RESUMO
BACKGROUND: Mannan-binding lectin (MBL) - associated serine protease 2 (MASP-2) co-activates the lectin pathway of complement in response to several viral infections. The quality of this response partly depends on MASP2 gene polymorphisms, which modulate MASP-2 function and serum levels. In this study we investigated a possible role of MASP2 polymorphisms, MASP-2 serum levels and MBL-mediated complement activation in the susceptibility to HIV/AIDS and HBV/HCV coinfection. METHODS: A total of 178 HIV patients, 89 (50%) coinfected with HBV/HCV, 51.7% female, average age 40 (12-73) years, and 385 controls were evaluated. MASP-2 levels and MBL-driven complement activation were evaluated by enzyme-linked immunosorbent assay and 11 MASP2 polymorphisms from the promoter to the last exon were haplotyped using multiplex sequence-specific PCR. RESULTS: Genotype distribution was in Hardy-Weinberg equilibrium and differed between HIV+ patients and controls (P=0.030), irrespective of HBV or HCV coinfection. The p.126L variant, which was associated with MASP-2 levels <200ng/mL (OR=5.0 [95%CI=1.3-19.2] P=0.019), increased the susceptibility to HIV infection (OR=5.67 [95%CI=1.75-18.33], P=0.004) and to HIV+HBV+ status (OR=6.44 [95%CI=1.69-24.53, P=0.006). A similar association occurred with the ancient haplotype harboring this variant, AGCDV (OR=2.35 [95%CI=1.31-4.23], P=0.004). On the other hand, p.126L in addition to other variants associated with low MASP-2 levels-p.120G, p.377A and p.439H, presented a protective effect against AIDS (OR=0.25 [95%CI=0.08-0.80], P=0.020), independently of age, sex, hepatic function and viral load. MASP-2 serum levels were lower in HIV+ and HIV+HBV+ patients than in controls (P=0.0004). Among patients, MASP-2 levels were higher in patients with opportunistic diseases (P=0.001) and AIDS (P=0.004). MASP-2 levels correlated positively with MBL/MASP2-mediated C4 deposition (r=0.29, P=0.0002) and negatively with CD4+ cell counts (r=-0.21, P=0.018), being related to decreased CD4+ cell counts (OR=5.8 [95%CI=1.23-27.5, P=0.026). CONCLUSIONS: Genetically determined MASP-2 levels seem to have a two-edge effect in HIV and probably HCV/HBV coinfection, whereas low levels increase the susceptibility to infection, but on the other side protects against AIDS.
Assuntos
Infecções por HIV/genética , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Síndrome da Imunodeficiência Adquirida/enzimologia , Síndrome da Imunodeficiência Adquirida/genética , Síndrome da Imunodeficiência Adquirida/imunologia , Adolescente , Adulto , Idoso , Criança , Coinfecção/enzimologia , Coinfecção/genética , Coinfecção/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Predisposição Genética para Doença/genética , Genótipo , Infecções por HIV/enzimologia , Infecções por HIV/imunologia , Hepatite B/enzimologia , Hepatite B/genética , Hepatite B/imunologia , Hepatite C/enzimologia , Hepatite C/genética , Hepatite C/imunologia , Humanos , Masculino , Serina Proteases Associadas a Proteína de Ligação a Manose/imunologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
AIM: To elucidate the mechanism(s) by which S-adenosyl-L-methionine (SAM) decreases hepatitis C virus (HCV) expression. METHODS: We examined the effects of SAM on viral expression using an HCV subgenomic replicon cell culture system. Huh7 HCV-replicon cells were treated with 1 mmol/L SAM for different times (24-72 h), then total RNA and proteins were isolated. cDNA was synthesized and real time-PCR was achieved to quantify HCV-RNA, superoxide dismutase 1 and 2 (SOD-1, SOD-2) catalase, thioredoxin 1, methionine adenosyltransferase 1A and 2A (MAT1A, MAT2A) expression, and GAPDH and RPS18 as endogenous genes. Expression of cellular and viral protein was evaluated by western-blot analysis using antibodies vs HCV-NS5A, SOD-1, SOD-2, catalase, thioredoxin-1, MAT1A, MAT2A, GAPDH and actin. Total glutathione levels were measured at different times by Ellman's recycling method (0-24 h). Reactive oxidative species (ROS) levels were quantified by the dichlorofluorescein assay (0-48 h); Pyrrolidin dithiocarbamate (PDTC) was tested as an antioxidant control and H2O2 as a positive oxidant agent. RESULTS: SAM exposition decreased HCV-RNA levels 50%-70% compared to non-treated controls (24-72 h). SAM induced a synergic antiviral effect with standard IFN treatment but it was independent of IFN signaling. In addition, 1 mmol/L SAM exposition did not modify viral RNA stability, but it needs cellular translation machinery in order to decrease HCV expression. Total glutathione levels increased upon SAM treatment in HCV-replicon cells. Transcriptional antioxidant enzyme expression (SOD-1, SOD-2 and thioredoxin-1) was increased at different times but interestingly, there was no significant change in ROS levels upon SAM treatment, contrary to what was detected with PDTC treatment, where an average 40% reduction was observed in exposed cells. There was a turnover from MAT1A/MAT2A, since MAT1A expression was increased (2.5 fold-times at 48 h) and MAT2A was diminished (from 24 h) upon SAM treatment at both the transcriptional and translational level. CONCLUSION: A likely mechanism(s) by which SAM diminish HCV expression could involve modulating antioxidant enzymes, restoring biosynthesis of glutathione and switching MAT1/MAT2 turnover in HCV expressing cells.
Assuntos
Antioxidantes/metabolismo , Antivirais/farmacologia , Glutationa/biossíntese , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Hepatócitos/efeitos dos fármacos , Metionina Adenosiltransferase/metabolismo , S-Adenosilmetionina/farmacologia , Replicação Viral/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hepacivirus/genética , Hepacivirus/crescimento & desenvolvimento , Hepatite C/enzimologia , Hepatite C/genética , Hepatócitos/enzimologia , Interações Hospedeiro-Patógeno , Humanos , Metionina Adenosiltransferase/genética , Estresse Oxidativo/efeitos dos fármacos , RNA Viral/biossíntese , Fatores de Tempo , TransfecçãoRESUMO
Myeloperoxidase (MPO) is an important enzyme in the front-line protection against microorganisms. In peripheral blood, it is accepted that MPO is only produced by myeloid-lineage cells. Thus, MPO presence is unexpected in lymphocytes. We showed recently that B1-lymphocytes from mice have MPO. Here, we showed that subsets of human peripheral B, CD4(+) and CD8(+) T lymphocytes express MPO. The content of MPO in lymphocytes was very low compared to neutrophils/monocytes with a preferential distribution in the nucleus and perinuclear region. Also, we performed a MPO mRNA expression analysis from human blood cells derived from microarray raw data publicly available, showing that MPO is modulated in infectious disease. MPO was increased in CD4(+) T lymphocytes from HIV chronic infection and in CD8(+) T lymphocytes from HCV-positive patients. Our study points out MPO as a multifunctional protein due to its subcellular localization and expression modulation in lymphocytes indicating alternative unknown functions for MPO in lymphocytes.
Assuntos
Linfócitos B/enzimologia , Linfócitos T CD4-Positivos/enzimologia , Linfócitos T CD8-Positivos/enzimologia , Peroxidase/biossíntese , Linfócitos B/imunologia , Western Blotting , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Separação Celular , Citometria de Fluxo , Infecções por HIV/enzimologia , Infecções por HIV/imunologia , Hepatite C/enzimologia , Hepatite C/imunologia , Humanos , Imunofenotipagem , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Análise de Sequência com Séries de Oligonucleotídeos , Peroxidase/imunologia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Several studies have demonstrated that HIV/hepatitis C virus (HCV)-coinfected patients experience more rapid fibrosis progression. In this study, to estimate the annual rate of direct liver fibrosis progression, we used analyses of paired biopsy samples from HIV/HCV-coinfected patients without prior treatment of hepatitis and assessed the possible association of fibrosis progression with certain clinical variables. We evaluated 30 HIV/HCV-coinfected patients, with no history of prior treatment of hepatitis C, who underwent paired liver biopsies. All patients were under antiretroviral therapy at first and second biopsies. The average annual progression rate was 0.13 fibrosis unit/year, with 36.7% of patients defined as progressors. Liver fibrosis progression was associated with alanine aminotransferase (ALT; P < .001) and aspartate aminotransferase (AST; P < .0340) levels over 3 times the upper limit of normal present at first biopsy. Elevated ALT and AST levels appear to be associated with more accelerated liver fibrosis progression among HIV/HCV-coinfected patients.
Assuntos
Infecções por HIV/patologia , Hepatite C/patologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biópsia , Coinfecção , Progressão da Doença , Feminino , Infecções por HIV/enzimologia , Infecções por HIV/virologia , Hepatite C/enzimologia , Hepatite C/virologia , Humanos , Fígado/patologia , Cirrose Hepática/enzimologia , Masculino , Pessoa de Meia-IdadeRESUMO
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. In Egypt, the incidence of HCC has doubled over the last decade. Matrix metalloproteinase-9 (MMP-9) plays a key role in cancer invasion and metastasis by degrading the extracellular matrix and basement membrane barriers. A cytosine (C)/thymidine (T) single nucleotide polymorphism at position -1562 in the MMP-9 promoter is reported to influence the expression of the MMP-9 gene. The association between MMP-9 gene polymorphisms and HCC patients with hepatitis C and B viruses (HCV and HBV) was examined in 91 patients with HCC and viral hepatitis (55 HCV and 36 HBV). The results were compared with those of 42 HCC patients without viral hepatitis and 60 healthy individuals with no liver infection. Polymorphisms of the MMP-9 gene were investigated by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis. The serum MMP-9 level was quantitatively determined using a human MMP-9 enzyme-linked immunosorbent assay, which showed that homozygosity of the MMP-9 promoter (TT) was more frequent in patients with HCC and chronic HCV or HBV infection when compared with the control group (49.1, 52.8, and 35.7%, respectively). In addition, we observed significant elevation of serum MMP-9 levels in all HCC groups compared to controls. It was concluded that patients with the MMP-9 TT genotype are at risk of developing HCC and HBV or HCV. People with significantly elevated serum levels of MMP-9 are at risk of developing HCC.
Assuntos
Carcinoma Hepatocelular/enzimologia , Hepatite B/enzimologia , Hepatite C/enzimologia , Neoplasias Hepáticas/enzimologia , Metaloproteinase 9 da Matriz/genética , Polimorfismo Genético , Sequência de Bases , Carcinoma Hepatocelular/etiologia , Estudos de Casos e Controles , Primers do DNA , Hepatite B/complicações , Hepatite C/complicações , Humanos , Neoplasias Hepáticas/complicações , Metaloproteinase 9 da Matriz/sangue , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The tumor suppressor PTEN is a phosphoinositide phosphatase regulating the PI3K/Akt signaling pathways and mutated or deleted in a variety of human cancers. Recent evidence indicates that dysregulated PTEN expression and activity in the liver critically affect hepatic insulin sensitivity and trigger the development of non-alcoholic fatty liver diseases. As well, PTEN expression/activity is also affected with HBV and HCV infection, or following alcohol-related injury. Finally, PTEN mutations/deletions or low PTEN expression are associated with diverse liver malignancies thus suggesting a critical role for PTEN in hepatic cancers. This review will focus on our current knowledge of the regulation of PTEN expression/activity and the role of this phosphatase in liver diseases.
Assuntos
Hepatopatias/enzimologia , Neoplasias Hepáticas/enzimologia , Fígado/enzimologia , PTEN Fosfo-Hidrolase/metabolismo , Transdução de Sinais , Inibidores Enzimáticos/farmacologia , Fígado Gorduroso/enzimologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Hepatite B/enzimologia , Hepatite C/enzimologia , Humanos , Insulina/metabolismo , Resistência à Insulina , Fígado/efeitos dos fármacos , Hepatopatias/tratamento farmacológico , Hepatopatias/genética , Hepatopatias Alcoólicas/enzimologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Mutação , PTEN Fosfo-Hidrolase/antagonistas & inibidores , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
The prevalences of chronic infection by hepatitis C virus (HCV) and its genotypes vary among countries and ethnic groups. Among patients with end-stage renal disease (ESRD) and transplant recipients, the evolution of hepatic disease seems atypical and has not been established. In this study we compared the prevalence and HCV genotypic distribution among Brazilian patients with ESRD on dialysis or with transplantations. Moreover, we sought to compare the behavior of biochemical markers of hepatic activity of HCV infection in both groups. We prospectively evaluated 87 ESRD patients on dialysis and 105 transplant patients. Blood samples were obtained to perform qualitative HCV-RNA, genotyping, and, periodically, serum levels of aminotransferases (ALT, AST), gamma-glutamyltransferase (GGT), alpha-fetoprotein (AFT), and albumin. The prevalence of HCV in ESRD patients was similar to recipients (19.5% vs 25.7%; P = NS) and the most frequent genotype was 1a. There was no difference in the mean values of ALT, GGT, AFT, and serum albumin between both groups with HCV infection. The mean values of aminotransferases were slightly elevated and a high frequency of patients evolved with persistently normal parameters. In contrast, the mean values of the GGT were 3 or 4 times above the reference limit and a greater frequency of patients evolved with values persistently elevated in the 2 groups. In conclusion, in the 2 groups the prevalence of HCV infection was elevated; the most frequent genotype was 1a. Among the biochemical parameters, GGT seemed to be useful as an indirect marker of liver disease.
Assuntos
Hepatite C/enzimologia , Falência Renal Crônica/enzimologia , Transplante de Rim/fisiologia , Terapia de Substituição Renal/efeitos adversos , gama-Glutamiltransferase/sangue , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Brasil , Feminino , Hepatite C/epidemiologia , Humanos , Falência Renal Crônica/cirurgia , Falência Renal Crônica/virologia , MasculinoRESUMO
CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Infecções por HIV/tratamento farmacológico , Fígado/efeitos dos fármacos , Adolescente , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Criança , Métodos Epidemiológicos , Feminino , Hepatite C/induzido quimicamente , Hepatite C/enzimologia , Humanos , Fígado/enzimologia , Masculino , Carga ViralRESUMO
BACKGROUND: At present it is not clearly established if hepatitis C virus (HCV)-RNA levels and genotype distribution have any peculiar aspect in HCV-infected end-stage renal disease (ESRD) patients. The aim of this study was to evaluate in HCV-infected ESRD patients, the alanine aminotransferase (ALT) profile, HCV-RNA levels and genotype distribution, comparing them with HCV-infected patients with normal renal function. METHODS: A cross-sectional study was performed in 66 hemodialysis patients (group 1) and 264 subjects with normal renal function (group 2). All participants in both groups had detectable HCV-RNA. Mean ALT levels were determined in all subjects as well the viral load and the genotype. RESULTS: Groups were similar according to gender and age. ALT was normal in 74% patients in group 1 and in 23% in group 2 (p<0.001). The median viral load was 5.3 x 10(5) IU/mL in group 1 and 6.6 x 10(5) IU/mL in group 2 (p=0.23). Genotype 1b was the most prevalent in both groups (56% vs. 57%; p=0.38). CONCLUSION: HCV-infected ESRD patients have lower ALT levels, but the viral load and the genotype distribution are similar to those observed in HCV-infected individuals with normal renal function.
Assuntos
Alanina Transaminase/sangue , Hepacivirus/genética , Hepatite C/genética , Falência Renal Crônica/virologia , Rim/virologia , RNA Viral , Diálise Renal , Carga Viral , Adulto , Brasil , Estudos Transversais , Feminino , Genótipo , Hepatite C/enzimologia , Humanos , Rim/enzimologia , Falência Renal Crônica/enzimologia , Falência Renal Crônica/genética , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6 percent male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 percent (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95 percent confidence interval (CI), 1.50-8.70; aOR, 3.58; 95 percent CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95 percent CI, 1.60-53.08; aOR, 9.05; 95 percent CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.
CONTEXTO E OBJETIVO: Reações adversas a drogas são um problema significativo em pacientes sob terapia antiretroviral (TARV). Determinamos a freqüência de valores elevados de enzimas hepáticas em um grupo de crianças e adolescentes infectados pelo HIV sob TARV e os fatores de risco associados. TIPO DE ESTUDO E LOCAL: Estudo transversal, realizado na Divisão de Imunodeficiência em Pediatria, Hospital das Clínicas, Universidade Estadual de Campinas. MÉTODOS: Foram analisados prontuários médicos de 152 crianças e adolescentes (54,6 por cento masculino) infectados pelo HIV sob TARV, com dosagens de enzimas hepáticas, em média, 2,6 exames por paciente. A mediana de idade foi 7,48 anos. Clinicamente os pacientes foram classificados nas categorias N (6), A (29), B (78) e C (39). Foram avaliados os níveis séricos de aspartato aminotransferase e alanina aminotransferase. O sistema de escore da hepatotoxicidade foi: grau 1 (1,1 a 4,9 x limite superior ao normal, i.e., LSN), grau 2 (5,0 - 9,9 x LSN), grau 3 (10,0 - 15,0 x LSN) e grau 4 (>15,0 x LSN). Para determinar os fatores de risco de hepatotoxicidade, foram avaliados odds ratio (OR) e odds ratio ajustado (aOR) para idade, gênero, contagem de linfócitos TCD4+ e uso de medicações. RESULTADOS: Observamos hepatotoxicidade grau 1 em 19,7 por cento (30/152) pacientes. Não foi detectada hepatotoxicidade grau 2, 3 ou 4. Houve uma associação significativa entre a hepatotoxicidade e uso de sulfas (OR, 3,61; IC 95 por cento, 1,50 -8,70; ORajustado, 3,58; IC 95 por cento, 1,44 - 8,85) e agentes antituberculose (OR, 9,23; IC 95 por cento, 1,60 - 53,08; ORajustado, 9,05, IC 95 por cento, 1,48 - 55,25), mas não estava associada com TARV. CONCLUSÃO: Um quinto dos pacientes apresentaram hepatotoxicidade leve, atribuída ao uso de agentes antituberculose e sulfas. Nossos resultados sugerem que TARV foi bem tolerada.
Assuntos
Adolescente , Criança , Feminino , Humanos , Masculino , Doença Hepática Induzida por Substâncias e Drogas , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Fígado/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Métodos Epidemiológicos , Hepatite C/induzido quimicamente , Hepatite C/enzimologia , Fígado/enzimologia , Carga ViralRESUMO
BACKGROUND AND AIM: To what extent the serum levels of alanine aminotransferase (ALT) are related to histological characteristics of liver damage caused by hepatitis C virus (HCV) infection among patients with end-stage renal disease (ESRD) remains unclear. METHODS: Patients with a positive anti-HCV antibody titer confirmed by supplemental tests were evaluated by liver biopsy. We compared ALT levels in patients with and without renal damage, with similar histological grades and stages of inflammation and fibrosis. Results: Patients were divided into two groups: patients with ESRD (n = 25) and patients without ESRD renal damage (n = 39). RESULTS: The ALT level was 42.1 +/- 24.3 IU/L for the ESRD group, compared with 109.9 +/- 55.8 IU/L for the non-ESRD group (P < 0.001). Liver inflammation (modified Knodell grade) was 4.0 +/- 2.1 in the ESRD group versus 5.2 +/- 2.4 in the non- ESRD group; fibrosis (6-point scale) was 1.1 +/- 1.2 versus 1.7 +/- 1.5, respectively. CONCLUSIONS: Despite histological evidence of liver inflammation, ALT levels in the ESRD group were normal, while ALT levels were significantly higher in the non-ESRD group with similar levels of liver inflammation. In conclusion, ALT levels are not a useful indicator of HCV infection in patients with ESRD and liver biopsies should be recommended for kidney transplant candidates.
Assuntos
Alanina Transaminase/metabolismo , Hepatite C , Falência Renal Crônica/complicações , Adulto , Biópsia , Feminino , Seguimentos , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/complicações , Hepatite C/enzimologia , Hepatite C/patologia , Anticorpos Anti-Hepatite C/análise , Humanos , Técnicas Imunoenzimáticas , Falência Renal Crônica/enzimologia , Falência Renal Crônica/patologia , Fígado/enzimologia , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Viral/análise , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: During the years preceding this study, we noticed a relatively unusual high number of individuals with elevated alanine aminotransferase (ALT) levels in O'Brien, a small rural town in Argentina. Moreover, four individuals from this town underwent liver transplantation owing to hepatitis C virus (HCV)-induced liver cirrhosis. These findings prompted us to conduct a large population-based survey to evaluate the prevalence of HCV in this community. METHODS AND RESULTS: A total of 1637 individuals were studied. The overall HCV-seroprevalence was 5.7% (93/1637), being slightly higher in men (45/769; 5.9%) than in women (48/868; 5.5%). HCV seroprevalence increased with age, reaching a peak rate of 23.9% among individuals between 61 and 70 years of age. HCV RNA was present in 82.7% of all HCV seropositive individuals identified and 100% of them were infected with genotype 1b. ALT elevations were detected in 44% of HCV+ patients and were only observed among viremic individuals. Hepatitis B virus infection was also prevalent (52%) among HCV-seropositive patients. The most common risk factor associated with HCV transmission identified was the apparent use of inadequately sterilized glass syringes by a health care provider serving the community; however, other risk factors may have also played a role in the dissemination of HCV. CONCLUSIONS: Our findings provide an explanation for the relative high number of individuals with elevated ALT levels observed in this community and form the basis of future prospective studies on the natural history of genotype 1b infection.
Assuntos
Hepatite C/epidemiologia , Hepatite C/virologia , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Argentina/epidemiologia , Criança , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/genética , População Rural , Estudos SoroepidemiológicosRESUMO
BACKGROUND: Elevated liver enzymes are infrequent in patients with hepatitis C virus (HCV) infection undergoing chronic hemodialysis (HD), suggesting that the alanine aminotransferase (ALT) is a poor predictor of hepatocellular damage in this population. OBJECTIVE: To establish a more appropriate cut-off value of ALT to identify biochemical activity due to HCV infection in HD patients. STUDY DESIGN: A total of 217 patients, with an average age of 51.2 years, were evaluated between January and October 2002; 130 were males (60%). Serum ALT was measured by a kinetic method in five consecutive monthly blood samples, from which an average was obtained and divided by the upper limit of normal (ULN). HCV antibodies were determined using an enzyme immunoassay, the serum HCV-RNA by nested-PCR and HCV genotype by hybridization of the amplified sequence from the 5'-non-coding region. The cut-off value of ALT was obtained from a ROC curve. RESULTS: Within the 217 patients, 18 (8.3%) were anti-HCV-positive, 17 (7.8%) of whom were also HCV-RNA-positive. Genotype distribution was: 1a=47%; 1b=18%; 3a=35%. Mean ALT/ULN (0.77+/-0.57) of the 18 anti-HCV-positive cases was higher (p<0.001) than the negative group (0.38+/-0.23). The mean ALT/ULN (0.81+/-0.57) of the 17 HCV-RNA-positive cases was also higher (p<0.0001) than the negative cases (0.37+/-0.23). The cut-off value of ALT to distinguish the anti-HCV-positive from negative patients was 0.50% or 50% of the ULN (sensitivity=67%; specificity=83%). According to the HCV-RNA, the cut-off value of ALT was 0.45% or 45% of the ULN (sensitivity=71%; specificity=80%). CONCLUSION: Reducing the cut-off of ALT by half, enables a better identification of biochemical activity in patients with HCV infection on chronic HD.
Assuntos
Alanina Transaminase/sangue , Hepacivirus/isolamento & purificação , Hepatite C/fisiopatologia , Diálise Renal , Viremia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/enzimologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , Reação em Cadeia da Polimerase , RNA Viral/sangue , RNA Viral/genética , Valores de ReferênciaRESUMO
The patients with chronic renal failure in hemodialysis present low levels of serum alanine aminotransferases. In order to establish a better cutoff value for ALT in hepatitis C screening of hemodialysis patients, the ALT levels were measured monthly in 235 patients, being excluded those that presented average above the upper limit of normality. The cutoff value was identified by construction of a ROC curve (receiver operating characteristic). Among 202 patients, 15 (7.4%) presented antibodies to hepatitis C virus (anti-HCV) and 187 (92.6%) were anti-HCV negative, with an ALT average of 0.7 and of 0.5 from ULN (p <0.0001), respectively. The better cutoff value for ALT was at 0.6 from ULN, with sensitivity of 67% and specificity of 75% in anti-HCV screening. These results suggest that ULN of ALT could be reduced for 60% from conventional limit, when we are evaluating patients with CRF in hemodialysis.
Assuntos
Alanina Transaminase/sangue , Hepatite C/diagnóstico , Falência Renal Crônica/enzimologia , Diálise Renal/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Hepatite C/enzimologia , Hepatite C/etiologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Curva ROC , Padrões de Referência , Sensibilidade e EspecificidadeRESUMO
The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.
Assuntos
Alanina Transaminase/sangue , Doadores de Sangue , Anticorpos Anti-Hepatite C/sangue , Adulto , Estudos de Coortes , Feminino , Seguimentos , Hepatite C/sangue , Hepatite C/enzimologia , Hepatite C/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Medição de RiscoRESUMO
OBJECTIVES: To delineate the importance of non-A, non-B, non-C (non-ABC) hepatitis, and the role of GB virus C (GBV-C) in children. METHODS: From 1980 to 1995, acute-onset viral hepatitis was diagnosed in 166 inpatients and categorized into type A, B, C, and non-ABC hepatitis according to the serologic markers or the results of polymerase chain reaction assay for HBV DNA or HCV ribonucleic acid (RNA) in the National Taiwan University Hospital. Non-ABC hepatitis was diagnosed in 57 patients (34%). GBV-C RNA was investigated by reverse transcription and nested polymerase chain reaction in 32 of the 57 patients with non-ABC hepatitis. The clinical and laboratory features of patients with acute non-ABC hepatitis were compared with the features of those with acute hepatitis A and B. RESULTS: The degree of abnormality in aminotransferase activities was milder in patients with non-ABC hepatitis than in those with hepatitis B; chronicity was noted in 12%. Fulminant hepatitis occurred in 16%, and the mortality rate was 56%. Young age carried a significantly higher risk of having a fulminant course (1.9 +/- 0.2 years of age vs 6.4 +/- 5.1 years of age in acute course; p < 0.05). Compared with fulminant hepatitis B, fulminant non-ABC hepatitis had a trend of a longer interval from onset to death (119.2 +/- 144.8 vs 15.2 +/- 8.4 days; p = 0.079). GBV-C RNA was detected in only two of the patients tested, both of whom had received transfusions; one had persistent viremia and fluctuating aminotransferase values. CONCLUSIONS: Non-ABC hepatitis plays an important role in the etiology of pediatric viral hepatitis; however, the role of GBV-C is minor. A search for other unknown viral agent(s) responsible for non-ABCG hepatitis is needed.
Assuntos
Flaviviridae , Hepatite C/virologia , Hepatite E/virologia , Doença Aguda , Pré-Escolar , Doença Crônica , DNA Viral/análise , Feminino , Flaviviridae/genética , Hepatite C/enzimologia , Hepatite C/mortalidade , Hepatite E/enzimologia , Hepatite E/mortalidade , Humanos , Fígado/enzimologia , Testes de Função Hepática , Masculino , RNA Viral/análise , Estudos Retrospectivos , Taxa de Sobrevida , Transaminases/metabolismoRESUMO
Introduçao. A hepatite crônica pelo vírus C apresenta tendência evolutiva para cirrose hepática e hepatocarcinoma. Tratamento, com drogas antivirais, está indicado numa tentativa de modificar a evoluçao da doença. Objetivo. Avaliar a resposta de pacientes com hepatite crônica ou cirrose pós-hepatite C ao tratamento com interferon alfa recombinante e identificar os fatores associados com boa resposta terapêutica. Métodos. Foram estudados 38 pacientes com hepatite crônica ativa ou cirrose pelo vírus C, tratados com 2,5 a 3,0MU de interfon três vezes por semana, por períodos de 6 a 12 meses. Considerou-se resposta completa e duradoura quando a ALT e AST se mantinham normais por período de seis meses após o término do tratamento, e resposta completa com recidiva naqueles em que houve elevaçao das enzimas após a suspensao da droga. Resultados. Houve normalizaçao da ALT e AST em 17 dos 38 pacientes (44,7 por cento). Deste grupo, 9/17 tiveram resposta completa e duradoura, e em 8/17 houve aumento das enzimas após a interrupçao do tratamento. Houve uma tendência de melhor resposta ao interferon nos pacientes jovens e naqueles com hepatite crônica ativa (ao invéz da cirrose). Os efeitos colaterais mais frequentes foram febre (80 por cento), mialgia (60 por cento), astenia (50 por cento), cefaléia (40 por cento) e artralgia (36 por cento). Conclusoes. O tratamento com interfon alfa recombinante mostrou resposta satisfatória e duradoura em 23 por cento dos casos, com melhor resultado em pacientes jovens e sem cirrose associada.
Assuntos
Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Adulto , Interferon Tipo I/uso terapêutico , Hepatite C/terapia , Hepatite Crônica/terapia , Cirrose Hepática/terapia , Aspartato Aminotransferases/sangue , Idoso de 80 Anos ou mais , Seguimentos , Hepatite C/enzimologia , Alanina Transaminase/sangue , Hepatite Crônica/diagnóstico , Hepatite Crônica/enzimologia , Cirrose Hepática/enzimologia , Cirrose Hepática/etiologia , Fatores EtáriosRESUMO
We reviewed the records of all patients with a diagnosis of malignancy who were treated at our center and who had not had chemotherapy for at least 18 months, to assess the prevalence of chronic hepatitis B surface antigen (HBsAg)-negative hepatitis, to assess the prevalence of a marker of hepatitis C virus infection, and to determine the severity of chronic liver disease. Of 557 eligible patients, 38 (6.8%) had chronic HBsAg-negative hepatitis. Of these 38 patients, 20 (52.6%) had a marker of hepatitis C virus infection. The prevalence of chronic HBsAg-negative hepatitis was higher in patients previously treated for leukemia than in patients treated for another malignancy (11.8% vs 4.6%; p = 0.004). The liver biopsy revealed chronic active hepatitis or cirrhosis or both in 8 (28%) of 28 patients with clinical chronic HBsAg-negative hepatitis. Four patients without hepatitis C virus infection who underwent liver biopsy had hepatitis B virus antigen in the liver, confirmed by immunohistochemistry studies. One patient uninfected with hepatitis C virus had hemochromatosis. We conclude that infection with hepatitis C virus was the major cause of chronic HBsAg-negative hepatitis in pediatric patients previously treated for malignancy; the cause remained unidentified in 30% of the patients.
Assuntos
Antígenos de Superfície da Hepatite B/análise , Hepatite C/epidemiologia , Hepatite Crônica/epidemiologia , Neoplasias/tratamento farmacológico , Alanina Transaminase/sangue , Anticorpos Antivirais/análise , Autoanticorpos/análise , Transfusão de Sangue , Criança , Pré-Escolar , Feminino , Hepacivirus/imunologia , Hepatite/enzimologia , Hepatite/epidemiologia , Anticorpos Anti-Hepatite/análise , Hepatite C/enzimologia , Hepatite Crônica/enzimologia , Humanos , Lactente , Itália/epidemiologia , Leucemia/tratamento farmacológico , Masculino , PrevalênciaRESUMO
Few data on chronic non-A, non-B hepatitis (NANB-CH) have been published so far in our country. We have studied 85 patients classified into four groups: I. post-transfusional (PT), 35 patients (41.2%); II. risk group (GR), including health professionals and drug addicts, 11 (12.9%); III. sporadic with a well defined beginning (EBD), 19 (22.4%) and IV. sporadic with ill-defined beginning (END), 20 (23.5%). The mean age in group I was significantly higher than in groups II and III. A polyphasic pattern of serum aminotransferases and severe histological forms were observed in all groups. It is concluded that the way of infection has probably no prognostic importance.