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Abstract: Background: Failure of anti-TNF treatment in inflammatory bowel disease (IBD) patients can take on several forms, each posing distinct etio-pathogenic considerations and management dilemmas. Aim: The aim of this study is to review the mechanisms responsible for the various forms of anti-TNF failures in IBD and to elucidate strategies for optimizing clinical efficacy. Results: Primary failures of anti-TNF induction therapy occur in up to 40% of patients in clinical trials and in 10–20% in clinical series. Longer disease duration, smoking and several genetic mutations are predisposing factors for primary failures. Curiously, primary non-response is probably not a class-effect phenomenon since switching to another anti-TNF is effective in over 50% of such patients. Secondary loss of response is also a common clinical problem with incidence ranging between 23 and 46% at 12months after anti-TNF initiation. Underlying mechanisms are often related to increased anti-TNF clearance by anti-drug antibodies, but may also include other causes for recalcitrant IBD activity as well as disorders that are unrelated to IBD itself. Astute management begins with verifying the presence of uncontrolled inflammatory IBD activity as a cause for patient's symptoms. Next, it is prudent to consider a trial of wait-and-see approach, since in some patients with mild-moderate symptoms, loss of response may resolve without alteration of therapy. If it does not, measuring anti-TNF trough levels and anti-drug antibodies may clarify the underlying mechanism in individual patients although there are still limited and conflicting data regarding the role of these measurements in guiding the choice between dose-intensification, switch to another anti-TNF or to another immuno-modulator, and the addition of an immuno-modulator as a combination therapy with the failing anti-TNF. Anti-TNF re-induction after prior drug-holiday is a distinct clinical scenario and scarce evidence suggests re-induction outcome to be dependent on the circumstances when drug-holiday was commenced. Finally, discontinuation of anti-TNF in patients with stable deep clinico-biologic and mucosal remission may be a viable option, as in these carefully selected patients the majority may enjoy long-term remission without the need for continued anti-TNF treatment. [Copyright &y& Elsevier]

Objective: To examine the prevalence, etiology, risk factors, and outcomes of liver abnormality in pregnancy, in a tertiary medical center, and to study the potential impact of artificial reproduction techniques (ART) on the incidence and the outcome of pregnancy-related liver abnormality. Design: A retrospective case-control study using an electronic database and patients’ files. Setting: Tertiary referral center. Patient(s): Women in the third trimester of pregnancy who were hospitalized for delivery. Intervention(s): None. Main Outcome Measure(s): Development of significant elevation of alanine aminotransferase (ALT ≥100 IU/L). Secondary outcomes included development of maternal and fetal complications. Result(s): The upper limit of normal of ALT was ≥1.5 times and it occurred in 440 (1.6%) pregnancies; of those, 228 (0.8%) had ALT ≥100 IU/L. The etiology of significant liver test abnormality was idiopathic in 47% of patients. Compared with spontaneous pregnancies (295/23,793), ART was significantly associated with liver test abnormality (145/4, 520). The presence of ALT ≥100 IU/L in the third trimester was associated with higher rates of cesarean sections, prematurity, low birthweight, and fetal complications. Conclusion(s): A definite etiology was not determined in about half of pregnancy-associated liver test abnormality. The ART was significantly associated with liver test elevation. Significant liver test abnormality in the third trimester may have an impact on maternal and fetal/neonatal outcomes. [ABSTRACT FROM AUTHOR]