Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis

Ulcerative colitis(UC) is an immune-mediated, chronic inflammatory disease of the large intestine. Its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor(anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants. Therapeutic response to these agents is not uniform and a large percentage of patients either fail to improve(primary non-response) or lose response after a period of improvement(secondary non-response/loss of response). In addition, the use of anti-TNF agents has been related to uncommon but potentially serious adverse effects that preclude their administration or lead to their discontinuation. Finally, use of these medications is associated with a considerable cost for the health system. The identification of parameters thatmay predict response to anti-TNF drugs in UC would help to better select for patients with a high probability to respond and minimize risk and costs for those who will not respond. Analysis of the major clinical trials and the accumulated experience with the use of anti-TNF drugs in UC has resulted to the report of such prognostic factors. Included are clinical and epidemiological characteristics, laboratory markers, endoscopic indicators and molecular(immunological/genetic) signatures. Such predictive parameters of long-term outcomes may either be present at the commencement of treatment or determined during the early period of therapy. Validation of these prognostic markers in large cohorts of patients with variable characteristics will facilitate their introduction into clinical practice and the best selection of UC patients who will benefit from anti-TNF therapy.

Management of hepatitis B virus infection in patients with inflammatory bowel disease under immunosuppressive treatment

Hepatitis B remains a significant global clinical problem,despite the implementation of safe and effective vaccination programs.The prevalence of hepatitis B virus(HBV)in patients with inflammatory bowel disease(IBD)largely follows the regional epidemiologic status.Serological screening with hepatitis B surface antigen(HBsAg),and antibodies to hepatitis B surface(anti-HBs)and core(anti-HBc)proteins is a key element in the management of IBD patients and,ideally,should be performed at IBD diagnosis.Stratification of individual cases should be done according to the serologic profile and the IBD-specific treatment,with particular emphasis in patients receiving immunosuppressive regimens.In patients who have not contracted HBV,vaccination is indicated to accomplish protective immunity.Vaccination in immunosuppressed patients,however,is a challenging issue and several strategies for primary and revaccination have been proposed.The risk of HBV reactivation in patients with IBD should be considered in both HBsAg-positive and HBsAg-negative/anti-HBc-positive patients,when immunosuppressive therapies are administered.HBV reactivation is preventable via the administration of prophylactic nucleot(s)ide analogues and should be the standard approach in HBsAg-positive patients.HBsAg-negative/anti-HBcpositive patients represent a non-homogeneous group and bear a significantly lower risk of HBV reactivation.Biochemical,serological and molecular monitoring is currently the recommended approach for anti-HBc patients.Acute HBV infection is rarely reported in IBD patients.In the present review,we outline the problems associated with HBV infection in patients with IBD and present updated evidence for their management.