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Biomedical subjects

P Caraceni

Publications and source records attributed to P Caraceni.

At least 19 recordsLinked to original sources
PubMed2006

Malignant progression of a small HCC nodule: hypovascular 'early HCC' converted to hypervascular 'small HCC' within six months.

We report a case of hepatocellular carcinoma superimposed on chronic hepatitis C virus (HCV) hepatitis in which final diagnosis of hepatocellular carcinoma was delayed because there was no consensus on hypervascularity with two diagnostic methods at the time of presentation. A 3 cm lesion was initially observed as hypovascular at multidetector-row computed tomography. Conversely, two months later the lesion appeared hypervascular at contrast-ultrasonography and gadolinium-enhanced dynamic magnetic resonance, and hyperintense after superparamagnetic iron oxide-enhanced T2W studies. Only in the late follow-up it was definitively confirmed as hypervascular in the arterial phase of multidetector-row computed tomography. This case clearly highlights some pitfalls in the European Association for the study of the liver guidelines for hepatocellular carcinoma management, which were readdressed in the last American Association for the Study of Liver Diseases (AASLD) and in the forthcoming international proposals, leading to more pragmatic suggestions for clinical practice.

Adult↗
PubMed2006

Successful treatment of CCL4-induced acute liver failure with portal vein arterialization in the rat.

INTRODUCTION: Optimization of the conditions for regeneration of the native diseased liver is a major goal in patients with acute liver failure. This study sought to determine whether portal vein arterialization (PVA), which increases the oxygen supply to the liver, was protective in a rat model of liver failure. METHODS: At 24 hours after CCl(4) intoxication, Sprague-Dawley rats (six per group) were assigned to receive PVA or as controls. We determined blood tests, histology, and 10-day survivals. Hepatocyte regeneration was assessed by the mitotic index and bromodeoxyuridine (BrdU) incorporation. RESULTS: Serum transaminases were significantly lower in PVA-treated rats than in control animals: liver necrosis resolved rapidly after PVA. The BrdU staining and mitotic index were severalfold higher among PVA-treated than in untreated rats. Survival was 100% among rats with PVA and 40% in untreated animals (P < .01). CONCLUSIONS: PVA led to resolution of CCl(4)-induced massive liver necrosis in the rat. This effect was probably mediated by activation of rapid and extensive hepatocyte regeneration. PVA might provide a novel, alternative approach to treat acute liver failure.

Alanine Transaminase↗
PubMed2006

Portal vein arterialization for the treatment of post resection acute liver failure in the rat.

INTRODUCTION: Hyperoxygenation of the liver has been suggested to improve its regenerative capacity. Thus, this study sought to determine whether an additional supply of oxygenated blood delivered by portal vein arterialization (PVA) was protective against acute liver failure induced by hepatectomy. METHODS: Sprague-Dawley rats (six per each group) were divided to either undergo PVA or be untreated after extended hepatectomy. Liver injury was evaluated by the serum alanine aminotransferase (ALT) levels. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine staining. The 10-day survival was assessed in separate experimental groups. RESULTS: The pO(2) in portal blood increased significantly following PVA. Serum ALT levels were significantly reduced in arterialized versus nonarterialized rats. PVA promotes liver regeneration. Finally, PVA significantly improved host survival compared to the controls: 90% versus 30%, respectively. CONCLUSION: These data suggested that an additional supply of arterial oxygenated blood through PVA promoted a rapid regeneration, leading to a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool to optimize hepatocyte regeneration.

Alanine Transaminase↗
PubMed2006

Technical aspects of portal vein arterialization for acute liver failure: from rat lab to man.

Survival rates of patients with acute liver failure (ALF) without transplantation are poor. However, many of them die awaiting a transplant because of the donor organ shortage. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself thus avoiding transplantation is a major goal in their multidisciplinary treatment. Animal experimental studies have shown that portal vein arterialization (PVA) enhances the regenerative capacity of hepatocytes by increasing the oxygen supply to the liver after extended hepatectomy or in toxin-induced ALF models. Furthermore, we have reported the application of PVA in patients with ALF. We herein have described the technical aspects of the PVA procedure both in preclinical models and in man.

Acute Disease↗
PubMed2006

Protective effect of portal vein arterialization in acute liver failure induced by hepatectomy in normal and fatty liver rat.

AIM: We sought to determine whether an additional supply of oxygenated blood achieved by partial portal vein arterialization (PPVA) was protective on normal or fatty liver (FL) in rats with acute liver failure (ALF) induced by hepatectomy. METHODS: Sprague-Dawley rats with normal or FL were segregated either to receive or not to undergo PPVA after hepatectomy. FL was induced by feeding a choline-deficient diet (5 days). PPVA was performed by anactamasing the left renal artery to the splenic vein with a stent following a left nephrectomy and splenectomy; the control rats underwent left nephrectomy and splenectomy only. Liver injury was evaluated by the serum alanine aminotransferase (ALT) level. The animals were sacrificed at 24 hours, 48 hours, and 7 days to collect blood and liver tissue samples for biochemical analysis. The 7-day survival was assessed in separate experimental groups. RESULTS: PPVA significantly increased Po2 and oxygen saturation in the portal blood compared to non PPVA rats. PPVA significantly improved the 7-day survival compared with controls in both groups: hepatectomy of normal liver (90% vs 30%) and hepatectomy of FL (75% vs 25%). Serum ALT levels were slightly lower in the PPVA groups compared with the non-PPVA groups without a significant difference. Prothrombin activity decreased soon after hepatectomy in the normal and the FL liver groups but recovered rapidly thereafter without differences between the PPVA and non-PPVA treated animals. CONCLUSION: An additional supply of arterial oxygenated blood through a PPVA promotes rapid resolution of ALF after partial hepatectomy in rats with normal or fatty livers, significantly improving 7-day survivals compared to hepatectomy controls.

Anastomosis, Surgical↗
PubMed2005

Oxidative injury in rat fatty liver exposed to ischemia-reperfusion is modulated by nutritional status.

BACKGROUND AND AIMS: Oxidative stress contributes to ischemia-reperfusion injury in fatty livers. This study aimed to determine whether glycogen depletion influences this oxidative injury and whether the administration of glucose can be protective. METHODS: Rats with choline deficiency-induced fatty liver underwent hepatic ischemia-reperfusion. Experimental groups: (1) fed rats; (2) 18 h fasted rats; (3) 18 h fasted rats supplemented with glucose prior to surgery. The thiobarbituric acid-reactive substances, protein carbonyls and total glutathione concentrations were measured in liver tissue and isolated mitochondria as parameters of oxidative stress before and after ischemia and during reperfusion. The mitochondrial F1-ATPase content and the serum alanine transaminase were also determined. RESULTS: With respect to fed rats, fasted rats exhibited an increased oxidative injury in both liver tissue and isolated mitochondria throughout the experiment with the only exception of thiobarbituric acid-reactive substances, which were not affected by the nutritional status in liver tissue. Fasted rats showed a significantly lower F1-ATPase content and higher alanine transaminase levels. Glucose supplementation significantly reduced the fasting-associated exacerbation of oxidative stress and liver injury and the F1-ATPase exhaustion. CONCLUSIONS: These data indicate that the pre-existing hepatic glycogen content modulates the oxidative damage in rat fatty livers exposed to ischemia-reperfusion injury and that the energetic substrate supplementation may represent a clinically feasible protective strategy.

Alanine Transaminase↗
PubMed2005

Transthoracic electrical bioimpedance: a non-invasive technique for the evaluation of the haemodynamic alterations in patients with liver cirrhosis.

BACKGROUND/AIM: Transthoracic electrical bioimpedance is a non-invasive technique for the evaluation of systemic haemodynamics. Compared to Doppler ultrasound, it has the advantage of being operator-independent, providing continuous monitoring and being less influenced by postural changes. Until now, transthoracic electrical bioimpedance has been applied to a very limited extent in liver cirrhosis. We, therefore, aimed to compare transthoracic electrical bioimpedance and echocardiography in the assessment of haemodynamic status in cirrhotic patients. PATIENTS/METHODS: Thirteen patients with compensated cirrhosis, 10 patients with cirrhosis and ascites and 12 controls were enrolled. Haemodynamic parameters (stroke volume, cardiac output, heart rate, mean arterial pressure and vascular peripheral resistance) were assessed simultaneously by transthoracic electrical bioimpedance monitoring with BioZ.com for at least 10 min and Doppler ultrasound. RESULTS: The absolute mean values of haemodynamic parameters obtained by the two techniques were quite similar in all groups; furthermore, a good agreement between transthoracic electrical bioimpedance and echocardiography measurements was found for all the parameters. Finally, transthoracic electrical bioimpedance proved easy to employ and provided continuous real-time monitoring of cardio-circulatory variations. CONCLUSIONS: The present study showed a significant correlation between transthoracic electrical bioimpedance and echocardiography in the assessment of systemic haemodynamics in patients with cirrhosis, supporting the employment of transthoracic electrical bioimpedance in pathophysiological studies requiring real-time continuous monitoring of haemodynamic parameters.

Adult↗
PubMed2003

Adaptation of subcellular glutathione detoxification system to stress conditions in choline-deficient diet induced rat fatty liver.

The response of fatty liver to stress conditions (t-butyl hydroperoxide [t-BH] or 36 h of fasting) was investigated by assessing intracellular glutathione (GSH) compartmentation and redox status, GSH peroxidase (GSH-Px) and reductase (GSSG-Rx) activities, lipid peroxidation (TBARs) and serum ALT levels in rats on a choline-deficient diet. Baseline cytosolic GSH was similar between fatty and normal livers, while the mitochondrial GSH content was significantly lower in fatty livers. With the except of cytosolic GSH-Px activity, steatosis was associated with significantly higher GSH-related enzymes activities. Liver TBARs and serum ALT levels were also higher. Administration of t-BH significantly decreased the concentration of cytosolic GSH, increased GSSG levels in all the compartments, and increased TBARs levels in cytosol and mitochondria and serum ALT; all these alterations were more marked in rats with fatty liver. Fasting decreased the concentration of GSH in all the compartments both in normal and fatty livers, increased GSSG, TBARs and ALT levels, and decreased by 50% the activities of GSH-related enzymes. Administration of diethylmaleimide (DEM) resulted in cytosolic and microsomal GSH pool depletion. Administration of t-BH to DEM-treated rats further affected cytosolic GSH and enhanced ALT levels, whereas the application of fasting to GSH depleted rats mainly altered the mitochondrial GSH system, especially in fatty livers. This study shows that fatty livers have a weak compensation of hepatic GSH regulation, which fails under stress conditions, thus increasing the fatty liver's susceptibility to oxidative damage. Differences emerge among subcellular compartments which point to differential adaptation of these organelles to fatty degeneration.

Alanine Transaminase↗
PubMed2002

Evidence of oxidative imbalance in long-term liver transplant patients.

BACKGROUND: Oxidative stress in patients undergoing liver transplantation results both from the pre-existing cirrhosis and ischaemia-reperfusion injury related to surgery. Previous studies have provided information limited to the immediate post-operative period. It remains to be established whether this oxidative imbalance is reversed in a longer time. AIM, METHODS AND PATIENTS: This study aimed to compare plasma concentrations of thiobarbituric acid-reactant substances and alpha-tocopherol in 20 cirrhotic patients before liver transplantation and 22 patients in whom transplant had been carried out at least 6 months previously. Thirty healthy age and sex-matched volunteers served as controls (cross-sectional study). Five patients were evaluated before and after liver transplantation (longitudinal study). RESULTS AND CONCLUSIONS: Pre-transplant patients showed greater thiobarbituric acid-reactant substances and lower alpha-tocopherol levels than controls. Transplanted patients presented lower thiobarbituric acid-reactant substances and greater alpha-tocopherol levels than cirrhotic patients without reaching, however, the levels observed in controls. No correlations were found between oxidative parameters and liver tests. Hypertransaminasaemia, liver disease recurrence, and rejection episodes did not significantly influence the oxidative parameters. In the longitudinal study, transplantation induced a significant decrease in plasma thiobarbituric acid-reactant substances and a rise in alpha-tocopherol. Although a long-term improvement in the oxidative injury observed in cirrhotic patients occurs after liver transplantation, mild oxidative stress persists even in successfully transplanted patients.

Adult↗
PubMed2001

Increased generation of reactive oxygen species in isolated rat fatty liver during postischemic reoxygenation.

BACKGROUND: Whether fatty infiltration of the liver influences the generation of reactive oxygen species (ROS) during reperfusion is unclear. Thus, this study aimed to compare the ROS formation that occurs during postanoxic reoxygenation in isolated normal and fatty livers. METHODS: Isolated livers from fed Sprague-Dawley rats with normal or fatty livers induced by a choline-deficient diet were reperfused at 37 degrees C for 60 min with an oxygenated medium containing 10 microM of lucigenin after 1 hr of warm ischemia. Superoxide anion generation was assessed by the chemiluminescence (CLS) signal emitted from the organ surface. The hepatic content of malondialdehyde (MDA) and glutathione was determined at the end of reperfusion. Tissue injury was evaluated by the liver histology and the alanine aminotransferase (ALT) release in the perfusate. RESULTS: CLS started rapidly with reoxygenation and it diffused to the whole organ in both groups. However, CLS emission was significantly higher in fatty liver (after 10 min: 812.425+/-39.898 vs. 294.525+/-21.068 photons/cm2/sec; P<0.01). A greater concentration of MDA was measured at the end of reoxygenation in fatty liver. Finally, the liver histology and the ALT release indicated a greater injury in steatotic than normal liver. CONCLUSIONS: The CLS technique allows a direct visualization and comparison of ROS generation from the organ surface. Fatty infiltration increases ROS generation in the liver during postischemic reoxygenation, likely leading to the greater lipid peroxidation observed in these experiments. The increased oxidative stress may contribute to the reduced tolerance of steatotic livers to ischemia-reperfusion injury.

Alanine Transaminase↗
PubMed2001

Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status.

BACKGROUND: It is not established whether virological status affects the efficiency of alpha-fetoprotein (AFP) as a hepatocellular carcinoma (HCC) marker among patients with chronic liver disease (CLD). METHODS: We enrolled in a case-control study 170 HCC and 170 CLD patients, matched for age, sex, CLD and HBsAg/anti-HCV status. The AFP sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. PPV and NPV were evaluated for three additional HCC prevalences (5, 10, and 20%). RESULTS: The best discriminating AFP value was 16 ng/ml. A value of 20 ng/ml (above which investigations for HCC are recommended) had equivalent sensitivity (60.0 vs. 62.4%) and specificity (90.6 vs. 89.4%). PPV of 20 ng/ml was 84.6% but decreased to 25.1% at 5% tumor prevalence. NPV was 69.4% and rose to 97.7% at 5% prevalence. In the different groups of infected patients PPV ranged from 80.0 to 90.9%, falling to 17.4-34.5% at 5% prevalence. In noninfected patients PPV was 100% at any HCC prevalence. NPV ranged from 59.0 to 73.0%, reaching 96.5-98.1% at 5% prevalence. CONCLUSIONS: In CLD patients, AFP monitoring misses many HCCs and inappropriately arouses suspicion of malignancy in many patients. Its usefulness is barely affected by the infection responsible for CLD. An AFP elevation could be more indicative of HCC in non-infected patients.

Aged↗
PubMed2001

Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: effect of the nutritional status.

Hepatic steatosis is associated with mitochondrial oxidative alterations. This study aimed to characterize in a choline-deficient model of rat fatty liver whether this oxidative imbalance is related to an impairment of the capacity of ATP synthesis both under fed conditions and after starvation, which may sensitize mitochondria to oxidative injury. Mitochondria were isolated from normal and fatty livers of fed or 18-hour fasted rats. Oxidative injury was evaluated by measuring the mitochondrial content of thiobarbituric reactive substances, protein carbonyls, glutathione, and protein sulfhydryls. The mitochondrial F(0)F(1)-ATP synthase content, tissue ATP concentration, and liver histology were also determined. Compared with normal liver, under fed conditions, fatty livers showed a greater mitochondrial content of oxidized lipids and proteins together with a low concentration of sulfhydryls and glutathione. The mitochondrial catalytic beta-F(1) subunit of the F(0)F(1)-ATP synthase was about 35% lower in fatty livers. Hepatic ATP was also significantly reduced in fatty liver. Starvation exacerbated mitochondrial oxidative injury in both groups but to a greater extent in fatty livers. In the steatotic group, fasting induced a significant decrease of the ATP levels, which was accompanied by a 70% fall of the catalytic beta-F(1) subunit. These data indicate that the mitochondrial oxidative alterations in fatty livers are associated with an important reduction of the F(0)F(1)-ATP synthase. These changes, which are greatly exacerbated after starvation, may account for the reduced synthesis of the hepatic ATP observed in the presence of fatty infiltration.

ATP Synthetase Complexes↗
PubMed2001

Food deprivation exacerbates mitochondrial oxidative stress in rat liver exposed to ischemia-reperfusion injury.

Mitochondria undergo oxidative damage during reperfusion of ischemic liver. Although nutritional status affects ischemia-reperfusion injury in the liver, its effect on mitochondrial damage has not been evaluated. Thus, this study was designed to determine whether starvation influences the oxidative balance in mitochondria isolated from livers exposed to warm ischemia-reperfusion. Fed and 18- and 36-h food-deprived rats underwent partial hepatic ischemia followed by reperfusion. Mitochondria were isolated before and after ischemia and during reperfusion. Serum alanine transaminase was measured to assess liver injury. The mitochondrial concentrations of malondialdehyde, protein carbonyls and glutathione were determined as indicators of oxidative injury. Cell ultrastructure was assessed by transmission electron microscopy. Transaminase levels were greater in 18-h food-deprived than fed rats (after 120 min of reperfusion: 3872 +/- 400 vs. 1138 +/- 59 U/L, P < 0.01). Mitochondrial glutathione was lower in food-deprived than fed rats before and after ischemia, and during reperfusion. Food deprivation also was associated with significantly greater lipid and protein oxidative damage. Finally, more ultrastructural damage was observed during reperfusion in mitochondria from food-deprived rats. Prolonging the length of food deprivation to 36 h exacerbated significantly both the mitochondrial oxidative injury and the release of serum transaminases in rats (after 120 min of reperfusion: 5438 +/- 504 U/L, P < 0.01). Food deprivation was associated with greater mitochondrial oxidative injury in rat livers exposed to warm ischemia-reperfusion, and the extent of oxidative damage in mitochondria increased with the length of food deprivation.

Alanine Transaminase↗
PubMed2000

Starvation impairs antioxidant defense in fatty livers of rats fed a choline-deficient diet.

Although fatty liver (FL) is considered an innocuous condition, the frequent incidence of graft failure when FL are transplanted has renewed interest in the intracellular disorders causative of or consequent to fatty degeneration. Oxidative stress and nutritional status modulate the tolerance to reperfusion injury in control livers (CL), but very little is known in the case of FL. This study was designed to compare the oxidative balance in CL and FL from fed and food-deprived rats. Serum and liver samples were collected from fed and starved (18 h) rats with CL or FL induced by a choline-deficient diet. Hepatic injury was assessed by transaminase activities and histology. The hepatic concentrations of glutathione (GSH), vitamin C, alpha-tocopherol, thiobarbituric acid-reactive substances (TBARS) and protein carbonyls (PC) were measured. Fed rats with FL had significantly greater TBARS and lower alpha-tocopherol and vitamin C levels than those with CL, whereas GSH and PC concentrations were not affected. Starvation impaired the oxidative balance in both groups. However, compared with the other groups, FL from food-deprived rats generally had the lowest hepatic concentrations of alpha-tocopherol, vitamin C and GSH. Unlike in CL, protein oxidation occurred in FL. These data indicate that fatty liver induced by consumption of a choline-deficient diet is associated with a lower level of antioxidants, which results in lipid peroxidation. Starvation further affects these alterations and extends the damage to proteins. In conclusion, steatosis and starvation may act synergistically on the depletion of antioxidants, predisposing fatty livers to a reduced tolerance to oxidative injury.

Animals↗
PubMed1999

Ischemia-reperfusion injury in rat fatty liver: role of nutritional status.

Fatty livers are more sensitive to the deleterious effects of ischemia-reperfusion than normal livers. Nutritional status greatly modulates this injury in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats with normal or fatty liver induced by a choline deficient diet underwent 1 hour of lobar ischemia and reperfusion. Rat survival was determined for 7 days. Serum transaminases, liver histology and cell ultrastructure were assessed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion. Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced survival in rats with fatty liver (14% vs. 64%, P <.01). Accordingly, fasting and fatty degeneration had a synergistic effect in exacerbating liver injury. Mitochondrial damage was a predominant feature of ultrastructural hepatocyte injury in fasted fatty livers. Glucose supplementation partially prevented the fasting-induced depletion of glycogen and improved the 7-day rat survival to 45%. These data indicate that rat fatty livers exposed to normothermic ischemia-reperfusion injury are much more sensitive to fasting than histologically normal livers. Because glucose supplementation improves both the hepatic glycogen stores and the rat survival, a nutritional repletion procedure may be part of a treatment strategy aimed to prevent ischemia-reperfusion injury in fatty livers.

Alanine Transaminase↗
PubMed1999

Autonomic dysfunction and hyperdynamic circulation in cirrhosis with ascites.

Patients with advanced cirrhosis frequently show hemodynamic abnormalities. Autonomic dysfunction (AD) is also common and, owing to the importance of autonomic function in cardiovascular homeostasis, it may be involved in the pathogenesis of the hyperdynamic circulation. We, therefore, evaluated the hemodynamic status and autonomic function in 30 patients with cirrhosis, most of them with an advanced stage of the disease. Autonomic function was assessed with 7 cardiovascular tests exploring the vagal or sympathetic function. Each test was scored from 1 to 3 (normal, borderline, altered). Cardiac index (CI) was measured by an echocardiogram. Twenty-four (80%) patients showed an AD, this being definite in 14 (47%) patients. A vagal dysfunction (VD) was found in 19 patients (63%), this being definite in 11 patients (37%), and a sympathetic dysfunction (SD) in 7 patients (definite in 3 [10%] patients). The patients with AD showed a faster heart rate (P =.021), lower indicized peripheral vascular resistance (P =.013), and increased CI (P =.004) than patients without AD whereas mean arterial pressure did not differ. Similar results were seen by grouping patients according to the VD. AD score was directly correlated with heart rate (r = 0.53; P =.002) and CI (r = 0.45; P =. 016), and inversely correlated with peripheral vascular resistance (r = 0.46; P =.013). Even closer correlations were found with vagal score. AD (mainly VD) may be involved in the pathogenesis of the hyperdynamic circulatory syndrome of patients with advanced cirrhosis.

Adult↗