RESUMEN
The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) markers in families of HBsAg-positive patients with chronic liver disease. Serum anti-HBc, HBsAg and anti-HBs were determined by enzyme immunoassay and four subpopulations were considered: genetically related (consanguineous) and non-genetically related (non-consanguineous) Asian subjects and genetically related and non-genetically related Western subjects. A total of 165 and 186 relatives of Asian and Western origin were enrolled, respectively. The occurrence of HBsAg and anti-HBs antibodies was significantly higher (P < 0.0001) in family members of Asian origin (81.8%) than in family members of Western origin (36.5%). HBsAg was also more frequent among brothers (79.6 vs 8.5%; P < 0.0001), children (37.9 vs 3.3%; P < 0.0001) and other family members (33.9 vs 16.7%; P < 0.0007) of Asian than Western origin, respectively. No difference between groups was found for anti-HBs, which was more frequently observed in fathers, spouses and other non-genetic relatives. HBV infection was significantly higher in children of Asian than Western mothers (P < 0.0004). In both ethnic groups, the mothers contributed more to their children's infection than the fathers (P < 0.0001). Furthermore, HBsAg was more frequent among consanguineous members and anti-HBs among non-consanguineous members. These results suggest the occurrence of vertical transmission of HBV among consanguineous members and probably horizontal sexual transmission among non-consanguineous members of a family cluster. Thus, the high occurrence of dissemination of HBV infection characterizes family members as a high-risk group that calls for immunoprophylaxis. Finally, the study showed a high familial aggregation rate for both ethnic groups, 18/19 (94.7%) and 23/26 (88.5%) of the Asian and Western origin, respectively.
Asunto(s)
Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/etnología , Adolescente , Adulto , Pueblo Asiatico , Biomarcadores/sangre , Brasil/etnología , Niño , Familia , Femenino , Hepatitis B Crónica/sangre , Hepatitis B Crónica/transmisión , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Población BlancaRESUMEN
The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) markers in families of HBsAg-positive patients with chronic liver disease. Serum anti-HBc, HBsAg and anti-HBs were determined by enzyme immunoassay and four subpopulations were considered: genetically related (consanguineous) and non-genetically related (non-consanguineous) Asian subjects and genetically related and non-genetically related Western subjects. A total of 165 and 186 relatives of Asian and Western origin were enrolled, respectively. The occurrence of HBsAg and anti-HBs antibodies was significantly higher (P < 0.0001) in family members of Asian origin (81.8 percent) than in family members of Western origin (36.5 percent). HBsAg was also more frequent among brothers (79.6 vs 8.5 percent; P < 0.0001), children (37.9 vs 3.3 percent; P < 0.0001) and other family members (33.9 vs 16.7 percent; P < 0.0007) of Asian than Western origin, respectivelly. No difference between groups was found for anti-HBs, which was more frequently observed in fathers, spouses and other non-genetic relatives. HBV infection was significantly higher in children of Asian than Western mothers (P < 0.0004). In both ethnic groups, the mothers contributed more to their children's infection than the fathers (P < 0.0001). Furthermore, HBsAg was more frequent among consanguineous members and anti-HBs among non-consanguineous members. These results suggest the occurrence of vertical transmission of HBV among consanguineous members and probably horizontal sexual transmission among non-consanguineous members of a family cluster. Thus, the high occurrence of dissemination of HBV infection characterizes family members as a high-risk group that calls for immunoprophylaxis. Finally, the study showed a high familial aggregation rate for both ethnic groups, 18/19 (94.7 percent) and 23/26 (88.5 percent) of the Asian and Western origin, respectively.
Asunto(s)
Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/etnología , Pueblo Asiatico , Biomarcadores/sangre , Brasil/etnología , Población Blanca , Familia , Hepatitis B Crónica/sangre , Hepatitis B Crónica/transmisión , Técnicas para Inmunoenzimas , Estudios ProspectivosRESUMEN
The shortage of donor organs and the long waiting lists have increased the need to better select liver transplant candidates using predictors of success. We reviewed the results of 29 liver transplantations performed from January 2002 to February 2003 analyzing the correlations with early mortality (30 days) of patient data, pretransplant laboratory data, warm ischemia time, intraoperations blood unit transfusions, and postoperative complications of prolonged mechanical ventilation, dialysis, and infection. Overall early mortality was 27.6% and 44% in fulminant hepatic failure (n = 9), there were four retransplants with one death, and two intraoperative deaths. Only pretransplant bilirubin (P =.045) and postoperative lactate levels (P =.002) were significantly different between alive versus dead patients. In this small population bilirubin was more related to death than the MELD score. Lactate levels, nonspecific predictor of death in shock syndromes were probably related to septic complications.
Asunto(s)
Bilirrubina/sangre , Trasplante de Hígado/mortalidad , Adulto , Anciano , Biomarcadores/sangre , Creatinina/sangre , Demografía , Femenino , Humanos , Relación Normalizada Internacional , Hepatopatías/clasificación , Hepatopatías/cirugía , Fallo Hepático Agudo/cirugía , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Análisis de Supervivencia , Factores de TiempoRESUMEN
The aim of the present study was to determine the prevalence of celiac disease in children of short stature and to assess whether some of the routine laboratory examinations performed to determine the cause of short stature could suggest the presence of celiac disease. A total of 106 children of short stature and no gastrointestinal symptoms were studied. An extensive endocrine work-up had been negative for all of them and an additional investigation was performed by measuring the concentration of antiendomysial antibody. Patients who were positive for antiendomysial antibody ( > or = 1:10) or who exhibited IgA deficiency (less than 5 mg/dl) were referred for an endoscopic intestinal biopsy. We detected a pathological titer of antiendomysial IgA in six of these patients. Five of them showed histological abnormalities compatible with celiac disease and one had normal histology and was considered to have potential celiac disease. The prevalence of celiac disease in the population studied was 4.7 percent (with another 0.9 percent of the subjects being considered to have potential celiac disease). The children with celiac disease did not differ in any of the parameters tested when compared to those without celiac disease, though they showed an improvement in growth velocity after treatment with a gluten-free diet. We conclude that it is important to test all children with short stature for celiac disease by measuring antiendomysial IgA.
Asunto(s)
Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Enfermedad Celíaca , Trastornos del Crecimiento , Autoanticuerpos , Biopsia , Estatura , Brasil , Enfermedad Celíaca , Técnica del Anticuerpo Fluorescente , Deficiencia de IgA , PrevalenciaRESUMEN
The aim of the present study was to determine the prevalence of celiac disease in children of short stature and to assess whether some of the routine laboratory examinations performed to determine the cause of short stature could suggest the presence of celiac disease. A total of 106 children of short stature and no gastrointestinal symptoms were studied. An extensive endocrine work-up had been negative for all of them and an additional investigation was performed by measuring the concentration of antiendomysial antibody. Patients who were positive for antiendomysial antibody (> or =1:10) or who exhibited IgA deficiency (less than 5 mg/dl) were referred for an endoscopic intestinal biopsy. We detected a pathological titer of antiendomysial IgA in six of these patients. Five of them showed histological abnormalities compatible with celiac disease and one had normal histology and was considered to have potential celiac disease. The prevalence of celiac disease in the population studied was 4.7% (with another 0.9% of the subjects being considered to have potential celiac disease). The children with celiac disease did not differ in any of the parameters tested when compared to those without celiac disease, though they showed an improvement in growth velocity after treatment with a gluten-free diet. We conclude that it is important to test all children with short stature for celiac disease by measuring antiendomysial IgA.
Asunto(s)
Enfermedad Celíaca/complicaciones , Trastornos del Crecimiento/etiología , Adolescente , Autoanticuerpos/sangre , Biopsia , Estatura , Brasil , Enfermedad Celíaca/diagnóstico , Niño , Preescolar , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Deficiencia de IgA/sangre , Lactante , MasculinoRESUMEN
The hypothesis of the role of iron overload associated with HFE gene mutations in the pathogenesis of nonalcoholic steatohepatitis (NASH) has been raised in recent years. In the present study, biochemical and histopathological evidence of iron overload and HFE mutations was investigated in NASH patients. Thirty-two NASH patients, 19 females (59%), average 49.2 years, 72% Caucasians, 12% Mulattoes and 12% Asians, were submitted to serum aminotransferase and iron profile determinations. Liver biopsies were analyzed for necroinflammatory activity, architectural damage and iron deposition. In 31 of the patients, C282Y and H63D mutations were tested by PCR-RFLP. Alanine aminotransferase levels were increased in 30 patients, 2.42 1.12 times the upper normal limit on average. Serum iron concentration, transferrin saturation and ferritin averages were 99.4 31.3 g/dl, 33.1 12.7% and 219.8 163.8 g/dl, respectively, corresponding to normal values in 93.5, 68.7 and 78.1% of the patients. Hepatic siderosis was observed in three patients and was not associated with architectural damage (P = 0.53) or with necroinflammatory activity (P = 0.27). The allelic frequencies (N = 31) found were 1.6 and 14.1% for C282Y and H63D, respectively, which were compatible with those described for the local population. In conclusion, no evidence of an association of hepatic iron overload and HFE mutations with NASH was found. Brazilian NASH patients comprise a heterogeneous group with many associated conditions such as hyperinsulinism, environmental hepatotoxin exposure and drugs, but not hepatic iron overload, and their disease susceptibility could be related to genetic and environmental features other than HFE mutations.
Asunto(s)
Hígado Graso/etiología , Antígenos de Histocompatibilidad Clase I/genética , Sobrecarga de Hierro/complicaciones , Proteínas de la Membrana/genética , Mutación , Adulto , Anciano , Alanina Transaminasa/análisis , Biopsia , Estudios de Cohortes , Hígado Graso/genética , Hígado Graso/patología , Femenino , Ferritinas/análisis , Proteína de la Hemocromatosis , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Transferrina/análisisRESUMEN
The hypothesis of the role of iron overload associated with HFE gene mutations in the pathogenesis of nonalcoholic steatohepatitis (NASH) has been raised in recent years. In the present study, biochemical and histopathological evidence of iron overload and HFE mutations was investigated in NASH patients. Thirty-two NASH patients, 19 females (59 percent), average 49.2 years, 72 percent Caucasians, 12 percent Mulattoes and 12 percent Asians, were submitted to serum aminotransferase and iron profile determinations. Liver biopsies were analyzed for necroinflammatory activity, architectural damage and iron deposition. In 31 of the patients, C282Y and H63D mutations were tested by PCR-RFLP. Alanine aminotransferase levels were increased in 30 patients, 2.42 + or - 1.12 times the upper normal limit on average. Serum iron concentration, transferrin saturation and ferritin averages were 99.4 + or - 31.3 g/dl, 33.1 + or - 12.7 percent and 219.8 + or - 163.8 æg/dl, respectively, corresponding to normal values in 93.5, 68.7 and 78.1 percent of the patients. Hepatic siderosis was observed in three patients and was not associated with architectural damage (P = 0.53) or with necroinflammatory activity (P = 0.27). The allelic frequencies (N = 31) found were 1.6 and 14.1 percent for C282Y and H63D, respectively, which were compatible with those described for the local population. In conclusion, no evidence of an association of hepatic iron overload and HFE mutations with NASH was found. Brazilian NASH patients comprise a heterogeneous group with many associated conditions such as hyperinsulinism, environmental hepatotoxin exposure and drugs, but not hepatic iron overload, and their disease susceptibility could be related to genetic and environmental features other than HFE mutations
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Hígado Graso , Sobrecarga de Hierro , Mutación , Alanina Transaminasa , Biopsia , Estudios de Cohortes , Hígado Graso , Ferritinas , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , TransferrinaAsunto(s)
Colangitis Esclerosante/genética , Antígenos HLA-DR/genética , Factor de Necrosis Tumoral alfa/genética , Adolescente , Adulto , Brasil , Estudios de Casos y Controles , Niño , Femenino , Predisposición Genética a la Enfermedad , Cadenas HLA-DRB1 , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Regiones Promotoras Genéticas/genéticaRESUMEN
BACKGROUND: Antibodies to soluble liver antigen/liver pancreas (SLA/LP) are specific markers of autoimmune hepatitis. Their target antigen has recently been cloned. AIMS: To establish standardised immunoassays using the recombinant antigen, and to assess the frequency and significance of seropositivity in patients from different countries. METHODS: An enzyme linked immunoassay was developed using purified recombinant antigen and validated by testing sera from 200 healthy blood donors and 1026 patients with various liver and non-liver diseases. The assay was then applied to 454 sera from 419 patients with autoimmune hepatitis from different countries. All sera were also tested by inhibition immunoassay and western blot. RESULTS: Antibodies were reliably detected by the recombinant immunoassay and occurred exclusively in patients with autoimmune liver disease. Twenty three of 149 patients from the USA (15%), 23/132 from Brazil (17%), 21/108 from Germany (19%), and 2/30 from Japan (7%) were seropositive. Clinical features at presentation were similar between seropositive and seronegative patients. However, relapse after corticosteroid withdrawal or during maintenance therapy occurred more commonly in seropositive patients. CONCLUSIONS: Antibodies to SLA/LP can be reliably detected by these standardised immunoassays based on recombinant antigen. Antibodies to SLA/LP occur with similar frequencies in different geographical regions, races, and age groups, and are of exquisite diagnostic specificity. Whether SLA/LP positive patients represent a clinically distinct subgroup remains to be determined; relapse during treatment reduction appeared to be more common in the SLA/LP group.
Asunto(s)
Anticuerpos Monoclonales/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Hepatitis Autoinmune/diagnóstico , Antígenos de Histocompatibilidad Clase I , Adolescente , Adulto , Anticuerpos Monoclonales/inmunología , Biomarcadores/sangre , Brasil , Niño , Preescolar , Femenino , Alemania , Hepatitis Autoinmune/terapia , Antígenos de Histocompatibilidad Clase II , Humanos , Lactante , Recién Nacido , Japón , Masculino , Proteínas Recombinantes , Recurrencia , Sensibilidad y Especificidad , Resultado del Tratamiento , Estados UnidosRESUMEN
The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53%) were homozygous and one (7%) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil.
Asunto(s)
Antígenos HLA/genética , Antígenos HLA-A/genética , Hemocromatosis/genética , Antígenos de Histocompatibilidad Clase I/genética , Proteínas de la Membrana , Mutación/genética , Adulto , Edad de Inicio , Anciano , Sustitución de Aminoácidos , Secuencia de Bases , Brasil/epidemiología , Pruebas Genéticas , Hemocromatosis/epidemiología , Proteína de la Hemocromatosis , Heterocigoto , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53 percent) were homozygous and one (7 percent) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil
Asunto(s)
Humanos , Animales , Masculino , Adulto , Persona de Mediana Edad , Hemocromatosis , Antígenos HLA-A , Edad de Inicio , Sustitución de Aminoácidos , Secuencia de Bases , Brasil , Pruebas Genéticas , Hemocromatosis , Heterocigoto , Homocigoto , Mutación , PrevalenciaRESUMEN
The detection of anti-actin (AAA) by immunofluorescence is hindered by the presence of a serum factor. To better understand how it interferes with AAA detection, we tested sera from 20 patients with autoimmune hepatitis, and from 21 healthy adults, diluted 1:10 and prepared as follows: (A) diluted with PBS; (B) inactivated at 56 degrees C, and diluted with PBS; (C) diluted with 34 mM EDTA/PBS; (D) heated and diluted with EDTA/PBS. To reveal AAA, a fluorescein-labelled anti-human IgG was used in the process of indirect immunofluorescence. In a parallel assay, the substrate, acetone-fixed human fibroblasts, was preincubated with sera prepared as if it were to identify AAA, but instead, a rhodamine-phalloidin was used to identify F-actin, by direct immunofluorescence. All sera from patients were reactive to AAA when heat-inactivated and/or calcium-chelated, and 60% of them when diluted with unmodified sera (P=0.004). F-actin continued to be present after preincubation with heat-inactivated or calcium-chelated sera from patients and healthy controls, and in 41.5% of reactions with unmodified serum (P=0.0000001). The heat inactivation and the calcium chelation were both efficient procedures for maintaining the microfilament structure intact after serum incubation and, therefore, for identifying AAA.
Asunto(s)
Actinas/inmunología , Actinas/metabolismo , Autoanticuerpos/sangre , Calcio/fisiología , Calor , Proteínas de Microfilamentos/fisiología , Factores Despolimerizantes de la Actina , Actinas/sangre , Adulto , Autoanticuerpos/análisis , Calcio/sangre , Destrina , Técnica del Anticuerpo Fluorescente , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/inmunología , Humanos , Proteínas de Microfilamentos/sangre , Polímeros/metabolismoRESUMEN
Parvovirus B19 has been associated by some investigators with cases of severe hepatitis. The aim of the present study was to determine the presence of active parvovirus B19 infection among 129 Brazilian patients with non-A-E hepatitis. The patients were assayed for antibodies against parvovirus B19, IgM class, by ELISA. In IgM-positive cases, parvovirus B19 DNA was assayed by PCR in serum and liver tissue and parvovirus VP1 antigen in liver tissue was assayed by immunohistochemistry. Antibodies against parvovirus B19, IgM class, were detected in 3 (2.3 percent) of 129 patients with non-A-E hepatitis. Previous surgery and blood transfusions were reported by these 3 patients. One patient was a 56-year-old female with severe hepatitis, with antimitochondrial antibody seropositivity and submassive necrosis at liver biopsy, who responded to corticosteroid therapy. Strong evidence for active parvovirus B19 infection was found in this patient, with parvovirus B19 DNA being detected by PCR in liver tissue. Furthermore, parvovirus VP1 antigen was also detected in liver tissue by immunohistochemistry. The other two IgM-positive patients were chronic hepatitis cases, but active infection was not proven, since neither viral DNA nor antigen were detected in their liver tissues. This and other reports suggest a possible relation between parvovirus B19 infection and some cases of hepatitis
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Hepatitis Viral Humana/virología , Parvovirus B19 Humano/aislamiento & purificación , Enfermedad Aguda , Anticuerpos Antivirales/aislamiento & purificación , Antígenos Virales/aislamiento & purificación , Enfermedad Crónica , ADN Viral/aislamiento & purificación , Electroforesis en Gel de Agar , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina M/aislamiento & purificación , Hígado/patología , Hígado/virología , Parvovirus B19 Humano/inmunología , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND/AIMS: Susceptibility to autoimmune hepatitis (AIH) has been linked to different HLA-DR antigens. Recently, AIH type 1 was associated with polymorphisms in the tumor necrosis factor alpha gene promoter (TNFA) at position -308. In this respect, the frequency of the TNFA*2 allele, in linkage disequilibrium with HLA-DRB1*0301, was shown to be significantly increased in whites with AIH type 1. The aim of this study was to assess the role of TNFA alleles in conferring susceptibility to AIH, studying a population where the disease is not primarily associated with HLA-DRB1*03. METHODS: The determination of HLA-DRB1 and TNFA alleles was performed in 92 patients with AIH type 1, 29 subjects with AIH type 2 and 83 healthy controls by polymerase chain reaction-based techniques. RESULTS: The distribution of TNFA alleles was similar in patients with AIH types 1 and 2, when compared with controls. In addition, the TNFA*2 allele was identified in patients carrying HLA-DR antigens other than HLA-DRB1*03. Interestingly, higher gammaglobulin levels were observed in TNFA*2 positive patients. CONCLUSIONS: Our data indicate that susceptibility to AIH remains primarily linked to the HLA-DRB1 locus, and suggest that the association of AIH with TNFA*2 previously observed in whites might be secondary to a linkage disequilibrium with HLA-DRB1*0301.
Asunto(s)
Ligamiento Genético , Hepatitis Autoinmune/genética , Polimorfismo Genético/genética , Factor de Necrosis Tumoral alfa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Niño , Preescolar , Femenino , Predisposición Genética a la Enfermedad/genética , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Parvovirus B19 has been associated by some investigators with cases of severe hepatitis. The aim of the present study was to determine the presence of active parvovirus B19 infection among 129 Brazilian patients with non-A-E hepatitis. The patients were assayed for antibodies against parvovirus B19, IgM class, by ELISA. In IgM-positive cases, parvovirus B19 DNA was assayed by PCR in serum and liver tissue and parvovirus VP1 antigen in liver tissue was assayed by immunohistochemistry. Antibodies against parvovirus B19, IgM class, were detected in 3 (2.3%) of 129 patients with non-A-E hepatitis. Previous surgery and blood transfusions were reported by these 3 patients. One patient was a 56-year-old female with severe hepatitis, with antimitochondrial antibody seropositivity and submassive necrosis at liver biopsy, who responded to corticosteroid therapy. Strong evidence for active parvovirus B19 infection was found in this patient, with parvovirus B19 DNA being detected by PCR in liver tissue. Furthermore, parvovirus VP1 antigen was also detected in liver tissue by immunohistochemistry. The other two IgM-positive patients were chronic hepatitis cases, but active infection was not proven, since neither viral DNA nor antigen were detected in their liver tissues. This and other reports suggest a possible relation between parvovirus B19 infection and some cases of hepatitis.
Asunto(s)
Hepatitis Viral Humana/virología , Parvovirus B19 Humano/aislamiento & purificación , Enfermedad Aguda , Anciano , Anticuerpos Antivirales/aislamiento & purificación , Antígenos Virales/aislamiento & purificación , Enfermedad Crónica , ADN Viral/aislamiento & purificación , Electroforesis en Gel de Agar , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina M/aislamiento & purificación , Hígado/patología , Hígado/virología , Masculino , Persona de Mediana Edad , Parvovirus B19 Humano/inmunología , Reacción en Cadena de la PolimerasaRESUMEN
Susceptibility to autoimmune hepatitis type I (AIH-1) has been associated with HLA-DR3, DR52, and DR4 antigens in Caucasian and Oriental patients. However, in Brazil, disease susceptibility is primarily linked to DR13 and DR52. In this highly admixed population, we find different DR13-associated haplotypes, presenting a unique opportunity to discriminate relevant genes within a tightly linked genomic region. To identify the primary susceptibility locus, we sequenced DR13 alleles of 39 patients with AIH-1 and 22 controls. Patients were almost exclusively DRB1*1301, but half of controls typed DRB1*1302. HLA-DQ haplotypes were varied. Oligotyping of DRB3 locus of all patients and also within the HLA-DR13 positive group showed an allele distribution comparable to controls, confirming that the stronger association lies in the DRB1 locus. On the other hand, if DRB1*1301 is the major susceptibility factor in our sample, the only amino acid different from DRB1*1302 in position 86, corresponding to pocket 1 in the peptide-presenting groove, may be important. We propose that peptide presentation leading to pathogenesis of AIH-1 may be quite stringent, but will also be affected by other strong genetic or environmental susceptibility factors, which would explain the various HLA molecules associated to the disease in the different populations.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Antígenos HLA/genética , Haplotipos/inmunología , Hepatitis Autoinmune/genética , Hepatitis Autoinmune/inmunología , Alelos , Secuencias de Aminoácidos/genética , Marcadores Genéticos/inmunología , Antígenos HLA-DQ/genética , Cadenas alfa de HLA-DQ , Cadenas beta de HLA-DQ , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Cadenas HLA-DRB3 , Hepatitis Autoinmune/clasificación , Hepatitis Autoinmune/etiología , Prueba de Histocompatibilidad , HumanosRESUMEN
BACKGROUND: Use of polyclonal anti-hepatitis B surface antigen immunoglobulin (HBIg) has been shown to reduce hepatitis B virus (HBV) recurrence after liver transplantation (LT) and to decrease the frequency of acute cellular rejection (ACR). However, the protective role of HBIg against ACR remains controversial, since HBV infection has been also associated with a lower incidence of ACR. AIM: To assess the relationship between HBIg immunoprophylaxis and the incidence of rejection after LT. METHODS: 260 patients (158 males, 43 +/- 14 years old) submitted to LT were retrospectively evaluated and divided into three groups, according to the presence of HBsAg and the use of HBIg. Group I was comprised of HBsAg-positive patients (n = 12) that received HBIg for more than 6 months. Group II was comprised of HBsAg-positive patients that historically have not received HBIg or have been treated irregularly for less than 3 months (n = 10). Group III was composed of 238 HBsAg-negative subjects that have not received HBIg. RESULTS: HBIg-treated patients (group I) had significantly less ACR episodes, when compared to group II and III. No differences between groups II and III were observed. CONCLUSIONS: Long-term HBIg administration contributes independently to reduce the number of ACR episodes after LT.
Asunto(s)
Rechazo de Injerto/prevención & control , Anticuerpos contra la Hepatitis B/uso terapéutico , Hepatitis B Crónica/cirugía , Trasplante de Hígado/inmunología , Receptores de Antígenos de Linfocitos B/uso terapéutico , Enfermedad Aguda , Adulto , Antígenos de Superficie/inmunología , Antígenos de Superficie/uso terapéutico , Femenino , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Anticuerpos contra la Hepatitis B/inmunología , Hepatitis B Crónica/inmunología , Humanos , Masculino , Receptores de Antígenos de Linfocitos B/inmunología , Estudios RetrospectivosRESUMEN
UNLABELLED: Familial amyloidotic polyneuropathy type 1 (FAP1) is an inherited systemic amyloidosis that is secondary to the deposition of transthyretin (TTR) variants in peripheral nerves and in certain visceral organs. More than 50 distinct mutations have already been described in the TTR gene. Yet, the most common mutation found worldwide is a substitution of valine for methionine in position 30 (Val30Met). Currently, the variants of TTR in Brazilian FAP1 patients remain largely unknown and the aim of this study was to analyze the frequency of the TTR Val30Met mutation in such Brazilian subjects. METHODS: Thirty-two FAP1 patients belonging to 24 different families were studied for the presence of Val30Met variant by PCR-RFLP. RESULTS: All Brazilian FAP1 subjects studied were positive for the TTR Val30Met variant. As expected, all of them were heterozygous for the mutation. CONCLUSION: TTR Val30Met mutation was the sole TTR variant found in Brazilian FAP1 patients in this cohort, and it was present even in those subjects without a clear history of Portuguese ancestry.