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Biomedical subjects

A Gatta

Publications and source records attributed to A Gatta.

At least 55 records · Page 3Linked to original sources
PubMed1999

Comparison of thrice weekly vs daily human leucocyte interferon-alpha therapy for chronic hepatitis C. TVVH Study Group.

Standard treatment for chronic hepatitis C currently consists of 3-6 million units (MU) of interferon-alpha (IFN-alpha) given thrice weekly (t.i.w.) for 12 months, obtaining rates of sustained response (SR) that usually do not exceed 15-25%. Some recent reports have suggested that daily administration of IFN-alpha may be more efficacious. More than 7 years ago, when standard therapy for hepatitis C was usually given for 6 months, we conducted a randomized clinical trial comparing daily vs t.i.w. treatment. In this study, 149 patients with chronic hepatitis C were randomized to received 3 MU of IFN-alpha either t.i.w. for 6 months or daily for 3 months followed by t.i.w. for 3 months. All patients were treated with human leucocyte IFN-alpha and were followed-up for up to 72 months after inclusion. Overall, patients treated daily or t.i.w. had similar rates of virological response after 3 months of induction [24/49 (50%) vs 40/100 (40%)], at the end of therapy [15/49 (31%) vs 36/100 (36%)] and at the end of follow-up [6/49 (12%) vs 9/100 (9%)]. However, when patients infected with HCV types other than HCV-1 were studied, there was a trend favouring the daily schedule that was associated with a higher [5/20 (25%) vs 5/48 (10%)] rate of long-term SR. All patients with a virological response - hepatitis C virus (HCV) RNA negative in serum as determined using the polymerase chain reaction - at 6 months after therapy remained in biochemical and virological remission at long-term follow-up, while seven of eight subjects who had normal alanine aminotransferase (ALT) levels but were serum positive for HCV RNA at 6 months, relapsed later, indicating that serum HCV RNA is better than ALT at predicting long-term cure after IFN-alpha therapy in chronic hepatitis C.

Adult↗
PubMed1999

Effect of chronic treatment with nadolol plus isosorbide mononitrate on liver blood flow and liver metabolic activity in cirrhosis.

OBJECTIVE: To assess the long-term effect of the addition of long-acting nitrates to beta-blockers on liver blood flow and liver metabolic activity in patients with cirrhosis and portal hypertension. METHODS: Eleven patients with cirrhosis and portal hypertension were investigated by using hepatic vein catheterization and indocyanine green (ICG) constant infusion on baseline conditions, after 1 month of treatment with nadolol, after 3 months of treatment with nadolol plus isosorbide mononitrate, and (in seven cases) after 1 year of combined treatment. RESULTS: The hepatic venous pressure gradient decreased significantly after nadolol, and more so after addition of isosorbide mononitrate. Hepatic blood flow, and ICG intrinsic hepatic clearance did not change significantly, although few cases showed an increase or decrease in either parameter. A significant correlation was found between changes in ICG intrinsic hepatic clearance and in hepatic venous pressure gradient (r = 0.62, P = 0.04). CONCLUSIONS: Liver blood flow and liver metabolic activity are not consistently affected by addition of isosorbide mononitrate to nadolol. Substantial decreases in portal pressure may be associated with a decrease in ICG intrinsic hepatic clearance.

Adrenergic beta-Antagonists↗
PubMed1999

Portal hypertension: state of the art.

In the last decade, the knowledge of the pathogenesis of portal hypertension has increased dramatically. Indeed, apart from the well-known pathogenetic importance of structural factors, the role of vasoactive factors, which enhance the increase in intrahepatic resistance, has been highlighted. The two pathogenetic factors of portal hypertension are: the increase in portal outflow resistance and an increase in splanchnic blood flow, which worsens and maintains the increased pressure in the portal vein. The increase in portal inflow is part of the hyperdynamic circulatory syndrome, which is a haemodynamic characteristic of cirrhotic patients. In portal hypertensive patients, almost all the known vasoactive systems/substances are activated or increased and the most recent studies have stressed the importance of the endothelial factors, such as endothelins, nitric oxide and prostaglandins. Knowledge of the haemodynamic mechanisms allows a pathogenetic approach to the treatment of portal hypertension, particularly as far as medical therapy is concerned. The main categories of drugs used are: the vasoconstrictors (i.e., vasopressin, glypressin, somatostatin, non-selective beta-blockers), which act by decreasing portal inflow, and the vasodilators (i.e., nitroderivatives), which act mainly by decreasing intrahepatic portal resistance. Moreover, technological developments have introduced new tools for diagnosis, such as echo-colour-Doppler, and therapy, like variceal banding and transjugular intrahepatic porto-systemic shunt.

Hemodynamics↗
PubMed1998

Splenic impedance indices: a useful method to monitor patients after liver transplantation?

Splenic Doppler impedance indices are influenced, in portal hypertensive patients, by the resistance of the portal system. The aim of the study was to verify the usefulness of these indices in evaluating the presence of a pathological increase in portal resistance in patients with complications after liver transplantation. Splenic impedance indices have been evaluated in 46 patients before orthotopic liver transplantation (OLT), and 2 days, 1, 4, 8, and 12 to 18 months after transplantation. The results showed that spleen size slowly decreased after liver transplantation. From a baseline longitudinal diameter value of 18.0+/-3.6 cm (M+/-SD), the decrease was by 0%+/-3%, 8%+/-8%, 13%+/-9%, 15%+/-11%, and 14%+/-11% at 2 days and 1, 4, 8, and 12 to 18 months after liver transplantation. Splenic impedance indices-resistance index = (peak systolic - end diastolic) / peak systolic velocity; pulsatility index = (peak systolic - end diastolic) / mean velocity-which were increased before liver transplantation, showed a rapid decrease to normal values: resistance index: from 0.62+/-0.08 to 0.55+/-0.08 after 2 days, and to 0.49+/-0.09, 0.51+/-0.10, 0.54+/-0.10, 0.55+/-0.11 after 1, 4, 8, 12-18 months; pulsatility index: from 0.96+/-0.21 to 0.82+/-0.17 after 2 days, and to 0.69+/-0.19,0.72+/-0.21, 0.81+/-0.26, 0.84+/-0.26 after 1, 4, 8, and 12 to 18 months. Patients who had a good outcome, without any major complications, showed a clear and steady decrease in splenic impedance indices. On the contrary, patients who had complications affecting portal resistance (e.g., acute rejection, relapse of chronic hepatitis C virus-related hepatitis or cirrhosis, stenosis of portal anasthomosis, portal thrombosis), showed a lack of decrease, or, after an initial decrease, a subsequent re-increase in splenic impedance indices to pathological values. Splenic impedance indices measured in patients with complications were higher than those of patients without complications (P < .0004). Specificity and sensitivity of splenic impedance indices in the evaluation of the presence of complications increasing portal resistance were good. In conclusion, after OLT, splenic impedance indices could be useful aspecific parameters for identifying patients with complications that are able to affect or increase portal resistance.

Adult↗
PubMed1998

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.

Adult↗
PubMed1998

Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites.

The effects of the acute administration of arterial vasoconstrictors on renal plasma flow (RPF) and urinary sodium excretion (UNaV) in cirrhotic patients with ascites with or without hepatorenal syndrome (HRS) are still controversial. As a consequence, vasoconstrictors are not actually used in the treatment of renal sodium retention or HRS in these patients, regardless of the several lines of evidence suggesting that these renal functional abnormalities are related to a marked arterial vasodilation. The lack of an orally available effective arterial vasoconstrictor probably represents a further reason for this omission. Consequently, the present study was made to evaluate the acute effects of the oral administration of midodrine, an orally available -mimetic drug, on systemic and renal hemodynamics and on UNaV in cirrhotic patients with ascites. Mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), systemic vascular resistance (SVR), left forearm blood flow (LFBF), left leg blood flow (LLBF), RPF, glomerular filtration rate (GFR), UNaV, plasma renin activity (PRA), plasma concentration of antidiuretic hormone (ADH), and the serum levels of nitrite and nitrate (NOx) were evaluated in 25 cirrhotic patients with ascites (17 without HRS and 8 with type 2 HRS) before and during the 6 hours following the oral administration of 15 mg of midodrine. During the first 3 hours after the drug administration, a significant increase in MAP (89.6 +/- 1.7 vs. 81.80 +/- 1.3 mm Hg; P < .0001) and SVR (1, 313.9 +/- 44.4 vs. 1,121.2 +/- 60.1 dyn . sec . cm-5; P < .0001) accompanied by a decrease in HR (69 +/- 2 vs. 77 +/- 3 bpm; P < .005) and CI (2,932.7 +/- 131.4 vs. 3,152.5 +/- 131.4 mL . min-1 . m2 BSA; P < .0025) was observed in patients without HRS. No change was observed in LFBF and LLBF. The improvement in systemic hemodynamics, which was also maintained during the the 3- to 6-hour period after midodrine administration, was accompanied by a significant increase in RPF (541.5 +/- 43.1 vs. 385.7 +/- 39.9 mL . min-1; P < .005), GFR (93.1 +/- 6.5 vs. 77.0 +/- 6.7 mL . min-1; P < .025), and UNaV (92.7 +/- 16.4 vs. 72.2 +/- 10.7 microEq . min-1; P < .025). In addition, a decrease in PRA (5.33 +/- 1.47 vs. 7.74 +/- 2.17 ng . mL-1 . h; P < .05), ADH (1.4 +/- 0.2 vs. 1.7 +/- 0.2 pg . mL-1; P < .05), and NOx (33.4 +/- 5.0 vs. 49.3 +/- 7.3 micromol-1; P < .05) was found. In patients with HRS, the effects of the drug on the systemic hemodynamics was smaller and shorter. Accordingly, regardless of a significant decrease in PRA (15.87 +/- 3.70 vs. 20.70 +/- 4.82 ng . mL-1 . h; P < .0025) in patients with HRS, no significant improvement was observed in RPF, GFR, or UNaV. In conclusion, the acute oral administration of midodrine is associated with a significant improvement in systemic hemodynamics in nonazotemic cirrhotic patients with ascites. As a result, renal perfusion and UNaV also improve in these patients. By contrast, midodrine only slightly improves systemic hemodynamics in patients with type 2 HRS, with no effect on renal hemodynamics and renal function.

Administration, Oral↗
PubMed1998

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.

Adult↗
PubMed1998

Doppler sonography and hepatic vein catheterization in portal hypertension: assessment of agreement in evaluating severity and response to treatment.

BACKGROUND/AIM: The study was designed to assess to what extent portal hemodynamic parameters obtained by duplex Doppler ultrasonography may be substituted for the measurement of hepatic venous pressure gradient in evaluating the severity of portal hypertension and the response to medical treatment with beta-blockers or beta-blockers plus nitrates in patients with cirrhosis and portal hypertension. METHODS: In 39 of these patients hepatic venous pressure gradient was determined by hepatic vein catheterization, and portal blood flow velocity and the congestion index of the portal vein were measured by duplex Doppler ultrasonography. In 19 of these patients the changes in hepatic venous pressure gradient and in Doppler parameters were also assessed after chronic administration of nadolol. In 11 of the 19 patients the changes after chronic administration of nadolol plus isosorbide-5-mononitrate were also measured. RESULTS: In the whole series, no significant correlation was found between hepatic venous pressure gradient and duplex Doppler parameters, but, when the 12 patients with a patent para-umbilical vein were excluded, significant linear correlations were found between hepatic venous pressure gradient and portal blood velocity (r=-0.39; p=0.05) or congestion index (r=0.37; p=0.05). Considering together the changes induced by nadolol and nadolol plus isosorbide-5-mononitrate, no correlation was apparent between changes in duplex Doppler parameters and in hepatic venous pressure gradient. Agreement between hepatic venous pressure gradient and duplex Doppler parameters in defining good and poor responders was insufficient. CONCLUSIONS: These data suggest that portal blood velocity and the congestion index of the portal vein are related to portal hypertension in patients without a patent para-umbilical vein, but are of limited value in discriminating good responders from poor responders to medical treatment for portal hypertension.

Adrenergic beta-Antagonists↗
PubMed1998

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.

Adult↗
PubMed1998

Q-T interval prolongation in liver cirrhosis. Reversibility after orthotopic liver transplantation.

The aim of this work was to study the prevalence of Q-T prolongation in patients with liver cirrhosis and the modifications of the Q-T interval after liver transplantation. Q-T interval corrected for heart rate (QTc) and dispersion of Q-T interval were evaluated in 75 cirrhotic patients and in 24 controls by means of a 12-lead electrocardiogram. In addition, 15 patients were evaluated before and after liver transplantation. Forty-five patients (60%) had a prolonged Q-Tc. Compared with controls, both patients with alcoholic and non alcoholic cirrhosis had increased Q-Tc (414 +/- 28 msec1/2, 463 +/- 31 and 444 +/- 32 respectively; p < 0.001 and < 0.001); Q-Tc was significantly higher in alcoholic than in non-alcoholic cirrhosis (p < 0.02). Q-T dispersion was normal in cirrhotics. No correlation was found between Q-Tc interval and severity of the cirrhosis, haemodynamic variables (stroke volume, cardiac output) and s-calcium and potassium concentrations. After transplantation, Q-Tc decreased significantly (415 +/- 26 msec1/2 vs 449 +/- 31; p < 0.0001) returning to the values of the normal subjects, but no modification of the Q-T dispersion was observed. These data show that 1) prolongation of Q-T interval is frequent in cirrhosis, being higher in alcoholic than in non-alcoholic cirrhosis, 2) is not related to the severity of the disease, and 3) is reversible after transplantation.

Aged↗
PubMed1998

Updating prognosis of cirrhosis by Cox's regression model using Child-Pugh score and aminopyrine breath test as time-dependent covariates.

BACKGROUND AND AIMS: The determination of aminopyrine breath test on entry into the study was recently shown to improve the accuracy of prediction of death based on the Child-Pugh classification, but the possible usefulness of serial determinations of both parameters has not been assessed. In the present study, we aimed at evaluating whether serial determinations of aminopyrine breath test and Child-Pugh score improve prognostic accuracy in patients with cirrhosis, compared with determinations obtained only on admission. PATIENTS: In 74 patients with liver cirrhosis aminopyrine breath test and Child-Pugh score were obtained upon entry into the study. Patients were followed with sequential aminopyrine breath tests and assessments of the Child-Pugh score every 4-6 months. A total number of 232 determinations were obtained. During follow-up 45 patients died, on average after 12 months of follow-up. RESULTS: Child-Pugh score improved in the beginning of follow-up, and then remained fairly constant; aminopyrine breath test showed no improvement in the beginning of follow-up, but rather a slowly progressive decline. In patients who died, both the Child-Pugh score and the metabolism of aminopyrine were significantly more impaired in the last year preceding death (p < 0.05). Applying Cox's regression model with time-dependent covariates, Child-Pugh score and aminopyrine breath test were independent significant predictors of survival. The model with time-dependent covariates explained the observed survival much better than the model with time-fixed covariates (chi-sq. explained by regression = 31.45 vs 11.97; d.f. = 2; p = 0.0000001 vs 0.003). CONCLUSIONS: These data suggest that serial determinations of Child-Pugh score and aminopyrine breath test can be used to efficiently update prognosis of cirrhosis.

Aminopyrine↗
PubMed1997

Eicosanoid excretion in hepatic cirrhosis. Predominance of 20-HETE.

The cytochrome P450 system transforms AA to hydroxyeicosatetraenoic acid (HETE) metabolites that are vasoactive and affect transport in several nephron segments. A principal product of this system, 20-HETE, participates in key mechanisms that regulate the renal circulation and extracellular fluid volume. We hypothesized that excess production of 20-HETE, which constricts the renal vasculature, contributes to the renal functional disturbances in patients with hepatic cirrhosis, particularly the depression of renal hemodynamics. The development of a precise and sensitive gas chromatographic/mass spectrometric method makes it possible to measure 20-HETE and the subterminal HETEs (16-,17-,18-, and 19-HETEs) in biological fluids. As 20-HETE was excreted as the glucuronide conjugate, measurement of 20-HETE required treatment of urine with glucuronidase. We measured HETEs in the urine of patients with cirrhosis, and compared these values to those of normal subjects. Urinary excretion rate of 20-HETE was highest in patients with ascites; 12.5+/-3.2 ng/min vs. 5.0+/-1.5 and 1.6+/-0.2 ng/min in cirrhotic patients without ascites and in normal subjects, respectively. Excretion of 16-, 17-, and 18-HETEs was not increased. In patients with cirrhosis, the excretory rate of 20-HETE was several-fold higher than those of prostaglandins and thromboxane, whereas in normal subjects 20-HETE and prostaglandins were excreted at similar rates. Of the eicosanoids, only increased excretion of 20-HETE in subjects with cirrhosis was correlated (r = -0.61; P < 0.01) with reduction of renal plasma flow (RPF).

Adult↗
PubMed1997

Effects of chronic therapy with nadolol on portal hemodynamics and on splanchnic impedance indices using Doppler sonography: comparison between acute and chronic effects.

BACKGROUND/AIMS: Beta-blockers are currently used for chronic therapy of portal hypertension. Duplex Doppler ultrasonography has been proposed for non-invasive evaluation of splanchnic pharmacodynamics, but the chronic effects of beta-blockers on portal hemodynamics and on splanchnic arterial impedance indices have not been analyzed with this method. This was the aim of the study. METHODS: The effects of acute (80 mg p.o.) and chronic (2 months at a dosage sufficient to reduce heart rate by at least 25% in respect of basal values) nadolol administration on portal blood flow velocity and volume, and on splanchnic and renal arterial impedance indices [pulsatility index = (peak systolic velocity-minimum velocity)/mean velocity] were evaluated in patients with cirrhosis. Twenty-eight patients with cirrhosis and portal hypertension were investigated. Nineteen patients received nadolol, and nine received placebo. RESULTS: Placebo caused no significant hemodynamic change. Portal blood flow mean velocity decreased after chronic therapy (11.7 +/- 2.9 cm/s to 9.1 +/- 2.3, p < 0.001). In the 16 patients with acute and chronic evaluation, portal blood flow mean velocity decreased after acute therapy (11.8 +/- 3.0 cm/s to 10.4 +/- 3.0, p < 0.01), and even more so after chronic therapy (to 9.2 +/- 2.4, p < 0.01). No parallel was found between acute and chronic effects. Hepatic, mesenteric and splenic pulsatility indices increased after chronic therapy (1.26 +/- 0.33 to 1.39 +/- 0.28, p < 0.02; 2.04 +/- 0.41 to 2.50 +/- 0.61, p < 0.01; 0.92 +/- 0.22 to 1.18 +/- 0.27, p < 0.001 respectively); renal pulsatility index increased (1.12 +/- 0.20 to 1.40 +/- 0.28, p < 0.001). CONCLUSIONS: Chronic therapy with nadolol decreased portal blood flow velocity and volume, and increased splanchnic and renal impedance indices. Chronic effects of nadolol on portal inflow cannot be predicted from its acute effects. Evaluation of the effect of nadolol on portal blood velocity and volume should be performed after chronic therapy. Duplex Doppler ultrasonography allows venous and arterial splanchnic pharmacodynamics to be studied separately.

Adrenergic beta-Antagonists↗
PubMed1997

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.

Adult↗
PubMed1997

The effect of flumazenil on subclinical psychometric or neurophysiological alterations in cirrhotic patients: a double-blind placebo-controlled study.

It is not yet clear if benzodiazepine receptor ligands, implicated in the pathophysiology of hepatic coma, also have a role in subclinical cognitive or neurophysiological alterations in cirrhotic patients. Therefore, we carried out a double-blind, placebo-controlled study to evaluate the effectiveness of flumazenil, a benzodiazepine antagonist, on brainstem auditory evoked responses and on the number connection test in cirrhotic patients with subclinical neurophysiological or cognitive alterations. Thirteen cirrhotic subjects with subclinical neurophysiological or cognitive alterations were studied. A total of 3 mg of flumazenil or saline was infused intravenously. Before and after the infusion, the number connection test was administered and brainstem auditory evoked responses recorded. After 72 h, patients were crossed over. Flumazenil did not influence brainstem auditory evoked responses or the number connection test. A screening test for benzodiazepines was negative in all subjects. We conclude that benzodiazepine receptor ligands have a negligible role, if any, in the pathophysiology of subclinical neurophysiological or cognitive alterations of cirrhotic patients.

Cognition↗
PubMed1997

Hemodynamic evaluation of the addition of isosorbide-5-mononitrate to nadolol in cirrhotic patients with insufficient response to the beta-blocker alone.

The association beta-blockers plus isosorbide-5-mononitrate (I5M) has been proposed for the treatment of portal hypertension in patients with insufficient response to beta-blockers alone, according to hemodynamic criteria. The mechanism of action in these patients is not clearly defined. Fifteen patients with cirrhosis and esophageal varices were evaluated by hepatic venous pressure gradient (HVPG) measurement and duplex-Doppler ultrasonography before and after 1 month of treatment with nadolol. Nine patients who did not exhibit a decrease in HVPG to 12 mm Hg or a percent decrease greater than 20% were classified as poor responders, and were studied again with the same methodology after 3 months of chronic administration of nadolol + I5M 20 mg twice per day. In poor responders, mean HVPG decrease after nadolol was 8.9% +/- 2.8%, and after the combination, it was 25.7% +/- 1.7% (P = .004). All patients except one became good responders to the association. Portal blood flow (PBF) decreased significantly after nadolol (P = .004), and remained unchanged after the addition of nitrates. Resistance to portal blood flow (RPBF) increased after nadolol (P = .02) and returned to baseline values during combined treatment (P = .03). In good responders, an adequate decrease in HVPG was associated with a decrease in PBF (P = .06) but no change in RPBF. A wide spectrum of combined changes in PBF and in RPBF after nadolol was observed in poor responders, ranging from no change in either parameter to a marked decrease in PBF counterbalanced by a marked increase in RPBF. The addition of I5M was followed in most cases by larger effects on resistance than on flow. Doppler parameters were not significantly correlated with the HVPG response to nadolol alone or associated with I5M. It is concluded that good hemodynamic responders to nadolol differ from poor responders in the lack of increase in RPBF after the drug. The addition of nitrates to nadolol is effective in decreasing portal pressure in most poor responders to nadolol alone. A decrease in outflow resistance is the main mechanism involved.

Adrenergic beta-Antagonists↗
PubMed1996

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.

Adult↗