Sleep and circadian rhythms in hospitalized patients with decompensated cirrhosis: effect of light therapy.

Patients with liver cirrhosis often exhibit sleep-wake abnormalities, which are, at least to some extent, circadian in origin. A relatively novel non-pharmacological approach to circadian disruption is appropriately timed bright light therapy. The aims of this pilot study were to investigate sleep-wake characteristics of a well-characterized population of inpatients with cirrhosis, and to evaluate the efficacy of bright light therapy in the hospital setting. Twelve consecutive inpatients with cirrhosis underwent complete sleep-wake assessment, to include qualitative and semi-quantitative (actigraphic) indices of night-time sleep quality, daytime sleepiness, diurnal preference, habitual sleep timing, quality of life, mood and circadian rhythmicity [i.e. urine collections for measurement of the melatonin metabolite 6-sulphatoxymelatonin (aMT6s)]. Patients showed extremely impaired night sleep quality (Pittsburg Sleep Quality Index global score: 16.3 ± 2.1) and daytime sleepiness was common (Epworth Sleepiness Scale: 8.3 ± 3.2). Five patients were randomly assigned to a single room in which lighting was controlled in relation to timing, spectral composition and intensity (lights on at 06:30 and off at 22:30, blue-enriched, more intense light in the morning, red-enriched, less intense light in the afternoon/evening); the others stayed in identical rooms with standard lighting. Sleep diaries revealed poor sleep quality, prolonged sleep latency (67 ± 138 min) and a reduced sleep efficiency (69 ± 21%). These features were confirmed by actigraphy (sleep efficiency: 71 ± 13%; fragmentation index: 55 ± 15%). Quality of life was globally impaired, and mood moderately depressed (Beck Depression Inventory: 19.4 ± 7.9). Seven patients underwent serial urine collections: no circadian aMT6s rhythm was detected in any of them, neither at baseline, nor during the course of hospitalization in either room (n = 4). In conclusion, sleep and circadian rhythms in hospitalized, decompensated patients with cirrhosis are extremely compromised. Treatment with bright light therapy did not show obvious, beneficial effects, most likely in relation to the severity of disturbance at baseline.

Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost.

BACKGROUND: Intravenous administration of a third-generation cephalosporin is optimal antibiotic treatment for spontaneous bacterial peritonitis. AIMS: To compare an intravenous-oral step-down schedule with ciprofloxacin (switch therapy) to intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis, and to evaluate the impact of terlipressin and albumin in the treatment of type 1 hepatorenal syndrome on mortality. METHODS: A total of 116 cirrhotic patients with spontaneous bacterial peritonitis, were randomly given switch therapy with ciprofloxacin (61 patients) or intravenous ceftazidime (55 patients). All patients who developed type 1 hepatorenal syndrome were treated with terlipressin (2-12 mg/day) and albumin (20-40 g/day). RESULTS: Resolution of infection was achieved in 46/55 patients treated with ceftazidime (84%) and in 49/61 patients treated with ciprofloxacin (80%, P = N.S.). An intravenous-oral step-down schedule was possible in 50/61 patients (82%) who received ciprofloxacin; 45/61 patients (74%) were discharged before the end of antibiotic treatment and completed it at home. The mean saving per patient due to the reduction of hospital stay in the ciprofloxacin group was 1150 . Type 1 hepatorenal syndrome was treated successfully in 12/19 patients (63%). As a consequence, the in-hospital mortality rate due to infection was 10%. CONCLUSIONS: Switch therapy with cephalosporin is more cost-effective than intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in cirrhotic patients who are not on prophylaxis with quinolones.

Comparison between nifedipine and carvedilol in the treatment of de novo arterial hypertension after liver transplantation: preliminary results of a controlled clinical trial.

There is no controlled clinical trial on the treatment of de novo arterial hypertension after liver transplantation (LT) a common complication using calcineurin inhibitors (CNI) for immunosuppressive therapy. The aim of this study was to compare the efficacy and safety of nifedipine, a calcium channel blocker, and carvedilol, an alpha1- and beta-blocker. The study included 50 patients who developed arterial hypertension after LT. The data on the first 30 patients who have completed 12-month follow-up are reported herein. Eighteen patients received nifedipine, and 12 patients received carvedilol. Patients were evaluated monthly at the outpatient clinic for 1 year. If patients developed severe adverse effects to nifedipine, they were switched to carvedilol and vice versa (therapy failure). The two groups were similar for clinical features, indications for LT, immunosuppressive therapy, and baseline blood pressures. A failure of treatment was observed in 9 of 18 patients treated with nifedipine (50.0%) and one of 12 patients treated with carvedilol (8%, P < .025). Nifedipine was effective in 4 of 18 patients, carvedilol, in 4 of 12 patients (22.21% vs 33.3%, P = NS). Two of the nine nonresponders to nifedipine responded to carvedilol. The efficacy of monotherapy was observed in 11 of 40 randomized patients (27.5%). Carvedilol monotherapy is as effective as nifedipine but far better tolerated.

[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.

[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.

Comparison of sublingual captopril and nifedipine in immediate treatment of hypertensive emergencies. A randomized, single-blind clinical trial.

Sublingual captopril (25 mg) was compared with sublingual nifedipine (10 mg) to determine their effectiveness and safety in the treatment of hypertensive emergencies. In nine of 10 patients who received sublingual captopril, mean (+/- SD) systolic blood pressure and diastolic blood pressure dropped from 245 +/- 39 to 190 +/- 25 mm Hg (P less than .0025) and from 144 +/- 8 to 115 +/- 8 mm Hg (P less than .001) at 50 minutes, respectively. The hypotensive effect of the drug was maintained for a mean of 4 hours. In six of nine responders to sublingual captopril, blood pressure-lowering effect was associated with a clear improvement of end-organ failure within 60 minutes. There were no side effects, including a dangerous fall in blood pressure or reflex tachycardia. Sublingual nifedipine lowered diastolic blood pressure and systolic blood pressure in eight of 10 patients. The hypotensive effect of nifedipine was more rapid than that of captopril (10 vs 20 minutes for diastolic blood pressure and 20 vs 30 minutes for systolic blood pressure, respectively), but no difference was observed in the time or in the magnitude of peak hypotensive effect between the two treatments, nor was a difference observed in the duration of hypotensive effect. In six of eight responders to nifedipine therapy, a clear improvement of symptoms and signs of end-organ failure was observed within 60 minutes. In three patients, minor side effects were observed. We conclude that sublingual captopril effectively and safely lowers arterial blood pressure in patients with hypertensive emergencies.