RESUMEN
BACKGROUND: Identification of all possible HIV reservoirs is an important aspect in HIV eradication efforts. The urinary tract has however not been well studied as a potential HIV reservoir. In this pilot study we molecularly characterized HIV-1 viruses in urine and plasma samples to investigate HIV-1 replication, compartmentalization and persistence in the urinary tract. METHODS: Prospectively collected urine and blood samples collected over 12-36 months from 20 HIV-1 infected individuals were analysed including sampling points from prior to and after ART initiation. HIV-1 pol gene RNA and DNA from urine supernatant and urine pellets respectively were analysed and compared to plasma RNA viruses from the same individual. RESULTS: HIV-1 nucleic acid was detected in urine samples from at least one time point in 8/20 (40%) treatment-naïve subjects compared to 1/13 (7.7%) individuals on antiretroviral treatment (ART) during periods of plasma viral suppression and 1/7 (14.3%) individuals with virological failure. HIV-1 RNA was undetectable in urine samples after ART initiation but HIV-1 DNA was detectable in one patient more than 6 months after treatment initiation. There was co-clustering of urine-derived pol sequences but some urine-derived sequences were interspersed among the plasma-derived sequences. CONCLUSIONS: Suppressive ART reduces HIV-1 replication in the urinary tract but HIV-1 DNA may persist in these cells despite treatment. A larger number of sequences would be required to confirm HIV compartmentalization in the urinary tract.
Asunto(s)
Genotipo , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/aislamiento & purificación , Sistema Urinario/virología , Adulto , Antirretrovirales/uso terapéutico , ADN Viral/genética , ADN Viral/aislamiento & purificación , Femenino , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Masculino , Proyectos Piloto , Plasma/virología , Estudios Prospectivos , ARN Viral/genética , ARN Viral/aislamiento & purificación , Análisis de Secuencia de ADN , Carga Viral , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
BACKGROUND: Although the use of highly active antiretroviral therapy in HIV positive individuals has proved to be effective in suppressing the virus to below detection limits of commonly used assays, virological failure associated with drug resistance is still a major challenge in some settings. The prevalence and effect of pre-treatment resistance associated variants on virological outcomes may also be underestimated because of reliance on conventional population sequencing data which excludes minority species. We investigated long term virological outcomes and the prevalence and pattern of pre-treatment minority drug resistance mutations in individuals initiating HAART at a local HIV clinic. METHODS: Patient's records of viral load results and CD4 cell counts from routine treatment monitoring were used and additional pre-treatment blood samples for Sanger sequencing were obtained. A selection of pre-treatment samples from individuals who experienced virological failure were evaluated for minority resistance associated mutations to 1 % prevalence and compared to individuals who achieved viral suppression. RESULTS: At least one viral load result after 6 months or more of treatment was available for 65 out of 78 individuals followed for up to 33 months. Twenty (30.8 %) of the 65 individuals had detectable viremia and eight (12.3 %) of them had virological failure (viral load > 1000 RNA copies/ml) after at least 6 months of HAART. Viral suppression, achieved by month 8 to month 13, was followed by low level viremia in 10.8 % of patients and virological failure in one patient after month 20. There was potentially reduced activity to Emtricitabine or Tenofovir in three out of the eight cases in which minority drug resistance associated variants were investigated but detectable viremia occurred in one of these cases while the activity of Efavirenz was generally reduced in all the eight cases. CONCLUSIONS: Early viral suppression was followed by low level viremia for some patients which may be an indication of failure to sustain viral suppression over time. The low level viremia may also be representing early stages of resistance development. The mutation patterns detected in the minority variants showed potential reduced drug sensitivity which highlights their potential to dominate after treatment initiation. TRIAL REGISTRATION: Not applicable.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/genética , Adulto , Anciano , Recuento de Linfocito CD4 , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación , Tasa de Mutación , Prevalencia , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
Approximately 1 million South Africans are infected with Hepatitis C virus (HCV). The standard of care (SOC) in South Africa is combination therapy (pegylated interferon and ribavirin). HCV genotypes and/or mutations in the core/non-structural regions have been associated with response to therapy and/or disease progression. This study examines mutations in the core (29-280 amino acids, including â¼ 90 E1 amino acids) and NS5B (241-306 amino acids) regions on pre-treatment isolates from patients attending Johannesburg hospitals or asymptomatic South African blood donors. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Samples grouped into subtypes 1a(N = 10) 1b(N = 12), 3a(N = 5), 4a(N = 3) and 5a(N = 61). Two mutations, associated with interferon resistance-R70Q and T110N-were present in 29 genotype 5a core sequences. No resistance mutation to NS5B nucleotide inhibitors, sofosbuvir was found. Six putative CD8+ and one CD4+ T-cell epitope sequence in the core region showed binding scores of <300 IC50nM to HLA alleles frequently observed in the South African population. No known CD8+ and CD4+ T-cell epitopes were mapped in the NS5B region. The analysis begs the question whether those infected with genotype 5a will benefit better on interferon-free combination therapies. This study provides new insight into one of the lesser studied HCV genotypes and compares the diversity seen in a large pre-treatment cohort with other subtypes.
Asunto(s)
Hepacivirus/genética , Mutación , Proteínas del Núcleo Viral/genética , Proteínas no Estructurales Virales/genética , Antivirales/farmacología , Secuencia de Bases , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Farmacorresistencia Viral/genética , Quimioterapia Combinada , Epítopos de Linfocito T/genética , Femenino , Frecuencia de los Genes , Genotipo , Antígenos HLA/inmunología , Hepacivirus/efectos de los fármacos , Hepacivirus/inmunología , Hepatitis C/sangre , Hepatitis C/tratamiento farmacológico , Hepatitis C/inmunología , Hepatitis C/virología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/genética , Humanos , Interferones/uso terapéutico , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , ARN Viral/genética , Ribavirina/uso terapéutico , Análisis de Secuencia de Proteína , SudáfricaRESUMEN
The HCV stem-loop subdomains III-a, -b and -c have been shown to reflect the characteristics of the virus and identify isolates by genus, genotype and subtype. The aim of this study was to investigate the genotype-specific PNS within the 5'UTR of prevalent HCV genotypes (1 and 5a) found in South Africa. The genotype 5a (N = 35) and genotype 1 sequences (N=20) were from patients presenting with liver disease or haemophilia, respectively. PNS HCV typing characteristics, defined previously, were observed. The PNS method differentiated subtypes 1a and 1c from subtype 1b by the base change at nucleotide position 243. A lack of structural data from the variable loci V1 of the 5'UTR did not allow us to further differentiate the subtypes of 1. A nucleotide change from a thymine (T) to a cytosine (C) at position 183 was found among genotype 5a sequences. This mutation changed the stable U-AA bond to a Y AA bulge at base-pair position 32. There was an insertion of a single adenine (A) at position 207. At present PNS analysis is labour intensive but, with development of further software to aid the computer analysis, it has the potential to provide a rapid, reliable alternative to phylogenetic analysis.
Asunto(s)
Variación Genética , Hepacivirus/clasificación , Hepacivirus/genética , Secuencias Invertidas Repetidas , ARN Viral/genética , Secuencia de Bases , Genotipo , Hepacivirus/aislamiento & purificación , Humanos , Datos de Secuencia Molecular , Alineación de Secuencia , SudáfricaRESUMEN
Treatment effects of Fast ForWord, hypothesized to ameliorate temporal processing deficits, were demonstrated by magnetoencephalography in a child with dyslexia using four paradigms: Word/Non-word Reading (NW), Grapheme-to-Phoneme Matching (GP), Verbal, and Spatial Working Memory (VWM, SWM). Shifts in brain activation from right inferior frontal and temporal to left frontal, bilateral supramarginal, and transverse temporal regions occurred during GP. During NW, shifts progressed from (1) right or bilateral anterior and superior to (2) left, inferior frontal, to (3) left, superior posterior temporoparietal, to (4) left, inferior, posterior temporooccipital regions. Reading and written language improvements were noted in passage comprehension and spelling.
Asunto(s)
Corteza Cerebral/fisiopatología , Dislexia/terapia , Terapia del Lenguaje/métodos , Percepción del Habla , Terapia Asistida por Computador/métodos , Estimulación Acústica/métodos , Atención , Niño , Dislexia/fisiopatología , Femenino , Humanos , Terapia del Lenguaje/instrumentación , Magnetoencefalografía , Resultado del TratamientoRESUMEN
Visual evoked cortical magnetic field (VEF) waveforms were recorded from both hemifields in 21 patients with temporo-parieto-occipital mass lesions to identify preserved visual pathways. Fifteen patients had visual symptoms pre-operatively. Magnetoencephalographic (MEG) VEF responses were detected, using single equivalent current dipole (ECD), in 17/21 patients studied. Displaced or abnormal responses were seen in 15 patients with disruption of pathway in one patient. Three of 21 patients had alterations in the surgical approach or the planned resection based on the MEG findings. The surgical outcome for these three patients suggests that the MEG study may have played a useful role in pre-surgical planning.
Asunto(s)
Encefalopatías/fisiopatología , Encefalopatías/cirugía , Potenciales Evocados Visuales/fisiología , Magnetoencefalografía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Estudios RetrospectivosRESUMEN
A variety of techniques are available for imaging magnetoencephalographic (MEG) data to the corresponding cortical structures. Each performs a functional optimization that includes mathematical and physical restrictions on source activity. Unlike other imaging techniques, MR-FOCUSS (Multi-Resolution FOCal Underdetermined System Solution) utilizes a wavelet statistical operator that allows spatial resolution to be chosen appropriately for focal or extended sources. Control of focal imaging properties is achieved by specifying P in an l(P) norm distribution template used to construct the wavelets. In addition, incorporation of a multi-resolution wavelet operator desensitizes the mathematical algorithm to noise, (regularization). Like the FOCUSS imaging technique, an initial estimate of cortical activity is recursively enhanced to obtain the final high resolution imaging results. Studies of model MEG data representing all regions of a realistic cortical model are performed to quantify MR-FOCUSS imaging properties. These modeled data studies included single and multiple dipole sources as well as an extended source model. Thus, MR-FOCUSS is found to be very effective for imaging language processing for pre-surgical planning and provides a high-resolution method to image sequential activation of multiple correlated sources involved in language processing.
Asunto(s)
Mapeo Encefálico/métodos , Corteza Cerebral/fisiología , Magnetoencefalografía/métodos , Procesamiento de Señales Asistido por Computador , Algoritmos , Artefactos , Potenciales Evocados/fisiología , Humanos , Lenguaje , Pruebas del Lenguaje , Modelos Neurológicos , Procedimientos Neuroquirúrgicos/métodos , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Conducta Verbal/fisiologíaRESUMEN
OBJECTIVE: To demonstrate noninvasive localization of cognitive cortical areas involved in language processing with magnetoencephalography (MEG) interpreted by multiresolution FOCUSS (MR-FOCUSS), a current density imaging technique. METHOD: MEG data were collected during verb-generation and picture-naming tasks from 18 right-handed control subjects and 24 right-handed patients with epilepsy. RESULTS: The averaged epic data from the verb-generation task, analyzed by MR-FOCUSS, showed initial activation in the left supramarginal gyrus, superior temporal gyrus, and angular gyrus at 239 +/- 31 ms in all subjects, consistent with other language mapping studies. Average amplitude of underlying cortical sources was approximately 452 pAm. The averaged epic data from the picture-naming task, analyzed by MR-FOCUSS, showed activation in the left inferior frontal gyrus (IFG) area starting at 436 +/- 40 ms in all subjects. Average amplitudes of underlying cortical sources were approximately 380 pAm. CONCLUSION: The time course of neuronal language processing can be imaged noninvasively with millisecond resolution by magnetoencephalography using the multiresolution FOCUSS technique.
Asunto(s)
Corteza Cerebral/fisiología , Epilepsia/fisiopatología , Lenguaje , Magnetoencefalografía , Potenciales Evocados , Femenino , Humanos , MasculinoRESUMEN
We investigate and characterize the magnetoencephalographic waveforms from patients during spontaneous and visually induced migraine aura. Direct current neuromagnetic fields were measured during spontaneous onset of migraine auras in 4 migraine patients, and compared with recordings from 8 migraine-with-aura patients and 6 normal controls during visual stimulation of the occipital cortex. Complex direct current magnetoencephalographic shifts, similar in waveform, were observed in spontaneous and visually induced migraine patients, but not in controls. Two-dimensional inverse imaging showed multiple cortical areas activated in spontaneous and visually induced migraine aura patients. In normal subjects, activation was only observed in the primary visual cortex. Results support a spreading, depression-like neuroelectric event occurring during migraine aura that can arise spontaneously or be visually triggered in widespread regions of hyperexcitable occipital cortex.
Asunto(s)
Magnetoencefalografía , Migraña con Aura/diagnóstico , Migraña con Aura/fisiopatología , Lóbulo Occipital/fisiopatología , Adulto , Mapeo Encefálico , Depresión de Propagación Cortical , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Corteza Visual/fisiopatologíaRESUMEN
Hepatitis B virus (HBV) was partitioned into type, subtype and isolate categories and the average evolutionary distances within and between categories was plotted at each of 54 points along the genome. The graphs showed alternating variable and conserved domains within and between HBV subtypes and revealed that some specimens assigned to different groups are more similar across several contiguous intervals than specimens belonging to the same group. Isolates were screened individually to determine their conformation to type and mosaic structure was identified in 14/65 specimens. Two entire clades (six specimens) of genotype B had a B/C sequence switch in the core gene region, whereas six genotype D specimens showed D/A switching in one or more regions of the genome. Genotype E was not separate from genotype D in the X and C subgenomic regions. The nature and distribution of polymorphic sites in mosaic regions was mapped at both the nucleotide and protein levels and the position of the variant fragments was related to mutational hot spots and linear epitopes of HBV. Mosaic structure was demonstrated statistically in 11 isolates using bootstrap resampling and recombination, rather than random change, appeared to be the mechanism responsible. The sequence between and including the two DR regions was represented in all putative recombinants. The distribution of genetic distances over subgenomic regions showed that substitution rates are not constant among the lineages of HBV in the preS regions. Genotype F is the most diverse group. Only genotypes A, C and F partition consistently into subtypes.
Asunto(s)
Genoma Viral , Virus de la Hepatitis B/genética , Recombinación Genética , Animales , Secuencia de Bases , Secuencia Conservada , ADN Viral/genética , Evolución Molecular , Variación Genética , Genotipo , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Mosaicismo , Pan troglodytes/virología , FilogeniaRESUMEN
Magnetic fields arising from the rabbit cortex during spreading cortical depression (SCD) were measured in order to study the currents in the neocortex during SCD. SCD was constrained to propagate in a rectangular cortical strip perpendicular to the midline. This simplified in vivo cortical preparation enabled us to correlate magnetoencephalographic (MEG) signals to their underlying currents within the cortical strip. The propagation of SCD was monitored with an array of electrodes placed along the strip. The propagation speed for SCD in the lissencephalic rabbit brain was 3. 5+/-0.3 mm/min (mean+/-S.E.M., n=14). Slow, quasi-dc, MEG signals were observed as the SCD entered into the longitudinal fissure. The currents giving rise to the MEG signals were perpendicular to the cortical surface and directed from the surface to deeper layers of the cortex. A distributed dipolar source model was used to relate the data to the underlying cortical current. The moment of the single equivalent current dipole source was 38+/-9 nA-m (n=17). This study clarified the nature of the cortical currents during SCD in a lissencephalic in vivo preparation.
Asunto(s)
Corteza Cerebral/anomalías , Depresión de Propagación Cortical/fisiología , Magnetoencefalografía , Neocórtex/fisiología , Animales , Modelos Animales de Enfermedad , Lateralidad Funcional , Neocórtex/fisiopatología , ConejosRESUMEN
Currents produced during spreading cortical depression (SCD) in a gyrencephalic species (swine) were studied with magnetoencephalography (MEG) and electrocorticography (ECoG). SCD, initiated using electrical stimulation of the cortex, was constrained to propagate within a rectangular cortical strip in order to simplify the interpretation of the underlying currents. The ECoG signals monitored along the strip revealed that SCD propagated from an initiation site on the gyrus at a rate of 7.9+/-3.2 mm/min (n=23), entered the deep coronal sulcus and in most cases emerged from the other side of the sulcus, continuing to propagate across the next gyrus at a rate of 5.9+/-2.7 mm/min (n=22). The apparent propagation velocity within the sulcus was reduced to 1.7+/-0.8 mm/min (n=21). Strong MEG signals were observed as SCD entered the sulcus. The direction of magnetic field was opposite for SCD's on opposite banks of the sulcus. The currents were directed from a superficial layer to deeper layers of the cortex. The characteristics of SCD and associated MEG patterns from a gyrencephalic species may be similar to those in human patients during migraine aura.
Asunto(s)
Encéfalo/anomalías , Corteza Cerebral/fisiología , Magnetoencefalografía , Animales , Corteza Cerebral/fisiopatología , Modelos Animales de Enfermedad , Estimulación Eléctrica , Electroencefalografía , Lateralidad Funcional , Humanos , Trastornos Migrañosos/fisiopatología , PorcinosRESUMEN
OBJECTIVES: Threshold for generation of magnetophosphenes has been reported to be lower in migraine. We compared the threshold for eliciting phosphenes by transcranial magnetic stimulation and the ability to visually trigger headache in a select group of individuals with migraine with and without aura to normal controls. METHODS: Transcranial magnetic stimulation was performed using the Cadwell MES-10 stimulator. A circular coil, 9.5 cm in diameter, was applied to the occipital scalp (7 cm above the inion). Stimulator intensity was increased in 10% increments until subjects reported visual phenomena or 100% intensity was reached. Stimulator intensity was then fine-tuned to determine the threshold at which phosphenes were seen. In the same subjects, visual stimulation was given in 3.0 T MRI and if a headache occurred the response was recorded. RESULTS: Fifteen subjects with migraine were compared to 8 controls. A significant proportion of the migraineurs (86.7%) developed phosphenes compared to the controls (25%) (P = .006). The probability of triggering a headache was also higher in the migraineurs (53%); no headache was triggered in the controls (P = .019). A significant correlation was found between the threshold for phosphenes on transcranial magnetic stimulation and visually triggered headache (P = .002). When only migraine was considered, there was again a significant trend (P = .084). CONCLUSIONS: There is a difference in threshold for excitability of occipital cortex in migraineurs and controls. The hyperexcitable visual cortex in migraine is predisposed to visually triggered headache.
Asunto(s)
Magnetoencefalografía , Trastornos Migrañosos/fisiopatología , Lóbulo Occipital/fisiopatología , Adulto , Depresión de Propagación Cortical/fisiología , Estimulación Eléctrica , Campos Electromagnéticos , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Ilusiones Ópticas/fisiología , Fosfenos/fisiología , Umbral Sensorial/fisiología , Percepción Visual/fisiologíaRESUMEN
The preS2/S genes of hepatitis B virus isolated from 29 acutely or chronically infected individuals in the Gauteng province of South Africa were sequenced. Phylogenetic analysis of these sequences in comparison with global isolates from the GenBank database showed that 24 sequences clustered with genotypic group A, three with genotypic group D and one each with genotypic groups B and C. Group A isolates had greater identity with groups D (variation of 6.6%) and E (6.8%) than with the Eastern groups B (7.4%) and C (8.1%) and were most different from group F (11.0%). Of the South African group A specimens, 59.1% clustered with two global sequences to form a discrete segment which we have called subgroup A. The amino acid differences that set these isolates apart from the rest of group A tended to cluster in the preS2 region (amino acids 7, 10, 32, 35, 47, 48, 53 and 54), with a few changes occurring in the major surface antigen (amino acid sites 207 and 209). Analysis of isolates showed that there was a 9-fold higher prevalence of the ay determinant in South Africa than previously reported.
Asunto(s)
Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/genética , Precursores de Proteínas/genética , Secuencia de Aminoácidos , Secuencia de Bases , ADN Viral , Variación Genética , Genotipo , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Datos de Secuencia Molecular , Filogenia , SudáfricaRESUMEN
We examined the methylation status of CCGG sites in hepatitis B virus (HBV) DNA to determine whether methylation could be responsible for the selective expression of the HBV surface gene in chronic hepatitis B infection and hepatocellular carcinoma. Infected liver tissue from patients with low levels of viral replication was analyzed for HBV DNA copy number per haploid cell genome. Total cellular DNA, with sufficient HBV DNA, was digested with the restriction endonucleases Msp I and Hpa II, to determine whether the HBV DNA was methylated, or HindIII, to determine whether the HBV DNA was integrated or episomal. The cleavage fragments were analyzed by Southern blotting and hybridization to 32P-labeled HBV DNA. In replicative chronic hepatitis B, hypomethylation of the HBV genome correlated with HBV expression in both virions and infected tissue. In carriers with nonreplicative infection, it was difficult to ascertain the role of methylation as copy number was low. HBV DNA copy number was also low in 17 out of 29 of the tumor tissues tested and as many as 14 out of 16 of the adjacent non-neoplastic tissues tested. Integrated sequences were hypermethylated in the PLC/PRF/5 cell line and in six of the tumor tissues suggesting that methylation plays a role in HBV gene repression. However, since DNA from five other tumors was hypomethylated, the belief that methylation per se is an absolute determinant of HBV core gene repression does not hold for human hepatocellular carcinoma tissue. Additional factors, such as gene rearrangements, therefore, must influence HBV expression in hepatocellular carcinoma.
Asunto(s)
Carcinoma Hepatocelular/microbiología , ADN Viral/análisis , Genes Virales , Virus de la Hepatitis B/genética , Hepatitis B/microbiología , Neoplasias Hepáticas/microbiología , Secuencia de Bases , Replicación del ADN , Antígenos de Superficie de la Hepatitis B/análisis , Antígenos e de la Hepatitis B/análisis , Humanos , Hígado/microbiología , Replicación ViralRESUMEN
Two patients in whom asymptomatic and small hepatocellular carcinomas (HCC) were detected by alpha-fetoprotein (AFP) screening are reported. Both patients were hepatitis B surface antigen-positive. In the first patient, the tumour grew slowly and was resected more than 2 years after a significant elevation in serum AFP levels had been first detected and 13 months after hepatic angiography confirmed the presence of a vascular tumour. In the second patient, a small encapsulated HCC was diagnosed by AFP screening and hepatic imaging. The clinical course in these 2 patients illustrates that small, asymptomatic and encapsulated HCCs do occur in southern African black hepatitis B carriers. Regular screening of patients at risk may be justified.
Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Portador Sano , Hepatitis B/complicaciones , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/análisis , Adulto , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Antígenos de Superficie de la Hepatitis B/análisis , Humanos , Hígado/patología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana EdadRESUMEN
We have examined serological markers of replicative and nonreplicative infection in 124 adult, black South African carriers of hepatitis B virus (HBV), in whom this infection is predominantly acquired in early childhood. The mean age of the group was 36 years. Antibody to hepatitis B e antigen (anti-HBe) was present in the serum of 93.5% of these carriers. Only 25.8% of the carriers were positive for HBV DNA in serum, and in the majority of these only trace amounts were detectable. IgM antibody to hepatitis B core antigen (IgM anti-HBc) was negative in 54% of the carriers, and only 26% had IgM anti-HBc in high titer. A significantly greater proportion of carriers who were positive for anti-HBe were positive for IgM anti-HBc (43.1%) than were positive for HBV DNA (24.5%). Serum aminotransferases were less than twofold elevated in 90.3% of the carriers. Only one carrier has thus far developed hepatocellular carcinoma. These results suggest that there is an inexorable progression to predominantly nonreplicative infection in the majority of southern African adult, black carriers, an occurrence that may take several decades. In areas endemic for HBV infection, antiviral agents effective against replicative HBV will have to be administered in childhood.
Asunto(s)
Portador Sano/microbiología , Virus de la Hepatitis B/fisiología , Hepatitis B/microbiología , Adulto , Alanina Transaminasa/sangre , ADN Viral/sangre , Femenino , Hepatitis B/sangre , Hepatitis B/epidemiología , Hepatitis B/inmunología , Anticuerpos contra la Hepatitis B/análisis , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/análisis , Antígenos e de la Hepatitis B/análisis , Antígenos e de la Hepatitis B/inmunología , Humanos , Inmunoglobulina M/análisis , Masculino , Persona de Mediana Edad , Sudáfrica , Replicación Viral , alfa-Fetoproteínas/análisisRESUMEN
We measured serum markers of hepatitis B virus replication in two HBsAg-, HBeAg-positive hepatitis B carriers with chronic active hepatitis and cirrhosis. The first of these patients was HBsAg-, HBeAg-, HBV DNA- and HBV DNA polymerase-positive initially and spontaneously lost HBV DNA polymerase and HBV DNA. During the HBeAg-positive, DNA polymerase-negative "window phase", an increase in viral replication, characterized by the reappearance of HBV DNA and HBV DNA polymerase occurred, together with an aggravation of the underlying chronic hepatitis. In the second HBsAg-, HBeAg-positive carrier, spontaneous fluctuations in HBV replication were associated with clinical deterioration. Delta agent and hepatitis A virus superinfection were excluded. These observations suggest that spontaneous low-grade fluctuations of HBV replication accompanied by an increase in the biochemical activity of the underlying chronic hepatitis can be observed in certain HBV carriers.