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| 1 | Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists显示文摘Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected. | Raúl J Andrade Mercedes Robles Alejandra Fernández-Castaer Susana López-Ortega M Carmen López-Vega M Isabel Lucena | 2007 | World Journal of Gastroenterology2007，13，3： | 18 |
| 2 | drug-induced autoimmune liver disease:a diagnostic dilemma of an increasingly reported disease显示文摘The aetiology of autoimmune hepatitis(AIH) is uncer-tain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs.AIH usually develops in individuals with a genetic back-ground mainly consisting of some risk alleles of the major histocompatibility complex(HLA).Many drugs have been linked to AIH phenotypes,which sometimes persist after drug discontinuation,suggesting that they awaken latent autoimmunity.At least three clini-cal scenarios have been proposed that refers to drug- induced autoimmune liver disease(DIAILD):AIH with drug-induced liver injury(DILI); drug induced-AIH(DI-AIH); and immune mediated DILI(IM-DILI).In addi-tion,there are instances showing mixed features of DI-AIH and IM-DILI,as well as DILI cases with positive autoantibodies.Histologically distinguishing DILI from AIH remains a challenge.Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however,a detailed standard-ised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diag-nosis between both entities.Growing information on the relationship of drugs and AIH is being available,being drugs like statins and biologic agents more fre-quently involved in cases of DIAILD.In addition,there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepa-totoxicity.Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of | Agustin Castiella Eva Zapata M Isabel Lucena Raúl J Andrade | 2014 | World Journal of Hepatology2014，6，4： | 13 |
| 3 | Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation显示文摘Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral Published online: January 27, 2019 recurrence after LT.Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT. | Maria J Citores Jose L Lucena Sara de la Fuente Valentin Cuervas-Mons | 2019 | World Journal of Hepatology2019，11，1： | 12 |
| 4 | Association between Helicobacterpylori, Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas显示文摘AIM To correlate Helicobacter pylori(H. pylori), Epstein-Barr virus(EBV) and human papillomavirus(HPV) with gastric cancer(GC) cases in Pará State, Brazil.METHODS Tissue samples were obtained from 302 gastric adenocarcinomas. A rapid urease test was used to detect the presence of H. pylori, and the presence of the cagA gene in the HP-positive samples was confirmed by PCR. An RNA in situ hybridization test designed to complement Eber1 RNA was used to detect the presence of EBV in the samples, and the L1 region of HPV was detected using nested PCR. Positive HPV samples were genotyped and analyzed for E6 and E7 viral gene expression. Infections were also correlated with the clinical and pathological characteristics of the patients.RESULTS The majority of the 302 samples analyzed were obtained from men(65%) aged 55 years or older(67%) and were classified as the intestinal subtype(55%). All three pathogens were found in the samples analyzed in the present study(H. pylori : 87%, EBV: 20%, HPV: 3%). Overall, 78% of the H. pylori-positive(H. pylori+) samples were cag A +(H. pylori-cag A+), and there was an association between the cytotoxic product of this gene and EBV. Coinfections of H. pylori-cagA+ and EBV were correlated with the most advanced tumor stages. Although only 20% of the tumors were positive for EBV, infection with this virus was associated with distant metastasis. Only the HPV 16 and 18 strains were found in the samples, although no expression of the E6 and E7 oncoproteins was detected. The fundus of the stomach was the region least affected by the pathogens.CONCLUSION HPV was not involved in gastric tumorigenesis. Prophylactic and therapeutic measures against H. pylori and EBV may prevent the development of GC, especially the more aggressive forms. | Carolina Rosal Teixeira de Souza Marcelli Carolini Alves Almeida Andre Salim Khayat Emerson Lucena da Silva Paulo Cardoso Soares Luiz Claudio Chaves Rommel Mario Rodriguez Burbano | 2018 | World Journal of Gastroenterology2018，24，43： | 6 |
| 5 | Preclinical models of idiosyncratic drug-induced liver injury(iDILI):Moving towards prediction显示文摘Idiosyncratic drug-induced liver injury(iDILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the liver.iDILI remains a major public health problem and a major cause of drug attrition.Given the lack of biomarkers for iDILI prediction,diagnosis and prognosis,searching new models to predict and study mechanisms of iDILI is necessary.One of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant iDILI.Thus,major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI patients.However,there are many gaps for explaining all the complexity of iDILI susceptibility and mechanisms.Therefore,there is a need to optimize preclinical human in vitro models to reduce the risk of iDILI during drug development.Here,the current experimental models and the future directions in iDILI modelling are thoroughly discussed,focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal iDILI models.We also comment about in silico approaches and the increasing relevance of patient-derived cellular models. | Antonio Segovia-Zafra Daniel E.Di Zeo-Sanchez Carlos Lopez-Gomez Zeus Perez-Valdes Eduardo Garcıa-Fuentes Raul J.Andrade M.Isabel Lucena Marina Villanueva-Paz | 2021 | Acta Pharmaceutica Sinica B2021，11，12： | 3 |
| 6 | Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats显示文摘AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia(HEEP) leaves on gastric ulcer healing.METHODS In this rat study involving males, intact(cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity.RESULTS Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males(52.44%), intact females(85.22%), and ovariectomized females(65.47%), confirming that HEEP accelerates the healing of acetic acidinduced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor(intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2(intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed.CONCLUSION In gastric ulcers, HEEP-induced healing(modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration. | Larissa Lucena Périco Vinícius Peixoto Rodrigues Rie Ohara Gabriela Bueno Vania Vasti Alfieri Nunes Raquel Cássia dos Santos Ana Carolina Lima Camargo Luis Antuio Justulin Joior Sérgio Faloni de Andrade Viviane Miranda Bispo Steimbach Luísa Mota da Silva Lúcia Regina Machado da Rocha Wagner Vilegas Catarina dos Santos Clélia Akiko Hiruma-Lima | 2018 | World Journal of Gastroenterology2018，24，38： | 3 |
| 7 | Drugs Associated with Hepatotoxicity and their Reporting Frequency of Liver Adverse Events in VigiBase(TM)显示文摘 | Suzuki Ayako Andrade Raul J Bjornsson Einar Lucena M Isabel Lee William M Yuen Nancy A Hunt Christine M Freston James W | 2010 | Drug Safety2010，，6： | 2 |
| 8 | Comparison of two clinical scales for causality assessment in hepatotoxicity显示文摘 | Ma Isabel Lucena Raquel Camargo Raúl J. Andrade Carlos J. Perez-Sanchez Felipe Sanchez De La Cuesta | 2001 | Hepatology2001，，1： | 2 |
| 9 | Adverse hepatic reactions associated with calcium carbimide and disulfiram therapy: Is there still a role for these drugs?显示文摘四乙秋兰姆化二硫和钙 carbimide 是二白酒威慑然而,广泛地在那里在酒精中毒治疗使用的狂言存在对他们的安全的大担心。hepatotoxicity 上的报告主要与四乙秋兰姆化二硫治疗有关,被出版了。钙 carbimide 的肝毒素的潜力是很好描绘的更少。这里,我们描述与被提交到 hepatotoxicity 的一张注册表并且当规定这些混合物时,指出我们面对的限制的这个治疗学的组有关的肝损坏的四个案例。对在白酒依赖的管理的这些混合物的角色的重估清楚地被需要。 | Carmen Verge M Isabel Lucena Enrique López-Torres M José Puche-García Enrique Fraga Manuel Romero-Gomez Raúl J Andrade | 2006 | World Journal of Gastroenterology2006，12，31： | 2 |
| 10 | Use of intra-arterial chemotherapy for retinoblastoma:results of a survey显示文摘·AIM: To obtain baseline knowledge about the current use of intra-arterial chemotherapy(SSOAIC) in centers worldwide.·METHODS: A survey including questions about the use of SSOAIC was emailed to retinoblastoma experts.·RESULTS:Seventy-nine(response rate 69.9%) doctors from 63 centers in 35 countries responded. Thirty-one centers from 19 countries use SSOAIC. Twelve performed more than 50 procedures. Melphalan is the most commonly used drug but 15 centers use more than one drug. First line therapy for advanced unilateral disease is the most common use of SSOAIC(74.2%). Centers with larger experience(>50 applications) were less likely using melphalan alone(P =0.06) and significantly more likely using SSOAIC in more situations such as second line in preference to radiotherapy P =0.05. Nineteen(61.2%)stated that SSOAIC improved their results and 21(77.8%)reported less toxicity compared to other treatments.Three centers reported that SSOAIC did not improve their results. There were regional variations in the use of SSOAIC which is used more frequently as secondary treatment in Europe compared to the USA and Japan.Ten centers identified cost is the major limiting factor for SSOAIC.· CONCLUSION: SSOAIC is used in an increasing number of centers worldwide with regional variations.Centers with more experience in SSOAIC use it in more situations including other drugs than melphalan. The majority of the centers using this technique reportedimproved results and few complications. | Nathalia Grigorovski Evandro Lucena Clarissa Mattosinho Andreu Parareda Sima Ferman Jaume Catalá Guillermo Chantada | 2014 | International Journal of Ophthalmology(English edition)2014，7，4： | 2 |
| 11 | Human origin of Bacteroides fragilis bacteriophages present in the environment 显示文摘 | TARTERA C LUCENA F JOFRE J | 1989 | Applied and Environmental Microbiology1989，55，10： | 1 |
| 12 | Drug-induced liver injury:an analysis of 461 incidences submitted to the Spanish registry over a10-year period显示文摘 | Andrade ILl Lucena MI Femamdez MC | | 0，，： | 1 |
| 13 | Evaluation of Bacteroides fragilis bacteriophages as indicators of the virological quality of water显示文摘 | JOFRE J BOSCH A LUCENA F | 1986 | Water Science and Technology1986，18，10： | 1 |
| 14 | He- patic injury caused by acarbose 显示文摘 | Andradc R J Lucena M I Rodriguez Mendizabal M | 1999 | Annals of Internal Med- icine1999，124，： | 1 |
| 15 | Combined use of carbon nanotubes and ionic liquid to improve the determi- nation of antidepressants in urine samples by liquid chromatogra- phy显示文摘 | CRUZ-VERA M LUCENA R CARDENAS S | 2008 | Anal Bioanal Chem2008，391，4： | 1 |
| 16 | Phenotypic characterization of idiosyncratic drug-induced liver injury: the influence of age and sex显示文摘 | Lucena MI Andrade R J Kaplowitz N | 2009 | Hepatology2009，49，： | 1 |
| 17 | Pulmonary embolism and sudden-unexpected death:prospective study on 2477 forensic autopsies performed at the Institute of Legal Medicine in Seville显示文摘 | Lucena J Rico A Vázquez R | | 0，，04： | 1 |
| 18 | Efficacy assessment oftwo antibiotic prophylaxis regimens in oral and maxillofacialtrauma surgery: preliminary results显示文摘 | Campos G B Lucena E E da Silva J S | 2015 | Int J Clin Exp Med2015，8，2： | 1 |
| 19 | Ultrasound guided core needle biopsy of breast masses: How many cores are necessary to diagnose cancer? 显示文摘 | De Lucena C E Dos Santos Junior J L De Lima Resende C A | 2007 | J Clin Ultrasound2007，35，7： | 1 |
| 20 | Reactivity of synthetic Fe chelates with soils and soil components显示文摘 | Ana Alvarez-Fernandez Miguel A Sierra Juan J Lucena | 2002 | Plant and Soil2002，，241： | 1 |
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