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1.
Clin Ophthalmol ; 18: 1225-1233, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737596

RESUMEN

Purpose: To investigate refractive, visual, and safety outcomes of cataract surgery performed after scleral buckling (SB) for retinal detachment (RD). Patients and methods: A chart review at an academic medical center identified eyes with history of SB followed by subsequent cataract extraction between 2010 and 2022. Eyes with less than 3 weeks follow-up, silicone oil at time of biometry measurement, previous cornea surgery, or co-existing pathology impacting refractive outcomes were excluded. Predicted postoperative spherical equivalents (SE) were calculated with the Barrett Universal II (BU2), Kane, and SRK/T formulas for the implanted intraocular lens (IOL), and complications occurring within 1 year of surgery were abstracted. Results: Sixty eyes of 60 patients met criteria for inclusion, and 40 (66.7%) had postoperative refraction recorded. Absolute prediction errors were 0.49, 0.45, and 0.52D with BU2, Kane, and SRK/T, respectively. Actual postoperative refraction was within 0.5 and 1.0 D of predicted in 26 (65.0%) and 36 (90.0%) using BU2, 23 (58%) and 37 (93%) using Kane, and 21 (52.5%) and 36 (90.0%) using SRK/T. In eyes with macula-on RD, corrected distance visual acuity (CDVA) of logMAR 0.301 (≈20/40) and logMAR 0.544 (≈20/70) or better was achieved in 12 (75.0%) and 15 (93.8%) of eyes. For macula-off RD eyes, these proportions were 19 (63.3%) and 24 (80.0%), respectively. Posterior capsular opacification requiring Nd: YAG capsulotomy was the most frequent complication in 30 (56.7%) eyes. Conclusion: Refractive outcomes of cataract surgery following SB may be modestly reduced, even when using modern formulas. Nevertheless, cataract surgery in this population results in favorable visual outcomes.


The retina is the part of the eye that is responsible for converting incoming light into a signal that the brain can interpret. A retinal detachment is an emergent condition in which the retina is torn away from its normal position. Scleral buckling is one method of surgically reattaching the retina. Although quite successful, scleral buckling can cause changes to the shape of the eye, and also increases the risk of opacification of the natural lens of the eye, otherwise known as a cataract. The purpose of this study is to investigate the outcomes of cataract surgery in eyes with prior scleral buckle surgery. The results show that despite advancements in methods of measuring the shape of the eye, calculating the appropriately powered IOL to implant, and surgical technique, cataract surgery in eyes with prior scleral buckling may result in poorer outcomes compared to eyes with no history of scleral buckling.

2.
J Pediatr Ophthalmol Strabismus ; 61(2): 90-97, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37489626

RESUMEN

PURPOSE: To assess pediatric ophthalmology-related information on TikTok (ByteDance). METHODS: The 12 most commonly searched terms from the American Association for Pediatric Ophthalmology and Strabismus website were queried as TikTok hashtags. The top 20 videos for each hashtag were analyzed for views, likes, comments, saves, shares, author status and gender, content, and engagement level ratio (ELR). Subanalysis of the educational videos for quality, understandability and actionability, and medical accuracy using the modified DISCERN (mDISCERN), Patient Education Materials Assessment Tool (PEMAT), and modified Medical Information and Content Index (mMICI) was performed. RESULTS: Analysis of 222 videos revealed a cumulative 191,337,973 views. Patients/families created the most videos (60.4%), followed by optometrists (14.4%), other (laypeople/unknown) (9.0%), ophthalmologists (7.7%), non-ophthalmology physicians (4.5%), and nurses (4.1%). Content was predominantly patient experience (56.8%), followed by educational (25.2%), humor (11.7%), self-promotional (3.6%), procedures (0.9%), other (0.9%), advertisements (0.5%), and career (0.5%). Educational videos had a lower ELR than humorous (3.3 vs 8.2, P < .001) and patient experience (3.3 vs 5.3, P < .001) videos, but more saves than patient experience videos (74 vs 25, P = .009). The mDISCERN scores were greater for videos authored by ophthalmologists (3, P < .001) and optometrists (2.5, P < .001) compared to lay-people (1.5). Ophthalmologist PEMAT understandability scores were greater than non-ophthalmology providers' (95.5% vs 67.4%, P = .002). There was no difference in PEMAT actionability (P = .743) or mMICI scores among the author subgroups (P = .206). CONCLUSIONS: Pediatric ophthalmology content on Tik-Tok ranges in quality and understandability. Additional research is needed to help promote posts created by eyecare providers to ensure evidence-based medical content reaches pediatric patients and their families. [J Pediatr Ophthalmol Strabismus. 2024;61(2):90-97.].


Asunto(s)
Oftalmólogos , Oftalmología , Medios de Comunicación Sociales , Estrabismo , Humanos , Niño
3.
Am J Ophthalmol ; 247: 79-87, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36370839

RESUMEN

PURPOSE: To develop and test a novel index (Cooke-Riaz-Wendelstein [CRW1]) that uses swept-source optical coherence tomography (SS-OCT) biometry measurements (IOLMaster700, Zeiss Meditec), including total keratometry, to alert clinicians that previous myopic laser vision correction (M-LVC) was present in a measured eye. DESIGN: Retrospective, multicenter, comparative diagnostic analysis. METHODS: The study took place at 6 centers in the United States and Austria. Anonymized SS-OCT biometry datasets acquired between 2018 and 2020 and containing 49,199 eyes were analyzed. The LVC status, as identified by the biometrist, was used to segregate eyes into LVC and non-LVC eyes. Data were split into training (10,780 eyes) and validation (38,419 eyes) sets. Subset analysis was performed for CRW1 Index accuracy compared to posterior/anterior corneal curvature ratio (Rpost/Rant), topography with corneal analysis software (Atlas 9000 with Pathfinder II, Zeiss Meditec), tomography (Pentacam, Oculus), dual Scheimpflug-Placido system (Galilei G6, Ziemer), and a cloud-based platform for cataract surgery planning (Veracity, Zeiss Meditec). A positive predictive value (PPV) of ≥90% was targeted for the CRW1 index. True positives, true negatives, sensitivity, and specificity were recorded. RESULTS: The CRW1 Index compared favorably against Rpost/Rant showing a higher PPV (93% vs 65%), with fewer false-positive results (29 vs 180). CRW1 performed similarly to topography software and better than the corneal imaging devices. The CRW1 cutoff value can be adjusted to increase sensitivity (CRW1-IS) to detect additional M-LVC eyes. CONCLUSIONS: The CRW1 and CRW1-IS indices offer surgeons and researchers a readily accessible method to use only SS-OCT biometry measurements to detect eyes with a high probability of previous M-LVC.


Asunto(s)
Miopía , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Estudios Retrospectivos , Córnea/anatomía & histología , Miopía/cirugía , Biometría/métodos , Rayos Láser , Reproducibilidad de los Resultados , Longitud Axial del Ojo
4.
J Oncol Pract ; 14(4): e238-e250, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29466074

RESUMEN

PURPOSE: Cancer-associated weight loss is associated with poor prognosis in advanced malignancy; however, its pretreatment prevalence and survival impact are inadequately described in large cohorts. Such data, stratified by tumor type and stage, may facilitate the optimal and timely allocation of complementary care, leading to improvements in patient survival and quality of life. METHODS: We performed a retrospective cohort study of 3,180 consecutively treated adult patients with lung or GI (including colorectal, liver, and pancreatic) cancer. Pretreatment cancer-associated weight loss was based on the international consensus definition of cachexia. Prevalence and survival impact of pretreatment cancer-associated weight loss were evaluated using the Kaplan-Meier method and compared using log-rank test. RESULTS: Cancer-associated weight loss was observed at the time of cancer diagnosis in 34.1% of patients. Pretreatment weight loss was documented in 17.6%, 25.8%, 36.6%, and 43.3% of stage I, II, III, and IV cancers, respectively. Wasting was common regardless of tumor type, with prevalence at diagnosis ranging from 27.3% in patients with colorectal cancer to 53.4% in patients with gastroesophageal cancer. Pretreatment weight loss was associated with reduced overall survival after adjusting for stage, size, grade, comorbidity, age, sex, and tobacco history (hazard ratio, 1.26; 95% CI, 1.13 to 1.39). CONCLUSION: Pretreatment cancer-associated weight loss is common, even in early-stage disease, and is independently associated with reduced survival. Minimal weight loss represents a clinically distinct entity with an associated overall survival intermediate to that of no weight loss and overt wasting. Early diagnosis and treatment of cancer-associated wasting offers a novel therapeutic avenue for reducing cancer mortality.


Asunto(s)
Neoplasias/complicaciones , Neoplasias/mortalidad , Pérdida de Peso , Anciano , Caquexia/epidemiología , Caquexia/etiología , Caquexia/mortalidad , Comorbilidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias/diagnóstico , Neoplasias/epidemiología , Cuidados Paliativos , Prevalencia , Pronóstico , Sistema de Registros
5.
Radiother Oncol ; 119(3): 501-4, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27156652

RESUMEN

PURPOSE/OBJECTIVE: The aim of this study is to predict early distant failure in early stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) using clinical parameters by machine learning algorithms. MATERIALS/METHODS: The dataset used in this work includes 81 early stage NSCLC patients with at least 6months of follow-up who underwent SBRT between 2006 and 2012 at a single institution. The clinical parameters (n=18) for each patient include demographic parameters, tumor characteristics, treatment fraction schemes, and pretreatment medications. Three predictive models were constructed based on different machine learning algorithms: (1) artificial neural network (ANN), (2) logistic regression (LR) and (3) support vector machine (SVM). Furthermore, to select an optimal clinical parameter set for the model construction, three strategies were adopted: (1) clonal selection algorithm (CSA) based selection strategy; (2) sequential forward selection (SFS) method; and (3) statistical analysis (SA) based strategy. 5-cross-validation is used to validate the performance of each predictive model. The accuracy was assessed by area under the receiver operating characteristic (ROC) curve (AUC), sensitivity and specificity of the system was also evaluated. RESULTS: The AUCs for ANN, LR and SVM were 0.75, 0.73, and 0.80, respectively. The sensitivity values for ANN, LR and SVM were 71.2%, 72.9% and 83.1%, while the specificity values for ANN, LR and SVM were 59.1%, 63.6% and 63.6%, respectively. Meanwhile, the CSA based strategy outperformed SFS and SA in terms of AUC, sensitivity and specificity. CONCLUSIONS: Based on clinical parameters, the SVM with the CSA optimal parameter set selection strategy achieves better performance than other strategies for predicting distant failure in lung SBRT patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirugia , Anciano , Algoritmos , Área Bajo la Curva , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Redes Neurales de la Computación , Insuficiencia del Tratamiento
6.
Cancer Biol Ther ; 16(5): 657-61, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25800036

RESUMEN

Renal Cell Carcinoma (RCC) is a common malignancy world-wide that is rising in incidence. Up to 10% of RCC patients present with inferior vena cava (IVC) tumor thrombus (IVC-TT). Although surgery is the only treatment with proven efficacy for IVC-TT, the surgical management of advanced (level III and IV) IVC-TT is difficult with high morbidity and mortality, and offers a poor survival outcome. Currently, there are no treatment options in the setting of recurrent or unresectable RCC IVC-TT. Even though RCC may be resistant to conventionally fractionated radiation therapy, hypofractionated radiation has shown excellent control rates for both primary and metastatic RCC. We report our experience treating 2 RCC patients with Level IV IVC-TT -one recurrent and the other unresectable-with stereotactic ablative radiation therapy (SABR). The first patient is a 75-year-old gentleman with a level IV RCC IVC-TT who presented 9 months after his radical nephrectomy and thrombectomy with a growing level IV IVC-TT that became refractory to 4 targeted agents. He received SABR of 50Gy in 5 fractions and at 2-year follow-up is doing well with a significant decrease in the enhancement and size of the IVC-TT. The second patient is an 83-year-old gentleman who presented with metastatic RCC and level IV IVC-TT but was not a surgical candidate. After progression on temsirolimus, he received SABR of 36Gy in 4 fractions to his IVC-TT and survived 18 months post-SABR. Both patients improved symptomatically and did not experience any acute or late treatment-related toxicity. Their survival of 24 months and 18 months are comparable to the reported median survival of 20 months in patients with level IV IVC-TT that underwent surgical resection. Therefore, SABR can be a potentially safe treatment option in the unresectable setting for RCC patients with IVC-TT and should be further evaluated in prospective trials.


Asunto(s)
Neoplasias Renales/radioterapia , Neoplasias Renales/cirugía , Radiocirugia/métodos , Vena Cava Inferior/patología , Trombosis de la Vena/etiología , Anciano , Anciano de 80 o más Años , Humanos , Neoplasias Renales/patología , Masculino , Pronóstico , Resultado del Tratamiento
7.
J Thorac Oncol ; 10(2): 280-5, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25299234

RESUMEN

INTRODUCTION: The hematologic indices of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are correlated with clinical outcomes after stereotactic radiation. METHODS: We retrospectively evaluated the pretreatment NLR and PLR in patients treated with stereotactic radiation for early stage non-small-cell lung cancer at our institution. A total of 149 patients treated for non-small-cell lung cancer were identified, and 59 had stage I disease with neutrophil, platelet, and lymphocyte levels within a 3-month period before treatment. Receiver operating characteristic (ROC) analysis was performed to examine cutoff values for survival and nonlocal failure followed by Kaplan-Meier analysis for survival. RESULTS: With a median follow-up of 17 months, 28 deaths were observed, and the median overall survival for all patients was 43 months. Based on the ROC analysis, NLR and PLR cutoff values for further survival analysis were determined based on the ROC analysis to be 2.98 and 146. The median overall survival was not reached for patients with low NLR or PLR but the survival was 23 months for patients with high NLR or PLR. There was no correlation between NLR and nonlocal failure, but on multivariate analysis PLR was found to be associated with freedom from nonlocal failure. Nonlocal failure rates were 11% for patients with PLR less than 250 and 58% for PLR greater than 250 (p < 0.001). CONCLUSION: The pretreatment NLR and PLR represented significant prognostic indicators of survival in patients treated for early-stage non-small-cell lung carcinoma with stereotactic radiation. The PLR may be used as a prognostic indicator for nonlocal failure after stereotactic radiation for early-stage lung cancer.


Asunto(s)
Plaquetas/patología , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/cirugía , Linfocitos/patología , Neutrófilos/patología , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Radiocirugia/métodos , Estudios Retrospectivos , Análisis de Supervivencia
8.
BMC Cancer ; 14: 971, 2014 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-25518879

RESUMEN

BACKGROUND: Treatment of cancer in the lung in octogenarians is limited by their health and functional status. Stereotactic ablative radiotherapy is an established noninvasive treatment option for medically inoperable patients, with a toxicity profile that may be more tolerable in elderly patients. METHODS: Patients more than 80 years old treated with stereotactic ablative radiotherapy for malignant tumors in the lung between January 2007 and August 2012 at a single institution were identified and retrospectively analyzed for toxicity and survival. RESULTS: Thirty patients were identified with a total of 32 lesions treated. Patients ranged in age from 80.8 to 90.7 years old (median 84.9) at the time of treatment. Twenty patients had ECOG performance status 0-1, and 10 had performance status 2-3. Stage distribution at treatment was: stage I (20 patients), stage III (1), stage IV (1), and 8 recurrent tumors. Patients were treated to a median total dose of 54 Gy in 3 fractions (range 20-60 Gy in 1 to 5 fractions). Median follow up was 13 months (range 2-60 months). Fifteen patients were still living at last review. There was one failure in field and one failure in the same lobe that was treated. One patient died with progressive regional disease, and four died of progressive metastatic disease. Three patients had late grade 3 pulmonary dyspnea with no grade 4 or 5 toxicities. One patient had late grade 2 pneumonitis, and 3 patients had late grade 1 pneumonitis. Three patients had grade 1 chest wall pain. CONCLUSIONS: Octogenarians tolerated ablative treatment with minimal toxicity. Stereotactic ablative body radiotherapy is an option to consider in treatment of elderly patients.


Asunto(s)
Neoplasias Pulmonares/cirugía , Radiocirugia/efectos adversos , Anciano de 80 o más Años , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
9.
PLoS One ; 5(2): e9032, 2010 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-20140258

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) has six major genotypes, and patients infected with genotype 1 respond less well to interferon-based therapy than other genotypes. African American patients respond to interferon alpha-based therapy at about half the rate of Caucasian Americans. The effect of HCV's genetic variation on treatment outcome in both racial groups is poorly understood. METHODOLOGY: We determined the near full-length pre-therapy consensus sequences from 94 patients infected with HCV genotype 1a or 1b undergoing treatment with peginterferon alpha-2a and ribavirin through the Virahep-C study. The sequences were stratified by genotype, race and treatment outcome to identify HCV genetic differences associated with treatment efficacy. PRINCIPAL FINDINGS: HCV sequences from patients who achieved sustained viral response were more diverse than sequences from non-responders. These inter-patient diversity differences were found primarily in the NS5A gene in genotype 1a and in core and NS2 in genotype 1b. These differences could not be explained by host selection pressures. Genotype 1b but not 1a African American patients had viral genetic differences that correlated with treatment outcome. CONCLUSIONS & SIGNIFICANCE: Higher inter-patient viral genetic diversity correlated with successful treatment, implying that there are HCV genotype 1 strains with intrinsic differences in sensitivity to therapy. Core, NS3 and NS5A have interferon-suppressive activities detectable through in vitro assays, and hence these activities also appear to function in human patients. Both preferential infection with relatively resistant HCV variants and host-specific factors appear to contribute to the unusually poor response to therapy in African American patients.


Asunto(s)
Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Adulto , Negro o Afroamericano/estadística & datos numéricos , Antivirales/uso terapéutico , Quimioterapia Combinada , Femenino , Frecuencia de los Genes , Variación Genética , Genoma Viral , Genotipo , Hepacivirus/clasificación , Hepatitis C/etnología , Hepatitis C/genética , Humanos , Interferón alfa-2 , Masculino , MicroARNs/genética , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Filogenia , Proteínas Recombinantes , Ribavirina/uso terapéutico , Proteínas del Núcleo Viral/genética , Proteínas no Estructurales Virales/genética , Población Blanca/estadística & datos numéricos
10.
J Clin Invest ; 119(1): 225-36, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19104147

RESUMEN

Hepatitis C virus (HCV) is a common RNA virus that causes hepatitis and liver cancer. Infection is treated with IFN-alpha and ribavirin, but this expensive and physically demanding therapy fails in half of patients. The genomic sequences of independent HCV isolates differ by approximately 10%, but the effects of this variation on the response to therapy are unknown. To address this question, we analyzed amino acid covariance within the full viral coding region of pretherapy HCV sequences from 94 participants in the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep-C) clinical study. Covarying positions were common and linked together into networks that differed by response to therapy. There were 3-fold more hydrophobic amino acid pairs in HCV from nonresponding patients, and these hydrophobic interactions were predicted to contribute to failure of therapy by stabilizing viral protein complexes. Using our analysis to detect patterns within the networks, we could predict the outcome of therapy with greater than 95% coverage and 100% accuracy, raising the possibility of a prognostic test to reduce therapeutic failures. Furthermore, the hub positions in the networks are attractive antiviral targets because of their genetic linkage with many other positions that we predict would suppress evolution of resistant variants. Finally, covariance network analysis could be applicable to any virus with sufficient genetic variation, including most human RNA viruses.


Asunto(s)
Antivirales , Redes Reguladoras de Genes , Variación Genética , Genoma Viral , Hepacivirus , Hepatitis C , Adulto , Secuencia de Aminoácidos , Antivirales/farmacología , Antivirales/uso terapéutico , Ensayos Clínicos como Asunto , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/genética , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Fenotipo , Valor Predictivo de las Pruebas , Resultado del Tratamiento
11.
PLoS One ; 3(5): e2123, 2008 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-18463735

RESUMEN

BACKGROUND: Pegylated interferon plus ribavirin therapy for hepatitis C virus (HCV) fails in approximately half of genotype 1 patients. Treatment failure occurs either by nonresponse (minimal declines in viral titer) or relapse (robust initial responses followed by rebounds of viral titers during or after therapy). HCV is highly variable genetically. To determine if viral genetic differences contribute to the difference between response and relapse, we examined the inter-patient genetic diversity and mutation pattern in the full open reading frame HCV genotype 1a consensus sequences. METHODOLOGY/PRINCIPAL FINDINGS: Pre- and post-therapy sequences were analyzed for 10 nonresponders and 10 relapsers from the Virahep-C clinical study. Pre-therapy interpatient diversity among the relapsers was higher than in the nonresponders in the viral NS2 and NS3 genes, and post-therapy diversity was higher in the relapsers for most of HCV's ten genes. Pre-therapy diversity among the relapsers was intermediate between that of the non-responders and responders to therapy. The average mutation rate was just 0.9% at the amino acid level and similar numbers of mutations occurred in the nonresponder and relapser sequences, but the mutations in NS2 of relapsers were less conservative than in nonresponders. Finally, the number and distribution of regions under positive selection was similar between the two groups, although the nonresponders had more foci of positive selection in E2. CONCLUSIONS/SIGNIFICANCE: The HCV sequences were unexpectedly stable during failed antiviral therapy, both nonresponder and relapser sequences were under selective pressure during therapy, and variation in NS2 may have contributed to the difference in response between the nonresponder and relapser groups. These data support a role for viral genetic variability in determining the outcome of anti-HCV therapy, with those sequences that are more distant from an optimal sequence being less able to resist the pressures of interferon-based therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00038974.


Asunto(s)
Variación Genética , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Sistemas de Lectura Abierta/efectos de los fármacos , Sistemas de Lectura Abierta/genética , Ribavirina/uso terapéutico , Adulto , Antivirales/uso terapéutico , Secuencia Conservada , Evolución Molecular , Variación Genética/efectos de los fármacos , Genotipo , Hepacivirus/clasificación , Hepacivirus/efectos de los fármacos , Hepatitis C/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Recurrencia , Insuficiencia del Tratamiento , Proteínas Virales/efectos de los fármacos , Proteínas Virales/genética
12.
J Virol ; 81(15): 8211-24, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17522222

RESUMEN

Pegylated alpha interferon and ribavirin therapy for hepatitis C virus (HCV) genotype 1 infection fails for half of Caucasian American patients (CA) and more often for African Americans (AA). The reasons for these low response rates are unknown. HCV is highly genetically variable, but it is unknown how this variability affects response to therapy. To assess effects of viral diversity on response to therapy, the complete pretreatment genotype 1 HCV open reading frame was sequenced using samples from 94 participants in the Virahep-C study. Sequences from patients with >3.5 log declines in viral RNA levels by day 28 (marked responders) were more variable than those from patients with declines of <1.4 log (poor responders) in NS3 and NS5A for genotype 1a and in core and NS3 for genotype 1b. These correlations remained when all T-cell epitopes were excluded, indicating that these differences were not due to differential immune selection. When the sequences were compared by race of the patients, higher diversity in CA patients was found in E2 and NS2 but only for genotype 1b. Core, NS3, and NS5A can block the action of alpha interferon in vitro; hence, these genetic patterns are consistent with multiple amino acid variations independently impairing the function of HCV proteins that counteract interferon responses in humans, resulting in HCV strains with variable sensitivity to therapy. No evidence was found for novel HCV strains in the AA population, implying that AA patients may be infected with a higher proportion of the same resistant strains that are found in CA patients.


Asunto(s)
Variación Genética , Hepacivirus/genética , Hepatitis C/terapia , Sistemas de Lectura Abierta , Adulto , Negro o Afroamericano/genética , Secuencia de Aminoácidos , Antivirales/metabolismo , Antivirales/uso terapéutico , Portadores de Fármacos/metabolismo , Hepacivirus/metabolismo , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes , Ribavirina/uso terapéutico , Alineación de Secuencia , Análisis de Secuencia de ADN , Población Blanca/genética
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