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Liver cirrhosis (LC), contributing to more than 1 million of deaths annually, is a major healthcare concern worldwide. Hepatitis B virus (HBV) is a major LC etiological factor, and 15% of patients with chronic HBV infection (CHB) develop LC within 5 years. Recently, novel host genetic determinants were shown to influence HBV lifecycle and CHB course. DNA repair enzymes can affect dynamics of liver damage and are involved in HBV covalently closed circular DNA (cccDNA) formation, an essential step for viral replication. This study aimed to evaluate the possible role of genes representing key DNA-repair pathways in HBV-induced liver damage. MALDI-TOF MS genotyping platform was applied to evaluate variations within XRCC1, XRCC4, ERCC2, ERCC5, RAD52, Mre11, and NBN genes. Apart from older age (p < 0.001), female sex (p = 0.021), portal hypertension (p < 0.001), thrombocytopenia (p < 0.001), high HBV DNA (p = 0.001), and high aspartate aminotransferase (AST) (p < 0.001), we found that G allele at rs238406 (ERCC2, p = 0.025), T allele at rs25487 (XRCC1, p = 0.012), rs13181 GG genotype (ERCC2, p = 0.034), and C allele at rs2735383 (NBN, p = 0.042) were also LC risk factors. The multivariate logistic regression model showed that rs25487 CC (p = 0.005) and rs238406 TT (p = 0.027) were independently associated with lower risk of LC. This study provides evidence for the impact of functional and potentially functional variations in key DNA-repair genes XRCC1 and ERCC2 in HBV-induced liver damage in a Caucasian population.
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OBJECTIVES: The outcomes of hepatitis B virus (HBV) infection vary substantially among affected individuals, providing evidence of the role of host genetic background in the susceptibility to HBV persistence and the dynamics of liver injury progression to cirrhosis and hepatocellular carcinoma (HCC). METHODS: Six single-nucleotide polymorphisms within the interleukin 10 gene (IL10) were genotyped by MALDI-TOF mass spectrometry in 857 patients with chronic HBV infection (CHB), 48 patients with resolved HBV infection, and 100 healthy volunteers. Associations of the selected polymorphisms with susceptibility to chronic HBV infection, liver injury progression, and outcomes were investigated. RESULTS: IL10 -819T (rs1800871), -592A (rs1800872), and +504T (rs3024490) alleles were associated with treatment-induced hepatitis B surface antigen (HBsAg) seroclearance. Additionally, IL10 ATAC haplotype increased the chance of HBsAg loss and was significantly more frequent in patients with less liver injury. Moreover rs1800871TT, rs1518110TT, rs1800872AA, and rs3024490TT genotypes were identified as predictors of a lower FIB-4 score (<0.5). CONCLUSIONS: This study indicates that polymorphisms within the promoter region and intronic sequences of IL10 are associated with chronicity of hepatitis B and with HBV-induced liver damage.
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Hepatite B Crônica/genética , Interleucina-10/genética , Adulto , Alelos , Progressão da Doença , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/metabolismo , Hepatite B Crônica/imunologia , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Hepatitis B virus (HBV) utilizes proteins encoded by the host to infect hepatocytes and replicate. Recently, several novel host factors have been identified and described as important to the HBV lifecycle. The influence of host genetic background on chronic hepatitis B (CHB) pathogenesis is still poorly understood. OBJECTIVES: Here, we aimed to investigate the association of NTCP, FXRα, HNF1α, HNF4α, and TDP2 genetic polymorphisms with the natural course of CHB and antiviral treatment response. STUDY DESIGN: We genotyped 18 single-nucleotide polymorphisms using MALDI-TOF mass spectrometry in 136 patients with CHB and 100 healthy individuals. We investigated associations of the selected polymorphisms with biochemical, serological and hepatic markers of disease progression and treatment response. RESULTS: No significant differences in genotypic or allelic distribution between CHB and control groups were observed. Within TDP2, rs3087943 variations were associated with treatment response, and rs1047782 modified the risk of advanced liver inflammation. Rs7154439 within NTCP was associated with HBeAg seroconversion after 48 weeks of nucleos(t)ide analogue treatment. HNF1α genotypes were associated with treatment response, liver damage and baseline HBeAg presence. HNF4α rs1800961 predicted PEG-IFNα treatment-induced HBsAg clearance in long-term follow up. CONCLUSIONS: This study indicates host genetic background relevance in the course of CHB and confirms the role of recently described genes for HBV infection. The obtained results might serve as a starting point for validation studies on the clinical application of selected genetic variants to predict individual risks of CHB-induced liver failure and treatment response.
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Antivirais/uso terapêutico , Proteínas de Ligação a DNA/genética , Hepatite B Crônica/tratamento farmacológico , Fator 1-alfa Nuclear de Hepatócito/genética , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Diester Fosfórico Hidrolases/genética , Polimorfismo de Nucleotídeo Único , Simportadores/genética , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Anticorpos Anti-Hepatite B/metabolismo , Antígenos E da Hepatite B/imunologia , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Humanos , Masculino , Soroconversão , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Resultado do TratamentoRESUMO
BACKGROUND: Hepatitis B virus (HBV) infections are a major threat worldwide. Disease progression and outcome is diverse and depends on host genetic background. Recently, a high rate of HBV reactivation in individuals receiving tumor necrosis factor-α (TNF-α) antagonists showed the importance of this cytokine in HBV infection control. Here, we investigated the influence of TNF-α promoter polymorphisms on susceptibility to chronic HBV infection (CHB), liver injury progression and outcomes. METHODS: A total of 231 patients with CHB constituted the study group and 100 healthy volunteers-the local control group. TNF-α -1031T/C, -863C/A, -857C/T, -308G/A, and -238G/A were genotyped using MALDI-TOF mass spectrometry. RESULTS: TNF-α -1031C and -863A alleles were observed more frequently in CHB group than in healthy controls. Carriers of TNF-α -1031C and -863A variant alleles had lower baseline levels of serum HBV DNA and lower liver necroinflammatory activity than dominant homozygotes. A -857CT genotype predisposed to higher necroinflammatory activity. No associations between TNF-α variants and liver fibrosis were found. CONCLUSION: This study indicates that TNF-α -863A and -1031C alleles are associated with increased susceptibility to CHB in individuals from northern Poland. The same variants determine the course of CHB, lowering viremia and reducing necroinflammatory activity of the liver.
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Hepatite B Crônica/patologia , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , DNA Viral/sangue , Progressão da Doença , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/genética , Homozigoto , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Regiões Promotoras GenéticasRESUMO
Coinfection with hepatitis D virus (HDV) in chronic hepatitis B is associated with more rapid progression to liver cirrhosis. We present two cases of infection with hepatitis D, B and C viruses. Both male patients were primarily diagnosed as infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), HBsAg-positive and anti-HCV-positive. The first patient was treated with interferon, lamivudine and pegylated interferon. A full virological and biochemical response was achieved. The second patient was treated with interferon and ribavirin, lamivudine and twice with pegylated interferon. In the ultrasound elastography progression of liver fibrosis to F4 was described. HDV infection should be considered in patients with HBV minireplication, high activity of aminotransferases and progression of liver disease despite a good virological response to anti-HBV treatment. Efficacy of interferon in HDV infection is severely limited.
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The hepatitis B virus (HBV) genome exists in two forms: circular covalently closed DNA (cccDNA) and relaxed circular DNA (RCDNA). Here, we investigated the presence of differences in the sequences of both forms in paired samples of serum and liver tissue. The serum and liver biopsy samples were collected at the same time from 67 chronically infected patients. The genotyping of the RCDNA and cccDNA was performed using mass spectrometry analysis. The HBV mutations located in the HBV pol (P) and the HBV basal core promoter/pre-core (BCP/PC) regions were included. The BCP/PC and P sequences of the RCDNA extracted from liver and blood samples were different in 39% and 16% of patients, respectively. Differences were also found between RCDNA and cccDNA extracted from the same liver specimen. Moreover, the cccDNA BCP/PC region sequence had an impact on various virological and clinical parameters. We demonstrated that there are differences between the RCDNA and cccDNA sequences that were extracted from the same liver tissue. However, further investigations are needed to analyze whether the mutations in the cccDNA are conserved and whether cccDNA serves as a 'mutation storage' pool for HBV. This result could have profound implications for the subsequent therapy choices for treatment-experienced patients.
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DNA Circular , DNA Viral/sangue , Vírus da Hepatite B/genética , Análise de Sequência de DNA , Adolescente , Adulto , Biópsia , Feminino , Genoma Viral , Técnicas de Genotipagem , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Fígado/patologia , Fígado/virologia , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Mutação , Polimorfismo Genético , Regiões Promotoras Genéticas , Adulto JovemRESUMO
Chronic HBV infection affects more than 240 million people worldwide and is associated with a broad range of clinical manifestations including liver cirrhosis, liver failure and hepatocellular carcinoma. Because of the lack of an efficient cure for chronic hepatitis B, the main goal of antiviral therapy is the prevention of liver disease progression coupled with prolonged survival of patients. Because HBV viral load has been shown to be a crucial determinant of the progression of liver damage, these goals can be achieved as long as HBV replication can be suppressed. Unfortunately, long-term therapy with the low-to-moderate genetic barrier drugs, which are still recommended in a majority of developing countries, are strongly associated with HBV resistance development and treatment failure. In such cases, the precise and accurate determination of drug-resistant variants in an individual patient before treatment is important for a proper choice of first-line potent therapy. Nowadays, a number of techniques are available to study HBV quasispecies evolution. This review describes the advantages and limitations of various assays detecting drug-resistant HBV variants. Copyright © 2016 John Wiley & Sons, Ltd.
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Antivirais/uso terapêutico , Variação Genética , Técnicas de Genotipagem/métodos , Vírus da Hepatite B/classificação , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Mutação , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , HumanosRESUMO
OBJECTIVES: To evaluate the frequency, co-occurrence, and risk factors for hematological complications at the time of diagnosis of chronic hepatitis C (CHC). METHODS: This study included 1237 patients with CHC aged 18-88 years diagnosed in the years 1998-2010 in the Pomeranian region of Poland. Clinical data, cell blood count, liver biopsy, and biochemistry results were obtained retrospectively. RESULTS: Hematological complications were found in 31% of patients. The most frequent complication was thrombocytopenia (23.8%). The multivariate analysis showed a 5.1-fold increased risk (P<0.05) of at least one additional hematological complication in patients with thrombocytopenia. The greatest increase in risk (7.3) was related to leukopenia and cryoglobulinemia (2.3). The risk of leukopenia was correlated with the severity of thrombocytopenia. The risk of leukopenia and thrombocytopenia increased significantly from, respectively, stages 3 and 2 of liver fibrosis compared with patients without fibrosis. CONCLUSION: In patients with CHC, decreases in cell blood count occur quite frequently. The most often is mild and solitary thrombocytopenia, but if severe, it may be accompanied by leukopenia, especially in women. The presence of thrombocytopenia and leukopenia in patients with CHC may indicate advanced liver fibrosis or its final stage: cirrhosis.
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Crioglobulinemia/epidemiologia , Hepatite C Crônica/epidemiologia , Leucopenia/epidemiologia , Trombocitopenia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Crioglobulinemia/sangue , Crioglobulinemia/diagnóstico , Feminino , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Humanos , Leucopenia/sangue , Leucopenia/diagnóstico , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Polônia/epidemiologia , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Success in treating hepatitis B virus (HBV) infection with nucleoside analogues drugs is limited by the emergence of drug-resistant viral strains upon prolonged therapy. In addition to mutation patterns in the viral polymerase gene, host factors are assumed to contribute to failure of treatment in chronic HBV infections. The aim of this study was to analyze the correlation between efficacy of antiviral therapy and the prevalence of HBV pretreatment drug-resistant variants. We also analyzed the role of heterogeneity in the promoter region of the IL-10 on the HBV pol/s gene polymorphisms and efficacy of analogues-driven therapy. MATERIAL AND METHODS: HBV DNA was extracted from 54 serum samples from chronic hepatitis B (CHB) patients. Drug-resistance mutations were analyzed using MALDI-TOF mass spectrometry technology (MALDI-TOF MS) and Multi-temperature single-strand conformation polymorphism (MSSCP). IL-10 gene promoter region polymorphisms at positions -1082, -819, and -592 were determined in allele-specific PCR reactions (AS-PCR). RESULTS: Drug-resistance mutations were detected in 74% of naïve and 93% of experienced patients, but the effect of pre-existence of drug-resistant HBV variants on antiviral therapy was not statistically significant (p=0.86). The role of polymorphisms at positions -1082 (p=0.88), -819 (p=0.26), and -592 (p=0.26) of IL-10 promoter region polymorphisms was excluded from the response-predicting factors. The main host factors predicting successful response to antiviral therapy were female sex (p=0.007) and young age (p=0.013). CONCLUSIONS: The presence of drug-resistant HBV variants in baseline is not a viral predictor of good response to nucleoside/nucleotide analogues therapy. Only low HBV viral load predicted positive response to antiviral therapy. The ideal candidate for antiviral therapy is an immunocompetent, young female with low HBV viral load and elevated ALT activity.
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Antivirais/farmacologia , Farmacorresistência Viral/genética , Hepatite B Crônica/tratamento farmacológico , Fatores Celulares Derivados do Hospedeiro/genética , Interleucina-10/genética , Adenina/análogos & derivados , Adenina/farmacologia , Adulto , Fatores Etários , Quimioterapia Combinada , Feminino , Hepatite B Crônica/virologia , Humanos , Lamivudina/farmacologia , Pessoa de Meia-Idade , Mutação/genética , Nucleosídeos/farmacologia , Organofosfonatos/farmacologia , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Regiões Promotoras Genéticas/genética , Fatores Sexuais , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Tenofovir , Carga ViralRESUMO
Long-term antiviral therapy of chronic hepatitis B virus (HBV) infection can lead to the selection of drug-resistant HBV variants and treatment failure. Moreover, these HBV strains are possibly present in treatment-naive patients. Currently available assays for the detection of HBV drug resistance can identify mutants that constitute ≥5% of the viral population. Furthermore, drug-resistant HBV variants can be detected when a viral load is >10(4) copies/ml (1,718 IU/ml). The aim of this study was to compare matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and multitemperature single-strand conformation polymorphism (MSSCP) with commercially available assays for the detection of drug-resistant HBV strains. HBV DNA was extracted from 87 serum samples acquired from 45 chronic hepatitis B (CHB) patients. The 37 selected HBV variants were analyzed in 4 separate primer extension reactions on the MALDI-TOF MS. Moreover, MSSCP for identifying drug-resistant HBV YMDD variants was developed and turned out to be more sensitive than INNOLiPA HBV DR and direct sequencing. MALDI-TOF MS had the capability to detect mutant strains within a mixed viral population occurring with an allelic frequency of approximately 1% (with a specific value of ≥10(2) copies/ml, also expressed as ≥17.18 IU/ml). In our study, MSSCP detected 98% of the HBV YMDD variants among strains detected by the MALDI-TOF MS assay. The routine tests revealed results of 40% and 11%, respectively, for INNOLiPA and direct sequencing. The commonly available HBV tests are less sensitive than MALDI-TOF MS in the detection of HBV-resistant variants, including quasispecies.
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Antivirais/farmacologia , Farmacorresistência Viral , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/virologia , Polimorfismo Conformacional de Fita Simples , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , DNA Viral/genética , DNA Viral/isolamento & purificação , Vírus da Hepatite B/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana/métodos , Soro/virologiaRESUMO
BACKGROUND: Iron overload is frequently observed in patients with chronic hepatitis C (CHC) and is associated with the increased risk of liver fibrosis and carcinogenesis. Hepcidin is a regulator of iron homeostasis and a component of innate immunity. Based on experimental studies, iron overload might be a result of low hepcidin synthesis in CHC. OBJECTIVES: The aim of this case-control study was to assess hepcidin mRNA expression in liver tissue of patients with CHC in terms of iron metabolism parameters, hemochromatosis (HFE) gene mutations, disease activity, and efficacy of antiviral treatment with pegylated interferon and ribavirin. PATIENTS AND METHODS: A total of 31 patients with CHC, who were qualified for antiviral therapy, were compared with 19 patients with chronic hepatitis B (CHB). In both groups, liver function tests and serum iron parameters were assayed and hepcidin mRNA expression was measured in liver specimens using real time PCR with normalization to reference genes mRNA of stable expression. RESULTS: Patients with CHC had lower hepcidin mRNA expression and more frequently iron deposits in hepatocytes than subjects with CHB did. In CHC group, hepcidin mRNA expression was positively correlated with alanine aminotransferase activity and serum iron concentration. Low expression of hepcidin had no correlation with tissue iron overload in those with CHC. In univariate analysis, HCV viral load and efficacy of antiviral treatment were not significantly associated with hepcidin mRNA expression. CONCLUSIONS: Further studies on the role of hepcidin in pathogenesis of CHC are needed to assess the potency of its use in antiviral treatment.
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BACKGROUND: Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non-alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. METHODS: A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. RESULTS: Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serum markers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. CONCLUSIONS: Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.
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Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Hepatite C Crônica/complicações , Antígenos de Histocompatibilidade Classe I/genética , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/complicações , Cirrose Hepática/patologia , Proteínas de Membrana/genética , Adulto , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Feminino , Ferritinas/sangue , Hemocromatose/sangue , Hemocromatose/genética , Hemocromatose/patologia , Proteína da Hemocromatose , Hepatite C Crônica/patologia , Hepatócitos/metabolismo , Humanos , Ferro/sangue , Metabolismo dos Lipídeos , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Polimorfismo Genético , Índice de Gravidade de Doença , Transferrina/metabolismoRESUMO
UNLABELLED: Available data on prevalence of HCV genotypes in Poland are insufficient. The aim of the study was the analysis of distribution of HCV genotypes in Poland over the period of recent 10 years regarding the age of patients and the regions of the country. MATERIAL AND METHODS: Analysis of HCV genotypes in Poland was carried out between 2003 and 2012, and included 14 651 patients from 22 centers where patients with chronic viral hepatitis C are diagnosed and treated. Genotypes were analyzed in age groups (< 20 years of age, 20-40 years of age, > 40 years of age) as well as in populations of HBV and HIV co-infections. RESULTS: Genotype (G) 1 infection was demonstrated in 79.4%, G2 -0.1%, G3- 13.8%, G4- 4.9%, G6-0.09% and mixed infections in 1.6%. There was no infection with genotype 5. The highest prevalence of G1 was observed in the Lódzkie voivodship (89.2%) and the Slaskie voivodship (86.7%) while the lowest one in the Warminsko-mazurskie (62.0%) and the Podlaskie voivodships (68.2%). Genotype 3 most commonly occurs in the Warminsko-mazurskie (28.1%), and the Podlaskie voivodships (23.0%) and is least common in the Malopolskie (7.9%) and the Lódzkie voivodships (9.0%). Genotype 4 is more common in the Kujawsko-pomorskie (11.7%) and the Podlaskie voivodships (8.6%) and relatively less common in the Lubelskie (1.1%) and the Lódzkie voivodships (1.8%). Prevalence of G1 infection in 2003-2004 was 72% and increased up to 85.6% in 2011-2012, that was accompanied by decrease of G3 prevalence from 17% to 8% in this period. In HBV co-infected (n = 83), G1 infection was demonstrated in 85.5%, G3 - in 7.2%, G4 -4.8%, and mixed genotypes in 6%. Among HIV co-infected (n = 391), a much lower prevalence of G1 (33.0%) and a high of G3 (40.4%) as well as G4 (24.0%) were observed. CONCLUSIONS: There is a geographic variability of HCV genotypes prevalence in Poland. Increase of HCV G1 infections and decrease of G3 and G4 were observed in the last 10 years. Genotypes G3 and G4 occur more often in HCV/HIV co-infected than in HCV mono-infected patients.
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Frequência do Gene , Genótipo , Hepacivirus/genética , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , RNA Viral/genética , Adolescente , Adulto , Hepacivirus/classificação , Humanos , Pessoa de Meia-Idade , Polônia/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Fatores de Risco , População Rural/estatística & dados numéricos , Análise de Sequência/métodos , População Urbana/estatística & dados numéricos , Adulto JovemRESUMO
Literature data indicate an association between the presence of Helicobacter spp. in the liver and the development of hepatocellular carcinoma (HCC). However, the role of H. pylori infections in chronic liver diseases (CLD) remains controversial. The aim of this study was to detect Helicobacter spp. DNA in patients with CLD, and to investigate the host response to the presence of the bacterium in the liver. Helicobacter spp. DNA was detected in 59% samples. H.pylori was the most prevalent species (94%). We estimated the expression level of IL-1 and IL-8 genes. The presence of Helicobacter spp. did not have a significant effect on the gene expression of IL-8 and IL-1.
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Infecções por Helicobacter/microbiologia , Helicobacter/genética , Hepatopatias/microbiologia , Biópsia , Carcinoma Hepatocelular/microbiologia , Doença Crônica , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Helicobacter/classificação , Helicobacter/isolamento & purificação , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/classificação , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Interações Hospedeiro-Patógeno , Humanos , Interleucina-1/genética , Interleucina-8/genética , Hepatopatias/epidemiologia , Neoplasias Hepáticas/microbiologia , Polônia/epidemiologia , Reação em Cadeia da Polimerase , RNA/genética , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
BACKGROUND: Increased liver iron stores may contribute to the progression of liver injury and fibrosis, and are associated with a higher risk of hepatocellular carcinoma development. Pre-transplant symptoms of iron overload in patients with liver cirrhosis are associated with higher risk of infectious and malignant complications in liver transplant recipients. HFE gene mutations may be involved in the pathogenesis of liver iron overload and influence the progression of chronic liver diseases of different origins. This study was designed to determine the prevalence of iron overload in relation to HFE gene mutations among Polish patients with liver cirrhosis. METHODS: Sixty-one patients with liver cirrhosis included in the study were compared with a control group of 42 consecutive patients subjected to liver biopsy because of chronic liver diseases. Liver function tests and serum iron markers were assessed in both groups. All patients were screened for HFE mutations (C282Y, H63D, S65C). Thirty-six of 61 patients from the study group and all controls had liver biopsy performed with semiquantitative assessment of iron deposits in hepatocytes. RESULTS: The biochemical markers of iron overload and iron deposits in the liver were detected with a higher frequency (70% and 47% respectively) in patients with liver cirrhosis. There were no differences in the prevalence of all HFE mutations in both groups. In patients with a diagnosis of hepatocellular carcinoma, no significant associations with iron disorders and HFE gene mutations were found. CONCLUSIONS: Iron disorders were detected in patients with liver cirrhosis frequently but without significant association with HFE gene mutations. Only the homozygous C282Y mutation seems to occur more frequently in the selected population of patients with liver cirrhosis. As elevated biochemical iron indices accompanied liver iron deposits more frequently in liver cirrhosis compared to controls with chronic liver disease, there is a need for more extensive studies searching for the possible influence of non-HFE iron homeostasis regulators and their modulation on the course of chronic liver disease and liver cirrhosis.
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Hemocromatose/genética , Antígenos de Histocompatibilidade Classe I/genética , Sobrecarga de Ferro/genética , Cirrose Hepática/genética , Proteínas de Membrana/genética , Mutação , Adulto , Biomarcadores/sangue , Biópsia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Hemocromatose/complicações , Hemocromatose/diagnóstico , Hemocromatose/epidemiologia , Proteína da Hemocromatose , Homozigoto , Humanos , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/epidemiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Testes de Função Hepática , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polônia/epidemiologia , Prevalência , Medição de Risco , Fatores de RiscoRESUMO
Hepatitis B virus (HBV) infection is one of the major human health problems worldwide. It is estimated that chronic HBV infection affects more than 350 million people globally. It is one of the leading causes of liver cirrhosis and hepatocellular carcinoma. High genetic variability is a characteristic feature of HBV as the viral polymerase lacks proofreading activity. The nucleotide substitution rate for HBV is 10-fold higher than for other DNA viruses. Genetic variations of HBV influence the clinical outcome of HBV infection. There are eight genotypes of hepatitis B virus (A-H) that have a distinct geographical distribution. There is clinical significance of HBV genotype in terms of disease activity, risk of progression to cirrhosis, the development of hepatocellular carcinoma and response to antiviral treatments. Moreover, polymorphism in HBV viral polymerase influences the development of HBV mutants resistant to nucleotide analogue treatment that is a consequence of treatment failure.
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Progressão da Doença , Vírus da Hepatite B/genética , Hepatite B/genética , Hepatopatias/genética , Polimorfismo Genético , Humanos , Hepatopatias/etiologiaRESUMO
Liver is a key organ responsible for organism's homeostasis. A proper function of this organ is crucial for detoxification of metabolic products and regulation of metabolic processes of macromolecules (proteins, lipids, carbohydrates). The most important infectious factors, leading to liver damage, are primary hepatotropic viruses, particularly those causing chronic inflammation of the organ (HBV, HCV, HDV), which may subsequently cause cirrhosis and/or primary hepatocellular carcinoma. There has been a growing interest in Helicobacter spp. liver infections as a potential factor promoting injury of the organ towards hepatocellular carcinoma. The association between hepatocellular carcinoma and the presence of Helicobacters in the liver has been well documented in animal models (Helicobacter hepaticus versus liver cancer in mice). Some reports also indicate similar association in humans, where the presence of Helicobacter antigens in patients with liver cancer is detected more often in comparison to healthy or chronically infected population. Although the molecular mechanisms underlying such a phenomenon are not well known, the knowledge on this subject has considerably increased during recent years. The review presents data on the association between the presence of Helicobacter spp. in the liver and injuries of the organ, as well as the role that is played by the bacteria in chronic liver diseases.
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Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/microbiologia , Infecções por Helicobacter/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/microbiologia , Animais , Helicobacter pylori/isolamento & purificação , HumanosRESUMO
Many Helicobacter spp. were isolated from the stomach, intestinal tract, and liver of different animals and humans. The association between Helicobacter spp. and hepatobiliary diseases, including hepatocellular carcinoma, was thoroughly examined, indicating a potential role of the bacteria in the progression toward cancer. In our work, we screened 97 liver biopsies from patients with chronic liver diseases for the presence of Helicobacter spp. DNA. With the use of genus-specific polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) and subsequent sequencing, we found that the majority of Helicobacter spp. DNA detected was similar to Helicobacter rodentium DNA (71%). The DNA of other detected Helicobacter spp. was similar to Helicobacter pylori DNA. This is the first indication of H. rodentium-like DNA presence in human liver tissue. We also conclude that PCR-DGGE is a useful screening method for assigning species designation and heterogeneity.
Assuntos
Técnicas Bacteriológicas , DNA Bacteriano/isolamento & purificação , Infecções por Helicobacter/diagnóstico , Helicobacter/genética , Helicobacter/isolamento & purificação , Hepatopatias/microbiologia , Adolescente , Adulto , Idoso , Biópsia , Doença Crônica , DNA Bacteriano/genética , Eletroforese em Gel de Gradiente Desnaturante , Feminino , Helicobacter/classificação , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Adulto JovemRESUMO
BACKGROUND: Iron overload observed in chronic hepatitis C (CHC) has been suggested to be one of the negative prognostic factors influencing liver disease progression and failure of treatment with recombinant interferon in monotherapy or in combination with ribavirin. The aim of this study was to assess occurrence of iron overload in relation to polymorphism of the HFE and the influence of both these factors on efficacy of antiviral treatment with pegylated interferon and ribavirin in patients with CHC. MATERIAL/METHODS: Liver function tests, serum indices of iron metabolism, and HFE mutations were assayed in 152 patients with CHC from Poland. Histopathological examination of the liver biopsy specimen was performed in 138 patients. Sixty-one patients were treated with pegylated interferon alfa-2 and ribavirin. The comparative analysis was performed in 2 groups of patients: those with and those without elevated serum indices of iron metabolism. RESULTS: Increased biochemical iron metabolism parameters correlated with older age, higher ALT activity, more advanced liver fibrosis and treatment failure. Iron deposits in liver specimens were not accompanied by exacerbation of necro-inflammatory activity and advanced fibrosis. Elevated biochemical values of iron metabolism parameters and presence of hepatic iron deposits correlated positively with C282Y mutations. The lack of sustained viral response after treatment with pegylated interferon and ribavirin was observed more frequently in carriers of HFE mutations. CONCLUSIONS: Iron overload was frequently detected in patients with CHC, and was associated only with C282Y alleles. Biochemical markers of iron overload and HFE gene mutations were negative prognostic factors of antiviral treatment.