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1.
EClinicalMedicine ; 40: 101099, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34490415

RESUMO

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. Methods: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). Findings: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. Interpretation: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funding: Funded by Roche Sequencing Solutions, Inc.

2.
Diagnostics (Basel) ; 11(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34441435

RESUMO

Liver stiffness (LS) at sustained virological response (SVR) after direct-acting antivirals (DAA)-based therapy is a predictor of liver events in hepatitis C virus (HCV)-infected patients. The study aim was to identify genetic factors associated with LS changes from the moment of starting anti-HCV therapy to SVR. This prospective study included HCV-infected patients from the GEHEP-011 cohort who achieved SVR with DAA-based therapy, with LS pre-treatment ≥ 9.5 kPa and LS measurement available at SVR. Plink and Magma software were used to carry out genome-wide single-nucleotide polymorphism (SNP)-based and gene-based association analyses, respectively. The ShinyGO application was used for exploring enrichment in Gene Ontology (GO) categories for biological processes. Overall, 242 patients were included. Median (quartile 1, quartile 3) LS values at pre-treatment and at SVR were 16.8 (12, 28) kPa and 12.0 (8.5, 19.3) kPa, respectively. Thirty-five SNPs and three genes reached suggestive association with LS changes from the moment of starting anti-HCV therapy to SVR. GO categories related to DNA packaging complex, DNA conformation change, chromosome organization and chromatin organization were significantly enriched. Our study reports possible genetic factors associated with LS changes during HCV-infection cure. In addition, our results suggest that processes related to DNA conformation are also involved in these changes.

3.
Transbound Emerg Dis ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34405560

RESUMO

Whether people living with HIV (PLWH) are at greater risk of acquiring SARS-CoV-2 infection is currently unknown. Prospective serologic studies may allow seroincidence analyses, where all infections are accurately identified. Because of this, we evaluated the incidence of associated factors with and the clinical outcome of SARS-CoV-2 infection in PLWH in Southern Spain. This prospective cohort study included PLWH from a Tertiary University Hospital in Southern Spain. Patients were enrolled in the study if (1) they had attended as outpatients our Unit from 1 August 2019 to 8 February 2020 and (2) had two subsequent evaluations from 9 February 2020 to 4 March 2021. SARS-CoV-2 infections were diagnosed by PCR, antigen detection or serology. Seven hundred and nine PLWH were included in the study. Of them, 55 [7.8%, 95% confidence interval (95% CI) 5.9%-9.9%] patients developed SARS-CoV-2 infection. Between 18 May and 29 November 2020, the rate of seroconversion was 5.3% (95% CI: 3.1%-9.0%) for the general population in the area of Seville and 2.3% (95% CI: 1.3%-2.6%) for PLWH in this study (p = .001). After multivariable analysis, adjusted by age, sex, and risk factors for HIV infection, active tobacco use and CDC stage, active tobacco smoking was the only factor independently associated with lower risk of SARS-Cov-2 infection [Incidence rate ratio: 0.29 (95% CI 0.16-0.55) p < .001]. In conclusion, the incidence of SARS-CoV-2 infection among PLWH in Southern Spain during the ongoing pandemic was lower than that reported for the general population in the same area.

4.
Front Aging Neurosci ; 13: 632673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33889082

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the globe causing coronavirus disease 2019 (COVID-19). Because it affects the respiratory system, common symptoms are cough and breathing difficulties with fever and fatigue. Also, some cases progress to acute respiratory distress syndrome (ARDS). The acute phase of COVID-19 has been also related to nervous system symptoms, including loss of taste and smell as well as encephalitis and cerebrovascular disorders. However, it remains unclear if neurological complications are due to the direct viral infection of the nervous system, or they appear as a consequence of the immune reaction against the virus in patients who presented pre-existing deficits or had a certain detrimental immune response. Importantly, the medium and long-term consequences of the infection by SARS-CoV-2 in the nervous system remain at present unknown. This review article aims to give an overview of the current neurological symptoms associated with COVID-19, as well as attempting to provide an insight beyond the acute affectation.

5.
PLoS One ; 16(4): e0249036, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33831011

RESUMO

BACKGROUND: Hydroxychloroquine is not efficacious as post-exposure prophylaxis against coronavirus disease 2019 (COVID-19). It is not known whether as pre-exposure prophylaxis it may prevent COVID-19. OBJECTIVE: To compare the incidence of COVID-19 in Spanish patients with autoimmune rheumatic diseases treated with and without hydroxychloroquine. PATIENTS AND METHODS: Retrospective electronic record review, from February 27th to June 21st, 2020, of patients with autoimmune inflammatory diseases followed at two academic tertiary care hospitals in Seville, Spain. The cumulative incidence of confirmed COVID-19, by PCR or serology, was compared between patients with and without hydroxychloroquine as part of their treatment of autoimmune inflammatory diseases. RESULTS: Among 722 included patients, 290 (40%) were receiving hydroxychloroquine. During the seventeen-week study period, 10 (3.4% [95% CI: 1.7%-6.7%] cases of COVID-19 were registered among patients with hydroxychloroquine and 13 (3.0% [1.6%-5.1%]) (p = 0.565) in those without hydroxychloroquine. COVID-19 was diagnosed by PCR in four (1.4%, 95% CI 0.38%-3.5%) subject with hydroxychloroquine and six (1.4%, 95% CI 0.5%-3.0%) without hydroxychloroquine (p = 0.697). Three patients on hydroxychloroquine and four patients without hydroxychloroquine were admitted to the hospital, none of them required to be transferred to the intensive care unit and no patient died during the episode. CONCLUSIONS: The incidence and severity of COVID-19 among patients with autoimmune rheumatic diseases with and without hydroxychloroquine was not significantly different.


Assuntos
COVID-19 , Hidroxicloroquina/administração & dosagem , Profilaxia Pós-Exposição , Profilaxia Pré-Exposição , Doenças Reumáticas/tratamento farmacológico , SARS-CoV-2 , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Reumáticas/epidemiologia , Fatores de Risco , Espanha/epidemiologia
6.
J Viral Hepat ; 28(6): 878-886, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33721377

RESUMO

Elbasvir/grazoprevir (EBR/GZR) use in drug users on opiate agonist therapy (OAT) is supported by the C-EDGE Co-STAR trial. SVR rates in this study were within those found in the rest of patients included by the EBR/GZR development programme. In clinical practice, however, efficacy could theoretically be lower. Thus, we aimed at evaluating the SVR rates of EBR/GZR among people who injected drugs (PWID) with and without OAT in clinical practice. Patients starting EBR/GZR included in the HEPAVIR-DAA (NCT02057003), recruiting HIV/HCV-coinfected patients or the GEHEP-MONO (NCT02333292), including HCV-monoinfected individuals, prospective cohorts were analysed. Overall SVR12 (ITT), discontinuations due to adverse effects and drop-outs were evaluated. The same analysis was carried out for PWID with and without OAT. 336 patients had started EBR/GZR and reached the SVR12 evaluation date. 318 [95%, 95% confidence interval (95% CI): 92%-98%] patients achieved SVR12. SVR12 was 97% (95% CI: 93%-99%, n/N = 141/145) among people who never used injecting drugs, 94% (95% CI: 88%-97%, n/N = 117/125) among PWIDs without OAT and 91% (95% CI: 81%-97%, n/N = 60/66) among PWIDs with OAT (p = 0.134). Five (1.5%) patients showed relapses, and two (0.6%) individuals showed viral breakthrough. The SVR12 rate for recent drug users was 69% (n/N = 18/26) compared with 97% (n/N = 276/284) for individuals without recent drug use (in the prior year) (p < 0.001). Among recent drug users, three (12%) showed relapses, and five (19%) were lost-to-follow-up. The SVR rates achieved with EBR/GZR were high in real-world conditions of use. However, PWID with recent drug use reach suboptimal response rates with EBR/GZR.


Assuntos
Hepatite C , Preparações Farmacêuticas , Amidas , Analgésicos Opioides , Antivirais/efeitos adversos , Benzofuranos , Carbamatos , Ciclopropanos , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Humanos , Imidazóis , Estudos Prospectivos , Quinoxalinas/efeitos adversos , Sulfonamidas
7.
Sci Rep ; 10(1): 20958, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262433

RESUMO

The impact of drug-drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69-85%) patients, and in 33 (26%, 95% CI 19-35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10-731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04-0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.


Assuntos
Antivirais/efeitos adversos , COVID-19/tratamento farmacológico , Lopinavir/efeitos adversos , Lopinavir/uso terapêutico , Inibidores de Proteases/efeitos adversos , Ritonavir/efeitos adversos , Ritonavir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Estudos Transversais , Combinação de Medicamentos , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteases/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Espanha
8.
AIDS ; 34(1): 25-32, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634193

RESUMO

OBJECTIVES: Complement C3d receptor 2 (CR2) is the main receptor for complement protein C3d and plays an important role in adaptive immune responses. CR2 genetic variants are associated with susceptibility to systemic lupus erythematosus as well as to HIV-1 infection. In addition, CR2 function can be subverted by HIV-1 for an efficient entry into target cells; in a process known as antibody-dependent enhancement of viral infection. We sought to determine the association between CR2 gene variants with HIV-1 acquisition after vaccination with recombinant gp120 protein (Vax004 clinical trial). DESIGN AND METHODS: This is a retrospective cross-sectional study, comprising male volunteers of European ancestry including infected (n = 273) and uninfected (n = 402) vaccinees and placebo, who were genotyped for three single nucleotide polymorphisms (SNPs) in the CR2 gene region. RESULTS: An interaction was observed between the baseline sexual behavior and the SNP rs3813946 for higher risk of infection in vacinees (interaction term P = 0.02). This SNP was associated with increased susceptibility to HIV-1 infection after vaccination in volunteers with low behavioral risk odds ratio (95% confidence interval): 5.5 (1.4-21.7) P = 0.006 but not vaccinees with high behavioral risk or volunteers given placebo (P = 0.7). Moreover, CR2 genotype was strongly associated with the rate of HIV-1 acquisition after vaccination in low-risk volunteers [hazard odds ratio (95% confidence interval): 3.3 (1.6-7.0), P = 0.001]. CONCLUSION: The current study suggests that CR2 may play a role in HIV-1 acquisition after vaccination with rgp120 proteins.


Assuntos
Vacinas contra a AIDS/uso terapêutico , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/prevenção & controle , Receptores de Complemento 3d/genética , Adulto , Estudos Transversais , Predisposição Genética para Doença , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/genética , Humanos , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Comportamento Sexual , Vacinação , Vacinas Sintéticas/uso terapêutico
9.
Liver Int ; 39(10): 1918-1926, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31206233

RESUMO

BACKGROUND: A low proportion of individuals repeatedly exposed to the hepatitis C virus (HCV) remain uninfected. This condition could have a genetic basis but it is not known whether or not it is mainly driven by a high-penetrance common allele. OBJECTIVE: To explore whether low susceptibility to HCV infection is mainly driven by a high-penetrance common allele. METHODS: In this genome-wide association study (GWAS), a total of 804 HCV-seropositive individuals and 27 high-risk HCV-seronegative (HRSN) subjects were included. Plink and Magma software were used to carry out single nucleotide polymorphism (SNP)-based and gene-based association analyses respectively. RESULTS: No SNP nor any gene was associated with low susceptibility to HCV infection after multiple testing correction. However, SNPs previously associated with this trait and allocated within the LDLR gene, rs5925 and rs688, were also associated with this condition in our study under a dominant model (24 out of 27 [88.9%] rs5925-C carriers in the HRSN group vs 560 of 804 [69.6%] rs5925-C carriers in the HCV-seropositive group, P = 0.031, odds ratio [OR] = 3.48; 95% confidence interval [CI] = 1.04-11.58; and 24 out of 27 [88.9%] rs688-T carriers in the HRSN group vs 556 of 804 [69.1%] rs688-T carriers in the HCV-seropositive group, P = 0.028, OR = 3.57, 95% CI = 1.65-11.96). CONCLUSIONS: Low susceptibility to HCV infection does not seem to be mainly driven by a high-penetrant common allele. By contrast, it seems a multifactorial trait where genes such as LDLR could be involved.


Assuntos
Hepatite C/genética , Polimorfismo de Nucleotídeo Único , Receptores de LDL/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hepacivirus , Humanos , Masculino , Pessoa de Meia-Idade , Espanha
10.
Acta Neuropathol ; 138(2): 251-273, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31006066

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aß) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer's disease) mice and found specifically expressed in microglia associated with Aß plaques. Single-nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aß. Gal3 deletion decreased the Aß burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aß monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aß aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2-DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD.


Assuntos
Doença de Alzheimer/imunologia , Galectina 3/fisiologia , Glicoproteínas de Membrana/fisiologia , Microglia/metabolismo , Receptores Imunológicos/fisiologia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Amiloide/imunologia , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Galectina 3/toxicidade , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Humanos , Inflamação , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Microglia/imunologia , Terapia de Alvo Molecular , Polimorfismo de Nucleotídeo Único , Agregação Patológica de Proteínas
11.
AIDS ; 33(7): 1167-1174, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30845068

RESUMO

OBJECTIVE: To assess the impact of HIV coinfection on the risk of developing liver-related complications in HCV-infected patients with advanced fibrosis treated with direct-acting antivirals (DAA) after sustained virological response (SVR). DESIGN: Prospective cohort study. SETTING: Multicenter. SUBJECTS: Patients from the GEHEP and HEPAVIR cohorts were selected if they fulfilled the following criteria: treatment against HCV with all oral DAA combination; SVR achievement, defined as undetectable plasma HCV RNA 12 weeks after the end of therapy; pretreatment liver stiffness equal to or higher than 9.5 kPa; liver stiffness measurement at the time of SVR. MAIN OUTCOME MEASURE(S): The primary variable was the time until the development of a liver complication or requiring liver transplant. RESULTS: Seven hundred and seventeen patients were included and 507 (71%) were coinfected with HIV. After a median follow-up time of 21 (14-25) months, 15 (2.1%) patients developed a liver complication and/or underwent a liver transplant and 15 (2.0%) died. The probability of remaining free of hepatic complications or transplant at 1 and 2 was, respectively, 99 and 96% in HCV-monoinfected patients and 99 and 98% in coinfected patients (P = 0.648). In a multivariate analysis, in which nonliver-related death was considered as a competing event, HIV coinfection was not associated with the appearance of hepatic complications or requiring liver transplant [hazard ratio = 0.24; 95% CI (0.03-1.93), P = 0.181]. Having presented hepatic decompensation prior to SVR [hazard ratio = 29.06; 95% CI (3.91-216.16), P < 0.001] and the value of liver stiffness at the SVR time-point (hazard ratio = 1.12; 95% CI (1.07-1.18), P < 0.001] were associated with a higher probability of development of liver events. CONCLUSION: HIV coinfection is not associated with a higher probability of developing liver complications in HCV-infected patients with advanced fibrosis, who achieved SVR with interferon-free regimens.


Assuntos
Antivirais/uso terapêutico , Coinfecção/virologia , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Quimioterapia Combinada , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepatite C/complicações , Hepatite C/virologia , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Resposta Viral Sustentada , Transplantados , Carga Viral
12.
Sci Rep ; 8(1): 14905, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30297726

RESUMO

Hepatitis C virus (HCV) response to direct-acting antivirals (DAAs) may be influenced by the presence of resistance-associated substitutions (RASs). This study aimed to assess if NS5A baseline RAS-guided treatment enhances the rate of sustained viral response (SVR) in naïve HCV-infected patients in clinical practice. All HCV-infected patients who initiated treatment with interferon (IFN)-free DAA-based regimens between March 2016 and May 2017 in 17 Spanish hospitals and who had evaluable SVR 12 weeks (SVR12) after the end of therapy were included. Patients had to be DAA naïve, with the exception of sofosbuvir with/without IFN. In one hospital, participants received therapy guided by the presence of NS5A-RASs (RGT population). Patients enrolled in the remaining hospitals, without baseline RASs testing, constituted the control population. A total of 120 and 512 patients were included in the RGT and control populations, respectively. Nine (7.5%) individuals in the RGT population showed baseline NS5A-RASs. All of them achieved SVR12. The SVR12 rate in the RGT population was 97.2% (three relapses) whereas it was 98.8% (six relapses) in the control population (p = 0.382). Our findings suggest that testing for baseline NS5A-RASs in naïve HCV-infected patients does not enhance the rate of SVR to DAA-based IFN-free therapy in clinical practice.


Assuntos
Antivirais/uso terapêutico , Farmacorresistência Viral , Hepatite C/tratamento farmacológico , Interferons/uso terapêutico , Antivirais/farmacologia , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Resposta Viral Sustentada , Proteínas não Estruturais Virais/genética
13.
AIDS Rev ; 19(1): 35-46, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28182612

RESUMO

Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking. Hepatic steatosis in HIV infection may also be secondary to antiretroviral drugs or HCV-related factors in HCV-coinfected subjects. However, more recent data suggest that hepatic steatosis in HIV infection represents true non-alcoholic fatty liver disease. As such, management of non-alcoholic fatty liver disease in HIV infection should follow the same principles as in the general population.


Assuntos
Infecções por HIV/complicações , Hepatopatia Gordurosa não Alcoólica/etiologia , Coinfecção/complicações , Progressão da Doença , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Humanos , Cirrose Hepática/diagnóstico , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/terapia
15.
PLoS One ; 11(12): e0168265, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27973562

RESUMO

Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hundred and thirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.12-3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.23-6.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95% confidence interval = 1.01-11.70). Our results strongly suggest that the rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients.


Assuntos
Infecções por HIV/genética , Infecções por HIV/fisiopatologia , Hepatite C Crônica/genética , Hepatite C Crônica/fisiopatologia , Lipase/genética , Cirrose Hepática/genética , Proteínas de Membrana/genética , Adulto , Alelos , Coinfecção/virologia , Estudos Transversais , Progressão da Doença , Técnicas de Imagem por Elasticidade , Fígado Gorduroso/genética , Feminino , Marcadores Genéticos , Variação Genética , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Transplante de Fígado , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Polimorfismo Genético , Estudos Retrospectivos
16.
Eur J Gastroenterol Hepatol ; 28(11): 1253-7, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27415157

RESUMO

BACKGROUND: The drug options and strategies for treatment against hepatitis C virus (HCV) infection have changed considerably in the last few years. The aim of this study was to compare the changes in the proportion of nonresponders and patients who achieved a sustained virologic response (SVR) from 1999 to 2015 in one single cohort. PATIENTS AND METHODS: A total of 522 patients treated against chronic hepatitis C were included prospectively. The time periods were 1999-2002 [interferon (IFN)/ribavirin (RBV)], 2002-2009 (pegylated-IFN/RBV), 2010-2011 (use of IL28B genotype), 2012-2014 (pegylated-IFN/RBV/direct-acting antivirals) and 2015 (IFN-free direct-acting antiviral-based therapy). RESULTS: The numbers of nonresponders in the study periods in chronological order were as follows: 14 (40%), 76 (21.3%), 7 (8%), 10 (13%), and 0; P=1.1×10 and r=0.837. The corresponding numbers of patients who achieved SVR were 9 (25.7%), 14 (40.9%), 44 (50.6%), 51 (66.2%), and 64 (90.1%), P=3.3×10 and r=0.997. Characteristics that may impair SVR, such as advanced fibrosis, genotype 1 infection, HIV coinfection, or treatment experience, did not decrease in the last time periods. CONCLUSION: The proportion of nonresponders was significantly reduced using the IL28B genotype as a predictive tool and direct-acting antivirals further improved treatment outcome. Concomitantly, the rates of SVR showed a linear increase.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Adulto , Feminino , Genótipo , Infecções por HIV/complicações , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/genética , Humanos , Interferons , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/sangue , Resposta Viral Sustentada , Falha de Tratamento
17.
AIDS ; 29(15): 1927-35, 2015 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-26352879

RESUMO

OBJECTIVE: Fatty liver disease (FLD) is frequently observed in HIV-infected patients and a cause of advanced liver disease. Genetic factors could play a role in determining risk for FLD development in those patients. The aim of this study was to evaluate the association of those single nucleotide polymorphisms (SNPs) previously found to be related to nonalcoholic FLD by genome-wide association analyses in the general population with the presence of FLD, including steatohepatitis, in HIV-infected individuals. DESIGN: This is a transversal study. METHODS: A total of 431 HIV-infected patients were included in this study. All of them underwent a transient elastography with the controlled attenuation parameter examination and were genotyped for 19 selected SNPs. A controlled attenuation parameter value higher than 238 dB/m was selected to define the presence of FLD. Elevated alanine aminotransferase levels and presence of FLD was considered as a surrogate marker of steatohepatitis. RESULTS: A total of 179 (41.5%) individuals showed FLD, including 122 (28.3%) with steatohepatitis. The rs12743824 and rs738491 SNPs were independently associated with FLD and steatohepatitis, respectively. For rs12743824, among 252 individuals without FLD, 182 (72.2%) were A-allele carriers vs. 111 (62%) of 179 patients with this disease (multivariate P = 0.006; adjusted odds ratio = 0.51; 95% confidence interval = 0.33-0.83). For rs738491, 20 (16.4%) of 122 patients with steatohepatitis were TT carriers vs. 18 (5.8%) of 309 patients without this condition (multivariate P = 0.005; adjusted odds ratio = 2.94; 95% confidence interval = 1.39-6.20). CONCLUSION: LPPR4 and SAMM50 allelic variants are independent risk factors for FLD and steatohepatitis development, respectively, in HIV-infected individuals.


Assuntos
Predisposição Genética para Doença , Infecções por HIV/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Adulto , Testes Diagnósticos de Rotina , Feminino , Estudo de Associação Genômica Ampla , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Fosfatidato Fosfatase/genética , Polimorfismo de Nucleotídeo Único , Medição de Risco
18.
AIDS ; 29(14): 1895-7, 2015 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-26372394

RESUMO

The interferon (IFN)L4 polymorphism rs368234815 is associated with hepatitis C virus (HCV) spontaneous clearance and response to IFN-based treatments. The role of this polymorphism in HIV-1 infection is controversial. We investigated whether genetic variation at IFNL4 is associated to HIV-1 acquisition. The HCV protective allele TT was associated with decreased likelihood of HIV-1 infection in male intravenous drug users [odds ratio (OR): 0.3; P = 0.006], and this association was not modified by the genotype of CCR5. These results suggest that genetic susceptibility to HCV and HIV-1 infection shares common molecular pathways.


Assuntos
Resistência à Doença , Infecções por HIV/genética , Infecções por HIV/imunologia , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , HIV-1 , Hepatite C/genética , Hepatite C/imunologia , Humanos , Masculino , Estudos Prospectivos
19.
J Infect ; 71(5): 571-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26212868

RESUMO

OBJECTIVES: To assess the incidence of hepatitis C virus (HCV) reinfections after therapy-induced clearance in HIV-coinfected patients with prior chronic hepatitis C. METHODS: Eighty-four HIV-infected subjects, who had previously achieved sustained virological response (SVR) after being treated of chronic hepatitis C, were analyzed. In all of them, at least yearly HCV RNA determinations were carried out during a median (range) of 34 (12-146) months. RESULTS: Seventy-two (86%) subjects had been people who inject drugs (PWID), of whom 11 (15%) continued to use snorted or injected drugs during the follow-up. Four (4.76%) patients showed HCV reinfection (incidence 1.21 [95% confidence interval: 0.3-3.09] cases per 100 person-years). These patients maintained risk factors for HCV infection. In three cases, HCV genotype switched. Phylogenetic analysis of the remaining case suggested reinfection from his sexual partner. CONCLUSION: The incidence of HCV reinfection in the overall population of HIV-coinfected patients who achieved SVR after being treated against chronic hepatitis C is low. A low frequency of risk behavior is the main factor accounting for this modest rate of reinfection. The possibility of reinfection should not be considered a reason against treatment of HCV infection with direct acting antivirals in PWID.


Assuntos
Usuários de Drogas , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/virologia , Adulto , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Coinfecção/imunologia , Coinfecção/virologia , Feminino , Seguimentos , Hepacivirus/genética , Hepacivirus/imunologia , Hepacivirus/fisiologia , Hepatite C/complicações , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/imunologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Viral/genética , Recidiva , Fatores de Risco , Espanha/epidemiologia
20.
J Clin Microbiol ; 52(11): 4027-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25143567

RESUMO

The accuracy of LiPA 2.0 for hepatitis C virus 1 (HCV-1) subtype classification was analyzed. LiPA 2.0 genotype results from 101 HCV-1-infected patients were compared to genotype findings determined by direct core sequencing. Eleven (11%) samples were misclassified. Given the influence of the HCV-1-subtype in the anti-HCV therapy response, an alternative classification method is warranted.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/virologia , Adulto , Feminino , Genótipo , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , RNA Viral/genética , Análise de Sequência de DNA
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