TL1A is a novel TNF-like factor that acts as a costimulator of IFN-γ secretion through binding to the death domain-containing receptor, DR3. The aim of this study was to test the hypothesis that TL1A may play an important role in inflammatory bowel disease (IBD) by functioning as a Th1-polarizing cytokine. The expression, cellular localization, and functional activity of TL1A and DR3 were studied in intestinal tissue specimens as well as isolated lamina propria mononuclear cells from IBD patients and controls. TL1A mRNA and protein expression was up-regulated in IBD, particularly in involved areas of Crohn’s disease (CD; p < 0.03 vs control). TL1A production was localized to the intestinal lamina propria in macrophages and CD4+ and CD8+ lymphocytes from CD patients as well as in plasma cells from ulcerative colitis patients. The amount of TL1A protein and the number of TL1A-positive cells correlated with the severity of inflammation, most significantly in CD. Increased numbers of immunoreactive DR3-positive T lymphocytes were detected in the intestinal lamina propria from IBD patients. Addition of recombinant human TL1A to cultures of PHA-stimulated lamina propria mononuclear from CD patients significantly augmented IFN-γ production by 4-fold, whereas a minimal effect was observed in control patients. Our study provides evidence for the first time that the novel cytokine TL1A may play an important role in a Th1-mediated disease such as CD.

Infliximab is not superior to placebo in preventing clinical recurrence after CD-related resection. However, infliximab does reduce endoscopic recurrence. ClinicalTrials.gov ID NCT01190839.

Infliximab 5 mg/kg or 10 mg/kg, given every 8 weeks, is effective for the maintenance of remission and maintenance of fistula healing in patients who have responded to infliximab induction therapy. Adalimumab 40 mg weekly or every other week is effective for the maintenance of remission in patients who have responded to adalimumab induction therapy. Certolizumab pegol 400 mg every 4 weeks is effective for the maintenance of remission in patients who have responded to certolizumab induction therapy. No comparative trials have evaluated the relative efficacy of these agents. Adverse events are similar in the infliximab, adalimumab, and certolizumab groups compared with placebo, but study size and duration generally are insufficient to allow an adequate assessment of serious adverse events associated with long-term use.

Severe coagulopathy in fulminant hepatic failure (FHF) is difficult to correct by conventional means. Recombinant activated factor VII (rFVIIa) is an antihemophilic factor that has shown promise in treating coagulopathy in liver disease. Our aim is to review our experience with rFVIIa in treating the coagulopathy of FHF and compare these results with those of conventional therapy. Fifteen patients with FHF who met King's College criteria for orthotopic liver transplantation were studied. All were ascertained from our liver disease registry. Eight consecutive patients were administered fresh frozen plasma (FFP) alone, whereas seven consecutive patients were administered FFP and rFVIIa (40 g/kg intravenous bolus). The two groups, with similar demographic characteristics, were compared in terms of measured parameters of coagulopathy (prothrombin time and international normalized ratio), amount of plasma infused, development of anasarca, ability to undergo intracranial pressure (ICP) transducer placement, bleeding complications, ability to undergo transplantation, and survival. All patients administered rFVIIa (after a single dose) versus none administered FFP alone had temporary (2-to 6-hour) correction of coagulopathy (P < .0002). All patients administered rFVIIa versus 38% administered FFP alone were able to have an ICP transducer placed (P ‫؍‬ .03). The rFVIIa group had less anasarca (P ‫؍‬ .04). An equal number of patients underwent transplantation from each group, but overall survival was slightly better in the rFVIIa group (P ‫؍‬ .04). Five of seven patients in the rFVIIa group were administered one or more subsequent doses of rFVIIa after placement of the ICP monitor (two patients, for additional procedures; three patients, prophylactically in the first 24 hours after ICP transducer placement) at the discretion of the attending physicians. We conclude that rFVIIa is effective in transiently correcting laboratory parameters of coagulopathy in patients with FHF. It facilitates the performance of invasive procedures and is associated with less frequent anasarca compared with conventional therapy. Our preliminary experience supports the need for further studies to define the optimal dosing, safety, and efficacy of rFVIIa in patients with FHF. (Liver Transpl 2003;9:138-143.)

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