Search PubMed⌕ Search

Biomedical subjects

I Di Fazio

Publications and source records attributed to I Di Fazio.

14 recordsLinked to original sources

Neuropsychiatric effects and type of IFN-alpha in chronic hepatitis C.

Chronic hepatitis is often associated with neuropsychiatric disorders. Interferon (IFN) is the drug most widely used to treat this disease, and its side effects, such as depression, often involve the central nervous system (CNS). Symptoms include a slowing down of psychomotor functions, loss of interest, frontal lobe dysfunction, parkinsonism, and delirium. The occurrence of these complications calls for dropping out of IFN treatment or for a significant dose reduction and administration of antidepressants. Efficacy and side effects vary on the basis of the IFN type employed. The aim of our study was to evaluate if the frequency, form, and degree of depression induced are related to the type of IFN employed. We studied 96 patients with chronic hepatitis C. Our study series was divided into four groups according to the type of IFN-alpha administered. Depression degree was clinically evaluated using the Hamilton Depression Rating Scale (HAM-D). All patients were tested before treatment and 1, 3, and 6 months (15 days after the end of treatment) later. Our results showed that the type of IFN used seemed to influence the depression onset rate, with the leukocyte type inducing the lowest level of depression. However, when a number of symptoms associated with the depression were considered, the results of other types of IFN-alpha were found to be better. Use of the most suitable type of IFN-alpha could thus lead to more personalized treatment, with fewer side effects. The type of IFN used seems to influence the psychological side effects and the adaptation rate to therapy. It would be appropriate to choose the type of IFN on the basis of a neuropsychiatric assessment carried out before treatment.

Adult↗

Alpha-interferon (IFN-alpha) treatment of chronic hepatitis C: analysis of some predictive factors for the response.

Interferon (IFN)-alpha is recognized today as the treatment of choice for chronic hepatitis virus C-related disease. Several factors are able to influence the response to the therapy. In the last few years, several types of IFN-alpha have been used with varying therapeutic results. In order to define the role played by the type of IFN-alpha, as a predictive factor of response to therapy, we studied clinical and biological features of 128 patients (80 males and 48 females, mean age 58.5+/-9.7 years) divided into four homogeneous groups. Four types of IFN-alpha were administered at the same dose and for an identical period. Lymphoblastoid was administered to Group A; recombinant 2a to Group B; recombinant 2b to Group C and leukocyte to Group D. The results showed that the best response was achieved using natural IFN. Statistical evaluation of the predictive factors was carried out using bivariate and multivariate analysis. IFN-alpha was associated with different response rates for viral and biochemical remission at the end of the treatment and at the end of 12 months' follow-up period. Therefore, the type of IFN administered may influence the response to therapy and important independent single predictive factors of response should be taken into account. The type of IFN used may determine how well the disease is controlled.

Antiviral Agents↗

Increase of serum beta2-microglobulin in patients affected by HCV correlated hepatocellular carcinoma.

OBJECTIVE: HLA antigens influence tumour growth and spreading, but the mechanism is still unclear. Increased serum levels of beta2-microglobulin (beta2MG) have been found in several chronic inflammatory and tumour diseases. The aim of the present study was to analyse the relationship between serum beta2MG levels and some markers of tumour progression, to verify the reliability of this parameter as a marker of hepatocellular carcinoma (HCC) progression. DESIGN: We studied 50 patients with hepatitis C virus (HCV) correlated HCC, 50 patients affected by chronic hepatitis C and 20 healthy controls. We performed a statistical analysis on the data obtained from haematological withdrawals in patients and healthy subjects. METHODS: Serum beta2MG levels were determined by an immunoturbidimetric method (normal values range from 0.8 to 27 microg/ml). Diagnosis of HCC was performed on the basis of haematochemical parameters (alpha-fetoprotein) and instrumental examinations (ultrasonography and computed tomography). In order to perform the statistical analysis we used the Wilcoxon non-parametric rank test and the Spearman log-rank correlation test RESULTS: Patients with HCC showed higher serum beta2MG levels than did chronic hepatitis C patients (36+/-16.5 microg/ ml versus 2.3+/-0.8 microg/ml; P<0.0001) or healthy subjects (36+/-16.5 microg/ml versus 1.6+/-0.4 microg/ml; P<0.0001). We found a positive correlation between beta2MG and interleukin-6 (IL-6) (r = +0.3; P = 0.05), beta2MG and alpha-fetoprotein (r = +0.4; P = 0.005), beta2MG and tumour size (r = +0.3; P = 0.02). CONCLUSIONS: An increase in the beta2MG serum level reflects the tumour size and seems to be a consequence of the stimulation on hepatocytes by humoral components of immunological response, such as IL-6. Weakening of the immune system, due to IL-6, may be responsible for a more severe progression of HCC and the hyperexpression of beta2MG.

Adult↗

Rapid evolution of chronic viral hepatitis into hepatocellular carcinoma after beta-interferon treatment.

A 62-year-old man, affected by Chronic Active Hepatitis (discovered in 1993) and treated with interferon, referred to our department with increased abdominal volume, persistent abdominal pain, continuous-remittent fever and jaundice. CT scan of the liver revealed a hypodense, not capsulated, infiltrative, solid formation in the right lobe. US guided biopsy showed multinucleated giant cells, with eosinophilic cytoplasm and pleomorphism of the nuclei, arranged in several thick trabecula lined by endothelial cells or formed bile containing acini. In our case, the rapid evolution of chronic viral hepatitis towards HCC calls for a careful evaluation of the role of IFN therapy, since this drug is widely used in chronic liver diseases.

Antiviral Agents↗

Haematologic pattern in healthy elderly subjects.

BACKGROUND: A more prolonged life expectancy is associated with an increased morbidity rate with marked alterations of physiologic and metabolic functions in the body. The haematologic pattern can be modified during ageing because of reduced cellular replication and enhanced fibrosis in the bone marrow. Nevertheless it is not clear whether ageing represents the cause or the result of these phenomena. METHODS: In order to evaluate wide variation of data on the haematologic pattern in elderly subjects, we studied one hundred eight healthy subjects (27 males, 81 females; ranging from 50 to 99 years), living in their home. RESULTS: We observed a reduction in serum iron and transferrin and an increase in serum ferritin levels during ageing, with a consequential iron tissue stores increase. CONCLUSIONS: Our data suggested that senescence was associated with an increased incidence of anemia, which cannot be considered a normal feature of aging, the physicians must investigate each cause of anemia in elderly subjects. Haematological pattern is in the normal range in healthy elderly subjects, even if we found significant age-linked changes. We conclude that a progressive impairment of bone marrow functions is the most important factor in determining significant changes of hematopoiesis in healthy elderly subjects.

Aged↗

Interferon alpha-induced depression in chronic hepatitis C patients: comparison between different types of interferon alpha.

IFN alpha treatment is able to produce dose-related side effects, such as depression, in the central nervous system. We assessed the effects on depression of four different types of IFN alpha (recombinant IFN alpha 2a, recombinant IFN alpha 2b, lymphoblastoid IFN alpha, leukocyte IFN alpha), administered at the same doses in four homogeneous groups of chronic hepatitis C patients (96 patients; 24 patients for each group). A group of 18 untreated hepatitis C patients was considered as a control group. Depression was measured using Zung's self-rating depression scale (SDS scale) before starting IFN alpha therapy and at the 1st, 3rd and 6th month of treatment. In all patients evaluated, mean SDS values increased from mild to moderate depression, but never attained severe depression (SDS > 70). More elevated SDS values were observed in the 1st month of treatment, with a progressive decrease during the end points above-mentioned. The recombinant IFN alpha 2a and lymphoblastoid IFN alpha arms presented higher SDS mean scores compared to the recombinant IFN alpha 2b and leukocyte IFN alpha arm. Only in the leukocyte IFN alpha arm SDS values returned to basal values at the 6-month end point. Leukocyte IFN alpha seemed to present a more elevated tolerability than other IFN alpha types available for clinical practice. A very careful selection of hepatitis C patients is required before starting IFN alpha therapy.

Aged↗

Efficacy of different schedules in the management of chronic hepatitis C with interferon-alpha.

The best results in terms of clinical remission in chronic hepatitis C are achieved by interferon (IFN)-alpha treatment. We studied 255 patients affected by chronic hepatitis C infection (HCV) and divided into 3 groups. A different IFN-alpha therapeutic schedule was adopted in each group: A) 3 million units (MU) three times per week for 6 months; B) 3 MU three times per week for 12 months; C) 6 MU three times per week for 6 months. A sustained biohumoural and virological remission was observed in only 14.5% of the patients included in group A, in 21.6% of the patients included in group B and in 8% of the patients included in group C. The adoption of more aggressive therapeutic regimens did not offer an improvement in response or patient compliance. At present, the long term efficacy of treatment may be evaluated on the basis of both biochemical and virological data.

Adolescent↗

Elevation of interleukin 6 levels in patients with chronic hepatitis due to hepatitis C virus.

Interleukin 6 (IL-6) is a pleiotropic cytokine produced by a wide variety of lymphoid and non-lymphoid tissues. We studied the relationship between IL-6 and the liver in an attempt to elucidate this cytokine's role in hepatitis C-induced liver inflammation. We investigated the behavior of serum IL-6 in 25 patients with chronic hepatitis C (divided into three groups depending on severity) and in 27 healthy controls. Our results showed a significant elevation (P < 0.0001) in serum IL-6 levels in the patients with chronic hepatitis C, correlated with the histological activity index (HAI) and their HCV-RNA serum levels. This rise may represent the expression of the hepatitis C virus-induced inflammatory state.

Case-Control Studies↗

Decrease of interferon gamma serum levels in patients with chronic hepatitis C.

Cytokines can play a crucial role in defending the organism from viral infections. One of these, interferon gamma (IFN-gamma), possesses marked immunomodulating activity. As cell immunity seems to be involved in chronic hepatitis C virus (HCV), study of the events regulated by IFN-gamma may be useful in evaluating the host's immunological response. We studied 63 patients (36 males, 27 females) affected by chronic HCV and 28 (14 males, 14 females) healthy controls. IFN-gamma concentrations were significantly lower in the former, and were positively correlated with the histological activity index, suggesting that low IFN-gamma values play a part in determining chronicity. We believe they may be an unfavorable factor and may be useful in detecting patients who are not capable of eradicating the virus.

Adult↗

Serum beta2-microglobulin in chronic hepatitis C.

beta2-Microglobulin (beta2-MG) plays a key role in influencing the immune response to viral infections as it is an integrating part of the main histocompatibility system (HLA). We attempted to evaluate the changes in class I HLA antigens by comparing the serum beta2-MG behavior in a group of patients affected by chronic hepatitis C with that observed in a group of healthy controls. Our study revealed that the patients presented higher serum beta2-MG levels than healthy controls (P = 0.0003). beta2-MG levels were correlated with duration and degree of the disease. Furthermore, there was a statistically significant correlation between beta2-MG and HCV RNA levels, while no correlations were observed between serum beta2-MG levels and HCV genotypes. The increment in serum beta2-MG values accompanying the progression of liver disease may be an expression of augmented production rather than altered excretion.

Adult↗

Serum interleukin 6 concentrations in chronic hepatitis C patients before and after interferon-alpha treatment.

IFN-alpha represents the treatment of choice in chronic hepatitis C. It acts directly on the cells infected by the virus and indirectly via the cytokine network. We studied the behavior of interleukin 6 (IL-6), a cytokine that is particularly active in the liver and considered an index of liver inflammation and necrosis, in order to evaluate the relationships between IFN-alpha administration and serum levels of this cytokine. Our study series was composed of 60 patients (32 males, 28 females, mean age 53.03 +/- 12.7 years) affected by chronic hepatitis C and 24 healthy controls (14 males, 13 females, mean age 45.8 +/- 5.9 years). We determined serum IL-6 concentrations before and after 3,000,000 IU of IFN-alpha t.i.w./6 months in the former and compared them with levels observed in the controls. Pre- and post-treatment serum IL-6 levels were higher in chronic hepatitis patients and correlated with HAI score and HCV RNA prior to treatment. Diversely, this correlation was less significant after completion of the treatment. Furthermore, IL-6 concentrations depended on the type of response to treatment, i.e. they decreased in complete responders, while increased in partial and non-responders. Our data indicate that IL-6 concentrations, before treatment, are expression of viral-induced inflammation and that, after treatment, may be increased by the action of IFN-alpha treatment.

Adult↗

[Role of interleukin 6 in hepatocellular carcinoma].

Interleukin 6 (IL-6) is a pleiotropic cytokine which possesses a broad spectrum of action in diverse pathological conditions. It is mainly produced and metabolised in the liver where it carries out one of its best known actions in the mediation of the acute phase response. We studied its behaviour in hepatocellular carcinoma to evaluate its clinical prognostic role. We determined serum IL-6 concentrations in 39 patients with hepatocarcinoma (27 males and 12 females) and 25 healthy controls (15 males and ten females). Our results showed a significant increase in serum IL-6 concentrations in hepatocarcinoma subjects compared with controls (P < 0.005) and an elevated positive correlation (r = 0.616) between IL-6 and size of the hepatocarcinoma. Our study demonstrated that IL-6 is able to influence hepatocarcinoma progression by acting as an autocrine tumoral growth factor and depleting immune surveillance.

Adult↗

Interleukin-6 in hepatitis C cirrhosis.

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in numerous diseases but the correlation between liver fibrosis and IL-6 role is not clear. We studied IL-6 levels in 50 HCVAb+ patients with liver cirrhosis (grouped into A, B and C, Child classes) and in 27 healthy control subjects. IL-6 serum levels were significantly increased in the former (p < 0.005) suggesting that IL-6 stimulates and sustains liver fibrosis. In cirrhotic subjects, the rise in IL-6 serum levels is due to impaired hepatic clearance of this cytokine, while its production remains steady.

Adult↗

[Erythropoietin in hepatocellular carcinoma].

Hemopoietic alterations may occur during tumoral diseases, determining anemia. In most cases, serum EPO levels were lower than normal values. Hepatocellular carcinoma (HCC), one of the most frequent malignancies world-wide, is often characterized by mild anemia and increased serum EPO levels. We studied 30 HCC patients and 20 healthy subjects. We found that HCC patients presented higher serum EPO levels than healthy controls. In HCC patients, there was a significant inverse correlation between serum EPO levels and red blood cell count or hemoglobin levels. We postulated that the elevated serum EPO levels observed in these patients may be due to reduced hepatic clearance of EPO, and to the influence of cytokine-mediated inflammatory factors.

Aged↗