A Spadaro

Publications (14)34.2 Total impact

• Article: Insulin-like growth factor-II is a useful marker to detect hepatocellular carcinoma?

  C Morace, M Cucunato, R Bellerone, G De Caro, S Crinò, A Fortiguerra, F Spadaro, A Zirilli, A Alibrandi, P Consolo, C Luigiano, M L Resta, O Ferraù, A Spadaro
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  ABSTRACT: Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. The utility of serum alpha-fetoprotein (α-FP) in its detection is questionable. Over-expression and high circulating levels of insulin-like growth factor-II (IGF-II) were reported in tissue and in serum of patients with HCC. We investigated the diagnostic application of IGF-II in the diagnosis of HCC. Serum IGF-II and α-FP levels were measured in 178 patients (82 with HCC and 96 with liver cirrhosis) and in 30 healthy controls. Spearman test, non parametric combination test and confidence interval analysis were used for statistical evaluation of data. The best cut-off values selected by ROC curves were 796 ng/ml for IGF-II and 132 ng/ml for α-FP. IGF-II mean values were higher in patients with HCC than in those with liver cirrhosis (LC) (p=0.0001) but lower in LC than in controls (p=0.0001). Serum IGF-II levels above cut-off were found in 22% of patients with HCC, in 9.3% of those with cirrhosis and in 20% of controls. α-FP serum levels >132 ng/ml were observed in 48% of HCC, in 3.1% of LC and in none of control group. By correlation study, serum IGF-II levels were significantly correlated with serum α-FP levels (r=0.427, p=0.0001) and with nodules' diameter (r=0.252, p=0.0130) but not with nodules' number (p>0.050). Finally, IGF-II showed lower sensitivity, specificity and predictive values than α-FP. Circulating IGF-II is not a useful marker for HCC. Further researches are however needed to evaluate its diagnostic accuracy before and after nutritional adjustment.
  European Journal of Internal Medicine 09/2012; 23(6):e157-61. · 2.00 Impact Factor
• Article: Prognostic factors of survival in complicated viral and alcoholic cirrhosis without hepatocellular carcinoma. A retrospective study.

  A Spadaro, C Luigiano, G De Caro, C Morace, V Tortorella, C Bonfiglio, N Pagano, P Consolo, A Alibrandi, A Ajello, O Ferraù, M A Freni
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  ABSTRACT: In several studies, attention is needed to one specific complication, in particularly to hepatocellular carcinoma, which modifies the natural history of liver cirrhosis. Thus, we performed a retrospective cohort analysis to clarify which complications, alone or in combination, are predictive factors of mortality in patients with viral or alcoholic cirrhosis without hepatocellular carcinoma. Case records of 255 patients with decompensated viral or alcoholic cirrhosis between January 1990 and December 2000 were retrospectively analyzed. Relevant clinical and laboratory parameters, and their relationship to mortality, were studied. The mean duration of follow-up period was 29 months in which 178 patients (69.8%) died and 77 (31.8%) survived. None of the patients underwent liver transplantation. The cumulative mortality rate of patients with complicated cirrhosis was 38.8% after 1 year, 51.7% after 2 years, 61.1% after 3 years and 65.1% after 8 years. A multivariate Cox's model identified the following variables as significant: age (P=0.001), gastrointestinal bleeding (GB)-ascites combination (P=0.000), encephalopathy-GB-ascites (P=0.028), hepatorenal syndrome (HRS) (P=0.000), GB-spontaneous bacterial peritonitis (SBP) (P=0.001), alkaline phosphatase (ALP) (P=0.004) and the Child-Pugh score (P=0.000). The mortality in a group of patients with alcoholic cirrhosis is longer than in those with viral cirrhosis . Moreover, ascites in combination with other complications, HRS and hemorrage-SBP association are independent predictors of mortality in patients with complicated liver cirrhosis.
  Minerva gastroenterologica e dietologica 01/2008; 53(4):311-9.
• Article: Premature discontinuation of interferon plus ribavirin for adverse effects: a multicentre survey in 'real world' patients with chronic hepatitis C.

  G B Gaeta, D F Precone, F M Felaco, R Bruno, A Spadaro, G Stornaiuolo, M Stanzione, T Ascione, R De Sena, A Campanone, G Filice, F Piccinino
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  ABSTRACT: Interferon-alpha plus ribavirin therapy for chronic hepatitis C is associated with adverse effects that lead to therapy discontinuation in up to 27% of patients in randomized controlled trials. To examine the causes and predictive factors for therapy discontinuation in patients treated in current clinical practice. We retrospectively enrolled 441 consecutive patients, scheduled to receive interferon-alpha + ribavirin for chronic hepatitis C, in five centres. Patients had been treated with 3 or 6 MU interferon-alpha three times a week plus ribavirin, 800-1200 mg daily, for 6 or 12 months. One hundred and eight [24.5%; confidence interval (CI), 20.5-28.8%] patients failed to finish combination therapy because of adverse events. The discontinuation rate was higher during the first 6 months of treatment; anaemia was an important cause (36.1% of discontinuations); unexplained lipothymia resulted in discontinuation in 11 patients. Female gender [hazard ratio (HR) = 1.85; CI, 1.17-2.92], an interferon-alpha dose > 15 MU/week (HR = 1.79; CI, 1.12-2.86) and no previous interferon-alpha treatment (HR = 1.63; CI, 1.04-2.57) were independent factors associated with discontinuation. The simultaneous presence of these factors identified patients at high risk for discontinuation [odds ratio (OR) = 10; CI, 3.98-25.13]. The study identified some predictive factors for adverse event-related discontinuation, which may improve the safety profile and effectiveness of interferon-alpha + ribavirin combination therapy in chronic hepatitis C.
  Alimentary Pharmacology & Therapeutics 09/2002; 16(9):1633-9. · 3.77 Impact Factor
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  Available from: nih.gov

  Article: Antibodies to hepatitis A virus in Italian patients with chronic liver disease.

  E Sagnelli, G Rossi, N Coppola, C Scolastico, M Onofrio, P Filippini, M Chiaramonte, E Pizzigall, A Aceti, A Spadaro, G Raimondo, F Piccinino
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  ABSTRACT: To improve our knowledge for future hepatitis A virus (HAV) vaccination strategies we carried out a multicentre study on naturally acquired immunological protection against HAV in patients with chronic hepatitis in Italy. We enrolled 830 consecutive patients with chronic hepatitis on their first observation at one of the six Italian liver units participating in the study. Six hundred and fifty-eight patients (79.3%) were positive for total anti-HAV and 172 (20.7%) were negative. The anti-HAV negative patients were younger (median age 33, range 11-78) than the anti-HAV positive (median age 56, 18-87). There was a higher prevalence of cases with circulating anti-HAV among the 508 patients residing in southern Italy than in the 322 residing in northern Italy (88.8% vs. 64%, P < 0.001). No significant difference in the anti-HAV prevalence was observed between patients from northern Italy and those from southern Italy aged 0-30 years or in those over 60 years, while in those 31-60 years old there was a higher prevalence of anti-HAV positive patients from southern Italy (90.2% vs. 65.8%, P < 0.0001). Of the patients with liver cirrhosis in this study, only 3 of the 26 (11.5%) from northern Italy and 8 of the 228 (3.5%) from southern Italy had no immunological protection against HAV infection. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV is substantial in Italy, particularly in the north of the country, and that new vaccination strategies are needed.
  Epidemiology and Infection 10/2001; 127(2):341-6. · 2.84 Impact Factor
• Article: Focal lymphocytic aggregates in chronic hepatitis C: occurrence, immunohistochemical characterization, and relation to markers of autoimmunity.

  M A Freni, D Artuso, G Gerken, C Spanti, T Marafioti, N Alessi, A Spadaro, A Ajello, O Ferraù
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  ABSTRACT: Intrahepatic lymphocytic aggregates are observed in chronic hepatitis C as well as in autoimmune chronic hepatitis. Autoantibodies and autoimmune manifestations may occur in hepatitis C. It has been suggested that the lymphocytic aggregates play a role in the liver injury of chronic hepatitis C by an immune-mediated mechanism. We studied the occurrence of intrahepatic lymphocytic aggregates and of autoantibodies in a consecutive series of 128 patients with chronic hepatitis C. For the phenotypic characterization of the lymphocytic aggregates cryostat sections and microwaved paraffin embedded sections were immunostained with monoclonal antibodies directed against T cell subsets, B cells, killer/natural killer cells, follicular dendritic cells, and macrophages. Autoantibodies were tested by immunofluorescence (antinuclear, anti-smooth muscle, antimitochondrial) and by enzyme-linked immunosorbent assay (anti-soluble liver antigen, anti-liver/kidney microsome, anti-human receptor for asialoglycoprotein). Focal lymphocytic aggregates in portal tracts were observed in 76 of 128 (59%) patients. The cellular composition of the aggregates was constant: a core of B cells mixed with many T helper/inducer lymphocytes, and an outer ring was prominently formed by T suppressor/cytotoxic lymphocytes. A germinal center was rarely identifiable. The presence of lymphocytic aggregates was inversely correlated with the degree of fibrosis. Lymphocytic aggregates appeared more frequently in chronic persistent and chronic active hepatitis in comparison with cirrhosis and in the presence of bile duct damage. No correlation was found between lymphocytic aggregates and autoantibodies or other markers of autoimmunity. The lymphocytic aggregates are frequent in chronic hepatitis C. Their cellular composition is similar to that of primary lymphoid follicles in lymph nodes. Their presence does not seem to be correlated with features of autoimmunity.
  Hepatology 09/1995; 22(2):389-94. · 11.66 Impact Factor
• Article: [Assessment of portal hypertension in hepatic cirrhosis in relation to etiologic factors].

  A Aiello, I Calapristi, M A Freni, A Fava, E M Scarpignato, A Spadaro, O Ferraú
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  ABSTRACT: Hundred-forty-one patients, 78 affected by alcoholic liver cirrhosis and 63 by posthepatitic cirrhosis were studied in order to assess the degree of portal hypertension in liver cirrhosis of different etiology taking into account the developing stages of the disease. Etiological assessment was based on anamnesis, laboratory data, needle liver biopsy and patients of each group were divided into 3 subgroups (grade A, B, C) according to Child-Turcotte classification. A > 1.3 cm diameter of portal vein and a > 13 cm spleen size evaluated by means of real-time ultrasonography together with the occurrence of esophageal varices at endoscopy were considered as signs of portal hypertension. Our study shows that such signs are more frequent in patients affected by posthepatitic cirrhosis in comparison with those affected by alcoholic cirrhosis. If the severity of the disease was considered, at the early stage (grade A) no significant difference was reported in portal diameters while splenomegaly and esophageal varices appeared more frequent in posthepatitic cirrhosis. In grade B patients the increase of portal and spleen size proved significantly greater in posthepatitic cirrhosis whereas prevalence of esophageal varices was similar in the two groups. The lack of differences in the three considered parameters at the end stage of the disease may be due to severe changes in liver morphology actually similar in the 2 groups apart from etiological factors.
  Minerva gastroenterologica e dietologica 04/1993; 39(1):1-5.
• Article: HCV infection, hepatic HLA display and composition of the mononuclear cell inflammatory infiltrate in chronic alcoholic liver disease.

  M A Freni, A Ajello, M L Resta, G B Gaeta, A Spadaro, A Fava, I Calapristi, N Alessi, O Ferraù
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  ABSTRACT: Viral infection may play a role in alcoholic liver disease with histological features of chronic active hepatitis (CAH). Human leucocyte antigen (HLA) hepatocellular display is supposed to allow HLA-restricted T-lymphocyte cytotoxicity in chronic viral hepatitis. We studied the presence of serum anti-hepatitis C virus (HCV) antibodies, the hepatic HLA display and the composition of the mononuclear cell infiltrate in 16 patients with alcoholic liver disease and histological features of CAH and in 11 patients with alcohol-related degenerative changes. All patients were negative for hepatitis B virus (HBV) markers. Anti-HCV were tested by microplate ELISA. Class I HLA A, B, class II HLA DR, lymphocytes pan T, T helper/inducer, T suppressor/cytotoxic, B, and K NK cells were stained on liver cryostat sections by monoclonal antibodies and double indirect immunoperoxidase. Anti-HCV were present in all the patients with features of CAH and absent in those with only degenerative changes. In livers with features of CAH the mononuclear cell infiltrate consisted largely of T lymphocytes with marked prevalence of suppressor/cytotoxic cells in periportal and lobular areas. K NK cells were rare. Class I HLA, diffusely displayed on bile duct epithelium and on sinusoidal cells, also appeared on liver cells in the areas of periportal and lobular necrosis, namely on the hepatocytes in close contact with suppressor/cytotoxic T cells. In livers with only degenerative changes class I HLA were diffusely displayed on bile duct epithelium and on sinusoidal cells but absent on the hepatocytes. In all the specimens HLA DR antigens were expressed on sinusoidal and inflammatory cells.(ABSTRACT TRUNCATED AT 250 WORDS)
  European Journal of Clinical Investigation 01/1992; 21(6):586-91. · 3.02 Impact Factor
• Article: Delta infection in eastern Sicily

  A. Smedile, M. A. Freni, L. Caruso, A. AJello, C. Trischitta, M. L. Resta, G. Bertino, G. Berlinghieri, S. Rapisarda, L. Geronimo, A. Spadaro, O. Ferrau
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  ABSTRACT: Sera from 619 HBsAg+ subjects living in eastern Sicily, consecutively collected from 1975–1985, were tested for markers of delta virus (HDV) infection: delta antigen (HDAg), antibodies to delta (anti-HDIg), and also for antibodies to HBcore of IgM type (anti-HBcIgM) and for the system HBe-anti-HBe. The subjects included 210 asymptomatic carriers, 238 patients with acute hepatitis and 171 patients with chronic liver disease.HDAg was not found in any of the samples. Anti-HD was found in 28/171 (16.3%) patients with chronic liver disease, in 13/210 (6%) asymptomatic HBsAg carriers and in 13/238 (5.4%) patients with acute hepatitis. None of our patients were drug addicts. One had a history of blood transfusion, and nine came from the same family unit.The prevalence of HDV infection in eastern Sicily is lower than in other areas of Sicily possibly because of the lower percentage of HBsAg carriers in the local population. Parenteral transmission of HDV does not seem to play a major role in our area, while the familial clustering suggests close body contact as an important way of spread.
  European Journal of Epidemiology 11/1987; 3(4):386-389. · 4.71 Impact Factor
• Article: [Behavior of anti-HBc IgM in acute and chronic hepatitis].

  A Ajello, M A Freni, A Smedile, M L Resta, G Berlinghieri, A Spadaro, I Calapristi, O Ferraù
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  ABSTRACT: Anti-HBV core IgM antibodies (anti-HBc IgM) were tested by RIA in the sera from 269 patients with acute viral hepatitis (AVH), from 39 patients with chronic HBSAg+ hepatitis (CH) at various stage of evolution, in 41 asymptomatic HBsAg carriers and in 30 healthy volunteers. Anti-HBc IgM were found in 100/108 HBsAg+ AVH, in 6/161 HBsAg--AVH, in 9/39 with CH and only 1 asymptomatic HBsAg carrier. Among the chronic patients with anti-HBc IgM, 3 were HBeAg+ and 6 were anti-HBe+. The test of anti-HBc IgM results useful in the early aetiological diagnosis of acute hepatitis since it is always positive in HBV acute hepatitis even in the subjects who early seroconvert to anti-HBs; the absence of anti-HBc IgM in the HBsAg+ acute hepatitis suggests other overinfecting agents. The presence of anti-HBc IgM in CH seems not to be related to an active viral replication.
  Minerva medica 11/1985; 76(41):1907-10. · 0.90 Impact Factor
• Article: Ten year follow-up of patients with chronic hepatitis C treated with interferon.

  A Ajello, M A Freni, A Spadaro, N Alessi, F Impellizzeri, P Consolo, M L Resta, O Ferraú
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  ABSTRACT: The impact of the treatment with interferon (IFN) on the natural history of chronic hepatitis C is not defined. The aim of this study was to evaluate the long term effect of the treatment in patients with chronic hepatitis C. In 31 patients with chronic hepatitis C (9 with cirrhosis) consecutively treated with recombinant alpha 2a interferon (r alpha 2a IFN), the evolution of the disease at 10 years from the therapy was evaluated by means of upper endoscopy, liver ultrasonography (US), liver function tests and hepatitis C virus (HCV) viremia. Among 10/31 patients previously classified as responders, only 1 has signs of evolution to cirrhosis; HCV-RNA is still present in 2. Among 21 non-responder patients, 5 developed hepatocarcinoma (HCC) and 4 died during the follow-up; HCV-RNA is present in all the patients still alive. The 6 patients already cirrhotic when treated have clinical signs of progression to Child class B and C. The biochemical, ultrasonographical and endoscopical evaluation shows onset of cirrhosis in 7 of the others. Patients with chronic hepatitis C who respond to treatment with interferon have good outcome and rare evolution to cirrhosis. The treatment does not seem to influence the natural history of the disease in non-responders.
  Hepato-gastroenterology 46(28):2447-50. · 0.66 Impact Factor
• Article: Class I HLA antigens hepatic display and beta-2-microglobulin serum values in chronic hepatitis C: effect of treatment with recombinant alpha interferon.

  M A Freni, A Ajello, A Spadaro, A Fava, I Calapristi, T Marafioti, N Alessi, M L Resta, O Ferraù
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  ABSTRACT: Enhanced hepatocellular display of class I HLA antigens together with rising serum beta-2-microglobulin (a subunit of class I HLA molecule) and transaminases is reported in patients with chronic hepatitis B during treatment with interferon as an index of immune lysis of virus infected cells. We studied class I HLA antigens and beta-2-microglobulin display in the livers of 23 patients with chronic hepatitis C before and after a 12 month treatment with recombinant alpha interferon. Beta-2-microglobulin serum values were monitored. In all the patients before treatment, class I HLA antigens and beta-2-microglobulin were diffusely displayed in the bile duct epithelium, in the sinusoidal lining cells, in approximately 50% of the inflammatory cells and in the hepatocyte membrane with marked staining in the areas of periportal and lobular necrosis. At the end of the treatment, class I HLA antigens and beta-2-microglobulin were no longer or only faintly detectable in the hepatocytes of 12 patients who showed clinical and histological improvement. The immunohistochemical pattern was unchanged in the 11 patients who did not respond to the therapy. Baseline serum beta-2-microglobulin values were high in all the patients and decreased significantly only in the group of responders. No peaks of transaminases were registered. The disappearance or reduction of HLA hepatocellular display without acute increase of serum beta-2-microglobulin values and transaminases during successful treatment with interferon in chronic hepatitis C suggests a clearance of the virus due to direct antiviral rather than immunologically mediated mechanism.
  Hepato-gastroenterology 44(17):1295-301. · 0.66 Impact Factor
• Article: Interferon retreatment of patients with chronic hepatitis C. A long-term follow-up.

  A Spadaro, M A Freni, A Ajello, N Alessi, E Barbaro, M L Resta, O Ferraü
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  ABSTRACT: We retrospectively evaluated the long-term efficacy of interferon retreatment in patients with chronic hepatitis C, who did not have a sustained response to a 1st cycle of treatment. Sixty-six patients, 43 non-responder and 23 relapser to alpha interferon treatment, were retreated with alpha interferon, 6 MU thrice weekly for 12 months. Response was defined as negative HCV viremia. Responders underwent long-term follow-up (27-43 months). The response rates were 14% and 35% at the end of retreatment, 7% and 22% at 6 months, and 2% and 13% at long-term follow-up in non-responders and relapsers respectively. The outcome of retreatment was not statistically influenced by age, cirrhosis, viral genotype, dose and duration of previous treatment. Interferon retreatment, for sustained viral eradication, is not effective in non-responders and useful in few relapsers. Whereas, retreatment could prove effective in slowing down the activity of the disease and reducing the incidence of hepatocarcinoma, since some relapses occur late during the follow-up. Therefore, retreatment should be confined to relapsers with contraindications to new more efficient therapeutic strategies.
  Hepato-gastroenterology 46(30):3229-33. · 0.66 Impact Factor
• Article: Prevalence of anti-HCV antibodies in patients with chronic liver disease and its relationship to HBV and HDV infections.

  G B Gaeta, M Rapicetta, C Sardaro, A Spadaro, F Chionne, A M Freni, A Ajello, A Costantino, G Giusti
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  ABSTRACT: The prevalence of anti-HCV, anti-HDV and of HBV markers has been investigated in a series of 209 consecutive patients (age 18-74 years) with chronic liver disease. Among 155 HBsAg negative patients (53 chronic hepatitis cases and 102 cirrhosis cases), anti-HCV were found in 69% of the cases. 67% of the 155 patients also carried anti-HBc, with no difference between patients positive or negative for anti-HCV. Among the 54 HBsAg positive patients, 10 (18.5%) also had anti-HCV, 22 (40.7%) were anti-HDV positive and 12 (22.2%) had serum HBV-DNA. One patient had concomitant anti-HDV and anti-HCV and another presented anti-HCV and serum HBV-DNA. 21/54 patients had liver cirrhosis on presentation and among these 17 (81%) were anti-HCV and/or anti-HDV positive. On the whole, 123/209 patients had liver cirrhosis on presentation and in 107 of them HCV infection may have played a role.
  Infection 18(5):277-9. · 2.66 Impact Factor
• Article: High serum resistin in chronic viral hepatitis is not a marker of metabolic disorder.

  C Morace, A Spadaro, M Cucunato, V Tortorella, P Consolo, C Luigiano, G Stabile, C Bonfiglio, R Bellerone, A Fortiguerra, A Alibrandi, S Crinò, A Carducci, M L Resta, O Ferraù, M A Freni
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  ABSTRACT: The role of resistin, an adipocyte-secreted hormone, in insulin resistance and in inflammation is controversial. In chronic hepatitis C, insulin resistance, type 2 diabetes and liver steatosis are frequent and inconsistently correlated to circulating resistin levels. In this study we assessed if viral aetiology and host metabolic parameters influence serum resistin in patients with HCV- and HBV- related chronic hepatitis. Serum resistin was measured by ELISA and correlated to viral aetiology, age, gender, BMI, HOMA-IR, liver steatosis, hepatitis staging and grading, blood glucose, triglycerides and cholesterol in 43 patients with chronic hepatitis C, in 16 with chronic hepatitis B and in 29 healthy controls. In both groups of patients resistin was significantly higher than in controls, with higher values in HBV- than in HCV-patients (p = 0.0007). Resistin levels were correlated to aetiology and, inversely, to age (p = 0.026), diabetes (p = 0.036) and steatosis (p = 0.029). Multiple regression analysis showed that resistin concentration was dependent only on the aetiology of liver disease (p = 0.001). In chronic viral hepatitis serum resistin levels are high and not associated with altered metabolic parameters or with the histological activity of the disease. The meaning of higher resistin in HBV- than in HCV- chronic hepatitis is unclear.
  Hepato-gastroenterology 57(102-103):1215-9. · 0.66 Impact Factor