The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants (RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These pre-existing RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.

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Project management, coordination, formal analysis, data preservation, first draft, revision and editing of the manuscript, methodology and research. Pilar Navajas Hernández: Data collection and preservation, revision and editing of the manuscript. María del Mar Martín Rodríguez: Data collection and preservation, revision and editing of the manuscript. Marta Lázaro Sáez: Data collection and preservation, formal analysis, first draft, revision and editing of the manuscript. Raúl Olmedo Martín: Data collection and preservation, revision and editing of the manuscript. Andrea Núñez Ortiz: Data collection and preservation, revision and editing of the manuscript. Federico Arguelles Arias: Data collection and preservation, revision and editing of the manuscript. María Carmen Fernández Cano: Data collection and preservation, revision and editing of the manuscript. Francisco Gallardo Sánchez: Data collection and preservation, revision and editing of the manuscript. Sandra Marín Pedrosa: Data collection and preservation, revision and editing of the manuscript.Javier González García: Data collection and preservation, revision and editing of the manuscript.Juan María Vázquez Morón: Project management, coordination, methodology, data collection and preservation, revision and editing of the manuscript. Conflicts of interest:A. Hernández has received payments as fees-for-service, participation in scientific meetings and funding for attendance from Abbvie, Ferring, Janssen, MSD, Pfizer, Sandoz and Takeda; M.M. Martín has received payments for advisory, participation in scientific meetings and attendance from MSD, Takeda, Janssen, Abbvie, Tillots Pharma, Chiesi and Ferring; M. Lázaro has received payments as fees-for-service, participation in scientific meetings and funding for attendance from Janssen, Pfizer and Takeda; R.Olmedo has received payments as fees-for-service and advisory from MSD, Abbvie, Takeda, Ferring, FAES Farma and Janssen; F. Arguelles has received payments for advisory, consultancy and research fundings from Janssen, MSD, Abbvie,

Background: Vitamin D has an immunoregulatory action in Inflammatory Bowel Disease (IBD) as well as other immune-mediated disorders. Its influence on intestinal permeability, innate and adaptive immunity, and the composition and diversity of the microbiota contribute to the maintenance of intestinal homeostasis. Patients with IBD have a greater prevalence of vitamin D deficiency than the general population, and a possible association between this deficit and a worse course of the disease. However, intervention studies in patients with IBD have proved inconclusive. Objective: To review all the evidence concerning the role of vitamin D as an important factor in the pathophysiology of IBD, review the associations found between its deficiency and the prognosis of the disease, and draw conclusions for the practical application from the main intervention studies undertaken. Method: Structured search and review of basic, epidemiological, clinical and intervention studies evaluating the influence of vitamin D in IBD, following the basic principles of scientific data. Results: Vitamin D deficiency is associated with disease activity, quality of life, the consumption of social and healthcare resources, and the durability of anti-TNFα biological treatment. Determination of new metabolites of vitamin D, measurement of its absorption capacity and questionnaires about sun exposure could help identify groups of IBD patients with a special risk of vitamin D deficiency. Conclusion: Well-designed intervention studies are needed in IBD, with probably higher objective plasma doses of vitamin D to establish its efficacy as a therapeutic agent with immunomodulatory properties. Meanwhile, vitamin D deficiency should be screened for and corrected in affected patients in order to achieve adequate bone and phosphocalcic metabolism.

Vedolizumab is a humanized IgG1 monoclonal antibody that selectively blocks the lymphocyte integrin α4β7 and prevents its interaction with endothelial adhesion molecules and subsequent transmigration to the gastrointestinal tract. The drug was approved in 2014 for the induction and maintenance treatment of ulcerative colitis and moderate to severe Crohn's disease that is refractory or intolerant to conventional treatment with corticoids and immunosuppressants and/or anti-TNFα drugs. However, inflammatory bowel disease has a variable behavior following liver transplant. One third of patients with ulcerative colitis associated with primary sclerosing cholangitis are expected to deteriorate despite receiving immunosuppression to prevent rejection. There is limited experience with anti-TNFα agents in patients with inflammatory bowel disease in the setting of liver transplantation and the studies to date involve a limited number of cases. The efficacy and safety data of vedolizumab in this situation are unreliable and very preliminary. We present two cases with the aim to present the efficacy and safety of vedolizumab after one year of treatment in two patients who underwent a transplant due to primary sclerosing cholangitis. One case had de novo post-transplant ulcerative colitis refractory to two anti-TNFα drugs (golimumab and infliximab). The other patient had a colostomy due to fulminant colitis and developed severe ulcerative proctitis refractory to infliximab after reconstruction with an ileorectal anastomosis.