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Hepatocellular carcinoma risk after viral response in hepatitis C virus-advanced fibrosis: Who to screen and for how long?

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World Journal of Gastroenterology 2021年第40期27卷 6737-6749页

作者： Adriana Ahumada Laura Rayón Clara Usón Rafael Bañares sonia alonso lopez Liver Unit Hospital General Universitario Gregorio MarañónMadrid 28007Spain Liver Unit Instituto de Investigación Sanitaria Gregorio Marañón(IiSGM)Madrid 28007Spain Medicine Universidad Complutense de MadridMadrid 28006Spain Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain

Hepatitis C virus(HCV)chronic infection is associated with fibrosis progression,end-stage liver complications and *** surprisingly,HCV infection is a leading cause of liver-related morbidity and mortality *** sustained virological response(SVR),the risk of developing hepatocellular carcinoma is not completely eliminated in patients with established cirrhosis or with advanced ***,lifelong surveillance is currently *** strategy is likely not universally cost-effective and harmless,considering that not all patients with advanced fibrosis have the same risk of developing *** related to the severity of liver disease and its potential to improve after SVR,the molecular and epigenetic changes that occur during infection and other associated comorbidities might account for different risk levels and are likely essential for identifying patients who would benefit from screening programs after *** to develop predictive models and risk calculators,biomarkers and genetic panels and even deep learning models to estimate the individual risk of HCC have been made in the direct-acting antiviral agents era,when thousands of patients with advanced fibrosis and cirrhosis have reached *** tools could help to identify patients with very low HCC risk in whom surveillance might not be *** this review,factors affecting the probability of HCC development after SVR,the benefits and risks of surveillance,suggested strategies to estimate individualized HCC risk and the current evidence to recommend lifelong surveillance are discussed.

关键词： Hepatitis C virus Hepatocellular carcinoma Liver fibrosis Surveillance Sustained virologic response Epigenetic changes Predictive models Cost-effectiveness

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Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico

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World Journal of Gastroenterology 2015年第41期21卷 11552-11566页

作者： Omar Ramos-lopez Erika Martinez-lopez sonia Roman Nora A Fierro Arturo Panduro Department of Molecular Biology in Medicine Civil Hospital of Guadalajara "Fray Antonio Alcalde" Guadalajara Jalisco Mexico and Health Sciences Center University of Guadalajara

Liver cirrhosis(LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features.

关键词： Genomic medicine Polymorphisms Viral hepatitis Obe

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Well-controlled autoimmune hepatitis treatment withdrawal may be safely accomplished without liver-biopsy guidance

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Gastroenterology Report 2018年第4期6卷 284-290,I0002页

作者： John Guirguis Yilien alonso Rocio lopez William Carey Department of Internal Medicine Blake Medical CenterBradentonFLUSA Department of Gastroenterology Ochsner Health SystemNew OrleansLAUSA Department of Quantitative Health Sciences Cleveland ClinicClevelandOHUSA Digestive Disease Institute Department of Gastroenterology and HepatologyCleveland ClinicClevelandOHUSA

Background:Autoimmune hepatitis may flare up after treatment withdrawal,especially in those who had not achieved histological remission but had normal liver *** European Association for the Study of the Liver(EASL)and the American Association for the Study of Liver Disease(AASLD)Guidelines recommend performing liver biopsy before treatment *** aim of the study is to define the outcome of treatment withdrawal in adults with wellcontrolled disease for 2 years with and without liver-biopsy ***:A retrospective observational study was conducted on biopsy-proven autoimmune hepatitis patients who were treated for 2 years and with persistently normal aspartate aminotransferase(AST)and alanine aminotransferase(ALT)or nearly so for 6 months prior to treatment *** were:juvenile onset autoimmune hepatitis and prior treatment or use of agents other than corticosteroids and *** primary endpoint was to define freedomfrom flare-ups for 1 year after treatment ***:Thirty-four consecutive subjectsmeeting study criteria were *** withdrawal was accomplished in 24 subjects without liver-biopsy guidance and 10 had pre-treatment withdrawal liver ***,immunosuppressive usage,pre-treatment cirrhosis and pre-treatment liver enzymes were similar between the two groups,and 25%had an enzyme flare-up within 12months after treatment withdrawal,which was similar in the two groups(20.8 vs 30.0%,P=0.57).Conclusions:Adults with autoimmune hepatitis and excellent response to therapy for 2 years are candidates for treatment withdrawal without the need for liver biopsy.

关键词： Autoimmune hepatitis liver biopsy treatment withdrawal liver enzyme

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Genome-based nutrition:An intervention strategy for the prevention and treatment of obesity and nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2015年第12期21卷 3449-3461页

作者： sonia Roman Claudia Ojeda-Granados Omar Ramos-lopez Arturo Panduro Department of Molecular Biology in Medicine Civil Hospital of Guadalajara "Fray Antonio Alcalde"GuadalajaraJalisco Mexico and Health Sciences Center University of Guadalajara

Obesity and nonalcoholic steatohepatitis are increasing in westernized countries, regardless of their geographiclocation. In Latin America, most countries, including Mexico, have a heterogeneous admixture genome with Amerindian, European and African ancestries. However, certain high allelic frequencies of several nutrientrelated polymorphisms may have been achieved by past gene-nutrient interactions. Such interactions may have promoted the positive selection of variants adapted to regional food sources. At present, the unbalanced diet composition of the Mexicans has led the country to a 70% prevalence rate of overweightness and obesity due to substantial changes in food habits, among other factors. International guidelines and intervention strategies may not be adequate for all populations worldwide because they do not consider disparities in genetic and environmental factors, and thus there is a need for differential prevention and management strategies. Here, we provide the rationale for an intervention strategy for the prevention and management of obesity-related diseases such as nonalcoholic steatohepatitis based on a regionalized genome-based diet. The components required to design such a diet should focus on the specific ancestry of each population around the world and the convenience of consuming traditional ethnic food.

关键词： Latin America Mexico Gene-nutrient interactions Ev

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Effect of snow on mountain river regimes： an example from the Pyrenees

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Frontiers of Earth Science 2017年第3期11卷 515-530页

作者： Alba SANMIGUEL-VALLELADO Enrique MORAN-TEJEDA Esteban alonso-GONZALEZ Juan Ignacio lopez-MORENO Pyrenean Institute of Ecology CSIC (Spanish Research Council) Zaragoza Spain Department of Geography University of the Balearic Islands Palma de Mallorca Spain

The purpose of this study was to characterize mountain river regimes in the Spanish Pyrenees and to assess the importance of snow accumulation and snowmelt on the timing of river flows. Daily streamflow data from 9 gauging stations in the Pyrenees were used to characterize river regimes. These data were analyzed by hydrological indices, with a focus on periods when snow accumulation and snowmelt occurred. These results were combined with data on Snow Water Equivalent （SWE）（from measure- ments of depth and density of snow in the main river basins and also simulated by a process-based hydrological model）, snowmelting （simulated by a process-based hydrological model）, precipitation （from observations）, and temperature （from observations）. Longitude. and elevation gradients in the Pyrenees explain the transition of river regimes from those that mostly had low nival signals （in the west and at low elevations） to those that mostly had high nival signals （low winter runoff and late spring peakflow, in the east and at high elevations）. Although trend analyses indicated no statistically signifi- cant changes, there was a trend of decreased nival signal over time in most of the analyzed rivers. Our results also demonstrated that snow processes cannot explain all of the interannual variability of river regimes, because the temporal distribution of liquid precipitation and tempera- ture play key roles in hydrography.

关键词： river regime precipitation snow indices,Spanish Pyrenees streamflow

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Brillouin expanded time-domain analysis based on dual optical frequency combs

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Light(Science & Applications) 2024年第8期13卷 1534-1544页

作者： Jae Hyeong Youn Kwang Yong Song sonia Martin-lopez Miguel Gonzalez-Herraez María R.Fernández-Ruiz Dept.of Physics Chung-Ang UniversitySeoulKorea Dept.of Electronics Universidad de AlcaláMadridSpain

Brillouin Optical Time-Domain Analysis(BOTDA)is a widely-used distributed optical fiber sensing technology employing pulse-modulated pump waves for local information retrieval of the Brillouin gain or loss *** spatial resolution of BOTDA systems is intrinsically linked to pulse duration,so high-resolution measurements demand high electronic bandwidths inversely proportional to the *** paper introduces Brillouin Expanded Time-Domain Analysis(BETDA)as a modified BOTDA system,simultaneously achieving high spatial resolution and low detection *** two optical frequency combs(OFCs)with different frequency intervals as pump and probe,local Brillouin gain spectra are recorded by their spectral beating traces in an expanded time domain.A 2-cm-long hotspot located in a 230m single-mode fiber is successfully measured in the time domain with a detection bandwidth of less than 100 kHz using dual OFCs with tailored spectral phase,line spacing,and bandwidth.

关键词： pump optical fiber

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An imbalance between innate and adaptive immune cells at the maternal-fetal interface occurs prior to endotoxin-induced preterm birth

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Cellular & Molecular Immunology 2016年第4期13卷 462-473页

作者： Marcia Arenas-Hernandez Roberto Romero Derek St Louis sonia S Hassan Emily B Kaye Nardhy Gomez-lopez Department of Obstetrics & Gynecology Wayne State University School of Medicine Detroit Michigan USA perinatology Research Branch Program for Perinatal Research and Obstetrics Division of Intramural Research Eunice Kennedy ShriverNational Institute of Child l~ealth and Human DevelopmentNIC.HD/NIHDHHS Bethesda Maryland and Detroit Michigan USA Departme.nt of Obstetrics and Gynecology University of M chigan Ann ArborMichigan USA Department of Epidemiology and Biostatistics Michigan State University East Lansing Michigan USA Department of Molecular Obstetrics and Genetics Wayne State University Detroit Michigan USA Department of ImmunoLogy & MicrobioLogy Wayne State University School of Medicine Detroit Michigan USA

Preterm birth （PTB） is the leading cause of neonatal morbidity and mortality worldwide. A transition from an anti-inflammatory state to a pro-inflammatory state in the mother and at the maternal-fetal interface has been implicated in the pathophysiology of microbial-induced preterm labor. However, it is unclear which immune cells mediate this transition. We hypothesized that an imbalance between innate and adaptive immune cells at the maternal-fetal interface will occur prior to microbial-induced preterm labor. Using an established murine model of endotoxin-induced PTB, our results demonstrate that prior to delivery there is a reduction of CD4 ＋ regulatory T cells （Tregs） in the uterine tissues. This reduction is neither linked to a diminished number of Tregs in the spleen, nor to an impaired production of ILIO, CCL17, or CCL22 by the uterine tissues. Endotoxin administration to pregnant mice does not alter effector CD4＋ T cells at the maternal-fetal interface. However, it causes an imbalance between Tregs （CD4＋ and CD8＋）, effector CD8＋ T cells, and Th17 cells in the spleen. In addition, endotoxin administration to pregnant mice leads to an excessive production of CCL2, CCL3, CCL17, and CCL22 by the uterine tissues as well as abundant neutrophils. This imbalance in the uterine microenvironment is accompanied by scarce APC-like cells such as macrophages and MHC II ＋ neutrophils. Collectively, these results demonstrate that endotoxin administration to pregnant mice causes an imbalance between innate and adaptive immune cells at the maternal-fetal interface.

关键词： antigen-presenting cells effector T cells inflammation labor lipopolysaccharide macrophages microbial product neutrophils pregnancy preterm labor regulatory T cells

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Immunologic, metabolic and genetic factors in hepatitis C virus infection

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World Journal of Gastroenterology 2014年第13期20卷 3443-3456页

作者： Nora A Fierro Karina Gonzalez-Aldaco Rafael Torres-Valadez Erika Martinez-lopez sonia Roman Arturo Panduro Department of Molecular Biology in Medicine Civil Hospital of Guadalajara"Fray Antonio Alcalde" and Health Sciences CenterUniversity of GuadalajaraGuadalajara 44280JaliscoMexico

The mechanisms that regulate disease progression during hepatitis C virus(HCV)infection and the response to treatment are not clearly *** studies have demonstrated that a strong host immune response against HCV favors HCV *** addition,genetic factors and metabolic machinery,particularly cholesterol modulation,are involved in HCV *** is likely that the interplay between all of these factors contributes to the outcome of HCV *** recent years,the world has experienced its largest epidemic of *** and the United States are the leading sufferers from this epidemic at the global *** is associated with the development ofnumerous pathologies including hypercholesterolemia which is one of the eight most important risk factors for mortality in *** may be related to the course of HCV infection in this ***,we focus on the urgent need to study the progression of HCV infection in relation to ethnic *** are discussed that hold promise in identifying immune,metabolic and genetic factors that,in conjunction,could be therapeutic targets or predictors of the progression of HCV infection.

关键词： Hepatitis C virus Immune response Lipids Metabolism Genetics

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Time-expanded phase-sensitive optical time-domain reflectometry

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Light(Science & Applications) 2021年第3期10卷 443-454页

作者： Miguel Soriano-Amat Hugo F.Martins Vicente Duran Luis Costa sonia Martin-lopez Miguel Gonzalez-Herraez Maria R.Fernandez-Ruiz Departamento de Electronica Universidad de AlcalaEscuela Politecnica Superior28805 MadridSpain Instituto deóptica"Daza de Valdes" IO-CSICC/Serrano 12128006 MadridSpain GROC-UJI Institute of New Imaging TechnologiesUniversity Jaume112071 CastellonSpain

Phase-sensitive optical time-domain reflectometry(CDOTDR)is a well-established technique that provides spatiotemporal measurements of an environmental variable in real *** unique capability is being leveraged in an everincreasing number of applications,from energy transportation or civil security to *** date,a wide number of different approaches have been implemented,providing a plethora of options in terms of performance(resolution,acquisition bandwidth,sensitivity or range).However,to achieve high spatial resolutions,detection bandwidths in the GHz range are typically required,substantially increasing the system cost and ***,we present a novel OOTDR approach that allows a customized time expansion of the received optical ***,the presented technique reaches cm-scale spatial resolutions over t km while requiring a remarkably low detection bandwidth in the MHz *** approach relies on the use of dual-comb spectrometry to interrogate the fibre and sample the backscattered *** phase-spectral coding is applied to the employed combs to maximize the signal-to-noise ratio of the sensing scheme.A comparison of the proposed method with alternative approaches aimed at similar operation features is provided,along with a thorough analysis of the new *** results demonstrate a radically novel high-resolution OOTDR scheme,which could promote new applications in metrology,borehole monitoring or aerospace.

关键词： optical phase expanded

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CD36 genetic variation, fat intake and liver fibrosis in chronic hepatitis C virus infection

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World Journal of Hepatology 2016年第25期8卷 1067-1074页

作者： Omar Ramos-lopez sonia Roman Erika Martinez-lopez Nora A Fierro Karina Gonzalez-Aldaco Alexis Jose-Abrego Arturo Panduro Department of Molecular Biology in Medicine Civil Hospital of Guadalajara "Fray Antonio Alcalde" Health Sciences University Center University of Guadalajara

AIM To analyze the association of the CD36 polymorphism(rs1761667) with dietary intake and liver fibrosis(LF) in chronic hepatitis C(CHC) patients. METHODS In this study, 73 patients with CHC were recruited. The CD36 genotype(G > A) was determined by a TaqM an real-time PCR system. Dietary assessment was carried out using a three-day food record to register the daily intake of macronutrients. Serum lipids and liver enzymes were measured by a dry chemistry assay. LF evaluated by transient elastography(Fibroscan~)and APRI score was classified as mild LF(F1-F2) and advanced LF(F3-F4).RESULTS Overall, the CD36 genotypic frequencies were AA(30.1%), AG(54.8%), and GG(15.1%), whereas the allelic A and G frequencies were 57.5% and 42.5%, respectively. CHC patients who were carriers of the CD36 AA genotype had a higher intake of calories attributable to total fat and saturated fatty acids than those with the non-AA genotypes. Additionally, aspartate aminotransferase(AST) serum values were higher in AA genotype carriers compared to non-AA carriers(91.7 IU/L vs 69.8 IU/L, P = 0.02). Moreover, the AA genotype was associated with an increase of 30.23 IU/L of AST(β = 30.23, 95%CI: 9.0-51.46, P = 0.006). Likewise, the AA genotype was associated with advanced LF compared to the AG(OR = 3.60, 95%CI: 1.16-11.15, P = 0.02) or AG + GG genotypes(OR = 3.52, 95%CI: 1.18-10.45, P = 0.02).CONCLUSION This study suggests that the CD36(rs1761667) AA genotype is associated with higher fat intake and more instances of advanced LF in CHC patients.

关键词： Hepatitis C virus infection CD36 receptor Lipids Liver fibrosis Mexico

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