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Old patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought for the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥65 years) were categorized according to age: “young” (

Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease.

[Background & Aims] Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period., [Methods] Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected., [Results] A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974–0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994–0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy’s law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%)., [Conclusions] AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management., [Lay summary] Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes., The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI19/00883, PI16/01748, PI18/00901, PI18/01804, PI-0285-2016, PI-0274-2016, PI-0310-2018, PT17/0017/0020) and Agencia Española del Medicamento. CIBERehd and Plataforma ISCIII Ensayos Clinicos are funded by Instituto de Salud Carlos III. MRD holds a Joan Rodes (JR16/00015)/Acción B clinicos investigadores (B-0002-2019) and JSC a Rio Hortega (CM17/00243) research contract from ISCIII and Consejería de Salud de Andalucía.

1 p. Dysbiosis and gut-liver axis alteration have been pointed as important contributors to obesity and non-alcoholic fatty liver disease (NAFLD) development. Modulation of intestinal microbiota (IM) emerge as a promising therapeutic strategy for obesity-associated NAFLD. This study aims to determine the effect of IM transplantation and quercetin supplementation in a high fat diet (HFD)-based NAFLD model in germ free mice (GFm). Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16) SI

Background: The presence of a family history implies an increased risk for developing colorectal cancer (CRC), and may require a different screening strategy. The aim of this study was to evaluate lesions found during colonoscopies of patients that had a family history of CRC. Material and methods: A retrospective study was conducted that included consecutive colonoscopies performed on patients with a family history of CRC at a referral center within the period from April 2000 to January 2012. The colonoscopic findings were analyzed in relation to sex, age, and the presence or absence of symptoms. Results: Data from 3,792 colonoscopies were collected. The mean age of the patients was 53.14 years (SD 12.22), and 57.4% were women. Colonoscopy was normal in 71.7% of the cases, with hyperplastic polyps being detected in 7.1%, and adenomatous polyps in 19.8% (39.4% of them were high risk). There was a 1.5% presence of adenocarcinomas in the subjects. Polyps and CRC were predominant in men (P=.001 and P=.027, respectively) and there was a linear increase with age. Symptomatic patients had a higher CRC detection rate (P

1 p. Gut microbiota is involved in obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Quercetin may have the ability to modulate the intestinal microbiota composition, suggesting therapeutic potential in NAFLD. The present study aims to investigate the beneficial effect of quercetin treatment on dysbiosis, intestinal barrier dysfunction and gut-liver axis alteration in high-fat diet (HFD)-fed mice. Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16) SI

The purpose of this study was to investigate whether antipyrine estimation in saliva provides valid information on plasma antipyrine clearance (APCl) and can be useful as an index of changes in drug metabolism with age. Antipyrine kinetics was studied in 93 elderly (mean age 82 years) and 23 young (mean age 29 years) volunteers. Plasma antipyrine half-life ( AP t 1 2 ) increased and plasma APCl declined with age. No significant difference between plasma- and saliva-derived parameters was found in either young or old subjects. However, the saliva/plasma ACCl ratio tended to increase with age. A highly significant correlation between saliva and plasma APCl or AP t 1 2 was found in young subjects. Values were less closely related in the elderly and the slope of the saliva/plasma APCl relationship was significantly different in both groups of subjects. Residual variance was higher in the regressions corresponding to the elderly. The findings in the study indicate that the relationship between saliva and plasma kinetics in young subjects becomes less reproducible with age.

Objectives: we analyzed the characteristics of patients withgastric tumors diagnosed with multiple malignant primary neo-plasm (MMPN) in the Health District of Leon.Material and methods:using the information in the TumorRegistry at Leon Hospital patients selected were those with gastricneoplasms diagnosed between 1993 and 2002. A follow-up wasperformed until December 31, 2004, and the characteristics ofpatients diagnosed with a second neoplasm were analyzed.Results: MMPN prevalence was 1,96%; 56% of patients hada history of cancer in first-degree relatives. The most frequent sec-ond neoplasms were digestive (26%) and urologic (21%); 87% ofpatients were diagnosed with a second neoplasm within the firsttwo years. No significative differences in survival were observedamong patients with synchronous or metachronous MMPN.Conclusions: MMPN in patients with gastric neoplasms is arelevant problem. While external carcinogenic agents could act aspromoters in the development of second neoplasms, these pa-tients seem to have a genetic background favoring the develop-ment of MMPN. Secondary prevention is the best measure toavoid MMPN development.Key words:Multiple neoplasms. Synchronous. Metachronous.Prostate. Survival. Prognosis. Oncology.

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-naive (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.

OBJETIVOS: Analizar las características de los pacientes diagnosticados de CCRM en el área sanitaria de León, el impacto sobre la supervivencia y las posibles variables pronósticas. MATERIAL Y MÉTODOS: Utilizando los datos del Registro de Tumores del Hospital de León se han analizado las características de aquellos pacientes con tumores colo-rectales diagnosticados entre 1993 y 2002, clasificándolos dos grupos: el primero constituido por 74 pacientes diagnosticados de CCRM y el segundo formado por 1342 pacientes con tumores únicos diagnosticados en el bienio 1996-1997. RESULTADOS: La frecuencia de CCRM fue del 2,7%. La edad de los pacientes con CCRM fue 2 años mayor con respecto a la de los pacientes con neoplasias únicas, con una elevada proporción (38%) de antecedentes familiares oncológicos en familiares de primer grado. No se observaron diferencias significativas en cuanto a la localización y el estadio del primer tumor colo-rectal con respecto al grupo de tumores únicos. La supervivencia de los pacientes con CCRM metacrónico fue netamente inferior, posiblemente en relación con un mayor número de segundas neoplasias diagnosticadas en estadios tempranos en los pacientes con CCRM sincrónico. Las variables que influyeron en el pronóstico fueron la edad, el sexo, y el padecimiento de un CCRM sincrónico o metacrónico. CONCLUSIONES: El CCRM es una entidad frecuente en nuestro medio. La tasa de antecedentes familiares oncológicos en estos pacientes es muy elevada. No se encontraron diferencias significativas en cuanto al pronóstico de estos pacientes respecto al de los pacientes con neoplasias únicas.

Objetivos: Analizar las características de los pacientes con tumores prostáticos que desarrollaron una neoplasia primaria maligna múltiple (NPMM) en el área sanitaria de León, el impacto sobre la supervivencia y las posibles variables pronósticas. Material y métodos: Utilizando los datos del Registro de Tumores del Hospital de León se han seleccionado aquellos pacientes con tumores prostáticos diagnosticados entre 1993 y 2002, creando dos grupos: el primero constituido por 67 pacientes con NPMM y el segundo formado por 145 pacientes con tumores únicos diagnosticados entre 1996 y 1997. Resultados: La prevalencia de NPMM fue del 5,57%. Los pacientes con NPMM fueron 3 años más jóvenes que los pacientes con tumores únicos, con una elevada proporción (41%) de antecedentes familiares oncológicos en familiares de primer grado. La asociación más frecuente fue el cáncer urológico sincrónico. El 86% de los pacientes fueron diagnosticados del segundo tumor en los primeros dos años. La supervivencia de los pacientes con NPMM metacrónicas fue inferior a la de los pacientes con NPMM sincrónicas, siendo las variables con significación pronóstica la edad, el padecimiento de una NPMM metacrónica, el estadio del segundo tumor y el padecimiento de un segundo tumor urológico. Conclusiones: Las NPMM en pacientes con tumores prostáticos son relativamente frecuentes en nuestro medio. Parece existir una base genética en estos pacientes. El pronóstico de los pacientes con NPMM metacrónicas es peor. No existen diferencias significativas en cuanto al pronóstico con respecto a los pacientes con tumores únicos.

Introducción: Aunque se han realizado múltiples estudios para conocer los factores pre-tratamiento que pueden predecir la respuesta al tratamiento con interferón (IFN), se desconoce si las lesiones histológicas características de la hepatitis crónica C (HCC) sirven para predecir dicha respuesta. Objetivos: Valorar si los parámetros histológicos pueden predecir la respuesta mantenida al tratamiento con IFN en los pacientes con HCC, y estudiar otros parámetros (epidemiológicos y analíticos) ya descritos como factores predictivos de respuesta. Métodos: Se estudiaron de forma retrospectiva 201 pacientes, tratados con IFN durante al menos 3 meses en cuatro hospitales de Castilla y León. La variable dependiente analizada fue la respuesta mantenida al tratamiento. Como factores predictivos de respuesta se estudiaron las siguientes variables histológicas: diagnóstico histológico, índice de Knodell total y por apartados, grado y estadio, y lesiones características de la HCC. Además, se analizaron parámetros epidemiológicos y analíticos. Resultados: El 16% de los pacientes presentó una respuesta mantenida. Ninguno de los parámetros histológicos sirvió para predecir dicha respuesta. Demostraron ser factores predictivos en el análisis bivariante la edad, el tiempo de evolución de la HCC, la vía de transmisión, la GGT, la ferritina y el genotipo viral. El factor predictivo más importante fue el genotipo viral, y el único asociado independientemente a la respuesta mantenida ("odds ratio" de respuesta al tratamiento de 8,6). Conclusiones: Los parámetros histológicos no predicen la respuesta al tratamiento con IFN. Otros factores, fundamentalmente el genotipo viral, se asocian a un mayor porcentaje de respuestas, aunque ninguno sirve para decidir con exactitud qué pacientes responderán.

Drug metabolizing capacity is generally reduced in the elderly, and physical exercise has been reported to increase drug oxidative metabolism. The purpose of this investigation was to study the effects of engagement in a program of regular physical exercise on the clearance and metabolite excretion of antipyrine, a marker of oxidative metabolism, in elderly subjects. The saliva clearance of antipyrine and the production clearances of antipyrine metabolites were studied in 37 elderly women (mean age 66 years). Subjects attended 60-min sessions three times a week for 12 weeks. Each session consisted of both aerobic (training of cardiorespiratory capacity) and nonaerobic (training of muscular strength/endurance and flexibility/coordination) exercises performed at 50–75% of maximum oxygen uptake. Antipyrine was administered orally and pharmacokinetic parameters were obtained from saliva and urine samples. After 3 months of participation in the exercise program, salivary antipyrine clearance was significantly increased by 17% mean (SEM) 0.42 (0.02) vs 0.36 (0.02) ml/min/kg; P < 0.05) and the half-life of antipyrine was significantly reduced by 18% (17.9 (1.1) vs 22.3 (1.3) h; P < 0.05). No significant change with exercise was observed in the renal clearance of antipyrine or in the norantipyrine formation clearance, but significant increases were found for hydroxymethylantipyrine [42 (5) vs 32 (4) μl/kg/min; P < 0.05; +31%] and 4-hydroxyantipyrine [243 (18) vs 194 (17) μl/kg/min; P < 0.05; +25%] formation clearances. These findings indicate that regular exercise leads to increased disposition of antipyrine in the elderly and that the main metabolic pathways of the compound are changed differentially.

The purpose of this study was to identify variables that can account for the decline of antipyrine clearance (Cl AP ) in elderly adults and that may help predict a reduction in metabolizing capacity. For comparison, Cl AP was determined in 177 elderly (mean age 82 years) and 25 young (mean age 29 years) volunteers. Antipyrine (1 g) was administered orally and Cl AP was determined by the one-sample saliva method. Mean Cl AP was reduced by 38% and antipyrine half-life increased by 64% in old subjects. Multiple regression analysis of Cl AP revealed an independent value for age, serum aspartate transaminase (AST), and height in the elderly. The independent variables collectively accounted for 27% of the variance explained. Age, high serum AST, use of diuretics, and no consumption ofdrugs known to stimulate oxidative metabolism were selected by multivariate analysis (logistic model) as independent predictors of a low metabolizing capacity. The findings indicate that factors other than age may contribute to impaired hepatic oxidative metabolism in the elderly.