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.
Key Advances in Gastroenterology & Hepatology
The Key Advances in Gastroenterology & Hepatology collection offers a unique series of specially commissioned ‘Year in Review’ articles that highlight the key discoveries made each year. In these articles, leading experts in the field describe their pick of the top 3–8 key advances of the year, outlining their clinical impact and implications for current and future research.
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.
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, 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.
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 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 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.
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.
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.
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, 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.
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.
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, 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.
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.
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.
Current related Reviews
The prevalence of nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is projected to continue to increase worldwide. In this Review, Huang, El-Serag and Loomba discuss the global epidemiology and risk factors for NAFLD-related HCC, and propose strategies to tackle this problem.
A gluten-free diet is currently the only effective treatment for coeliac disease but an increased understanding of disease pathogenesis has led to the identification of several potential therapeutic targets. This Review provides a broad overview of current and emerging therapies for coeliac disease.
The management of viral hepatitis in the setting of pregnancy requires special consideration. This Review examines each hepatitis virus individually to address the effect of pregnancy on the natural history of infection and how the viral infections influence maternal and infant outcomes, including mother-to-child transmission.
Therapeutic drug monitoring (TDM) has been suggested as a useful tool for managing patients with inflammatory bowel disease on biologic therapy. This Perspective examines evidence and guidelines related to TDM in inflammatory bowel disease management and also strategies to optimize biologic treatment where TDM is not available.
Food addiction is an eating behaviour that reflects alterations in brain–gut–microbiome (BGM) interactions and a shift towards hedonic mechanisms. This Review summarizes the physiology of food addiction in obesity as it relates to BGM interactions and provides insights into treatment targets for food addiction aimed at each level of the BGM axis.
Viral hepatitis is a global public health problem. In this Viewpoint, we asked a selection of scientists and clinicians working in the viral hepatitis field to provide their opinions on progress and pitfalls towards the 2030 viral hepatitis elimination goals.
Modern therapies for malignant liver tumours integrate neoadjuvant and adjuvant strategies. This broad Review discusses these approaches, including advances in staged surgeries, systemic therapies, ablation therapies and liver transplantation.
The neoplastic epithelium of pancreatic cancer exists within a dense stroma that is recognized as a critical mediator of disease progression. This Review discusses our current understanding of the three principal constituents of pancreatic cancer stroma, their effect on the prevalent immune landscape and promising therapeutic targets within this compartment.
As the number of novel drugs for inflammatory bowel disease (IBD) increases, comparison of therapeutic options has become a key challenge in IBD trials. Here, the authors provide an overview of IBD trial design with a focus on comparative research and the head-to-head trials format.
The gut microbiota has been linked to non-alcoholic fatty liver disease (NAFLD), but metabolic confounding factors, such as obesity and diabetes, complicate analysis. This Review provides a broad insight into microbiome signatures for human NAFLD and explores issues with disentangling them from underlying metabolic disorders.
The enteric nervous system (ENS) is essential for life and controls the function of the gastrointestinal tract. Here, an overview of sensory transduction and neural circuits in the ENS is provided, yielding insights into the generation of gastrointestinal motility.
Organoid technology has emerged as a powerful method for studying gastrointestinal cancers. This Review describes organoid models of gastrointestinal cancers, such as colorectal and liver cancer, and discusses how they can be used in basic and translational research in fields such as drug discovery and personalized medicine.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. This Review summarizes the epidemiology, risk factors (including viral hepatitis and NAFLD), molecular profiles and treatment of HCC, providing insights into how the global burden of HCC can be reduced.
This Review discusses the genetics of nonalcoholic fatty liver disease (NAFLD), including evidence of shared genetic modifiers and possible pleiotropic effects between NAFLD and other liver diseases or metabolic disorders. The translational implications and future challenges are also discussed.
The design of clinical trials for hepatocellular carcinoma is complicated by a number of obstacles. In this Review, the authors discuss the advances in systemic therapy for hepatocellular carcinoma and critically discuss trial designs in the context of past successes and failures.
Macrophages are the gatekeepers of intestinal immune homeostasis. This Review discusses the molecular and cellular mechanisms involved in the differentiation and function of intestinal macrophages in homeostasis and inflammation, and their role in resolving the inflammatory process.
The hepatic consequence of metabolic syndrome and obesity, nonalcoholic fatty liver disease (NAFLD), underlies many cases of hepatocellular carcinoma (HCC). In this Review, the authors discuss NAFLD-associated HCC, including its epidemiology, key features that promote hepatocarcinogenesis and the management of HCC in patients with obesity.
This Review summarizes current knowledge concerning the molecular subtyping of pancreatic cancer and explores future strategies using molecular taxonomy to guide therapeutic development and therapy with the overall goal of improving outcomes for this disease.
The intestinal epithelium undergoes constant replenishment, fuelled by continuously dividing stem cells residing in crypts. In this Review, Gehart and Clevers discuss the signals, cell types and mechanisms that control intestinal stem cell homeostasis and explore how imbalance in key signalling pathways can cause disease.