Terlipressin and albumin in patients with cirrhosis and type I hepatorenal syndrome.

PURPOSE: Hepatorenal syndrome (HRS) is a pre-renal-like dysfunction that generally onsets in cirrhotic patients presenting ascites. We investigated the improvement of renal function in subjects with hepatorenal syndrome after terlipressin administration and the survival times after this treatment. Fifty-two patients affected by cirrhosis, with diagnosis of hepatorenal syndrome were treated with intravenous terlipressin plus albumin (group A) or with albumin alone (group B). Liver and renal function, plasma renin activity, and aldosterone plasma levels were monitored. RESULTS: Patients from group A showed a significant improvement (p < 0.001) of renal function valued by creatinine rate compared with the results obtained in group B. The probability of survival was higher in the group A (p < 0.0001). CONCLUSIONS: Our results seem to confirm that the administration of terlipressin plus albumin improves renal function in patients with cirrhosis and type I HRS and that a reversal of hepatorenal syndrome is strongly associated with improved survival.

Psychiatric symptoms induced by antiviral therapy in chronic hepatitis C: comparison between interferon-alpha-2a and interferon-alpha-2b.

BACKGROUND AND OBJECTIVE: Interferon-alpha treatment is associated with a large number of adverse effects. Depressive symptoms are not unexpected, and potentially dangerous psychiatric adverse effects can induce life-threatening conditions. We compared the incidence of depressive symptoms in patients with chronic hepatitis C during treatment with pegylated interferon-alpha-2a (IFNalpha-2a) and pegylated interferon-alpha-2b (IFNalpha-2b). PATIENTS AND DESIGN: We randomly divided 186 subjects with chronic hepatitis C into two treatment groups: group A, treated with IFNalpha-2a, and group B, treated with IFNalpha-2b. Treatment was continued for up to 48 weeks. Liver biopsy and hepatitis C virus RNA assay were carried out in all patients. Depressive symptoms and the prevalence of psychiatric adverse effects during treatment with IFN were evaluated using the Hamilton Depression Rating Scale, the Zung Self-Rating Depression Scale, and the Structured Clinical Interview for Diagnostic and Statistic Manual-IV axis disorders. RESULTS: At baseline 53% of subjects in group A and 57% of subjects in group B presented with depressive symptoms; at 12 weeks we found a high incidence of depressive symptoms in both groups (group A 61% and group B 65%) and three cases of life-threatening psychiatric symptoms (i.e. psychosis and delirium requiring discontinuation of antiviral therapy and admission to a psychiatric unit) in group A. CONCLUSIONS: Long-term administration of IFN can be associated with serious psychiatric adverse effects. It is very important that psychiatric symptoms are diagnosed early in IFN treatment so to improve treatment compliance and prevent fatal and/or life-threatening adverse events, as were documented in some subjects treated with IFNalpha-2a in our study.

Oxidative stress, nitric oxide, endothelial dysfunction and tinnitus.

To assess whether pathogenic endothelial dysfunction is involved in acute idiopathic tinnitus we enrolled 44 patients and 25 healthy volunteers. In blood from the internal jugular vein and brachial vein we determined malonaldehyde, 4-hydroxynonenal, myeloperoxidase, glutathione peroxidase, nitric oxide, L-arginine and L-ornitine, thrombomodulin (TM) and von Willebrand factor (vWF) activity during tinnitus and asymptomatic period. Higher plasma concentrations of oxidative markers and L-arginine, and lower nitric oxide and L-ornitine levels were observed in jugular blood of patients with tinnitus, there being a significant difference between brachial and jugular veins. TM and vWF activity were significantly higher in patients' jugular blood than in brachial blood. Our results suggest oxidant, TM, vWF activity production are increased and nitric oxide production reduced in brain circulation reflux blood of patients with acute tinnitus. These conditions are able to cause a general cerebro-vascular endothelial dysfunction, which in turn induce a dysfunction of microcirculation in the inner ear.

Effects of antioxidant supplementation on postprandial oxidative stress and endothelial dysfunction: a single-blind, 15-day clinical trial in patients with untreated type 2 diabetes, subjects with impaired glucose tolerance, and healthy controls.

BACKGROUND: Increased generation of reactive oxygen species (ROS) and oxidative stress may be of crucial importance in the pathogenesis of endothelial damage. Furthermore, there is understood to be a relationship between endothelial damage, glycemic control, disorders of lipid metabolism, and coagulative hemostatic disorders. OBJECTIVE: This study investigated within- and between-group changes in various circulating markers of oxidation-reduction balance and endothelial function after a balanced moderate-fat meal with and without antioxidant supplementation in patients with early-stage, untreated type 2 diabetes mellitus; subjects with impaired glucose tolerance (IGT); and healthy controls. METHODS: In this single-blind, controlled clinical study, groups of patients with type 2 diabetes and subjects with IGT were identified and compared with a group of healthy controls. All groups followed a controlled, well-balanced diet for 10 days before and throughout the study. Before and after consumption of a standardized moderate-fat meal, plasma levels of oxidants (malondialdehyde, 4-hydroxynonenal, oxidized low-density lipoprotein), the antioxidant glutathione peroxidase, and markers of endothelial function (NO, endothelin-1, von Willebrand factor [vWF], vascular cell adhesion molecule-1 [VCAM-1]) were determined. These measures were then reassessed after 15 days of standard antioxidant treatment consisting of a thiol-containing antioxidant (N-acetylcysteine 600 g/d), a bound antioxidant (vitamin E 300 g/d), and an aqueous phase antioxidant (vitamin C 250 mg/d). The efficacy of antioxidant treatment in reversing abnormalities in oxidation-reduction balance after a moderate-fat meal was assessed by evaluating changes in plasma levels of ROS on the morning of the 16th day following an overnight fast. Safety was monitored in terms of adverse events, vital signs, physical findings, and laboratory values. RESULTS: The study included 46 patients with type 2 diabetes (23 men, 23 women; mean [SD] age, 41 [3] years; mean body mass index [BMI], 24 [2] kg/m(2)), 46 with IGT (23 men, 23 women; mean age, 39 [3] years; mean BMI, 23 [3] kg/m(2)), and 46 control subjects (23 men, 23 women; mean age, 40 [1] years; mean BMI, 22 [1] kg/m(2)). Before supplementation, all 3 groups had significantly increased levels of oxidants, vWF, and VCAM-1 (all, P < 0.001) and significantly decreased levels of antioxidants and NO (both, P < 0.001) after consumption of a moderate-fat meal. After 15 days of antioxidant treatment, significant improvements in these measures were seen in all groups (P < 0.05). CONCLUSIONS: This study showed changes in oxidation-reduction balance, NO bioavailability, and nonthrombogenic endothelial factors after a moderate-fat meal in patients with type 2 diabetes and those with IGT, but these postprandial changes were reverse in all subjects after 15 days of standard antioxidant supplementation. These findings suggest that the use of anti-oxidants may have decreased oxidative stress in these subjects.

Can ultrasonographic findings of perihepatic lymphadenopathy promote investigations to detect possible presence of virus C infection in non-symptomatic subjects?

PURPOSE: Only early detection of non-symptomatic patients is able to arrest the diffusion of the non-symptomatic HCV infection and lead to prompt treatment. Our aim was to attempt to correlate the presence of perihepatic lymph nodes and hepatitis C infection and to assess whether ultrasonography can have a role to promote specific investigations for pre-clinical diagnosis of virus C infection. METHOD: We performed a controlled study on a cohort of 7974 subjects from a town of 27000 inhabitants on the eastern coast of Sicily. Serologic hepatitis A, B and C markers, alanine aminotransferase levels and abdominal ultrasound examination according to size and number of peri-hepatic lymph nodes were performed on blind basis. RESULTS: One or more pathological lymph nodes were present in 684/7974 subjects. Haematochemical tests revealed the presence of anti-HCV positivity in 528/684 subjects with pathological lymph nodes and in 8/7290 subjects without pathological lymph nodes, there being a significant difference (P<0.0001) between the two groups. CONCLUSION: Our results confirm the association between perihepatic lymph nodes and virus C infection. Correct diagnostic assessment of this datum could lead not only to early diagnosis by specific blood test for HCV and consequent prompt aimed treatment, but could pave the way for efficacious territorial prevention and detection of an elevated percentage of likely non-symptomatic carriers.

Controlled clinical trial to assess the response of recent heroin abusers with chronic hepatitis C virus infection to treatment with interferon alpha-n2b.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) is the most common infectious disease among heroin abusers, but it is recommended that specific treatment with interferon be delayed until at least 6 to 12 months after the end of drug addiction. OBJECTIVE: We investigated the response of heroin abusers to interferon treatment shortly after the end of detoxification treatment with methadone. METHODS: We studied 2 homogeneous groups of white Italian patients with chronic HCV infection: former male heroin abusers and males without a history of drug addiction. Tumor necrosis factor, interleukin-1beta, interleukin-2, activated monocytes, anti-HCV antibodies, HCV RNA, and alanine aminotransferase levels were assessed. Standard treatment was initiated with 5 MU interferon alpha-n2b administered subcutaneously once daily for 8 weeks. Patients with negative HCV-RNA findings at the end of 8 weeks received further treatment with 5 MU TIW subcutaneously for an additional 48 weeks. RESULTS: Thirty of 47 patients in group A (former heroin abusers) and 30 of 30 patients in group B (controls) completed the study. Heroin abusers presented a significantly enhanced response to treatment compared with the controls. After 8 weeks, HCV-RNA test results were negative in 27 of 30 patients in group A (90.0%) and in 25 of 30 in group B (83.3%) (P = NS). Onset of relapse occurred significantly later in heroin abusers (mean [SD], 53 [3] weeks) than in controls (26 [2] weeks) (P < 0.05). Cytokine levels and activated CD11 antigen-expressing monocytes were significantly (P < 0.001) higher in heroin abusers than controls. CONCLUSION: Heroin abusers with chronic HCV infection were successfully treated with interferon alpha-n2b soon after the end of detoxification treatment.