Review Articles in 2021

Fatty pancreas disease reportedly affects approximately 1 in 5 people in general populations. This Review discusses the up-to-date knowledge on the risk factors, diagnosis and pathophysiology of the disease and highlights the approaches to reducing intra-pancreatic fat.

Intestinal fibrosis is an important feature of inflammatory bowel disease (IBD) that remains poorly understood. Here, D’Alessio and Ungaro et al. review the cellular and molecular mechanisms contributing to intestinal fibrosis and discuss future therapeutic strategies for IBD-related fibrosis.

In this Review, Kupiec-Weglinski and colleagues describe the roles of macrophages, neutrophils, and platelets in liver ischaemia–reperfusion injury (LIRI) and discuss potential therapeutic strategies for treating LIRI in transplant recipients.

In this Review, Chu and Traverso provide an overview of gastrointestinal-based drug delivery, discussing conventional delivery methods and challenges posed by the gastrointestinal tract as a drug delivery environment, as well as emerging technologies.

Autoimmune pancreatitis and IgG4-related cholangitis are frequent manifestations of IgG4-related disease (IgG4-RD). Here, Löhr and colleagues present current understanding of the pathophysiology of IgG4-RD and describe all IgG4-RD manifestations in the digestive tract. Diagnosis, prognosis and treatment of IgG4-RD are also discussed.

Cancer development is a dynamic evolutionary process. This Review explores the mechanisms underlying clonal expansion and contraction as well as the evolutionary dynamics in Barrett oesophagus and its progression to dysplasia and oesophageal adenocarcinoma. The implications for patient management (including surveillance, risk stratification and therapy) are also explored.

In this Review, Arab and colleagues discuss management of alcohol use disorder in patients with alcohol-associated liver disease, particularly in the setting of liver transplantation. An integrative, multidisciplinary approach is proposed.

In this Review, Albillos and colleagues describe cirrhosis-associated immune dysfunction (CAID) and its components — systemic inflammation and immune deficiency — as well as the role of CAID in the pathogenesis of acute-on-chronic liver failure. Therapies that aim to modulate CAID are discussed.

Metabolomics and lipidomics approaches are being used to identify biomarkers for nonalcoholic fatty liver disease (NAFLD). This Review discusses the application of metabolomics and lipidomics in clinical studies and in the identification of key metabolic pathway alterations in NAFLD.

The complexity of hepatocellular carcinoma (HCC) hinders effective treatment. Here, Lee and colleagues summarize cancer stem cell (CSC) origin and plasticity, CSC–immune system interactions and the effects of the microenvironmental niche on cancer stemness in HCC. Potential CSC-based therapies for HCC are also presented.

The gut microbiota is increasingly recognized as an important factor in disease development, progression and treatment response. This Review highlights the promise of strategies that target the gut microbiome in the treatment of disease, including cancer and infectious and metabolic diseases.

Defaecation is a coordinated process that requires a morphologically intact gastrointestinal tract and the integration of multiple physiological systems (neuromuscular, hormonal and cognitive). This Review describes the physiology of human defaecation and continence, providing insights into the pathophysiology of defaecation and evacuation disorders.

Here, the authors describe the complex role of regulated cell death (RCD) in pancreatic tumorigenesis and treatment. They also discuss how RCD is reshaped in tumours at both molecular and metabolic levels and highlight the challenges and opportunities in this field.

This Review discusses the role of dietary fats and carbohydrates in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Studies on the dietary habits of patients with NAFLD, and the effect on liver fat accumulation of altering dietary macronutrients, are also reviewed.

In this Review, the authors describe the biology of IL-6 family cytokines relevant to metabolism, liver disease and gastrointestinal disease, and discuss the potential of IL-6 family members as therapeutic agents in these areas.

In this Review, Neurath discusses the implications of COVID-19 on immunosuppressive and biologic therapies as well as those of vaccination in gastrointestinal contexts such as inflammatory bowel disease, autoimmune hepatitis and liver transplantation.

This Review describes how functional genetic screens can shed light on various outstanding questions in liver cancer biology, including which genes can drive hepatocarcinogenesis, how to improve the efficacy of existing therapies and how to find novel therapeutic targets for liver cancer.

Pancreatic cancer is typically diagnosed at a late stage and early detection is a priority. This Review focuses on precancerous lesions of the pancreas, describing their pathological and molecular features and highlighting different DNA-based molecular approaches for early detection and their clinical utility.

Vast developments are being made within the field of pancreatic cancer genomics. This Review discusses the wide-ranging and most current research with the goal of integrating this information into a unifying description of the life history of pancreatic cancer.

Increasing levels of antibiotic resistance in Helicobacter pylori are a serious threat to human health globally. This Review discusses H. pylori infection and antibiotic resistance, and provides insights into the underlying mechanisms and clinical implications (including detection and management).