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P Almasio

Publications and source records attributed to P Almasio.

At least 37 records · Page 2Linked to original sources
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

Prognostic value of the galactose test in predicting survival of patients with cirrhosis evaluated for liver transplantation. A prospective multicenter Italian study. AISF Group for the Study of Liver Transplantation. Associazione Italiana per lo Studio del Fegato.

AIMS/METHODS: The present study aimed to examine whether the galactose elimination capacity can be used to predict the survival of patients with advanced liver disease. We studied 194 patients with cirrhosis, belonging to Child class B and C, for 2 years each. RESULTS: The overall probability of survival was 79% at 6 months, 72% at 1 year and 62% at 2 years. Variables significantly associated with the duration of survival, as assessed by univariate analysis, were the Child-Pugh score, presence of ascites, size of esophageal varices, prothrombin time, albumin, bilirubin, urea, creatinine, glucose and galactose elimination capacity. By a multivariable analysis, only Pugh score (p = 0.005), creatinine (p < 0.001), varices (p = 0.001) and galactose elimination capacity (p < 0.001) were independent predictors of mortality. The galactose elimination capacity was even more sensitive when the end-point was limited to deaths due to liver failure and hepatorenal syndrome. A new score obtained by summing the Pugh score with a score derived from galactose elimination capacity was quite simple and accurate for predicting survival. CONCLUSIONS: The quantitative measurement of liver function as the galactose elimination capacity could be of use to identify patients with cirrhosis and probable short survival who might benefit most from urgent transplantation.

Adolescent↗
PubMed1996

HCV viraemia is more important than genotype as a predictor of response to interferon in Sicily (southern Italy).

BACKGROUND/AIMS: To investigate host- and virus-related factors predictive of early and sustained alanine aminotransferase normalization after interferon therapy for HCV-related chronic liver disease, in an area where genotype 1 is highly prevalent. METHODS: We studied 100 patients with HCV-RNA positive chronic liver disease (73 chronic hepatitis and 27 cirrhosis) undergoing alpha-interferon treatment. Thirty-four patients had an early response but relapsed, 15 patients remained into sustained response for at least 12 months after therapy, and 51 patients did not respond. Serum HCV-RNA levels were assessed by bDNA (Chiron), and genotype by LiPA (Innogenetics) and by sequencing of the 5' non-coding region. RESULTS: Mean pre-treatment HCV-RNA level (x 10(3) genome equivalents/ml +/- SD) was lower in sustained responders (3854 +/- 7142) than in relapsers (9587 +/- 10163) or in non-responders (5709 +/- 6618). HCV subtype 1b was highly prevalent (82%), while types 1a, 2a, 3 and 4 were rare (about 5% each). However, the prevalence of 1b was much lower (31%) under 40 years of age. The prevalence of subtype 1b among sustained responders (74%) was similar to that observed among relapsers (82%) or non-responders (84%), but some nucleotide substitutions in the putative RNA loop of the 5' non-coding region were seen only among relapsers or non-responders. Multiple logistic regression model showed that early response to interferon was predicted by absence of cirrhosis and a pre-treatment HCV-RNA level below 350. Sustained response to interferon was predicted by pre-treatment HCV-RNA level below 350 and a low fibrosis score. CONCLUSIONS: Among patients with hepatitis C from an area where subtype 1b is highly prevalent, absence of cirrhosis and low pre-treatment serum HCV-RNA level are the most important predictors of response to IFN. Some nucleotide substitutions found in the 5' non-coding region of subtype 1b are associated with non-response or relapse.

Adult↗
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↗
PubMed1995

Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis.

To examine the morbidity of compensated cirrhosis type B, a cohort of 349 Western European, white patients (86% men; mean age, 44 years) with biopsy-proven cirrhosis was followed up for a mean period of 73 months and was studied for occurrence of hepatocellular carcinoma (HCC) and decompensation. At entry into the study all patients were tested for hepatitis B e antigen (HBeAg; 34% of patients were HBeAg-positive) and antibody to hepatitis delta virus (anti-HDV; 20% of patients were anti-HDV-positive); 48% of 252 patients tested were hepatitis B virus (HBV)-DNA-positive. During follow-up HCC developed in 32 (9%) of the 349 patients and decompensation was observed in 88 (28%) of 317 tumor-free patients. Five years after diagnosis, the probability of HCC appearance was 6% and the probability of decompensation was 23%. After the first episode of decompensation the probability of survival was 35% at 5 years. Cox's regression analysis identified three variables that independently correlated with HCC: age, serum levels of platelets, and liver firmness on physical examination. HBV (HBeAg or HBV-DNA) and HDV (anti-HDV) markers at presentation had no prognostic value for the development of HCC. In conclusion, a high proportion of patients with HBsAg-positive compensated cirrhosis do not experience worsening of their condition for several years, but once decompensation occurs life expectancy is poor. European, white patients with compensated cirrhosis type B are at consistent risk for HCC. Prognostic factors for HCC reflect an advanced stage of cirrhosis and support the hypothesis that development of a tumor could be the likely consequence of long-standing hepatic disease.

Aged↗
PubMed1994

Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. The Investigators of the European Concerted Action on Viral Hepatitis (EUROHEP).

A multicenter longitudinal study was performed to assess the survival of hepatitis B surface antigen positive compensated cirrhosis, primarily in relation to hepatitis B virus replication and hepatitis delta virus infection, and to construct a prognostic index based on entry characteristics. This cohort study involved nine university medical centers in Europe. Three hundred and sixty-six Caucasian HBsAg positive patients with cirrhosis who had never had clinical manifestations of hepatic decompensation were enrolled and followed for a mean period of 72 months (6 to 202 months). Inclusion criteria were biopsy-proven cirrhosis, information on serum hepatitis B e antigen and antibody to hepatitis D virus at the time of diagnosis and absence of complications of cirrhosis. At entry 35% of the patients were HBeAg positive, 48% of the patients tested were HBV-DNA positive and 20% anti-HDV positive. Death occurred in 84 (23%) patients, mainly due to liver failure (45 cases) or hepatocellular carcinoma (23 cases). The cumulative probability of survival was 84% and 68% at 5 and 10 years, respectively. Cox's regression analysis identified six variables that independently correlated with survival: age, albumin, platelets, splenomegaly, bilirubin and HBeAg positivity at time of diagnosis. According to the contribution of each of these factors to the final model, a prognostic index was constructed that allows calculation of the estimated survival probability. No difference in survival of hepatitis D virus infected and uninfected patients was observed. Termination of hepatitis B virus replication and/or biochemical remission during follow up correlated with a highly significant better survival. These data show that in compensated cirrhosis B, hepatitis B virus replication, age and indirect indicators of poor hepatic reserve and established portal hypertension significantly worsen the clinical course of the disease, whereas hepatitis D virus infection does not influence the prognosis. The highly significant improvement in life expectancy following cessation of hepatitis B virus replication and biochemical remission favors antiviral therapy in those patients with a guarded prognosis, as estimated by a prognostic index.

Adult↗
PubMed1994

Interferon-alpha for chronic hepatitis C: an analysis of pretreatment clinical predictors of response.

To identify predictors of short-term and sustained ALT normalization after interferon treatment in adult patients with chronic hepatitis C, we performed a meta-analysis of individual patients' data, with construction and cross-validation of a prediction rule, in 361 patients from two randomized trials. In one trial, 116 subjects with transfusion-related chronic hepatitis C were treated with lymphoblastoid interferon (5 MU/m2 three times a week for 2 mo, then 3 MU/m2 three times a week for 4 or 10 mo). In the other study, 245 patients with community-acquired chronic hepatitis C received recombinant interferon-alpha 2b (10 MU three times a week for 2 mo, then 5 MU three times a week for 4 mo; then random allocation of subjects with normal aminotransferase levels to stop or continue interferon for a further 6 mo). Overall, 164 subjects (45%; 95% confidence interval, 40% to 50%) had short-term responses; 61 (18%; 95% confidence interval, 14% to 22%) maintained sustained responses. Sixty patients (17%; 95% confidence interval, 13% to 21%) withdrew from treatment because of side effects or subjective intolerance. Logistic regression analysis showed that short-term and sustained response were independently predicted by lobular structure on pretreatment liver biopsy (p < 0.0001) and by short disease duration, defined as the time elapsed since transfusion in posttransfusion cases or since the first observation of abnormal aminotransferase levels in cryptogenic disease (p < 0.01). Rules to predict short-term and sustained response to interferon were derived from these items, showing a discriminatory ability of 0.73 and 0.70.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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

Alpha interferon treatment of chronic hepatitis C in beta-thalassaemia.

In this open, pilot study, interferon (IFN) alpha-2b seemed effective in the treatment of hepatitis C virus (HCV) infection in patients with beta-thalassaemia. In seven of nine patients who completed the study alanine aminotransferase activities returned to normal, and a completely stable response 24 months after treatment was seen in five. Liver biopsy specimen showed a clear reduction in portal, periportal, and lobular necroinflammation in all five cases. Three patients stopped treatment early because of side effects.

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↗
PubMed1993

[Ademetionine: the state of the art and future prospects].

Ademethionine is a biological molecule mostly produced in the liver and involved in several metabolic pathways. Two of them, the transmethylation and the transulfuration pathways, are particularly important for the physiological activity of the hepatocyte. The first one is responsive for the methylation of membrane phospholipids, a reaction which restores the membrane fluidity and therefore allows a normal and correct role of the hepatocyte. The transulfuration pathway leads to the synthesis of compounds such as glutathione and taurine, which are involved in detoxication processes. Patients with liver diseases of different etiology, and especially patients with chronic diseases, have endogenous ademethionine deficiency. This leads to a malfunctioning of the hepatocyte, which ends up to be damaged in its structure and normal activity. Besides the overplus of methionine, not used for the synthesis of ademethionine, gives rise to high plasma levels of the amino acid. The pharmacological supply of ademethionine enhances the two metabolic pathways and avoids the overplus of methionine. The regeneration of transmethylation and transulfuration restores the normal secretory and excretory activity of the liver cell, and therefore leads to a resolution of cholestasis and removal of toxic compounds from liver parenchyma and plasma. Several experimental and clinical studies have shown the therapeutic efficacy and tolerability of ademethionine in hepatopathic patients with cholestasis. Preliminary experimental data suggest for ademethionine not only an anticholestatic effect, but possibly an anti-fibrotic one.

Chronic Disease↗