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1.
Malays J Med Sci ; 23(6): 123-127, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28090187

RESUMO

A 32 year old woman presented with acute onset of abdominal pain and fever. An urgent computerised tomography (CT) of the whole abdomen showed dilated loop at the terminal ileum in the right lower abdomen with thickening of the wall and oedema. The CT was suggestive of distal small bowel obstruction at the ileum with surrounding wall oedema. Multiple biopsies taken from the terminal ileum and colon on colonoscopy were all unremarkable. She represented one-year later with a recurrence of intestinal obstruction. CT enteroclysis showed collapse at the distal 3 cm segment of the terminal ileum. There was no associated wall thickening, active inflammatory changes or ileitis. This was suspicious of post-inflammatory change or fibrosis. She was subsequently found to have selective IgA deficiency with recurrent infection in the terminal ileum resulting in intestinal obstruction. In conclusion, selective IgA deficiency should be considered in patients with recurrent intestinal obstruction without anatomical obstructions.

2.
Singapore Med J ; 56(5): e85-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26034326

RESUMO

Lymphocytic colitis is a chronic inflammatory disease affecting the bowel. The clinical course of lymphocytic colitis is believed to be benign with watery diarrhoea. We report herein what is, to the best of our knowledge, the first case of lymphocytic colitis complicated by a terminal ileal mass. A 23-year-old man presented with diarrhoea. Blind biopsies of samples taken from the terminal ileum, caecum and ascending colon showed features of lymphocytic colitis. He declined treatment with budesonide or 5-aminosalicylates. He presented 14 months later with pain over the right lumbar region and nausea. Computed tomographic enteroclysis showed a focal soft tissue enhancing mass at the terminal ileum. Excision of the soft tissue mass revealed that it was reactive nodular lymphoid hyperplasia with fibrous granulation tissue. In conclusion, an untreated lymphocytic colitis may result in the formation of an inflammatory mass lesion.


Assuntos
Colite Linfocítica/complicações , Íleo/patologia , Mucosa Intestinal/patologia , Biópsia , Budesonida/uso terapêutico , Ceco/patologia , Colite Linfocítica/terapia , Colonoscopia , Diarreia/complicações , Fibrose , Tecido de Granulação/patologia , Humanos , Hiperplasia , Inflamação , Masculino , Náusea , Tomografia , Resultado do Tratamento , Adulto Jovem
3.
Singapore Med J ; 55(2): e28-30, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24154554

RESUMO

The use of intrauterine devices (IUDs) have been widespread since the 1960s. In 2002, the World Health Organization estimated that approximately 160 million women worldwide use IUDs. However, IUDs are associated with short-term complications such as vaginal bleeding, pelvic discomfort, dyspareunia and pelvic infection. Herein, we report the case of a woman who had recurrent urinary tract infection (UTI) due to the use of an IUD, even after treatment. The patient developed four episodes of UTI within a seven-month period after IUD insertion. During each episode of UTI, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) was cultured from the patient's midstream urine. The IUD was finally removed, and culture of the removed IUD was positive for ESBL-producing E. coli. An infected IUD as a source of recurrent UTI should be considered in women with IUD in situ who develop recurrent UTI even after treatment.


Assuntos
Infecções por Escherichia coli/etiologia , Dispositivos Intrauterinos/efeitos adversos , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/enzimologia , beta-Lactamases/metabolismo , Adulto , Antibacterianos/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Testes de Sensibilidade Microbiana , Recidiva , Resultado do Tratamento , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/etiologia
4.
Malays J Med Sci ; 21(6): 70-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25897287

RESUMO

Tuberculous scar tumour is difficult to diagnose as it does not present with any respiratory symptoms and has a negative chest X-ray. This is a case report on the use of dual tracer 11C-acetate and 18F-fluorodeoxyglucose (18FDG) whole body positron emission tomography-computerised tomography (PET-CT) for detection of tuberculous scar tumour. A 44-year-old Chinese female was incidentally found to have a raised serum Ca 19.9. Magnetic resonance imaging of the whole abdomen, upper endoscopy, and colonoscopy were all unremarkable. A low-dose computed tomography (CT) of the thorax showed bilateral upper lobe fibrosis. Bronchoalveolar lavage for culture and cytology was negative. A dual tracer 11C-acetate and 18FDG whole body PET-CT showed that the left upper lobe fibrosis was hypermetabolic in nature. It was more avid for 11C-acetate than for 18FDG. The left upper lobe lesion was subsequently confirmed on open lung biopsy to be a moderately differentiated adenocarcinoma. Therefore, in a tuberculous endemic region, dual tracer whole body PET-CT with 11C-acetate and 18FDG may have a role in the early detection of tuberculous scar tumour in the lung.

5.
Singapore Med J ; 54(3): e66-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23546039

RESUMO

Endogenous lipoid pneumonia is an uncommon condition. This is a report of a 29-year-old woman diagnosed with endogenous lipoid pneumonia associated with Legionella pneumophila serogroup 1 infection. The patient's endogenous lipoid pneumonia resolved completely after treatment for Legionella pneumophila infection. This suggests that early diagnosis and aggressive treatment of the underlying infection may prevent any long-term sequelae of lipoid pneumonia.


Assuntos
Legionella pneumophila/classificação , Doença dos Legionários/diagnóstico , Pneumonia Lipoide/diagnóstico , Pneumonia Lipoide/microbiologia , Adulto , Antibacterianos/uso terapêutico , Compostos Aza/uso terapêutico , Azitromicina/uso terapêutico , Feminino , Fluoroquinolonas , Humanos , Doença dos Legionários/tratamento farmacológico , Doença dos Legionários/microbiologia , Moxifloxacina , Pneumonia Lipoide/tratamento farmacológico , Quinolinas/uso terapêutico , Resultado do Tratamento
6.
Malays J Med Sci ; 20(5): 86-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24643224

RESUMO

Periportal halos are an uncommon finding on computerised tomography (CT) of the liver. Here, reported a case of periportal halos and hepatomegaly in a patient with eosinophilic gastroenteritis. A 49-year-old male presented with a six week history of right lower quadrant pain and diarrhoea. A CT of the abdomen showed hepatomegaly and multiple hypodense periportal halos around the patent portal veins consistent with periportal oedema. A colonoscopy showed normal looking mucosa in the colon and terminal ileum. Blind biopsies taken throughout the terminal ileum and colon showed increased numbers of eosinophils (more than 25 per high-power field) consistent with eosinophilic gastroenteritis. A liver biopsy showed minimal non-specific chronic inflammatory infiltrates and eosinophils in the portal tracts with ductular proliferation. In conclusion, eosinophilic gastroenteritis should be considered in patients presenting with periportal halos, hepatomegaly, and diarrhoea.

7.
Singapore Med J ; 53(9): e195-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23023914

RESUMO

Tumours consisting of a glandular component, either an adenoma or adenocarcinoma, and a carcinoid component are uncommon. These tumours can be differentiated into collision, composite or amphicrine tumours. Most cases reported in the literature were mixed adenocarcinoma-carcinoid tumours. To date, only four cases of mixed adenoma carcinoid tumours have been reported in the literature. This case report describes a unique case of collision adenoma-carcinoid tumour in the colon complicated by carcinoid syndrome in a 45-year-old woman who presented with a one-month history of diarrhoea and weight loss. She developed recurrence of the carcinoid component of the tumour four months after endoscopic resection. We conclude that carcinoid syndrome can occur in an adenoma-carcinoid tumour; however, the prognosis of this condition is uncertain.


Assuntos
Adenoma/patologia , Neoplasias do Colo/patologia , Síndrome do Carcinoide Maligno/patologia , Tumor Carcinoide/patologia , Colonoscopia , Diarreia/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Redução de Peso
10.
Malays J Med Sci ; 18(1): 76-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22135578

RESUMO

Inflammation of the gallbladder without evidence of calculi is known as acute acalculous cholecystitis (AAC). AAC is frequently associated with a poor prognosis and a high mortality rate. Thus, early diagnosis and prompt surgical intervention has been recommended to improve the outcome of AAC. Herein, I present a case report of AAC complicating laparoscopic appendicectomy. Unlike previous studies that have reported the need for urgent intervention in patients with AAC, in this study, our patient responded to conservative management. Therefore, the management of AAC after laparoscopic appendicectomy should be individualised.

11.
J Gastroenterol Hepatol ; 24(5): 896-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19646018

RESUMO

BACKGROUND AND METHODS: Upper endoscopy records from 1998 to 2003 were reviewed. The demographic data, endoscopic diagnosis, results of rapid urease test and the absence or presence of intestinal metaplasia (IM) in histology were reviewed, to evaluate the prevalence of IM and Helicobacter pylori (Hp) infection over time in Hong Kong. RESULTS: Among 1805 endoscopies performed, 1751 had both rapid urease test and histology available. A significant drop in the prevalence of duodenal ulcers from 17.9% in 1998 to 9.8% in 2003 was found (P = 0.015). Prevalence of IM was 13.9%, 5.9% and 9.4% in Hp positive, Hp negative and overall respectively (P < 0.05). The prevalence of IM increased with age, and the patterns were similar amongst subjects in 1998-2000 and those in 2001-2003. There was progressive decrease in Hp prevalence from 58% in 1998 to 40% in 2001 (P = 0.014), but no further decrease was seen in 2002-3. There was no corresponding decrease in IM prevalence. Instead IM prevalence in 2002-2003 was significantly higher than the prevalence in previous few years (P = 0.04). CONCLUSION: The prevalence of IM did not change in the period from 1998 to 2003 despite a drop in the prevalence of Hp infection since 1994.


Assuntos
Neoplasias Esofágicas/epidemiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/patogenicidade , Lesões Pré-Cancerosas/epidemiologia , Neoplasias Gástricas/epidemiologia , Úlcera Gástrica/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Testes Respiratórios , Úlcera Duodenal/epidemiologia , Úlcera Duodenal/microbiologia , Úlcera Duodenal/patologia , Endoscopia Gastrointestinal , Neoplasias Esofágicas/microbiologia , Neoplasias Esofágicas/patologia , Esofagoscopia , Feminino , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Hong Kong/epidemiologia , Humanos , Masculino , Metaplasia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Prevalência , Distribuição por Sexo , Fatores Sexuais , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Úlcera Gástrica/microbiologia , Úlcera Gástrica/patologia , Fatores de Tempo , Adulto Jovem
12.
Antivir Ther ; 13(2): 253-62, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18505176

RESUMO

BACKGROUND: Silver nanoparticles have been shown to exhibit promising cytoprotective activities towards HIV-infected T-cells; however, the effects of these nanoparticles towards other kinds of viruses remain largely unexplored. The aim of the present study was to investigate the effects of silver nanoparticles on hepatitis B virus (HBV). METHODS: Monodisperse silver nanoparticles with mean particle diameters of approximately 10 nm (Ag10Ns) and approximately 50 nm (Ag50Ns) were prepared from AgNO3 in HEPES buffer. The in vitro anti-HBV activities of these particles were determined using the HepAD38 cell line as infection model. RESULTS: Ag10Ns and Ag50Ns were able to reduce the extracellular HBV DNA formation of HepAD38 cells by >50% compared with the vehicle control (that is, HepAD38 cells in the absence of silver nanoparticles). Silver nanoparticles had little effect on the amount of HBV covalently closed circular DNA (cccDNA), but could inhibit the formation of intracellular HBV RNA. Gel mobility shift assays indicated that Ag10Ns bound HBV double-stranded DNA at a DNA:silver molar ratio of 1:50; an absorption titration assay showed that the nanoparticles have good binding affinity for HBV DNA with a binding constant (Kb) of (8.8 +/- 1.0)x10(5) dm(3)mol(-1). As both the viral and Ag10Ns systems are in the nanometer size range, we found that Ag10Ns could directly interact with the HBV viral particles as revealed by transmission electronic microscopy. CONCLUSIONS: Silver nanoparticles could inhibit the in vitro production of HBV RNA and extracellular virions. We hypothesize that the direct interaction between these nanoparticles and HBV double-stranded DNA or viral particles is responsible for their antiviral mechanism.


Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Nanopartículas/química , Prata/farmacologia , Replicação Viral/efeitos dos fármacos , Antivirais/química , Linhagem Celular , DNA/genética , DNA/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/fisiologia , Humanos , RNA Viral/genética , RNA Viral/metabolismo , Prata/química , Prata/metabolismo , Vírion/metabolismo
13.
Hepatology ; 48(2): 1-10, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18452145

RESUMO

UNLABELLED: Whether preemptive anti- hepatitis B virus (HBV) therapy should be considered in all hepatitis B surface antigen (HBsAg)-negative patients with occult HBV infection receiving alemtuzumab containing chemotherapy is uncertain. We determined the outcome and effect on HBV-specific immunity of an alemtuzumab-containing chemotherapy regimen in occult HBV-infected patients. Twenty-one consecutive occult HBV-infected patients treated with an alemtuzumab containing chemotherapy regimen were studied. T cell reactivity to HBV antigens and -peptides were quantified by ELISpot and the T cell subset by flow cytometry. Six of the 21 patients (28.6%) developed HBsAg seroreversion. The median (range) time to development of HBsAg seroreversion after the end of chemotherapy was 1.8 months (0.2-2.3 months). Direct sequencing showed that the occult HBV infection of all six patients (100%) was reactivated. These six patients developed severe HBV-related hepatitis. At the end of follow-up, four of these six patients (66.7%) had become negative for HBsAg again. Recovery of CD4+ T cell count and CD4+T cell reactivity against hepatitis B core antigen (HBcAg) occurred 9 months after the end of chemotherapy. Loss of HBsAg occurred after recovery of the CD4+T cell count and increased CD4+T cell reactivity against HBcAg 9 months after the end of chemotherapy. CONCLUSION: An alemtuzumab-containing chemotherapy regimen is associated with a high risk of reactivation of occult HBV infection. Suppression of HBV immunity by an alemtuzumab-containing chemotherapy regimen would persist until 9 months after the end of chemotherapy. In occult HBV-infected patients receiving an alemtuzumab-containing chemotherapy regimen, preemptive anti-HBV therapy should be continued until 9 months after the end of chemotherapy, when recovery of HBV immunity has occurred.

14.
J Infect ; 56(5): 389-92, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18423876

RESUMO

A 37-year-old man was presented with incidental findings of neutropenia, atypical lymphocytosis, thrombocytopenia and deranged liver parenchymal enzymes. Four days later, he developed fever, sore throat and cervical lymphadenopathy, compatible with mononucleosis-like illness (MLI). Polymerase chain reaction (PCR) and viral culture of the nasopharyngeal swab showed human metapneumovirus (hMPV). There was a >/=4-fold rise in IgG against hMPV. This is the first case report illustrating the natural clinical course of hMPV-related MLI.


Assuntos
Imunocompetência , Mononucleose Infecciosa , Metapneumovirus/patogenicidade , Infecções por Paramyxoviridae , Adulto , Humanos , Mononucleose Infecciosa/fisiopatologia , Mononucleose Infecciosa/virologia , Masculino , Infecções por Paramyxoviridae/fisiopatologia , Infecções por Paramyxoviridae/virologia
15.
J Clin Gastroenterol ; 42(5): 533-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18344885

RESUMO

BACKGROUND: The modified histology activity index (HAI) score has been extensively used as an additional primary or secondary end point in most phase III pivotal therapeutic clinical trials on chronic hepatitis B. Improvement in modified HAI after antiviral therapy has usually been defined as a 2-point reduction in modified HAI score. AIM: We studied whether a 2-point change in modified HAI score after antiviral therapy for chronic hepatitis B is associated with progression to liver complications (decompensated cirrhosis or hepatocellular carcinoma). METHOD: Eighty-nine patients treated with interferon-alpha with liver biopsy before and at 6 to 12 months after the end of therapy were followed-up for a median 119.4 months. RESULTS: At the time of analysis, 11 patients (12.4%) had liver complications. Liver complications were higher in patients with a 2-point increase in modified HAI score [8 of 19 patients (42.1%) vs. 3 of 70 patients (4.3%), P=0.0002] and in those with severe fibrosis at end of therapy [6 of 19 patients (31.6%) vs. 5 of 70 patients (7.1%), P=0.010]. On Cox regression analysis, a 2-point increase in modified HAI score was associated with increased liver complications (relative risk 5.564, P=0.036). CONCLUSIONS: A 2-point increase in modified HAI score after antiviral therapy is associated with increased progression to liver complications.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Hepatite B Crônica/patologia , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Fígado/patologia , Adolescente , Adulto , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , DNA Viral/análise , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Anticorpos Anti-Hepatite B/análise , Antígenos de Superfície da Hepatite B/análise , Antígenos E da Hepatite B/análise , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Hong Kong/epidemiologia , Humanos , Incidência , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença , Fatores de Tempo
16.
J Hepatol ; 48(5): 714-20, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18207280

RESUMO

BACKGROUND/AIMS: In order to prevent the occurrence of drug-resistant mutants associated with treatment for chronic hepatitis B virus (HBV) infection, combination therapy is being developed. To determine the efficacy of adefovir dipivoxil (ADV) plus emtricitabine (FTC) combination therapy in chronic HBV infection. METHODS: Thirty treatment-nai ve, HBeAg-positive patients were randomized to combination ADV plus FTC (n=14) or ADV plus placebo monotherapy (n=16) for 96 weeks. HBV DNA was measured by polymerase chain reaction. Treatment was stopped in those with HBeAg seroconversion. RESULTS: The median decrease in HBV DNA at week 96 was higher in the combination group (-5.30 vs. -3.98 log(10)copies/ml, p=0.05). More patients in the combination group had normalization of alanine aminotransaminase and HBV DNA<300 copies/ml at week 96 when compared with the monotherapy group [11 of the 14 patients (78.6%) vs. 6 of the 16 patients (37.5%), p=0.03]. However, HBeAg seroconversion at week 96 was similar in the 2 groups [2/14 (14.3%) vs. 4/16 (25.0%), p=NS]. No ADV or FTC resistance was detected at week 96. In those with HBeAg seroconversion, 50.0% had post-treatment relapse. CONCLUSIONS: Combination ADV plus FTC resulted in more potent suppression of HBV DNA over 96 weeks of therapy.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Desoxicitidina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenina/uso terapêutico , Adulto , Alanina Transaminase/sangue , DNA Viral/sangue , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Farmacorresistência Viral , Quimioterapia Combinada , Emtricitabina , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/administração & dosagem , Organofosfonatos/efeitos adversos
17.
Hepatology ; 46(3): 690-8, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17680649

RESUMO

UNLABELLED: Recently, controversies have arisen about whether hepatitis B e antigen (HBeAg) seroconversion can result in regression of fibrosis, thus improving the clinical outcome of Chinese patients with chronic hepatitis B. In this study, we determined if spontaneous HBeAg seroconversion is associated with regression of fibrosis in Chinese chronic hepatitis B patients. We evaluated the histology of liver samples from 128 HBeAg-positive treatment-naive Chinese patients who had undergone 2 liver biopsies over the years. Regression of fibrosis was defined as a decrease in fibrosis stage of at least 1 point. Sustained disease remission was defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA < 10(4) copies/ml at follow-up liver biopsy. The mean duration (+/- standard error of the mean) between the initial and follow-up liver biopsies was 43.9 +/- 3.4 months. Regression of fibrosis was higher in patients with sustained disease remission (5 of 13 [38.5%] versus 22 of 115 [19.1%], P < 0.00005), patients who were younger (20-29 years old) at initial liver biopsy (17 of 54 [31.5%] versus 10 of 74 [13.5%], P = 0.0004), and patients with genotype B (17 of 43 [39.5%] versus 10 of 85 [11.8%], P = 0.004). On multivariate analysis, sustained disease remission (relative risk [RR] 3.00, 95% confidence interval [95% CI] 1.29-7.01, P = 0.01) and being 20-29 years old at initial liver biopsy (RR 2.94, 95% CI 1.01-8.62, P = 0.04) were independently associated with regression of fibrosis. The rate of fibrosis progression was lower in patients with sustained disease remission than in those who remained HBeAg positive (median 0 fibrosis units/year, range -2.00 to -0.70 fibrosis units/year, versus median 0.51 fibrosis units/year, range 0 to +2.03 fibrosis units/year, P = 0.02). CONCLUSION: Spontaneous sustained remission of disease is associated not only with little progression of fibrosis but also with regression of fibrosis.


Assuntos
Anticorpos Anti-Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Adulto , Povo Asiático , Biomarcadores/sangue , DNA Viral/sangue , Progressão da Doença , Feminino , Hepatite B Crônica/imunologia , Hepatite B Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Remissão Espontânea , Replicação Viral
18.
Antivir Ther ; 12(5): 705-18, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17713154

RESUMO

BACKGROUND: The patterns of hepatitis B viral dynamics during different antiviral therapies and the associated changes in HBV-specific T-cell reactivity are not well defined. METHODS: We investigated the impact of early viral load decline on virus-specific T-cell reactivity in 30 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B randomized to monotherapy with adefovir dipivoxil (ADV) or in combination with emtricitabine (ADV/FTC). Viral kinetics were analysed by mathematical modelling. T-cell reactivity to HBV core and/or surface antigens and natural killer T cell frequency were tested longitudinally, baseline to week 48, using EliSPOT assays and/or flow cytometry. RESULTS: Mathematical modelling of early HBV kinetics identified two subsets of patients: 11 fast responders (undetectable viraemia by week 12; eight on ADV/FTC three on ADV) and 19 slow responders who remained viremic (six on ADV/FTC 13 on ADV). The rate of infected hepatocyte loss was higher in fast than in slow responders (P = 0.0007), and correlated inversely with pre-treatment levels of intrahepatic covalently closed circular HBV DNA. The frequency of HBV core-specific CD4+ T-cells increased significantly only in fast responders, peaking between week 16 and 24, while the HBV surface-specific CD4+ T-cells increased in both subsets. These changes in CD4+ T-cell reactivity were transient however, and no increase in HBV-specific CD8+ T-cells was observed. By week 48, HBeAg seroconversion occurred only in 3/30 (10%) patients. CONCLUSIONS: Early viraemia clearance facilitates recovery of virus-specific CD4+ T-cell reactivity, but appears insufficient to establish clinically relevant antiviral immunity.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , DNA Viral/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Linfócitos T/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Adenina/farmacologia , Adenina/uso terapêutico , Adulto , Antivirais/farmacologia , DNA Viral/biossíntese , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Emtricitabina , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/crescimento & desenvolvimento , Vírus da Hepatite B/imunologia , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/virologia , Humanos , Imunidade Celular , Cinética , Masculino , Pessoa de Meia-Idade , Modelos Imunológicos , Organofosfonatos/farmacologia , Linfócitos T/virologia , Resultado do Tratamento , Carga Viral , Viremia/tratamento farmacológico , Viremia/genética , Viremia/imunologia , Viremia/virologia
19.
Virus Res ; 130(1-2): 285-91, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17601623

RESUMO

Chronic infection by Hepatitis C Virus (HCV) causes liver fibrosis, which is accelerated by unknown mechanisms in patients with HIV-1 coinfection. The evolution of HCV quasispecies in this setting of coinfection is not fully understood. To compare HCV quasispecies between HIV-HCV coinfection and HCV monoinfection, we sequenced 340 HCV clones from the HVR-1 and NS3 regions at two different time points in two groups of treatment-naïve patients with HCV-1a infection: (1) HIV-HCV positive (n=6); and (2) HIV negative-HCV positive (n=3). In HCV/HIV coinfection, we found a trend for reduced HCV genetic complexity and diversity, and a trend towards reduced dN/dS ratios in the HVR-1 region, especially in those patients with CD4<200cells/mm(3), who lost positive selective immune pressure in the HVR-1 region. Differences in immune regulation of HCV quasispecies in HIV coinfected individuals deserve further exploration to clarify the different outcomes of chronic hepatitis C noted between the immunocompromised and the immunocompetent host.


Assuntos
Variação Genética , Infecções por HIV/complicações , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/virologia , Adulto , Contagem de Linfócito CD4 , Análise por Conglomerados , Hepacivirus/isolamento & purificação , Hepatite C Crônica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , RNA Viral/genética , Análise de Sequência de DNA , Homologia de Sequência , Proteínas não Estruturais Virais/genética , Proteínas Virais/genética
20.
Hepatology ; 46(2): 395-401, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17628874

RESUMO

UNLABELLED: In view of the findings that high hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is associated with increased risk of chronic hepatitis B (CHB)-related complications, disease progression in CHB patients in the immune-tolerant phase is uncertain. We evaluated disease progression in 57 immune-tolerant CHB patients with high HBV DNA. Each subject underwent an initial liver biopsy. In those who remained in the immune-tolerant phase, a follow-up liver biopsy was performed after 5 years of follow-up. Patients who developed elevated serum alanine aminotransferase (ALT) levels were discontinued from the study after a follow-up liver biopsy. Disease progression was defined as a 1-point increase in fibrosis stage. Initial liver biopsies showed the median fibrosis stage of the study patients was 1 (range 0-1). By the end of follow-up, 9 of the 57 patients (15.8%) had developed elevated serum ALT. In those who remained in the immune-tolerant phase, follow-up fibrosis stage was comparable with the initial fibrosis stage (P = 0.58). However, disease progression was greater in patients who developed elevated serum ALT when compared with those who remained in the immune-tolerant phase (5 of 9 vs. 3 of 48, respectively, P = 0.001). The median rate of fibrosis progression of patients who remained in the immune-tolerant phase was lower than that of patients with high serum ALT (0 U/year [range -0.40-0.20 U/year] versus 0.21 U/year [range 0-1.11 U/year], respectively, P = 0.04). CONCLUSION: CHB patients in the immune-tolerant phase have mild disease. In those who remained in the immune-tolerant phase in the present study, disease progression was minimal. However, immune-tolerant patients who progressed to the immune clearance phase often faced disease progression.


Assuntos
Hepatite B Crônica/complicações , Adolescente , Adulto , Alanina Transaminase/sangue , DNA Viral/sangue , Progressão da Doença , Feminino , Seguimentos , Antígenos E da Hepatite B/análise , Hepatite B Crônica/imunologia , Hepatite B Crônica/patologia , Humanos , Tolerância Imunológica , Fígado/patologia , Masculino
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