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Introduction: Idiosyncratic DILI is a challenging condition, believed to involve the immune system. This hypothesis is supported by various identified HLA risk alleles. Objectives: To evaluate a potential role of the immune system in DILI through leukocyte immunophenotyping. Methods: Blood samples were collected from adjudicated DILI (n=12) and viral hepatitis (VH, 13) at day 1 (recognition), 7 and >30. A single blood sample was extracted from healthy liver controls (HLC, 54). Leukocyte populations and immune checkpoint expressions were determined based on cell surface receptors, except for CTLA-4 that was determined intracellularly, using multiparametric flow cytometry. Results: No differences were detected in leukocytes, lymphocytes or neutrophils counts at day 1. However, DILI (0.57 × 10E09/L, p=0.037) and HV (1.41 × 10E09/L, p

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.

Background and objective: Oral tacrolimus is an effective drug that induces clinical remission in patients with moderate to severe ulcerative colitis refractory to steroids. However, there is little data with regard to its medium to long-term efficacy and safety. The aim of this study was to assess the medium to long-term efficacy and safety of oral tacrolimus in this challenging clinical situation. Methods: This was a retrospective observational review of the clinical charts of 34 patients with moderate to severe ulcerative colitis refractory to steroids treated with oral tacrolimus at our hospital (July 2001-July 2016). Remission was defined as a Lichtiger index score < 3 and response was defined as a score < 10 with a reduction of at least three points compared to the baseline score. Results and conclusions: Seven patients (20.58%) required colectomy during the follow-up period (mean 65 months). Nine patients required rescue with infliximab (four patients during the first six months of follow-up and the other five after the first six months). The short to medium clinical efficacy combining both remission and clinical response was 82% at six months. Kaplan-Meier analysis showed that the percentage of patients free from colectomy and additional sequential rescue therapy was 75% at 54 months (median follow-up). The early introduction of thiopurines (< 2 months from start of tacrolimus) showed no significant improvement in prognosis (p = 0.72). Fifty-three per cent of patients experienced adverse effects, none of whom required treatment withdrawal. No severe infections were noted during the follow-up.