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Biomedical subjects

A Craxì

Publications and source records attributed to A Craxì.

At least 19 recordsLinked to original sources
PubMed1998

Long-term course of interferon-treated chronic hepatitis C.

BACKGROUND/AIMS: To evaluate whether sustained response to a-interferon improves clinical outcome in patients with chronic hepatitis C. METHODS: A cohort of 410 consecutive patients (65% with chronic hepatitis, 35% with cirrhosis) were treated with a-interferon in two trials (mean follow-up 62.1 months, range 7-109 months). All were serum HCV RNA positive before therapy and received first 10 then 5 million units of a-2b or a-nl interferon three times weekly for 6 to 12 months. Sustained response was defined as normal aminotransferases 12 months after stopping interferon. RESULTS: Sixty-two patients (15.1%: 54 with chronic hepatitis, eight with cirrhosis) were sustained responders. At the end of follow-up, 56 out of 62 sustained responders (90.3%) were serum HCV RNA negative. No biochemical relapse after 12 months was seen in sustained responders, regardless of initial histology, HCV genotype or persistence of HCV RNA. Although three died of non-hepatic causes, no liver-related events were observed among sustained responders. Complications of liver disease occurred in 34 relapsers/non-responders: nine hepatocellular carcinomas, 21 ascites and four portal hypertensive bleedings. Eleven relapsers/nonresponders died: eight of hepatic and three of non-hepatic causes. Event-free survival was significantly longer in sustained responders than in all the remaining patients. In a regression analysis, sustained response to interferon, low age and absence of cirrhosis were independent predictors of event-free survival. CONCLUSIONS: Hepatitis C virus is probably eradicated and progression of liver disease is prevented in most patients who remain HCV RNA negative with normal transaminases for more than 1 year after stopping treatment.

Adult↗
PubMed1998

Soluble complement receptor type 1 (sCR1) in chronic liver diseases: serum levels at different stages of liver diseases.

Complement receptor type 1 (CR1) is an integral membrane protein of many haematopoietic cells and plays an important role in the clearance of complement-associated immune complexes, favouring their transport to liver and spleen macrophages. A small amount of soluble CR1 (sCR1) is also found in plasma and might originate directly from release of leucocytes and other circulating cells. In previous studies, an increase in serum sCR1 level has been observed in liver cirrhosis and end-stage renal failure. High levels have also been found in patients with some haematologic malignancies. sCR1 serum levels were measured using a specific double sandwich ELISA assay. The present study demonstrates the correlation between mean serum sCR1 concentrations and disease severity in patients with chronic liver disease. In patients with liver cirrhosis, grouped according to the Child-Pugh classification, sCR1 rose as liver function decreased. The presence of neoplastic growth in the liver apparently does not play a role in the increase of sCR1. Serum sCR1 was not elevated in other solid malignancies. Since sCR1 accumulates in liver diseases, evaluation of its serum levels could be useful as a liver function test.

Carcinoma, Hepatocellular↗
PubMed1997

Long-term efficacy of alpha-interferon in beta-thalassemics with chronic hepatitis C.

Hepatitis C virus (HCV) infection is a common cause of liver disease among polytransfused thalassemics. We treated a cohort of subjects with beta-thalassemia major and chronic hepatitis C with alpha-interferon. The aims of the study were to assess the long-term biochemical and virologic efficacy of alpha-interferon and to evaluate the influence of HCV type and liver siderosis on the outcome of therapy. Seventy subjects (mean age, 14.1 years) with chronic HCV infection and abnormal aminotransferases received recombinant alpha-interferon for 12 months and were observed after therapy for at least 24 months. Sixty-three subjects (90%) were HCV-RNA positive at the start of therapy. HCV type 1b was found in 41 subjects (65.1%), non-1b types in 13 (20.6%), and mixed HCV types in 9 (14.3%). Liver biopsy showed cirrhosis in 11 subjects (15.7%) and siderosis grade 3-4 in 24 patients (34.2%). Three patients stopped therapy due to adverse events. Twenty-eight subjects (40%) had normal aminotransferases and had cleared HCV-RNA when last observed (mean follow-up, 36.5 months; range, 25 to 49 months). Of 41 patients who did not normalize aminotransferases, 9 had become HCV-RNA negative at the end of follow-up. The absence of cirrhosis, low liver iron content, and infection with non-1b HCV type were independently associated to complete sustained response upon multivariable analysis. In conclusion, alpha-interferon may induce a sustained virologic and biochemical remission of hepatitis in beta-thalassemic patients with chronic HCV infection and nonadvanced liver disease.

Adolescent↗
PubMed1997

A randomized controlled trial of high-dose maintenance interferon therapy in chronic hepatitis C.

In chronic hepatitis C virus (HCV) infection, the rate of sustained response to interferon is low. We evaluated, in patients responding to a 26-week course of interferon, the effect of high-dose maintenance therapy in preventing relapse. Three hundred and ten patients with chronic HCV infection (38.3% with cirrhosis, 80.6% with HCV type 1) received interferon alfa-2b for 26 weeks (10 MU tiw for 8 weeks, then 5 MU tiw for 18 weeks). One hundred and twenty-four subjects (40%) normalized aminotransferases, and were allocated randomly either to continue on 5 MU tiw for a further 26 weeks (prolonged therapy group: 60 patients) or to stop interferon (brief therapy group: 64 patients). Fifty-two weeks after stopping interferon the overall sustained biochemical response rate was 13.2% (41/310). The number of patients with normal aminotransferases was comparable between the prolonged and brief therapy groups (30% vs. 35.9%, P = n.s.), and the rate of HCV-RNA clearance was similar (48.8% vs. 42.4%, P = n.s.). The timing of posttreatment relapse was not influenced by the duration of therapy. Fifty-nine patients (19%) did not complete therapy due to adverse effects. Multivariate analysis identified four features predicting sustained biochemical response in subjects normalizing aminotransferases under therapy: negative HCV-RNA at end of therapy, normal aminotransferases at 4 weeks of therapy, high baseline aminotransferases, and high baseline platelets. Infection with HCV type 1 was not a significant predictor of response, due to its high prevalence in our population (80.6%). It is concluded that in patients with chronic hepatitis C mostly infected by HCV type 1, a prolonged high-dose interferon course (900 MU over 52 weeks) did not increase the rate of sustained biochemical response and of HCV-RNA clearance in comparison to a brief course (510 MU over 26 weeks).

Adolescent↗
PubMed1997

Decrease in HDV endemicity in Italy.

BACKGROUND/AIMS: To evaluate a possible variation in hepatitis D virus endemicity in Italy, the data from a multicentre study concerning HBsAg chronic carriers first observed in 31 liver units during 1992 were compared with the corresponding figures from a similar study performed in 1987. METHODS/RESULTS: In both studies the methodology for the recruitment of cases was the same. The overall anti-HD prevalence in 1992 was 14.4%, a significantly lower rate than that observed in 1987 (23.4%, p < 0.01). The decrease significantly (p < 0.01) affected both males and females; it occurred in all geographical areas, although to a greater extent in northern regions. It was evident in subjects below 50 years of age, but not in subjects older than 50. A significant reduction in the anti-HD prevalence was seen in all forms of chronic hepatitis. CONCLUSIONS: These findings indicate a lower level of hepatitis D virus endemicity in Italy, probably as a consequence of the reported decreased pool of HBsAg chronic carriers, the reduced size of families, the improved socio-economic conditions and changes in intravenous drug abuser behaviour. All these factors may have affected the strength of hepatitis D virus infection which has greatly reduced the spread of the virus.

Adolescent↗
PubMed1997

Moving towards the optimal treatment of chronic hepatitis C.

Almost 10 years after the first report of the effectiveness of interferon (IFN) for chronic NANB hepatitis, the optimal treatment for chronic hepatitis C is still a matter of debate. The issue of the relative importance of higher doses versus a longer period of therapy remains unsettled, since the long-term response may be a function of the total dose received. Controlled studies have shown that high doses of IFN (5-6 MU t.i.w.), a long period of therapy (> 12 months) and the administration of a large total dose are all associated with a higher cure rate. However, these measures can cause more adverse effects and certainly cost more than the current schedule of 3 MU t.i.w. for a period of 6 months. The standard schedule may be appropriate for subjects with pre-treatment features predictive of a good response (non-Ib genotype, low viraemia, absence of cirrhosis). Alternative treatment schedules or combination therapy with interferon/ribavirin should be considered in subjects with normalized alanine aminotransferase (ALT) levels, but who are still viremic after three months of therapy, as well as in relapsers and in non-responders.

Antiviral Agents↗
PubMed1996

Duration of HCV infection as a predictor of nonresponse to interferon.

Duration of hepatitis C virus (HCV) infection is a key feature in determining responsiveness to interferon (IFN). Studies assessing its value as a predictive factor in chronic HCV infection show that a long duration of infection reduces the likelihood of a sustained response to IFN (defined as ALT normalization and clearance of serum HCV-RNA). The effect of HCV infection duration is independent of the presence of cirrhosis and level of HCV viremia. Meta-analysis of IFN trials in acute HCV infection shows an obvious effect of the drug on long-term ALT normalization and HCV-RNA clearance. Treatment of HCV infection during the acute or early chronic phase could therefore maximize therapeutic effectiveness.

Acute Disease↗
PubMed1996

Interferon as treatment for acute hepatitis C. A meta-analysis.

The efficacy of short-course (three months), low-dose (3 million units three times a week) interferon as treatment for acute hepatitis C was evaluated in a meta-analysis of controlled trials. Nine studies (five randomized and four nonrandomized) found by MEDLINE search were eligible for analysis. The outcomes assessed were the rate of patients with normal serum aminotransferases (all trials) and without HCV RNA in blood (five trials) after posttreatment follow-up. Eight trials compared interferon to no treatment, and one compared different schedules of interferon. The methodological quality of the studies was high. However, all trials had been planned for a short-term evaluation based on biochemical and virological outcomes alone. Significant differences were observed between interferon and control groups for both the assessable end points. Overall rate differences were +0.31 (P < 0.0001; 95% confidence interval +0.20 to +0.41) for aminotransferases normalization and +0.44 (P < 0.0001; 95% confidence interval +0.33 to +0.56) for HCV RNA clearance. In conclusion, a short course of low-dose interferon administered to patients with acute hepatitis C is significantly more effective than no treatment in obtaining viral clearance and normal aminotransferases 12 months after stopping treatment. Further long-term prospective cohort studies assessing outcomes of clinical relevance (ie, the rate of chronicity of infection and disease) are necessary before recommending interferon for acute hepatitis C.

Acute Disease↗
PubMed1996

Transfusion-associated chronic hepatitis C: alpha-n1 interferon for 6 vs. 12 months.

AIMS: To compare the long-term effects of brief and prolonged therapy with alpha-n1 interferon for transfusion-associated chronic hepatitis C. METHODS: One hundred and sixteen subjects (male/female 48/68, mean age 46.9 years) were studied. Sixty patients were randomised to brief treatment (group 1: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 4 months), and 56 to prolonged treatment (group 2: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 10 months). All were followed for 12 months after stopping interferon. RESULTS: The early response rate was 47.4% (Group 1 [45%], Group 2[50%]. No "breakthrough" reactivations were observed. The early response rate was 19% in patients with and 63% in patients without cirrhosis. Twenty-three (19.8%) subjects stopped therapy. Among 54 evaluable early responders, 21 had a sustained response. The rate of sustained response was comparable in group 1 (18.3%) and group 2 (18.2%). All sustained response subjects and some non-responders were HCV-RNA negative at the end of follow-up. Histological improvement was seen only after sustained response. Cirrhosis developed in 20% of non-responders. Overall, interferon induced a long-lasting remission of chronic hepatitis C in about one of every five patients. CONCLUSIONS: In a population predominantly infected by hepatitis C virus type 1, 12 months of therapy with high doses of interferon does not confer any additional benefit on the early response or sustained response rates as compared to a 6-month course.

Adolescent↗
PubMed1996

Interferon and steroid treatment in patients with chronic hepatitis C and antinuclear or anti-liver-kidney microsomal antibodies.

Treatment of HCV-related chronic hepatitis is controversial when non-organ specific autoantibodies are present, due to potential severe autoimmune reactions under interferon. We evaluated, in an open study, a sequential approach (steroid->interferon) in 20 consecutive patients with biopsy-proven chronic hepatitis, anti-HCV positive (EIA2/RIBA2) and autoantibody positive at a titre > or = 1/80 (18 antinuclear and 2 anti-liver-kidney microsomal antibodies). Nine patients responded to steroids (ALT reduced by > or = 50% at 12 weeks) and continued on prednisone up to one year. Notably, ALT did not return to normal and steroid treatment was ineffective in controlling necroinflammation on follow-up biopsies. After stopping prednisone, ALT rebounded to pre-treatment levels in 6/9 cases. Four of these 6 then received interferon: 3 of them had a complete response (e.g. normal ALT at end of therapy), in 2 with loss of HCV RNA. Eleven patients were, instead, steroid resistant and after wash-out were switched to lymphoblastoid alfa-interferon (6 MU t.i.w. for 8 weeks, 3 MU t.i.w. for 16 weeks). Four cases had a complete response to interferon (3 with loss of HCV RNA) with follow-up biopsies showing definite reduction of necroinflammation. None of the 15 receiving interferon in the present study experienced ALT peaks, deterioration of liver disease, autoimmune-like phenomena. We suggest that antiviral treatment with alfa-interferon could be the first choice in chronic hepatitis C, even in autoantibody positive cases.

Adult↗
PubMed1994

Third-generation hepatitis C virus tests in asymptomatic anti-HCV-positive blood donors.

This study evaluated the performance of third-generation anti-HCV assays in blood donors who were positive by second-generation anti-HCV, and assessed any possible relationship between antibody patterns, HCV replication and liver damage. Fifty-two second-generation enzyme immunoassay-positive asymptomatic Italian blood donors were retested for anti-HCV by third-generation enzyme immunoassay and recombinant immunoblot assay (Ortho third-generation enzyme immunoassay, third-generation recombinant immunoblot assay), utilising recombinant C33c and NS5 and synthetic peptide C100 and C22 antigens, and for HCV-RNA by "nested" polymerase chain reaction with 5' region primers. Alanine aminotransferases were tested monthly for 6 months. Two out of 52 second-generation enzyme immunoassay-positive donors were third-generation enzyme immunoassay, third-generation recombinant immunoblot assay and HCV-RNA negative. Among 50 third-generation enzyme immunoassay-positive cases, two had a third-generation enzyme immunoassay optical density < or = 1: one was third-generation recombinant immunoblot assay and HCV-RNA negative, and the other was third-generation recombinant immunoblot assay "indeterminate" and HCV-RNA-positive. The remaining 48 cases had third-generation enzyme immunoassay optical density > 1: six were third-generation recombinant immunoblot assay negative (one HCV-RNA+ve), eight "indeterminate" (two HCV-RNA+ve) and 34 positive (22 HCV-RNA+ve). All "indeterminate" subjects reacted only to C22. HCV-RNA was positive in 22/34 cases with positive third-generation recombinant immunoblot assay (two or more Ags), 3/9 "indeterminate" and 1/11 negative. Alanine amino-transferases were abnormal in 13 cases with positive third-generation recombinant immunoblot assay, one was "indeterminate" and three were negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A multicenter randomized controlled trial of recombinant interferon-alpha 2b in patients with acute transfusion-associated hepatitis C.

To assess whether interferon-alpha might prevent non-A, non-B hepatitis from becoming chronic, 45 consecutive patients with transfusion-associated hepatitis were enrolled in a randomized clinical trial. Thirty-eight patients had hepatitis C virus infection, and 7 had non-A, non-B, non-C hepatitis. Twenty-six patients (22 with HCV) were given 3 MU of recombinant interferon-alpha 2b three times a week for 12 wk, whereas 19 (16 with HCV) were not. Biochemical and virological parameters were monitored at regular intervals during an 18-mo follow-up. At the end of the 3-mo therapy, 16 (73%) patients with hepatitis C had normal serum ALT activity, compared with 7 (44%) who were not treated (NS). Fifty-three percent of the treated patients and none of the untreated patients had normal ALT levels and no HCV RNA (p = 0.0087). At the end of the 18-mo follow-up, 13 (59%) treated patients had normal ALT levels, compared with 6 (37%) untreated controls (NS). Thirty-nine percent had normal ALT and no HCV RNA, compared with none of the controls (p = 0.035). Four patients (22%) had had sustained complete responses to interferon, defined as normal ALT levels and no HCV RNA at the end of the 3-mo treatment period and the 18-mo follow-up period. All seven patients with non-A, non-B, non-C hepatitis, treated and untreated, recovered uneventfully from hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Interferon treatment in patients with chronic hepatitis B: a meta-analysis of the published literature.

The randomised clinical trials testing the effectiveness of interferon treatment on Chronic Hepatitis B patients were reviewed by means of meta-analysis. Twenty-two trials, published between 1987 and 1990, have identified where 1290 adult patients had been studied. Overall, interferon increased the rates of serum HBV-DNA clearance and amino-transferases normalization about 3 times at one year. However, when an analysis of internal consistency, clinical relevance and methodology of these studies was made, the trials were not sufficient to confirm the clinical effectiveness of the treatment since they had been planned for short-term assessment based on biochemical and viral end points alone. The link of these end points to other outcomes of more obvious clinical relevance (i.e. evolution to cirrhosis or deterioration of cirrhosis, death) is, in fact, questionable and thus the value of a meta-analysis based on currently available trials is uncertain as a source for practical guidelines. We conclude that the effectiveness of interferon in patients with chronic hepatitis B has yet to be confirmed by long-term prospective studies which assess the outcome by clinically meaningful end points such as cirrhosis, liver failure, or death.

Adolescent↗
PubMed1993

Immunoblotting as a confirmatory test for antimitochondrial antibodies in primary biliary cirrhosis.

Primary biliary cirrhosis is characterised by the presence of antimitochondrial antibodies which are directed against components of mitochondrial dehydrogenase complexes. The specificity of antimitochondrial antibodies for primary biliary cirrhosis as detected by immunoblotting was investigated. Commercially available preparations of pyruvate and oxo-glutarate dehydrogenases and beef-heart mitochondria were used as source of antigens. Sera from 47 primary biliary cirrhosis patients (46 of whom were antimitochondrial antibody positive by immunofluorescence), 16 non-primary biliary cirrhosis patients (antimitochondrial antibody positive by immunofluorescence), 23 liver-kidney microsomal antibody positive chronic active hepatitis patients, and 32 patients with connective tissue diseases were examined. Of the 47 subjects with primary biliary cirrhosis, 43 (91%) and 13 (28%) tested positive by immunoblotting for pyruvate and oxo-glutarate dehydrogenase, respectively. Only three primary biliary cirrhosis patients were negative for both antigens, including the only one shown to be antimitochondrial antibody negative by immunofluorescence. The other two patients were positive by immunoblotting with beef-heart mitochondria. In contrast, only three of 16 (19%) non-primary biliary cirrhosis patients who were antimitochondrial antibody positive by immunofluorescence tested positive by immunoblotting (for both pyruvate dehydrogenase and beef-heart mitochondria). None of the 23 liver-kidney microsomal antibody positive and the 32 patients with rheumatic diseases were positive by immunoblotting with any antigen. Our data show that immunoblotting with commercially available oxo-acid dehydrogenases is a reproducible method for the detection of antimitochondrial antibodies highly specific for primary biliary cirrhosis.

Adult↗