Nehra, Avinash K

Abstract Background and Aims Our goal was to determine the importance of ileal inflammation at computed tomography or magnetic resonance enterography in Crohn’s disease patients with normal ileoscopy. Methods Patients with negative ileoscopy and biopsy within 30 days of CT or MR enterography showing ileal inflammation were included. The severity [0–3 scale] and length of inflammation within the distal 20 cm of the terminal ileum were assessed on enterography. Subsequent medical records were reviewed for ensuing surgery, ulceration at ileoscopy, histological inflammation, or new or worsening ileal inflammation or stricture on enterography. Imaging findings were classified as: Confirmed Progression [subsequent surgery or radiological worsening, new ulcers at ileoscopy or positive histology]; Radiologic Response [decreased inflammation with medical therapy]; or Unlikely/Unconfirmed Inflammation. Results Of 1471 patients undergoing enterography and ileoscopy, 112 [8%] had imaging findings of inflammation with negative ileoscopy, and 88 [6%] had negative ileoscopy and ileal biopsy. Half [50%; 44/88] with negative biopsy had moderate/severe inflammation at enterography, with 45%, 32% and 11% having proximal small bowel inflammation, stricture or fistulas, respectively. Two-thirds with negative biopsy [67%; 59/88] had Confirmed Progression, with 68%, 70% and 61% having subsequent surgical resection, radiological worsening or ulcers at subsequent ileoscopy, respectively. Mean length and severity of ileal inflammation in these patients was 10 cm and 1.6. Thirteen [15%] patients had Radiologic Response, and 16 [18%] had Unlikely/Unconfirmed Inflammation. Conclusion Crohn’s disease patients with unequivocal imaging findings of ileal inflammation at enterography despite negative ileoscopy and biopsy are likely to have active inflammatory Crohn’s disease. Disease detected by imaging may worsen over time or respond to medical therapy.

T cell–mediated rejection (TCMR) is common after liver transplantation (LT), and it is often thought to have a minimum impact on outcomes. Because alloimmune response changes over time, we investigated the role of the timing of TCMR on patient and allograft survival and examined the risk factors for early and late TCMR. We reviewed protocol liver biopsies for 787 consecutive LT recipients with an 8.6‐year follow‐up. The incidence of early TCMR (≤6 weeks after LT) was 33.5% with nonalcoholic steatohepatitis patients having the lowest incidence. Younger recipient age (P < 0.01), number of human leukocyte antigen mismatches (P < 0.01), and use of deceased donor allografts (P = 0.01) were associated with increased risk of early TCMR, which had no impact on allograft (hazard ratio [HR], 1.02; 95% CI, 0.79‐1.32; P = 0.89) or overall survival (HR, 1.03; 95% CI, 0.78‐1.34; P = 0.86). Late TCMR (>6 weeks after LT) was less common (17.7%) and was associated with different risk factors. The majority of late TCMR (56.2%) episodes had no antecedent early TCMR, although moderate‐to‐severe early TCMR (HR, 2.85; 95% CI, 1.55‐5.23; P < 0.01) and steroid resistance (HR, 3.62; 95% CI, 1.87‐6.99; P < 0.01) were associated with late TCMR. Late TCMR increased risk of mortality (HR, 1.89; 95% CI, 1.35‐2.65; P = 0.001) and graft loss (HR, 1.71; 95% CI, 1.23‐2.37; P = 0.001). Thus, these data suggest that the timing and histologic grade of TCMR determine its impact on patient and allograft survival. Early mild TCMR episodes after LT do not adversely impact patient or allograft survival provided that they are adequately treated. The occurrence of late TCMR carries deleterious effects with increased longterm risk of graft loss and decreased survival. Patients with moderate‐to‐severe early TCMR are at an increased risk for late TCMR and warrant closer clinical follow‐up.