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Abstract: Objectives: We sought to evaluate our transplant series in light of the parameters outlined in the quality criteria established by the Spanish Hepatic Transplant Society (Sociedad Española de Trasplante Hepático [SETH]). Methods: We retrospectively analyzed 240 hepatic transplantations performed in 223 patients from November 2001 to December 2009. Results: Among the series, 57% were in Child class C, 50% had cirrhosis without hepatocellular carcinoma, and 32% had this neoplasm. The most common cause for the illness was alcohol, followed by a virus, namely hepatitis C virus in 76% of cases. The average waiting list time was 45.14 days. The total graft ischemia averaged 460 minutes (range, 265–937). The 4.1% (n = 10), incidence of an urgent retransplantation was mainly due to primary graft failure or arterial thrombosis. During the perioperative period the mortality rate was 2.5% (n = 6) and the 1-month mortality rate was 6.6% (n = 16). The raw survival rates at 1, 3, and 5 years after the operation are 85%, 78%, and 72%, respectively. Conclusion: Our perioperative as well as the long-term results fall within the quality standards established by SETH. [Copyright &y& Elsevier]

Objectives: Limited screening and delays in diagnosis and linkage-to-care are barriers for hepatitis C virus (HCV) elimination. The LiverTAI study focused on patients tested for HCV using AI technologies to describe their demographic and clinical characteristics and pre-testing patient journeys, reflecting clinical practice in hospitals., Patients and Methods: LiverTAI is a retrospective, secondary analysis of electronic health records (EHRs) from 6 tertiary Spanish hospitals, extracting unstructured clinical data using natural language processing (NLP) EHRead® technology. Adult subjects with an HCV testing procedure from January 2014 to December 2018 were grouped according to HCV seropositivity and viremia., Results: From 2,440,358 patients, 16,261 patients were tested for HCV (13,602 [83.6%] HCV seronegative; 2659 [16.4%] seropositive). Active HCV viremia appeared in 37.7% (n=1003) of patients, 18.6% (n=494) had negative viremia, and 43.7% (n=1162) unknown viremia. Patient journeys showed core departments (Gastroenterology, Internal Medicine, and Infectious Disease) and others including Emergency perform ample HCV testing in Spanish hospitals, whereas Medical Oncology lags. Patients were PCR-tested and genotyped significantly faster in core departments (p<.001)., Conclusions: Our results highlight hospital departments responsible for HCV testing. However, further testing was sub-optimal during the study period. Therefore, we underscore the need for HCV screening and reflex testing to accelerate diagnosis and linkage-to-care., (Copyright © 2022 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Clinical management of transplant patients abruptly changed during the first months of COVID-19 pandemic (March to May 2020). The new situation led to very significant challenges, such as new forms of relationship between healthcare providers and patients and other professionals, design of protocols to prevent disease transmission and treatment of infected patients, management of waiting lists and of transplant programs during state/city lockdown, relevant reduction of medical training and educational activities, halt or delays of ongoing research, etc. The two main objectives of the current report are: 1) to promote a project of best practices in transplantation taking advantage of the knowledge and experience acquired by professionals during the evolving situation of the COVID-19 pandemic, both in performing their usual care activity, as well as in the adjustments taken to adapt to the clinical context, and 2) to create a document that collects these best practices, thus allowing the creation of a useful compendium for the exchange of knowledge between different Transplant Units. The scientific committee and expert panel finally standardized 30 best practices, including for the pretransplant period (n = 9), peritransplant period (n = 7), postransplant period (n = 8) and training and communication (n = 6). Many aspects of hospitals and units networking, telematic approaches, patient care, value-based medicine, hospitalization, and outpatient visit strategies, training for novelties and communication skills were covered. Massive vaccination has greatly improved the outcomes of the pandemic, with a decrease in severe cases requiring intensive care and a reduction in mortality. However, suboptimal responses to vaccines have been observed in transplant recipients, and health care strategic plans are necessary in these vulnerable populations. The best practices contained in this expert panel report may aid to their broader implementation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: The number of patients awaiting liver transplantation (LT) in Spain has halved from 2015 to 2019 due to the reduction of candidates with hepatitis C and the successful implementation of nonheart beating donation programs across the country. The Spanish Society for Liver Transplantation has committed to take advantage of this situation by developing consensus around potential areas to expand the current indications for LT. The consensus group was composed of 6 coordinators and 23 expert delegates, each one representing an LT institution in Spain., Methods: A modified Delphi approach was used to identify areas to expand indications for LT and to build consensus around paramount aspects, such as inclusion criteria and waitlist prioritization within each area. The scientific evidence and strength of recommendations were assessed by the "Grading of Recommendations Assessment, Development, and Evaluation" system., Results: The consensus process resulted in the identification of 7 potential areas to expand criteria in LT: recipient's age, hepatocellular carcinoma, alcoholic hepatitis, acute-on-chronic liver failure, hilar and intrahepatic cholangiocarcinoma, and unresectable liver metastases of colorectal cancer., Conclusions: We present the main recommendations issued for each topic, together with their core supporting evidence. These recommendations may allow for expanding criteria for LT homogenously in Spain and may provide a guidance to other countries/institutions facing a similar scenario., Competing Interests: The authors of the present manuscript have no conflict of interest to disclose as described by the Transplantation Journal., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cirrhosis as a result of alcohol-related liver disease is one of the most common indications for liver transplantation (LT) in Spain. Patients presenting for LT should be checked for alcohol abuse in clinical interviews and use of laboratory tests to confirm abstinence. The ethyl-glucuronide (EtG) test is very sensitive and can be positive in urine up to 5 days after consumption. Our main objective is to know the rate of alcohol abstinence by using the urine EtG test in patients evaluated for LT and to assess its correlation with the clinical interviews and laboratory test., Methods: We conducted a prospective analysis of the results of the EtG in urine of patients evaluated for LT from January 2017 to March 2019 and its correlation with the medical and psychiatric interviews and with the laboratory test., Results: We included 160 patients who were referred to LT evaluation. Among all cases, 84.1% were men, with an average age of 57.8 years. Alcohol-related liver disease was the most frequent cause (64.1%). Urine-EtG was positive in 10 patients (6.2%), 9 of them in patients with ALD and 1 in a patient with hepatitis C virus. The alcohol consumption was recognized by 80% of the patients in the clinical interview. Cases with positive EtG had higher levels of analytical parameters than those with a negative test., Conclusions: In our series, 6.2% of patients referred for LT evaluation had recently consumed alcohol. The determination of EtG in urine is probably an effective and objective technique in the detection of alcohol consumption to ensure abstinence in the LT candidates., (Copyright © 2020. Published by Elsevier Inc.)

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of "extra-target" RAS suggests the need for RAS screening in all three DAA target regions., Competing Interests: Declaration of competing interest We declare that no public or private company has had any role in the study design, data collection, experimental work, data analysis, decision to publish, or preparation of the manuscript. Roche Diagnostics S.L. provided support in the form of a salary for one of the authors [Josep Gregori], but the company did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No other Competing Interests to declare. Thus, our adherence to Antiviral Research policies on sharing data and materials is not altered., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: We describe the effectiveness and safety of the interferon-free regimen ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin (OBV/PTV/r ± DSV ± RBV) in a nationwide representative sample of the hepatitis C virus (HCV) monoinfected and human immunodeficiency virus-1/hepatitis C virus (HIV/HCV) coinfected population in Spain., Material and Methods: Data were collected from patients infected with HCV genotypes 1 or 4, with or without HIV-1 coinfection, treated with OBV/PTV/r ± DSV ± RBV at 61 Spanish sites within the initial implementation year of the first government-driven "National HCV plan." Effectiveness was assessed by sustained virologic response at post-treatment week 12 (SVR12) and compared between monoinfected and coinfected patients using a non-inferiority margin of 5% and a 90% confidence interval (CI). Sociodemographic and clinical characteristics or patients and adverse events (AEs) were also recorded., Results: Overall, 2,408 patients were included in the intention-to-treat analysis: 386 (16%) were patients with HIV/HCV. Patient selection reflected the real distribution of patients treated in each participating region in Spain. From the total population, 96.6% (95% CI, 95.8-97.3%) achieved SVR12. Noninferiority of SVR12 in coinfected patients was met, with a difference between monoinfected and coinfected patients of -2.2% (90% CI, -4.5% - 0.2%). Only genotype 4 was associated with non-response to OBV/PTV/r ± DSV ± RBV treatment (p<0.001) in the multivariate analysis. Overall, 286 patients (11.9%) presented AEs potentially related to OBV/PTV/r ± DSV, whereas 347 (29.0%) presented AEs potentially related to ribavirin and 61 (5.1%) interrupted ribavirin., Conclusions: Our results confirm that OBV/PTV/r ± DSV ± RBV is effective and generally well tolerated in a representative sample of the HCV monoinfected and HCV/HIV coinfected population in Spain within the experience of a national strategic plan to tackle HCV., Competing Interests: José Manuel Sousa has received fees as speaker from AbbVie, MSD and Gilead. Mercedes Vergara has received fees as an advisory board member from Gilead and has given lectures for AbbVie, Intercept, MSD, Janssen-Cilag and Gilead. Federico Pulido has received fees as speaker and advisor from AbbVie, Gilead, Janssen and MSD. Gloria Sánchez-Antolín has acted as speaker for AbbVie, MSD, Gilead Science, Novartis and Astellas. Diego Rincón has given lectures for AbbVie and MSD. Javier Salmerón has received speaker fees and grant funding from AbbVie; he declares no further conflict of interest. Luisa García-Buey has received speaker fees and travel grants from Abbvie, MSD and Gilead. José A. Carrión has received speaker fees from Abbvie, Gilead and MSD and has received fees as Advisor for AbbVie. Manuel Hernández-Guerra has been a consultant to Gilead Sciences, Intercept Pharmaceuticals, Abbvie and Bayer; he has received grant funding from Gilead Sciences and Abbvie. Nuria Espinosa has participated in Clinical Trials managed by Gilead and ViiV Healthcare; she has received advisory board, conference and course fees as well as expenses for attending congresses from Janssen-Cilag, Gilead Sciences, ViiV Healthcare, MSD and Abbvie. Rosa Mª Morillas has acted as a speaker for Gilead, Merck, AbbVie and Intercept, and has participated in advisory boards for AbbVie, Gilead and Intercept. Raul J. Andrade: Advisor/Speaker Bureau: Abbvie, Gilead Sciences, Merck Sharp and Dohme, Bristol-Myers Squibb, Janssen; Research Grants: Willmar Schwabe GmbH & Co, Gedeon Richter/Preglem S.A. Manuel Delgado has received scientific advisor fees from Abbie, Gilead, MSD. José M Moreno-Planas has received speaker fees from AbbVie, MSD, Gilead and Bayer. Fernando Menéndez has received fees as advisor from Bayer. Luis Morano has acted as speaker, advisor and/or investigator for Abbvie, Gilead Sciences, Merck Sharp and Dohme, Bristol-Myers Squibb, Janssen, Boehringer Ingelheim, Novartis, and Roche Farma. Manuel Rodríguez consults for and is on the speaker’s bureau for Gilead and AbbVie. Sara Lorente has received lecture fees from Abbvie, Gilead Sciences and MSD. Miguel Ángel Von-Wichmann has received fees as speaker and advisor from Abbvie, BMS, Gilead, Janssen, MSD and VIIV. Amanda Manzanares is employee of AbbVie and may hold stock or options. Lander Hijona, Fernando Carnicer, Beatriz Mateos-Muñoz, Antoni Jou, Benjamín Polo-Lorduy, Ángel Rubín, Ana Escarda, Patricia Aguilar, Teresa Aldámiz-Echevarría, Sonia Chimeno-Hernández, Adolfo Gallego, Marta Magaz, Ángel Estébanez, Mikel Rico, Blanca Sampedro, Sonia Izquierdo, José Manuel Zozaya, Senador Morán-Sánchez, Ignacio Martín-Granizo, Marcial Delgado declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The Spanish Association for the Study of the Liver (AEEH) is convinced that the elimination of hepatitis C virus (HCV) in Spain is possible as long as we are able to use the resources and tools necessary for it. This document reflects the position of the AEEH regarding the elimination of HCV, establishing a wide range of recommendations that can be grouped into five categories: 1) Screening of HCV according to age, of the existence of classic acquisition risk factors of infection, active search of previously diagnosed patients and development of microelimination strategies in vulnerable populations; 2) Simplification of HCV diagnosis (one-step diagnosis and diagnosis at the point of patient care); 3) Simplification of patient treatment and improvement of care circuits; 4) Health policy measures, and, finally, 5) Establishment of HCV elimination indicators.

Introduction: The socioeconomic burden of irritable bowel syndrome with constipation (IBS-C) has never been formally assessed in Spain., Patients and Methods: This 12-month (6-month retrospective and prospective periods) observational, multicentre study assessed the burden of moderate-to-severe IBS-C in Spain. Patients were included if they had been diagnosed with IBS-C (Rome III criteria) within the last 5 years and had moderate-to-severe IBS-C (IBS Symptom Severity Scale score [IBS-SSS] ≥175) at inclusion. The primary objective was to assess the direct cost to the Spanish healthcare system (HS)., Results: A total of 112 patients were included, 64 (57%) of which had severe IBS-C at inclusion. At baseline, 89 (80%) patients reported abdominal pain and distention. Patient quality of life (QoL), measured by the IBS-C QoL and EQ-5D instruments, was found to be impaired with a mean score of 59 and 57 (0-100, worst-best), respectively. Over the 6-month prospective period the mean IBS-C severity, measured using the IBS-SSS showed some improvement (315-234 [0-500, best-worst]). During the year, 89 (80%) patients used prescription drugs for IBS-C, with laxatives being the most frequently prescribed (n=70; 63%). The direct cost to the HS was €1067, and to the patient was €568 per year. The total direct cost for moderate-to-severe IBS-C was €1635., Discussion: The majority of patients reported continuous IBS-C symptoms despite that 80% were taking medication to treat their IBS-C. Overall healthcare resource use and direct costs were asymmetric, with a small group of patients consuming the majority of resources., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Direct-acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in the recurrence of hepatitis C virus (HCV) infection after liver transplant (LT). However, its effect on the severe recurrence and the risk of death remains controversial. We evaluated the efficacy, predictors of survival, and safety of DAC-based regimens in a large real-world cohort. A total of 331 patients received DCV-based therapy. Duration of therapy and ribavirin use were at the investigator's discretion. The primary end point was sustained virological response (SVR) at week 12. A multivariate analysis of predictive factors of mortality was performed. Intention-to-treat (ITT) and per-protocol SVR were 93.05% and 96.9%. ITT-SVR was lower in cirrhosis (n = 163) (96.4% vs. 89.6% P = 0.017); the SVR in genotype 3 (n = 91) was similar, even in advanced fibrosis (96.7% vs. 88%, P = 0.2). Ten patients (3%) experienced virological failure. Therapy was stopped in 18 patients (5.44%), and ten died during treatment. A total of 22 patients (6.6%) died. Albumin (HR = 0.376; 95% CI 0.155-0.910) and baseline MELD (HR = 1.137; 95% CI: 1.061-1.218) were predictors of death. DCV-based DAA treatment is efficacious and safe in patients with HCV infection after LT. Baseline MELD score and serum albumin are predictors of survival irrespective of viral response., (© 2017 Steunstichting ESOT.)

Background and Rational: Telaprevir-based therapy (TBT) has been extensively evaluated in clinical trials. So we designed a study to compare the efficacy and safety of TBT between patients with moderate fibrosis and those suffering from advanced fibrosis in clinical practice. A multicenter observational and ambispective study was conducted. It included 582 patients with chronic hepatitis C genotype 1, 214 with fibrosis F2, and 368 with F3/F4 (F3: 148; F4: 220)., Results: The mean patient age was 55 years, 67% male. Type of prior response was 22% naïve, 57% relapsers, and 21% partial/null responders, 69% had high viral load (> 800,000 IU/mL). HCV genotypes were 1a (19%), 1b (69%), and 1 (12%), respectively. Sixty-five percent were non-CC IL28B genotype. Week-12 sustained virologic response (SVR12) was significantly higher among F2-naïve patients (78%) compared with F3/F4-naïve patients (60%; p = 0.039) and among F2 non-responders (67%) compared with F3/F4 non-responders (42%; p = 0.014). SVR12 among relapsers was remarkably high in both groups (F2:89% vs. F3/F4:78%). Severe anemia and thrombocytopenia were more frequent among patients with F3/F4 than those with F2 (p < 0.01). Overall, 132 patients (22%) discontinued treatment: 58 due to adverse effects, 42 due to the stopping-rule, and 32 due to breakthrough. Premature discontinuation was more frequent among patients with F3/F4 (p = 0.028), especially due to breakthrough (p < 0.001)., Conclusions: This multicenter study demonstrates high efficacy and an acceptable safety profile with regard to TBT in F2-patients in clinical practice.

Background & Aims: (i) To describe the demographic, clinical, virological and histological characteristics of the patients undergoing evaluation for indication of triple therapy against hepatitis C virus genotype 1, and to identify the reasons why candidate patients are excluded; and (ii) to evaluate the characteristics of the healthcare environment related to treatment., Methods: Observational, prospective and multi-centred study involving 16 hospitals of Spain. Data were collected on 1122 patients receiving attention in the outpatient clinics between June and December 2012., Results: Of the 1122 patients evaluated, 769 were finally included in this study; 27% (211/769) had contraindications to the therapy. Of those without contraindications, 54% (301/558) did not receive the treatment, and so, only about a third of the patients (33%-257/769) underwent therapy. The reasons for not initiating therapy were as follows: patient refusal (30%), mild disease/awaiting new treatments (34%), restrictions by the health service (30%), other reasons (6%). In univariate analyses, the probability of receiving treatment was related to: age <60 years, male gender, high education level, advanced fibrosis, having had previous treatment, being assessed in a centre of excellence. In multivariate analyses, the factors independently related to the probability of receiving treatment were as follows: high education level of the patients (P = 0.004), advanced fibrosis (P < 0.001) and centres of excellence (P = 0.009)., Conclusion: Despite the high efficacy of triple therapy, only a small proportion of patients receive the treatment. The causes related to non-treatment depend on patient factors, disease stage and characteristics of the health-service provision., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The prevalence of HBV and HCV infections in patients with hepatocellular carcinoma may be related to variations in the geographic area of study. For this reason, we have analized the relative prevalence of HBV and HCV infections in 94 patients with hepatocellular carcinoma from Cantabria (North of Spain)., Patients and Methods: We have studied 94 patients with hepatocellular carcinoma from January 1988 to December 1993. Commercially available radioimmunoassay or ELISA were used for detection of HBsAg, anti-HBs and anti-HBc. The HBV DNA was analized by PCR. The HCV infection was assayed by ELISA-2 and RT-PCR., Results: The HBV infection was detected in 27 patients: 19 patients were HBsAg positive and 8 patients HBsAg negative, anti-HBc positive, DNA HBV positive by PCR. The HCV infection was found in 57 patients. Forty patients were infected with both viruses. Of the remain twenty-four, forty were alcoholics. We found in 61 patients more than one etiological factor. Hepatoma was the first manifestation of liver disease in 24 cases and these were more frequently in HCV than in those with HBV infection. Moreover, the first group were older and have lower alcohol intake., Conclusions: 1) In Cantabria, Spain, the majority of cases of hepatocellular carcinoma are related to HBV, HCV and alcohol. 2) Analysis of DNA HBV and RNA HCV by PCR allows the diagnosis of cryptic infections by both viruses, especially in the cases of HBV and HCV coinfection. 3) Hepatoma is the first manifestation of liver disease in a high percentage of cases.