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High prevalence of cholestasis, with increased conjugated bile acids in inflammatory bowel diseases patients

World Journal of Clinical Cases 2018年第4期6卷 44-53页

作者： Marc Girardin Antoine Hadengue Jean-Louis Frossard service of Gastroenterology and hepatology Geneva University Hospital

AIM To investigate the prevalence and causes of cholestasis in patients with inflammatory bowel diseases in the Swiss Inflammatory Bowel Diseases Cohort. METHODS A retrospective cohort study was performed of all the patients in the Swiss Inflammatory bowel disease Cohort. Total bile acid was measured for all patients and cholestasis was defined as a concentration > 8 μmol/L. The characteristics of patients with or without cholestasis were compared. Bile acid profiles were then determined for 80 patients with high total bile acid and 80 matched patients with low total bile acid. Bile acid profiles were compared for smokers vs nonsmokers, ileal vs colonic disease, and inflammatory vs non inflammatory *** Ninety-six patients had more than 8 μmol/L total bile acid, giving a prevalence of 7.15%. Patients with an obvious cause of cholestasis, such as primary sclerosing cholangitis, were then excluded, leaving 1190 participants with total bile acid 8 μmol/L. In multivariate analysis, calcium supplementation was significantly associated with cholestasis(odds ratio, 2.36, 95%CI: 1.00-5.21, P = 0.040) whereas current smoking significantly reduced the risk of cholestasis(odds ratio, 0.42, 95%CI: 0.17-0.91, P = 0.041). Levels of all conjugated bile acids were higher in the cholestasis group than in the control group. When we compared patients with ileal vs colonic disease, the former had higher levels of primary, secondary, and tertiary bile acids whereas patients with colonic disease had higher levels of conjugated bile *** Prevalence of cholestasis is high. Smoking appears to reduce cholestasis. Conjugated bile acids are higher in cholestasis and in colonic disease whereas unconjugated in ileal disease.

关键词： Lipid Liver Crohn’s disease Ulcerative colitis Cholestasis

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Immune responses to Helicobacter pylori infection

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World Journal of Gastroenterology 2014年第19期20卷 5583-5593页

作者： Mati Moyat Dominique Velin service of Gastroenterology and hepatology Department of MedicineLausanne University HospitalCH-1011 LausanneSwitzerland

Helicobacter pylori (H. pylori) infection is one of the most common infections in human beings worldwide. H. pylori express lipopolysaccharides and flagellin that do not activate efficiently Toll-like receptors and express dedicated effectors, such as γ-glutamyl transpeptidase, vacuolating cytotoxin (vacA), arginase, that actively induce tolerogenic signals. In this perspective, H. pylori can be considered as a commensal bacteria belonging to the stomach microbiota. However, when present in the stomach, H. pylori reduce the overall diversity of the gastric microbiota and promote gastric inflammation by inducing Nod1-dependent pro-inflammatory program and by activating neutrophils through the production of a neutrophil activating protein. The maintenance of a chronic inflammation in the gastric mucosa and the direct action of virulence factors (vacA and cytotoxin-associated gene A) confer pro-carcinogenic activities to H. pylori. Hence, H. pylori cannot be considered as symbiotic bacteria but rather as part of the pathobiont. The development of a H. pylori vaccine will bring health benefits for individuals infected with antibiotic resistant H. pylori strains and population of underdeveloped countries.

关键词： Helicobacter pylori Vaccine Immune response Peptic ulcer Gastric cancer

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Recurrent Clostridium difficile infections:The importance of the intestinal microbiota

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World Journal of Gastroenterology 2014年第23期20卷 7416-7423页

作者： Marie Céline Zanella Terrier Martine Louis Simonet Philippe Bichard Jean Louis Frossard service of General Internal Medicine Geneva University Hospital1211 GenevaSwitzerland service of Gastroenterology and hepatology Geneva University Hospital1211 GenevaSwitzerland

Clostridium difficile infections(CDI)are a leading cause of antibiotic-associated and nosocomial *** effective antibiotic treatments,recurrent infections are *** the recent emergence of hypervirulent isolates of ***,CDI is a growing epidemic with higher rates of recurrence,increasing severity and *** microbiota transplantation(FMT)is an alternative treatment for recurrent CDI.A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic *** is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent *** the first reported use of FMT for recurrent CDI in 1958,systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic *** article focuses on current guidelines for CDI treatment,the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy,adverse effects and acceptability.

关键词： Clostridium difficile infection Clostridium difficile recurrence Fecal microbiota transplantation Stool transplantation Microbiota

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Predictive factors associated with hepatitis C antiviral therapy response

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World Journal of hepatology 2015年第12期7卷 1617-1631页

作者： Lourianne Nascimento Cavalcante André Castro Lyra Hospital Sao Rafael-Gastro-hepatology service Department of Medicine Federal University of Bahia

Hepatitis C virus(HCV) infection may lead to significant liver injury, and viral, environmental, host, immunologic and genetic factors may contribute to the differences in the disease expression and treatment response. In the early 2000 s, dual therapy using a combinationof pegylated interferon plus ribavirin(PR) became the standard of care for HCV treatment. In this PR era, predictive factors of therapy response related to virus and host have been identified. In 2010/2011, therapeutic regimens for HCV genotype 1 patients were modified, and the addition of NS3/4a protease inhibitors(boceprevir or telaprevir) to dual therapy increased the effectiveness and chances of sustained virologic response(SVR). Nevertheless, the first-generation triple therapy is associated with many adverse events, some of which are serious and associated with death, particularly in cirrhotic patients. This led to the need to identify viral and host predictive factors that might influence the SVR rate to triple therapy and avoid unnecessary exposure to these drugs. Over the past four years, hepatitis C treatment has been rapidly changing with the development of new therapies and other developments. Currently, with the more recent generations of pangenotipic antiviral therapies, there have been higher sustained virologic rates, and prognostic factors may not have the same importance and strength as before. Nonetheless, some variables may still be consistent with the low rates of non-response with regimens that include sofosbuvir, daclatasvir and ledipasvir. In this manuscript, we review the predictive factors of therapy response across the different treatment regimens over the last decade including the new antiviral drugs.

关键词： Hepatitis C Direct acting antivirals Antiviraltherapy Interferon Sustained virologic response

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Sirtuins and nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2016年第46期22卷 10084-10092页

作者： Fatiha Nassir Jamal A Ibdah Research service Harry S Truman Memorial VA Hospital University of Missouri Department of Medicine Division of Gastroenterology and Hepatology University of Missouri

Mammalian sirtuins are seven members belonging to the silent information regulator 2 family, a group of Class Ⅲ histone/protein deacetylases. Sirtuins(SIRT 1-7) have different subcellular localization and function and they regulate cellular protein function through various posttranslational modifications. SIRT1 and 3, the most studied sirtuins, use the product of cellular metabolism nicotinamide adenine dinucleotide as a cofactor to post-translationally deacetylate cellular proteins and consequently link the metabolic status of the cell to protein function. Sirtuins have been shown to play a key role in the development and rescue of various metabolic diseases including non-alcoholic fatty liver disease(NAFLD). NAFLD is currently the most chronic liver disease due mainly to high-calorie consumption and lower physical activity. No pharmacological approach is available to treat NAFLD, the current recommended treatment are lifestyle modification such as weight loss through calorie restriction and exercise. Recent studies have shown downregulation of sirtuins in human as well as animal models of NAFLD indicating an important role of sirtuins in the dynamic pathophysiology of NAFLD. In this review, we highlight the recent knowledge on sirtuins, their role in NAFLD and their unique potential role as novel therapeutic target for NAFLD treatment.

关键词： SIRT1 SIRT3 Sirtuins Non-alcoholic fatty liver disease

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Doctor communication quality and Friends' attitudes influence complementary medicine use in inflammatory bowel disease

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World Journal of Gastroenterology 2015年第12期21卷 3663-3670页

作者： Réme Mountifield Jane M Andrews Antonina Mikocka-Walus Peter Bampton Department of Gastro-enterology and hepatology Flinders Medical Centre Flinders University of South Australia IBD service Department of Gastroenterology and Hepatology and School of Medicine University of Adelaide at Royal Adelaide Hospital School of Nursing and Midwifery University of South Australia

AIM: To examine the frequency of regular complementary and alternative therapy(CAM) use in three Australian cohorts of contrasting care setting and geography, and identify independent attitudinal and psychological predictors of CAM use across all cohorts. METHODS: A cross sectional questionnaire was administered to inflammatory bowel disease(IBD) patients in 3 separate cohorts which differed by geographical region and care setting. Demographics and frequency of regular CAM use were assessed, along with attitudes towards IBD medication and psychological parameters such as anxiety, depression, personality traits and quality of life(QOL), and compared across cohorts. Independent attitudinal and psychological predictors of CAM use were determined using binary logistic regression analysis. RESULTS: In 473 respondents(mean age 50.3 years, 60.2% female) regular CAM use was reported by45.4%, and did not vary between cohorts. Only 54.1%of users disclosed CAM use to their doctor. Independent predictors of CAM use which confirm those reported previously were: covert conventional medication dose reduction(P < 0.001), seeking psychological treatment(P < 0.001), adverse effects of conventional medication(P = 0.043), and higher QOL(P < 0.001).Newly identified predictors were CAM use by family or friends(P < 0.001), dissatisfaction with patient-doctor communication(P < 0.001), and lower depression scores(P < 0.001). CONCLUSION: In addition to previously identified predictors of CAM use, these data show that physician attention to communication and the patient-doctor relationship is important as these factors influence CAM use. Patient reluctance to discuss CAM with physicians may promote greater reliance on social contacts to influence CAM decisions.

关键词： Complementary medicine Alternative therapy Therapy

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Clinical value of predictive models based on liver stiffness measurement in predicting liver reserve function of compensated chronic liver disease

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World Journal of Gastroenterology 2022年第42期28卷 6045-6055页

作者： Rui-Min Lai Miao-Miao Wang Xiao-Yu Lin Qi Zheng Jing Chen Department of hepatology Hepatology Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhou 350005Fujian ProvinceChina Department of Endocrinology The 910th Hospital of The Joint Service Support ForceQuanzhou 362000Fujian ProvinceChina

BACKGROUND Assessment of liver reserve function(LRF)is essential for predicting the prognosis of patients with chronic liver disease(CLD)and determines the extent of liver resection in patients with hepatocellular *** To establish noninvasive models for LRF assessment based on liver stiffness measurement(LSM)and to evaluate their clinical *** A total of 360 patients with compensated CLD were retrospectively analyzed as the training *** new predictive models were established through logistic regression analysis and were validated internally in a prospective cohort(132 patients).RESULTS Our study defined indocyanine green retention rate at 15 min(ICGR15)≥10%as mildly impaired LRF and ICGR15≥20%as severely impaired *** constructed predictive models of LRF,named the mLPaM and sLPaM,which involved only LSM,prothrombin time international normalized ratio to albumin ratio(PTAR),age and model for end-stage liver disease(MELD).The area under the curve of the mLPaM model(0.855,0.872,respectively)and sLPaM model(0.869,0.876,respectively)were higher than that of the methods for MELD,albumin bilirubin grade and PTAR in the two cohorts,and their sensitivity and negative predictive value were the highest among these methods in the training *** addition,the new models showed good sensitivity and accuracy for the diagnosis of LRF impairment in the validation *** The new models had a good predictive performance for LRF and could replace the indocyanine green(ICG)clearance test,especially in patients who are unable to undergo ICG testing.

关键词： Liver stiffness measurement Chronic liver disease Liver reserve function Indocyanine green clearance test Predictive model

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Tenofovir vs lamivudine plus adefovir in chronic hepatitis B:TENOSIMP-B study

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World Journal of Gastroenterology 2017年第41期23卷 7459-7469页

作者： Manuel Rodríguez Juan Manuel Pascasio Enrique Fraga Javier Fuentes Martín Prieto Gloria Sánchez-Antolín Jose Luis Calleja Esther Molina María Luisa García-Buey María Angeles Blanco Javier Salmerón María Lucía Bonet Jose Antonio Pons Jose Manuel González Miguel Angel Casado Francisco Jorquera 无 Division of Gastroenterology and hepatology.Hospital Universitario Central de Asturias Unit for the Clinical Management of Digestive Diseases IBISHospital Universitario Virgen del Rocío Liver Transplantation and hepatology Unit Gastroenterology ServiceHospital Universitario Reina Sofía Digestive Medicine service Hospital Universitario Miguel Servet hepatology Unit Digestive Medicine ServiceHospital Universitari i Politècnic La Fe hepatology Unit Hospital Universitario Rio Hortega Liver Unit Hospital Universitario Puerta de Hierro de MajadahondaUniversidad Autónoma de Madrid Digestive Medicine service Hospital Clínico de Santiago de Compostela Liver Unit Hospital Universitario de La Princesa Digestive Medicine service Hospital General Universitario Gregorio Maranon Digestive Medicine Unit Complejo Hospitalario de Granada Digestive Medicine service Hospital Universitario Son Espases hepatology Unit IMIB Hospital Universitario Virgen de la Arrixaca Digestive Medicine service Hospital Clínico Universitario de Valladolid Pharmacoeconomics and Outcomes Research Iberia Division of Gastroenterology and hepatology Complejo Asistencial Universitario de León the TENOSIMP-B Research Group

AIM To demonstrate the non-inferiority(15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate(TDF) vs the combination of lamivudine(LAM) plus adefovir dipivoxil(ADV) in the maintenance of virologic response in patients with chronic hepatitis B(CHB) and prior failure with *** This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups(TDF and LAM+ADV) of adult patients with hepatitis B e antigen(HBe Ag)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were *** Forty-six patients were evaluated [median age: 55.4 years(30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DNA(HBV-DNA) remained undetectable, all patients remained HBe Ag negative, and hepatitis B surface antigen(HBs Ag) positive. Alanine aminotransferase(ALT) values at the end of the study were similar in the 2 groups(25.1± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects(AEs)(53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively(P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment(€4943 ± 1059 vs €5811 ± 1538, respectively, P < 0.001).CONCLUSION TDF monotherapy proved to be safe

关键词： Tenofovir Lamivudine+Adefovir Efficacy Safety Adherence Costs Hepatitis B

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Endoscopic management of complications of chronic pancreatitis

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World Journal of Gastroenterology 2013年第42期19卷 7308-7315页

作者： Jean-Marc Dumonceau Carlos Macias-Gomez Division of Gastroenterology and hepatology Geneva University Hospital1211 GenevaSwitzerland Gastrointestinal Endoscopy Unit Gastroenterology ServiceItalian Hospital1181 Buenos AiresArgentina

Pseudocysts and biliary obstructions will affect approximately one third of patients with chronic pancreatitis(CP).For CP-related,uncomplicated,pancreatic pseudocysts(PPC),endoscopy is the first-choice therapeutic *** advances have focused on endosonography-guided PPC transmural drainage,which tends to replace the conventional,duodenoscope-based coma immediately *** material is being tested to facilitate the endosonography-guided *** this review,the most adequate techniques depending on PPC characteristics are presented along with supporting *** CP-related biliary obstructions,endoscopy and surgery are valid therapeutic *** co-morbidities(e.g.,portal cavernoma)and expected patient compliance to repeat endoscopic procedures are important factors when selecting the most adapted *** should be reasonably ruled out before embarking on the endoscopic treatment of presumed CP-related biliary *** endoscopy,the gold standard technique consists of placing simultaneous,multiple,side-by-side,plastic stents for a oneyear *** covered self-expandable metal stents are challenging this method and have provided 50%mid-term success.

关键词： Biliary stricture Chronic pancreatitis Pseudocyst Endoscopic retrograde cholangio-pancreatography Endoscopic ultrasonography Stent

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Microwave ablation of hepatocellular carcinoma

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World Journal of hepatology 2015年第25期7卷 2578-2589页

作者： Guido Poggi Nevio Tosoratti Benedetta Montagna Chiara Picchi Oncology and hepatology Unit Institute of Care Città di Pavia R and E Unit HS Hospital Service SpA

Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma(HCC) in patients with well compensated cirrhosis,thermal ablation techniques provide a valid nonsurgical treatment alternative,thanks to their minimal invasiveness,excellent tolerability and safety profile,proven efficacy in local disease control,virtually unlimited repeatability and *** energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC *** them,radiofrequency(RF) currents are the most used,while microwave ablations(MWA) are becoming increasingly *** from the 90s',RF ablation(RFA) rapidly became the standard of care in ablation,especially in the treatment of small HCC nodules;however,RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat ***,first introduced in the Far Eastern clinical practice in the 80s',showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors,resulting in a poor coagulative performance and a relatively high complication rate,nowadays shows better results both in terms of treatment controllability and of overall coagulative performance,thanks to the improvement of *** this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems,and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications,both in absolute terms and in comparison with RFA.

关键词： Thermal ablation Hepatocellular carcinoma Microwave ablation Percutaneous microwave ablation Laparoscopic microwave ablation Complications

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