The appendix has recently garnered considerable attention in the study of gastrointestinal disease. Several pilot studies have suggested that appendectomy may have a beneficial impact on the clinical course of colitis in patients with ulcerative colitis. These protective effects may extend beyond ulcerative colitis. A national population-based cohort study from Denmark found that prior appendectomy was also associated with a milder disease course in patients with Crohn’s disease (Mark-Christensen et al.). Moreover, the management of acute appendicitis itself is currently the focus of considerable rethinking. A recent meta-analysis suggests that conservative management may be a viable option for adults with appendicitis in the absence of an appendicolith (Scheijmans et al.). In contrast, findings from a study in children led to a different recommendation: Given that one third of children initially managed conservatively ultimately require surgical intervention, and considering the relatively modest improvement in quality of life with nonsurgical treatment, the authors recommend surgery as the primary strategy in children (St. Peter et al.).

IL-23 antibodies have emerged as both effective and well-tolerated treatment options for inflammatory bowel disease. This is supported by data from the VIVID trial on the efficacy of mirikizumab in the treatment of Crohn’s disease (Ferrante et al.) and the QUASAR trial, which evaluated guselkumab in the treatment of ulcerative colitis (Rubin et al.). 

The success of immune checkpoint inhibitors remains confined to select tumor entities, among them microsatellite instability-high colorectal cancer. In patients with metastatic disease, combination therapy with nivolumab and ipilimumab showed superior progression-free survival compared to nivolumab monotherapy (André et al.), highlighting the therapeutic advantage of dual-agent immunotherapy.

In this issue, immunotherapy also features prominently in the field of hepatology, with several publications exploring various aspects of checkpoint inhibitors. Two studies in hepatocellular carcinoma investigated whether therapeutic efficacy could be enhanced by combining immunotherapy with transarterial chemoembolization and either bevacizumab (Sangro et al.) or lenvatinib (Kudo et al.). Another study introduced a histological score capable of predicting response to immunotherapy (Salié et al.). 

The VITALITY study assessed the influence of pre-transplant immunotherapy on post-liver transplant outcomes. Fortunately, in addition to demonstrating favorable efficacy, no significant safety outcomes – such as increased rates of graft rejection – were observed (Tabrizian et al.).

In the context of chronic hepatitis B infection, checkpoint inhibitor therapy may also offer potential for achieving virological endpoints. Consistent with this, patients with low HBsAg levels appear to derive particular benefit, with immunotherapy in some cases leading to HBsAg loss (Mon et al.).

In addition to these insights, this issue features a variety of articles that are directly applicable to clinical practice, as well as contributions that provide perspectives on the future of gastroenterology and hepatology. No matter what, we hope that you will find something that piques your interest.

Yours sincerely,

Peter Hasselblatt and Tobias Böttler
Department of Internal Medicine II, University Medical Center Freiburg (Germany)