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Biomedical subjects

M Buti

Publications and source records attributed to M Buti.

At least 37 records · Page 2Linked to original sources
PubMed2001

High-Dose interferon-alpha2b plus ribavirin for retreatment of interferon-nonresponsive patients infected with genotype 1 hepatitis C virus.

Ten patients with interferon-nonresponsive chronic hepatitis C were treated with high-dose interferon-alpha2b (IFN-alpha2b; 20 MU/day for two days, then 3 MU/day for 24 weeks, followed by 3 MU three times weekly for 24 more weeks) plus ribavirin (1000-1200 mg/day). End-of-treatment virologic responses occurred in 50% of cases and sustained virologic responses in 37.5%. Hepatitis C virus RNA decreased significantly (2.15 logs; P < 0.0001) after the two 20-MU interferon doses but rebounded when the interferon dose was lowered to 3 MU/day. Thereafter, hepatitis C virus RNA showed a progressive, significant decrease, most notably at week 10 (3.3 logs; P = 0.001). Patients with a sustained response exhibited a more pronounced hepatitis C virus RNA decrease, especially from weeks 3 to 8 (P = 0.036). Two patients discontinued therapy because of adverse events, and one patient required a ribavirin dose reduction. Retreatment with an initial high-dose IFN-alpha2b plus ribavirin significantly reduces viral load in genotype 1-infected, interferon-nonresponsive patients.

Adult↗
PubMed2001

Two years of lamivudine therapy in anti-HBe-positive patients with chronic hepatitis B.

There is no standard therapy for patients with anti-HBe-positive chronic hepatitis B. The aims of this study were to analyse the efficacy of lamivudine therapy for two years in these patients and to study the sequence variations in the precore and polymerase hepatitis B virus (HBV) regions in relation to therapy. Sixteen patients with chronic anti-HBe-positive hepatitis were treated with lamivudine (100 mg) once daily for 2 years. Levels of alanine aminotransferase (ALT), HBV-DNA and HBsAg were monitored during therapy. The polymerase and precore genes were amplified by polymerase chain reaction and their products were sequenced directly. Thirteen of 16 patients (81%) had a virological and biochemical response after 1 year of therapy and 11 (69%) maintained the complete response after 2 years of lamivudine therapy. Among the three patients without initial virological or biochemical response at year 1, prolonging therapy to 2 years was not associated with an increase in the response. YMDD variants were detected in 19% of cases in the first year and in 44% in the second year: YVDD being the most frequent mutations detected during year 1 and YIDD during year 2 of therapy. YMDD variants were found in 7-27% of cases with complete response depending on the duration of therapy. Our results show that prolonging lamivudine therapy is safe, well tolerated and maintains viral inhibition in anti-HBe-positive patients. However, its efficacy tends to decrease overtime and it is associated with an increase in YMDD variants, even in some cases, of complete response.

Adolescent↗
PubMed2001

Quantitative detection of hepatitis B virus DNA in serum by a new rapid real-time fluorescence PCR assay.

A sensitive and accurate HBV DNA quantification assay is essential for monitoring hepatitis B virus (HBV) replication. This study evaluated a real-time PCR method performed in the LightCycler analyser for quantitative HBV DNA assay. HBV DNA results with this method were compared with those obtained using a branched-chain DNA (bDNA) solution hybridization assay. Real-time PCR was performed using two adjacent fluorescently labelled probes and primers corresponding to the HBV core gene. The same standard employed in the bDNA assay was used for calibration. Serum samples came from 193 HBV surface antigen (HBsAg)-positive patients (34 HBV e antigen (HBeAg)-positive and 93 with antibody to HBeAg (anti-HBe)), and 66 asymptomatic HBV carriers. In addition, we analysed serum samples from 8 anti-HBe-positive patients who had been receiving lamivudine treatment for more than three years. A linear standard curve was seen in the range from 10(3) to 10(8) copies/mL. In the reproducibility analysis, intra-assay coefficient of variation (CVs) at two known HBV DNA concentrations were 4% and 2% and interassay CVs were 6% and 4%. The median of serum HBV DNA by real-time PCR was 9.2 x 10(8) copies/mL in HBeAg-positive patients with persistently elevated alanine aminotransferase (ALT) levels, 1.3 x 10(7) copies/mL in anti-HBe-positive cases with persistently elevated ALT levels, 3.7 x 10(4) copies/mL in anti-HBe-positive patients with fluctuating ALT levels and 10(4) copies/mL in asymptomatic HBV carriers. The differences in HBV DNA levels among the various groups studied were statistically significant (P < 0.05). The cut-off between chronic hepatitis patients and asymptomatic carriers was found to be at a serum HBV DNA concentration of 5 x 10(4) copies/mL. Of the 109 serum samples with a viral load < 7.5 x 10(5) (negative by bDNA assay) 44 (40%) were positive by real-time PCR: 24 (56%) chronic hepatitis and 20 (33%) asymptomatic carriers. There was a positive association between HBV DNA levels determined by real-time PCR and ALT levels (P < 0.05), which was not observed with the bDNA assay for HBV DNA quantification. At 12 months of lamivudine treatment, 6 patients (75%) showed HBV DNA levels < 5 x 10(4) copies/mL (range < 10(3)-2 x 10(3)), significantly lower than at baseline. At 36 months, 2 of 8 (25%) showed HBV DNA levels persistently lower than 5 x 10(4) copies/mL (1.7 x 10(3), 6 x 10(3)). The LightCycler quantitative real-time PCR is a practical, sensitive, reproducible single-tube assay with a wide dynamic range of detection. The assay is automatic except for DNA extraction and the running time is only 70 min. The LightCycler real-time PCR is useful for identifying different states of HBV infection and for evaluating the efficacy of viral therapy.

DNA, Viral↗
PubMed2001

Role of hepatitis B, C, and D viruses in dual and triple infection: influence of viral genotypes and hepatitis B precore and basal core promoter mutations on viral replicative interference.

The interactions among hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) were studied by measuring HBV-DNA and HCV-RNA levels and by determining the influence of viral genotypes and mutations in HBV basal core promoter (BCP) and precore regions. We included 65 consecutive patients, 25 HBV/HCV, 18 HBV/HDV, and 22 HBV/HCV/HDV. Controls consisted of 55 patients with chronic HBV and 55 with chronic HCV infection. HBV-DNA and HCV-RNA levels were lower in coinfections than in single infections (P <.05). HBV/HCV coinfection was associated with lower HBV viremia (8.2 x 10(4) copies/mL) and lower HCV-RNA levels (7 x 10(5) IU/mL), than the corresponding control group (P <.05), with more marked decrease in HBV replication (P <.05). Moreover, in HBV/HCV coinfection and in triple coinfection we observed an inverse relationship between HBV-DNA and HCV-RNA levels (P <.05). HBV/HDV coinfection was associated with lower HBV viremia (2.5 x 10(4) copies/mL) than that found in HBV infection (P <.05). Patients with triple coinfection showed lower HBV-DNA and HCV-RNA levels than control groups (P <.05). Prevalence of precore mutations was lower in HCV coinfections (P <.05). No significant association was observed between HCV-RNA levels and HBV precore mutations, BCP mutations or HBV genotypes, or between HBV-DNA levels and HCV genotypes (P <.05). In conclusion, HCV exhibited stronger inhibitory action in the reciprocal inhibition seen in HBV/HCV coinfection. HDV was the dominant virus in HBV/HDV coinfection and in triple coinfection, and had a greater unfavorable influence on HCV than on HBV replication. The reciprocal inhibition of viral replication seemed to be little influenced by the inherent genomic factors studied.

Adult↗
PubMed2000

Hepatitis A and B in children and adolescents--what can we learn from Puglia (Italy) and Catalonia (Spain)?

Viral hepatitis remains a major contributor to the global disease burden. Mass immunisation strategies against hepatitis B have been adopted by more than 90 developing and industrialised countries. Countries with low hepatitis A endemicity are experiencing cyclical outbreaks and an epidemiological shift, with larger numbers of individuals at risk of infection at an older age, resulting in increased morbidity. The high cost of outbreaks in these countries has made immunisation strategies cost-effective. The development of a vaccine against hepatitis A and a combined vaccine against hepatitis A and hepatitis B offers potentially exciting opportunities for a preventative approach in areas of both low and high endemicity. Existing mass immunisation programmes against hepatitis B will facilitate the adoption of joint strategies illustrated by the examples of Puglia (Italy) and Catalonia (Spain).

Adolescent↗
PubMed2000

[Prevalence and incidence of hepatitis A in patients with hepatitis B and C].

BACKGROUND: Patients with chronic hepatitis are in risk to acquire a fulminant hepatitis associated with hepatitis A virus superinfection. PATIENTS AND METHODS: Antibodies against hepatitis A were study in serum from 353 patients with chronic hepatitis B or C. RESULTS: The prevalence of IgG-HAV antibodies was 81% in chronic hepatitis C patients, and 77% in chronic hepatitis B patients. The presence of anti-HAV antibodies was related to the patients' age. None case of acute hepatitis A in chronic hepatitis patients was detected. CONCLUSIONS: The prevalence of anti-HAV antibodies is high in patients with chronic viral hepatitis but the incidence of the disease is low. Hepatitis A vaccination should do with previously screening.

Adolescent↗
PubMed2000

Prospects for vaccination against hepatitis A and B in Catalonia (Spain).

Catalonia is in an area of intermediate endemicity for hepatitis A virus (HAV) infection. An Expert Committee has recently proposed the implementation of universal hepatitis A vaccination for 12-year-olds, based on the fact that no risk factors can be identified for hepatitis A in 50% of cases, and also that selective vaccination targeted at high-risk groups has a limited potential to reduce the incidence of hepatitis A. The well-established programme of hepatitis B vaccination of pre-adolescents in Catalonian schools has high levels of vaccination coverage. This will provide a means to introduce hepatitis A vaccination in a cost-effective way in schools, by replacing the single vaccine with the combined hepatitis A and B vaccine. High-risk groups will also continue to be targeted. A pilot programme has commenced in the 1998/1999 school year and will be evaluated after 3 years. If it is successful, it will be extended indefinitely.

Adolescent↗
PubMed2000

HEV identified in serum from humans with acute hepatitis and in sewage of animal origin in Spain.

BACKGROUND/AIMS: Hepatitis E virus (HEV) is an enterically transmitted pathogen that appears sporadically in non-endemic countries. We studied HEV as a causal agent of acute hepatitis cases in the Spanish population, and the role of pigs as an animal reservoir. METHODS: The presence of HEV-RNA was analysed by nested polymerase chain reaction in 37 serum samples from patients with acute viral hepatitis, 48 porcine serum samples, 6 pig faecal samples and 12 slaughter-house sewage samples. Presence of antibodies was also tested in porcine sera. RESULTS: HEV-RNA was found in 3 human serum samples from patients presenting IgG anti-HEV antibodies. Nucleotide sequence analysis identified 2 strains with 93.4% identity, phylogenetically most closely related to the Greece1 isolate, and more closely related to North American and other European strains than to those from endemic regions. HEV-RNA was also detected in slaughterhouse sewage mainly from pigs, presenting 92-94% nucleotide similarity compared to the strains detected in the human sera. Twenty-five per cent of the pigs tested presented IgG anti-HEV antibodies. CONCLUSIONS: These data suggest that the HEV could be more widespread than previously thought, and present new evidence of the close relationship between HEV strains detected in pigs and those from acute hepatitis patients.

Acute Disease↗
PubMed2000

Quantification of serum hepatitis C virus RNA with daily or standard interferon doses plus ribavirin in nonresponder patients with chronic hepatitis C.

Less than 10% of patients with chronic hepatitis C infected with genotype 1 achieve a sustained response with 12 months of interferon therapy. Viral kinetics studies have shown that HCV may replicate in less than 24 hr, generating over 10(12) copies per day and suggesting the need for more aggressive therapy. The aim of the study was to determine the effect of a higher and daily dosage of IFN-alpha2b plus ribavirin on the viral load and on the response rate in patients infected by genotype 1 and previous nonresponders to interferon. Ten patients with chronic hepatitis C infected with genotype 1 were allocated to receive IFN-alpha2b, 5 MU daily or three times a week for four weeks followed by 5 MU three times a week until week 24 plus ribavirin for the entire period. At week 4 of therapy, a 2 log reduction in HCV RNA levels was achieved in three (60%) patients in the daily group and in one (20%) patient in the three times a week group. At week 24, HCV RNA was negative in four of the five patients in the three times a week group, and three of the four patients in the daily group had a virological response. However, in follow-up, none of these patients experienced a sustained response. The safety of and ability to tolerate the combination therapy was good, anemia being the most common adverse effect. In conclusion, patients previously not responding to interferon achieved a greater virological reduction early in combination therapy compared to a three times a week interferon schedule. However, the virological response at the end of therapy was similar between the two regimens, and no sustained response was observed in any of the treatment groups.

Adult↗
PubMed2000

Cost-effectiveness of combination therapy for naive patients with chronic hepatitis C.

BACKGROUND/AIMS: The higher initial cost of combination therapy is a factor which may discourage its use in naive patients with histologically mild or moderate chronic hepatitis C. However, chronic hepatitis C is a slowly progressive disease associated with a decrease in life expectancy and quality of life. The objective of this study was to determine if the incremental sustained response rate of combination therapy is sufficient to outweigh its extra cost. METHODS: Chronic hepatitis C progression was studied using a Markov model in which cohorts of patients were treated with combination therapy for 6-12 months or with interferon for 12 months. The sustained virological response rates applied were 43, 35 and 19%, respectively, for combination therapy for 12 months, for 6 months and for interferon for 12 months. Costs for each clinical state were calculated according to clinical practice in Spain. RESULTS: In a 30-year-old patient with moderate chronic hepatitis C, combination therapy for 12 months increases life expectancy by 4.1 years compared with interferon for 12 months. In mild disease, the increase in life expectancy is lower. The cost per life-year saved in patients with chronic hepatitis C ranges from 880 to 64.421 euros depending on the age of the patient, the degree of hepatic lesion and the type and duration of therapy. Compared to other treatments accepted as standard practice in other therapeutic areas, combination therapy for chronic hepatitis C is cost-effective. CONCLUSIONS: In patients of any age with moderate chronic hepatitis C and those with mild disease under 50 years of age, combination therapy for 12 months is the most cost-effective schedule, whereas in older patients with mild hepatitis, combination therapy for 6 months is the preferred option based on cost-effectiveness criteria.

Adult↗
PubMed2000

Rapid method for the detection of anti-HCV antibodies in patients with chronic hepatitis C.

OBJECTIVE: to evaluate the usefulness of a simple, rapid, qualitative technique (MedMira Rapid Test) to detect antibodies against hepatitis C virus (HCV) and compare this approach with an immunometric technique in patients with chronic hepatitis C infected with different genotypes. METHODS: anti-HCV antibodies were determined with the MedMira rapid technique and an immunometric method in samples from 138 patients with chronic hepatitis C infected with different HCV genotypes, and in 50 samples from healthy individuals. RESULTS: the MedMira rapid technique detected anti-HCV antibodies in 135 (98%) of 138 serum samples from patients with chronic hepatitis C, whereas the immunometric method gave positive results in all 138 samples. Three of the 138 anti-HCV-positive samples identified with the immunometric method and confirmed by inmunoblotting were repeatedly negative with the MedMira rapid technique. Two of these samples were genotype 1 and the third was not genotyped. All samples from the control group were negative for anti-HCV antibodies by both methods. The sensitivity and specificity of the MedMira rapid technique relative to the immunometric technique were 98% and 100% respectively. CONCLUSION: the MedMira rapid technique is a quick, specific and sensitive method that is easy to use by nonspecialized personnel, and is a good alternative to other, slower methods for the diagnosis of chronic hepatitis C.

DNA, Viral↗
PubMed1999

Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group.

This placebo controlled, double-blind study evaluated the efficacy and safety of lamivudine in patients with hepatitis B e antigen (HBeAg)-negative/hepatitis B virus (HBV) DNA-positive chronic hepatitis B. Patients were randomized to receive 100 mg lamivudine orally once daily for 52 weeks (n = 60) or placebo for 26 weeks (n = 65). Patients who were HBV DNA positive at week 24 were withdrawn at week 26. The primary efficacy endpoint was loss of serum HBV DNA plus normalization of alanine transaminase (ALT) at week 24. A significantly higher proportion of patients receiving lamivudine (63%) had a complete response at week 24 compared with patients receiving placebo (6%) (P <.001). Secondary efficacy parameters included histological response from baseline to week 52 in the lamivudine-treated patients. At week 52, 60% of lamivudine-treated patients with liver biopsy specimens available showed histological improvement (>/=2-point reduction in Knodell necro-inflammatory score), 29% showed no change, and 12% worsened. In a ranked assessment of pretreatment and post-treatment biopsy pairs 11% improved, 86% showed no change, and 2% worsened in fibrosis. At week 52, 27% of patients receiving lamivudine had YMDD (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) variant HBV. The incidence of adverse events and laboratory abnormalities was similar in both groups. In conclusion, lamivudine treatment results in a significant virological and biochemical improvement compared with placebo, induces an improvement or no change in histology in most patients, and is well tolerated. The response to lamivudine therapy in HBeAg-negative patients is similar to the response reported in previous studies of patients with HBeAg-positive chronic hepatitis B.

Adolescent↗
PubMed1999

Rapid detection of lamivudine-resistant hepatitis B virus polymerase gene variants.

The amino acid substitution from methionine to valine or isoleucine at the YMDD (tyrosine, methionine, aspartate, aspartate) motif of the HBV polymerase gene is the main mutation responsible for resistance to lamivudine treatment. Detection of emerging HBV variants by direct sequencing of the HBV genome is excessively time-consuming for studying large numbers of clinical samples. The aim of the study was to analyse the emergence of lamivudine-resistant HBV genotypes by means of restriction fragment length polymorphism (RFLP) of the PCR product generated from a fragment of domain C of the polymerase gene, in clinical samples from patients receiving treatment. The results with this method were compared with those obtained with a direct sequencing technique. In total, 139 serum samples were studied from 37 patients with chronic hepatitis B, obtained at pre-treatment and at 9, 12, 18 and 24 months of treatment. Variants were detected by cleavage of the products of the three PCRs with the following enzymes: FokI (identifies the normal variant, YMDD, and the mutant variant YVDD), SspI (identifies the mutant variant, YIDD) and Alw44I (identifies the variant, YVDD). The digested fragments were separated by electrophoresis in 3% agarose gel. Of the 139 serum samples analysed, the wild-type YMDD sequence was detected in 106 (76%), the YVDD variant in 20 (15%) and the YIDD variant in 13 (9%) cases. The non-mutated variant, YMDD, was detected in all the pre-treatment samples. After 9 months of treatment the mutant variant was detected in four of 37 serum samples analysed (11%) (two YVDD and two YIDD). At 12 months, 12 of the 37 serum samples (32%) showed mutations in the YMDD sequence (seven YVDD and five YIDD). Among the 16 serum samples obtained at 18 months, nine had the YMDD variant (56%) (seven YVDD and two YIDD). At 24 months, variants in the YMDD sequence were detected in eight of the 12 patients treated (66%) (four YVDD and four YIDD). HBV genotypes were confirmed by direct sequencing, with consistent results. In 45% of cases, the emergence of HBV variants was not associated with ALT breakthrough. The PCR-RFLP assay used in this study, in perfect concordance with direct sequencing, is an accurate method for genotyping lamivudine-resistant HBV variants. Since it is a rapid low-cost technique, PCR- RFLP is suitable for large-scale screening of these polymorphisms in clinical samples.

Antiviral Agents↗
PubMed1999

Genetic alterations in the S gene of hepatitis B virus in patients with acute hepatitis B, chronic hepatitis B and hepatitis B liver cirrhosis before and after liver transplantation.

BACKGROUND: Several studies have shown that hepatitis B immunoglobulin (HBIG) imposes a selection pressure on the hepatitis B virus (HBV) S gene, and that the emergence of mutations in this region would make reinfection after orthotopic liver transplantation (OLT) possible. AIMS: This study was undertaken to analyze the presence of HBV S-gene mutations in the different stages of HBV infection and the relationship between HBIG therapy and the emergence of mutations in liver transplant recipients. METHODS: The frequency and location of mutations in the coding region of the HBV S gene were studied by PCR and direct sequencing in 30 patients (7 with acute self-limited hepatitis B, 16 with chronic hepatitis B and 7 recipients of (OLT) for HBV-related end stage liver disease who became reinfected). RESULTS: The average number of amino acid changes was higher in patients with a more advanced stage of disease, 0.57 mutations/100 positions in acute hepatitis B and 1.57 in chronic hepatitis B (1.28 in HBeAg-positive and 1.8 in anti-HBe-positive patients). The average number of substitutions in the transplanted patients was 2.7 before OLT and 3 after OLT. No amino acid substitutions were detected in the "a" determinant of HBsAg in acute hepatitis B, however, 8 substitutions were observed in 6 chronic patients. In 3 OLT patients, 4 substitutions were observed in samples before and after OLT. One of these patients, who had protective levels of anti-HBs, showed 3 additional new amino acid substitutions after OLT, suggesting escape mutant selection by the effect of HBIG therapy. No changes were observed between the consensus sequences obtained several years before and after transplantation, indicating consensus sequence stability. CONCLUSION: These results show that there is an accumulation of HBV S-gene mutations in HBV-related end-stage liver disease. Prophylaxis with HBIG mainly obtained from acute self-limited hepatitis patients who have a highly homogeneous viral population, may be one factor underlying the reinfection after liver transplantation.

Acute Disease↗