (p < 0.01), an indicator of muscle protein compartment. While both serum T3 and T4 correlated directly with serum proteins and inversely with Child-Pugh score, only T4 was predictive of outcome. Patients with the low-T4 variant of sick euthyroid syndrome showed significantly lower short- and long-term survival rates compared to those with normal serum T4 concentrations (p < 0.008 at 3 months, p < 0.001 at 6 months and 1 year). A multivariate analysis using the proportional hazards Cox's regression procedure showed that serum T4, but not serum T3 or nutritional parameters, improves the prognostic capacity of Child-Pugh score (p < 0.01). CONCLUSIONS: These data indicate that the low T4-variant of sick euthyroid syndrome distinguishes a subgroup of patients with cirrhosis at risk for decreased survival. The inclusion of T4 in the Child-Pugh score, by improving its prognostic power, may optimize the selection of patients with advanced cirrhosis to receive specific therapy such as transplantation.

Nutritional and prognostic significance of insulin-like growth factor 1 in patients with liver cirrhosis.

Most of the traditional parameters for nutrition assessment have important limitations in patients with chronic liver disease. Insulin-like growth factor 1 (IGF-1) has been found to be regulated by nutrition and proposed as a nutritional marker. Its nutritional significance in patients with liver cirrhosis, however, has not been investigated. Serum IGF-1 as well as traditional anthropometric, visceral, and immunologic parameters were evaluated in 64 hospitalized cirrhotics, followed up clinically for 2 y. IGF-1Z-score averaged -2.16 +/- 1.08 and inversely correlated with Child-Pugh score (P < 0.01), the most reliable composite score reflecting the severity of liver disease. IGF-1Z-score was not different in patients with or without signs of energy malnutrition, as defined by values of midarm muscle circumference (MAMC) and/or triceps skinfold (TSF) < 5th percentile. Moreover, IGF-1Z-score did not correlate with MAMC or TSF. Despite its correlation with all visceral proteins, the reduction of IGF-1 was much greater and more frequent than that of visceral proteins. Patients with IGF-1Z-score < median values (-2.5) showed lower long-term survival rates compared with patients with IGF-1Z-score > -2.5 (P < 0.01). These data indicate that serum IGF-1 is not related to energy malnutrition in cirrhotic patients, while it appears to be a good predictor of survival and an early marker of liver dysfunction. Multiple factors, most of which are related to the severity of the liver disease, may contribute to the reduction of IGF-1. This multifactorial pathogenesis probably accounts for its prognostic significance.

[Nutritional therapy in chronic hepatopathy]. / La terapia nutrizionale nelle epatopatie croniche.

Severe protein-energy malnutrition, a common complication in patients with advanced liver disease, negatively influences clinical evolution and survival, while appropriate nutritional intervention has been found to improve liver function and prognosis. Although the importance of nutritional factors has been greatly emphasized in the last decade, nutritional therapy remains a controversial issue in clinical hepatology. Because a considerable heterogeneity exists among patients regarding both nutritional needs and the pathophysiology of malnutrition, adequate assessment of nutritional status is mandatory to identify the type and the degree of malnutrition for the individualization of therapy. In this paper we first summarize the pathophysiology of malnutrition and the principles for the assessment of nutritional status in patients with chronic liver disease. We then offer rational, cost-conscious recommendations for therapy, with special emphasis on the role of nutritional support in the prevention and treatment of several complications.

Malnutrition in alcoholic and virus-related cirrhosis.

The study aimed to define the prevalence, characteristics, and clinical importance of nutritional disorders in patients with liver cirrhosis. Nutritional status was evaluated in 120 hospitalized patients--77 with alcoholic and 43 with virus-related cirrhosis--by anthropometric, visceral, and immunologic measurements. Energy malnutrition, defined as triceps skinfold thickness (TSF) and/or midarm muscle circumference (MAMC) below the 5th percentile of standard values, was found in 34% of the study population. Patients below the 5th percentile for MAMC and/or TSF showed significantly lower survival rates at e, 6, 12, and 24 mo compared with patients above the 5th percentile. Protein malnutrition (low albumin, transthyretin, transferrin, and retinol-binding-protein concentrations) and immunoincompetence (abnormal response to skin tests) were much more frequent (81% and 59%) than energy malnutrition (34%). Serum proteins correlated with the degree of liver function impairment, but not with immunologic tests. The prevalence, characteristics, and severity of protein-energy malnutrition were comparable in alcoholic and viral cirrhosis. Malnutrition was correlated with the clinical severity of the liver disease. The study shows that protein-energy malnutrition is a common complication of liver cirrhosis. Nutritional disorders appear to be related to the degree of liver injury rather than to its etiology. Compared with other methods, which have important limitations in liver disease, anthropometry is currently the most reliable method for nutritional assessment in clinical practice and may be valuable for predicting survival in cirrhotic patients.

Cirrhosis and muscle cramps: evidence of a causal relationship.

The aim of the study was to define the features, prevalence, and pathophysiology of therapy for muscle cramps in cirrhotic patients. The first protocol study included 294 cirrhotic patients and 194 age- and sex-matched controls. Controls were defined as inpatients or outpatients without any clinical and laboratory evidence of liver disease. Features and prevalence of muscle cramps were defined on the basis of a standard questionnaire. As far as the pathophysiological associations of muscle cramps were concerned, the following parameters were evaluated: mean arterial pressure (MAP), nutritional status, liver function tests, plasma volume (PV), plasma renin activity (PRA), and electrolyte, mineral, and acid-base status. The prevalence of cramps was higher in cirrhotic patients than in controls, and it was related to the duration of recognized cirrhosis and to the severity of liver function impairment. At a multiple regression analysis, the presence of ascites, low values of MAP, and high values of PRA were the independent predictive factors for the occurrence of cramps in cirrhosis. In the second protocol study, the effects of a sustained expansion of the effective circulating volume induced by intravenous infusion of human albumin were compared with those of a placebo in 12 cirrhotic patients with more than three cramp crises a week. Compared with the placebo, albumin reduced the cramp frequency (P < .01). In conclusion, an increased prevalence of true muscle cramps occurs in patients with cirrhosis. Our data indicate that the pathophysiological link between cirrhosis and cramps may be represented by the reduction of the effective circulating volume. They also indicate that weekly infusion of human albumin may be an effective treatment for cramps in cirrhosis.

Optimizing the time-frame for the definition of bleeding-related death after acute variceal bleeding in cirrhosis.

OBJECTIVE: To identify the best time-frame for defining bleeding-related death after variceal bleeding in patients with cirrhosis. DESIGN: Prospective long-term evaluation of a cohort of 155 patients admitted with variceal bleeding. SETTING: Eight medical departments in seven hospitals in north-eastern Italy. METHODS: Non-linear regression analysis of a hazard curve for death, and Cox's multiple regression analyses using different zero-time points. RESULTS: Cumulative hazard plots gave two slopes, the first corresponding to the risk of death from acute bleeding, the second a baseline risk of death. The first 30 days were outside the confidence limits of the regression curve for the baseline risk of death. Using Cox's regression analysis, the significant predictors of overall mortality risk were balanced between factors related to severity of bleeding and those related to severity of liver disease. If only deaths occurring after 30 days were considered, only predictors related to the severity of liver disease were found to be of importance. CONCLUSION: Thirty days after bleeding is considered to be a reasonable time-frame for the definition of bleeding-related death in patients with cirrhosis and variceal bleeding.