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Biomedical subjects

G Bellati

Publications and source records attributed to G Bellati.

At least 37 records · Page 2Linked to original sources
PubMed1995

Emergence of hepatitis B virus S gene mutant in a liver transplant recipient.

Immunological and genomic analysis of the "a" determinant was carried out in seven patients with concurrent HBsAg and anti-HBs, four of whom were immunized against hepatitis B virus at liver transplant, two with histologically characterized chronic hepatitis B virus infection, and one HBsAg healthy carrier. The immune reactivity of the HBsAg "a" determinant was evaluated by binding to specific monoclonal antibodies, and the corresponding genomic sequence was studied by differential hybridization in microtiter plates and nucleotide sequence analysis. A double mutation generating an amino acid change (glycine to lysine) at residue 145, able to impair recognition by monoclonal antibodies, was observed in the post-transplant serum from one patient. No significant alteration of the "a" determinant sequence or reactivity was detected in the other patients. Amino acid residue 145 appears therefore to be critical for the recognition by anti-HBs antibodies. A previously undescribed glycine to lysine substitution at this level interferes with the immune reactivity of the "a" determinant.

Amino Acid Sequence↗
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

Fluctuations in viremia, aminotransferases and IgM antibody to hepatitis B core antigen in chronic hepatitis B patients with disease exacerbations.

We studied the relationships between the serum levels of viremia, aminotransferases and IgM anti-HBc, measured by monthly quantitative assays, in 52 untreated chronic hepatitis B patients (41 anti-HBe+, 11 HBeAg+) followed up for 12-20 months. Forty hepatitis exacerbations were observed in 17/41 anti-HBe+ (41.5%) and in 6/11 HBeAg+ patients (54.5%) (p = NS); all but one were clinically asymptomatic. We analyzed the fluctuations in the serum levels of the three parameters before, during and after the hepatitis exacerbations and found this chronological sequence of events in 96.2% of them: HBV-DNA increase-->ALT flare-->IgM anti-HBc increase. These results suggest that both antiviral immune reactions and ALT flares were triggered by quantitative variations in viremia. HBV-DNA baseline levels before flares were lower in anti-HBe+ (3.9 +/- 1.2 pg/ml) than in HBeAg+ patients (35.3 +/- 5.4 pg/ml) (p < 0.0001) and there was an inverse correlation between basal values and viremia level increases at the time of disease exacerbations (p < 0.001). This suggests that for a hepatitis exacerbation to occur, low basal viremia needed to increase markedly, while moderate increases in HBV-DNA serum levels were sufficient to trigger ALT flares in patients with elevated basal viremia. In conclusion, asymptomatic hepatitis B exacerbations are frequent in the natural history of chronic HBV infection, and monthly monitoring of HBV-DNA, ALT and IgM anti-HBc appears to be a suitable method to evaluate their frequencies and entities. This method can be a helpful guide for clinical and therapeutic decision-making in the single patient with chronic hepatitis B.

Adult↗
PubMed1994

The role of transplantation in small hepatocellular carcinoma complicating cirrhosis of the liver.

Of 176 hepatic transplants performed from 1986 to December 1992, 27 patients had small hepatocellular carcinoma (< or = 5 centimeters) complicating cirrhosis of the liver. All patients were asymptomatic for the hepatic malignancy and the diagnosis was established in each instance preoperatively by means of serial sonographic scans and alpha-fetoprotein levels. Cirrhosis was classified as Child's A in eight instances, as Child's B in 16 and Child C's in three. The cause was alcoholic in three patients, posthepatitic in 21 patients (eight hepatitis B virus [HBV] positive and 13 hepatitis C virus [HCV] positive) and undetermined in three. The in-hospital mortality rate was 11 percent (three of 27). Additionally, five patients died at different intervals after transplantation: only two died of neoplastic recurrence at 12 and 32 months, respectively (7.4 percent rate). Actuarial survival rates were 82 percent at one year and 71 percent at three years, with a mean follow-up period of 32 months (range six to 78 months). Morbidity related to the procedure was a relevant problem: 21 percent of the patients had prompt resumption of normal life while 37 percent required repeated hospitalization and 42 percent required strict control on an outpatient basis. The most frequent problem was HBV or HCV reinfection of the grafted liver, which occurred in 42 percent. Based on this experience, transplantation of the liver has shown an excellent oncologic accuracy for small hepatocellular carcinoma in cirrhosis of the liver, thus representing the most rational surgical procedure for patients with Child's B and Child's C cirrhosis classification. The relevant mortality and morbidity rates, strictly related to this procedure, suggest other options as more appropriate in those with Child A cirrhosis at this time.

Actuarial Analysis↗
PubMed1993

Role of IgM antibody to hepatitis B core antigen in the diagnosis of hepatitis B exacerbations.

IgM anti-HBc levels were measured by the IMx Core-M Abbott assay in 939 serum samples in order to define a specific and sensitive cut-off value for diagnosis of chronic hepatitis B. The sera used were obtained from 52 chronic HBV patients and 10 HBV carriers with HCV or HDV co-infections and 155 asymptomatic subjects without evidence of liver disease. A Youden index value of 95.4% with 98% sensitivity and 97.4% specificity was obtained for an IMx Index value of 0.204 as cut-off. A one-year follow-up study with monthly tests has shown that quantitative analysis of IgM anti-HBc can serve as a noninvasive tool for monitoring HBV infection, and provides an accurate diagnosis of hepatitis B exacerbations. Significant elevations of IgM anti-HBc levels were associated with hepatitis B exacerbations in 96.2% of the cases but with none of the ALT flare-ups observed in HCV or HDV infected individuals. These results suggest that quantitative analysis of IgM anti-HBc provides the highest degree of confidence in definition of spontaneous and therapy-induced exacerbations or remissions of hepatitis B.

Adolescent↗
PubMed1993

Antibodies developing against a single recombinant interferon protein may neutralize many other interferon-alpha subtypes.

Three hepatitis C patients out of 15 who received recombinant interferon-alpha 2a (rIFN-alpha 2a) therapy developed high levels of neutralizing antibody coincident with clinical relapse. On analysis, antibodies in their sera were found to also produce some neutralization of lymphoblastoid IFN. Purified lymphoblastoid IFN was separated chromatographically into 10 fractions, each containing one or two IFN-alpha subtypes, and these were used individually to examine the subtype specificity of the neutralizing antibodies in the patients' sera. All three sera neutralized all the subtypes present in the 10 lymphoblastoid IFN fractions. These findings may explain why some patients who develop antibody-mediated resistance to treatment with rIFN-alpha 2 preparations are unable to respond again when treated instead with a human cell derived preparation containing many IFN-alpha subtypes.

Antibody Specificity↗
PubMed1993

Problems in diagnosing viral hepatitis.

The most reliable method of making a specific aetiological diagnosis of chronic viral hepatitis would be to identify virus specific cytotoxic T lymphocytes responsible for the killing of virus infected hepatocytes in each patient's liver. Unfortunately, this can not be proposed for routine diagnosis and surrogate tests are required. The detection of virus markers, and even of the virus itself, does not imply that liver damage is caused by virus infection. Indirect markers of the host's antiviral immunoresponse have to be used to confirm more specifically the diagnosis of viral hepatitis. IgM antibodies against viral antigens implicated in the elimination of the virus seem to be suitable alternative candidates. Significant changes in the serum values of viraemia and aminotransferases occur within a few days, while a significant variation in liver histology takes much longer. Only the kinetics of the highly variable parameters can be used for an appropriate study of the relationship between viraemia, antiviral immunoresponse, and liver cell necrosis. Quantitative and dynamic analyses of hepatitis virus markers seem the most suitable and reliable methods of monitoring the patients eligible for antiviral treatment and identifying the most appropriate time to start this.

Antibodies, Viral↗
PubMed1991

Fibronectin, cholesterol and triglycerides ascitic fluid concentration in the prediction of malignancy.

There have been few trials comparing the efficacy of determinations of cholesterol, fibronectin and triglycerides for diagnosis of malignant ascites. In this study we measured these in 200 ascitic fluids from 93 cirrhotic patients (Group A), 47 hepatocellular-carcinoma patients (Group B), 60 extra-hepatic tumour patients (Group C), 44 of them with malignant cells (Group Cpos) and 16 without (Group Cneg). Anova one-way and the Bonferroni test for multiple comparisons showed that fibronectin and cholesterol were significantly higher in the ascitic fluids of patients of group C than of groups A and B (mean +/- ESM) (Cholesterol in A: 27.2 +/- 2.8; in B 23.5 +/- 1.5; in C: 68.6 +/- 5.3 mg/dl. Fibronectin in A: 32.7 +/- 2.8; in B 31.3 +/- 2.6; in C 127.7 +/- 11.1 mg/l). Both were significantly higher in Group Cpos than in Group Cneg (Cholesterol in Cneg: 41.2 +/- 6.7; in Cpos: 78.6 +/- 6.2 mg/dl. Fibronectin in Cneg: 55.0 +/- 11.2; in Cpos 154 +/- 12.3 mg/dl). We found no differences between cirrhotic ascites and malignant ascites due to primary liver hepatocellular-carcinoma. No difference at all in triglycerides were detected. With the Receiver-Operating Characteristic (ROC) curve, cholesterol had the best Youden Index (57%) at a cut-off of 32 mg/dl (sensitivity 78.3%, specificity 79.3% at this level); the best Youden Index (64%) for fibronectin had a cut-off of 60 mg/dl (sensitivity 65%, specificity 89.3%). Triglycerides appeared to be a great deal less effective as a diagnostic marker, with their best Youden Index (23%) at a cut-off 32 mg/dl (sensitivity 66.7%, specificity 56.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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↗