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Biomedical subjects

L Roffi

Publications and source records attributed to L Roffi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Antibodies to interferon (IFN) in hepatitis C patients relapsing while continuing recombinant IFN-alpha2 therapy.

A number of trials have demonstrated that IFN-alpha is effective in chronic hepatitis C virus infection. It is known, however, that a number of chronic hepatitis C patients experience, after an initial response to IFN, disease reactivation or relapse (also called 'breakthrough') while IFN therapy is still ongoing. Since in a number of clinical conditions a significant correlation between development of antibodies to IFN and failure of therapy has been established, we addressed the possibility that the development of antibodies to IFN may take part in the relapse occurring in hepatitis C patients during recombinant IFN-alpha (rIFN-alpha) therapy. The prevalence of neutralizing (NA) and binding antibodies (BA) to rIFN-alpha2 has been evaluated in 45 patients with chronic hepatitis C treated with rIFN-alpha2a who first normalized aminotransferase (ALT) levels, and subsequently showed disease reactivation while on treatment. The presence of NA and BA was tested before therapy, during the response to IFN treatment, and at the time when ALT started to rise again to abnormal levels. The results showed that no patients had detectable antibodies to IFN before therapy and during the period of response to the therapy, while most of them (88.9%) developed NA and/or BA to IFN-alpha2 concomitantly with disease reactivation. In particular, in 29 of the 45 patients (64.4%) ALT normalized on treatment and rose to abnormal levels when NA appeared in their serum, while in 11 of the 16 (68.8%) remaining patients the relapse was associated with BA development. The frequency of seroconversion in these patients is significantly higher than that observed in the control group. These data indicate that antibodies to IFN may be responsible for breakthrough in the majority of patients showing disease reactivation while rIFN-alpha therapy is still ongoing.

Adolescent↗
PubMed1996

Iron stores, response to alpha-interferon therapy, and effects of iron depletion in chronic hepatitis C.

We studied 81 patients with chronic hepatitis C to investigate the relationship between iron and alpha-interferon response. Sixty-one patients (group A) were given alpha-interferon irrespective of iron status, whereas 20 (group B) with iron overload, were iron depleted before alpha-interferon therapy. In group A, 21 patients responded to alpha-interferon and 40 were non-responders. Increased iron indices were significantly more frequent in non-responders than responders. Multivariate analysis showed that among the independent variables evaluated, only gamma-GT and liver iron concentration predicted therapy outcome. After phlebotomy treatment, serum alanine aminotransferase fell significantly both in patients of group B (196 +/- 122 IU/l vs 82 +/- 37 IU/l, p < 10(-6)) and in 12 non-responders of group A (198 +/- 89 IU/l vs 107 +/- 81 IU/l, p < 10(-6)). In 16 iron depleted patients, eight from each group, subsequent treatment with alpha-interferon produced a response in only one patient. These results suggest that increased liver iron is a negative prognostic factor for alpha-interferon response in chronic hepatitis C. Iron depletion had a beneficial effect on serum alanine aminotransferase in all the patients treated, but did not improve the response to alpha-interferon.

Adult↗
PubMed1995

Liver iron concentration in chronic viral hepatitis: a study of 98 patients.

OBJECTIVE: To compare the liver iron concentration (LIC) of Italian patients with chronic hepatitis B and C with those of controls, to evaluate increased LIC frequency in patients and to investigate the influence of the haemochromatosis gene in the development of liver iron overload. DESIGN AND SETTING: Prospective controlled trial in two northern Italian hospitals. PATIENTS: Ninety-eight patients (61 men and 37 women), 85 with chronic hepatitis C and 13 with chronic hepatitis B, and 38 control individuals (20 men and 18 women). METHODS: Atomic absorption spectrophotometry was used to determine LIC; standard lymphocytotoxicity test was used for HLA typing in patients with increased LIC; and family studies were performed for patients with major iron overload. RESULTS: Mean LIC was significantly higher in both patient groups than in the controls. Thirty-five patients (36%) had an increased LIC. Twenty-six of these patients had a minor iron overload, whereas nine (9.2%) had a major overload. HLA-A3 antigen was present in five out of the 26 and in four out of the nine patients, respectively. Family studies revealed two siblings HLA-identical to their own proband without evidence of iron overload and chronic hepatitis. CONCLUSION: Increased LIC is frequent in Italian patients with chronic hepatitis. The mechanism by which the hepatitis virus promotes liver iron accumulation is not known, but it can favour the development of major iron overload in some cases. HLA-A3 antigen prevalence and family studies suggest that in these cases a single haemochromatosis gene probably coexists with the viral infection. LIC should be determined as part of the screening evaluation in patients with suspected chronic hepatitis B or C.

Aged↗
PubMed1995

Breakthrough during recombinant interferon alfa therapy in patients with chronic hepatitis C virus infection: prevalence, etiology, and management.

Recombinant interferon alfa (r-IFN alpha 2) has been shown to normalize the aminotransferase levels in approximately 50% of patients with chronic hepatitis C virus (HCV). Few patients experience a relapse during the treatment, in spite of a complete initial response (breakthrough). We studied 191 HCV Ab-positive patients with histologically proven chronic hepatitis. All of them were treated with r-IFN alpha 2 (3 MU three times a week). A complete response was seen in 54.4%. However, 12 of 104 responders experienced a breakthrough. At the time of breakthrough, neutralizing IFN antibodies were positive in 6 of 12 patients. Binding IFN antibodies were positive in all of these 12 patients. Continued treatment with r-IFN alpha 2, even at higher doses, did not restore the previous response in any patient. All of them were then switched to natural lymphoblastoid IFN, and this rapidly restored a complete response in all of the patients.

Adolescent↗
PubMed1994

Time course of circulatory and humoral effects of rapid total paracentesis in cirrhotic patients with tense, refractory ascites.

BACKGROUND/AIMS: Tense ascites of cirrhosis can be treated with total paracentesis; however, the short-term effects of this procedure are poorly defined. METHODS: The circulatory and humoral changes induced by total paracentesis (250 mL/min) were studied in 12 cirrhotics with tense, refractory ascites. Data were collected before, during, and after paracentesis and 24 hours later (after albumin infusion). Hormonal parameters were recorded again 48 hours and 6 days thereafter. RESULTS: Paracentesis (10.7 +/- 4.4 L; 64 +/- 20 minutes) caused marked reduction of intra-abdominal, intrathoracic, right atrial, and pulmonary pressures. Heart rate did not change. Cardiac output and heart volumes increased. Systemic vascular resistances and mean arterial pressure slightly decreased. Baseline plasma renin and aldosterone levels were markedly increased; a reduction was already evident during paracentesis with the lowest values at the end of the procedure. All changes were maintained 24 hours later. Hormones regained baseline levels 6 days later. CONCLUSIONS: Rapid total paracentesis is accompanied by marked cardiovascular and humoral changes. Some of these changes can be explained by mechanical factors that are directly or indirectly related to the relief of abdominal pressure. However, other changes (systemic vasodilatation, humoral deactivation) have a non-mechanical nature and may depend on reflexes originating from cardiac volume receptor stimulation. Most changes may beneficially (albeit transiently) influence the cardiovascular system of cirrhotic patients with tense ascites.

Abdomen↗
PubMed1992

Liver damage in Italian patients with hereditary hemochromatosis is highly influenced by hepatitis B and C virus infection.

We evaluated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in 78 Italian patients with hereditary hemochromatosis as well as the relation between HCV antibody (anti-HCV) status, hepatitis B surface antigen (HBsAg) and liver histology. None of the patients had been transfused or ever consumed more than 60 g of alcohol per day. Eighteen showed histological signs of chronic hepatitis, active cirrhosis was present in 12, chronic active hepatitis in 4 and chronic persistent hepatitis in 2. Liver fibrosis or cirrhosis without inflammatory activity was observed in 31 subjects, whereas liver histology was normal except for iron overload in 18. The prevalence of HBsAg in the whole series was 5% and of anti-HCV was 20.5%. The prevalence of HBsAg and anti-HCV was significantly higher in the chronic hepatitis group than in the fibrosis/cirrhosis (p = 0.01) and the normal groups (p < 0.01). Fourteen of 18 hereditary hemochromatosis patients with chronic hepatitis were HBsAg (4) or anti-HCV (10) positive and all the latter subgroup had HCV-RNA in their serum as shown by the polymerase chain reaction. Although most of the patients with associated chronic hepatitis had cirrhosis, their serum ferritin levels and amount of mobilizable iron were significantly lower than those of the fibrosis/cirrhosis group (p < 0.01). This indicates that hepatitis viral infection acts synergistically with iron in accelerating the development of liver damage.

Adult↗
PubMed1990

Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy. A randomized double-blind casein-controlled trial. The Italian Multicenter Study Group.

In a double blind randomized study, branched-chain amino acids and placebo (casein) were compared as a treatment for chronic hepatic encephalopathy in cirrhosis. After a 15-day run-in period with controlled diet (45-65 g protein), the patients were administered, in addition to their diet, branched-chain amino acids (0.24 g/kg, 30 patients) or an equinitrogenous amount of casein (34 patients). One patient on branched-chain amino acids and two on casein were lost to the study. After 3 months, the index of portal-systemic encephalopathy significantly improved in patients on active treatment (from 40 [S.D. 14]% to 21 [17]), but was not in subjects receiving casein (from 37 [13]% to 36 [12]). Two or more parameters of the index improved in 24 patients treated with amino acids (80%; confidence limits, 61-92%), and only in 12 receiving casein (35%; confidence limits, 20-54%; p less than 0.001). Patients who did not improve were given an alternative treatment for 3 more months. Casein-treated patients given branched-chain amino acids rapidly improved. The changes in neuropsychologic function were associated with an improvement in semiquantitative nitrogen balance, which became consistently positive in amino acid-treated subjects; there was also a mild improvement in nutritional parameters and in liver function tests. The supplementation of oral branched-chain amino acids to the diet is superior to casein as a treatment for providing adequate nitrogen supply and improving the mental state of cirrhotic patients with chronic encephalopathy.

Adult↗
PubMed1987

Repeated paracentesis and i.v. albumin infusion to treat 'tense' ascites in cirrhotic patients. A safe alternative therapy.

To investigate the usefulness of paracentesis as an alternative treatment for ascites, 41 cirrhotic patients with 'tense' ascites were randomly assigned to treatment with either repeated paracenteses plus i.v. albumin infusion (n = 20) or diuretics (n = 21). Satisfactory mobilization of ascites was obtained with paracentesis in all but one case and with diuretics in all but two cases. Ascites disappeared within 3 or 4 days with paracentesis, but only after 15 days with diuretics. The rate of reaccumulation of ascites following paracentesis, without diuretic administration, exceeded 300 g/day in only 5 patients. The incidence of complications and the mortality rate were similar in both groups of patients during hospital stay and during follow-up. This was corroborated by the evidence that no negative changes were induced in clinical and laboratory parameters of hemodynamic, hepatic and renal function after evacuation of the ascites. These results confirm that repeated paracenteses combined with human albumin replacement are safe and effective for treating 'tense' ascites, and more rapid than traditional diuretic therapy.

Albumins↗
PubMed1984

Decrease in suppressor/cytotoxic T-cells with histamine receptors in patients with chronic active hepatitis.

A fluorescence assay was employed to measure the levels of circulating suppressor/cytotoxic T cells with membrane receptors for histamine (H+T cells) in 33 patients with chronic active hepatitis, in seven patients with metabolic and vascular liver disorders and in 25 healthy individuals. The H+T cells were decreased in patients with CAH (4.6 +/- 2.2 cells/mm3 vs 16 +/- 3.9 cells/mm3; p less than 0.001), but were normal in patients with metabolic or vascular liver diseases (17.6 +/- 6 cells/mm3 vs 16 +/- 3.9 cells/mm3; NS). Patients with HBsAg-negative CAH had fewer circulating H+T cells than those with HBsAg-positive CAH (p less than 0.05). The same was true for patients with cirrhosis as compared to those without. The lymphocyte alterations were independent of the nature and course of CAH, but correlated inversely with the serum levels of gammaglobulins and with the histological features of hepatic inflammation (p less than 0.05). Like other sets of lymphocytes, the H+T cells in CAH may have locally either immunomodulatory or cytotoxic effects. In analogy with other immune disorders (histiocytosis X, atopic dermatitis), one might speculate that the alterations in H+T cells in CAH represent derangement of the immunoregulatory cell network. The absence of systemic features of autoimmunity in viral CAH correlates with the demonstration that H + T cells exert their immunoregulatory effects at the sites of inflammation where histamine is being released.

Adolescent↗
PubMed1983

[Altered immunoregulation in chronic viral hepatitis. Deficiency of T-lymphocytes with membrane receptors for histamine].

To further characterize the defect of immunoregulation in chronic active hepatitis (CAH), we measured circulating T cells with membrane receptors for histamine (H + TLy), cells endowed with cytotoxic and suppressor functions, in a group of patients with viral CAH, in patients with non-immune liver disorders and in healthy individuals. Patients with CAH showed significantly lower mean numbers and percentage of H + TLy (p less than 0,001) than controls, while patients with non-immune liver disorders had H + TLy values which did not differ significantly from those found in healthy individuals. The lymphocyte alterations in CAH patients were independent of serum HBsAg, cirrhosis or steroid therapy, but correlated inversely with an in vivo index of plasma cell activity, i.e., serum gammaglobulin levels, and with the histological parameter of hepatic inflammation, i.e. portal and periportal mononuclear infiltration. The normal values of H + TLy in patients with non-immune liver diseases suggest that in CAH the decrease in circulating H + TLy is not secondary to the liver damage. The alteration of immunoregulation associated with CAH may have pathogenetic implications, although it is unlikely to represent the sole mechanism for the perpetuation and worsening of the disease process.

Adult↗
PubMed1977

Immunoelectrophoretic quantitation of alpha-fetoprotein.

We describe an immunoelectrophoretic method for alpha-fetoprotein quantitation. The sensitivity of the method, which is easy to perform in the routine laboratory, is under the best conditions 50 mug/liter, but 83 mug/liter can always be detected. With this test, sera from patients with various hepatic diseases and from pregnancies can be tested.

Female↗
PubMedDate not supplied

A multicenter, prospective study of posttransfusion hepatitis in Milan.

We studied the risk of posttransfusion hepatitis in recipients of blood collected from volunteer donors who tested negative for HBsAg and had serum ALT levels less than 1.5 times the upper limit of the normal range. Between October, 1983 and September, 1984, 676 consecutive patients who needed blood or plasma transfusions during or after elective surgery, who had no history of liver disease and had never received blood previously, were studied. The patients were given a total of 4,813 (mean = 7) units. Ninety-six patients developed posttransfusion hepatitis, which yielded a hepatic incidence of 20 cases per 1,000 units of transfused blood. Ninety-two patients had non-A, non-B hepatitis, 3 had hepatitis B and 1 had cytomegalovirus infection. The incubation periods for non-A, non-B hepatitis ranged from 2 to 26 (mean = 9.5 +/- 4) weeks. In 68 (73%) patients, the hepatitis was completely asymptomatic; only 24 (27%) patients developed symptoms, including jaundice and hepatomegaly. There were no cases of fulminant hepatitis. Sixty per cent of the patients still had elevated serum ALT levels 1 year after the onset of hepatitis. The 96 patients with hepatitis had received a mean of 9.6 blood units, as compared to a mean of 6.7 units for the unaffected patients (p less than 0.001). This study demonstrated that non-A, non-B hepatitis remains a common and important complication of blood transfusion despite screening of blood donors for HBsAg and elevated serum ALT levels.

Adolescent↗