RESUMO
PURPOSE: This study sought to identify the initiation of placental hormonal production as defined by the production of endogenous estradiol (E2) and progesterone (P4) in a cohort of patients undergoing programmed endometrial preparation cycles with single embryo transfers resulting in live-born singletons. METHODS: In this retrospective cohort study, patients undergoing either programmed frozen-thawed embryo transfer (FET) with autologous oocytes or donor egg recipient (DER) cycles with fresh embryos were screened for inclusion. Only patients who underwent a single embryo transfer, had a single gestational sac, and a resultant live-born singleton were included. All patients were treated with E2 patches and intramuscular progesterone injections. Main outcome measures were serial E2 and P4, with median values calculated for cycle days 28 (baseline), or 4w0d gestational age (GA), through 60, or 8w4d GA. The baseline cycle day (CD) 28 median value was compared to each daily median cycle day value using the Wilcoxon signed rank test. RESULTS: A total of 696 patients, 569 using autologous oocytes in programmed FET cycles and 127 using fresh donor oocytes, from 4/2013 to 4/2019 met inclusion criteria. Serum E2 and P4 levels stayed consistent initially and then began to increase daily. Compared to baseline CD 28 E2 (415 pg/mL), the serum E2 was significantly elevated at 542 pg/mL (P < 0.001) beginning on CD 36 (5w1d GA). With respect to baseline CD 28 P4 (28.1 ng/mL), beginning on CD 48 (6w6d GA), the serum P4 was significantly elevated at 31.6 ng/mL (P < 0.001). CONCLUSION: These results demonstrate that endogenous placental estradiol and progesterone production may occur by CD 36 and CD 48, respectively, earlier than traditionally thought.
Assuntos
Corpo Lúteo/metabolismo , Fertilização in vitro , Hormônios Placentários/biossíntese , Progesterona/biossíntese , Adulto , Coeficiente de Natalidade , Corpo Lúteo/crescimento & desenvolvimento , Criopreservação , Transferência Embrionária/tendências , Endométrio/crescimento & desenvolvimento , Endométrio/metabolismo , Feminino , Humanos , Nascido Vivo/genética , Oócitos/crescimento & desenvolvimento , Indução da Ovulação/métodos , Hormônios Placentários/genética , Gravidez , Taxa de Gravidez , Progesterona/genéticaRESUMO
PCOS remains one of the most intriguing endocrine disorders that physicians encounter even though it was first described over 80 years ago. Although the diagnostic criteria, nomenclature, and ideal therapeutic strategies are areas of active and ongoing debate, there is no doubt that we have made tremendous progress in improving the quality of life and reproductive outcomes of women who suffer from this wide-ranging disorder.
Assuntos
Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/terapia , Antagonistas de Androgênios/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Biomarcadores/sangue , Clomifeno/uso terapêutico , Anticoncepcionais Orais Combinados/uso terapêutico , Antagonistas de Estrogênios/uso terapêutico , Feminino , Hormônio Foliculoestimulante/sangue , Gonadotropinas/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Letrozol/uso terapêutico , Hormônio Luteinizante/sangue , Metformina/uso terapêutico , Progestinas/uso terapêutico , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangueRESUMO
BACKGROUND: Racial and socioeconomic disparities exist in access to medical and surgical care. Studies of national databases have demonstrated disparities in route of hysterectomy for benign indications, but have not been able to adjust for patient-level factors that affect surgical decision-making. OBJECTIVE: We sought to determine whether access to minimally invasive hysterectomy for benign indications is differential according to race independent of the effects of relevant subject-level confounding factors. The secondary study objective was to determine the association between socioeconomic status and ethnicity and access to minimally invasive hysterectomy. STUDY DESIGN: A cross-sectional study evaluated factors associated with minimally invasive hysterectomies performed for fibroids and/or abnormal uterine bleeding from 2010 through 2013 at 3 hospitals within an academic university health system in Philadelphia, PA. Univariate tests of association and multivariable logistic regression identified factors significantly associated with minimally invasive hysterectomy compared to the odds of treatment with the referent approach of abdominal hysterectomy. RESULTS: Of 1746 hysterectomies evaluated meeting study inclusion criteria, 861 (49%) were performed abdominally, 248 (14%) vaginally, 310 (18%) laparoscopically, and 327 (19%) with robot assistance. In univariate analysis, African American race (odds ratio, 0.80; 95% confidence interval, 0.65-0.97) and Hispanic ethnicity (odds ratio, 0.63; 95% confidence interval, 0.39-1.00) were associated with lower odds of any minimally invasive hysterectomy relative to abdominal hysterectomy. In analyses adjusted for age, body mass index, income quartile, obstetrical and surgical history, uterine weight, and additional confounding factors, African American race was no longer a risk factor for reduced minimally invasive hysterectomy (odds ratio, 0.82; 95% confidence interval, 0.61-1.10), while Hispanic ethnicity (odds ratio, 0.45; 95% confidence interval, 0.27-0.76) and Medicaid enrollment (odds ratio, 0.59; 95% confidence interval, 0.38-0.90) were associated with significantly lower odds of treatment with any minimally invasive hysterectomy. In adjusted analyses, African American women had nearly half the odds of receiving robot-assisted hysterectomy compared to whites (adjusted odds ratio, 0.57; 95%, confidence interval 0.39-0.82), while no differences were noted with other hysterectomy routes. Medicaid enrollment (compared to private insurance; odds ratio, 0.51; 95% confidence interval, 0.28-0.94) and lowest income quartile (compared to highest income quartile; odds ratio, 0.57; 95% confidence interval, 0.38-0.85) were also associated with diminished odds of robot-assisted hysterectomy. CONCLUSION: When accounting for the effect of numerous pertinent demographic and clinical factors, the odds of undergoing minimally invasive hysterectomy were diminished in women of Hispanic ethnicity and in those enrolled in Medicaid but were not discrepant along racial lines. However, both racial and socioeconomic disparities were observed with respect to access to robot-assisted hysterectomy despite the availability of robotic assistance in all hospitals treating the study population. Strategies to ensure equal access to all minimally invasive routes for all women should be explored to align delivery of care with the evidence supporting the broad implementation of these procedures as safe, cost-effective, and highly acceptable to patients.
Assuntos
Etnicidade/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde , Histerectomia/métodos , Laparoscopia/estatística & dados numéricos , Leiomioma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Hemorragia Uterina/cirurgia , Neoplasias Uterinas/cirurgia , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Índice de Massa Corporal , Estudos Transversais , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Histerectomia Vaginal/estatística & dados numéricos , Seguro Saúde , Modelos Logísticos , Medicaid , Pessoa de Meia-Idade , Razão de Chances , Philadelphia , Grupos Raciais , Fatores de Risco , Estados Unidos , População Branca/estatística & dados numéricosRESUMO
Robust angiogenesis in the corpus luteum is critical for maintenance of pregnancy and thus mammalian female fertility. During angiogenesis, blood vessels sprout from pre-existing vasculature and recruit pericytes to induce maturation and vessel quiescence. Pericytes are associated with capillaries and regulate endothelial cell proliferation, vessel diameter, and vascular permeability. Endothelial induction of Notch signaling in adjacent pericytes helps recruit and maintain pericyte coverage in some but not all tissue types. We have employed a Notch decoy, N110-24, which blocks Notch signaling in a ligand-specific manner, and determined that pharmacological inhibition of Notch ligand Jagged blocks luteal angiogenesis after normal ovulation, resulting in reduced luteal vasculature. Conversely, after ovarian hyperstimulation, a condition which occurs during fertility treatments, Jagged inhibition causes vascular dilation and hemorrhage. These results indicate that Jagged inhibition has effects in different ovarian angiogenic conditions, promoting vascular growth in the corpus luteum and vascular stability in hyperstimulated ovaries.
RESUMO
BACKGROUND: Aim of the study was to assess the correlation between clinical stage of HCV-related liver disease and viraemia to immune response to different viral antigens. METHODS: We considered 1330 patients with HCV chronic infection followed up from 6 months up to 6 years divided into two groups according to RIBA 3 (Abbott) response: Group I, 1231 patients with positivity for at least two bands (83 subjects with asymptomatic infection, 941 with chronic hepatitis, 201 with cirrhosis and 6 with HCC); Group II, 99 patients with positivity at only one band (45 with asymptomatic infection, 53 with chronic hepatitis and 1 cirrhotic). RESULTS: We noticed a major percentage of positive patients for at least three bands in more severe clinical forms (90% of chronic hepatitis or cirrhosis versus 60% of asymptomatics, p < 0.005, chi 2 test). Moreover we noticed a percentage increase of positivity for antibodies anti-c100 and anti-NS5 with the progression of liver damage, statistically significant differences between asymptomatics and patients with chronic forms. We also observed that viraemia is related neither to clinical stage nor to different reactivity to RIBA 3, albeit viraemia is usually detected more frequently among patients with liver damage, but unrelated to different reactivities. CONCLUSIONS: Our results show a clear correlation between number of reactivities towards HCV proteins and progression of liver damage, pointing out that immune response plays a direct role in the long-term outcome of HCV infection.
Assuntos
Anticorpos Anti-Hepatite C/sangue , Antígenos da Hepatite C/imunologia , Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Idoso , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/virologia , Progressão da Doença , Feminino , Anticorpos Anti-Hepatite C/biossíntese , Antígenos da Hepatite C/metabolismo , Hepatite C Crônica/sangue , Humanos , Immunoblotting , Cirrose Hepática/imunologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Kit de Reagentes para Diagnóstico , Viremia/sangue , Viremia/imunologia , Viremia/virologiaRESUMO
The combination of lamivudine and hepatitis B immunoglobulins (HBIg) to prevent recurrence of HBV hepatitis has significantly improved the survival of patients transplanted for HBV-related end-stage liver disease. Generally, HBIg are administered intravenously. We evaluated the efficacy, tolerability, and cost savings of long-term intramuscular HBIg and lamivudine in 28 patients (23 men and 5 women), who received liver transplants for acute or chronic HBV-related liver disease. Twelve patients started lamivudine before and 16 at the time of liver transplantation. HBIg were administered intravenously during the first week (50 to 70,000 IU) and intramuscularly thereafter (1200 IU every 3 to 6 weeks) to maintain an HbsAb titer >100 IU/L. Mean follow-up was 20 +/- 13 months. Only one patient experienced HBV recurrence (9 months after transplantation). This patient had failed to follow the scheduled prophylaxis. Cumulative survival at 3 years was 83%. Intramuscular HBIg were well tolerated in all cases. Cost analysis comparing intramuscular vs intravenous HBIg administration showed that 39,490 Euros were saved per patient per year. These preliminary results show that low-dose intramuscular HBIg and lamivudine are efficacious and cost-effective for long-term prophylaxis of hepatitis B recurrence after liver transplantation.
Assuntos
Vírus da Hepatite B/imunologia , Hepatite B/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Lamivudina/uso terapêutico , Transplante de Fígado/fisiologia , Antivirais , Custos e Análise de Custo , Feminino , Hepatite B/epidemiologia , Hepatite B/imunologia , Hepatite B/prevenção & controle , Humanos , Imunoglobulinas Intravenosas/economia , Itália , Lamivudina/economia , Falência Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Porphyria cutanea tarda (PCT) is a rare metabolic disorder characterized by an abnormal porphyrin metabolism and typical cutaneous lesions. Recently a strong association between PCT and hepatitis C virus (HCV) has been proposed. Studies in south Europe have shown high prevalence (53 to 91%) of HCV markers in patients with PCT. We studied HCV genotypes in 72 subjects: 40 with PCT and 32 patients with chronic liver disease. A high rate of HCV-RNA positive PCT patients (84%) was observed, reflecting an active HCV replication, the genotypes study showed a prevalence of genotype 1b in PCT patients (61.2%). These findings implicate HCV in the aetiology of PCT-associated liver disease suggesting that hepatitis C serological and virological testing could be indicated in all patients with PCT.
Assuntos
Hepacivirus/genética , Hepatite C/complicações , Porfiria Cutânea Tardia/complicações , Western Blotting , Estudos de Coortes , Primers do DNA/química , Eletroforese em Gel de Ágar , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/imunologia , Hepatite C/imunologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , Porfiria Cutânea Tardia/imunologia , Prevalência , RNA Viral/química , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
In this study, we evaluated the correlation between alanine aminotrasferase levels and hepatitis C virus genotypes in liver transplant patients. We studied 18 patients who had undergone orthotopic liver transplantation because of end-stage cirrhosis (n = 9) or hepatocellular carcinoma (n = 9) hepatitis C virus related. Serum HCV-RNA testing was performed monthly on all the 18 series of serum samples from the first week after liver transplant until the end of the follow up, this period ranging from 1 to 39 months. After liver transplantation, serum HCV-RNA was detected in 14 patients (78%). Of the 8 patients infected with subtype 1b. 1 remained asymptomatic, 2 developed acute liver failure and 5 developed chronic hepatitis. In patients infected with types 1a (Choo et al., 1989), 2a (Choo et al., 1989), with a mixed infection 1b/3 (Kuo et al., 1989) or with an undetermined genotype, significant laboratory abnormalities were not observed. Recurrence of hepatitis C virus infection after liver transplantation is common, and recurrent hepatitis occurs in 50% of cases. Genotype 1b appears to be associated with a higher rate of recurrent hepatitis, compared to other genotypes.
Assuntos
Hepacivirus/genética , Hepatite C/virologia , Transplante de Fígado , Adulto , Idoso , Alanina Transaminase/sangue , Anticorpos Antivirais/sangue , Biomarcadores/sangue , Seguimentos , Genótipo , Hepacivirus/classificação , Hepacivirus/isolamento & purificação , Hepatite C/prevenção & controle , Hepatite C/terapia , Humanos , Pessoa de Meia-Idade , Prevalência , RNA Viral/sangue , Recidiva , SorotipagemAssuntos
Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Transplante de Rim , Reação em Cadeia da Polimerase/métodos , Complicações Pós-Operatórias/diagnóstico , Sequência de Bases , Citomegalovirus/genética , Infecções por Citomegalovirus/etiologia , DNA Viral/sangue , DNA Viral/urina , Humanos , Dados de Sequência Molecular , OligodesoxirribonucleotídeosRESUMO
OBJECTIVE: A novel DNA virus, transfusion-transmitted virus (TTV) is identified from the serum of a patient from acute hepatitis non-A-E. Few reports have been published on patients with renal disease. Patients on dialysis were at high risk of blood-borne viral infections and little is known about the prevalence of this virus in dialysis patients. In order to verify the prevalence of infection from TTV in these patients, we have examined the incidence of TTV in Italian patients with dialysis. METHODS: Serum samples of 85 patients and 65 healthy individuals were examined. In order to evidence the presence of the TTV virus, a method of the seminested polymerase chain reaction (PCR) with TTV-specific primers derives from the N22 region deIl'ORF-1 of the virus has been used and products were analyzed by agarose-gel electrophoresis. All serum samples were also analyzed to markers HBV and HCV. RESULTS: The prevalence of TTV DNA in dialysis patients [35/85 (41.7%)] was significantly higher than in healthy population [7/65 (10.7%)]. Among TTV positive dialysis patients, HCV coinfection was present in six cases. The positivity rate for TTV-DNA tends to increase with age. CONCLUSION: Transfusion-transmitted virus had a high prevalence in Italian-dialysis patients. In our study the virus did not have an important clinical effect on patients; but remains the possibility that it may aggravate liver disease caused by HCV. However, the question of whether TTV infection might have a possible effect on dialysis patients requires further investigation in larger groups.
Assuntos
Infecções por Vírus de DNA/epidemiologia , Diálise Renal , Torque teno virus/isolamento & purificação , Doadores de Sangue/estatística & dados numéricos , Comorbidade , Infecções por Vírus de DNA/virologia , DNA Viral/sangue , Feminino , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/epidemiologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/epidemiologia , Humanos , Itália/epidemiologia , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Diálise Renal/estatística & dados numéricos , Viremia/epidemiologia , Viremia/virologiaRESUMO
In order to develop new anti-Helicobacter pylori agents, a series of N1-substituted 3,5-diphenyl pyrazolines P1-P13 was prepared and evaluated for their antibacterial activity. All synthesized compounds showed little or no activity against different species of Gram-positive and Gram-negative bacteria of clinical relevance and against various strains of pathogenic fungi. The same derivatives exhibited a significant degree of activity against a range of H. pylori strains, including those resistant to the reference compound metronidazole. Among the prepared compounds those with an N1-acetyl group and a 4-methoxy substituent in the 5-phenyl ring showed the best activity against H. pylori metronidazole resistant strains in the 1-4 microg/mL MIC range.
Assuntos
Antibacterianos/síntese química , Helicobacter pylori/efeitos dos fármacos , Pirazóis/síntese química , Antibacterianos/farmacologia , Resistência a Medicamentos , Humanos , Metronidazol , Testes de Sensibilidade Microbiana , Pirazóis/farmacologia , Especificidade da Espécie , Relação Estrutura-AtividadeRESUMO
We carried out a seroepidemiological study on 63 patients undergoing organ transplantation in order to determine viral markers like CMV, HTLV III, HS and V/Z. The antibodies valuation was carried out by enzyme-linked immunosorbent assays (ELISA-Abbott) and complement fixation test. All the tested markers give a high percentage of positivity even if the values relevant to anti-HTLV III antibodies can not be related to infection but, probably, to anti-HLA-Dr antibodies.
Assuntos
Soropositividade para HIV/epidemiologia , Transplante , Citomegalovirus/isolamento & purificação , Feminino , Soropositividade para HIV/complicações , Herpesvirus Humano 3/isolamento & purificação , Humanos , Técnicas Imunológicas , Falência Renal Crônica/terapia , Masculino , Diálise Renal , Simplexvirus/isolamento & purificaçãoRESUMO
The development of new immunodiagnostic systems to study antibodies anti-HCV based on the use of synthetic peptides are potentially very important in the evaluation of indeterminate samples. We have compared two immunodiagnostic tests, the 3-RIBA and LIA-HCV test system, to examine the samples rated as indeterminate by the 2-RIBA test. The results showed that the specificity of the new tests has improved, in fact 29/40 of the indeterminate samples studied became positive with both tests. However, the 3-RIBA test showed higher sensitivity, since two samples negative by LIA-HCV, were positive with this system.
Assuntos
Hepacivirus/imunologia , Anticorpos Anti-Hepatite/sangue , Hepatite C/sangue , Immunoblotting/métodos , Peptídeos , Ensaio de Imunoadsorção Enzimática , Estudos de Avaliação como Assunto , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C , Humanos , Sensibilidade e EspecificidadeRESUMO
Dialysis patients are at risk for infection by a variety of blood-borne agents transmitted within dialysis units. The development of the hepatitis C virus (HCV) screening test prompted many studies on the prevalence of anti-HCV among dialysis patients. The authors have evaluated the prevalence of anti-HCV in 405 hemodialysis patients both by Elisa screening and 4-RIBA test system with a follow-up of two years. The study showed a difference in the incidence of antibodies to HCV by year. In 1990, 15.2% were positive with an increase to 20.8% in 1991. There was an increase of 5% in dialysis patients and only 1.9% in the personnel working in the dialysis ward. Another control group of volunteers did not show any positivity. In addition, the correlations of the antibodies against HCV with markers of hepatitis B virus (HBV) and history of transfusion were evaluated. These findings suggest that the patients found to be positive should be dialyzed on separate machines and special precautions must be undertaken to reduce the risk of transmission.
Assuntos
Hepacivirus/imunologia , Anticorpos Anti-Hepatite/sangue , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C , Humanos , Immunoblotting , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos SoroepidemiológicosRESUMO
In this study the presence of Mycoplasma species in patients suffering from infertility was examined. 41 women and 37 men were examined, including 31 couples, and ten single women and six single men. Samples of vaginal and cervical mucus were taken from each woman, and samples of seminal fluid from each man. Identification and typing of the organisms were performed on the basis of microscopic and cultural characteristics and inhibition of growth by specific antibodies. Out of the 78 patients examined, 35 harboured Mycoplasma, either as Ureaplasma urealyticum or Mycoplasma hominis. Further investigation is needed to determine the clinical significance of these findings.
Assuntos
Infertilidade/microbiologia , Mycoplasma/isolamento & purificação , Técnicas Bacteriológicas , Colo do Útero/microbiologia , Feminino , Humanos , Masculino , Sêmen/microbiologia , Ureaplasma/isolamento & purificação , Vagina/microbiologiaRESUMO
An approach based on the 16 S rDNA polymerase chain reaction (16S PCR) and oligoprobe hybridization was applied to 77 cerebrospinal fluid samples submitted to the clinical microbiology laboratory for culture. Broad-range 16S rDNA primers were selected in conserved regions of the gene. Oligoprobes specific for Neisseria meningitidis, Haemophilus influenzae, Streptococcus spp., and Mycobacterium tuberculosis were selected in specific variable regions of the amplified 600 base pairs (bp) in the 16S rDNA. None of the oligoprobes cross hybridized with DNA from the other bacteria or from common contaminants. There were no false-negative results in culture-positive cerebrospinal fluid samples. Ten cases of meningitis caused by bacteria other than the four probes were not identified by any of the four probes. In culture-negative cerebrospinal fluid samples with some abnormal chemical parameters, there were 14 amplicons -- one of Haemophilus influenzae, three of Streptococcus spp., six of Mycobacterium tuberculosis, and four not identified -- while in normal cerebrospinal fluid samples there were no amplicons.
Assuntos
Meningites Bacterianas/diagnóstico , Meningites Bacterianas/microbiologia , Sondas de Oligonucleotídeos , Reação em Cadeia da Polimerase/métodos , Primers do DNA , Sondas de DNA , Glucose/líquido cefalorraquidiano , Humanos , Contagem de Leucócitos , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/classificação , Sensibilidade e EspecificidadeRESUMO
The significance of anti-hepatitis C virus (HCV) core immunoglobulin M (IgM) and its relationship with genotypes, alanine aminotransferase abnormality, and histological data were studied for 18 patients who had undergone orthotopic liver transplantation due to HCV-related end-stage disease. During follow-up, IgM response seemed to be associated with the recurrence of HCV infection but did not correlate with abnormal alanine aminotransferase levels and histological data. In addition, the results of this study indicated that the detection of HCV RNA is critical for diagnosis of reinfection in liver transplantation.
Assuntos
Hepacivirus/imunologia , Hepacivirus/isolamento & purificação , Anticorpos Anti-Hepatite C/imunologia , Hepatite C/diagnóstico , Imunoglobulina M/imunologia , Transplante de Fígado/efeitos adversos , Hepatite C/etiologia , Hepatite C/virologia , Anticorpos Anti-Hepatite C/análise , Humanos , Imunoglobulina M/análiseRESUMO
Mixed cryoglobulinaemia, when not secondary to other well-defined immunological disorders, is commonly associated with hepatitis C virus (HCV) infection. However, a minority of cases lack evidence of HCV infection and are, therefore, defined as 'true essential' mixed cryoglobulinaemias. We thoroughly investigated three such patients to determine the aetiology of this disorder. Antibodies to HCV (anti-HCV) and HCV RNA, detected by sensitive enzyme-linked immunosorbent and polymerase chain reaction assays in serum and in concentrated cryoglobulins, were repeatedly negative in the three patients. Despite the lack of evidence for HCV infection, two of them were still treated with interferon alpha-2a assuming unrecognized viral infection. Both patients demonstrated excellent clinical and laboratory responses, but cryoglobulinaemia relapsed after the withdrawal of therapy. At the time of relapse, HCV RNA genomic sequences were detected for the first time in the cryoprecipitates of both patients. In the third case, HCV RNA was demonstrated for the first time during a flare of cryoglobulinaemia coincident with varicella infection. In all three patients anti-HCV antibodies remained negative throughout follow-up. We conclude that some apparently 'essential' forms of mixed cryoglobulinaemia can be caused by occult HCV infection. Interferon therapy can be taken into consideration in such HCV-negative cases.
Assuntos
Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/etiologia , Hepatite C/complicações , Adulto , Antivirais/farmacologia , Antivirais/uso terapêutico , Feminino , Anticorpos Anti-Hepatite C/sangue , Humanos , Interferon alfa-2 , Interferon-alfa/farmacologia , Interferon-alfa/uso terapêutico , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas RecombinantesRESUMO
Patients with hepatitis C virus (HCV) infection may have different patterns of antibody response to various structural and non-structural viral antigens. We have correlated the serological patterns to the clinical features of chronic infection and to viral replication in 68 HCV-Ab-positive patients with chronic liver disease at different stages (19 with cirrhosis-hepatocellular carcinoma, 38 with chronic active hepatitis and 11 with chronic persistent hepatitis). Serum samples from each patient were assayed for HCV-IgM by enzyme immunoassay and for HCV-RNA by the polymerase chain reaction using primer sets derived from the 5'-non-coding region. The prevalence of HCV-IgM was high (54 patients (79.4%)) and the study showed a good correlation between high values of anti-HCV-IgM and the presence of HCV-RNA in serum, since HCV-RNA was detected in 35 of the 54 IgM-positive patients (64.8%) and notably in 19 of the 20 subjects with high levels of specific IgM. Conversely, all the 35 sera containing HCV-RNA were also reactive for HCV-IgM, while none of the HCV-IgM-negative sera was HCV-RNA reactive. Positivity rates for both HCV-RNA and IgM anti-HCV were higher in the more advanced stages of disease; thus, the clinical pattern of HCV chronic hepatitis seems to be strictly related to the serological pattern and the presence of HCV-RNA.