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Biomedical subjects

P Andreone

Publications and source records attributed to P Andreone.

At least 19 recordsLinked to original sources
PubMed1999

Interferon-alpha plus ribavirin in chronic hepatitis C resistant to previous interferon-alpha course: results of a randomized multicenter trial.

BACKGROUND/AIMS: Interferon-alpha plus ribavirin seem to be more efficacious than interferon monotherapy in chronic hepatitis C. In a multicenter randomized trial, we evaluated the efficacy of this association for interferon-alpha resistant chronic hepatitis C. METHODS: Fifty patients who were non-responders to recombinant or lymphoblastoid interferon-alpha were randomized to receive either ribavirin (800 mg/day) plus leucocytic interferon-alpha (3 mega units thrice weekly) or the same dose of interferon-alpha alone, for 6 months. Effects of therapy were evaluated by serum aminotransferase and hepatitis C virus RNA levels and control liver biopsies. RESULTS: At the end of treatment, aminotransferase levels become normal in 9/26 patients receiving combination therapy (35% [confidence interval, 16% to 53%]) and in 2/24 receiving interferon-alpha alone (8% [confidence interval, -3% to 19%]) (p = 0.03). Aminotransferase normalization was never associated with hepatitis C virus RNA clearance. All patients with normal aminotransferase relapsed after discontinuation of therapy. At the end of treatment, mean hepatitis C virus RNA levels significantly decreased only in the group receiving combination therapy, but returned to pretreatment values 6 months thereafter. No histological improvement was observed in either group. CONCLUSIONS: There is no indication for treatment with interferon-alpha at the dose of 3 mega units thrice weekly plus 800 mg/day of ribavirin for 6 months in chronic hepatitis C resistant to interferon-alpha.

Antiviral Agents↗
PubMed1999

Serum pancreatic enzyme concentrations in chronic viral liver diseases.

Serum amylase and lipase concentrations were determined in 78 patients with chronic liver diseases [26 chronic active hepatitis (CAH) and 52 liver cirrhosis] and in 15 healthy subjects. Pancreatic isoamylase concentrations and macroamylase complexes were assayed in hyperamylasemic sera. Serum amylase levels were abnormally elevated in 27 patients (35%; 22 liver cirrhosis, 5 CAH), whereas serum lipase levels were elevated in 16 patients (21%; 15 liver cirrhosis, 1 CAH). In 9 of the 27 hyperamylasemic patients, the hyperamylasemia was of pancreatic type. Macroamylasemic complexes were not detected in hyperamylasemic sera. Patients with liver cirrhosis had serum levels of amylase and lipase significantly higher than both the healthy subjects and the patients with CAH, while no significant differences were found in serum levels of these enzymes in patients with CAH as compared to the healthy subjects. A decreased liver metabolism of serum amylase and lipase in patients with chronic infective liver disease, especially in those having liver cirrhosis, may lead to an accumulation of these enzymes in the blood.

Adolescent↗
PubMed1999

Gross pathologic types of hepatocellular carcinoma in Italy.

The prevalence and independent predictors of the different macroscopic types of hepatocellular carcinoma (HCC) were assessed in 1,073 unselected patients of 14 hospitals in Italy from May 1996 to May 1997. Solitary HCC was the most common cancer type (44.6%), followed by multinodular (44.2%), diffuse (8.4%) and massive (2.8%) types. After adjustment for the influence of confounders by multiple logistic regression analysis, Child-Pugh grades B and C were found to be independent predictors of multinodular (odds ratio, OR, 2.0; 95% confidence interval (CI) = 1.5-2.6) and diffuse (OR 2.6; 95% CI = 1.6-4.4) HCC types. These findings indicate that the majority of HCC cases are not detected at a potentially treatable stage. Delayed detection of HCC is associated with a higher likelihood of the multinodular or diffuse gross pathologic type.

Carcinoma, Hepatocellular↗
PubMed1998

Prevalence of monoclonal gammopathies in patients with hepatitis C virus infection.

BACKGROUND: An association between monoclonal gammopathies and chronic liver diseases has been reported. OBJECTIVE: To determine the prevalence of monoclonal gammopathies in patients with chronic hepatitis C virus (HCV) infection and the possible association of monoclonal gammopathies with HCV genotypes. DESIGN: Prospective study. SETTING: Departments of internal medicine and hematology at two university hospitals in Italy. PATIENTS: 239 HCV-positive and 98 HCV-negative patients with chronic liver diseases were recruited consecutively. MEASUREMENTS: Clinical data were gathered, liver histologic examination was done, serum immunoglobulin and cryoglobulin levels were measured, and immunoelectrophoresis was done for monoclonal component detection. Patients with monoclonal gammopathy had serum HCV RNA measured and HCV genotype determined by polymerase chain reaction and had histologic examination of bone marrow. RESULTS: Monoclonal band was detected in 11% of HCV-positive patients and in 1% of HCV-negative patients (P = 0.004). The prevalence of HCV genotype 2a/c was higher in patients with monoclonal gammopathies than in those without (50% compared with 18%; P = 0.009). CONCLUSION: The prevalence of monoclonal gammopathies in patients with HCV-related chronic liver disease is striking and is often associated with genotype 2a/c infection.

Adolescent↗
PubMed1998

Characteristics of hepatocellular carcinoma in Italy.

BACKGROUND/AIMS: This study aimed to assess the main features of hepatocellular carcinoma at the time of diagnosis in Italy, particularly in relation to the presence or absence of underlying cirrhosis, hepatitis virus marker patterns, age of the subjects and alpha-foetoprotein values. METHODS: A total of 1148 patients with hepatocellular carcinoma seen at 14 Italian hospitals in the 1-year period from May 1996 to May 1997 were the subjects of this prevalence study. Both newly diagnosed cases (incident cases) and cases diagnosed before May 1996 but still attending the hospitals during the study period (prevalent cases) were included. RESULTS: We found that 71.1% of cases were positive for hepatitis C virus antibodies but negative for HBsAg; in contrast, 11.5% were negative for anti-HCV but positive for HBsAg; 5.3% were positive for both markers; and 12.1% were negative for both viruses. The mean age of detection was over 60 years, with a younger mean age in HBsAg-positive compared to anti-HCV-positive patients (59.3 years vs. 65.6 years, p<0.01). The male-to-female ratio among HBsAg-positive patients was 10.4:1, in contrast to 2.8:1 among anti-HCV-positive patients (p<0.01). The majority of cases (93.1%) had underlying cirrhosis. Cirrhotic patients were more likely to be anti-HCV positive than non-cirrhotic cases (73.2% vs 43.9%; p<0.01); conversely, absence of hepatitis virus markers was more frequently observed in the non-cirrhotic than in the cirrhotic population (40.9% vs. 10.0%; p<0.01). Overall, the alpha-foetoprotein level was altered (>20 ng/ml) in 57.9% of patients; only 18% of cases presented diagnostic (>400 ng/ml) values. Anti-HCV positivity (O.R. 2.0; CI 95%=1.3-3.1) but not HBsAg positivity (O.R. 1.0; CI 95%=0.6-1.8) was shown to be an independent predictor of the likelihood of altered alpha-foetoprotein values by multivariate analysis. CONCLUSIONS: These findings point to differences in the characteristics of the populations infected by hepatitis B and hepatitis C. Factors other than the hepatitis viruses are important in non-cirrhotic patients. A change in the relative prevalence of hepatitis virus markers among hepatocellular carcinoma cases was demonstrated, reflecting a significant change in the rate of HBV endemicity in the Italian population. Finally, the increased trend in the mortality rate from liver cancer in Italy from 4.8 per 100,000 in 1969 to 10.9 in 1994 may reflect the large cohort of subjects infected with HCV via the iatrogenic route during 1950s and 1960s when glass syringes were commonly used for medical treatment.

Adult↗
PubMed1998

Lamivudine treatment for acute hepatitis B after liver transplantation.

BACKGROUND/AIMS: Acute hepatitis caused by recurrent or de novo hepatitis B virus (HBV) infection after liver transplantation frequently induces aggressive disease leading to liver failure. The aim of this study was to determine the efficacy and safety of lamivudine treatment in post-transplant acute hepatitis B. METHOD: Twelve patients with acute hepatitis B were started on lamivudine 100 mg p.o. daily within 8 weeks of the appearance of HBsAg. One patient was excluded after 1 month because of hepatocellular carcinoma recurrence. Patients were followed for an average of 68.6 weeks (range 32-108), and were clinically and biochemically evaluated on a monthly basis. They had a histological assessment at baseline, after at least 6 months, and whenever clinically indicated. RESULTS: Basal HBV-DNA ranged between 13 and 1288 pg/ml and serum alanine aminotransferase between 97 and 1036 U/l. HBV-DNA became undetectable within 8 weeks and transaminases normalized within 24 weeks in all cases. At the last visit, eight patients (73%) remained HBV-DNA negative by liquid hybridization and had normal or close to normal alanine aminotransferase. Five patients (45%) were also HBsAg negative and HBV-DNA negative by polymerase chain reaction. HBV-DNA and transaminase breakthrough occurred in three patients (27%). Histology after 6-9 months showed chronic hepatitis in seven patients. Lamivudine was well tolerated without serious adverse reactions. CONCLUSIONS: These results indicate that lamivudine treatment induces sustained inhibition of viral replication and normalization of transaminases in the majority of post-transplant patients with acute hepatitis B. HBsAg loss may be achieved in a considerable number of cases. Although viral resistance is relatively frequent, early initiation of lamivudine appears to be effective and safe.

Acute Disease↗
PubMed1996

A randomized controlled trial of thymosin-alpha1 versus interferon alfa treatment in patients with hepatitis B e antigen antibody--and hepatitis B virus DNA--positive chronic hepatitis B.

It has recently been shown that thymosin-alpha1(T-alpha1), a synthetic polypeptide of thymic origin, is able to promote disease remission and inhibition of hepatitis B virus (HBV) replication in patients affected by hepatitis B e antigen (HBeAg)-positive chronic active hepatitis. We evaluated the efficacy and safety of T-alpha1 treatment in patients with hepatitis B e antibody (anti-HBe) and HBV-DNA-positive chronic hepatitis. Thirty-three patients were randomly assigned to receive either T-alpha1 900 microg/m2 body surface area twice weekly (17 patients) or 5 MU of interferon alfa (IFN-alpha) three times weekly (16 patients) for 6 months. At baseline, both groups were comparable concerning age, sex, liver histology, and alanine transaminase (ALT) levels. At the end of treatment, complete response (defined as ALT normalization and HBV-DNA loss) occurred in 5 of 17 (29.4%) in the T-alpha1 group and in 7 of 16 (43.8%) in the IFN-alpha group (P = not significant). After a follow-up period of 6 months, a complete response was observed in 7 of 17 (41.2%) in the T-alpha1 group and in 4 of 16 (25%) in the IFN-alpha group (P = n.s.). Compared with the results observed in a group of 15 patients never treated with IFN-alpha and followed for 12 months, the rate of complete response was significantly higher in the IFN-alpha group at the end of therapy (1 of 15 vs. 7 of 16, respectively; P < .05) and in the T-alpha1 group at the end of follow-up (1 of 15 vs. 7 of 17, respectively; P < .05). Unlike IFN-alpha, T-alpha1 was well tolerated by all patients. The only side effect, reported by some, was local discomfort at injection sites. The results of this trial suggest that T-alpha1 is able to reduce HBV replication in patients affected by anti-HBe-positive chronic hepatitis. Furthermore, compared with IFN-alpha, T-alpha1 is better tolerated and seems to induce a gradual and more sustained ALT normalization and HBV-DNA loss. In conclusion, T-alpha1 appears to be a safe and effective alternative treatment for anti-HBe-positive chronic hepatitis. The benefit of this agent in producing long-term inhibition of HBV replication must be confirmed by future trials.

Adult↗
PubMed1996

A double-blind, placebo-controlled, pilot trial of thymosin alpha 1 for the treatment of chronic hepatitis C.

A randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy and safety of thymosin alpha 1 (alpha 1) in treating chronic hepatitis C. Nineteen Italian patients with chronic active hepatitis C, proven by biopsy were randomly assigned to receive a six month course of thymosin alpha 1 (900 micrograms/m2 of body surface area twice weekly) or a placebo. All had HCV-RNA in their serum (by PCR), with serum ALT levels more than double the upper limit of the normal range for at least six months before enrollment. After treatment, patients were followed for an additional six months. All patients completed the trial. One patient treated with thymosin alpha 1, but no patient in the placebo group, normalized serum ALT levels by the end of the treatment. This patient, however, relapsed at the sixth month of the follow up. Overall, there were no significant changes in mean serum ALT levels in either group during the treatment or follow-up period. No patient cleared HCV-RNA. No side effects were reported except for local discomfort at the injection sites, reported by some patients treated with thymosin alpha 1. In conclusion, this regimen of thymosin alpha 1 is not effective in the treatment of chronic hepatitis C.

Adult↗
PubMed1996

Incidence of hepatitis C virus infection in Italian patients with idiopathic pulmonary fibrosis.

BACKGROUND: A viral cause of idiopathic pulmonary fibrosis (IPF) was recently suggested by a Japanese study in which a high prevalence of anti-hepatitis C virus (HCV) antibodies was detected. A subsequent British study failed to confirm these results. METHODS: Antibodies to HCV were evaluated in 60 patients with IPF, 130 patients with non-interstitial lung disease, and in 4614 blood donors. HCV-RNA and HCV genotypes were evaluated in the anti-HCV positive patients with IPF. Anti-HCV antibodies were evaluated by ELISA and confirmed by recombinant immunoblotting assay (RIBA). HCV-RNA and genotypes were detected by reverse transcriptase polymerase chain reaction (PCR). RESULTS: Eight patients with IPF had anti-HCV antibodies detected by ELISA (13.3%). In the blood donor control group the prevalence of HCV antibodies was lower (0.3%). In patients with non-interstitial lung disease HCV antibody prevalence was 6.1%. In all eight patients with IPF found to be anti-HCV positive by ELISA, HCV antibodies were also detected by RIBA. Furthermore, all were HCV-RNA positive by PCR assay. HCV genotypes were identified in four of these eight patients. In all four genotype II was present and in two it was associated with genotype III and/or genotype IV. In the remaining four cases the genotype was not identified. CONCLUSION: Italian patients with IPF show an increased prevalence (approximately 13%) of HCV infection and viral replication, but the prevalence of anti-HCV antibodies does not differ from other lung diseases.

Adult↗
PubMed1995

Hemodynamic and renal effects of ascites apheresis, concentration and reinfusion in advanced cirrhosis.

BACKGROUND/AIMS: We studied the effects of ascites apheresis, concentration and reinfusion, a new form of treatment for tense or refractory ascites, on systemic hemodynamics and renal function. METHODS: Twelve patients with advanced cirrhosis (two belonging to Child-Pugh's class B and the remainder to class C) were monitored. They were evaluated under baseline conditions, just after the treatment, and 24 and 48 h after baseline assessment. In addition to systemic hemodynamics--as evaluated by Doppler echocardiography--and renal function, indirect markers of effective volemia, such as atrial natriuretic factor, plasma renin activity and aldosterone concentration, and plasma norepinephrine were also measured. RESULTS: The technique led to significant changes in systemic hemodynamics, such as an increase in stroke volume and cardiac output. However, due to a striking reduction in peripheral vascular resistance, mean arterial pressure also declined. The hemodynamic changes were associated with a parallel increase in atrial natriuretic factor. Despite the reduction in arterial pressure, plasma renin activity also significantly declined, while plasma norepinephrine did not undergo significant changes. Although an improvement in glomerular filtration rate and renal sodium excretion occurred, neither change reached statistical significance. All the hemodynamic, renal and neuro-humoral changes described above subsided almost entirely after 48 h, when no significant changes with respect to baseline values were any longer detectable with the exception of a slight reduction in mean arterial pressure. CONCLUSIONS: In advanced cirrhosis ascites apheresis, concentration and reinfusion enhance central volemia, but an exaggerated peripheral vasodilation largely wastes the potential favourable effect on arterial volemia. As a result, no significant improvement in renal perfusion and sodium excretion can ensue.

Adult↗
PubMed1994

Indomethacin enhances serum 2'5'-oligoadenylate synthetase in patients with hepatitis B and C virus chronic active hepatitis.

Activation of the arachidonic acid metabolism seems to be one of the post-receptor mechanisms by which interferon-alpha induces antiviral protein synthesis. In this study, we evaluated the changes on serum 2'5'-oligoadenylate synthetase levels induced by acute administration of interferon-alpha, indomethacin and interferon-alpha plus indomethacin in 21 patients with hepatitis B or C virus chronic active hepatitis. Serum samples for 2'5'-oligoadenylate synthetase determination were collected in basal conditions and 8 h after the administration of interferon-alpha, indomethacin and interferon-alpha plus indomethacin. Compared to control value (mean +/- SE) (40.2 +/- 7.9 pg/dl) serum 2'5'-oligoadenylate synthetase concentration was significantly increased 1.5-fold after interferon-alpha (63.4 +/- 11, p < 0.001), 2.8-fold after indomethacin (115.5 +/- 21, p < 0.001) and 3.7-fold after interferon-alpha plus indomethacin (148.9 +/- 25.1, p < 0.001). When patients with different viral infections were considered separately, basal 2'5'-oligoadenylate synthetase concentrations were similar in both HBeAg- and HBeAb-positive patients, but about 2-fold higher in hepatitis C virus. Compared to the control value, interferon-alpha caused a 1.5-fold increase in HBeAg- and hepatitis C virus-positive and a 2-fold increase in HBeAb-positive patients. Indomethacin led to a 1.8-fold increase in HBeAg, a 2-fold increase in hepatitis C virus-positive and surprisingly a 6.8-fold increase in HBeAb-positive patients. Simultaneous administration of the two drugs had an additive effect on the 2'5'-oligoadenylate synthetase increase in HBeAg-positive (2.4-fold increase) and a synergistic effect in hepatitis C virus- and HBeAb-positive patients (2.7- and 10.2-fold increase, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1993

Renal sodium retention during upright posture in preascitic cirrhosis.

BACKGROUND: Renal sodium handling in preascitic cirrhosis is not clearly defined. This issue was addressed by evaluating renal sodium metabolism with different postures. METHODS: Renal function and plasma atrial natriuretic factor (ANF), aldosterone, and norepinephrine levels were determined after 2 hours of standing and 30, 60, and 120 minutes after taking up the supine position in 10 patients and 10 healthy subjects. RESULTS: When upright, patients' glomerular filtration rate and plasma ANF and norepinephrine levels did not differ from those of controls. Conversely, renal sodium excretion was reduced. Plasma aldosterone levels, which were slightly elevated, inversely correlated with renal sodium excretion. In the supine position, natriuresis increased by 308% +/- 99% in patients and 113% +/- 29% in controls (P = 0.016), so that it no longer differed between the two groups. Plasma norepinephrine and aldosterone levels decreased to a similar extent in controls and cirrhotics, whereas the increase in plasma ANF level was greater in patients. The changes in natriuresis correlated with those in plasma ANF levels and plasma aldosterone-ANF ratios in both controls and patients. CONCLUSIONS: Aldosterone-dependent sodium retention develops in preascitic cirrhosis during standing. The supine position is the means whereby standing-induced sodium retention can be balanced.

Adult↗