Publications by authors named "Isabel Carmona"

22 Publications

  • Page 1 of 1

Schizotypal personality traits and the social learning of fear.

Sci Rep 2021 Nov 29;11(1):23048. Epub 2021 Nov 29.

Department of Psychology, University of Almería, 04120, Almería, Spain.

Schizotypy can be defined as a combination of traits qualitatively similar to those found in schizophrenia, but milder in their expression, that can be found in clinical and non-clinical populations. In this research, we explore, to our knowledge, for the first time, whether schizotypal personality traits may affect the acquisition of conditioned fear by social means only. Apart from being an essential capacity to ensure learning in safe environments, social fear learning shares important characteristics with direct fear acquisition, which also makes it a great candidate for developing successful extinction procedures. Undergraduate students (n = 72) performed a task of social fear learning. In this task, participants watched a video of a person that simulated to receive electric shocks (unconditioned stimulus; US) paired with a coloured square (conditioned stimulus plus; CS+), while another coloured square was never paired (conditioned stimulus minus; CS-) with the shock. After that, they were presented with a similar sequence of coloured screens. Their Skin Conductance Responses (SCRs) were registered during the whole process. Once they finished, they completed the Schizotypal Personality Questionnaire (SPQ). Our results revealed that participants with a low score in the Cognitive-Perceptual factor of the SPQ exhibited higher SCRs when they saw the US than when they saw the CS- (all ps < 0.01) during the learning phase. Nevertheless, those with higher scores did not present any difference in their SCRs toward both stimuli (all ps > 0.05), a pattern that has been similarly found in schizophrenia. During the final trials of the test phase, participants with the highest scores in the Disorganized factor were the only ones that maintained a higher SCR towards the CS+ than towards the CS- (p = 0.006), which could be associated with an impairment in their extinction processes.
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http://dx.doi.org/10.1038/s41598-021-02336-6DOI Listing
November 2021

A 2-Step Strategy Combining FIB-4 With Transient Elastography and Ultrasound Predicted Liver Cancer After HCV Cure.

Am J Gastroenterol 2021 Sep 9. Epub 2021 Sep 9.

Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Spain.

Introduction: Despite the direct-acting antiviral therapy has dramatically decreased the likelihood of having liver-related complications and extrahepatic outcomes, the risk of developing hepatocellular carcinoma (HCC) is not totally eliminated after sustained virological response (SVR). We aimed to develop an easy-to-apply strategy to be adopted in clinical practice for accurately classifying the HCC risk in hepatitis C virus patients after SVR.

Methods: Prospective and multicenter study enrolling hepatitis C virus patients with advanced fibrosis (transient elastography [TE] > 10 kPa) or cirrhosis by ultrasound showing SVR. They were followed up until HCC, liver transplantation, death, or until October 2020, which occurred first, with a minimum follow-up period of 6 months after SVR (follow-up: 49 [interquartile range 28-59] months).

Results: Patients with cirrhosis by ultrasound represented 58% (611/1,054) of the overall cohort. During the study, HCC occurrence was 5.3% (56/1,054). Multivariate analyses revealed that Fibrosis-4 (FIB-4) > 3.25 (hazard ratio [HR] 2.26 [1.08-4.73]; P = 0.030), TE (HR 1.02 [1.00-1.04]; P = 0.045) and cirrhosis by ultrasound (HR 3.15 [1.36-7.27]; P = 0.007) predicted HCC occurrence. Baseline HCC screening criteria (TE > 10 kPa or cirrhosis) identified patients at higher risk of HCC occurrence in presence of FIB-4 > 3.25 (8.8%; 44/498) vs FIB-4 < 3.25 (2.4%; 12/506), while those with only FIB > 3.25 had no HCC (0%; 0/50) (logRank 22.129; P = 0.0001). A combination of baseline FIB-4 > 3.25 and HCC screening criteria had an annual incidence >1.5 cases per 100 person-years, while the rest of the groups remained <1 case. Patients who maintained post-treatment FIB-4 > 3.25 and HCC screening criteria remained at the highest risk of HCC occurrence (13.7% [21/153] vs 4.9% [9/184]; logRank 7.396, P = 0.007).

Discussion: We demonstrated that a two-step strategy combining FIB-4, TE, and ultrasound could help stratify HCC incidence risk after SVR.
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http://dx.doi.org/10.14309/ajg.0000000000001503DOI Listing
September 2021

Spatial Recognition Memory: Differential Brain Strategic Activation According to Sex.

Front Behav Neurosci 2021 1;15:736778. Epub 2021 Sep 1.

Department of Psychology, University of Almería, Almeria, Spain.

Human spatial memory research has significantly progressed since the development of computerized tasks, with many studies examining sex-related performances. However, few studies explore the underlying electrophysiological correlates according to sex. In this study event-related potentials were compared between male and female participants during the performance of an allocentric spatial recognition task. Twenty-nine university students took part in the research. Results showed that while general performance was similar in both sexes, the brain of males and females displayed a differential activation. Males showed increased N200 modulation than females in the three phases of memory process (encoding, maintenance, and retrieval). Meanwhile females showed increased activation of P300 in the three phases of memory process compared to males. In addition, females exhibited more negative slow wave (NSW) activity during the encoding phase. These differences are discussed in terms of attentional control and the allocation of attentional resources during spatial processing. Our findings demonstrate that sex modulates the resources recruited to performed this spatial task.
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http://dx.doi.org/10.3389/fnbeh.2021.736778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441006PMC
September 2021

Role of Leptin in Non-Alcoholic Fatty Liver Disease.

Biomedicines 2021 Jun 30;9(7). Epub 2021 Jun 30.

Department of Medical Biochemistry and Molecular Biology, School of Medicine, Virgen Macarena University Hospital, University of Seville, 41073 Seville, Spain.

Non-alcoholic fatty liver disease (NAFLD), which affects about a quarter of the global population, poses a substantial health and economic burden in all countries, yet there is no approved pharmacotherapy to treat this entity, nor well-established strategies for its diagnosis. Its prevalence has been rapidly driven by increased physical inactivity, in addition to excessive calorie intake compared to energy expenditure, affecting both adults and children. The increase in the number of cases, together with the higher morbimortality that this disease entails with respect to the general population, makes NAFLD a serious public health problem. Closely related to the development of this disease, there is a hormone derived from adipocytes, leptin, which is involved in energy homeostasis and lipid metabolism. Numerous studies have verified the relationship between persistent hyperleptinemia and the development of steatosis, fibrinogenesis and liver carcinogenesis. Therefore, further studies of the role of leptin in the NAFLD spectrum could represent an advance in the management of this set of diseases.
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http://dx.doi.org/10.3390/biomedicines9070762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301314PMC
June 2021

Implicit outcomes expectancies shape memory process: Electrophysiological evidence.

Biol Psychol 2020 11 1;157:107987. Epub 2020 Nov 1.

Department of Psychology, University of Almería, Spain; CERNEP Research Center, University of Almería, Spain. Electronic address:

The simple manipulation of pairing specific outcomes with the sample stimuli strongly affects discriminative learning and memory processes. This procedure has been named the Differential Outcomes Procedure (DOP) and is usually compared to a control condition (the non-differential procedure, NOP) consisting in the random administration of the outcomes after each correct response. Recent research has revealed that the DOP effect arises even under unconscious conditions. In this study, we explored the temporal dynamics of short-term memory processes in both the DOP and the NOP in the absence of awareness of either the outcome (Experiment 1A) or the initial sample stimulus (Experiment 1B) through the evoked-related potentials technique. Results showed distinctive electrophysiological activation patterns in the DOP compared with the NOP at encoding, maintenance and retrieval phases. The present findings provide electrophysiological evidence of implicit-prospective processes involved in the DOP. They elucidate the processes that result in improved visual recognition memory.
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http://dx.doi.org/10.1016/j.biopsycho.2020.107987DOI Listing
November 2020

Electrophysiological correlates of the differential outcomes effect in visual short-term memory.

Int J Psychophysiol 2020 09 26;155:184-193. Epub 2020 Jun 26.

Department of Psychology, University of Almería, Spain; CERNEP Research Center, University of Almería, Spain; Department of Psychology, University of Almería, 04120, Spain.. Electronic address:

The differential outcomes procedure (DOP) consists in applying a specific outcome after each discriminative stimulus-correct response pairing, leading to improved performance in both memory and learning tasks (faster acquisition and/or higher response accuracy), compared to the non-differential outcomes procedure (NOP). The main aim of this study was to explore the electrophysiological correlates (ERPs) of the DOP in a visual short-term memory task, and to test whether a differential activation pattern would be observed depending on the outcomes condition (DOP vs. NOP). The ERP signals showed differences between both outcomes condition in all three phases of the short-term memory task: encoding, maintenance and retrieval. Our results are in accordance with the view that in the DOP condition the probe stimulus triggers a representation of the unique outcome, which remains active over the maintenance period (prospective process). In the NOP condition, in contrast, a representation of the probe stimulus is maintained (retrospective process). In addition, these results suggested that stimuli associated with unique outcomes captured attention involuntary at retrieval, decreasing the interference from distractor stimuli in the retrieval phase.
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http://dx.doi.org/10.1016/j.ijpsycho.2020.06.010DOI Listing
September 2020

Semantic Negative Priming From an Ignored Single-Prime Depends Critically on Prime-Mask Inter-Stimulus Interval and Working Memory Capacity.

Front Psychol 2020 9;11:1227. Epub 2020 Jun 9.

School of Psychology, University of Wales Bangor, Bangor, United Kingdom.

The aim of this study is to examine the link between working memory capacity and the ability to exert cognitive control. Here, participants with either high or low working memory capacity (WMC) performed a semantic negative priming (NP) task as a measure of cognitive control. They were required to ignore a single prime word followed by a pattern mask appearing immediately or after a delay. The prime could be semantically related or unrelated to an upcoming target word where a forced-choice categorization was required. Each type of mask (immediate vs. delayed) appeared randomly from trial to trial. Results demonstrated that, when the ignored prime was immediately followed by the mask, neither of the groups (high or low WMC) showed reliable NP. In clear contrast, when the mask onset was delayed responses latencies were reliably slower for semantically related trials than for unrelated trials (semantic NP), but only for the high WMC group. The present results clearly demonstrate that semantic NP from single ignored primes depends on both the masking pattern that follows the prime (immediate vs. delayed mask), and on working memory capacity.
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http://dx.doi.org/10.3389/fpsyg.2020.01227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296074PMC
June 2020

Enhanced learning and retention of medical information in Alzheimer's disease after differential outcomes training.

PLoS One 2020 16;15(4):e0231578. Epub 2020 Apr 16.

Departamento de Psicología, Universidad de Almería, Almería, Spain.

Background: Adherence to treatment is a crucial factor for patients who have chronic illnesses or multiple morbidities and polypharmacy, which is frequently found in older adults. The non-adherence to medications has important economic and social consequences as well as impacts on the health of the patients. One of the reasons that can explain the low adherence to treatment, is the memory deficits that are characteristics of this population and that are even more evident in cases that involve neurodegenerative diseases.

Methods And Findings: In this study, we explore whether the differential outcomes procedure (DOP), which has been shown to be useful in improving discriminative learning and memory in different populations, may facilitate learning and retention of medical recommendations in older adults who have been diagnosed with Alzheimer's disease. The results demonstrate that when this procedure was applied, the patients showed improvements in learning and long-term retention of two pill/time of day associations in a situation that simulates adherence to medical prescriptions.

Conclusions: These findings contribute new data about the potential benefits of the DOP in patients with neurodegenerative disorders, highlighting the important role that this procedure could play in addressing important issues related to the health and quality of life of older adults, with or without neurodegenerative diseases, such as low adherence to medical treatments.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231578PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162503PMC
July 2020

Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb-V and dialysis in Spanish clinical practice - Vie-KinD study.

PLoS One 2019 24;14(9):e0221567. Epub 2019 Sep 24.

Infectious Diseases Unit, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Córdoba, Spain.

Background And Aims: Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r ± DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015.

Material And Methods: Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and tolerability data were collected from medical records.

Results: Data from 135 patients with a mean age (SD) of 58.3 (11.4) years were analyzed: 92.6% GT1 (81.6% GT1b and 17.6% GT1a) and 7.4% GT4, 14 (10.4%) HIV/HCV co-infected, 19.0% with fibrosis F3 and 28.1% F4 by FibroScan®, 52.6% were previously treated with pegIFN and RBV. 11.1%, 14.8% and 74.1% of patients had CKD stage IIIb, IV and V respectively. 68.9% of patients were on hemodialysis; 8.9% on peritoneal dialysis and 38.5% had history of renal transplant. A total of 125 (96.2%) of 135 patients were treated with 3D, 10 (7.4%) with 2D and 30.4% received RBV. The overall intention-to-treat (ITT) sustained virologic response at week 12 (SVR12) was 92.6% (125/135) and the overall modified-ITT (mITT) SVR12 was 99.2% (125/126). The SVR12 rates (ITT) per sub-groups were: HCV mono-infected (91.7%), HCV/HIV co-infected (100%), GT1 (92.0%), GT4 (100%), CKD stage IIIb (86.7%), stage IV (95%) and stage V (93%). Among the 10 non-SVR there was only 1 virologic failure (0.7%); 4 patients had missing data due lost to follow up (3.0%) and 5 patients discontinued 3D/2D regimen (3.7%): 4 due to severe adverse events (including 3 deaths) and 1 patient´s decision.

Conclusions: These results have shown that 3D/2D regimens are effective and tolerable in patients with advanced CKD including those in dialysis with GT 1 or 4 chronic HCV mono-infection and HIV/HCV coinfection in a real-life cohort. The overall SVR12 rates were 92.6% (ITT) and 99.2% (mITT) without clinically relevant changes in eGFR until 12 weeks post-treatment. These results are consistent with those reported in clinical trials.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221567PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759177PMC
March 2020

Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C previously treated with DAAs.

J Hepatol 2019 10 14;71(4):666-672. Epub 2019 Jun 14.

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Hospital Universitario Virgen del Rocío, Seville, Spain.

Background & Aims: Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents do not achieve sustained virological response (SVR). The currently approved retreatment regimen for prior DAA failure is a combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little data on its use in clinical practice. The aim of this study was to analyse the effectiveness and safety of SOF/VEL/VOX in the real-world setting.

Methods: This was a prospective multicentre study assessing the efficacy of retreatment with SOF/VEL/VOX in patients who had experienced a prior DAA treatment failure. The primary endpoint was SVR 12 weeks after the completion of treatment (SVR12). Data on safety and tolerability were also recorded.

Results: A total of 137 patients were included: 75% men, 35% with liver cirrhosis. Most were infected with HCV genotype (GT) 1 or 3. The most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevir/r+dasabuvir. A total of 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients with cirrhosis (89%, p = 0.05) and those with GT3 infection (80%, p <0.001). Patients with GT3 infection and cirrhosis had the lowest SVR12 rate (69%). Of the patients who did not achieve SVR12, 1 was reinfected and 7 experienced treatment failure (6 GT3, 1 GT1a). The presence of resistance-associated substitutions did not impact SVR12. Adverse effects were mild and non-specific.

Conclusion: Real-world data show that SOF/VEL/VOX is an effective, safe rescue therapy for patients with prior DAA treatment failure despite the presence of resistance-associated substitutions. However, patients with liver cirrhosis infected by GT3 remain the most-difficult-to-treat group.

Lay Summary: Treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks is the current recommendation for the 5% of patients infected with HCV who do not achieve eradication of the virus under treatment with direct-acting antivirals. In a Spanish cohort of 137 patients who failed a previous combination of direct-acting antivirals, a cure rate of 95% was achieved with SOF/VEL/VOX. Genotypic characteristics of the virus (genotype 3) and the presence of cirrhosis were factors that decreased the rate of cure. Treatment with SOF/VEL/VOX is an effective and safe rescue therapy due to its high efficacy and very good safety profile.
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http://dx.doi.org/10.1016/j.jhep.2019.06.002DOI Listing
October 2019

Does the implicit outcomes expectancies shape learning and memory processes?

Cognition 2019 08 13;189:181-187. Epub 2019 Apr 13.

Department of Psychology, Universidad de Almería, Spain; CERNEP Research Center, Universidad de Almería, Spain. Electronic address:

Does the explicit or implicit knowledge about the consequences of our choices shape learning and memory processes? This seems to be the case according to previous studies demonstrating improvements in learning and retention of symbolic relations and in visuospatial recognition memory when each correct choice is reinforced with its own unique and explicit outcome (the differential outcomes procedure, DOP). In the present study, we aim to extend these findings by exploring the impact of the DOP under conditions of non-conscious processing. To test for this, both the outcomes (Experiment 1A) and the sample stimuli (Experiment 1B) were presented under subliminal (non-conscious) and supraliminal conditions in a delayed visual recognition memory task. Results from both experiments showed a better visual recognition memory when participants were trained with the DOP regardless the awareness of the outcomes or even of the stimuli used for training. To our knowledge, this is the first demonstration that the DOP can be effective under unconscious conditions. This finding is discussed in the light of the two-memory systems model developed by Savage and colleagues to explain the beneficial effects observed on learning and memory when differential outcomes are applied.
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http://dx.doi.org/10.1016/j.cognition.2019.04.007DOI Listing
August 2019

Differential Outcomes Training Ameliorates Visual Memory Impairments in Patients With Alzheimer's Disease: A Pilot Study.

Front Psychol 2018 11;9:2671. Epub 2019 Jan 11.

Department of Psychology, University of Almería, Almería, Spain.

It is well known that Alzheimer's disease (AD), the most common form of dementia, is associated with deficits in cognitive processes including visual memory impairments. One technique that might be used to ameliorate these impairments is the differential outcomes procedure (DOP) that involves associating each to-be-remembered stimulus with a specific outcome. Previous research has demonstrated that the DOP can be used to reduce or eliminate the learning and memory deficits associated with animal models of amnesia and dementia. Furthermore, this procedure has been shown to improve delayed facial recognition in healthy older adults as well as in patients diagnosed with AD. The main aim of the present study is twofold: to extend these findings to other types of visual stimulus and to investigate the effect of the DOP in memory retention in AD patients. Ten patients diagnosed with AD and 10 healthy controls participated in this study. The experiment included two phases. In the first one, they had to perform a delayed matching-to-sample task. In the second phase, participants performed a recognition memory task, designed to assess long-term retention, 1 h and 1 week after the training. Participants showed a better memory-based performance as well as a higher long-term retention of the information when trained under the differential outcomes condition, relative to the non-differential outcomes condition. The DOP seems to be an effective, easy-to-implement, technique to enhance visual memory in AD patients.
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http://dx.doi.org/10.3389/fpsyg.2018.02671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336689PMC
January 2019

Effectiveness and safety of elbasvir/grazoprevir therapy in patients with chronic HCV infection: Results from the Spanish HEPA-C real-world cohort.

J Viral Hepat 2019 01 25;26(1):55-64. Epub 2018 Oct 25.

Complejo Hospitalario Universitario de Pontevedra and IISGS, Pontevedra, Spain.

In randomized controlled trials of patients with chronic HCV infection, elbasvir/grazoprevir (EBR/GZR) demonstrated high cure rates and a good safety profile. This study assessed the effectiveness and safety of EBR/GZR, with and without ribavirin, in a real-world HCV patient cohort. HEPA-C is a collaborative, monitored national registry of HCV patients directed by the Spanish Association for the Study of the Liver and the Networked Biomedical Research Centre for Hepatic and Digestive Diseases. Patients entered into HEPA-C between December 2016 and May 2017, and treated with EBR/GZR with at least end-of-treatment response data, were included. Demographic, clinical and virologic data were analysed, and adverse events (AEs) recorded. A total of 804 patients were included in the study. The majority were male (57.9%), with a mean age of 60 (range, 19-92) years. Genotype (GT) distribution was GT 1, 86.8% (1a, 14.3%; 1b, 72.5%); GT 4, 13.2% and 176 patients (21.9%) were cirrhotic. Overall, among 588 patients with available data, 570 (96.9%) achieved sustained virologic response at 12 weeks post-treatment (SVR12). SVR12 rates by genotype were GT 1a, 97.7%; GT 1b, 98.6%; and GT 4, 98.1%. No significant differences in SVR12 according to fibrosis stage were observed. Eighty patients experienced an AE, resulting in treatment discontinuation in three. In this large cohort of patients with chronic HCV managed in a real-world setting in Spain, EBR/GZR achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with a similarly good safety profile.
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http://dx.doi.org/10.1111/jvh.13008DOI Listing
January 2019

Duration of the acute hepatic encephalopathy episode determines survival in cirrhotic patients.

Therap Adv Gastroenterol 2018 26;11:1756283X17743419. Epub 2017 Nov 26.

Liver Unit, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129 08035 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid.

Background: Episodes of hepatic encephalopathy (HE) have been related to low survival rate. However, the relation between its clinical evolution and mortality has not been assessed.

Methods: A retrospective analysis of 245 cirrhotic patients admitted for an acute episode of HE (⩾grade 2) or who developed an HE episode after an upper gastrointestinal bleeding (UGIB) event was performed to assess the relation between time in HE and transplant-free survival.

Results: Median (IQR) time in HE was 48 h (24-96 h) in the whole cohort. Patients who presented a longer time in HE (>48 h; = 89) exhibited a lower transplant-free survival at 28 days (67.2% 88.9%, < 0.001), 90 days (48.7% 73.8%, < 0.001) and 365 days (30.3% 53.2%, < 0.001), as compared to those with less time in HE (⩽48 h; = 156). Survival rates remained significantly different, with lower percentages in the group with time in HE >48 h, when comparing patients according to baseline HE grade (2 ⩾3) or model for end-stage liver disease (MELD) function (⩽15 >15). Time in HE was also an independent risk factor for mortality at each time point, hazard ratio (HR) (95 CI%) 28 days 2.59 (1.39-4.84); 90 days 1.98 (1.28-3.1) and 365 days 1.5 (1.08-2.19).

Conclusions: The duration of the acute HE episode determines survival in cirrhotic patients independently of liver function and baseline HE grade.
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http://dx.doi.org/10.1177/1756283X17743419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784576PMC
November 2017

Impact of comorbidities on patient outcomes after interferon-free therapy-induced viral eradication in hepatitis C.

J Hepatol 2018 05 28;68(5):940-948. Epub 2017 Dec 28.

Unit of Digestive Diseases, Virgen del Rocio University Hospital, Sevilla, Spain; Institute of Biomedicine of Seville and University of Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. Electronic address:

Background & Aims: Patients with advanced liver fibrosis remain at risk of cirrhosis-related outcomes and those with severe comorbidities may not benefit from hepatitis C (HCV) eradication. We aimed to collect data on all-cause mortality and relevant clinical events within the first two years of direct-acting antiviral therapy, whilst determining the prognostic capability of a comorbidity-based model.

Methods: This was a prospective non-interventional study, from the beginning of direct-acting antiviral therapy to the event of interest (mortality) or up to two years of follow-up, including 14 Spanish University Hospitals. Patients with HCV infection, irrespective of liver fibrosis stage, who received direct-acting antiviral therapy were used to build an estimation and a validation cohort. Comorbidity was assessed according to Charlson comorbidity and CirCom indexes.

Results: A total of 3.4% (65/1,891) of individuals died within the first year, while 5.4% (102/1,891) died during the study. After adjusting for cirrhosis, platelet count, alanine aminotransferase and sex, the following factors were independently associated with one-year mortality: Charlson index (hazard ratio [HR] 1.55; 95% CI 1.29-1.86; p = 0.0001), bilirubin (HR 1.39; 95% CI 1.11-1.75; p = 0.004), age (HR 1.06 95% CI 1.02-1.11; p = 0.005), international normalized ratio (HR 3.49; 95% CI 1.36-8.97; p = 0.010), and albumin (HR 0.18; 95% CI 0.09-0.37; p = 0.0001). HepCom score showed a good calibration and discrimination (C-statistics 0.90), and was superior to the other prognostic scores (model for end-stage liver disease 0.81, Child-Pugh 0.72, CirCom 0.68) regarding one- and two-year mortality. HepCom score identified low- (≤5.7 points: 2%-3%) and high-risk (≥25 points: 56%-59%) mortality groups, both in the estimation and validation cohorts. The distribution of clinical events was similar between groups.

Conclusions: The HepCom score, a combination of Charlson comorbidity index, age, and liver function (international normalized ratio, albumin, and bilirubin) enables detection of a group at high risk of one- and two-year mortality, and relevant clinical events, after starting direct-acting antiviral therapy.

Lay Summary: The prognosis of patients with severe comorbidities may not benefit from HCV viral clearance. An algorithm to decide who will benefit from the treatment is needed to manage the chronic HCV infection better.
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http://dx.doi.org/10.1016/j.jhep.2017.12.019DOI Listing
May 2018

New records of sabellids and serpulids (Polychaeta: Sabellidae, Serpulidae) from the Tropical Eastern Pacific.

Zootaxa 2016 Nov 7;4184(3):zootaxa.4184.3.1. Epub 2016 Nov 7.

Laboratorio de Sistemática de Invertebrados Marinos (LABSIM), Universidad del Mar, campus Puerto Ángel, Ciudad Universitaria, Apdo. Postal 47, Puerto Ángel, Oaxaca, 70902, México..

Sabellids and serpulids are two well represented families in the polychaete fauna of the Tropical Eastern Pacific, with 31 and 34 species respectively; however, most records come from the Gulf of California or the western coast of Baja California Peninsula. Only a few records are from localities in the large expanse of the central and southern Mexican Pacific. Thus, sabellids and serpulids were collected from several shallow water habitats along the coast of Mexican Pacific, such as coastal lagoons, coral reefs, rocky shores and from man-made structures as marinas, piers and ships of several harbors; additionally, specimens from national collections were revised. More than 8,400 specimens of sabellids and serpulids from the states of Baja California, Baja California Sur, Sonora, Sinaloa, Michoacán, Guerrero, Oaxaca and Chiapas, and some specimens from Panamá and Perú were examined. In the present work we record new localities of four sabellids and 24 serpulids. One sabellid, Branchiomma bairdi, is an exotic/invasive species in Oaxaca, Sinaloa and Baja California Sur, while four species of serpulids are exotic and/or cryptogenic species: Ficopomatus uschakovi, Hydroides dirampha, H. elegans and H. sanctaecrucis. Additionally, the geographical range has been extended for five species: the sabellids Pseudobranchiomma punctata from Oahu, Hawaii to La Paz Bay, and Parasabella pallida from California to Puerto Escondido, Baja California Sur; and for three serpulids, Hydroides inermis from the Galápagos Islands to Agua Blanca, Oaxaca, H. gairacensis from Panamá to Puerto Ángel, Oaxaca, and H. panamensis from Panamá to Huatulco, Oaxaca and Faro de Bucerías, Michoacán. Hydroides cf. amri, previously recorded as H. brachyacantha from Oahu, Hawaii, is more similar to H. amri from Australia. The number of sabellids recorded for the Tropical Eastern Pacific increased to 33, the serpulid species to 35.
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http://dx.doi.org/10.11646/zootaxa.4184.3.1DOI Listing
November 2016

Effectiveness and safety of first-generation protease inhibitors in clinical practice: Hepatitis C virus patients with advanced fibrosis.

World J Gastroenterol 2015 Aug;21(30):9163-74

Javier Salmerón, Carmen Vinaixa, Juan Manuel Pascasio, Manuel Romero-Gómez, José Antonio Pons, Francisco Jorquera, Ana Gila, Paloma Muñoz de Rueda, Rosa Quiles, CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain.

Aim: To evaluates the effectiveness and safety of the first generation, NS3/4A protease inhibitors (PIs) in clinical practice against chronic C virus, especially in patients with advanced fibrosis.

Methods: Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1, treatment-naïve (TN) or treatment-experienced (TE), who underwent triple therapy with the first generation NS3/4A protease inhibitors, boceprevir (BOC) and telaprevir (TVR), in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up.

Results: One thousand and fifty seven patients were included, 405 (38%) were treated with BOC and 652 (62%) with TVR. Of this total, 30% (n = 319) were TN and the remaining were TE: 28% (n = 298) relapsers, 12% (n = 123) partial responders (PR), 25% (n = 260) null-responders (NR) and for 5% (n = 57) with prior response unknown. The rate of sustained virologic response (SVR) by intention-to-treatment (ITT) was greater in those treated with TVR (65%) than in those treated with BOC (52%) (P < 0.0001), whereas by modified intention-to-treatment (mITT) no were found significant differences. By degree of fibrosis, 56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients, both TN and TE. In the analysis by groups, the TN patients treated with TVR by ITT showed a higher SVR (P = 0.005). However, by mITT there were no significant differences between BOC and TVR. In the multivariate analysis by mITT, the significant SVR factors were relapsers, IL28B CC and non-F4; the type of treatment (BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients, treated with BOC (46%) or with TVR (45%). 28% of the patients interrupted the treatment, mainly by non-viral response (51%): this outcome was more frequent in the TE than in the TN patients (57% vs 40%, P = 0.01). With respect to severe haematological disorders, neutropaenia was more likely to affect the patients treated with BOC (33% vs 20%, P ≤ 0.0001), and thrombocytopaenia and anaemia, the F4 patients (P = 0.000, P = 0.025, respectively).

Conclusion: In a real clinical practice setting with a high proportion of patients with advanced fibrosis, effectiveness of first-generation PIs was high except for NR patients, with similar SVR rates being achieved by BOC and TVR.
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http://dx.doi.org/10.3748/wjg.v21.i30.9163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533049PMC
August 2015

Profiles and clinical management of hepatitis C patients in Spain: disHCovery study.

Rev Esp Quimioter 2015 Jun;28(3):145-53

Maria Buti, Internal Medicine and Hepatology, Hospital Vall d´Hebron and Ciberehd del Institut Carlos III, Passeig de la Vall d´Hebron 119, Barcelona, 08035 Spain.

Introduction: To assess the clinical profile and management of patients with hepatitis C (HCV) infection in an observational study in Spanish hospitals.

Methods: The study included an initial cross-sectional phase (study phase I), in which investigators at 48 hospitals from 14 Spanish regions collected data from approximately 20 consecutive patients each (a total of 1,000 patients) to assess the general features of HCV-infected patients of any genotype. During the second phase (study phase II), data from 878 patients that were infected exclusively with genotype 1 HCV were assessed retrospectively. Eight pre-defined clinical profiles were established, in order to assess clinical and previous treatments characteristics.

Results: Among the HCV-infected individuals that were analysed during the first part, HCV genotype 1 was found to be predominant (with a prevalence of 76.6%), prevailing the subtype 1b (69.8%), with other significant groups infected by genotype 3 (12.3%) and 4 (7.4%). In the second part of the study, 44% of the HCV genotype 1-infected patients were at a F3/F4 fibrosis stage. 15.9% had never been treated, and previously unsuccessfully treated patients that were no longer receiving anti-HCV treatment accounted for 50.8% of cases. Individuals with a sustained virologic response (SVR) to previous dual therapies (based on Interferon and Ribavirin) were only 14.5% and patients under treatment during the study accounted for the remaining 18.8%. A total of 713 patients (81.2%) in the second phase were not receiving any type of therapy over the period analysed, mainly due to the anticipation of new anti-HCV drugs (41.8%), SVR achievement (17.8%) and unresponsiveness to therapies available at the time of the study (9.5%).

Conclusions: HCV genotype 1, predominately 1b, is the most prevalent type in Spain. Advanced fibrosis or cirrhosis is frequent in this group, mainly patients not yet cured.
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June 2015

[The value of genetics in the era of hepatitis C triple therapy].

Gastroenterol Hepatol 2014 Aug-Sep;37(7):427-37. Epub 2014 Jun 16.

CIBERehd, Instituto de Salud Carlos III, Madrid, España; UGC de Aparato Digestivo, Hospital Universitario San Cecilio, Granada, España. Electronic address:

Despite the introduction of protease inhibitors (PI) in the treatment of hepatitis C, the sensitivity of interferon continues to be essential to achieve a sustained virological response (SVR) and to eradicate the viral infection. Currently, pegylated interferon (PEG-IFN) and ribavirin (RBV) are required to avoid selection of PI-resistance mutations. The likelihood of obtaining an SVR with dual therapy in treatment-naïve patients with genotype 1 infection varies from 40% to 50%. That is, almost half of these patients would not require a PI, thus avoiding their adverse effects and considerably reducing the cost of the treatment. Identifying which patients could potentially respond to dual therapy is one of the main challenges in clinical practice. The genetic variability of the host is one of the main factors affecting the sensitivity of PEG-IFN and therefore in the response to current treatment. Other baseline factors related to the host, the virus and, especially, to intratreatment factors such as rapid virological response (RVR) are strongly associated with the probability of achieving an SVR. The evidence on the decision to prescribe dual or triple therapy according to the factors predictive of response is based on retrospective studies or post-hoc analyses of pivotal studies on PI. Study of the polymorphisms of the IFNL3 gene (IL28B), ITPA, IFN-stimulated genes (ISGs), TT/ΔG (ss469415590; IFNL4)) and RBV transporters could help in the decision to prescribe dual or triple therapy in treatment naïve patients.
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http://dx.doi.org/10.1016/j.gastrohep.2014.04.004DOI Listing
June 2016

Effect of sustained virological response to treatment on the incidence of abnormal glucose values in chronic hepatitis C.

J Hepatol 2008 May 15;48(5):721-7. Epub 2008 Jan 15.

Unit for the Clinical Management of Digestive Diseases and CIBEREHD, Hospital Universitario de Valme, Seville, Spain.

Background/aims: To investigate the effect of sustained virological response (SVR) on impaired fasting glucose (IFG) and/or type 2 diabetes (T2DM); to assess the influence of glucose abnormalities on the SVR rate.

Methods: 1059 patients with chronic HCV; normal glucose (< 100 mg/dl) in 734, IFG (between 100 and 125 mg/dl) in 218, and T2DM (126 mg/dl) in 107 cases, were treated with interferon plus ribavirin over 24 or 48 weeks, depending on viral genotype.

Results: The SVR rate was lower in patients with IFG and/or T2DM than in patients with normal glucose concentrations [143/325 (44%) vs. 432/734 (58.8%); P=0.002]. In the follow-up, abnormal glucose concentrations were observed in 74 of 304 (24.3%) non-responders and in 49 of 430 (11.4%) sustained responders (log-rank: 13.8; P=0.00002). Reverse stepwise logistic regression analysis identified the independent variables predictive of IFG or T2DM development as: sustained response (OR: 0.44; 95%CI=0.20-0.97; P=0.004) and fibrosis stage (OR: 1.46; 95%CI=1.06-2.01;P=0.02). Family history of DM, steatosis, gender, HCV viral load, genotype, triglycerides, cholesterol and BMI did not enter the multivariate analysis equation.

Conclusions: SVR reduces the risk of IFG and/or T2DM development in patients with chronic hepatitis C while altered glucose metabolism impairs sustained response to viral treatment.
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http://dx.doi.org/10.1016/j.jhep.2007.11.022DOI Listing
May 2008

HLA-C and KIR genes in hepatitis C virus infection.

Hum Immunol 2005 Nov 9;66(11):1106-9. Epub 2006 Mar 9.

Servicio de Inmunología, Hospital Universitario Virgen del Rocío, Sevilla, Spain.

Natural killer (NK) cells are key components of the innate antiviral immune response. NK cell function is regulated by the interaction of major histocompatibility complex class I molecules with NK inhibitory receptors. The aim of this study was to investigate the role of the HLA-C/KIR pair in hepatitis C virus clearance in our population. A total of 196 hepatitis C virus-infected patients (65 resolved and 131 with persistent infection) were included in the study. Genotyping of HLA-C was carried out using polymerase chain reaction followed by a reverse sequence-specific oligonucleotide probe detection system. NK receptor-specific polymerase chain reaction typing of KIR2DL1, KIR2DL2, and KIR2DL3 was performed on the same patient group. Frequencies of the KIR2DL2 gene and the KIR2DL2/KIR2DL2 genotype were lower among patients with persistent infection (32.3% vs 45.4% among resolved, P = 0.01, OR = 0.57, 95% CI = 0.36-0.91; and 16.2% vs 32.3% among resolved, P = 0.02, OR = 0.41, 95% CI = 0.19-0.87). Nevertheless, the frequency of the KIR2DL3 gene was higher among patients with persistent infection (66.9% vs 54.6% among resolved P = 0.02, OR = 1.68, 95% CI = 1.07-2.65). Trends toward lower frequencies of the HLA-C2C2 genotype and NK-HLA interactions with strong and moderate affinity among the patients with persistent infection were also observed.
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http://dx.doi.org/10.1016/j.humimm.2006.02.001DOI Listing
November 2005

Biliary tract disease: a rare manifestation of eosinophilic gastroenteritis.

Dig Dis Sci 2003 Mar;48(3):624-7

Division of Gastroenterology, Department of Pathology, Hospital Virgen Macarena, Seville, Spain.

Eosinophilic gastroenteritis (EGE) is a rare inflammatory disease characterized by diffuse or scattered eosinophilic infiltration of the digestive tract and usually by peripheral blood eosinophilia. The most common presenting symptoms of EGE are abdominal pain, vomiting and diarrhea, but clinical features depend on which layers or location of gastrointestinal tract are involved. Treatment with corticosteroids results in clinical and histological remission in most patients and surgery can be avoided if a correct diagnosis is made. Previous history of allergy is a key to diagnosing EGE, but peripheral eosinophilia may be absent in some patients under concomitant treatment with corticosteroids. Radiological and endoscopic findings are also nonspecific and diagnosis must always be histologically confirmed. The gastrointestinal involvement is patchy in distribution, so more than one panendoscopic examination is often necessary to establish the diagnosis, and surgical or CT-guided full-thickness biopsy is needed in patients with muscular or serosal involvement. It emphasises the importance of a high index of clinical suspicion, which mainly depends on knowledge of natural history of the disease. We report here a case of EGE associated with transmural eosinophilic cholecystocholangitis, in a patient who presented with dyspeptic symptoms and recurrent cholestasis responsive to corticoesteroids. To our knowledge, this patient represents the second case, in the English literature, in which corticoid-responsive cholangitis was associated to histologically proven eosinophilic cholecystitis and gastrointestinal involvement, suggesting that EGE must always be considered in the differential diagnosis of biliary tract disease in patients with eosinophilia and/or atopic diseases.
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http://dx.doi.org/10.1023/a:1022521707420DOI Listing
March 2003
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