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1.
J Infect Dis ; 221(8): 1304-1314, 2020 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-31074790

RESUMEN

Despite the emergence of new direct-acting antivirals, hepatitis C virus (HCV) chronic infection and its consequent fibrosis and hepatocarcinoma remain a significant burden for public health, thus requiring an effective preventive vaccine. Our group previously showed that a subunit vaccine based on recombinant soluble E2 (sE2) can induce broadly neutralizing antibodies. To improve the immunogenicity of sE2, we designed and produced a fusion protein (sE2-ferritin) comprising sE2 and a ferritin unit in Drosophila S2 cells, which self-assembled into a nanoparticle with sE2 displayed on the surface. The sE2 moiety on the sE2-ferritin nanoparticle not only had nearly natural conformation but also had better affinities than the unfused sE2 to neutralizing antibodies, receptor, and patient serum. Mouse immunization studies showed that sE2-ferritin was more potent than sE2 in inducing anti-HCV broadly neutralizing antibodies. Our results demonstrate that sE2-ferritin is a vaccine candidate superior to previously developed sE2, providing a new possibility for controlling HCV.


Asunto(s)
Hepacivirus/inmunología , Hepatitis C Crónica/microbiología , Nanopartículas/química , Vacunas contra Hepatitis Viral/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Drosophila/inmunología , Genotipo , Anticuerpos contra la Hepatitis C/inmunología , Hepatitis C Crónica/virología , Inmunización/métodos , Ratones , Proteínas Recombinantes/inmunología , Vacunas de Subunidad/inmunología , Proteínas del Envoltorio Viral/inmunología , Vacunas contra Hepatitis Viral/química
2.
New Microbiol ; 43(2): 99-102, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32510160

RESUMEN

Cryptococcus species is still a very common opportunistic infection in AIDS patients. However, it is increasingly responsible for disease in otherwise immunocompromised individuals, such as transplant recipients and the heterogeneous group of patients with underlying immunologic diseases, hematologic disorders and organ failure syndromes. Clinical presentation, prognosis, and outcomes are difficult to define given these varied host groups, and tailoring treatments to fit the necessities of each patient is likewise challenging. Our patient was on treatment with steroids and direct-acting antiviral agents (DAAs) for a chronic HCV-related hepatitis, worsened by cryoglobulinemia, membranoproliferative glomerulonephritis and a lowgrade B cells lymphoma. We report a case of systemic cryptococcal infection in an immunosenescent, HIV-negative patient.


Asunto(s)
Criptococosis/diagnóstico , Hepatitis C Crónica/complicaciones , Inmunosenescencia , Antivirales , Criptococosis/virología , Seronegatividad para VIH , Hepatitis/virología , Hepatitis C Crónica/microbiología , Humanos
3.
Scand J Gastroenterol ; 54(8): 1033-1041, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31361979

RESUMEN

Objectives: Proton pump inhibitors (PPI), a class of drugs commonly used, are known to be associated with changes in the intestinal microbiota. Published studies were done in heterogeneous cohorts which could hamper conclusions drawn as effects of diseases were not taken into consideration. We aimed to elucidate differences in the intestinal microbiota being associated to the use of PPI in a cohort study of patients with chronic hepatitis C. Material and Methods: The 16S rDNA gene was analyzed in stool samples of patients with and without PPI use. Patients with concomitant medication influencing the microbiota were excluded. Results were compared with the clinical course of hepatitis C patients with decompensated liver cirrhosis. Results: No differences in alpha diversity could be observed, while the microbial community structure differed significantly, especially in patients with liver cirrhosis. The relative abundance of Streptococcus spp., Enterobacter spp. and Haemophilus spp. was significantly increased in patients with PPI use irrespectively of the stage of liver disease. Finally, in patients with decompensated liver cirrhosis due to chronic HCV infection only in these using PPI bacterial phylotypes were isolated. Conclusions: PPI use was associated with significant alterations in the microbial community in patients with chronic hepatitis C, which were even pronounced in patients with liver cirrhosis. In patients with decompensated liver cirrhosis due to chronic HCV infection, the use of PPI may promote infections either directly or indirectly through changes in the microbial community structure. Future studies should further investigate long-term impact on the microbiota and the clinical outcome.


Asunto(s)
Bacterias/clasificación , Microbioma Gastrointestinal/efectos de los fármacos , Hepatitis C Crónica/microbiología , Cirrosis Hepática/microbiología , Inhibidores de la Bomba de Protones/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Tracto Gastrointestinal/microbiología , Hepacivirus , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/virología , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/uso terapéutico , Factores de Riesgo
4.
Liver Int ; 38(1): 50-58, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28561276

RESUMEN

BACKGROUND & AIMS: The importance of the intestinal microbiota for the onset and clinical course of many diseases, including liver diseases like non-alcoholic steatohepatitis and cirrhosis, is increasingly recognized. However, the role of intestinal microbiota in chronic hepatitis C virus (HCV) infection remains unclear. METHODS: In a cross-sectional approach, the intestinal microbiota of 95 patients chronically infected with HCV (n=57 without cirrhosis [NO-CIR]; n=38 with cirrhosis [CIR]) and 50 healthy controls (HC) without documented liver diseases was analysed. RESULTS: Alpha diversity, measured by number of phylotypes (S) and Shannon diversity index (H'), decreased significantly from HC to NO-CIR to CIR. S and H' correlated negatively with liver elastography. Analysis of similarities revealed highly statistically significant differences in the microbial communities between HC, NO-CIR and CIR (R=.090; P<1.0×10-6 ). Stratifying for HCV genotypes even increased the differences. In addition, we observed distinct patterns in the relative abundance of genera being either positive or negative correlated with diseases status. CONCLUSIONS: This study shows that not only the stage of liver disease but also HCV infection is associated with a reduced alpha diversity and different microbial community patterns. These differences might be caused by direct interactions between HCV and the microbiota or indirect interactions facilitated by the immune system.


Asunto(s)
Bacterias/clasificación , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiología , Hepacivirus/patogenicidad , Hepatitis C Crónica/microbiología , Cirrosis Hepática/microbiología , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/virología , Interacciones Huésped-Patógeno , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Adulto Joven
5.
Clin Infect Dis ; 64(1): 44-52, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-27737953

RESUMEN

BACKGROUND: The development of direct-acting antivirals in recent years has dramatically enhanced rates of viral eradication to >90% in patients with chronic hepatitis C virus (HCV) infection. To determine true treatment efficacy and define the most appropriate retreatment, it is important to distinguish virologic relapse from reinfection when patients in whom HCV is eradicated during treatment become infected with a new HCV strain after treatment. METHODS: We investigated the prevalence of late recurrent viremia (patients with sustained virologic response 12 weeks after the end of treatment but detectable HCV RNA at follow-up week 24) and used refined phylogenetic analysis of multiple HCV genes to distinguish virologic relapse from reinfection. RESULTS: Across 11 phase 3 clinical trials of ledipasvir-sofosbuvir (SOF) and SOF, only 12 of 3004 patients had detectable HCV RNA following sustained virologic response 12 weeks after the end of treatment. Of these 12 patients with late recurrent viremia, 11 had the same HCV genotype/subtype at baseline and at recurrence. Phylogenetic analysis demonstrated that 58% (7 of 12) of these patients were successfully treated with the SOF-based regimen, with HCV eradication achieved, but became reinfected with a different HCV strain after treatment. The remaining 5 patients with late recurrent viremia had virologic relapse in which the HCV present at baseline persisted in the liver or another compartment and reemerged in the blood 24 weeks after treatment. CONCLUSIONS: The incidence of late recurrent viremia was low. Distinguishing reinfection from virologic relapse has implications for determining true treatment efficiency and selecting optimal retreatment strategies.


Asunto(s)
Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/microbiología , Antivirales/uso terapéutico , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Filogenia , Prevalencia , ARN Viral , Recurrencia , Retratamiento , Análisis de Secuencia de ADN , Sofosbuvir/uso terapéutico , Resultado del Tratamiento , Carga Viral , Proteínas no Estructurales Virales/genética , Viremia/tratamiento farmacológico , Viremia/epidemiología , Viremia/virología
6.
BMC Infect Dis ; 17(1): 389, 2017 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-28577353

RESUMEN

BACKGROUND: This Phase 3, open-label, rollover study (NCT01323244) investigated the efficacy and safety of simeprevir plus peginterferon α-2a (PegIFNα-2a) and ribavirin (RBV) in a well-characterized population of HCV genotype 1 (GT1)-infected treatment-experienced patients. METHODS: Patients who had failed PegIFNα/RBV treatment in the placebo arm of a previous Phase 2/3 simeprevir study (Phase 2/3 group, n = 125), or had been exposed to HCV direct-acting antivirals (simeprevir or other) for up to 14 days in a selected Phase 1 study (Phase 1 group, n = 16), were eligible. Phase 2/3 group patients were classified according to prior relapse, breakthrough, or non-response (null response, partial response, non-classifiable non-response) to PegIFNα/RBV. Eight patients in the Phase 1 group received short-term (≤14 days) simeprevir. Treatment comprised simeprevir 150 mg once daily (QD) plus PegIFNα-2a/RBV for 12 weeks followed by PegIFNα-2a/RBV for 12 or 36 weeks (using response-guided therapy [RGT] to determine total treatment duration in Phase 2/3 prior relapsers or breakthrough) or 36 weeks fixed (Phase 2/3 group non-responders and Phase 1 group). The primary endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). RESULTS: Phase 2/3 group: SVR12 rate was 69.6% (87/125) overall; 92.7% (51/55), 60.0% (6/10), 64.3% (18/28), and 36.7% (11/30) in patients with prior relapse, viral breakthrough, partial response, or null response, respectively. SVR12 rates were similar for patients with HCV GT1a (66.0% [33/50]) and GT1b infection (72.0% [54/75]) and among HCV GT1a-infected patients with/without a baseline Q80K polymorphism (66.7% [8/12] and 65.8% [25/38], respectively). The majority of RGT-eligible patients (prior viral relapse or breakthrough) met RGT criteria (89.2% [58/65]); of these, 89.7% (52/58) achieved SVR12. Overall, 16.0% (20/125) of patients experienced on-treatment failure and 14.4% (18/125) experienced post-treatment failure (15 relapses, 3 missing data). Phase 1 group (simeprevir-naïve and -experienced patients combined): SVR12 rate was 37.5% (6/16). Safety and tolerability findings were comparable to those of the feeder studies. CONCLUSIONS: The majority of RGT-eligible patients met criteria for shortening treatment to 24 weeks in total. Simeprevir 150 mg QD with PegIFNα-2a/RBV led to a high SVR rate among prior relapsers with HCV GT1 infection. No new safety signals were noted. TRIAL REGISTRATION: NCT01323244 . (date of registration: March 24, 2011).


Asunto(s)
Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Simeprevir/uso terapéutico , Adulto , Anciano , Antivirales/uso terapéutico , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/patogenicidad , Hepatitis C Crónica/microbiología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Resultado del Tratamiento
7.
Med Sci Monit ; 22: 625-32, 2016 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-26912163

RESUMEN

BACKGROUND Haemophilus species are the most common microbiota in humans. The aim of this paper was to investigate Haemophilus spp., mainly H. parainfluenzae prevalence, in the upper respiratory tract of chronic hepatitis C (CHC-positive) patients with or without therapy using pegylated interferon alfa and ribavirin. MATERIAL AND METHODS We collected 462 samples from 54 healthy people and 100 CHC-positive patients at various stages: before (group A), during (group B), and after (group C) antiviral therapy. Identification of bacterial isolates including biotypes and antimicrobials susceptibility was accomplished by means of standard microbiological methods. RESULTS In 70.4% of healthy people (control group) and in 27.0% of CHC-positive patients, the presence of haemophili, mainly H. parainfluenzae was observed, and those differences were statistically significant (p<0.0001). Statistically significant differences in Haemophilus spp. colonization were also observed among healthy people and CHC-positive patients from group A (p=0.0012) and from B or C groups (p<0.0001). Resistance to ampicillin in beta-lactamase-positive isolates and multidrug resistance (MDR) of H. parainfluenzae was detected mainly in group A. CONCLUSIONS The obtained data suggest that chronic hepatitis C, together with antiviral therapy, may influence the respiratory tract microbiota composition as found using haemophili, mainly H. parainfluenzae.


Asunto(s)
Haemophilus/fisiología , Hepatitis C Crónica/microbiología , Microbiota , Sistema Respiratorio/microbiología , Adulto , Anciano , Candida/fisiología , Recuento de Colonia Microbiana , Farmacorresistencia Microbiana , Haemophilus/aislamiento & purificación , Humanos , Persona de Mediana Edad , Nasofaringe/microbiología , Sistema Respiratorio/patología
8.
Pneumonol Alergol Pol ; 83(4): 298-302, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26166791

RESUMEN

Lung cancer and pulmonary tuberculosis (TB) are highly prevalent and representing major public health issues. They share common risk factors and clinical manifestations. It is also suggested that TB predicts raised lung cancer risk likely related to chronic inflammation in the lungs. However, it does not seem to influence the clinical course of lung cancer provided that it is properly treated. We present a case report of a 57-year old male with concurrent TB and lung cancer. He was diagnosed with positive sputum smear for acid fast bacilli (AFB) and subsequent culture of Mycobacterium tuberculosis. Besides, his comorbid conditions were chronic hepatitis C virus (HCV) infection and peripheral artery disease (PAD). Later while on anti-tuberculous treatment (ATT) squamous cell lung cancer (SCC) was confirmed with computed tomography (CT) guided biopsy. Due to poor general condition the patient was not fit for either surgery or radical chemo- and radiotherapy. He was transferred to hospice for palliative therapy. We want to emphasize that both TB and lung cancer should be actively sought for in patients with either disorder. In addition, there is no doubt that these patients with lung cancer and with good response to TB treatment should be promptly considered for appropriate anticancer therapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/complicaciones , Tuberculosis Pulmonar/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/microbiología , Diagnóstico Diferencial , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/microbiología , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/diagnóstico , Factores de Riesgo , Esputo/microbiología , Tomografía Computarizada por Rayos X , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología
9.
J Infect Public Health ; 17(10): 102524, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39241484

RESUMEN

BACKGROUND: Altered bacterial translocation is associated with changes in hepatic function and the progression from compensated to decompensated cirrhosis. Child-Turcotte-Pugh (CTP) score is an essential indicator of liver severity. Thus, we aimed to study differences in the blood microbiome together with metabolome profile between HCV-infected patients with CTP class B (CTP-B, significant functional compromise) and patients with CTP class A (CTP-A, well-compensated cirrhosis). METHODS: We conducted a cross-sectional study in patients with advanced HCV-related cirrhosis (n = 88) stratified by CTP-B and CTP-A. Bacterial 16S rRNA sequencing was sequenced by MiSeq Illumina technology and non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI- to complement the analysis. RESULTS: Patients with CTP-B had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level than patients with CTP-A. Likewise, we observed significant differences in beta diversity between groups at phylum, class, and order levels, showing lower diversity in patients with CTP-B. Higher relative abundance of Proteobacteria (p = 0.012), Alphaproteobacteria (p = 0.005), Sphingomonadales (p = 0.012) and Sphingomonadaceae (p = 0.016) were significantly associated with CTP-B. The phylum Proteobacteria was positively correlated with ethanolamine and oleic acid (p = 0.005 and p = 0.004, respectively) and negatively with p-cresol (p = 0.006). In addition, the order Sphingomonadales and the family Sphingomonadaceae was also negatively correlated with p-cresol (p = 0.001 and p = 0.001). CONCLUSIONS: Blood microbial diversity was significantly decreased in patients with CTP-B, who presented an enrichment of Proteobacteria, Alphaproteobacteria, Sphingomonadales and Sphingomonadaceae compared to patients with CTP-A.


Asunto(s)
Cirrosis Hepática , Microbiota , ARN Ribosómico 16S , Humanos , Masculino , Cirrosis Hepática/sangre , Cirrosis Hepática/microbiología , Cirrosis Hepática/virología , Femenino , Persona de Mediana Edad , Estudios Transversales , ARN Ribosómico 16S/genética , Anciano , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Índice de Severidad de la Enfermedad , Adulto , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/sangre , Hepatitis C Crónica/microbiología , Metaboloma , Metabolómica , Sangre/microbiología , Sangre/virología
10.
Front Cell Infect Microbiol ; 14: 1371429, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650735

RESUMEN

Background: Achieving sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) reduces all-cause mortality. However, the mechanisms and risk factors for liver fibrosis and portal hypertension post-SVR remain incompletely understood. In the gut-liver axis, mucosa-associated microbiota (MAM) substantially influence immune and metabolic functions, displaying spatial heterogeneity at the anatomical intestinal site. We analyzed MAM composition and function to isolate the locoregional MAM involved in chronic liver disease progression in HCV post-SVR patients. Methods: We collected MAM samples from three intestinal sites (terminal ileum, ascending colon, and sigmoid colon) via brushing during colonoscopy in 23 HCV post-SVR patients and 25 individuals without liver disease (controls). The 16S rRNA of bacterial DNA in specimens collected with a brush and in feces was sequenced. The molecular expression of intestinal tissues and hepatic tissues were evaluated by quantitative real-time PCR. Results: In the post-SVR group, the microbial ß-diversity of MAM, especially in the ascending colon, differed from the control group and was associated with liver fibrosis progression. In PICRUSt analysis, MAM in the ascending colon in the liver cirrhosis (LC) group showed compromised functions associated with the intestinal barrier and bile acid production, and FGF19 expression was markedly decreased in the terminal ileum biopsy tissue in the LC group. At the genus level, six short-chain fatty acid (SCFA)-producing bacterial genera, Blautia, Alistipes, Roseburia, Agathobaculum, Dorea, and Pseudoflavonifractor were reduced in the ascending colon of post-SVR LC patients. Conclusion: In patients of HCV post-SVR, we identified the association between the degree of liver fibrosis and dysbiosis of mucosa-associated SCFA-producing bacterial genera that may be related to intestinal barrier and bile acid production in the ascending colon.


Asunto(s)
Colon Ascendente , Disbiosis , Microbioma Gastrointestinal , Mucosa Intestinal , Cirrosis Hepática , ARN Ribosómico 16S , Respuesta Virológica Sostenida , Humanos , Cirrosis Hepática/virología , Cirrosis Hepática/microbiología , Masculino , Persona de Mediana Edad , Femenino , ARN Ribosómico 16S/genética , Colon Ascendente/microbiología , Colon Ascendente/patología , Mucosa Intestinal/microbiología , Mucosa Intestinal/virología , Hepacivirus/genética , Heces/microbiología , Heces/virología , Anciano , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/microbiología , Hepatitis C Crónica/virología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Adulto , ADN Bacteriano/genética , Ácidos y Sales Biliares/metabolismo
11.
Ann Pharmacother ; 47(2): 228-36, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23386076

RESUMEN

OBJECTIVE: To review the literature regarding current strategies for the management of anemia associated with treatment for chronic viral hepatitis C (HCV) in adults. DATA SOURCES: The MEDLINE/PubMed, EMBASE, and Cochrane databases were searched (January 1980-October 2012) for articles in English using the search terms anemia, ribavirin, dose reduction, erythropoietin stimulating agents, hepatitis C, HIV, liver transplant, telaprevir, and boceprevir. STUDY SELECTION AND DATA EXTRACTION: All relevant original studies, meta-analyses, systematic reviews, guidelines, and review articles were assessed for inclusion. References from pertinent articles were examined for additional content not found during the initial search. DATA SYNTHESIS: Standard of care for patients infected with HCV genotype 1 now requires a triple therapy regimen including an HCV NS3 protease inhibitor. These regimens lead to significantly higher rates of anemia compared to prior dual therapy regimens. Development of an optimal management strategy should begin with risk stratification. Ribavirin dose reductions have been recommended in the package inserts for the pegylated interferon products and studies have demonstrated the need for maintenance of 80% of the initial ribavirin dose to achieve optimal sustained virologic response (SVR) with dual therapy. The use of erythropoietin-stimulating agents has been shown to be effective for anemia caused by peginterferon and ribavirin without compromising SVR rates. Limited data have been published regarding the management of anemia with triple therapy; however, efficacy studies for boceprevir and telaprevir have used ribavirin dose reduction and erythropoietin-stimulating agents to successfully manage anemia. CONCLUSIONS: Anemia is a common adverse event associated with the use of ribavirin, and, more recently, the new HCV protease inhibitors. Ribavirin dose reduction should continue to be used as an initial anemia management strategy, with the use of erythropoietin alfa 40,000 units once weekly reserved for patients whose hemoglobin does not adequately respond to initial management strategies.


Asunto(s)
Anemia/prevención & control , Antivirales/efectos adversos , Hematínicos/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Inhibidores de Serina Proteinasa/efectos adversos , Anemia/inducido químicamente , Anemia/tratamiento farmacológico , Anemia/epidemiología , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Monitoreo de Drogas , Quimioterapia Combinada/efectos adversos , Eritropoyetina/agonistas , Eritropoyetina/biosíntesis , Hepacivirus/efectos de los fármacos , Hepacivirus/enzimología , Hepatitis C Crónica/sangre , Hepatitis C Crónica/microbiología , Humanos , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Oligopéptidos/uso terapéutico , Prolina/administración & dosificación , Prolina/efectos adversos , Prolina/análogos & derivados , Prolina/uso terapéutico , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Ribavirina/uso terapéutico , Factores de Riesgo , Inhibidores de Serina Proteinasa/uso terapéutico , Proteínas no Estructurales Virales/antagonistas & inhibidores
12.
Gastroenterology ; 141(4): 1220-30, 1230.e1-3, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21726511

RESUMEN

BACKGROUND & AIMS: Chronic infection with hepatitis B or C virus (HBV or HCV) is a leading cause of cirrhosis by unknown mechanisms of pathogenesis. Translocation of gut microbial products into the systemic circulation might increase because of increased intestinal permeability, bacterial overgrowth, or impaired clearance of microbial products by Kupffer cells. We investigated whether the extent and progression of liver disease in patients with chronic HBV or HCV infection are associated with microbial translocation and subsequent activation of monocytes. METHODS: In a retrospective study, we analyzed data from 16 patients with minimal fibrosis, 68 with cirrhosis, and 67 uninfected volunteers. We analyzed plasma levels of soluble CD14 (sCD14), intestinal fatty acid binding protein, and interleukin-6 by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) by the limulus amebocyte lysate assay, at presentation and after antiviral treatment. RESULTS: Compared with uninfected individuals, HCV- and HBV-infected individuals had higher plasma levels of LPS, intestinal fatty acid binding protein (indicating enterocyte death), sCD14 (produced upon LPS activation of monocytes), and interleukin-6. Portal hypertension, indicated by low platelet counts, was associated with enterocyte death (P=.045 at presentation, P<.0001 after therapy). Levels of sCD14 correlated with markers of hepatic inflammation (P=.02 for aspartate aminotransferase, P=.002 for ferritin) and fibrosis (P<.0001 for γ-glutamyl transpeptidase, P=.01 for alkaline phosphatase, P<.0001 for α-fetoprotein). Compared to subjects with minimal fibrosis, subjects with severe fibrosis at presentation had higher plasma levels of sCD14 (P=.01) and more hepatic CD14+ cells (P=.0002); each increased risk for disease progression (P=.0009 and P=.005, respectively). CONCLUSIONS: LPS-induced local and systemic inflammation is associated with cirrhosis and predicts progression to end-stage liver disease in patients with HBV or HCV infection.


Asunto(s)
Traslocación Bacteriana , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Interacciones Huésped-Patógeno , Intestinos/virología , Cirrosis Hepática/virología , Monocitos/virología , Biomarcadores/sangre , Biopsia , Muerte Celular , Progresión de la Enfermedad , Enfermedad Hepática en Estado Terminal/microbiología , Enfermedad Hepática en Estado Terminal/virología , Enterocitos/microbiología , Enterocitos/patología , Enterocitos/virología , Ensayo de Inmunoadsorción Enzimática , Proteínas de Unión a Ácidos Grasos/sangre , Femenino , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/microbiología , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/microbiología , Humanos , Hipertensión Portal/microbiología , Hipertensión Portal/virología , Interleucina-6/sangre , Intestinos/inmunología , Intestinos/microbiología , Intestinos/patología , Macrófagos del Hígado/microbiología , Macrófagos del Hígado/virología , Prueba de Limulus , Receptores de Lipopolisacáridos/sangre , Lipopolisacáridos/sangre , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/inmunología , Cirrosis Hepática/microbiología , Modelos Logísticos , Masculino , Maryland , Persona de Mediana Edad , Monocitos/inmunología , Monocitos/microbiología , Oportunidad Relativa , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
13.
Gastroenterology ; 135(1): 226-33, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18457674

RESUMEN

BACKGROUND & AIMS: Human immunodeficiency virus (HIV)-1 infection has been associated with enhanced microbial translocation, and microbial translocation is a mechanism through which alcohol and some enteric conditions cause liver disease. We hypothesized that HIV promotes liver disease by enhancing microbial translocation. METHODS: We studied human cohorts in which hepatitis C virus (HCV) and HIV outcomes were carefully characterized. RESULTS: HIV-related CD4(+) lymphocyte depletion was strongly associated with microbial translocation as indicated by elevated levels of circulating lipopolysaccharide (LPS), LPS-binding protein, soluble CD14, and fucose-binding lectin (AAL) reactive to immunoglobulin G specific for the alpha-galactose epitope and suppressed levels of endotoxin core antibodies (EndoCAb IgM) in HIV-infected subjects compared with the same persons before they had HIV infection and compared with HIV-uninfected subjects. The same measures of microbial translocation were strongly associated with HCV-related liver disease progression (cirrhosis), eg, LPS, odds ratio, 19.0 (P = .002); AAL, odds ratio, 27.8 (P < .0001); in addition, levels of LPS were elevated prior to recognition of cirrhosis. CONCLUSIONS: Microbial translocation may be a fundamental mechanism through which HIV accelerates progression of chronic liver disease.


Asunto(s)
Traslocación Bacteriana/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/microbiología , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/microbiología , Adulto , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Infecciones por VIH/epidemiología , Seropositividad para VIH , Hepatitis C Crónica/epidemiología , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/inmunología , Cirrosis Hepática/microbiología , Masculino , Persona de Mediana Edad , Prevalencia
14.
Ann Clin Lab Sci ; 49(3): 380-384, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31308039

RESUMEN

OBJECTIVE: The study retrospectively analyzed the effects of hepatic iron depletion on the therapy of chronic hepatitis C patients. MATERIALS: A total of 195 patients from Hamad General Hospital were studied retrospectively. Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and g-glutamyl transferase (GGT) tests were implemented; descriptive analysis and mean testing were performed to analyze the data. RESULTS: It has been observed that ferritin increases with HCV, displaying R-value =0.450 and p-value=0.182. Levels of ALT (P-value=0.812) and GGT (P-value=0.723) may increase slightly with the treatment. Chronic hepatitis C patients develop iron deficiency that can be marked by evaluating various iron markers in the body. CONCLUSION: The study identified that iron markers may decrease markedly among HCV patients; yet, researches consider the occurrence as support to management modality to improve response, delivered towards the treatment.


Asunto(s)
Hepatitis C Crónica/metabolismo , Hierro/metabolismo , Hígado/metabolismo , Biomarcadores/metabolismo , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/microbiología , Humanos , Hígado/enzimología , Masculino , Estudios Retrospectivos , Carga Viral
15.
Hum Pathol ; 39(2): 213-6, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17949788

RESUMEN

Helicobacter DNA has been reported in hepatocellular carcinoma tissues in several studies from varying geographic locations, raising the possibility that Helicobacter infection may contribute to the pathogenesis of hepatocellular carcinoma. Other known risk factors for hepatocellular carcinoma show significant geographic variability, but whether the same holds for Helicobacter is unknown. We studied the prevalence of Helicobacter DNA in a US cohort of hepatocellular carcinoma, where the prevalence of Helicobacter infection is low in the general population. Liver tissues from 57 individuals were examined. Thirty-five individuals had paired tumor/nontumor samples, including 21 cases of hepatocellular carcinoma, for a total of 92 samples studied. Both Helicobacter genus and Helicobacter pylori species-specific polymerase chain reaction was performed. Helicobacter DNA was detected in 5 (9%) of 57 cases, all in nonneoplastic cirrhotic liver tissues from individuals with hepatitis C infection (n = 4) or alcohol liver disease (n = 1). Tissues from 22 hepatocellular carcinomas and 10 cholangiocarcinomas were all negative as were tissues from 8 benign primary hepatic tumors. In conclusion, Helicobacter DNA was detectable in 9% of liver tissues in this cohort but was not found in primary benign or malignant liver tumors. These findings indicate that Helicobacter infection is unlikely to be etiologically associated with hepatocellular carcinoma in this cohort. If Helicobacter infection does contribute to the development of hepatocellular carcinoma in general, then significant regional variability must exist.


Asunto(s)
Neoplasias de los Conductos Biliares/microbiología , ADN Bacteriano/análisis , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/genética , Hepatitis C Crónica/microbiología , Neoplasias Hepáticas/microbiología , Hígado/microbiología , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/microbiología , Conductos Biliares Intrahepáticos/patología , Carcinoma Hepatocelular/microbiología , Carcinoma Hepatocelular/patología , Colangiocarcinoma/microbiología , Colangiocarcinoma/patología , Femenino , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Hepatitis C Crónica/patología , Humanos , Hígado/química , Hígado/patología , Cirrosis Hepática/microbiología , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos
16.
J Chemother ; 30(2): 129-130, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28925824

RESUMEN

Current interest in HCV therapy with direct acting antivirals is focused on shortening treatment length. We managed two cirrhotics who achieved virological cure after 4 weeks of ombitasvir/paritaprevir/ritonavir, dasabuvir, ribavirin treatment. Analysis to identify potential predictive factors for a successful outcome with a shorter treatment course was conducted.


Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/microbiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Tiempo
17.
Arab J Gastroenterol ; 19(1): 33-36, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29503077

RESUMEN

BACKGROUND AND STUDY AIMS: Occult hepatitis B infection (OBI) is known to be mostly prevalent in chronic hepatitis C (CHC) patients and OBI reactivation might be life-threatening in patients undergoing interferon (IFN)-free direct acting antiviral (DAA) therapy. As previous studies have revealed a relationship between OBI and non-response to IFN-based antiviral therapy, the aim of the current study was to determine if there was a higher prevalence of OBI in IFN non-responders than responders. PATIENTS AND METHODS: This retrospective cross-sectional study was conducted in CHC patients who had previously received IFN-based antiviral therapy. Serum samples of 100 HBsAg negative CHC patients were tested for HBV DNA, anti-HBc IgG, anti-HBs, ALT and AST. The presence of OBI was compared between 50 IFN responders and 50 IFN non-responders. Patients with a history of previous HBV infection, patients with evidence of cirrhosis and patients who had received IFN therapy within the last one year were excluded from the study. RESULTS: Anti-HBc IgG positivity was determined in 53% of the patients. HBV DNA positivity, indicating OBI was determined in 1 (1%) patient. This patient was anti-HBc IgG positive, anti-HBs negative, ALT and AST levels were normal. The HBV DNA and anti-HBc IgG positivity rates were higher in the non-responder group than in the responder group, but the difference was not statistically significant (p = 0.31 and p = 0.07 respectively). CONCLUSION: According to the results of this study, the prevalence of OBI is lower than expected amongst CHC patients in Turkey and it may not be necessary to apply routine screening to IFN non-responders for OBI infection before DAA therapy. However, there is a need for multicentre studies with larger patient series.


Asunto(s)
Antivirales , Virus de la Hepatitis B , Hepatitis B Crónica , Hepatitis C Crónica , Interferones , Antivirales/administración & dosificación , Antivirales/efectos adversos , Coinfección , ADN Viral/aislamiento & purificación , Femenino , Anticuerpos contra la Hepatitis B/aislamiento & purificación , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/microbiología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/microbiología , Humanos , Interferones/administración & dosificación , Interferones/efectos adversos , Masculino , Persona de Mediana Edad , Prevalencia , Estadística como Asunto , Turquía/epidemiología , Activación Viral/inmunología
18.
World J Gastroenterol ; 24(32): 3617-3625, 2018 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-30166857

RESUMEN

Both Helicobacter pylori (H. pylori) infection and liver diseases, including nonalcoholic fatty liver disease (NAFLD), viral hepatitis, and hepatocellular carcinoma (HCC), have high prevalences worldwide, and the relationship between H. pylori infection and liver disease has been discussed for many years. Although positive correlations between H. pylori and NAFLD have been identified in some clinical and experimental studies, negative correlations have also been obtained in high-quality clinical studies. Associations between H. pylori and the pathogenesis of chronic viral hepatitis, mainly disease progression with fibrosis, have also been suggested in some clinical studies. Concerning HCC, a possible role for H. pylori in hepatocarcinogenesis has been identified since H. pylori genes have frequently been detected in resected HCC specimens. However, no study has revealed the direct involvement of H. pylori in promoting the development of HCC. Although findings regarding the correlations between H. pylori and liver disease pathogenesis have been accumulating, the existing data do not completely lead to an unequivocal conclusion. Further high-quality clinical and experimental analyses are necessary to evaluate the efficacy of H. pylori eradication in ameliorating the histopathological changes observed in each liver disease.


Asunto(s)
Carcinoma Hepatocelular/patología , Infecciones por Helicobacter/patología , Helicobacter pylori/patogenicidad , Hepatitis C Crónica/patología , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Carcinogénesis/patología , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/microbiología , Carcinoma Hepatocelular/prevención & control , Progresión de la Enfermedad , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/aislamiento & purificación , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/microbiología , Hepatitis C Crónica/prevención & control , Humanos , Hígado/microbiología , Hígado/patología , Cirrosis Hepática/epidemiología , Cirrosis Hepática/microbiología , Cirrosis Hepática/prevención & control , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/microbiología , Neoplasias Hepáticas/prevención & control , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Prevalencia , Factores de Riesgo , Resultado del Tratamiento
19.
Autoimmunity ; 39(2): 129-35, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16698669

RESUMEN

AIM: Intrahepatic bile ducts are the targets for inflammation in primary biliary cirrhosis (PBC), but their pathogenesis is not known. Gram-positive bacterial DNA was detected recently in gallbladder bile of PBC patients. In the present study, we assessed the possible pathological role of lipoteichoic acid (LTA), the gram-positive bacterial cell wall component, in PBC. METHODS: Liver samples, obtained from 20 patients with PBC (stage 1-2 with CNSDC: stage 3-4 with loss of bile ducts = 10:10) and from 13 patients with chronic hepatitis due to hepatitis C virus (CH-C) with lymphocytic cholangitis, were subjected to immunohistochemical staining with polyclonal rabbit anti-LTA as the primary antibody. Serum reactivities to LTA were studied by ELISA. After 1 microg of purified LTA was placed in a 96-well microplate as an antigen, an antibody capture assay was carried out using serum samples from PBC (n = 20), CH-C (n = 13) and healthy subjects (n = 11). RESULTS: LTA was localized around the sites of chronic non-suppurative destructive cholangitis (CNSDC) in the portal area in stage 1-2 PBC but was not detected in the portal area in CH-C. In stage 3-4 PBC, LTA was localized around sites of ductular proliferation at the periphery of portal tracts. IgM class anti-LTA serum titers were significantly higher in PBC than in CH-C. IgA class anti-LTA serum titers were significantly higher in PBC than in healthy subjects. CONCLUSIONS: In the PBC livers, the profile of immunoreactivity to LTA changed markedly as the disease progressed. Sera from PBC showed higher levels of anti-LTA titers than CH-C (IgM) or from healthy subjects (IgA). The LTA-mediated immune system might affect the initiation and/or progression of PBC.


Asunto(s)
Lipopolisacáridos/inmunología , Cirrosis Hepática Biliar/etiología , Ácidos Teicoicos/inmunología , Adulto , Anciano , Anticuerpos Antibacterianos/sangre , Conductos Biliares Intrahepáticos/efectos de los fármacos , Conductos Biliares Intrahepáticos/metabolismo , Conductos Biliares Intrahepáticos/microbiología , Conductos Biliares Intrahepáticos/patología , Femenino , Bacterias Grampositivas/inmunología , Bacterias Grampositivas/patogenicidad , Hepatitis C Crónica/etiología , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/microbiología , Hepatitis C Crónica/patología , Humanos , Lipopolisacáridos/metabolismo , Cirrosis Hepática Biliar/inmunología , Cirrosis Hepática Biliar/microbiología , Cirrosis Hepática Biliar/patología , Persona de Mediana Edad , Ácidos Teicoicos/metabolismo
20.
PLoS One ; 10(3): e0118643, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25785448

RESUMEN

BACKGROUND: Microbial translocation (MT) contributes to immune activation during HIV and HCV infections. We investigated the kinetics of MT markers during anti-HCV and anti-HIV treatments, and if baseline plasma levels of lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) could predict anti-HCV treatment outcome. METHODS: Plasma from 78 HIV-infected patients was evaluated for LPS, LBP and sCD14. The patients starting anti-HCV treatment (with ongoing antiretroviral (ART) treatment) were categorized into sustained viral responders (SVR; n = 21) or non-responders (NR; n = 15) based on treatment outcome. ART starting subjects--were categorized into chronically HCV-infected (CH; n = 24) and mono-infected (HIV; n = 18), based on the HCV infection status. Samples were collected before start (at baseline) of pegylated-interferon-alpha/ribavirin (peg-IFN/RBV) or antiretroviral-therapy and two years after treatment start (at follow up). χ2-test, non-parametric statistics and logistic regression were applied to determine the associations with treatment response and changes of the soluble markers. RESULTS: Plasma levels of LPS and sCD14 were elevated in all subjects before antiviral-treatment but remained unchanged at follow-up. Elevated levels of LBP were present in patients with HIV and HIV/HCV co-infection and were reduced by ART. Additionally, higher levels of LBP were present at baseline in NR vs. SVR. Higher levels of LBP at baseline were associated with non-response to peg-IFN/RBV treatment in both bivariate (OR: 0.19 95% CI: 0.06-0.31, p = 0.004) and multivariate analysis (OR: 1.43, 95% CI: 1.1-1.86, p = 0.07). CONCLUSION: In HIV/HCV co-infected patients high baseline LBP levels are associated with non-response to peg-IFN/RBV therapy. Plasma LBP (decreased by ART) may be a more relevant MT marker than LPS and sCD14.


Asunto(s)
Proteínas Portadoras/sangre , Coinfección/tratamiento farmacológico , Coinfección/microbiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/microbiología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/microbiología , Glicoproteínas de Membrana/sangre , Proteínas de Fase Aguda , Adulto , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Aspartato Aminotransferasas/metabolismo , Biomarcadores/sangre , Coinfección/inmunología , Coinfección/metabolismo , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , VIH-1/efectos de los fármacos , VIH-1/fisiología , Hepacivirus/efectos de los fármacos , Hepacivirus/fisiología , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/metabolismo , Humanos , Interferón-alfa/farmacología , Interferón-alfa/uso terapéutico , Cinética , Receptores de Lipopolisacáridos/sangre , Receptores de Lipopolisacáridos/química , Lipopolisacáridos/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Ribavirina/farmacología , Ribavirina/uso terapéutico , Solubilidad , Factores de Tiempo , Resultado del Tratamiento
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