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Publisher: John Wiley and Sons   (Total: 1580 journals)

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Showing 1 - 200 of 1580 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 13, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 65, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 47, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 52, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 158, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 6, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 6, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 4)
Addiction     Hybrid Journal   (Followers: 35, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 13, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 27, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 268, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 7, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 10)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 15, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 6, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 31, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 145, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 90, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 28, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 33, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 16, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 272, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 17, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 136, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 18)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 196)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 219, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 39, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 47, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 9, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 25, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 90, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 49, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 7, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 70, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 206, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 49, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 246, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 50, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 26, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 323, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 6, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 15, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 4, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 47, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 4, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 29, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 14, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 408, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 5, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 72, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 20, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 36, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 11, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 24, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 9, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 16, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 4, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 42, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 36, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 160, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 38, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 6, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 243, SJR: 2.083, h-index: 125)

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Journal Cover Alimentary Pharmacology & Therapeutics
  [SJR: 2.833]   [H-I: 138]   [33 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0269-2813 - ISSN (Online) 1365-2036
   Published by John Wiley and Sons Homepage  [1580 journals]
  • Market share and costs of biologic therapies for inflammatory bowel
           disease in the USA
    • Authors: H. Yu; D. MacIsaac, J. J. Wong, Z. M. Sellers, A. A. Wren, R. Bensen, C. Kin, K. T. Park
      Abstract: BackgroundReal-world data quantifying the costs of increasing use of biologics in inflammatory bowel disease (IBD) are unknown.AimTo determine the outpatient IBD drug utilization trends, relative market share, and costs in the USA during a 9-year period.MethodsThe Truven MarketScan® Database was analysed for patients with Crohn's disease (CD) and ulcerative colitis (UC) during 2007-2015. National drug codes were used to identify prescription drugs; Healthcare Common Procedure Coding System J-codes were used to capture biologic out-patient infusions. Proportion of drug usage, relative market share and per-member per-year (PMPY) costs were analysed for biologics, immunomodulators, 5-ASAs and corticosteroids.ResultsIn 415 405 patients (188 842 CD; 195 183 UC; 31 380 indeterminate colitis; 54.67% female), utilization trends show a consistent rise in the market share of biologics during the 9-year study period. The proportion of patients using biologics increased from 21.8% to 43.8% for CD and 5.1%-16.2% for UC. This contrasts a small decrease in immunomodulator and 5-ASA use for CD and relative constancy of other classes including corticosteroids-only use as primary IBD medication from 2007 to 2015. The average biologic-taking patient accounted for $25 275 PMPY in 2007 and $36 051 PMPY in 2015. The average paediatric biologic-taking patient accounted for $23 616 PMPY in 2007 and $41 109 PMPY in 2015. In all patients, the share of costs for biologics increased from 72.9% in 2007 to 85.7% in 2015 (81.7% in 2007 to 94.9% in 2015 in paediatrics).ConclusionThe vast majority of costs allocated to out-patient IBD medications in the USA is attributed to increasing use of biologic therapies despite the relative minority of biologic-taking patients.
      PubDate: 2017-11-22T04:20:24.871853-05:
      DOI: 10.1111/apt.14430
  • Long-term safety of adalimumab in clinical trials in adult patients with
           Crohn's disease or ulcerative colitis
    • Authors: J.-F. Colombel; W. J. Sandborn, W. Reinisch, L. Peyrin-Biroulet, R. Panaccione, P. Rutgeerts, S. B. Hanauer, S. Ghosh, G. Van Assche, A. M. Robinson, W. Lau, J.-F. Maa, B. Huang, B. Pappalardo, H. Read
      Abstract: BackgroundAdalimumab is used to treat moderate to severe Crohn's disease (CD) and ulcerative colitis (UC) when conventional therapies fail.AimTo update long-term adalimumab safety from CD and UC trials; the previous report was CD only, 3160 patients/3402 patient-years (PYs).MethodsTreatment-emergent adverse events (AEs; first dose to 70 days after last dose/December 31, 2015) in adults in phase 2/3 and 3/3b trials and open-label extensions were coded using Medical Dictionary for Regulatory Activities (MedDRA-v18.1). Rates were assessed as events/100 (E/100 PYs).ResultsThe database (16 trials; CD, N = 3606; UC, N = 1739) represented 4145 and 3397 PYs of exposure, respectively. For CD, incidences of any AEs with adalimumab were 60.8%-65.1%, depending on dose, and 71.5% with placebo; for UC, the incidences were 53.5%-54.8% and 56.1%, respectively. Rates of any AEs (CD, 605 E/100 PYs; UC, 361 E/100 PYs), serious AEs (CD, 36.1 E/100 PYs; UC, 18.9 E/100 PYs), and malignancies (CD, 1.2 E/100 PYs; UC, 1.0 E/100 PYs) were similar between current and prior analyses. Apparent rate of opportunistic infections was lowered to 0.3 and 0.2 E/100 PYs for CD and UC, respectively, by recent MedDRA changes excluding oral candidiasis and tuberculosis. Standardised incidence ratios for malignancies were similar to the general population (CD, 1.45 [95% CI, 0.90-2.22]; UC, 1.36 [95% CI, 0.84-2.07]). Demyelinating disorders were uncommon (CD, 0.1 E/100 PYs; UC,
      PubDate: 2017-11-21T04:26:42.102355-05:
      DOI: 10.1111/apt.14420
  • Exposure-response relationship of certolizumab pegol induction and
           maintenance therapy in patients with Crohn's disease
    • Authors: N. Vande Casteele; B. G. Feagan, S. Vermeire, M. Yassine, J. Coarse, G. Kosutic, W. J. Sandborn
      Abstract: BackgroundTherapeutic drug monitoring may optimize therapy for Crohn's disease (CD).AimTo use a population pharmacokinetic model that accounts for the time-varying nature of covariates to simulate certolizumab pegol (CZP) concentrations to evaluate the exposure-response relationship for CZP in Crohn's disease.MethodsAdults (N = 2157) with Crohn's disease were treated with CZP in nine clinical trials. Simulated CZP concentrations were compared to outcomes at weeks 6 and 26, including Crohn's disease activity index (CDAI) response (decrease from baseline ≥ 100 points), remission (CDAI ≤ 150), C-reactive protein (CRP) ≤ 5 mg/L, faecal calprotectin (FC) ≤ 250 μg/g, and a composite endpoint of CDAI ≤ 150 and FC ≤ 250 μg/g. Multivariable analyses identified covariates associated with outcomes and receiver operating characteristic analyses determined optimal CZP concentrations.ResultsCZP concentrations at weeks 2, 4 and 6 were higher in patients with clinical response, remission, CRP ≤ 5 mg/L or FC ≤ 250 μg/g at week 6 than without. In multivariable analyses, higher CZP concentrations at week 6 were associated with the composite outcome at weeks 6 and 26 (P 
      PubDate: 2017-11-21T04:20:51.514372-05:
      DOI: 10.1111/apt.14421
  • Genetic risk factors for perception of symptoms in GERD: an observational
           cohort study
    • Authors: A. Patel; S. Hasak, B. D. Nix, G. S. Sayuk, R. D. Newberry, C. P. Gyawali
      Abstract: BackgroundGenetic polymorphisms in G-protein beta-3 subunit (GNβ3) and beta-2 adrenergic receptor (ADRB2) are associated with pain and gut hypersensitivity, which can overlap with gastroesophageal reflux disease (GERD).AimTo evaluate relationships between single nucleotide polymorphisms (SNPs) within GNβ3 and ADRB2 systems, and reflux symptom burden, GERD phenotypes from ambulatory reflux monitoring, and quality of life.MethodsSymptomatic adults undergoing ambulatory reflux testing were recruited and phenotyped based on acid burden and symptom reflux association; major oesophageal motor disorders and prior foregut surgery were exclusions. A comparison asymptomatic control cohort was also identified. Subjects and controls completed questionnaires assessing symptom burden on visual analog scales, short-form health survey-36 (SF-36), and Beck Anxiety and Depression Inventories (BAI and BDI). Genotyping was performed from saliva samples; 6 SNPs selected from each of the two genes of interest were compared.ResultsSaliva from 151 study subjects (55.3 ± 1.2 years, 63.6% F) and 60 control subjects (50.9 ± 2.2 years, 66.7%) had sufficient genetic material for genotyping. Study subjects had higher symptom burden, worse total and physical health, and higher anxiety scores compared to controls (P ≤ .002). Tested SNPs within ADRB2 were similar between study subjects and controls (P> .09). Study subjects with recessive alleles in 3 GNβ3 SNPs (Rs2301339, Rs5443, and Rs5446) had worse symptom severity (P = .011), worse mental health (P = .03), and higher depression scores (P = .005) despite no associations with GERD phenotypes or reflux metrics.ConclusionsGenetic variation within GNβ3 predicts oesophageal symptom burden and affect, but not oesophageal acid burden or symptom association with reflux episodes.
      PubDate: 2017-11-17T02:15:53.228489-05:
      DOI: 10.1111/apt.14414
  • Early drug and anti-infliximab antibody levels for prediction of primary
           nonresponse to infliximab therapy
    • Authors: H. Bar-Yoseph; N. Levhar, L. Selinger, U. Manor, M. Yavzori, O. Picard, E. Fudim, U. Kopylov, R. Eliakim, S. Ben-Horin, Y. Chowers, B. Ungar
      Abstract: BackgroundPrimary nonresponse, defined as lack of clinical benefit during the induction phase, occurs in up to 30% of IBD patients treated with infliximab. The mechanisms underlying primary nonresponse have not yet been clearly defined.AimTo evaluate the association of early (week 2 and week 6) induction infliximab and anti-infliximab antibody levels with primary nonresponse.MethodsA retrospective observational case-control study of inflammatory bowel disease patients treated with infliximab and followed at Sheba Medical Center between 2009 and 2016 was performed. Pre-infusion infliximab and antibodies to infliximab (ATI) levels were measured by our previously described drug-tolerant ELISA assay.ResultsThirty-five primary nonresponders have been identified and matched with 105 primary responders (1:3 ratios). Both week 2 and week 6 infliximab levels were significantly lower among primary nonresponders compared to responders (week 2, 6: median level 7.2, 2.2 μg/mL vs 13.5, 9.5 μg/mL, P = .0019, P 
      PubDate: 2017-11-09T20:05:22.197671-05:
      DOI: 10.1111/apt.14410
  • Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease
           in the Veterans Health Administration
    • Authors: Y. A. Patel; E. J. Gifford, L. M. Glass, R. McNeil, M. J. Turner, B. Han, D. Provenzale, S. S. Choi, C. A. Moylan, C. M. Hunt
      Abstract: BackgroundWith its increasing incidence, nonalcoholic fatty liver disease (NAFLD) is of particular concern in the Veterans Health Administration (VHA).AimsTo evaluate risk factors for advanced fibrosis in biopsy-proven NAFLD in the VHA, to identify patients at risk for adverse outcomes.MethodsIn randomly selected cases from VHA databases (2005-2015), we performed a retrospective case-control study in adults with biopsy-defined NAFLD or normal liver.ResultsOf 2091 patients reviewed, 399 met inclusion criteria. Normal controls (n = 65) had normal liver function. The four NAFLD cohorts included: NAFL steatosis (n = 76), nonalcoholic steatohepatitis (NASH) without fibrosis (n = 68), NAFLD/NASH stage 1-3 fibrosis (n = 82), and NAFLD/NASH cirrhosis (n = 70). NAFLD with hepatocellular carcinoma (HCC) was separately identified (n = 38). Most patients were older White men. NAFLD patients with any fibrosis were on average severely obese (BMI>35 kg/m2). Diabetes (54.4%-79.6%) and hypertension (85.8%-100%) were more common in NAFLD with fibrosis or HCC. Across NAFLD, 12.3%-19.5% were enrolled in diet/exercise programs and 0%-2.6% had bariatric surgery. Hispanics exhibited higher rates of NASH (20.6%), while Blacks had low NAFLD rates (1.4%-11.8%), particularly NAFLD cirrhosis and HCC (1.4%-2.6%). Diabetes (OR 11.8, P 
      PubDate: 2017-11-08T05:15:23.700922-05:
      DOI: 10.1111/apt.14411
  • Proton pump inhibitors are associated with accelerated development of
           cirrhosis, hepatic decompensation and hepatocellular carcinoma in
           noncirrhotic patients with chronic hepatitis C infection: results from
    • Authors: D. K. Li; P. Yan, A-B. Abou-Samra, R. T. Chung, A. A. Butt
      Abstract: BackgroundProton pump inhibitors are among the most commonly prescribed medications in the United States. Their safety in cirrhosis has recently been questioned, but their overall effect on disease progression in noncirrhotic patients with chronic liver disease remains unclear.AimTo determine the impact of proton pump inhibitors on the progression of liver disease in noncirrhotic patients with hepatitis C virus (HCV) infection.MethodsUsing the electronically retrieved cohort of HCV-infected veterans (ERCHIVES) database, we identified all subjects who received HCV treatment and all incident cases of cirrhosis, hepatic decompensation and hepatocellular carcinoma. Proton pump inhibitor use was measured using cumulative defined daily dose. Multivariate Cox regression analysis was performed after adjusting univariate predictors of cirrhosis and various indications for proton pump inhibitor use.ResultsAmong 11 526 eligible individuals, we found that exposure to proton pump inhibitors was independently associated with an increased risk of developing cirrhosis (hazard ratio [HR]: 1.32; 95% confidence interval: [1.17, 1.49]). This association remained robust to sensitivity analysis in which only patients who achieved sustained virologic response were analysed as well as analysis excluding those with alcohol abuse/dependence. Proton pump inhibitor exposure was also independently associated with an increased risk of hepatic decompensation (HR: 3.79 [2.58, 5.57]) and hepatocellular carcinoma (HR: 2.01 [1.50, 2.70]).ConclusionsIn patients with chronic HCV infection, increasing proton pump inhibitor use is associated with a dose-dependent risk of progression of chronic liver disease to cirrhosis, as well as an increased risk of hepatic decompensation and hepatocellular carcinoma.
      PubDate: 2017-11-03T04:10:50.836659-05:
      DOI: 10.1111/apt.14391
  • Angiotensin receptor blocker use and gastro-oesophageal cancer survival: a
           population-based cohort study
    • Authors: J. Busby; Ú. McMenamin, A. Spence, B. T. Johnston, C. Hughes, C. R. Cardwell
      Abstract: BackgroundAngiotensin receptor blockers (ARBs; including candesartan, losartan, olmesartan and valsartan) are widely used to treat hypertension, heart failure and diabetic neuropathy. There is considerable pre-clinical evidence that ARBs can reduce cancer progression, particularly for gastric cancer. Despite this, epidemiological studies have yet to assess the impact of ARB use on gastro-oesophageal cancer survival.AimTo investigate the association between post-diagnosis ARB use and gastro-oesophageal cancer survival.MethodsWe selected a cohort of patients with newly-diagnosed gastro-oesophageal cancer between 1998 and 2012 from English cancer registries. We linked to prescription and clinical records from the Clinical Practice Research Datalink, and to death records from the Office for National Statistics. We used time-dependant Cox-regression models to calculate hazard ratios (HRs) comparing gastro-oesophageal cancer-specific mortality between post-diagnosis ARB users and non-users, after adjusting for demographics, comorbidities and post-diagnosis aspirin or statin use.ResultsOur cohort included 5124 gastro-oesophageal cancer patients, of which 360 used ARBs, and 3345 died due to their gastro-oesophageal cancer during follow-up. After adjustment, ARB users had moderately lower risk of gastro-oesophageal cancer mortality than the non-users (HR = 0.83, 95% CI 0.71-0.98). There was evidence of a dose–response relationship with the lowest HRs observed among patients receiving at least 2 years of prescriptions (HR = 0.42, 95% CI 0.25-0.72).ConclusionsIn this large population-based gastro-oesophageal cancer cohort, we found moderately reduced cancer-specific mortality among ARB users. However, confirmation in further independent epidemiological studies with sufficient staging information is required.
      PubDate: 2017-11-03T04:00:23.651656-05:
      DOI: 10.1111/apt.14388
  • Randomised clinical study: the effects of oral taurine 6/day g vs placebo
           daily on portal hypertension
    • Authors: R. Schwarzer; D. Kivaranovic, M. Mandorfer, R. Paternostro, D. Wolrab, B. Heinisch, T. Reiberger, M. Ferlitsch, C. Gerner, M. Trauner, M. Peck-Radosavljevic, A. Ferlitsch
      Abstract: BackgroundThe amino sulphonic acid taurine reduces oxidative endoplasmatic reticulum stress and inhibits hepatic stellate cell activation, which might lead to reduction of portal pressure in cirrhosis.AimTo assess the haemodynamic effects of taurine supplementation in patients with cirrhosis and varices.MethodsPatients with hepatic venous pressure gradient (HVPG) ≥12 mm Hg were included in this prospective proof of concept study. Concomitant nonselective beta-blockers therapy was not allowed. Patients received either 4 weeks of oral taurine (6 g/day), or placebo, prior to evaluation of HVPG response.ResultsThirty patients were screened and 22 included in the efficacy analysis (12 taurine/10 placebo; 64% male, mean age: 52 ± 11 years, Child A: 9%, B:64%, C:27%, ascites:68%).In the taurine group, mean HVPG dropped from 20 mm Hg (±4) at baseline to 18 mm Hg (±4) on day 28 (mean relative change: −12%, P = .0093). In the placebo group, mean HVPG increased from 20 mm Hg (±5) at baseline to 21 mm Hg (±5) on day 28 (mean relative change:+2%, P = .4945). Taurine had no significant effects on systemic haemodynamics. Seven of 12 patients (58%) on taurine achieved a HVPG response>10%, compared to none in the placebo group (P = .0053). In a multivariate linear model, HVPG reduction was significantly larger in the taurine group compared to placebo group (P = .0091 and P = .0109 for absolute and relative change respectively). Treatment-related adverse events included gastrointestinal discomfort and fatigue, and were usually mild and comparable between treatment groups.ConclusionTaurine is safe and may reduce portal pressure in cirrhotic patients. More studies on the underlying mechanisms of action and long-term effects of taurine supplementation are warranted.
      PubDate: 2017-11-03T03:55:28.288893-05:
      DOI: 10.1111/apt.14377
  • Systematic review with meta-analysis: the significance of histological
           disease severity in lean patients with nonalcoholic fatty liver disease
    • Authors: S. Sookoian; C. J. Pirola
      Abstract: BackgroundCurrent evidence suggests that lean and obese patients with nonalcoholic fatty liver disease (NAFLD) share an altered metabolic and cardiovascular profile. However, there is an incomplete understanding of the natural history of “lean-NAFLD.” Indeed, an unanswered question is whether lean (BMI ≤ 25 Kg/m2) NAFLD-patients are protected from severe histological outcomes.AimTo perform a meta-analysis with the goal of providing a quantitative estimation of the magnitude of fibrosis, as well as histological features associated with the disease severity, in lean versus overweight/obese-NAFLD patients.MethodsThrough a systematic search up to July 2017, we identified eight studies that compared histological outcomes in lean (n = 493) versus overweight/obese (n = 2209) patients.ResultsRelative to lean-NAFLD, overweight/obese-NAFLD patients showed significantly (P = .032) higher fibrosis scores; the observed difference in means between the two groups, which is the absolute difference between the mean value of fibrosis score [0-4] ± standard error, was 0.28 ± 0.13. The risk of having nonalcoholic steatohepatitis-NASH (OR 0.58 95% CI 0.34-0.97) was significantly lower in lean-NAFLD (n = 322) than in overweight/obese-NAFLD (n = 1357), P = .04. Relative to lean-NAFLD, overweight/obese-NAFLD patients also have significantly greater NAFLD activity (difference in means ± SE: 0.58 ± 0.16, P = .0004) and steatosis (difference in means ± SE: 0.23 ± 0.07, P = .002) scores.ConclusionsLean-NAFLD patients tend to show less severe histological features as compared to overweight/obese-NAFLD patients. Subsequent longitudinal assessment is needed to understand the clinical impact of these findings; however, the significant ~ 25% increment of mean fibrosis score in overweight/obese patients suggests that obesity could predict a worse long-term prognosis.
      PubDate: 2017-10-30T04:41:36.583017-05:
      DOI: 10.1111/apt.14401
  • Review article: the gut microbiome as a therapeutic target in the
           pathogenesis and treatment of chronic liver disease
    • Authors: C. A. Woodhouse; V. C. Patel, A. Singanayagam, D. L. Shawcross
      Abstract: BackgroundMortality from chronic liver disease is rising exponentially. The liver is intimately linked to the gut via the portal vein, and exposure to gut microbiota and their metabolites translocating across the gut lumen may impact upon both the healthy and diseased liver. Modulation of gut microbiota could prove to be a potential therapeutic target.AimTo characterise the changes in the gut microbiome that occur in chronic liver disease and to assess the impact of manipulation of the microbiome on the liver.MethodsWe conducted a PubMed search using search terms including ‘microbiome’, ‘liver’ and ‘cirrhosis’ as well as ‘non-alcoholic fatty liver disease’, ‘steatohepatitis’, ‘alcohol’ and ‘primary sclerosing cholangitis’. Relevant articles were also selected from references of articles and review of the website.ResultsReduced bacterial diversity, alcohol sensitivity and the development of gut dysbiosis are seen in several chronic liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease and primary sclerosing cholangitis. Perturbations in gut commensals could lead to deficient priming of the immune system predisposing the development of immune-mediated diseases. Furthermore, transfer of stool from an animal with the metabolic syndrome may induce steatosis in a healthy counterpart. Patients with cirrhosis develop dysbiosis, small bowel bacterial overgrowth and increased gut wall permeability, allowing bacterial translocation and uptake of endotoxin inducing hepatic and systemic inflammation.ConclusionsManipulation of the gut microbiota with diet, probiotics or faecal microbiota transplantation to promote the growth of “healthy” bacteria may ameliorate the dysbiosis and alter prognosis.
      PubDate: 2017-10-30T04:25:47.016947-05:
      DOI: 10.1111/apt.14397
  • Randomised clinical trial: yoga vs a low-FODMAP diet in patients with
           irritable bowel syndrome
    • Authors: D. Schumann; J. Langhorst, G. Dobos, H. Cramer
      Abstract: BackgroundIrritable bowel syndrome is the most frequent gastrointestinal disorder. It is assumed that lifestyle interventions might be a rational treatment approach.AimTo examine the effect of a yoga-based intervention vs a low-FODMAP diet on patients with irritable bowel syndrome.MethodsFifty-nine patients with irritable bowel syndrome undertook a single-blind, randomised controlled trial involving yoga or a low-FODMAP diet for 12 weeks. Patients in the yoga group received two sessions weekly, while patients in the low-FODMAP group received a total of three sessions of nutritional counselling. The primary outcome was a change in gastrointestinal symptoms (IBS-SSS). Secondary outcomes explored changes in quality of life (IBS-QOL), health (SF-36), perceived stress (CPSS, PSQ), body awareness (BAQ), body responsiveness (BRS) and safety of the interventions. Outcomes were examined in weeks 12 and 24 by assessors “blinded” to patients’ group allocation.ResultsNo statistically significant difference was found between the intervention groups, with regard to IBS-SSS score, at either 12 (Δ = 31.80; 95%CI = −11.90, 75.50; P = .151) or 24 weeks (Δ = 33.41; 95%CI = −4.21, 71.04; P = .081). Within-group comparisons showed statistically significant effects for yoga and low-FODMAP diet at both 12 and 24 weeks (all P < .001). Comparable within-group effects occurred for the other outcomes. One patient in each intervention group experienced serious adverse events (P = 1.00) and another, also in each group, experienced nonserious adverse events (P = 1.00).ConclusionsPatients with irritable bowel syndrome might benefit from yoga and a low-FODMAP diet, as both groups showed a reduction in gastrointestinal symptoms. More research on the underlying mechanisms of both interventions is warranted, as well as exploration of potential benefits from their combined use.
      PubDate: 2017-10-27T00:41:45.418827-05:
      DOI: 10.1111/apt.14400
  • Colectomy prior to diagnosis of primary sclerosing cholangitis is
           associated with improved prognosis in a nationwide cohort study of 2594
           PSC-IBD patients
    • Authors: C. Nordenvall; O. Olén, P. J. Nilsson, E. von Seth, A. Ekbom, M. Bottai, P. Myrelid, A. Bergquist
      Abstract: BackgroundDespite the close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), the association between colectomy and the prognosis of PSC remains controversial.AimTo explore whether colectomy prior to PSC-diagnosis is associated with transplant-free survival.MethodsA nationwide cohort study in Sweden including all patients aged 18 to 69 years in whom both PSC and IBD was diagnosed between 1987 and 2014 was undertaken. Each patient was followed from date of both PSC and IBD diagnoses until liver transplantation or death, or 31 December 2014. Patients with colon in situ, and colectomy prior to PSC-diagnosis were compared. Survival analyses were performed using the Kaplan-Meier method and multivariable Cox regression models.ResultsOf the 2594 PSC-IBD patients, 205 patients were treated with colectomy before PSC-diagnosis. During follow-up, liver transplantations were performed in 327 patients and 509 died. The risk of liver transplantation or death was lower in patients treated with colectomy prior to PSC-diagnosis (HR 0.71, 95% CI 0.53-0.95) than in patients with colon in situ. Male gender, longer time between IBD and PSC-diagnosis and older age were all associated with an increased risk of liver transplantation or death. Colectomy after PSC-diagnosis was however not associated with an increased risk of liver transplantation or death during long-term follow-up.ConclusionsIn PSC-IBD patients, colectomy prior to PSC-diagnosis is associated with a decreased risk of liver transplantation or death.
      PubDate: 2017-10-24T05:31:28.811844-05:
      DOI: 10.1111/apt.14393
  • The taxonomic composition of the donor intestinal microbiota is a major
           factor influencing the efficacy of faecal microbiota transplantation in
           therapy refractory ulcerative colitis
    • Authors: P. Kump; P. Wurm, H. P. Gröchenig, H. Wenzl, W. Petritsch, B. Halwachs, M. Wagner, V. Stadlbauer, A. Eherer, K. M. Hoffmann, A. Deutschmann, G. Reicht, L. Reiter, P. Slawitsch, G. Gorkiewicz, C. Högenauer
      Abstract: BackgroundFaecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown.AimsTo establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success.MethodsThis is an open controlled trial of repeated faecal microbiota transplantation after antibiotic pre-treatment (FMT-group, n = 17) vs antibiotic pre-treatment only (AB-group, n = 10) in 27 therapy refractory ulcerative colitis patients over 90 days. Faecal samples of donors and patients were analysed by 16SrRNA gene-based microbiota analysis.ResultsIn the FMT-group, 10/17 (59%) of patients showed a response and 4/17 (24%) a remission to faecal microbiota transplantation. Response to faecal microbiota transplantation was mainly influenced by the taxonomic composition of the donor's microbiota. Stool of donors with a high bacterial richness (observed species remission 946 ± 93 vs no response 797 ± 181 at 15367 rps) and a high relative abundance of Akkermansia muciniphila (3.3 ± 3.1% vs 0.1 ± 0.2%), unclassified Ruminococcaceae (13.8 ± 5.0% vs 7.5 ± 3.7%), and Ruminococcus spp. (4.9 ± 3.5% vs 1.0 ± 0.7%) were more likely to induce remission. In contrast antibiotic treatment alone (AB-group) was poorly tolerated, probably because of a sustained decrease of intestinal microbial richness.ConclusionsThe taxonomic composition of the donor's intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in ulcerative colitis patients. The design of specific microbial preparation might lead to new treatments for ulcerative colitis.
      PubDate: 2017-10-20T02:45:31.669983-05:
      DOI: 10.1111/apt.14387
  • Genetic polymorphisms associated with smoking behaviour predict the risk
           of surgery in patients with Crohn's disease
    • Authors: B. M. Lang; L. Biedermann, W. T. Haaften, C. Vallière, M. Schuurmans, S. Begré, J. Zeitz, M. Scharl, M. Turina, T. Greuter, P. Schreiner, H. Heinrich, T. Kuntzen, S. R. Vavricka, G. Rogler, N. Beerenwinkel, B. Misselwitz,
      Abstract: BackgroundSmoking is a strong environmental factor leading to adverse outcomes in Crohn's disease, but a more benign course in ulcerative colitis. Several single nucleotide polymorphisms (SNPs) are associated with smoking quantity and behaviour.AimsTo assess whether smoking-associated SNPs interact with smoking to influence the clinical course of inflammatory bowel diseases.MethodsGenetic and prospectively obtained clinical data from 1434 Swiss inflammatory bowel disease cohort patients (821 Crohn's disease and 613 ulcerative colitis) were analysed. Six SNPs associated with smoking quantity and behaviour (rs588765, rs1051730, rs1329650, rs4105144, rs6474412 and rs3733829) were combined to form a risk score (range: 0-12) by adding the number of risk alleles. We calculated multivariate models for smoking, risk of surgery, fistula, Crohn's disease location and ulcerative colitis disease extent.ResultsIn Crohn's disease patients who smoke, the number of surgeries was associated with the genetic risk score. This translates to a predicted 3.5-fold (95% confidence interval: 2.4- to 5.7-fold, P7 had a significantly shorter time to first intestinal surgery. The genetic risk score did not predict surgery in ulcerative colitis or occurrence of fistulae in Crohn's disease. SNP rs6265 was associated with ileal disease in Crohn's disease (P
      PubDate: 2017-10-20T02:25:43.252457-05:
      DOI: 10.1111/apt.14378
  • Direct medical costs associated with the extrahepatic manifestations of
           hepatitis C virus infection in France
    • Authors: P. Cacoub; M. Vautier, A. C. Desbois, D. Saadoun, Z. Younossi
      Abstract: BackgroundThe economic impact of extrahepatic manifestations of hepatitis C virus (HCV) infection remains unknown for France.AimTo estimate the prevalence of extrahepatic manifestations of HCV and the direct medical costs associated with them.MethodsEstimates of 13 extrahepatic manifestations prevalence were obtained from (1) a retrospective data analysis of HCV-infected patients in a specialised centre and the baseline prevalence in the general French population and (2) an international systematic review. Per-patient-per-year costs to treat these manifestations were obtained from the literature, national databases or expert opinion. The impact of achieving HCV cure after anti-viral therapy was applied to the French healthcare costs.ResultsUsing approach (1), increased prevalence rates in HCV patients compared to the general population were observed for most extrahepatic manifestations. The mean per-patient-per-year cost of these manifestations in the tertiary centre was 3296 € [95% CI 1829; 5540]. In France, HCV-extrahepatic manifestations amounted to a total cost of 215 million (M) € per year [144; 299]. Using approach (2), the mean per-patient-per-year cost was estimated to be 1117 €. The estimated total cost reduction in France associated with HCV cure was 13.9 M€ for diabetes, 8.6 M€ for cryoglobulinemia vasculitis, 6.7 M€ for myocardial infarction, 2.4 M€ for end-stage renal disease and 1.4 M€ for stroke.ConclusionExtrahepatic manifestations of HCV infection substantially add to the overall economic burden of the disease in France. HCV cure after anti-viral therapy is expected to significantly reduce the total costs of managing these manifestations in France.
      PubDate: 2017-10-18T00:45:19.720181-05:
      DOI: 10.1111/apt.14382
  • Review article: the gut microbiome in inflammatory bowel disease—avenues
           for microbial management
    • Authors: J. McIlroy; G. Ianiro, I. Mukhopadhya, R. Hansen, G. L. Hold
      Abstract: BackgroundThe concept of an altered collective gut microbiota rather than identification of a single culprit is possibly the most significant development in inflammatory bowel disease research. We have entered the “omics” era, which now allows us to undertake large-scale/high-throughput microbiota analysis which may well define how we approach diagnosis and treatment of inflammatory bowel disease (IBD) in the future, with a strong steer towards personalised therapeutics.AimTo assess current epidemiological, experimental and clinical evidence of the current status of knowledge relating to the gut microbiome, and its role in IBD, with emphasis on reviewing the evidence relating to microbial therapeutics and future microbiome modulating therapeutics.MethodsA Medline search including items ‘intestinal microbiota/microbiome’, ‘inflammatory bowel disease’, ‘ulcerative colitis’, ‘Crohn's disease’, ‘faecal microbial transplantation’, ‘dietary manipulation’ was performed.ResultsDisease remission and relapse are associated with microbial changes in both mucosal and luminal samples. In particular, a loss of species richness in Crohn's disease has been widely observed. Existing therapeutic approaches broadly fall into 3 categories, namely: accession, reduction or indirect modulation of the microbiome. In terms of microbial therapeutics, faecal microbial transplantation appears to hold the most promise; however, differences in study design/methodology mean it is currently challenging to elegantly translate results into clinical practice.ConclusionsExisting approaches to modulate the gut microbiome are relatively unrefined. Looking forward, the future of microbiome-modulating therapeutics looks bright with several novel strategies/technologies on the horizon. Taken collectively, it is clear that ignoring the microbiome in IBD is not an option.
      PubDate: 2017-10-16T04:51:26.948958-05:
      DOI: 10.1111/apt.14384
  • Short-term risk of hepatocellular carcinoma after hepatitis C virus
           eradication following direct-acting anti-viral treatment
    • Authors: E. Ogawa; N. Furusyo, H. Nomura, K. Dohmen, N. Higashi, K. Takahashi, A. Kawano, K. Azuma, T. Satoh, M. Nakamuta, T. Koyanagi, M. Kato, S. Shimoda, E. Kajiwara, J. Hayashi,
      Abstract: BackgroundWith the development of direct-acting anti-virals (DAAs), almost all patients with chronic hepatitis C virus (HCV) infection can achieve sustained viral response (SVR).AimTo evaluate the short-term risk of HCC among patients with SVR by DAAs, including those with cirrhosis or previous HCC.MethodsThis large-scale, multicentre cohort study included 1,675 consecutive patients who achieved SVR by treatment with interferon-free sofosbuvir-based regimens, divided into groups with (n = 152) or without previous HCC (n = 1,523). The Kaplan-Meier method and Cox proportional hazard analysis were used to calculate the cumulative HCC incidence and related factors of HCC.ResultsDuring the follow-up period (median: 17 months), 46 (2.7%) patients developed HCC. The 1-year cumulative rates of de novo HCC were 0.4% and 4.9% for the noncirrhosis and cirrhosis groups respectively (log-rank test: P 
      PubDate: 2017-10-16T04:41:13.121672-05:
      DOI: 10.1111/apt.14380
  • Hepatitis B core-related antigen (HBcrAg): an emerging marker for chronic
           hepatitis B virus infection
    • Authors: L.-Y. Mak; D. K.-H. Wong, K.-S. Cheung, W.-K. Seto, C.-L. Lai, M.-F. Yuen
      Abstract: BackgroundChronic hepatitis B (CHB) cannot be completely eradicated due to the presence of covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes. While quantification of intrahepatic cccDNA requires liver biopsies, serological markers can be non-invasive alternatives to reflect intrahepatic viral replicative activity. Recently, hepatitis B core-related antigen (HBcrAg) has been advocated as a novel serum marker for disease monitoring and prognostication of CHB.AimTo examine the virological aspect and clinical application of HBcrAg with respect to the natural history and treatment of CHB.MethodsWe reviewed all papers published in the PubMed journal list and abstracts from major international meetings that included the keyword “HBcrAg” or “hepatitis B core-related antigen” until March 2017. Selected studies were compared and summarised on the basis of existing theories, as well as the authors’ experience.ResultsHBcrAg exhibited good correlation with intrahepatic (ih) cccDNA, ih total hepatitis B virus (HBV) DNA, serum HBV DNA and to a lesser extent HBV surface antigen (HBsAg). In situations where serum HBV DNA levels become undetectable or HBsAg loss is achieved, HBcrAg can still be detectable. This marker is helpful in differentiation of HBeAg-negative chronic hepatitis from HBeAg-negative chronic infection, predicting spontaneous or treatment-induced HBeAg seroconversion, sustained response to nucleos(t)ide analogue (NA), risk of HBV reactivation in occult HBV infection under immunosuppressive therapies, and risk of hepatocellular carcinoma (HCC) development as well as post-operative HCC recurrence.ConclusionsHBcrAg is a potential surrogate marker of cccDNA. It may soon become a useful marker for disease monitoring, predicting treatment response and disease outcome of chronic hepatitis B.
      PubDate: 2017-10-16T04:25:47.988712-05:
      DOI: 10.1111/apt.14376
  • The albumin-bilirubin grade uncovers the prognostic relationship between
           hepatic reserve and immune dysfunction in HIV-associated hepatocellular
    • Authors: D. J. Pinato; R. Sharma, C. Citti, H. Platt, M. Ventura-Cots, E. Allara, T.-Y. Chen, A. Dalla Pria, M. Jain, B. Mínguez, L. Kikuchi, E. Kaufman West, M. Merli, D. E. Kaplan, H. Hasson, K. Marks, M. Nelson, M. Núñez, A. Aytaman, M. Bower, N. Bräu,
      Abstract: BackgroundHepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease.AimTo evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection.MethodsUsing uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded.ResultsA total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P 
      PubDate: 2017-10-16T04:17:30.130116-05:
      DOI: 10.1111/apt.14356
  • Efficacy and safety of golimumab in Crohn's disease: a French national
           retrospective study
    • Authors: C. Martineau; B. Flourié, P. Wils, T. Vaysse, R. Altwegg, A. Buisson, A. Amiot, G. P. Chambrun, V. Abitbol, M. Fumery, X. Hébuterne, S. Viennot, D. Laharie, L. Beaugerie, S. Nancey, H. Sokol,
      Abstract: BackgroundAnti-tumour necrosis factor (TNF) agents have improved the care of Crohn's disease (CD). After the first anti-TNF discontinuation, it is possible to switch to another anti-TNF. Three anti-TNF agents are available for ulcerative colitis (infliximab, adalimumab and golimumab), but only the first 2 have been approved for CD because golimumab has not been studied for this indication.AimTo report the efficacy and safety of golimumab in CD.MethodsCrohn's disease patients who received golimumab were identified in 12 French tertiary centres and were retrospectively analysed. The primary endpoint was the duration of golimumab treatment before escalation or discontinuation. The clinical response was defined as a decrease of more than 3 points in the Harvey-Bradshaw index or by global physician assessment.ResultsOne hundred and fifteen patients were included. The golimumab treatment duration was 9.8 months (0.55-44), and 48.7% of the patients were still under treatment at the end of follow-up. Clinical response was observed in 55.8% of the patients after a mean duration of 3.8 months. The probability of remaining under treatment without escalation at 6, 12 and 24 months was 54.6%, 34.9% and 19.3% respectively. In multivariate analysis, discontinuation of the first anti-TNF agent due to intolerance (odds ratio, OR = 2.16; 95% CI, confidence interval [1.25-3.86]; P = .005) and co-immunosuppression for more than 6 months (OR = 3.98; 95% CI [2.3-7.1]; P < .0001) were predictive factors of efficacy. Six per cent of the patients discontinued treatment due to intolerance.ConclusionAfter failure of infliximab or adalimumab for Crohn's disease, golimumab was safe and seemed beneficial in half of the patients.
      PubDate: 2017-10-13T04:45:30.221522-05:
      DOI: 10.1111/apt.14371
  • Review article: consensus statements on therapeutic drug monitoring of
           anti-tumour necrosis factor therapy in inflammatory bowel diseases
    • Authors: N. Mitrev; N. Vande Casteele, C. H. Seow, J. M. Andrews, S. J. Connor, G. T. Moore, M. Barclay, J. Begun, R. Bryant, W. Chan, C. Corte, S. Ghaly, D. A. Lemberg, V. Kariyawasam, P. Lewindon, J. Martin, R. Mountifield, G. Radford-Smith, P. Slobodian, M. Sparrow, C. Toong, D. Langenberg, M. G. Ward, R. W. Leong,
      Abstract: BackgroundTherapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti-tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines.AimTo develop evidence-based consensus statements for TDM-guided anti-TNF therapy in IBD.MethodsA committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted.Results22/24 statements met criteria for consensus. For anti-TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3-8 and 5-12 μg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints—such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision-making. In stable clinical response, TDM-guided dosing may avoid future relapse. Data indicate drug-tolerant anti-drug antibody assays do not offer an advantage over drug-sensitive assays. Further data are required prior to recommending TDM for non-anti-TNF biological agents.ConclusionConsensus statements support the role of TDM in optimising anti-TNF agents to treat IBD, especially in situations of treatment failure.
      PubDate: 2017-10-13T02:50:28.389829-05:
      DOI: 10.1111/apt.14368
  • HBeAg levels at week 24 predict response to 8 years of tenofovir in
           HBeAg-positive chronic hepatitis B patients
    • Authors: D. Wong; M. Littlejohn, L. Yuen, K. Jackson, H. Mason, J. Bayliss, G. Rosenberg, A. Gaggar, K. Kitrinos, M. Subramanian, P. Marcellin, M. Buti, H. L. A. Janssen, E. Gane, S. Locarnini, A. Thompson, P. A. Revill
      Abstract: BackgroundHepatitis B e antigen (HBeAg) seroconversion is a treatment endpoint for HBeAg-positive CHB, and a necessary precursor to HBsAg loss. Biomarkers that predict serological outcomes would be useful.AimTo evaluate the utility of measuring HBeAg levels for predicting HBeAg seroconversion and HBsAg loss under long-term tenofovir (TDF) therapy.MethodsA total of 266 patients were enrolled into a phase III study of TDF vs adefovir (ADV) for 48 weeks in HBeAg-positive patients, followed by open-label TDF up to 384 weeks. Serum HBeAg levels were measured for subjects with samples available at both baseline and week 24 of treatment (n = 200). Analysis compared subjects who achieved HBeAg seroconversion by week 384 vs no HBeAg seroconversion.ResultsHBeAg seroconversion rate was 52% by week 384. Time to HBeAg seroconversion was 80 weeks (IQR: 36-162). HBeAg decline at week 24 was associated with HBeAg seroconversion (1.63 vs 0.90 log10 PEIU/mL, P = .002). The optimal threshold for identifying HBeAg seroconversion was HBeAg decline ≥2.2 log10 PEIU/mL at week 24, with HBeAg seroconversion achieved by 76% of patients, compared to 44% if HBeAg decline
      PubDate: 2017-10-11T04:35:54.991115-05:
      DOI: 10.1111/apt.14362
  • Cholangiopathy in critically ill patients surviving beyond the intensive
           care period: a multicentre survey in liver units
    • Authors: L. Laurent; C. Lemaitre, A. Minello, A. Plessier, G. Lamblin, A. Poujol-Robert, A. Gervais-Hasenknopf, E.-A. Pariente, P. Belenotti, N. Mostefa-Kara, P. Sogni, M. Legrand, J.-M. Cournac, F. Tamion, G. Savoye, P. Bedossa, D.-C. Valla, V. Vilgrain, O. Goria
      Abstract: BackgroundThe outcome of cholangiopathy developing in intensive care unit (ICU) is not known in patients surviving their ICU stay.AimTo perform a survey in liver units, in order to clarify the course of cholangiopathy after surviving ICU stay.MethodsThe files of the liver units affiliated to the French network for vascular liver disease were screened for cases of ICU cholangiopathy developing in patients with normal liver function tests on ICU admission, and no prior history of liver disease.ResultsBetween 2005 and 2015, 16 cases were retrieved. Extensive burns were the cause for admission to ICU in 11 patients. Serum alkaline phosphatase levels increased from day 11 (2-46) to a peak of 15 (4-32) × ULN on day 81 (12-511). Magnetic resonance cholangiography showed irregularities or frank stenosis of the intrahepatic ducts, and proximal extrahepatic ducts contrasting with a normal aspect of the distal common bile duct. Follow-up duration was 20.6 (4.7-71.8) months. Three patients were lost to follow-up; 2 patients died from liver failure and no patient was transplanted. One patient had worsening strictures of the intrahepatic bile ducts with jaundice. Nine patients had persistent but minor strictures of the intrahepatic bile ducts on MR cholangiography, and persistent cholestasis without jaundice. One patient had normal liver function tests.ConclusionsIn patients surviving their ICU stay, ICU cholangiopathy is not uniformly fatal in the short term or clinically symptomatic in the medium term. Preservation of the distal common bile duct appears to be a finding differentiating ICU cholangiopathy from other diffuse cholangiopathies.
      PubDate: 2017-10-11T04:20:25.363144-05:
      DOI: 10.1111/apt.14367
  • Systematic review and meta-analysis: assessment of factors affecting
           disability in inflammatory bowel disease and the reliability of the
           inflammatory bowel disease disability index
    • Authors: B. Lo; M. V. Prosberg, L. L. Gluud, W. Chan, R. W. Leong, E. List, M. Have, H. Sarter, C. Gower-Rousseau, L. Peyrin-Biroulet, I. Vind, J. Burisch
      Abstract: BackgroundThe Inflammatory Bowel Disease Disability Index (IBD-DI) has recently been developed for patients with Crohn's disease (CD) and ulcerative colitis (UC).AimTo assess the severity of disability and associated factors using the IBD-DI, and review the validity of the IBD-DI as a tool.MethodSystematic review of cross-sectional studies. Patients included had UC or CD and were classified as active, in remission, or needing surgery, biological and/or steroid treatment. We included studies assessing disability using the IBD-DI and that were captured by electronic and manual searches (January 2017). The possibility of bias was evaluated with the Newcastle-Ottawa Scale.ResultsNine studies were included with 3167 patients. Comparatively, patients with active disease had higher disability rates than those in remission (SMD [CI95] = 1.49[1.11, 1.88], I2 = 94%, P
      PubDate: 2017-10-09T22:50:33.19294-05:0
      DOI: 10.1111/apt.14373
  • Beta-blockers in hospitalised patients with cirrhosis and ascites:
           mortality and factors determining discontinuation and reinitiation
    • Authors: A. Q. Bhutta; G. Garcia-Tsao, K. R. Reddy, P. Tandon, F. Wong, J. G. O'Leary, C. Acharya, D. Banerjee, J. G. Abraldes, T. M. Jones, J. Shaw, Y. Deng, M. Ciarleglio, J. S. Bajaj
      Abstract: BackgroundIt has been suggested that beta-blockers may increase mortality in patients with cirrhosis and refractory ascites but the effect of beta-blockers discontinuation or reinitiation has not been examined.AimsTo compare, in hospitalised patients with cirrhosis and ascites, the effect of BB on survival and to examine the effect/predictors of beta-blockers discontinuation and reinitiation.MethodsSub-analysis of NACSELD (North American consortium for the study of end-stage liver disease, database containing prospective data on hospitalised patients with cirrhosis) data from 7 centres enrolling>100 patients with ascites. Data on BB discontinuation and reinitiation were collected by chart review.ResultsSeven hundred and sixteen patients, 307 (43%) on beta-blockers at admission and 366 (51%) with refractory ascites, were followed to death or hospital discharge. Beta-blocker use was associated with a lower white blood cell count at admission. Beta-blocker use in hospitalised patients with ascites was not associated with a higher mortality, even in those with refractory ascites. No significant changes in mean arterial pressure (MAP) were observed between groups. Discontinuation of beta-blockers (49%) was driven by low MAP, infection and acute kidney injury at time of discontinuation but was not associated with a higher mortality. Beta-blocker reinitiation occurred in 40% prior to discharge and was mainly driven by an increase in MAP.ConclusionsBeta-blocker use is safe in patients with cirrhosis and ascites (including those with refractory ascites) provided beta-blockers are discontinued in the presence of a low MAP and reinitiated once MAP reincreases. A potentially beneficial anti-inflammatory effect of beta-blockers is suggested.
      PubDate: 2017-10-09T22:20:23.091394-05:
      DOI: 10.1111/apt.14366
  • Systematic review with meta-analysis: rifaximin for the prophylaxis of
           spontaneous bacterial peritonitis
    • Authors: A. Goel; U. Rahim, L. H. Nguyen, C. Stave, M. H. Nguyen
      Abstract: BackgroundThe primary and secondary prevention of spontaneous bacterial peritonitis (SBP) is recommended in high-risk patients with cirrhosis. Several studies evaluating the efficacy of rifaximin for SBP prophylaxis have yielded conflicting results. Rifaximin has the potential advantage of preventing bacterial overgrowth and translocation without the systemic side effects of broad-spectrum antibiotics.AimTo evaluate the efficacy of rifaximin in the primary and secondary prevention of SBP.MethodsA literature search using five databases was performed to identify studies on the association between rifaximin and SBP. We performed two meta-analyses: (1) rifaximin compared to systemic antibiotics and (2) rifaximin compared to no antibiotics. Random-effect modelling was conducted to determine overall pooled estimates and 95% confidence intervals (CIs).ResultsFive studies with 555 patients (295 rifaximin, 260 systemic antibiotics) compared rifaximin with systemic antibiotics. The pooled odds ratio (OR) for SBP was 0.45 (95% CI 0.16-1.27; P = .13) in patients receiving rifaximin and strengthened on sensitivity analysis (OR 0.38, 95% CI 0.19-0.76, P = .01). In the analysis comparing rifaximin with no antibiotics, there were five studies with 784 patients (186 rifaximin, 598 no antibiotics). The OR for SBP was 0.34 (95% CI 0.11-0.99; P < .05) in patients receiving rifaximin. In subgroup analysis, rifaximin reduced the risk of SBP by 47% compared to no antibiotics for primary prophylaxis and by 74% compared to systemic antibiotics for secondary prophylaxis.ConclusionRifaximin may be effective in preventing SBP in patients with cirrhosis and ascites compared to systemically absorbed antibiotics and compared to placebo.
      PubDate: 2017-10-09T22:00:26.565739-05:
      DOI: 10.1111/apt.14361
  • The negative impact of HBV/HCV coinfection on cirrhosis and its
    • Authors: S. Pol; G. Haour, H. Fontaine, C. Dorival, V. Petrov-Sanchez, M. Bourliere, J. Capeau, P. Carrieri, D. Larrey, C. Larsen, P. Marcellin, J.-M. Pawlostky, P. Nahon, F. Zoulim, P. Cacoub, V. Ledinghen, P. Mathurin, F. Negro, G.-P. Pageaux, Y. Yazdanpanah, L. Wittkop, J.-P. Zarski, F. Carrat,
      Abstract: BackgroundHepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series.AimTo compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study.Patients and MethodsOf the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti-HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis.ResultsF3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P < .0001), but similar in HCV-monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) (P < .003). Multivariable analysis confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients (OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42-22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22-7.44).ConclusionsHCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients.
      PubDate: 2017-10-09T21:55:29.869436-05:
      DOI: 10.1111/apt.14352
  • The PAC-SYM questionnaire for chronic constipation: defining the minimal
           important difference
    • Authors: Y. Yiannakou; J. Tack, H. Piessevaux, D. Dubois, E. M. M. Quigley, M. Y. Ke, S. Da Silva, A. Joseph, R. Kerstens
      Abstract: BackgroundThe Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire is frequently used in clinical trials of constipation. However, the threshold for reduction in total PAC-SYM score used to define a clinical response on this 0-4 point scale has not undergone formal appraisal, and its relationship with clinical benefit as perceived by patients has not been defined.AimTo determine the minimal important difference in PAC-SYM score, and the optimum cut-off value for defining responders.MethodsThe minimal important difference was estimated using data from six international phase 3/4, double-blind, randomised controlled trials of prucalopride in patients with chronic constipation (NCT01147926, NCT01424228, NCT01116206, NCT00485940, NCT00483886, NCT00488137), with anchor- and distribution-based approaches. Five appropriate patient-reported outcomes were selected as anchors. In addition, receiver operating characteristics (ROC) curve analyses were used to investigate responder discrimination for each anchor.ResultsData from 2884 patients were included. Minimal important difference estimates ranged from –0.52 to –0.63 across the five anchors. Estimates were not affected by study location but were consistently lower for rectal symptoms than for abdominal and stool symptoms. Distribution-based estimates were considerably lower than anchor-based estimates. ROC curve analyses showed optimum cut-off scores for discriminating responders to be similar to anchor-based minimal important difference estimates.ConclusionsAnchor-based methods gave consistent results for the minimal important difference, at approximately –0.6, and this value was close to the ROC-determined optimal cut-off scores for responder discrimination. This value could be considered in clinical practice. A slightly more conservative threshold (eg –0.75) could be used in clinical trials to reduce the placebo response rate.
      PubDate: 2017-10-06T02:48:10.048356-05:
      DOI: 10.1111/apt.14349
  • Incidence and predictors of osteoporotic fractures in patients with
           Barrett's oesophagus: a population-based nested case-control study
    • Authors: S. Kumar; M. T. Drake, C. D. Schleck, M. L. Johnson, J. A. Alexander, D. A. Katzka, P. G. Iyer
      Abstract: BackgroundProton pump inhibitors (PPI) are inconsistently associated with osteoporotic fractures. Barrett's oesophagus (BO) patients are treated with high PPI doses for prolonged periods, but there are limited data on the incidence of osteoporosis and fractures in this group pf patients.AimTo estimate the incidence of (and risk factors for) low bone mass (osteoporosis and/or osteopenia) related fractures in a population-based BO cohort.MethodsAll subjects with BO and a diagnosis of osteoporosis and fractures were identified using Rochester Epidemiology Project resources. The incidence rates of all and osteoporotic fractures in these subjects were compared to an age- and gender similar population in Olmsted County to determine standardised incidence ratios (SIR). Predictors were assessed using Cox proportional hazards models.ResultsFive hundred and twenty-one patients were included (median [IQR] age 61 [52, 72] years; 398 [76%] men) of whom 113 (21.7%) had fractures, and 46 (8.8%) had osteoporotic fractures. The incidence of all fractures and osteoporotic fractures was comparable to that of an age- and gender-matched population (SIR 1.09; 95% CI 0.92-1.29: SIR 1.05; 95% CI 0.85-1.29). PPI use, dose or duration of use was not associated with osteoporotic fracture risk (HR 0.87; 95% CI 0.12-6.39). Independent risk factors for osteoporotic fractures included older age, female gender and higher co-morbidity index.ConclusionsThe incidence of osteoporotic fractures was not increased in BO patients compared to the general population. In addition, PPI use was not associated with increased fracture risk regardless of the duration of therapy or dose.
      PubDate: 2017-10-05T03:00:35.503106-05:
      DOI: 10.1111/apt.14345
  • Survival after treatment with curative intent for hepatocellular carcinoma
           among patients with vs without non-alcoholic fatty liver disease
    • Authors: C. R. Wong; B. Njei, M. H. Nguyen, A. Nguyen, J. K. Lim
      Abstract: BackgroundNon-alcoholic fatty liver disease (NAFLD) is expected to become a leading aetiology of hepatocellular carcinoma (HCC)-related mortality in the United States. HCC treatments with curative intent (OLT, orthotopic liver transplantation; resection; RFA, radiofrequency ablation) can improve survival in carefully selected patients.AimTo compare survival after receipt of curative treatment for NAFLD and non-NAFLD-HCC aetiologies (HCV, chronic hepatitis C; HBV, chronic hepatitis B; ALD, alcoholic liver disease) and by treatment was performed.MethodsA cohort of 17 664 patients was assembled using linked Surveillance, Epidemiology, and End Results and Medicare data from 1991 to 2011 with confirmed diagnosis of HCC.ResultsThe cohort was mostly male, aged 70 (21-106) years, without cardiovascular disease, and had liver cirrhosis without decompensation, metastatic HCC or large tumour size (>5 cm). The NAFLD-HCC group was mostly female and older with more cardiovascular disease, metastatic HCC, and large tumour size and less cirrhosis and decompensated liver disease than the non-NAFLD-HCC groups. The NAFLD group was 47% less likely to receive any curative treatment as compared with non-NAFLD aetiologies (OR 0.53, P 
      PubDate: 2017-09-28T04:45:43.882686-05:
      DOI: 10.1111/apt.14342
  • Declining trend in the incidence of biopsy-verified coeliac disease in the
           adult population of Finland, 2005-2014
    • Authors: L. J. Virta; M. M. Saarinen, K.-L. Kolho
      Abstract: BackgroundThe frequency of coeliac disease (CD) has been on the rise over the past decades, especially in Western Europe, but current trends are unclear.AimTo research the recent temporal changes in the incidence of adult, biopsy-verified coeliac disease and dermatitis herpetiformis (DH) in Finland, a country with a high frequency of coeliac disease.MethodsAll coeliac disease and DH cases diagnosed at age 20-79 years during 2005-2014 were retrieved from a nationwide database documenting all applicants for monthly compensation to cover the extra cost of maintaining a gluten-free diet. This benefit is granted on the basis of histology, not socioeconomic status. Temporal trends in the annual incidences were estimated using Poisson regression analyses.ResultsThe total incidence of coeliac disease decreased from 33/100 000 during the years 2005-2006 to 29/100 000 during 2013-2014. The mean annual incidence of coeliac disease was nearly twice as high among women as among men, 42 vs 22 per 100 000, respectively. For middle- and old-aged women, the average rate of decrease in incidence was 4.8% (95% CI 3.9-5.7) per year and for men 3.0% (1.8-4.1) (P for linear trend
      PubDate: 2017-09-21T04:05:34.73651-05:0
      DOI: 10.1111/apt.14335
  • Editorial: the non-invasive diagnosis of atrophic gastritis
    • Authors: P. Malfertheiner
      Pages: 1112 - 1113
      Abstract: Linked ContentThis article is linked to Zagari et al paper. To view this article visit
      PubDate: 2017-11-03T03:46:18.77976-05:0
      DOI: 10.1111/apt.14340
  • Editorial: therapeutic drug monitoring for anti-TNF agents—has it
           all been said'
    • Authors: E. Domènech; F. Cañete, M. Mañosa
      Pages: 1113 - 1114
      Abstract: Linked ContentThis article is linked to Nakase and Nakase et al papers. To view these articles visit and
      PubDate: 2017-11-03T03:46:21.892973-05:
      DOI: 10.1111/apt.14350
  • Editorial: therapeutic drug monitoring for anti-TNF agents—has it all
           been said' Author's reply
    • Authors: H. Nakase
      Pages: 1114 - 1115
      Abstract: Linked ContentThis article is linked to Nakase et al and Domenèch et al papers. To view these articles visit and
      PubDate: 2017-11-03T03:46:20.705459-05:
      DOI: 10.1111/apt.14365
  • Editorial: ribavirin continues to play a role in treatment with
           direct-acting antivirals for hepatitis C virus-infected patients with
           decompensated cirrhosis
    • Authors: J. Waldenström; M. Lagging
      Pages: 1115 - 1116
      Abstract: Linked ContentThis article is linked to van Tilborg et al paper. To view this article visit
      PubDate: 2017-11-03T03:46:18.856329-05:
      DOI: 10.1111/apt.14354
  • Letter: questions regarding the diagnostic performance of serum assays for
           atrophic gastritis
    • Authors: D. Y. Graham
      Pages: 1117 - 1118
      Abstract: Linked ContentThis article is linked to Zagari et al and Zagari and Greenwood papers. To view these articles visit and
      PubDate: 2017-11-03T03:46:18.703137-05:
      DOI: 10.1111/apt.14339
  • Letter: questions regarding the diagnostic performance of serum assays for
           atrophic gastritis—Authors' reply
    • Authors: R. M. Zagari; D. C. Greenwood
      Pages: 1118 - 1119
      Abstract: Linked ContentThis article is linked to Zagari et al and Graham papers. To view these articles visit and
      PubDate: 2017-11-03T03:46:18.223669-05:
      DOI: 10.1111/apt.14369
  • Letter: reproducible evidence shows that exclusive enteral nutrition
           significantly reduces faecal calprotectin concentrations in children with
           active Crohn's disease
    • Authors: M. Logan; U. Z. Ijaz, R. Hansen, K. Gerasimidis, R. K. Russell
      Pages: 1119 - 1120
      Abstract: Linked ContentThis article is linked to Swaminath et al and Feathers et al papers. To view these articles visit and
      PubDate: 2017-11-03T03:46:21.164231-05:
      DOI: 10.1111/apt.14351
  • Letter: reproducible evidence shows that exclusive enteral nutrition
           significantly reduces faecal calprotectin concentrations in children with
           active Crohn's disease—Authors' reply
    • Authors: A. Feathers; A. Swaminath, A. N. Ananthakrishnan, L. Falzon, S. Li Ferry
      Pages: 1121 - 1121
      Abstract: Linked ContentThis article is linked to Swaminath et al and Logan et al papers. To view these articles visit and
      PubDate: 2017-11-03T03:46:19.47692-05:0
      DOI: 10.1111/apt.14360
  • Letter: rifaximin is more than helping hepatic encephalopathy—it
           also saves lives
    • Authors: Y.-L. Wang; H.-J. He, X.-X. Xiao, Y. Lin, B.-Q. Wang, S.-L. Zhu, G.-S. Yang, S.-S. Huang, Q.-G. Yang
      Pages: 1122 - 1123
      Abstract: Linked ContentThis article is linked to Kang et al paper. To view this article visit
      PubDate: 2017-11-03T03:46:21.537799-05:
      DOI: 10.1111/apt.14353
  • Letter: statins and cirrhosis
    • Authors: V. G. Athyros; N. Katsiki, D. P. Mikhailidis
      Pages: 1123 - 1124
      Abstract: Linked ContentThis article is linked to Bang et al paper. To view this article visit
      PubDate: 2017-11-03T03:46:18.293117-05:
      DOI: 10.1111/apt.14355
  • Letter: safety and efficacy of using statins in patients with cirrhosis
    • Authors: J. Zhao; H. Tian, C. Liang
      Pages: 1124 - 1125
      Abstract: Linked ContentThis article is linked to Bang et al papers. To view these articles visit and
      PubDate: 2017-11-03T03:46:18.946344-05:
      DOI: 10.1111/apt.14357
  • Letter: safety and efficacy of using statins in patients with
           cirrhosis—authors' reply
    • Authors: U. C. Bang; T. Benfield, F. Bendtsen
      Pages: 1125 - 1126
      Abstract: Linked ContentThis article is linked to Zhao et al and Bang et al papers. To view these articles visit and
      PubDate: 2017-11-03T03:46:19.418608-05:
      DOI: 10.1111/apt.14364
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