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1.
Comput Struct Biotechnol J ; 24: 603-610, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39421530

RESUMO

Background and objective: This article uses three different probabilistic convolutional architectures applied to ultrasound image analysis for grading Fatty Liver Content (FLC) in Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) patients. Steatosis is a new silent epidemic and its accurate measurement is an impelling clinical need, not only for hepatologists, but also for experts in metabolic and cardiovascular diseases. This paper aims to provide a robust comparison between different uncertainty quantification strategies to identify advantages and drawbacks in a real clinical setting. Methods: We used a classical Convolutional Neural Network, a Monte Carlo Dropout, and a Bayesian Convolutional Neural Network with the goal of not only comparing the goodness of the predictions, but also to have access to an evaluation of the uncertainty associated with the outputs. Results: We found that even if the prediction based on a single ultrasound view is reliable (relative RMSE [5.93%-12.04%]), networks based on two ultrasound views outperform them (relative RMSE [5.35%-5.87%]). In addition, the results show that the introduction of a "not confident" category contributes to increase the percentage of correctly predicted cases and to decrease the percentage of mispredicted cases, especially for semi-intrusive methods. Conclusions: The possibility of having access to information about the confidence with which the network produces its outputs is a great advantage, both from the point of view of physicians who want to use neural networks as computer-aided diagnosis, and for developers who want to limit overfitting and obtain information about dataset problems in terms of out-of-distribution detection.

2.
Aliment Pharmacol Ther ; 47(12): 1705-1712, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29722439

RESUMO

BACKGROUND: The efficacy of direct-acting anti-viral (DAA) therapy in patients with a history of hepatocellular carcinoma (HCC) is unknown. AIM: We prospectively evaluated whether previously treated HCC affects DAA efficacy in a large real-life cohort of cirrhotic patients. METHODS: From January to December 2015 all consecutive HCV mono-infected patients with cirrhosis and/or history of HCC attending 10 Italian tertiary liver centres were enrolled. Baseline characteristics and response to therapy were recorded. 1927 patients were enrolled (mean age: 62.1 ± 10.9 years; 1.205 males). Genotype 1 was the most frequent (67.9%) followed by genotypes 3 (12.4%), 2 (11.2%) and 4 (8.6%). 88.4% and 10.9% of cases were classified Child A and B, respectively, and 14 (<1%) cases were classified Child C. Ascites and hepatic encephalopathy occurred in 10.7% and 3.2% of patients, respectively. Varices were detected in 39.3% of patients. Suboptimal and optimal treatment was prescribed: 15.9% of patients received sofosbuvir/simeprevir, 33.4% sofosbuvir/ledipasvir, 20.2% a Viekirax + Exviera regimen, 15.7% sofosbuvir/ribavirin, 9.9% sofosbuvir/daclatasvir and 3.4% Viekirax; 1.3% of patients received an interferon-based regimen. RESULTS: The sustained virologic response (SVR) rate at intention-to-treat analysis was 95.1%. It differed significantly across Child classes, that is, 96.3%, 86.1% and 71.4% Child A, B and C, respectively (P < 0.0001) and across genotypes (P = 0.002). The SVR rate did not differ between patients with (95.0%) and those without previous HCC (95.1%). At multivariable analysis, SVR was significantly associated with HCV genotype, Child class. CONCLUSION: This large real-life study proves that the efficacy of DAA in cirrhotic patients is not impaired by successfully treated HCC.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Idoso , Benzimidazóis/administração & dosagem , Carbamatos , Carcinoma Hepatocelular/etiologia , Estudos de Coortes , Quimioterapia Combinada , Feminino , Fluorenos/administração & dosagem , Genótipo , Hepacivirus/genética , Encefalopatia Hepática/epidemiologia , Humanos , Imidazóis/administração & dosagem , Interferons/uso terapêutico , Itália , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirrolidinas , Ribavirina/uso terapêutico , Simeprevir/administração & dosagem , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/análogos & derivados , Valina/análogos & derivados
3.
J Viral Hepat ; 25(8): 911-919, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29577518

RESUMO

The interplay between hepatitis B (HBV) and delta (HDV) viruses is complex and not always characterized during chronic HDV infection. We assessed the clinical usefulness of new quantitative assays for HBV and HDV serum markers in a retrospective cross-sectional study. Sera obtained from 122 HDV genotype 1 and HBV genotype D coinfected, anti-HIV-negative patients (71 males; median age 49.8 [21.7-66.9] years), recruited consecutively in two geographical areas (Italy 69 patients, Romania 53 patients) with different HBV and HDV epidemiology, were tested for HBsAg, HBV-DNA, HBcrAg, total anti-HBc, HDV-RNA, IgM and total anti-HDV using quantitative assays. Cirrhosis, which showed comparable prevalence in the two cohorts, was diagnosed in 97 of 122 (79.5%) patients. At multivariate analysis, cirrhosis was associated with lower total anti-HBc/IgM anti-HDV ratio (OR 0.990, 95% CI 0.981-0.999, P = .038), whereas disease activity was associated with higher total anti-HDV (OR 10.105, 95% CI 1.671-61.107, P = .012) and HDV-RNA levels (OR 2.366, 95% CI 1.456-3.844, P = .001). HDV-RNA serum levels showed a positive correlation with HBV-DNA (ρ = 0.276, P = .005), HBsAg (ρ = 0.404, P < .001) and HBcrAg (ρ = 0.332, P < .001). The combined quantitative profiling of HBV and HDV serum markers identifies specific patterns associated with activity and stage of chronic hepatitis D (CHD). HDV pathogenicity depends on the underlying active HBV infection in spite of the inhibition of its replication. HDV-RNA, IgM anti-HDV, total anti-HDV, total anti-HBc, HBsAg and HBcrAg serum levels qualify for prospective studies to predict progressive CHD and identify candidates to antiviral therapy.


Assuntos
Biomarcadores/sangue , Coinfecção/patologia , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Hepatite D Crônica/patologia , Adulto , Idoso , Estudos Transversais , DNA Viral/sangue , Feminino , Genótipo , Anticorpos Anti-Hepatite/sangue , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Humanos , Imunoglobulina M/sangue , Itália , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Retrospectivos , Romênia , Adulto Jovem
4.
J Viral Hepat ; 21(7): 458-65, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24750327

RESUMO

Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 µg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and <0.001, respectively). Among the 22 patients with the strongest direct antiviral effects of IFN (ε ≥ 0.800), those treated with P/R + V (10) reached lower HCV-RNA levels (P = 0.026) at week 16. HCV E1E2MF59 vaccine in combination with Peg-IFNα2a + RBV was safe and elicited E1E2 neutralizing antibodies and specific CD4 + T cell proliferation. Upon early response to IFN, vaccinations were associated with an enhanced second phase viral load decline. These results prompt phase II trials in combination with new antiviral therapies.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antivirais/uso terapêutico , Hepatite C Crônica/terapia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Polissorbatos/administração & dosagem , Ribavirina/uso terapêutico , Esqualeno/administração & dosagem , Vacinas contra Hepatite Viral/imunologia , Adjuvantes Imunológicos/efeitos adversos , Anticorpos Neutralizantes/sangue , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Injeções Intramusculares , Polissorbatos/efeitos adversos , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Esqualeno/efeitos adversos , Resultado do Tratamento , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas contra Hepatite Viral/administração & dosagem , Vacinas contra Hepatite Viral/efeitos adversos , Vacinas contra Hepatite Viral/genética , Carga Viral
6.
Clin Vaccine Immunol ; 18(11): 1943-50, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21880853

RESUMO

The Elecsys hepatitis B surface antigen (HBsAg) II quantitative assay is a new quantitative electrochemiluminescence immunoassay which uses onboard dilution and a simple algorithm to determine HBsAg levels expressed in international units (IU)/ml (standardized against the World Health Organization [WHO] Second International Standard). This study evaluated its performance using routine serum samples from a wide range of HBsAg carriers and patients with chronic hepatitis B (CHB). HBsAg levels were measured in serum samples collected independently by five centers in Europe, Australia, and Asia. Serial dilution analyses were performed to assess the recommended dilution algorithm and determine the assay range free of hook effect. Assay precision was also established. Following assessment of serial dilutions (1:100 to 1:1,000,000) of the 611 samples analyzed, 70.0% and 85.6% of samples tested with analyzers incorporating 1:100 (Elecsys 2010 and cobas e 411) and 1:400 (Modular Analytics E170) onboard dilution, respectively, fell within the linear range of the assay, providing a final result on the first test. No high-dose hook effect was seen up to the maximum HBsAg serum level tested (870,000 IU/ml) using the dilution algorithm. HBsAg levels were reliably determined across all hepatitis B virus (HBV) genotypes, phases of HBV infection, and stages of disease tested. Precision was high across all analyzers (% coefficient of variation [CV], 1.4 to 9.6; HBsAg concentrations, 0.1 to 37,300 IU/ml). The Elecsys HBsAg II quantitative assay accurately and reliably quantifies HBsAg in routine clinical samples. Onboard dilution minimizes retesting and reduces the potential for error.


Assuntos
Técnicas de Laboratório Clínico/métodos , Antígenos de Superfície da Hepatite B/sangue , Hepatite B/diagnóstico , Kit de Reagentes para Diagnóstico , Ásia , Austrália , Europa (Continente) , Humanos , Imunoensaio/métodos
7.
Clin Pharmacol Ther ; 84(2): 212-5, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18388885

RESUMO

A novel biomathematical model that analyzes the combined alanine transaminase (ALT) and viral-load kinetics during the first month of pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy was successfully applied in 90 of 97 (93%) chronic hepatitis C patients in order to compute the number of infected cells at the end of therapy (I(eot)). The I(eot) indices were lower in sustained virological responders than in relapsers (RELs) and nonresponders (NRs) (median values: 31 vs. 2,190 vs. 1,090,000; P < 0.001), and were independently associated with treatment outcomes (P = 0.003). A threshold of 250 I(eot) was shown to identify sustained virological response (SVR) with high positive predictive value (93%) and good diagnostic accuracy (81%). The time taken to attain 250 I(eot) ranged from 3 to 11 months in patients with hepatitis C virus (HCV) genotypes 2 or 3 and from 3 to 18 months in those with HCV genotypes 1 or 4. Overall, the duration of therapy would have been 49 months less than that suggested by the most recent algorithms based on a rapid virological response (RVR) at week 4.


Assuntos
Alanina Transaminase/sangue , Antivirais/uso terapêutico , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Interleucina-2/análogos & derivados , Ribavirina/uso terapêutico , Carga Viral , Adulto , Antivirais/administração & dosagem , Biomarcadores/sangue , Portadores de Fármacos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/enzimologia , Humanos , Interleucina-2/administração & dosagem , Interleucina-2/uso terapêutico , Cinética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Modelos Teóricos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico , Valor Preditivo dos Testes , RNA Viral/isolamento & purificação , Curva ROC , Ribavirina/administração & dosagem , Resultado do Tratamento
8.
J Antimicrob Chemother ; 60(2): 341-9, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17567633

RESUMO

OBJECTIVES: We studied the impact of hepatitis B virus (HBV) polymerase/reverse transcriptase (Pol/Rt) heterogeneity on adefovir rescue therapy in 34 consecutive chronic hepatitis B patients with viral breakthrough during lamivudine monotherapy. METHODS: The Pol/Rt A-F domains were directly sequenced in all patients at baseline, and 12 and 24 months. Response to therapy was evaluated at 3, 6, 12 and 24 months by quantitative HBV-DNA. RESULTS: Primary treatment failures did not occur. At 6 months 24/34 (70.6%) patients had viraemia<10(4) copies/mL [initial viral response (IVR)]; at 12 and 24 months 23 (71.9%) and 26 (81.3%) of 32 had HBV-DNA<200 copies/mL [complete viral response (CVR)]. IVR or CVR patients did not show viral breakthroughs, which occurred in one of the six remaining patients. All but three patients had baseline rtM204I/V substitutions associated with rtL180M in 23, rtL80I/V in 14, rtV173L in 4, rtT184S in 3, rtQ215S in 2 and rtA181S in 2 cases. rtA181S without rtM204I/V was found in one patient. Four of the six patients (67%) without 24 month CVR showed rtA181S or rtT184S substitutions either alone or with typical lamivudine resistance profiles. Baseline HBV-DNA levels were negatively associated with IVR (univariate analysis, P=0.023). At least one of rtA181S and rtT184S substitutions correlated negatively with IVR and CVR (univariate analysis, P=0.001) and was independently associated with absence of CVR (P = 0.016). CONCLUSIONS: Lamivudine monotherapy favours the emergence of viral quasispecies that influence the response rate to adefovir rescue therapy independently from baseline viraemia and lower the susceptibility to other nucleos(t)ide analogues.


Assuntos
Antivirais/farmacologia , DNA Polimerase Dirigida por DNA/genética , Farmacorresistência Viral/genética , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Lamivudina/farmacologia , DNA Polimerase Dirigida por RNA/genética , Adenina/análogos & derivados , Adenina/farmacologia , Adenina/uso terapêutico , Adulto , Idoso , Antivirais/uso terapêutico , DNA Viral/genética , Feminino , Seguimentos , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Nucleosídeos/farmacologia , Nucleotídeos/farmacologia , Organofosfonatos/farmacologia , Organofosfonatos/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Viremia/virologia
9.
J Viral Hepat ; 14(5): 360-9, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17439526

RESUMO

Liver stiffness was measured by transient elastography (FibroScan) in 228 consecutive patients with chronic viral hepatitis, with (115) or without cirrhosis (113), to study its correlations with serum transaminases [alanine aminotransferase (ALT)], fibrosis stage and surrogate noninvasive markers of fibrosis (APRI, FORNS, FibroTest and hyaluronic acid). The dynamic profiles of serum transaminases and liver stiffness were compared by multiple testing in 31 patients during a 6-month follow-up. We identified 8.3 and 14 kPa as the fibrosis >/=F2 and cirrhosis cut-offs, respectively: their sensitivities were 85.2%/78.3%; specificities 90.7%/98.2%; positive predictive values 93.9%/97.8%; negative predictive values 78.8%/81.6%; diagnostic accuracies 87.3%/88.2%. FibroScan performed better than the other surrogate markers of fibrosis (P < 0.001). Other than fibrosis, other factors independently associated with liver stiffness were ALT for all patients and chronic hepatitis patients (P < 0.001), and 12-month persistently normal ALT (biochemical remission, P < 0.001) in cirrhotics. In patients with biochemical remission either spontaneous or after antiviral therapy (48 of 228, 21%), liver stiffness was lower than in patients with identical fibrosis stage, but elevated ALT (P < 0.001). The liver stiffness dynamic profiles paralleled those of ALT, increasing 1.3- to 3-fold during ALT flares in 10 patients with hepatitis exacerbations. Liver stiffness remained unchanged in 21 with stable biochemical activity (P = 0.001). In conclusion, transient elastography is a new liver parameter that behaves as a reliable surrogate marker of fibrosis in chronic viral hepatitis patients, provided that its relationship with major changes of biochemical activity is taken into account.


Assuntos
Alanina Transaminase/sangue , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/patologia , Adulto , Idoso , Biomarcadores/sangue , Biópsia , Elasticidade , Feminino , Seguimentos , Humanos , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade , Fatores de Tempo
10.
Gut ; 56(5): 699-705, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17127704

RESUMO

OBJECTIVE: In a trial of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 24 week post-treatment biochemical and virological response rates with peginterferon alpha-2a with or without lamivudine were significantly higher than with lamivudine alone. The effect of pre-treatment factors on post-treatment responses was investigated. METHODS: Multivariate analyses were performed using available data from 518 patients treated with peginterferon alpha-2a with or without lamivudine, or with lamivudine alone. A post-treatment response was defined as alanine aminotransferase (ALT) normalisation and hepatitis B virus (HBV) DNA level of <20,000 copies/ml. RESULTS: In logistic regression analyses across all treatment arms, peginterferon alpha-2a (with or without lamivudine) therapy, younger age, female gender, high baseline ALT, low baseline HBV DNA and HBV genotype were identified as significant predictors of combined response at 24 weeks post-treatment. In the peginterferon alpha-2a and lamivudine monotherapy arms, patients with genotypes B or C had a higher chance of response than genotype D infected patients (p<0.001), the latter responding better to the combination than to peginterferon alpha-2a monotherapy (p = 0.015). At 1 year post-treatment, response rates by intention-to-treat analysis were 19.2% for the peginterferon alpha-2a, 19.0% for the combination, and 10.0% for the lamivudine groups, with genotypes B or C associated with a sustained combined response to peginterferon alpha-2a with or without lamivudine therapy. CONCLUSIONS: Baseline ALT and HBV DNA levels, patient age, gender, and infecting HBV genotype significantly influenced combined response at 24 weeks post-treatment, in patients treated with peginterferon alpha-2a and/or lamivudine. At 1 year post-treatment HBV genotype was significantly predictive of efficacy for patients treated with peginterferon alpha-2a with or without lamivudine.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Lamivudina/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Fatores Etários , Alanina Transaminase/sangue , Biomarcadores/sangue , DNA Viral/sangue , Quimioterapia Combinada , Feminino , Genótipo , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes , Fatores Sexuais , Resultado do Tratamento
11.
J Virol Methods ; 129(1): 64-74, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15993954

RESUMO

Hepatitis virus variants detection is useful in clinical practice; however, methods that are used for their identification may influence the results significantly. Three PCR-based assays for quantitation of G1896A precore HBV mutants: two allele specific PCRs, single tube (single-AS-PCR) with enzymatic restriction or separate tubes (twin-AS-PCR) and one oligohybridization assay (OA) with three probes were developed and standardized. Wild type and mutant plasmids and 10 sera were used as reference. All methods had sensitivity limits of 10(4)copies/ml and their specificity encompassed 3 logs (10(4)-10(7)copies/ml) with dynamic ranges of logs for OA, twin-AS-PCR and single-AS-PCR, respectively. Single-AS-PCR and OA detected minor viral populations when their relative prevalence was at least 10% of the overall viral population whereas their detection by twin-AS-PCR ranged from 0.1 to 10% for samples with 10(7) and 10(5)copies/ml viral loads, respectively. Twin-AS-PCR was the most sensitive to detect the minor viral population, whereas single-AS-PCR and OA were more accurate to quantify the relative proportions of the two viral populations independently of the overall viral load. In conclusion, an accurate characterization of HBV precore heterogeneity should be warranted by a careful choice of the most appropriate assay according to the aim of the study.


Assuntos
Antígenos do Núcleo do Vírus da Hepatite B/análise , Vírus da Hepatite B/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , DNA Viral/sangue , Antígenos do Núcleo do Vírus da Hepatite B/genética , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Mutação , Sensibilidade e Especificidade
12.
J Endocrinol Invest ; 28(3): 280-4, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15952415

RESUMO

We report a case of acute hepatitis of autoimmune origin which occurred in a 43-yr-old woman during iv glucocorticoid (GC) pulse therapy for Graves' ophthalmopathy (GO). Prior to therapy, liver function tests were normal with no previous history of liver disorders or conditions predisposing to GC-associated liver damage. After the administration of a 4.7-g cumulative dose of methylprednisolone acetate, there was a marked increase of liver enzymes, prompting immediate discontinuation of iv GC. Nevertheless, liver enzymes increased further, reaching a peak 45 days later, with values 30- to 50-fold greater than those prior to therapy, associated with evidence of impaired liver function. Liver biopsy showed a marked lymphocytic infiltration, likely indicating an autoimmune hepatitis. Based on the assumption that following GC-induced immune suppression, autoimmune hepatitis might have been precipitated by sudden re-activation of the immune system during interpulse periods, we treated the patient with im and then oral GC, in order to re-induce immune suppression. Within three days from re-institution of GC therapy, there was a marked reduction of liver enzymes and amelioration of liver function. Complete normalization was achieved two months later, while the patient was still receiving a low maintenance dose of oral prednisone.


Assuntos
Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Hepatite Autoimune/etiologia , Adulto , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Índice de Massa Corporal , Feminino , Doença de Graves/radioterapia , Humanos , Fígado/enzimologia , Fígado/patologia , Testes de Função Hepática , Linfócitos/fisiologia , Metilprednisolona/efeitos adversos , Metilprednisolona/uso terapêutico , Prednisona/uso terapêutico
13.
J Pharm Biomed Anal ; 37(1): 115-20, 2005 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-15664750

RESUMO

A method for the determination of cocaine (COC) and benzoylecgonine (BZE) in human urine using a column-switching liquid chromatography system is reported. A homemade precolumn (20 mm x 4.6 mm i.d.) dry-packed with Alltech ODS-C18 (35-750 microm) was employed as an extraction precolumn in order to extract and concentrate the COC and BZE from the human urine sample. The analytes were continuously transferred to the analytical column (Spherisorb-C8, 250 mm x 4.6 mm i.d.; dp = 5 microm) by means of the switching arrangement in the backflush mode. Detection was carried out at 235 nm in a UV-diode array detector. The validation of the method revealed analytes quantitative recoveries (96-102%) at three concentrations in the range from 0.25 to 4.00 and from 0.5 to 12.0 microg/mL for COC and BZE, respectively. These values demonstrate the excellent extraction efficiency of the precolumn. The detection limits for COC and BZE at a signal-to-noise ratio of 3 were 0.08 and 0.15 microg/mL when a sample volume of 50 microL was injected. The overlap of sample preparation, analysis and recondition of the precolumn increases the sample throughput to four samples per hour. The proposed method has been applied to the determination of COC and BZE in human urine samples from 73 suspecting drug addicts. Urine concentrations of 1.0-118.10 microg of BZE/mL and 0.1-41.0 microg of COC/mL were found.


Assuntos
Cocaína/análogos & derivados , Cocaína/urina , Análise de Injeção de Fluxo/métodos , Detecção do Abuso de Substâncias/métodos , Cromatografia Líquida/métodos , Cocaína/análise , Humanos
14.
J Med Virol ; 75(1): 20-6, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15543588

RESUMO

Albania is a Mediterranean country, still with a high endemicity level of hepatitis B virus (HBV) infection. The chronic hepatitis B profile was characterized in this geographical area and used as a model to investigate the impact of endemicity level on the prevalence of the two major forms of chronic hepatitis B (HBeAg-positive and HBeAg-negative chronic hepatitis B). A cross-sectional study was conducted among 62 chronic hepatitis B patients consecutively admitted to the most important tertiary health care center for the diagnosis and treatment of liver disease in Albania. HBV-DNA was measured with an in-house PCR with a sensitivity of 10(4) copies/ml which uses primers encompassing the pre-core/core region. PCR products were subjected to sequencing and oligohybridization assay. Of the 62 patients, 75.8% had HBeAg-negative chronic hepatitis B. Genotype D was found in all 39 patients with detectable HBV viremia, for whom the heterogeneity of the region modulating HBeAg expression was assessed. Basic core promoter (BCP) mutations (1762/1764) were observed more often in anti-HBe-positive and older patients. In more than 90% of the HBeAg-negative chronic hepatitis B patients with detectable viremia, HBV that carries the G to A pre-core mutation at nucleotide 1896 was found. Patients with HBeAg-positive chronic hepatitis B were younger than HBeAg-negative chronic hepatitis B patients, and for symptomatic and asymptomatic liver-disease patients, the age of peak prevalence was at least 10 years lower for HBeAg-positive chronic hepatitis B patients. In conclusion, the virological and clinical pattern of chronic hepatitis B in Albania is similar to that observed in other Mediterranean countries; it seems to be independent of the HBV endemicity level.


Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Adulto , Fatores Etários , Idoso , Albânia/epidemiologia , DNA Viral/sangue , DNA Viral/química , Variação Genética , Genótipo , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/classificação , Vírus da Hepatite B/isolamento & purificação , Humanos , Fígado/patologia , Pessoa de Meia-Idade , Epidemiologia Molecular , Hibridização de Ácido Nucleico , Mutação Puntual/genética , Regiões Promotoras Genéticas/genética , Análise de Sequência de DNA , Viremia
15.
Curr Pharm Des ; 10(17): 2063-75, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15279545

RESUMO

The aim of antiviral therapy of chronic hepatitis B is to control Hepatitis B Virus (HBV) replication and to cure liver disease avoiding the progression of chronic hepatitis to cirrhosis and the end stage complications of cirrhosis. HBeAg/anti-HBe seroconversion is the hallmark of response in hepatitis B "e" antigen (HBeAg) positive patients. In the patients with antibody against HBeAg (anti-HBe positive) the combination of HBV DNA and anti-HBc IgM tests provides adequate diagnostic accuracy. Patients with biochemical and/or histological disease activity are eligible to therapy. The drug choice is based on age, disease severity, risk of complications, side effects and compliance, particularly in anti-HBe positive patients where prolonged treatment is needed. Interferon (5-6 MU daily or 9-10 MU thrice weekly for 4-6 months) is the first line therapy for HBeAg positive patients and (5-6 MU thrice weekly for 12-24 months) for anti-HBe positive patients. When IFN is contraindicated or ineffective, Lamivudine (100 mg) or Adefovir Dipivoxil (10 mg) are given as long as 4-6 months after HBeAg/anti-HBe seroconversion or for long-term treatments in HBeAg positive non-responders and anti-HBe positive patients. Patients with more advanced forms of cirrhosis and portal hypertension are to be treated within liver transplantation programs. Fifteen to 30% of treated patients achieve sustained response and more than 60% of them experience long-term disease remission during therapy. In perspectives, currently available molecular and immunologic tools and modelling of viral dynamics will help to address the therapy issue with more complex, efficacious and individually tailored treatment schedules.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/terapia , Guias de Prática Clínica como Assunto , Conferências de Consenso como Assunto , Monitoramento de Medicamentos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Humanos , Imunoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Bone Marrow Transplant ; 33(10): 1057-9, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15048140

RESUMO

We describe the case of a HBsAg+, HBeAg+ carrier, treated with lamivudine, who experienced exacerbation of hepatitis after BMT from an anti-HBs+, anti-HBc+, anti-HBe+ donor. The serological profile of the donor and the timing of exacerbation suggested that the adoptive immunity transfer played a major pathogenetic role. Antilymphocyte globulin administration resulted in resolution of hepatitis and seroconversion to anti-HBs+. Therapy aimed at blocking the effector arm of liver damage could represent a novel approach to avoid the risk of progression to fulminant hepatitis without hampering the chances of recovery from hepatitis B.


Assuntos
Transferência Adotiva , Soro Antilinfocitário/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , Antígenos de Superfície da Hepatite B/genética , Hepatite B/patologia , Imunoterapia Adotiva/métodos , Animais , Antivirais/uso terapêutico , Criança , Progressão da Doença , Feminino , Vírus da Hepatite B/metabolismo , Heterozigoto , Teste de Histocompatibilidade , Cavalos , Humanos , Lamivudina/uso terapêutico , Fígado/patologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Fatores de Tempo , Doadores de Tecidos
17.
Talanta ; 64(5): 1364-70, 2004 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-18969755

RESUMO

A HPLC method with automated column switching and UV-diode array detection is described for the simultaneous determination of Vitamin D(3) and 25-hydroxyvitamin D(3) (25-OH-D(3)) in a sample of human plasma. The system uses a BioTrap precolumn for the on-line sample cleanup. A sample of 1ml of human plasma was treated with 2ml of a mixture of ethanol-acetonitrile (2:1 (v/v)). Following centrifugation, the supernatant was evaporated to dryness under a stream of dry and pure nitrogen. The residue was reconstituted in 250muL of a solution of methanol 5mmoll(-1) phosphate buffer, pH 6.5 (4:1 (v/v)), and a 200mul aliquot of this solution was injected onto the BioTrap precolumn. After washing during 5min with a mobile phase constituted by a solution of 6% acetonitrile in 5mmoll(-1) phosphate buffer, pH 6.5 (extraction mobile phase), the retained analytes were then transferred to the analytical column in the backflush mode. The analytical separation was then performed by reverse-phase chromatography in the gradient elution mode with the solvents A and B (Solvent A: acetonitrile-phosphate buffer 5mmoll(-1), pH 6.5; 20:80 (v/v); solvent B: methanol-acetonitrile-tetrahydrofuran, 65:20:15 (v/v)). The compounds of interest were detected at 265nm. The method was linear in the range 3.0-32.0ngml(-1) with a limit of quantification of 3.0ngml(-1). Quantitative recoveries from spiked plasma samples were between 91.0 and 98.0%. In all cases, the coefficient of variation (CV) of the intra-day and inter-day-assay precision was

20.
J Viral Hepat ; 10(3): 168-73, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12753334

RESUMO

Recurrent hepatitis and acute rejection share common features which make difficult for diagnosis in liver transplant hepatitis C virus (HCV) positive patients. We studied the usefulness of quantitative monitoring of HCV RNA and immunoglobulin (Ig)M anti-HCV in the differential diagnosis between recurrent hepatitis and acute rejection in 98 consecutive anti-HCV positive liver transplant patients. Aminotransferase levels, serum HCV RNA and IgM anti-HCV were measured at the time of transplantation and monthly thereafter. A liver biopsy (LB) was obtained when serum aminotransferase levels increased to twice or more than normal. During a mean follow-up of 16 months 86 aminotransferase flares were observed. Histology was compatible with recurrent hepatitis C in 44 cases and with acute rejection in 28, doubtful in 14. The fluctuations of HCV RNA serum levels were not significantly different in the three groups. Serum IgM anti-HCV levels increased (from negative to positive or with value variations > or = 0.18) in 36 of 44 cases with recurrent hepatitis C at the time of alanine aminotransferase (ALT) flare. IgM anti-HCV remained unchanged in all rejection cases (P < 0.001), but increased in 10 of 11 histologically doubtful cases that were diagnosed as hepatitis at the second LB. Increasing serum levels of IgM anti-HCV at the time of ALT flares are significantly associated with recurrent hepatitis C in liver transplant patients. The quantitative monitoring of IgM anti-HCV appears to be an additional diagnostic tool for distinguishing recurrent hepatitis C from acute graft rejection with a 100% specificity; 100% positive predictive value and 88.9% diagnostic accuracy.


Assuntos
Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C/diagnóstico , Imunoglobulina M/sangue , Transplante de Fígado/efeitos adversos , Adulto , Alanina Transaminase/metabolismo , D-Alanina Transaminase , Feminino , Rejeição de Enxerto , Hepatite C/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , RNA Viral/sangue , Recidiva , Sensibilidade e Especificidade
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