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Article: Predictive models for hepatocellular carcinoma development after sustained virological response in advanced hepatitis C.

Fraile-López, Miguel / Alvarez-Navascués, Carmen / González-Diéguez, María Luisa / Cadahía, Valle / Chiminazzo, Valentina / Castaño, Andrés / Varela, María / Rodríguez, Manuel

Gastroenterologia y hepatologia

2023 Volume 46, Issue 10, Page(s) 754–763

Abstract: ... sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification ...

Abstract	Background & aims: Life-long hepatocellular carcinoma (HCC) surveillance is recommended after sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification of patients who could be safely discontinued for surveillance is essential, we aimed to identify subsets of patients with low-risk HCC. Methods: 491 patients with advanced and compensated fibrosis (≥F3) were prospectively followed after achieving SVR with interferon-free therapies. Clinical-biological parameters and liver stiffness measurement (LSM) were performed before starting treatment (ST) and at SVR, and HCC surveillance was carried out. Results: During a median follow-up of 49.8 months, 29 (5.9%) patients developed HCC [incidence rate: 1.6/100 patient-years (PYs)]. Two predictive models based on LSM (Model-A) or FIB-4 score (Model-B) were proposed. Only SVR parameters were included in the models, because they showed a higher accuracy for predicting HCC than ST measurements. Variables independently associated with HCC were LSM (HR, 1.03; 95% CI, 1.01-1.05), age (HR, 1.04; 95% CI, 1.01-1.08) and albumin levels (HR, 0.90; 95% CI, 0.84-0.97) in Model-A, and FIB-4 (HR, 1.22; 95% CI, 1.08-1.37) and albumin (HR, 0.90; 95% CI, 0.84-0.97) in model-B. Both models allow HCC risk stratification, identifying low-risk groups with an HCC incidence rate of 0.16/100 and 0.25/100 PYs, respectively. An overall increased hazard of HCC was observed over time. Conclusion: Simple models based on non-invasive markers of liver fibrosis, LSM or FIB-4, together with age and albumin levels at SVR permit to identify subsets of patients with HCC risk clearly <1%/year, for whom HCC surveillance might not be cost-effective.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/epidemiology ; Carcinoma, Hepatocellular/etiology ; Liver Neoplasms/epidemiology ; Liver Neoplasms/etiology ; Liver Neoplasms/drug therapy ; Risk Factors ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/epidemiology ; Antiviral Agents/therapeutic use ; Hepatitis C/drug therapy ; Liver Cirrhosis/complications ; Hepacivirus ; Albumins/therapeutic use
Chemical Substances	Antiviral Agents ; Albumins
Language	Spanish
Publishing date	2023-01-27
Publishing country	Spain
Document type	Journal Article
ZDB-ID	632502-6
ISSN	0210-5705
ISSN	0210-5705
DOI	10.1016/j.gastrohep.2023.01.008
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Article ; Online: End-to-End Automated Synthesis of C(sp

Abdiaj, Irini / Cañellas, Santiago / Dieguez, Alejandro / Linares, Maria Lourdes / Pijper, Brenda / Fontana, Alberto / Rodriguez, Raquel / Trabanco, Andres / Palao, Eduardo / Alcázar, Jesus

Journal of medicinal chemistry

2022 Volume 66, Issue 1, Page(s) 716–732

Abstract: Herein, we report an end-to-end process including synthesis, work-up, purification, and post-purification with minimal human intervention using Negishi coupling as a key transformation to increase ... ...

Abstract	Herein, we report an end-to-end process including synthesis, work-up, purification, and post-purification with minimal human intervention using Negishi coupling as a key transformation to increase Fsp
MeSH term(s)	Humans ; Chromatography, High Pressure Liquid ; Indicators and Reagents
Chemical Substances	Indicators and Reagents
Language	English
Publishing date	2022-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.2c01646
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Article ; Online: HCV eradication in recurrent hepatitis C after liver transplantation normalizes enhanced endothelial activation.

Caballero-Marcos, Aránzazu / Romero-Cristóbal, Mario / Puerto, Marta / Fernández-Yunquera, Ainhoa / Dieguez, Lucia / Navarrete, Cristina / Clemente, Ana / Diaz-Fontenla, Fernando / Catalán, Pilar / Rincón, Diego / López-Baena, José-Ángel / Bañares Cañizares, Rafael / Salcedo, Magdalena

Transplant international : official journal of the European Society for Organ Transplantation

2021 Volume 34, Issue 11, Page(s) 2214–2225

Abstract: The increased risk of cardiovascular disease (CVD) conferred by hepatitis C virus (HCV) is ...

Abstract	The increased risk of cardiovascular disease (CVD) conferred by hepatitis C virus (HCV) is especially relevant after liver transplantation (LT), but its mechanism is still not well defined. This study aimed to evaluate the influence of HCV eradication in inflammatory and endothelial activation markers after LT. We evaluated inflammatory (TNF-alfa, IL-6, IL-8, and MCP-1) and endothelial activation (E-selectin, ICAM-1, VCAM-1, and MMP-9) markers before and after eradication in 45 LT recipients with HCV infection (LT+/HCV+) and 44 non-transplanted HCV-infected patients (LT-/HCV+). We also considered an additional group of 40 LT recipients without HCV infection (LT+/HCV-). LT+/HCV+ patients presented a higher endothelial activation status before eradication compared with LT+/HCV- patients. However, levels of E-selectin, ICAM-1, VCAM-1, and MMP-9 were comparable between LT+/HCV+ and LT-/HCV+ patients before eradication. HCV eradication decreased ICAM-1 (5466.55 pg/ml vs. 3354.88 pg/ml, P < 0.001) and VCAM-1 (10456.52 pg/ml vs. 6658.85 pg/ml, P < 0.001) levels in LT+/HCV+ and LT-/HCV+ patients. Remarkably, HCV eradication restored levels of endothelial activation markers of LT+/HCV+ patients compared with that of LT+/HCV- patients. HCV plays a major role in endothelial dysfunction after LT. Furthermore, HCV eradication restores endothelial activation despite the exposure to immunosuppressive therapy.
MeSH term(s)	Antiviral Agents/therapeutic use ; Hepacivirus ; Hepatitis C/complications ; Hepatitis C/drug therapy ; Hepatitis C, Chronic/drug therapy ; Humans ; Liver Transplantation
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2021-09-14
Publishing country	England
Document type	Journal Article
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.1111/tri.14000
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Article ; Online: Catalytic undirected borylation of tertiary C-H bonds in bicyclo[1.1.1]pentanes and bicyclo[2.1.1]hexanes.

Yu, Isaac F / Manske, Jenna L / Diéguez-Vázquez, Alejandro / Misale, Antonio / Pashenko, Alexander E / Mykhailiuk, Pavel K / Ryabukhin, Sergey V / Volochnyuk, Dmitriy M / Hartwig, John F

Nature chemistry

2023 Volume 15, Issue 5, Page(s) 685–693

Abstract: Catalytic borylations of ... ...

Abstract	Catalytic borylations of sp
Language	English
Publishing date	2023-03-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2464596-5
ISSN	1755-4349 ; 1755-4330
ISSN (online)	1755-4349
ISSN	1755-4330
DOI	10.1038/s41557-023-01159-4
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Article: Diabetes is not associated with an increased risk of hepatocellular carcinoma in patients with alcoholic or hepatitis C virus cirrhosis.

Rodríguez-Escaja, Carlos / Á Navascués, Carmen / González-Diéguez, Luisa / Cadahía, Valle / Varela, María / de Jorge, Miguel Ángel / Castaño-García, Andrés / Rodríguez, Manuel

Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva

2020 Volume 113, Issue 7, Page(s) 505–511

Abstract: ... on the risk of developing HCC in patients with alcohol- and hepatitis C virus (HCV)-related cirrhosis ...

Abstract	Background and aims: diabetes has been reported as a risk factor for hepatocellular carcinoma (HCC) in population-based studies but there are controversial data in patients with cirrhosis. Metformin could have a protective role in HCC development. The aim of this study was to determine the influence of diabetes on the risk of developing HCC in patients with alcohol- and hepatitis C virus (HCV)-related cirrhosis. Methods: a cohort of 982 Caucasian patients were analyzed with alcoholic or HCV cirrhosis, included from 1992 to 2014 in a HCC surveillance program and prospectively followed. The influence of diabetes on the development of HCC was analyzed by Kaplan Meier analysis and adjusted with a Cox regression for relevant co-factors. Results: after a median follow-up of 49.5 (24.0-96.0) months, 156 patients (15.8 %) developed HCC. There were no differences in the cumulative incidences of HCC after 20 years between diabetic and non-diabetic patients in the global (53.5 % vs 45.4 %; p = 0.26), alcoholic (50.4 % vs 45.4 %; p = 0.21) or HCV (60 % vs 43.1 %; p = 0.57) cirrhosis series. Diabetes did not constitute a risk factor after adjusting for other potential co-factors, neither in the whole series (hazard ratio [HR]: 1.12, 95 % CI: 0.78-1.51; p = 0.26), alcoholic (HR: 1.160, 95 % CI: 0.74-1.82; p = 0.50) or HCV cirrhosis cohort (HR: 1.17, 95 % CI: 0.63-2.19; p = 0.60). These figures did not change after excluding patients treated with metformin. Conclusions: in Caucasian patients with alcoholic or HCV cirrhosis, diabetes is not a risk factor for developing HCC. This lack of an association does not seem to be a consequence of the protective effect of metformin.
MeSH term(s)	Carcinoma, Hepatocellular/epidemiology ; Carcinoma, Hepatocellular/etiology ; Diabetes Mellitus ; Hepacivirus ; Hepatitis C/complications ; Hepatitis C/epidemiology ; Humans ; Liver Cirrhosis/complications ; Liver Cirrhosis/epidemiology ; Liver Cirrhosis, Alcoholic/complications ; Liver Cirrhosis, Alcoholic/epidemiology ; Liver Neoplasms/epidemiology ; Liver Neoplasms/etiology ; Risk Factors
Language	English
Publishing date	2020-11-26
Publishing country	Spain
Document type	Journal Article
ZDB-ID	1070381-0
ISSN	1130-0108 ; 0212-7512
ISSN	1130-0108 ; 0212-7512
DOI	10.17235/reed.2020.6953/2020
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Article: Changes in the characteristics of hospital admissions due to decompensated cirrhosis in the era of direct-acting antivirals against hepatitis C virus.

Fraile López, Miguel / Franco, Lissa / Álvarez Navascués, Carmen / Varela, María / Cadahía, Valle / Torner, María / Gómez Outomuro, Ana / González-Diéguez, María Luisa / Rodríguez García, Manuel

Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva

2020 Volume 112, Issue 7, Page(s) 538–544

Abstract: ... has revolutionized the treatment of hepatitis C virus (HCV) infection.: Aims: to determine if there ...

Abstract	Background: the development of interferon-free regimens, based on direct acting antivirals (DAAs) has revolutionized the treatment of hepatitis C virus (HCV) infection. Aims: to determine if there have been changes in the characteristics of hospital admissions due to decompensated cirrhosis in a general hospital since the introduction of DAAs. Patients and methods: this was a prospective study of all hospital admissions due to decompensated cirrhosis during two periods: October 2012-October 2014 (P-I) and July 2016-July 2018 (P-II). Clinical and demographic variables were collected and standard statistical methods were used for the analysis. Results: there were 746 hospital admissions; 347 in P-I and 399 in P-II. P-I patients were younger (59 vs 63 years; p = 0.034), while the proportion of admissions due to HCV-cirrhosis was lower in P-II (15.8 % vs 21.6 %; p = 0.041). There were no significant differences in the proportion of admissions due to other etiologies of cirrhosis between both periods. Patients in the P-II group presented an active viral infection (57.1 vs 97.3 %; p = 0.001) less frequently and had a higher rate of excessive alcohol consumption (55.5 vs 30.7 %; p = 0.003) when admitted, while HIV co-infection was less frequent (1.6 % vs 10.7 %; p = 0.039). Conclusion: the proportion of admissions due to decompensated HCV-related cirrhosis has decreased by almost 30 % since the introduction of the DAA. In addition, the characteristics of patients admitted have changed since the application of interferon-free regimens.
MeSH term(s)	Antiviral Agents/therapeutic use ; Hepacivirus ; Hepatitis C/complications ; Hepatitis C/drug therapy ; Hepatitis C/epidemiology ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/epidemiology ; Hospitals ; Humans ; Liver Cirrhosis/drug therapy ; Liver Cirrhosis/epidemiology ; Prospective Studies
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2020-06-03
Publishing country	Spain
Document type	Journal Article
ZDB-ID	1070381-0
ISSN	1130-0108 ; 0212-7512
ISSN	1130-0108 ; 0212-7512
DOI	10.17235/reed.2020.7024/2020
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Article: Newly Diagnosed Hepatitis C in the US Commercially Insured Population Before and After the 2012 Implementation of Expanded Screening Guidelines.

Pyenson, Bruce S / Dieguez, Gabriela / Ferro, Christine / Mavinkurve, Maushumi / Gonzalez, Yuri Sanchez

American health & drug benefits

2018 Volume 11, Issue 1, Page(s) 30–37

Abstract: ... chronic hepatitis C virus (HCV) infection, including many undiagnosed individuals. In 2012, the Centers ...

Abstract	Background: In the United States in 2014, more than 3 million individuals were estimated to have chronic hepatitis C virus (HCV) infection, including many undiagnosed individuals. In 2012, the Centers for Disease Control and Prevention expanded its HCV testing recommendations to target all adults born between 1945 and 1965, in addition to at-risk individuals, which has led to an increase in newly diagnosed patients. Few studies have explored the medical cost or clinical status of patients who are newly diagnosed with HCV. Objective: To compare the demographics, comorbidities, and medical costs of patients who are newly diagnosed and those who were previously diagnosed with HCV infection. Method: We conducted a retrospective study using 2013 claims data from the Truven Health MarketScan Commercial database to compare patients newly diagnosed with HCV infection in 2013 and patients who were diagnosed before 2013. The patients were divided into 2 cohorts based on the time of diagnosis before and after 2013. All patients were classified by disease stage and by comorbidities, and were required to have continuous health plan enrollment between January 2010 and December 2013. The full-year costs were tabulated for every patient, regardless of the date of diagnosis. Results: Of the 9193 patients with an HCV diagnosis in 2013 in the database, approximately 26% (N = 2428) were newly diagnosed in 2013, of whom 12% (N = 299) had advanced-stage HCV. The average age of the newly diagnosed patients was 49.5 years versus 54.1 years for previously diagnosed patients. Patients who were previously diagnosed had a higher prevalence of HIV, diabetes, and more severe cancers than patients who were newly diagnosed with HCV. Patients who were newly diagnosed with HCV had a higher prevalence of acute liver failure and drug-induced psychosis. The average annual per-patient per-month (PPPM) medical costs for both groups was approximately $2200 in 2013. The annual medical cost for a patient who was newly diagnosed increased sharply in the year before diagnosis, from approximately $588 PPPM for the 3 years before the diagnosis to approximately $854 PPPM in the year before diagnosis. Conclusion: In 2013, the healthcare costs of patients who were newly diagnosed with HCV were similar in their first year of diagnosis to the costs of patients who had been diagnosed previously, although patients who were previously diagnosed had more advanced-stage disease. Patients who were newly diagnosed had 3-fold the healthcare costs in their first year of diagnosis versus the costs in the 3 years before their diagnosis.
Language	English
Publishing date	2018-04-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2853721-X
ISSN	1942-2970 ; 1942-2962
ISSN (online)	1942-2970
ISSN	1942-2962
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Article: A gliclazide complex based on palladium towards Alzheimer's disease: promising protective activity against Aβ-induced toxicity in C. elegans

García-García, Amalia / Rojas, Sara / Rivas-García, Lorenzo / Navarro-Hortal, María D. / Romero-Márquez, Jose M. / Fernández-Bolaños, José G. / Choquesillo-Lazarte, Duane / Salinas-Castillo, Alfonso / López, Óscar / Quiles, José L. / Rodríguez-Diéguez, Antonio

Chemical communications. 2022 Feb. 1, v. 58, no. 10

2022

Abstract: A new palladium coordination compound based on gliclazide with the chemical formula [Pd(glz)₂] (where glz = gliclazide) has been synthesized and characterised. The structural characterization reveals that this material consists of mononuclear units ... ...

Abstract	A new palladium coordination compound based on gliclazide with the chemical formula [Pd(glz)₂] (where glz = gliclazide) has been synthesized and characterised. The structural characterization reveals that this material consists of mononuclear units formed by a Pd²⁺ ion coordinated to two molecules of the glz ligand, in which palladium ions exhibit a distorted plane-square coordination sphere. This novel material behaves like a good and selective inhibitor of butyrylcholinesterase, one of the most relevant therapeutic targets against Alzheimer's disease. Analysis of the enzyme kinetics showed a mixed mode of inhibition, the title compound being capable of interacting with both the free enzyme and the enzyme–substrate complex. Finally, the palladium compound shows promising protective activity against Aβ-induced toxicity in the Caenorhabditis elegans model, which has never been reported.
Keywords	Alzheimer disease ; Caenorhabditis elegans ; cholinesterase ; enzyme kinetics ; enzyme substrates ; ligands ; models ; palladium ; therapeutics ; toxicity
Language	English
Dates of publication	2022-0201
Size	p. 1514-1517.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	1472881-3
ISSN	1364-548X ; 1359-7345 ; 0009-241X
ISSN (online)	1364-548X
ISSN	1359-7345 ; 0009-241X
DOI	10.1039/d1cc04404d
Database	NAL-Catalogue (AGRICOLA)

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Book ; Online: Cuerpos memorables

Perrée, Caroline / Diéguez, Ileana / Diéguez, Ileana

(Antropología y Etnología)

2018

Series title	Antropología y Etnología
Keywords	History of the Americas ; memoria ; violencia ; México ; arte ; desaparición ; ciencias sociales y humanidades
Language	0\|s
Size	1 electronic resource (243 pages)
Publisher	Centro de estudios mexicanos y centroamericanos
Publishing place	Mexico
Document type	Book ; Online
Note	Spanish ; Open Access
HBZ-ID	HT021619745
ISBN	9782111528512 ; 211152851X
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Cytomegalovirus reactivation in liver transplant recipients due to hepatitis C cirrhosis is associated with higher cardiovascular risk - an observational, retrospective study.

Aguilera, Victoria / Di Maira, Tommaso / Conde, Isabel / Fornés-Ferrer, Victoria / Vinaixa, Carmen / Pallarés, Carmen / Carvalho-Gomes, Angela / Cubells, Almudena / García, María / Rubín, Ángel / Benlloch, Salvador / Gonzalez-Dieguez, Luisa / Molina, Jose Miguel / Puchades, Lorena / López-Labrador, F Xavier / Prieto, Martin / Berenguer, Marina

Transplant international : official journal of the European Society for Organ Transplantation

2018 Volume 31, Issue 6, Page(s) 649–657

Abstract: ... Baseline variables and endpoint measures (CVE, survival, severe recurrent hepatitis C, de novo tumors, and ...

Abstract	The association between cytomegalovirus (CMV) reactivation and cardiovascular risk has been reported in solid organ transplant populations; however, it has yet to be assessed in liver transplantation (LT). We aim to evaluate whether CMV reactivation is associated with cardiovascular events (CVE) in HCV-LT patients. LT patients (2010 and 2014) due to HCV cirrhosis were included. Clinically significant CMV (CS-CMV) was defined as viral load (VL) >5000 copies/ml, need of therapy or CMV disease. Baseline variables and endpoint measures (CVE, survival, severe recurrent hepatitis C, de novo tumors, and diabetes) were collected. One hundred and forty patients were included. At LT, a history of AHT was present in 23%, diabetes 22%, tobacco use 45%, obesity 20%, and renal impairment (eGFR < 60 ml/min) in 26.5%. CS-CMV reactivation occurred in 25% of patients. Twenty-six patients (18.5%) developed a CVE. Cox regression analysis revealed two factors significantly associated with CVE: Pre-LT DM [HR = 4.6 95% CI (1.6, 13), P = 0.004] and CS-CMV [HR = 4.7 95% CI (1.8, 12.5), P = 0.002]. CS-CMV was not independently associated with the remaining endpoints except for survival (P = 0.03). In our series, CS-CMV reactivation was associated with a greater risk of developing CVE, thus confirming data from other solid organ transplant populations and emphasizing the need for adequate CMV control.
MeSH term(s)	Aged ; Cardiovascular Diseases/complications ; Cardiovascular Diseases/virology ; Cytomegalovirus ; Cytomegalovirus Infections/complications ; Female ; Glomerular Filtration Rate ; Hepatitis C/complications ; Hepatitis C/surgery ; Humans ; Immunosuppression ; Liver Cirrhosis/complications ; Liver Cirrhosis/surgery ; Liver Cirrhosis/virology ; Liver Transplantation/adverse effects ; Male ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Tissue Donors ; Viral Load
Language	English
Publishing date	2018-03-26
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.1111/tri.13145
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