Acute Antibody-mediated rejection in liver transplantation: Impact and applicability of the Banff working group on liver allograft pathology 2016 criteria.

This study was aimed to examine the clinical utility and impact of the 2016 Banff criteria for acute antibody-mediated rejection (acute AMR) in patients with liver transplantation. Among adult patients with donor-specific antibody (DSA) assays performed between 2015 and 2020, cases with proved DSA (mean fluorescent index >2000) and matched liver biopsy available were reviewed. Among 55 patients identified, 28 (51%) had class I DSA, 45 (82%) had class II DSA and 18 (33%) had both. Mild, moderate and severe microvasculitis were observed in 11 (20%), 2 (4%) and 1 (2%) case, respectively. Diffuse immunoreactivity to C4d on portal microvascular endothelia was confirmed in 5 cases (9%), which met the criteria of definite (n = 2) or suspicious for acute AMR (n = 3). Cases of acute AMR more commonly had class I DSA (100% vs. 46%; p = 0.027) or both class I and II DSA (80% vs. 28%; p = 0.018) than cases of non-acute AMR. One case of pure acute AMR with veno-occlusion was successfully treated with plasma exchange. The remaining 4 cases had features of combined acute AMR/T cell-mediated rejection (TCMR), and two progressed to ductopenic rejection within 3 weeks. In conclusion, only 9% of DSA-positive patients met the Banff criteria for acute AMR, necessitating careful morphological and immunohistochemical assessments of the allograft biopsies according to the proposed standards. Combined acute AMR/TCMR was more common than isolated acute AMR, and additional AMR in TCMR cases may be associated with rapid progression to ductopenic rejection.

Guideline review: Tofacitinib for adults with moderately to severely active ulcerative colitis - NICE guidance.

Tofacitinib is an oral, Janus kinase (JAK) molecule, which selectively inhibits Janus-associated tyrosine kinases JAK1 and JAK3. It has already shown efficacy in the treatment of rheumatoid arthritis and the prevention of organ allograft rejection in kidney transplantation. Two separate phase III placebo-controlled trials, assessing 8-week efficacy of tofacitinib induction for ulcerative colitis (UC), demonstrated superiority when compared with placebo. Tofacitinib also demonstrated robust efficacy versus placebo in the 52-week maintenance component of the same study. Tofacitinib has been recommended by the National Institute for Health and Care Excellence as an effective treatment option for adult patients with moderate to severe UC when conventional therapy or a biological agent cannot be tolerated or the disease has responded inadequately or lost response to treatment. We review the guidelines and provide brief commentary on the post hoc analysis related to lipid increases and thromboembolism risk, which have lead to changes in current therapeutic guidance.