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Management of betablocked patients after sustained virological response in hepatitis C cirrhosis

World Journal of Gastroenterology 2019年第21期25卷 2665-2674页

作者： Marta Abadía María Luisa Montes Dolores Ponce Consuelo Froilán Miriam Romero Joaquín Poza Teresa Hernández Rubén Fernández-Martos Antonio Olveira Antonio Olveira Servicio de Aparato DigestivoHospital Universitario La PazMadrid 28046Spain Unidad VIH Servicio de Medicina InternaHospital Universitario La PazMadrid 28046Spain Servicio de Radiología Hospital Universitario La PazMadrid 28046Spain ciberehd idipaz Madrid 28029Spain

BACKGROUND Current guidelines do not address the post–sustained virological response management of patients with baseline hepatitis C virus (HCV) cirrhosis and oesophageal varices taking betablockers as primary or secondary prophylaxis of variceal bleeding. We hypothesized that in some of these patients portal hypertension drops below the bleeding threshold after sustained virological response, making definitive discontinuation of the betablockers a safe option. AIM To assess the evolution of portal hypertension, associated factors, non-invasive assessment, and risk of stopping betablockers in this population. METHODS Inclusion criteria were age > 18 years, HCV cirrhosis (diagnosed by liver biopsy or transient elastography > 14 kPa), sustained virological response after directacting antivirals, and baseline oesophageal varices under stable, long-term treatment with betablockers as primary or secondary bleeding prophylaxis. Main exclusion criteria were prehepatic portal hypertension, isolated gastric varices, and concomitant liver disease. Blood tests, transient elastography, and upper gastrointestinal endoscopy were performed. Hepatic venous pressure gradient (HVPG) was measured five days after stopping betablockers. Betablockers could be stopped permanently if gradient was < 12 mmHg, at the discretion of the attending physician. RESULTS Sample comprised 33 patients under treatment with propranolol or carvedilol: median age 64 years, men 54.5%, median Model for End-Stage Liver Disease (MELD) score 9, Child-Pugh score A 77%, median platelets 77.000 × 103/μL, median albumin 3.9 g/dL, median baseline transient elastography 24.8 kPa, 88% of patients received primary prophylaxis. Median time from end of antivirals to gradient was 67 wk. Venous pressure gradient was < 12 mmHg in 13 patients (39.4%). In univariate analysis the only associated factor was a MELD score decrease from baseline. On endoscopy, variceal size regressed in 19/27 patients (70%), although gradient was ≥ 12 mmHg in 12/19 patients. The elastography a

关键词： Hepatitis C virus Oesophageal varices Portal hypertension Betablocker Variceal bleeding

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Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype

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World Journal of Gastroenterology 2016年第11期22卷 3165-3174页

作者： Antonio Madejón Míriam Romero ángela Hernández Araceli García-Sánchez Marta Sánchez-Carrillo Antonio Olveira Javier García-Samaniego Hepatology Section Gastroenterology Department Hospital Universitario La Paz 28046 Madrid Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas (ciberehd) 28046 Madrid Spain Instituto de Investigación del Hospital Universitario La Paz (idipaz) 28046 Madrid Spain

AIM: To study the hepatitis B virus(HBV) and hepatitis D virus(HDV) replication interferences in patients with chronic hepatitis delta infected with different HBV genotypes.METHODS: We conducted a transversal study including 68 chronic hepatitis delta(CHD)(37 HIVpositive) patients and a control group of 49 chronic hepatitis B(CHB)(22 HIV-positive) patients. In addition, a dynamic follow-up was performed in 16 CHD patients. In all the samples, the surface antigen of hepatitis B(HBs Ag) serum titers were analyzed with the Monolisa HBs Ag Ultra system(Bio-Rad), using as quantification standard a serial dilution curve of an international HBs Ag standard. Serum HBV-DNA titers were analyzed using the Roche Cobas Taq Man(Roche, Barcelona, Spain), and the serum HDV-RNA using an in-house real-time q RT-PCR method, with Taq Man probes. HBV genotype was determined with the line immunoassay Li PA HBV genotyping system(Innogenetics, Ghent, Belgium). In those patients negative for Li PA assay, a nested PCR method of complete HBs Ag coding region, followed by sequence analysis was applied.RESULTS: No differences in the HBV-DNA levels were found in CHB patients infected with different HBV genotypes. However, in CHD patients the HBV-DNA levels were lower in those infected with HBV-A than in those with HBV-D, both in HIV negative [median(IQR): 1.25(1.00-1.35) vs 2.95(2.07-3.93) log10(copies/m L), P = 0.013] and HIV positive patients [2.63(1.24-2.69) vs 7.25(4.61-7.55) log10(copies/m L), P < 0.001]. This was confirmed in the dynamic study of the HBV/HDV patients. These differences induce an under-estimation of HBV-A incidence in patients with CHD analyzed with Li PA assay. Finally, the HBs Ag titers reflected no significant differences in CHD patients infected with HBV-A or D.CONCLUSION: Viral replication interference between HBV and HDV is HBV-genotype dependent, and more evident in patients infected with HBV-genotype A, than with HBV-D or E.

关键词： Hepatitis D virus Hepatitis B virus Delta hepatitis Replication interference Viral replication

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克罗恩病患者回结肠切除一期吻合手术的围手术期处理和术后近期并发症:对PRACTICROHN研究的数据分析

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Gastroenterology Report 2019年第3期7卷 168-175,I0001,I0002页

作者： Ana Gutierrez Montserrat Rivero Maria Dolores Martin-Arranz Valle Garcia Sanchez Manuel Castro Jesus Barrio Ruth de Francisco Manuel Barreiro-de Acosta Berta Julia Luis Cea-Calvo Cristina Romero Natalia Borruel Sainz Eugeni Domenech Gastroenterology Department General University Hospital of Alicante and Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas(CIBERehd)CarlosⅢHealth InstituteMadridSpain Gastroenterology Department Marques de Valdecilla General University HospitalSantanderSpain Gastroenterology Department La Paz General University HospitalInstituto de Investigacion Biomedica La Paz(IdiPaz)MadridSpain Clinical Management of Gastrointestinal Tract Diseases Unit Reina Sofia University HospitalMaimonides Institute of Biomedical Research of Cordoba(IMIBIC)Cordoba UniversityCordobaSpain Gastroenterology Department Valme University HospitalSevillaSpain Gastroenterology Department University HospitalRio HortegaValladolidSpain Gastroenterology Department University Hospital Central de AsturiasOviedoSpain Gastroenterology Department Inflammatory Bowel Disease UnitUniversity Hospital Complex of Santiago de CompostelaSantiago de CompostelaSpain Medical Department Merck Sharp and DohmeMadridSpain Crohn-Colitis Care Unit(UACC) Digestive Tract ServiceHospital Universitari Vall d’HebronBarcelonaSpain Gastroenterology Department Germans Trias i Pujol University Hospital and CIBERehdBadalonaSpain

背景:本研究旨在分析克罗恩病患者回结肠切除术后近期并发症的发生率及危险因素。方法:对PRACTICROHN研究队列进行回顾性分析,纳入2007年1月至2010年12月间行回结肠切除一期吻合的成人克罗恩病患者。术后近期并发症定义为术后30天内出... 详细信息

背景:本研究旨在分析克罗恩病患者回结肠切除术后近期并发症的发生率及危险因素。方法:对PRACTICROHN研究队列进行回顾性分析,纳入2007年1月至2010年12月间行回结肠切除一期吻合的成人克罗恩病患者。术后近期并发症定义为术后30天内出现的并发症,包括死亡、肠梗阻、吻合口漏、消化道出血、腹腔脓肿、切口感染、导管相关感染及其他腹腔外感染。结果:364例患者纳入分析,手术时患者的中位年龄38岁,男性占50%。手术适应证:狭窄型占46.4%,穿透型占31.3%,狭窄+穿透型占14.0%,药物难治性占5.8%。100例(27.5%)出现术后近期并发症,其中切口感染、腹腔脓肿和吻合口漏最为常见。出现并发症的患者其中位住院时间较未出现并发症者显著延长(16 vs 9天,P<0.001)。术后并发症更多发生于穿透型病变(36/114,31.6%)和药物难治性(9/21,42.9%)患者,而狭窄型(45/169,26.6%)和狭窄+穿透型(6/51,11.8%)患者并发症发生率相对较低(P=0.040)。术中才作出诊断的患者,术后并发症发生率较术前已明确诊断者显著升高[48.4%(15/31)vs.25.7%(85/331),P=0.013)。手术期间接受药物治疗并不会影响并发症发生率。结论:约四分之一的克罗恩病患者行回结肠切除术后会出现近期并发症,其中穿透型病变和急诊手术患者术后并发症风险增高。

关键词： Ileocolonic resection Crohn’s disease post-operative complications risk factors

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Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort

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World Journal of Gastroenterology 2019年第4期25卷 433-446页

作者： Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía Nú?ez María Fernández-Velasco Paloma Martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán Miguel ángel Peinado Lisardo Boscá Department of Metabolism and Physiopathology of Inflammatory Diseases Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (Ciber-CV) Instituto de Salud Carlos III (ISCIII) Laboratorio de Imagen Médica Hospital Universitario Gregorio Mara?ón Laboratorio de Proteómica Cardiovascular Centro Nacional de Investigaciones Cardiovasculares (CNIC) Instituto de Investigación Sanitaria del Hospital Universitario la Paz(idipaz) Programa de Medicina Predictiva y Personalizada del Cáncer (PMPPC) Fundación Instituto de investigación en ciencias de la salud Germans Trias i PujolCtra Can Ruti

BACKGROUND Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.AIM To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.METHODS Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F(PNGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap MS.RESULTS Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. M

关键词： Colon Carcinoma Cyclooxygenase Prostaglandin Proteomics High resolution magic angle spinning

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克罗恩病初次手术与多次手术患者的治疗及结局:基于PRACTICROHN研究数据

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Gastroenterology Report 2019年第6期7卷 411-418,I0001,I0002页

作者： Marisa Iborra Berta Juliá Maria Dolores Martín Arranz Manuel Barreiro-de Acosta Ana Gutiérrez Valle García-Sánchez Carlos Taxonera Javier P.Gisbert Luis Cea-Calvo Eugeni Domènech Gastroenterology Department Hospital La FeValenciaSpain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(ciberehd) MadridSpain Medical Department Merk Sharp and Dohme(MSD)MadridSpain Gastroenterology Unit Hospital Universitario La PazIdiPAZMadridSpain Gastroenterology Unit Complejo Hospitalario Universitario de SantiagoSantiago de CompostelaSpain Digestive Medicine Department Hospital General de AlicanteAlicanteSpain Unit of Clinical Management of Gastrointestinal Tract Hospital Universitario Reina SofiaMaimonides Institute of Biomedical Research of Cordoba(IMIBIC)Cordoba UniversityCordobaSpain Gastroenterology Department Hospital Clínico San CarlosMadridSpain Instituto de Investigación del Hospital Clínico San Carlos(IdISSC) MadridSpain Gastroenterology Department Hospital Universitario de La PrincesaInstituto de Investigación Sanitaria Princesa(IIS-IP)MadridSpain Gastroenterology Department Hospital Universitari Germans Trias i PujolBadalonaSpain

背景:克罗恩病(CD)手术往往预后不佳,常需再次手术。本研究旨在比较初次手术与多次手术CD患者的术后治疗及临床结局。方法:本研究为观察性研究,纳入2007年1月至2010年12月间西班牙26家医院收治的行回结肠切除吻合术的成人CD患者。从医... 详细信息

背景:克罗恩病(CD)手术往往预后不佳,常需再次手术。本研究旨在比较初次手术与多次手术CD患者的术后治疗及临床结局。方法:本研究为观察性研究,纳入2007年1月至2010年12月间西班牙26家医院收治的行回结肠切除吻合术的成人CD患者。从医疗记录中回顾性收集数据。结果:314例患者纳入分析,其中262例(83%)为初次手术病例,52例(17%)既往有过CD手术史。除狭窄型病变的患者比例再手术组相对较高以外(P=0.03),其余基线资料两组患者的差异均无统计学意义。术后接受预防性药物治疗的患者比例再手术组高于初次手术组(P=0.04)。再手术患者临床复发的时间与是否接受预防性药物治疗无关;但对于初次手术患者,接受预防性药物治疗者无复发生存时间更长(P=0.03)。结论:与初次手术者相比,既往有过CD手术史的患者术后更多接受了预防性药物(免疫调节剂)治疗。尽管预防性药物治疗可以预防初次手术者的临床复发,但并没有降低再次手术患者的复发风险。提示术后预防性药物治疗仍应仅限于初次手术患者。

关键词：初次手术观察性研究医疗记录克罗恩病药物治疗者狭窄型基线资料临床结局

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