RESUMO
The burden and impact of secondary superadded infections in critically ill coronavirus disease 2019 (COVID-19) patients is widely acknowledged. However, there is a dearth of information regarding the impact of COVID-19 in patients with tuberculosis, HIV, chronic hepatitis, and other concurrent infections. This review was conducted to evaluate the consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with concurrent co-infections based on the publications reported to date. An extensive comprehensive screening was conducted using electronic databases up to 3rd September 2020 after obtaining registration with PROSPERO (CRD420202064800). The observational studies or interventional studies in English, evaluating the impact of SARS-CoV-2 in patients with concurrent infections are included for the meta-analyses. Our search retrieved 20 studies, with a total of 205,702 patients. Patients with tuberculosis (RR = 2.10; 95% CI, 1.75-2.51; I2 = 0%), influenza (RR = 2.04; 95% CI, 0.15-28.25, I2 = 99%) have an increased risk of mortality during a co-infection with SARS-CoV-2. No significant impact is found in people living with HIV (RR = 0.99; 95% CI, 0.82-1.19; I2 = 30%), Chronic hepatitis (RR = 1.15; 95% CI, 0.73-1.81; I2 = 10%). Several countries (Brazil, Paraguay, Argentina, Peru, Colombia, and Singapore) are on the verge of a dengue co epidemic (cumulative 878,496 and 5,028,380 cases of dengue and COVID-19 respectively). The impact of COVID-19 in patients of concurrent infections with either tuberculosis or influenza is detrimental. The clinical outcomes of COVID-19 in HIV or chronic hepatitis patients are comparable to COVID-19 patients without these concurrent infections.
Assuntos
COVID-19/epidemiologia , COVID-19/microbiologia , Coinfecção/epidemiologia , Coinfecção/microbiologia , Coinfecção/virologia , Bases de Dados Factuais , Dengue/epidemiologia , Dengue/microbiologia , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Hepatite Crônica/epidemiologia , Hepatite Crônica/microbiologia , Humanos , Influenza Humana/epidemiologia , Influenza Humana/microbiologia , SARS-CoV-2/isolamento & purificação , Tuberculose/epidemiologia , Tuberculose/microbiologiaRESUMO
INTRODUCTION: Microbial translocation (MT) markers are indicators of HIV-related immune activation, but reference values are mostly derived from European or North American populations and could be substantially different in populations living in developing countries. Here we evaluate possible differences in MT markers levels in HIV+ pregnant women of different geographical provenance. METHODOLOGY: This study is nested within an observational study of pregnant women with HIV in Italy. Women were dichotomized on the basis of provenance in two groups of European (n = 14) and African (n = 26) origin. Soluble CD14, lipopolysaccharide-binding protein (LBP) and intestinal-fatty acid binding protein (I-FABP) were measured in plasma samples collected between the first and second trimester of pregnancy. RESULTS: Demographic and viroimmunological characteristics were similar between groups, although European women were more commonly smokers and HCV-coinfected. Irrespective of origin, LBP plasma levels were positively correlated with I-FABP (r = 0.467, p = 0.004) and sCD14 levels (r = 0.312 p = 0.060). Significantly higher levels of sCD14 (1885 vs. 1208 ng/mL, p = 0.005) LBP (28.5 vs. 25.3 µg/mL, p = 0.050) and I-FABP (573.4 vs. 358.2 pg/mL, p = 0.002) were observed in European compared with African women. A multivariable linear regression analysis, adjusted for smoking and HCV coinfection confirmed the association between sCD14 levels and women provenance (p = 0.03). CONCLUSIONS: Our observations indicate significant differences in soluble markers among women of different provenance. In the design and analysis of studies evaluating MT markers, population-specific reference values should be considered.
Assuntos
Proteínas de Transporte/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Infecções por HIV/sangue , Receptores de Lipopolissacarídeos/sangue , Glicoproteínas de Membrana/sangue , Complicações Infecciosas na Gravidez/sangue , Proteínas de Fase Aguda , Adulto , África , Biomarcadores/sangue , Coinfecção/sangue , Coinfecção/complicações , Coinfecção/microbiologia , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/microbiologia , Europa (Continente) , Feminino , Infecções por HIV/complicações , Infecções por HIV/microbiologia , HIV-1 , Hepatite Crônica/sangue , Hepatite Crônica/complicações , Hepatite Crônica/microbiologia , Humanos , Plasma/química , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/virologia , Primeiro Trimestre da Gravidez , Segundo Trimestre da GravidezRESUMO
It has been documented that Helicobacter hepaticus (H. hepaticus) infection is linked to hepatic inflammation and fibrosis. Interleukin 33 (IL-33) is a cytokine involved in inflammatory and fibrotic diseases, but its relevance to H. hepaticus infection-induced liver inflammation and fibrosis is unknown. In this study, we found that the expression of IL-33 in mice liver was significantly induced by H. hepaticus infection at 24 weeks post infection (WPI). Immunohistochemistry analysis revealed that IL-33 was transferred from the nucleus to the cytoplasm due to infection. The quantitation of inflammatory cytokine and histopathology evaluation showed that IL-33 knockdown attenuated the H. hepaticus-induced hepatic inflammation and fibrosis. More importantly, H. hepaticus promoted the expression of the IL-33 receptor ST2 on cell surfaces, and the expression of ST2 then activated the expression nuclear factor-κB (p65), α-SMA, and Erk1/2. These observations provide novel insights into the pathogenic mechanism of hepatic inflammation and fibrosis during H. hepaticus infection.
Assuntos
Infecções por Helicobacter/microbiologia , Helicobacter hepaticus/patogenicidade , Inflamação/microbiologia , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Cirrose Hepática/microbiologia , Fígado/patologia , Transdução de Sinais , Animais , Infecções por Helicobacter/patologia , Hepatite Crônica/complicações , Hepatite Crônica/microbiologia , Hepatite Crônica/patologia , Inflamação/complicações , Inflamação/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos BALB C , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Increasing evidence indicates a close relationship between HCC and the human microbiota. Herein, we reviewed the important potential of the human microbiota as a diagnostic biomarker of HCC. DATA SOURCES: Several innovative studies have investigated the characteristics of the gut and oral microbiomes in patients with HCC and proposed that the human microbiome has the potential to be a diagnostic biomarker of HCC. Literature from February 1999 to February 2019 was searched in the PubMed database using the keywords "microbiota" or "microbiome" or "microbe" and "liver cancer" or "hepatocellular carcinoma", and the results of clinical and experimental studies were analyzed. RESULTS: Specific changes occur in the human microbiome of patients with HCC. Moreover, the gut microbiome and oral microbiome can be used as non-invasive diagnostic biomarkers for HCC. Furthermore, they also have certain diagnostic potential for precancerous diseases of HCC. The diagnostic potential of the blood microbiota and ascites microbiota in HCC will be gradually discovered in the future. CONCLUSIONS: The human microbiome is valuable to the diagnosis of HCC and provides a novel strategy for targeted therapy of HCC. The human microbiome may be widely used in the diagnosis, treatment and prognosis for multiple system diseases or cancers in the future.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Microbioma Gastrointestinal , Hepatite Crônica/microbiologia , Neoplasias Hepáticas/diagnóstico , Boca/microbiologia , Lesões Pré-Cancerosas/microbiologia , Biomarcadores , Hepatite Crônica/virologia , Humanos , Cirrose Hepática/microbiologia , Hepatopatias Alcoólicas/microbiologia , Hepatopatia Gordurosa não Alcoólica/microbiologiaRESUMO
BACKGROUND: It has been documented that Helicobacter hepaticus (H hepaticus) infection is linked to chronic hepatitis and liver cancer. However, our understanding of the molecular mechanisms underlying progression of the H hepaticus-induced hepatic inflammation to cellular hepatocarcinoma is still limited. MATERIALS AND METHODS: In our study, male BALB/c mice were infected by H hepaticus for 8, 12, 16, 20, and 24 weeks. Histopathology, H hepaticus colonization dynamics, select signaling pathways, and expression of key inflammatory cytokines in the liver were examined. RESULTS: We found that H hepaticus was detectible in feces of mice at 7 days postinfection (DPI) by PCR, but it was not detected in the livers by PCR until 8 weeks postinfection (WPI). In addition, abundance of colonic and hepatic H hepaticus was progressively increased over the infection duration. H hepaticus-induced hepatic inflammation and fibrosis were aggravated over the infection duration, and necrosis or cirrhosis developed in the infected liver at 24 WPI H hepaticus infection increased levels of alanine aminotransferase and aspartate aminotransferase. Moreover, mRNA levels of Il-6 and Tnf-α were significantly elevated in the livers of H hepaticus-infected mice compared to uninfected control from 8 WPI to 24 WPI. Furthermore, Stat3, nuclear factor-κB (p65), and MAPK (Erk1/2 and p38) were activated by H hepaticus infection. CONCLUSIONS: These data demonstrated that male BALB/c mice can be used as a new mouse model of H hepaticus-induced liver diseases and that the H hepaticus-induced liver injury is triggered by NF-κB, Jak-Stat, and MAPK signaling pathways.
Assuntos
Fibrose/microbiologia , Helicobacter hepaticus , Hepatite Crônica/microbiologia , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Citocinas/biossíntese , Fezes/microbiologia , Infecções por Helicobacter/patologia , Helicobacter hepaticus/genética , Helicobacter hepaticus/isolamento & purificação , Fígado/microbiologia , Fígado/patologia , Neoplasias Hepáticas/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The broadening field of microbiome research has led to a substantial reappraisal of the gut-liver axis and its role in chronic liver disease. The liver is a central immunologic organ that is continuously exposed to food and microbial-derived antigens from the gastrointestinal tract. Mucosal-associated invariant T (MAIT) cells are enriched in the human liver and can be activated by inflammatory cytokines and microbial antigens. In chronic inflammatory liver disease, MAIT cells are depleted suggesting an impaired MAIT cell-dependent protection against bacterial infections.
Assuntos
Hepatite Crônica/imunologia , Fígado/imunologia , Células T Invariantes Associadas à Mucosa/imunologia , Animais , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Microbioma Gastrointestinal , Hepatite Crônica/diagnóstico , Hepatite Crônica/metabolismo , Hepatite Crônica/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Fígado/microbiologia , Fígado/patologia , Ativação Linfocitária , Células T Invariantes Associadas à Mucosa/metabolismo , Células T Invariantes Associadas à Mucosa/microbiologia , Células T Invariantes Associadas à Mucosa/patologia , FenótipoRESUMO
Inflammation is one of the most prominent characteristic features of chronic liver disease, liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Most of HCC cases develop in patients with cirrhosis and cirrhosis develops in patients with chronic liver inflammation. Therefore, there is no doubt that there exist some strong connection among inflammation, fibrosis, and cancer. In fact, chronic unresolved inflammation is associated with persistent hepatic injury and concurrent regeneration, leading to sequential development of fibrosis, cirrhosis, and eventually HCC. This review will discuss the common mechanism of inflammation and fibrosis in chronic liver diseases, and then demonstrate why HCC develops in inflammatory and fibrotic conditions.
Assuntos
Carcinoma Hepatocelular/etiologia , Hepatite Crônica/complicações , Inflamação , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Bactérias Gram-Negativas/crescimento & desenvolvimento , Hepatite Crônica/metabolismo , Hepatite Crônica/microbiologia , Humanos , Hipóxia , Lipopolissacarídeos/metabolismo , Fígado/metabolismo , Fígado/patologia , Receptores Toll-Like/metabolismoRESUMO
OBJECTIVE: To investigate clinical features and antifungal therapeutic effect of chronic severe hepatitis (CSH) patients with invasive fungal infection (IFI), and to improve the diagnosis and treatment. METHODS: Clinical manifestation, blood routine, imageology and mycetology characteristic, antifungal treatment perscription and therapeutic effect of 79 CSH patients with IFI were retrospectively analyzed. Antifungal therapeutic effect was compared between fluconazole and voriconazole. RESULTS: Thirteen (16.5%) patients received glucocorticoid or other immunodepressants for a relatively long time, 40 (50.6%) patients had invasive operation, and 61 (77.2 %) patients were administered 1-6 kinds of broad-spectrum antibiotics. Seventy-three patients had fever. Leucocytes and neutrophilic granulocyte increased in 96.2% of the patients. Lung (31.6%), intestinal tract (26.2%) and oral cavity (14%) infections were common. Fungus was found in 70.9% of the patients. Candida albicans (40.9%) and aspergillus (21.1%) were often seen. Halo signs and crescent signs on lung CT were relatively specific in 40% of the patients with fungal pneumonia. Voriconazole was more effective than fluconazole(71.4% vs. 39.0%, P<0.05). Twelve patients with lung aspergillus infection were administered voriconazole, 8 (66.7%) patients of whom was effective, and the other 4 (33.3%) patients died. CONCLUSION: There are high risk factors in major CSH patients with IFI. The most common clinical manifestations of CSH patients with IFI are fever, leukocytosis, lung and intestinal tract infection. Candida albicans and aspergillus infection are common. Voriconazole is more effective than fluconazole, and can increase the survival rate of CSH patients with IFI.
Assuntos
Antifúngicos/uso terapêutico , Hepatite Crônica/complicações , Micoses/complicações , Adulto , Idoso , Aspergilose/complicações , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Candidíase/complicações , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Hepatite Crônica/microbiologia , Humanos , Pessoa de Meia-Idade , Micoses/diagnóstico , Micoses/tratamento farmacológico , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Triazóis/uso terapêutico , Voriconazol , Adulto JovemRESUMO
BACKGROUND: Staphylococcus aureus increasingly is recognized as an important pathogen in patients with chronic liver diseases. The purpose of this study was to evaluate clinical features and the outcome of S. aureus infections in patients with chronic liver diseases. METHODS: From the database of a surveillance study for S. aureus infections, the data regarding S. aureus infections in patients with chronic liver diseases were analysed and compared with those in patients with other diseases. RESULTS: We identified 298 patients who had chronic liver diseases; 151 (50.7%) patients had cirrhosis, 76 (25.5%) had chronic hepatitis and the remaining 71 (23.8%) had other diseases. The most common type of S. aureus infection in patients with chronic liver diseases was primary bacteraemia (n=68, 22.8%) and 92 (30.9%) patients had concomitant bacteraemia. When compared with other disease group, bacteraemia and bone infection were more frequent in the liver disease group (P<0.05). The 30-day mortality rate of the liver disease group was significantly higher than that of the other disease group (29.4 vs. 16.7%, P<0.001). A multivariate analysis showed that chronic liver disease was a significant factor associated with mortality, along with old age, immunosuppressive treatment, intubated state, indwelling urinary catheter, pneumonia and concomitant bacteraemia. CONCLUSIONS: Bacteraemia was the most common type of S. aureus infection in patients with underlying liver diseases, predicting higher mortality rates. The mortality rate of patients with liver diseases was significantly higher than that of patients with other diseases when S. aureus infection developed.
Assuntos
Hepatopatias/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/patogenicidade , Idoso , Ásia/epidemiologia , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/patologia , Doença Crônica , Comorbidade , Feminino , Hepatite Crônica/microbiologia , Hepatite Crônica/mortalidade , Hepatite Crônica/patologia , Humanos , Cirrose Hepática/microbiologia , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Hepatopatias/mortalidade , Hepatopatias/patologia , Masculino , Vigilância da População , Estudos Prospectivos , Infecções Estafilocócicas/mortalidade , Infecções Estafilocócicas/patologia , Taxa de SobrevidaRESUMO
OBJECTIVE: To investigate the infection of Helicobacter pylori (Hp) in the liver tissue of patients with chronic liver disease and the association between Hp and chronic liver disease. METHODS: Liver tissue samples were obtained by liver biopsy and surgical resection from 30 healthy subjects, 30 patients with chronic hepatitis, 30 with cirrhosis and 30 with liver cancer. All the samples were confirmed by pathological examination. The gene fragment coding for 16SrRNA were amplified by PCR with sequence analysis. RESULTS: The PCR product of the 16SrRNA gene was 109 bp in length. Hp 16SrRNA was detected in 18 out of 30 liver biopsy samples from patients with primary cancer (60.0%), in 14 samples from patients with liver cirrhosis (47.0%), and in none of the samples from normal subjects or patients with chronic hepatitis. Sequencing analysis of Hp 16SrRNA gene in the liver tissue showed a 98.8% homology with the gene fragment encoding Hp 16SrRNA. CONCLUSION: Hp is identified in the liver tissue of patients with chronic liver disease, suggesting the possible correlation between Hp infection and hepatocellular carcinoma.
Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Hepatite Crônica/microbiologia , Cirrose Hepática/microbiologia , Neoplasias Hepáticas/microbiologia , Adulto , Idoso , Sequência de Bases , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Hepatite Crônica/complicações , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Adulto JovemRESUMO
We recently described helicobacter-associated progressive, proliferative, and dysplastic typhlocolitis in aging (18- to 24-month-old) Syrian hamsters. Other pathogens associated with typhlocolitis in hamsters, Clostridium difficile, Lawsonia intracellularis, and Giardia spp., were not indentified. The presence of Helicobacter genus-specific DNA was noted by PCR in cecal and paraffin-embedded liver samples from aged hamsters by the use of Helicobacter-specific PCR primers. By 16S rRNA analysis, the Helicobacter sp. isolated from the liver tissue was identical to the cecal isolates from hamsters. The six hamster 16S rRNA sequences form a genotypic cluster most closely related to Helicobacter sp. Flexispira taxon 8, part of the Helicobacter bilis/H. cinaedi group. Livers from aged helicobacter-infected hamsters showed various stages of predominantly portocentric and, to a lesser extent, perivenular fibrosis. Within nodules, there was cellular atypia consistent with nodular dysplasia. The livers also exhibited a range of chronic active portal/interface and lobular inflammation, with significant portal hepatitis being present. The inflammation was composed of a mixture of lymphocytes, neutrophils, and macrophages, indicative of its chronic-active nature in these aged hamsters infected with Helicobacter spp. The isolation of novel Helicobacter spp., their identification by PCR from the diseased livers of aged hamsters, and their taxonomic classification as belonging to the Helicobacter bilis cluster strengthen the argument that H. bilis and closely related Helicobacter spp. play an etiological role in hepatobiliary disease in both animals and humans.
Assuntos
Doenças Biliares/veterinária , Fibrose/veterinária , Infecções por Helicobacter/veterinária , Helicobacter/patogenicidade , Hepatite Crônica/veterinária , Hiperplasia/veterinária , Cirrose Hepática/veterinária , Animais , Doenças Biliares/microbiologia , Ceco/microbiologia , Análise por Conglomerados , Cricetinae , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , DNA Ribossômico/química , DNA Ribossômico/genética , Fibrose/microbiologia , Helicobacter/classificação , Helicobacter/genética , Helicobacter/isolamento & purificação , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Hepatite Crônica/microbiologia , Hepatite Crônica/patologia , Hiperplasia/microbiologia , Inflamação/patologia , Fígado/microbiologia , Fígado/patologia , Cirrose Hepática/microbiologia , Cirrose Hepática/patologia , Linfócitos/imunologia , Macrófagos/imunologia , Mesocricetus/microbiologia , Dados de Sequência Molecular , Neutrófilos/imunologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , RNA Bacteriano/genética , RNA Bacteriano/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
Helicobacter DNA has been detected in the liver specimens of patients with various hepato-biliary diseases. The aim of this study was to investigate the presence of H. pylori DNA in the liver tissue of Iranian patients with chronic liver diseases (CLD). Genomic DNA was extracted from the paraffin sections of 46 liver biopsies of patients with CLD and 13 from patients with metastatic adenocarcinoma as a control group. Polymerase chain reaction (PCR) analysis was carried out using primers for H. pylori 16S rRNA and cagA genes. On analysis, 17 of the 46 patient samples were positive in H. pylori 16S rRNA PCR and 2 of the 13 were positive from the control group. None of the samples were positive for the cagA gene. This study showed the greater presence of H. pylori-like DNA in the liver samples from patients with CLD than in controls.
Assuntos
DNA Bacteriano/isolamento & purificação , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Hepatopatias/microbiologia , Fígado/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Fígado Gorduroso/microbiologia , Feminino , Hepatite Crônica/microbiologia , Humanos , Cirrose Hepática/microbiologia , Masculino , Pessoa de Meia-Idade , Inclusão em Parafina , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Análise de Sequência de DNA , Adulto JovemRESUMO
BACKGROUND/AIMS: Peptic ulcers occur more commonly in patients with liver cirrhosis (LC). Helicobacter pylori is recognized as the most important etiology in the pathogenesis of peptic ulcers. We investigated the efficacy of proton pump inhibitor (PPI)-based triple therapy in patients with chronic liver disease and peptic ulcer. PATIENTS AND METHODS: One hundred sixty-three patients with LC or chronic hepatitis (CH) with a peptic ulcer and proven H. pylori infection were included. The combination of PPI, amoxicillin (1.0 g), and clarithromycin (500 mg), each given twice daily, was administered for 1 or 2 weeks. The eradication of H. pylori was determined by the rapid urease test, histology, or the 13C-urea breath test at least 4 weeks after completing the treatment. RESULTS: The eradication rate of H. pylori was similar between the LC and CH groups; 82.6% and 88.1%, respectively. In addition, there were no significant differences in eradication rates between the patients with Child-Pugh class A and Child-Pugh class B/C disease. The side effects in each group were generally mild. Only the serum ALT levels showed a significant correlation with the success of H. pylori eradication in both the LC and CH groups. CONCLUSION: The PPI-based triple therapy achieves high eradication rates for H. pylori infection, in patients with chronic liver disease, without significant side effects.
Assuntos
Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Hepatite Crônica/microbiologia , Cirrose Hepática/microbiologia , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/microbiologia , Adulto , Alanina Transaminase/sangue , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Testes Respiratórios , Claritromicina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Endoscopia do Sistema Digestório , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/diagnóstico , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Hepatite Crônica/microbiologia , Cirrose Hepática/microbiologia , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/microbiologia , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Endoscopia do Sistema Digestório , Infecções por Helicobacter/diagnóstico , Humanos , Úlcera Péptica/diagnóstico , Inibidores da Bomba de Prótons/uso terapêutico , Projetos de Pesquisa , Resultado do TratamentoRESUMO
Helicobacter hepaticus causes hepatitis in susceptible strains of mice. Previous studies indicated that A/JCr mice are susceptible and C57BL/6NCr mice are resistant to H. hepaticus-induced hepatitis. We used F1 hybrid mice derived from A/J and C57BL/6 matings to investigate their phenotype and determine their hepatic gene expression profile in response to H. hepaticus infection. F1 hybrid mice, as well as parental A/J and C57BL/6 mice, were divided equally into control and H. hepaticus-infected groups and euthanized at 18 months postinoculation. Hepatic lesions were evaluated histologically and the differential hepatic gene expression in F1 mice was determined by microarray-based global gene expression profiling analysis. H. hepaticus-infected parental strains including A/J and C57BL/6 mice, as well as F1 mice, developed significant hepatitis. Overall, hepatocellular carcinomas or dysplastic liver lesions were observed in 69% of H. hepaticus-infected F1 male mice and H. hepaticus was isolated from hepatic tissues of all F1 mice with liver tumors. Liver tumors, characterized by hepatic steatosis, developed in livers with high hepatitis scores. To identify gene expression specific to H. hepaticus-induced hepatitis and progression to hepatocellular carcinoma in F1 mice, a method using comparative group transcriptome analysis was utilized. The canonical pathway most significantly enriched was immunological disease. Fatty acid synthase and steaoryl-coenzyme A desaturase, the two rate-limiting enzymes in lipogenesis, were upregulated in neoplastic relative to dysplastic livers. This study suggests a synergistic interaction between hepatic steatosis and infectious hepatitis leading to hepatocellular carcinoma. The use of AB6F1 and B6AF1 mice, as well as genetically engineered mice, on a C57BL/6 background will allow studies investigating the role of chronic microbial hepatitis and steatohepatitis in the pathogenesis of liver cancer.
Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Predisposição Genética para Doença , Infecções por Helicobacter/genética , Hepatite Crônica/genética , Padrões de Herança , Animais , Carcinoma Hepatocelular/microbiologia , Ácido Graxo Sintases/biossíntese , Fígado Gorduroso/patologia , Feminino , Perfilação da Expressão Gênica , Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter hepaticus/fisiologia , Hepatite Crônica/complicações , Hepatite Crônica/imunologia , Hepatite Crônica/microbiologia , Fígado/microbiologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos A , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos , Índice de Gravidade de Doença , Estearoil-CoA Dessaturase/biossíntese , Regulação para CimaRESUMO
Bacterial cytolethal distending toxins (CDTs) containing DNase I-like activity can induce limited host DNA damage that leads to activation of the DNA-damage repair responses in cultured cell lines. However, in vivo experimental evidence linking CDTs to carcinogenesis is lacking. In this study, infection of A/JCr mice with an isogenic mutant of Helicobacter hepaticus lacking CDT activity (CDT mutant) induced chronic hepatitis comparable to wild-type H. hepaticus (Hh) infection at both 4 and 10 months post inoculation (MPI); however, the CDT mutant-infected mice did not develop hepatic dysplasic nodules at 10 MPI, whereas those infected with Hh did. There was no significant difference in hepatic colonization levels between the CDT mutant and Hh at both time points (P > 0.05). At 4 MPI, mice infected with Hh had significantly enhanced hepatic transcription of proinflammatory TNF-alpha, IFN-gamma and Cox-2, growth mediators IL-6 and TGF-alpha, anti-apoptotic Bcl-2 and Bcl-X(L), and increased hepatocyte proliferation (P < 0.05) compared with the control or the CDT mutant-infected mice. In addition, Hh infected male mice had upregulated hepatic mRNA levels of RelA (p65), p50, GADD45beta and c-IAP1, components of the NF-kappaB pathway compared with the CDT mutant-infected mice. At 10 MPI, Hh infection was associated with significant upregulation of IL-6 mRNA. Activation of the inflammatory NF-kappaB pathway and upregulation of proinflammatory cytokines plus IL-6 in the Hh but not in the CDT mutant-infected mice suggest that Hh CDT plays a key role in promoting the dysplastic changes in Hh-infected mouse livers.
Assuntos
Toxinas Bacterianas/metabolismo , Transformação Celular Neoplásica , Infecções por Helicobacter/patologia , Helicobacter hepaticus/fisiologia , Hepatite Crônica/patologia , Fígado/patologia , Ativação Transcricional , Animais , Toxinas Bacterianas/genética , Feminino , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter hepaticus/genética , Hepatite Crônica/metabolismo , Hepatite Crônica/microbiologia , Hepatócitos/microbiologia , Hepatócitos/patologia , Fígado/metabolismo , Fígado/microbiologia , Masculino , Camundongos , MutaçãoRESUMO
OBJECTIVE: We quantified cytochrome P-450 (CYP) 3A4 mRNA in the blood and liver of patients with viral liver diseases to determine whether CYP 3A4 expression is related to disease progression. DESIGN AND METHODS: Total RNA was extracted from 10 mL of blood from 12 normal volunteers, from 6 patients with acute hepatitis, 17 with chronic hepatitis, 12 with liver cirrhosis, and 16 with hepatocellular carcinoma. Total RNA from 1 mg of liver tissue was extracted simultaneously in 10 patients. CYP 3A4 mRNA was quantified by competitive reverse-transcription polymerase chain reaction and expressed as log copies/microliter. RESULTS: The CYP 3A4 mRNA titer in blood correlated with that of the liver (r = 0.65, P < 0.05). The CYP 3A4 mRNA titer was 1.6 +/- 0.4 in normal controls, 1.0 +/- 0.5 in acute hepatitis, 0.7 +/- 0.2 in chronic hepatitis, 0.5 +/- 0.2 in liver cirrhosis, 0.5 +/- 0.2 in hepatocellular carcinoma, and decreased with progression of liver disease (P < 0.05). CONCLUSION: These data suggest that the CYP 3A4 mRNA level in blood relates to progression of liver disease.
Assuntos
Carcinoma Hepatocelular/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Hepatite Viral Humana/metabolismo , Cirrose Hepática/genética , Hepatopatias/enzimologia , Hepatopatias/genética , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/virologia , Doença Crônica , Sistema Enzimático do Citocromo P-450/sangue , Progressão da Doença , Feminino , Vírus da Hepatite B/metabolismo , Hepatite C/microbiologia , Hepatite Crônica/microbiologia , Hepatite Viral Humana/complicações , Humanos , Cirrose Hepática/enzimologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Acute Coxiella burnetii infection is most commonly a mild and self-limiting disease with fever, pneumonia and hepatitis. Endocarditis is the most frequent clinical presentation of chronic infection. We report a 2-year-old child with Q fever who presented with acute pericarditis and cardiac tamponade and who developed a chronic hepatic infection.
Assuntos
Coxiella burnetii/isolamento & purificação , Hepatite Crônica/microbiologia , Pericardite/microbiologia , Febre Q/diagnóstico , Antibacterianos , Tamponamento Cardíaco/complicações , Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/terapia , Pré-Escolar , Terapia Combinada , Progressão da Doença , Quimioterapia Combinada/administração & dosagem , Feminino , Seguimentos , Hepatite Crônica/complicações , Hepatite Crônica/diagnóstico , Hepatite Crônica/terapia , Humanos , Testes de Função Hepática , Insuficiência de Múltiplos Órgãos/complicações , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/terapia , Pericardite/complicações , Pericardite/diagnóstico , Pericardite/terapia , Febre Q/complicações , Respiração Artificial , Índice de Gravidade de Doença , Choque Cardiogênico/complicações , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/terapiaRESUMO
OBJECTIVE: To investigate changes in intestinal microflora in patients with chronic severe hepatitis (CSH), and their role in this life-threatening disease. METHODS: We classified nineteen patients with chronic severe hepatitis as the CSH group, thirty patients with chronic hepatitis (CH) as the CH group and thirty-one healthy volunteer as the control group. Fecal flora from all subjects were analyzed. Concentrations of plasma endotoxin, serum cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and liver function were assessed. RESULTS: The number of fecal bifidobacterium (P < 0.001, P < 0.05 respectively), as well as bacteroidaceae (P < 0.001, P < 0.01 respectively) were significantly deceased in patients with chronic severe hepatitis compared with the CH and control groups, while the number of enterobacteriaceae (P < 0.001, P < 0.05 respectively) and yeasts (P < 0.01, P < 0.05 respectively) were significantly increased. Levels of plasma endotoxin, serum TNF-alpha, IL-1 beta and total bilirubin (TBiL) were significantly increased in the CSH group. The concentration of endotoxin positively correlated with levels of both TNF-alpha, IL-1 beta and TBiL (P < 0.001, respectively). Levels of plasma endotoxin were positively correlated with the number of fecal enterobacteriaceae and negatively correlated with bifidobacterium (P < 0.05, P < 0.001, respectively). CONCLUSION: Intestinal flora in patients with chronic severe hepatitis were severely disturbed and gut microbiological colonization resistance was impaired. Changes in intestinal flora may have a pivotal role in both the elevation of plasma endotoxin and further hepatic lesions resulting in liver failure.