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Biomedical subjects

M Buti

Publications and source records attributed to M Buti.

At least 55 records · Page 3Linked to original sources

[One year treatment with lamivudine in different hepatitis B virus related hepatic diseases].

BACKGROUND: Three month administration of lamivudine in patients with chronic hepatitis B produces a transitory inhibition of the DNA of the hepatitis B virus (HBV). AIM: The aim of this study was to evaluate the efficacy and safety of one year treatment with lamivudine in patients with chronic hepatitis B and liver transplantation (LTx) with recurrence of HBV infection. PATIENTS AND METHODS: Sixteen patients with chronic hepatitis B, 4 patients with decompensated hepatic cirrhosis and 4 patients having undergone LTx with recurrence of HVB infection were treated with the oral administration of 100 mg/day of lamivudine for one year. RESULTS: At 3 months of treatment, the HBV-DNA became negative in 94% of the cases of chronic hepatitis B, in 10% of those with decompensated hepatic cirrhosis and in 100% of the cases of LTx. At one year of treatment, the HBV-DNA was negative in 81% of the chronic hepatitis B, in 100% of the decompensated cirrhotics and in 100% of the LTX cases which survived. The tolerance to treatment was excellent in all the cases. In 34% of the cases, mutations were observed in the gene of the polymerase DNA at one year of treatment. CONCLUSIONS: Lamivudine produces intense, rapid inhibition in viral replication not only in chronic hepatitis B but also in cases of decompensated cirrhosis or recurrence following liver transplantation. Around 30% of the patients undergoing one year of treatment with lamivudine developed gene mutations of the HBV polymerase.

Adult↗

[Interferon treatment of chronic viral hepatitis in Catalonia, Spain. Retrospective analysis].

AIM: To analyze the results of interferon treatment in chronic hepatitis B and C in Catalonia, Spain, during the first two years of the Assessment Board of the therapeutic use of interferon. MATERIAL AND METHODS: A retrospective analysis of the results of 2,142 applications for interferon treatment for chronic hepatitis B (n = 158) and C (n = 1,970) from January, 1993 to December, 1994 presented to the Interferon Assessment Board, was performed by the study of the data of the applications-questionnaires send by the applying physicians. RESULTS: The global rate of response to the questionnaires was of 85%. For chronic hepatitis C, three treatment schedules were evaluated included 936 cases out of the 1,931 authorizations. A sustained response was observed in 20% of the cases treated with 3 MU of interferon for 6 months, in 32% of those treated over 12 months and 20% of those treated with 5-6 MU of interferon for 6 months. The patients with chronic hepatitis B were divided into 2 groups in relation to the presence or absence of HBeAg. Of the 153 applications, 34 belonging to HBeAg positive patients and 52 anti-HBe positive patients who received interferon treatment at 5-10 MU three times per week for 4-6 months were evaluated. Sustained response was observed in 44% of the chronic hepatitis HBeAg positive cases and in 25% of the anti-HBe cases treated. In general, response to treatment was higher in females and in those subjects under the age of 40 years than in male and in older subjects. No differences were observed in the response among the different types of interferon. Withdrawal from treatment due to adverse effects or because of the patient's wish was similar among the patients with chronic hepatitis B (5%) and C (3%), being higher in those undergoing treatment for a longer period of time. CONCLUSIONS: The data obtained from the Interferon Assessment Board for the treatment of viral hepatitis demonstrates the use of very variable schedules of this drug, especially in chronic 85% and complete evaluation was achieved in 54% of the chronic hepatitis B and in 48% of the cases of chronic hepatitis C.

Adult↗

Transient emergence of hepatitis B variants in a patient with chronic hepatitis B resistant to lamivudine.

BACKGROUND: Lamivudine is a cytosine nucleoside analogue that inhibits hepatitis B virus replication. Resistance to lamivudine monotherapy has been reported in patients who received lamivudine to prevent recurrent hepatitis B virus infection after liver transplantation. No cases of resistance have been described in patients who did not clear HBV DNA during lamivudine therapy. METHODS: We report the case of an adult patient with chronic HBeAg-positive hepatitis B who had a hepatitis flare during lamivudine therapy. The patient did not respond to lamivudine and, at 4 months of treatment, developed a significant serum alanine aminotransferase elevation. Alanine aminotransferase levels remained elevated for 4 months and returned to baseline spontaneously. Lamivudine therapy was administered for 1 year (52 weeks) and after withdrawal, alanine aminotransferase levels remained elevated. RESULTS: Sequencing studies of HBV DNA at week 52 showed the emergence of a lamivudine-resistant variant associated with two point mutations in the hepatitis B virus polymerase gene: one mutation led to amino acid substitution of methionine to valine at residue 552, in the highly conserved tyrosine-methionineaspartate-aspartate motif, part of the active site of the polymerase; the second mutation consisted of a substitution of leucine to methionine at residue 528. At week 54 of follow-up, both mutations were undetectable. CONCLUSION: This observation demonstrates the transient emergence of HBV variants in the course of therapy in a patient resistant to lamivudine therapy.

Adult↗

Hepatitis delta genotypes in chronic delta infection in the northeast of Spain (Catalonia).

BACKGROUND/AIMS: Based on genetic analysis of variants obtained around the world, three genotypes of the hepatitis delta virus have been defined. Hepatitis delta virus variants have been associated with different disease patterns and geographic distributions. To determine the prevalence of hepatitis delta virus genotypes in the northeast of Spain (Catalonia) and the correlation with transmission routes and clinical disease, we studied the nucleotide divergence of the consensus sequence of HDV RNA obtained from 33 patients with chronic delta hepatitis (24 were intravenous drug users and nine had no risk factors), and four patients with acute self-limited delta infection. METHODS: Serum HDV RNA was amplified by the polymerase chain reaction technique and a fragment of 350 nucleotides (nt 910 to 1259) was directly sequenced. RESULTS: Genetic analysis of the nucleotide consensus sequence obtained showed a high degree of conservation among sequences (93% of mean). Comparison of these sequences with those derived from different geographic areas and pertaining to genotypes I, II and III, showed a mean sequence identity of 92% with genotype I, 73% with genotype II and 61% with genotype III. At the amino acid level (aa 115 to 214), the mean identity was 87% with genotype I, 63% with genotype II and 56% with genotype III. Conserved regions included the RNA editing domain, the carboxyl terminal 19 amino acids of the hepatitis delta antigen and the polyadenylation signal of the viral mRNA. CONCLUSIONS: Hepatitis delta virus isolates in the northeast of Spain are exclusively genotype I, independently of the transmission route and the type of infection. No hepatitis delta virus subgenotypes were found, suggesting that the origin of hepatitis delta virus infection in our geographical area is homogeneous.

Adolescent↗

[Cost effectiveness of the treatment of chronic hepatitis C with interferon-alpha].

The purpose of this study was to assess the cost-effectiveness of the treatment of chronic hepatitis C with interferon in Spain. Disease progression was studied using a Markov model through which an untreated cohort of 1000 patients was compared with cohorts treated with interferon 3 MU three times per week for 6, 12 or 18 months. Treatment cost, patients quality of life, and survival were the parameters evaluated. Using the perspective of the National Health System, an 18 month treatment with alfa interferon offers a better cost-effectiveness ratio than a treatment of 6 or 12 months duration. The age of the patient at the start of treatment is one of the most influential factors on the cost-effectiveness of treatment. In patients under 45 years of age, a net cost saving is observed with all treatment schedules, especially with 18 months treatment, due to significant reductions in severe complications of disease progression. In patients aged 45-60, 18 months treatment incurs a net cost, although important gains are made in survival and quality of life. In patients over 65 years of age, the economic benefits of prolonged treatment do not compensate the extra cost. In conclusion, treatment of chronic hepatitis C with alfa interferon should begin as early as possible, especially in young patients. In cases of favourable response, treatment should be extended to 18 months, in order to obtain a higher rate of sustained response, avoid progression of hepatic disease and achieve a more favourable cost-effectiveness ratio.

Adult↗

[Study of HLA-II antigens in chronic hepatitis C and B and in acute hepatitis B].

The aim of this study was to analyze the variability of the HLA-II system in a series of patients with chronic hepatitis B, chronic hepatitis C and acute hepatitis B to know whether there is any relationship between the polymorphism of the HLA system, the different types of hepatitis and the evolution of the infection. HLA-II antigens were determined by a PCR technique in serum samples of 24 controls, 22 cases of chronic hepatitis C, 38 cases of chronic hepatitis B and 11 with acute hepatitis B. The prevalence of the HLA-DR4 antigen was lower in the cases of chronic hepatitis B (10.5%) and C (13.6%) than in the controls (33.3%), particularly the DRB1*0401 allele (p = NS). The prevalence of HLA-DR6 was similar in chronic hepatitis B (42.1%) and acute hepatitis B (45.5%). Predominance of the DRB1*1301 and DRB1*1302 alleles were, however, observed in acute hepatitis B (36.4%) versus chronic hepatitis B (13%). These data suggest that immunologic factors such as HLA antigens may influence in the susceptibility to infection by HBV and HCV. The use of PCR techniques which discriminate between the different alleles of the HLA antigens may provide better knowledge of the immune response.

Acute Disease↗

Chronic delta hepatitis: is the prognosis worse when associated with hepatitis C virus and human immunodeficiency virus infections?

Eighty-six patients were followed for 6.5 years to study the epidemiological, virological, and histological course of chronic delta hepatitis and the relationship of this disease with HIV and HCV infection. Patients were classified into four groups according to simultaneous HCV and/or HIV infection: group 1, HDV infection (20 cases); group 2, HDV and HCV infection (11 cases); group 3, HDV and HIV infection (12 cases), and group 4, HDV, HCV, and HIV infection (43 cases). All but 14 patients were asymptomatic at presentation. Liver histology showed chronic active hepatitis in 53 cases and cirrhosis in 19 cases. During followup, 52 patients remained asymptomatic, 34 developed hepatic dysfunction, 28 died, and 1 received a liver transplant. Among the 28 patients who died, 4 had HDV infection; 3 HDV and HCV infection; 3 HDV and HIV infection; and 18 HDV, HCV, and HIV infection. Death was due to liver failure in 16 (57%), AIDS in 10 (36%), and was unrelated to liver disease in 2 (8%) cases. There results demonstrate that chronic delta hepatitis is a severe disease, especially among drug users with HIV and HCV infection. The high morbidity and mortality of chronic delta hepatitis justifies the use of antiviral therapy to modify the natural course of the disease.

Adolescent↗

Interferon vs. adenine arabinoside 5'-monophosphate in patients with anti-HBe-positive chronic hepatitis.

Anti-HBe-positive patients with precore mutants may have severe, progressive liver disease. Therapy with interferon has been effective, but relapses are frequent. To evaluate and compare two antiviral treatments, lymphoblastoid interferon (ly-IFN) and adenine arabinoside 5'-monophosphate (ARA-AMP), 20 patients with anti-HBe-positive chronic hepatitis (5 cirrhosis and 15 CAH) and viral replication (HBcAg in the liver and HBV DNA in serum) were treated. Patients were randomized into two groups: 11 patients received ARA-AMP, 5 mg/kg/day during 7 weeks, and 9 received human ly-IFN, 5,000,000 units, three times per week, during 4 months. Baseline clinical, biochemical and histological features were not significantly different between the two groups. At the end of therapy, 8 (89%) patients in the interferon group and 5 (45%) in the ARA-AMP group showed normal ALT levels and no HBV DNA in serum by a liquid hybridization assay (P < 0.05). At 1 year of follow-up, a persistent response was observed in 33% of ly-IFN patients and in 27% of ARA-AMP patients, a transient response in 56% and 18%, and nonresponse in 11% and 55%, respectively. HBV DNA remained detectable by polymerase chain reaction (PCR) in 19 of the 20 patients. Among the responders, an improvement in histological lesion and the disappearance of intrahepatic HBcAg were observed; in the nonresponders, histological lesion remained stable or worsened. In conclusion, the efficacy of interferon and ARA-AMP was similar in treating anti-HBe-positive chronic hepatitis. Although interferon treatment led to initial improvement in a larger number of patients, there was a much higher rate of relapses with this drug.

Adult↗

Electrophysiological evaluation of spinal reflexes during epidural anesthesia in an experimental model.

We assessed the effects of epidural anesthesia with bupivacaine in the rat by serial recordings of spinal reflexes. The H wave from plantar muscles after electrical stimulation of the sciatic nerve evaluates a large nerve fiber spinal reflex arch. The extensor reflex response recorded from quadriceps muscle after stimulation of the contralateral tibial nerve assesses a reflex arch with small fiber afferents. After epidural injection of 0.2 mL of bupivacaine (0.25%, 0.5%, and 1.0% solutions) at the L5-L6 vertebral space, nociceptive, H, and extensor reflex responses were abolished within 1-3 min. Duration of complete blockade lasted 20-80 min, increasing with the anesthetic concentration, and complete recovery occurred after an additional period of 30-40 min. The responses recovered to amplitudes similar to preanesthesia controls, indicating that there was no damage to the nervous system. This study shows that electrophysiological recording and quantitation of nerve reflex responses is a useful and accurate method to evaluate the efficacy of local anesthetic agents.

Anesthesia, Epidural↗

The value of quantitative detection of HBV-DNA amplified by PCR in the study of hepatitis B infection.

BACKGROUND/AIMS: This study aimed to evaluate the usefulness of quantifying HBV-DNA amplified by polymerase chain reaction in chronic hepatitis B infection. METHODS: Serum samples were obtained from 32 asymptomatic HBV carriers and 99 chronic hepatitis B patients (62 positive for anti-HBe and 37 positive for HBeAg). In addition, serial serum samples were analyzed from 15 HBeAg positive patients undergoing antiviral therapy and 17 anti-HBe positive patients with precore mutation. HBV-DNA quantification was carried out using an enzyme immunoassay with an HBV-DNA plasma standard. RESULTS: The digoxigenin-incorporated polymerase chain reaction method detected HBV-DNA in 34.3% of the asymptomatic HBV carriers with a median HBV-DNA concentration of about 0.18 x 10(5) mol/ml (range 0.08-0.4), in 87% of the anti-HBe positive chronic hepatitis cases with a range of 0.2 to > 2 x 10(5) mol/ml and in 100% of the HBeAg positive patients, with a value in all cases over 2 x 10(5) mol/ml. We observed that after treatment, HBV-DNA tested negative in only two of the eight HBeAg positive chronic hepatitis patients who seroconverted to anti-HBe, and was positive in the seven remaining, with a median HBV-DNA value of about 0.2 x 10(5) mol/ml (0.09-0.4). In the precore mutants HBV-DNA values ranged from 0.2 to > 2 x 10(5) mol/ml. CONCLUSIONS: Polymerase chain reaction HBV-DNA quantification is a sensitive method for managing chronic hepatitis B patients, especially those with low viremia, and may be a valuable tool for evaluating the efficacy of antiviral therapy.

Adult↗

[Seroepidemiology of hepatitis A virus infection in medical and nursing students. The role of vaccination].

BACKGROUND: Recent seroepidemiologic studies have demonstrated a decrease in the prevalence of hepatitis A virus infection (HAV) in relation with an improvement in hygienic conditions. The prevalence of anti-HAV in a group of health care students was studied and a vaccination program initiated in this collective. METHODS: Serum anti-HAV determination was performed by an enzymoimmunoanalysis method. A inactivated hepatitis A vaccine was administered. RESULTS: Only 18.5% of the subjects between 17-23 years-old presented anti-HAV antibodies. The prevalence of anti-HAV was related with age and the number of partners. All of the 129 immunized individuals responded to the HAV vaccine with protector antibody titles. CONCLUSION: The present study demonstrates the decrease in HAV infection among youths as well as the immunogenicity of the anti-hepatitis A vaccine.

Adolescent↗

Hepatitis B virus infection: precore mutants and its relation to viral genotypes and core mutations.

The precore-core gene of hepatitis B virus (HBV) was directly sequenced from serum samples of 42 patients with chronic B hepatitis (19 hepatitis B e antigen [HBeAg]+ and 23 anti-HBE+). Viral genotypes were determined by comparison with 11 reference sequences and by restriction analysis. Genotype A was identified in 16 cases, genotype D in 24 cases, and other genotypes in 2 cases. Precore mutations, mainly M1 (stop at codon 28), were differently distributed among the viral genotypes: 3 cases (18.8%) with genotype A and 18 cases (75%) with genotype D. In sequences with precore mutants, the encapsidation signal was more stable (negative stabilization energy) than in sequences without precore mutants. In genotype A, the M1 mutation coexisted with a second mutation (C-->T at position 1858 in codon 15), and both mutations were paired in the secondary structure of the RNA encapsidation signal, which justified the rare presence of precore mutants in this genotype. The analysis showed different distribution of mutations depending on the viral genotype; patients with genotype D were more likely to have persistent HBV infection by selection of precore mutants. Multiple amino acid substitutions were detected in the core region, mainly in two subsequences that have been previously described as epitopes (flanked by codons 11 to 27 and 74 to 83); the presence of these mutations was significantly related to the presence of precore variants which abolished the expression of HBeAg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hepatitis E virus infection in acute hepatitis in Spain.

In order to study the prevalence of hepatitis E virus (HEV) infection in developed countries, IgG and IgM anti-HEV were determined in serum samples from 382 patients with acute viral hepatitis (244 hepatitis A, 48 hepatitis B and/or D, and 90 non-A, non-B, non-C hepatitis), 76 healthy subjects, 55 hemophiliacs and 50 patients on hemodialysis. IgG anti-HEV antibodies were detected and confirmed by a synthetic peptide-based EIA in 5 (5.6%) non-A, non-B, non-C acute hepatitis, in 3 (6.5%) B and D acute hepatitis, in 10 (4%) acute A hepatitis, in 3 (5.5%) of 54 healthy adults in none of the hemophiliacs and in 3 (6%) patients on hemodialysis. IgM anti-HEV antibodies were only detected in two cases of acute hepatitis B and/or D. Analysis of serial serum samples demonstrated IgG anti-HEV seroconversion in 3 of the 18 confirmed cases; one of them was also positive for IgM anti-HEV. All 3 acute anti-HEV-positive hepatitis cases occurred in adults, were community-acquired (two of them were intravenous drug addicts) and had a self-limited course. These results demonstrate that HEV is a minor cause of acute hepatitis in Spain. A similar low rate of IgG anti-HEV antibodies was detected in patients with different diseases, suggesting that HEV has a very low epidemiological impact. An apparent association of HEV infection with hepatitis B and D suggests a possible parenteral transmission of a mainly enteral pathogen.

Acute Disease↗