Year in Review

Deciphering the complex circuitry of liver homeostasis and repair is required to improve regenerative therapies for hepatic diseases. Studies in 2018 have identified subsets of hepatic cells that have unique reparative abilities and clarified the role of biomechanical forces and hepatobiliary reprogramming as sustainable modes of tissue repair.

Important studies published in 2018 highlight novel therapeutic strategies along the disease course of IBD, including potential specific dietary modifications at early stages and treatment with adipose-derived stem cells in perianal Crohn’s disease. A treat-to-target approach that involves proactive serial monitoring of inflammatory biomarkers can assist in timely treatment escalation and promises improved patient outcomes.

High stromal cellularity in pancreatic cancer is an important factor for ineffective treatment and molecular studies. In 2017, major advancements were made in transcriptional characterization, treatment delivery and clinical regimes, raising hope for a breakthrough against this deadly disease.

In 2017, there have been substantial advances in our understanding of the immunological and endocrine mechanisms of disease progression in NAFLD, paving the way for novel therapeutic strategies.

In 2017, the FDA approved regorafenib and nivolumab for the treatment of patients with hepatocellular carcinoma following prior sorafenib treatment, opening the door for an effective systemic second-line therapy in advanced disease. By contrast, the addition of sorafenib to transarterial chemoembolization with drug-eluting beads did not improve progression-free survival in the intermediate disease stage.

2017 has witnessed major advances in gut stem cell and cancer stem cell research, delivering key insights into their regulation, more defined culture methods and novel stem cell markers that collectively drive us ever closer to breakthroughs for regenerative medicine and cancer treatment in the clinic.

2017 has witnessed key advances in knowledge about the metabolic capacities of the gut microbiota, enabling the progression of our understanding of the principles driving xenobiotic–bacteria–host interplay. This research paves the way for the long road towards personalized medicine and nutrition, which could be based on gut microbial metabolism.

The central studies published in 2017 address novel IBD therapeutic strategies and prediction of the future disease course or response to a distinct therapy. Together, these studies contribute to the understanding of the regulation of mucosal homeostasis and at the same time serve to develop novel personalized treatment algorithms in patients in whom a severe disease course can be predicted.

The challenge to obtain needle biopsy samples from patients with cancer has steered the development of new blood-based diagnostics called 'liquid biopsy'. In 2016, major advances have been made in the use of circulating tumour cells and cell-free DNA for monitoring tumour evolution in patients with cancer of the gastrointestinal tract, with a focus on colorectal cancer.

In 2016, obeticholic acid became the first new licensed therapy for primary biliary cholangitis in >20 years. This therapeutic came at a time of improved disease understanding from biliary and immunological mechanistic insights.

Fascination about the gut microbiota shows no signs of slowing down. The launch of the US National Microbiome Initiative in 2016, and similar efforts across the globe, underscore the continued enthusiasm for microbiome studies in the USA and beyond. Indeed, 2016 has been yet another notable year for gut microbiota research.

In 2016, personalized medicine for IBD has been evolving. Increasing comfort with biosimilar infliximab was achieved with 'real-life' data. Drugs with alternative modes of action confirmed substantial benefit, even in patients failing anti-TNF agents. Adipose-derived mesenchymal stem cells yielded a new treatment option for perianal fistulas.

The burden of HBV infection remains high and new strategies to improve HBV vaccination and therapy are needed. Key research in 2016 highlights the efficacy of current approaches and proposes new concepts for some of the immunological defects that need to be overcome for HBV functional cure.

In 2016, key studies have increased our understanding of the part played by the brain–gut–microbiota axis in disorders as diverse as depression, obesity and autism spectrum disorder. The data indicate that alterations in gut-microbial composition can substantially affect central physiology, and that transplantation of the gut microbiota can transfer a behavioural or physiological phenotype.

Gut microbial communities often contain many Bacteroides or their close relatives, Prevotella, but not both. Prevotella strains are associated with plant-rich diets but are also linked with chronic inflammatory conditions. In 2015, papers probed the genomic diversity of Prevotella strains and interactions of Prevotella copri with its host and other bacteria.

In 2015, new treatment regimens were revealed that achieve >95% cure rates for all HCV genotypes. The HCV polymerase structure was solved in catalytically relevant HCV replication steps and in the context of nucleotide analogue inhibition. Moreover, HCV research taught us new links between innate antiviral responses, lipid metabolism and intracellular membrane formation.

In 2015, new tools were developed to modulate fibroblast and macrophage activity to halt liver fibrogenesis and stimulate resolution. Essential factors for resolution were identified and clinical trials yielded potential new antifibrotic drugs. Although innovations were made this year, clinical trials are still hampered by the lack of methods to monitor disease progression.

Late diagnosis and an inability to personalize treatment are major problems preventing reductions in pancreatic cancer mortality. In 2015, the identification of a highly discriminatory exosomal biomarker, culture systems that recapitulate human disease and new methods of analysing large data sets to identify prognostic markers have improved the future outlook for patients with this cancer.

Advances into understanding stem and progenitor cells and organoids of the gastrointestinal tract have continued apace. New research published in 2015 identified new cell populations involved in liver regeneration and highlighted the development of pancreatic and gastric organoids.

Several key papers published in 2015 highlight important emerging trends in endoscopic imaging that promise to improve patient diagnosis and guidance of therapy. These studies reflect the future role for 'smart' contrast agents and fluorescence endoscopes to provide a molecular basis for disease detection, identify precancerous lesions and determine optimal choice of therapy.