Year in Review

In 2021, our understanding of resistance to therapy in primary liver tumours improved drastically. By taking a holistic approach, three independent studies have characterized the tumour cell biodiversity across space, time and aetiologies in primary liver cancer, decoding the crosstalk between different cell types within the tumour ecosystem and their individual contributions to therapy resistance.

In 2020, there have been substantial advances in nonalcoholic fatty liver disease mechanisms, diagnostics and treatment. Key developments include the identification of a cellular and tissue signature to provide new insights into pathophysiology, advancements in non-invasive diagnostics and publication of interim results of the first phase III trial to demonstrate improvement in hepatic fibrosis.

In 2020, important advances were made across three major frontiers of pancreatic ductal adenocarcinoma (PDAC) research: risk factors, therapeutic resistance and tumour recurrence. Pathophysiology of obesity-mediated PDAC initiation was elucidated, novel stromal mechanisms of therapeutic resistance were unveiled and the genetic evolution of recurrent PDAC under therapeutic pressures was tracked in human samples.

In 2020, combination treatments have pushed the efficacy of systemic therapy for hepatocellular carcinoma (HCC) to an unprecedented high, providing a solid base for the future pursuit of further improved, highly efficacious systemic therapies for HCC.

In 2020, studies have used pure cultures of members of the gut microbiota to establish a molecular chain of causation for the role of these key bacteria in aggravating or alleviating cancer and metabolic diseases. These studies highlight the need for microbiome studies to move from associations back to cultures to demonstrate causality.

Key studies published in 2020 demonstrate that an impaired intestinal barrier precedes clinical diagnosis of inflammatory bowel disease (IBD) by years. Furthermore, studies identify novel regulators of the intestinal barrier, including intestinal macrophages and diurnal variations of diet–microbiome interactions, which could be future therapeutic strategies for IBD.

One of the most pleasurable, yet dangerous, activities of our daily life is eating. But once food has been swallowed, all we can do is to trust our gut. Several remarkable studies published in 2020 have expanded our knowledge on how the gut is intertwined with essential behaviours beyond food.

In 2020, major advances to the understanding of gastrointestinal inflammatory and infectious disease have been made using ‘mini-gut’ organoids. Key findings include the discovery of somatic inflammatory gene mutations in ulcerative colitis epithelium, a unique mutational signature in colorectal cancer caused by genotoxic Escherichia coli, and infection of intestinal organoids by SARS-CoV-2.

The World Health Organization’s targets for hepatitis C elimination by 2030 are ambitious, but, in 2020, global leadership demonstrated by Egypt, innovative strategies to improve linkage to treatment for marginalized populations and the broadened capacity of direct-acting antiviral therapy have been promising for enhanced global elimination efforts.

Important studies published in 2020 highlight that coeliac disease is a systemic autoimmune-like disorder with the potential to result in serious long-term health consequences that might also occur outside the gastrointestinal tract. Ultimately, the results of these studies will enable the development of better strategies for the management of coeliac disease.

In 2019, to help meet viral hepatitis targets from the WHO, studies have developed optimal strategies to enable transplantation of HCV-positive organs, assessed the real-world efficacy of salvage therapy for direct-acting antiviral therapy failures in chronic HCV infection and evaluated the risk of hepatocellular carcinoma with current first-line antiviral therapies for chronic HBV infection.

Key studies published in 2019 highlight novel concepts regarding the pathogenesis of inflammatory bowel disease: the emerging role of host–microorganism interactions and the regional microbiota as disease drivers, and the identification of new therapeutic targets. These findings suggest new avenues for research and define important hallmarks for clinical diagnosis and therapy.

Key studies published in 2019 shed new light on how complex motor patterns emerge from the functional organization of circuits in the enteric nervous system and, in turn, how extrinsic afferent neurons and common commensal microorganisms interface with these circuits to modulate intestinal motility.

In 2019, there have been substantial advances in our understanding of the gut microbiome. Key developments include an improved gut-on-a-chip system, a search for small proteins produced by the commensal gut microbiome and the publication of one of the most comprehensive multi-omic datasets for interrogating host–microorganism interactions in inflammatory bowel disease.

Advances have been made in the field of nonalcoholic fatty liver disease in 2019. One paper highlights the role of gut microbiota in hepatocellular carcinoma (HCC) pathogenesis, another presents a noninvasive algorithm for detecting advanced liver fibrosis and another suggests a potential novel approach to treating nonalcoholic steatohepatitis and suppressing HCC development.

In 2019, powerful single-cell analyses were applied to liver cancer biology at an unprecedented level. In parallel with this achievement was the identification of serum α-fetoprotein as a biomarker for patient selection in the use of ramucirumab for liver cancer and that β-catenin activation can distinguish between liver cancer immunotherapy responders and non-responders.

HBV and HCV infections continue to be major global health problems, causing over 1 million deaths annually. Key studies this year investigated the innate and adaptive immune responses in different clinical scenarios in HBV infection, whereas others evaluated the merits of transplanting HCV-infected organs into uninfected recipients.

In 2018, advances were made in immunotherapy for colorectal cancers with microsatellite instability but, by contrast, immunotherapy studies in microsatellite-stable colorectal cancer had disappointing results. However, novel insights into the tumour microenvironment barriers that might limit therapeutic efficacy were identified, thereby offering new strategies.

In 2018, there have been substantial advances in our understanding of the risk factors for advanced liver disease in nonalcoholic fatty liver disease, including genetic variants and the gut microbiota. Promising results have also arisen from drugs targeting metabolic pathways involved in the progression of liver damage.

In 2018, key studies shaped the way we think about environmental factors and their influence on the gut microbiota. These data highlight a new-found appreciation for the role of diet in modifying the gut microbiome and fortifying the intestinal barrier, which ultimately might lead to better treatments for chronic metabolic diseases.