Reviews & Analysis

Non-anatomical resection of colorectal liver metastases is the current preferred approach to maximize sparing of the hepatic parenchyma. A new study raises the question of whether resection in patients with KRAS-mutated colorectal liver metastases should be performed along segmental, anatomical lines to reduce the risk of local liver recurrence.

Patients who are obese and also consume excess alcohol are at increased risk of liver-related disease. In this Review, Parker and colleagues discuss how alcohol and obesity affect adipose tissue function, and describe the importance of the adipose-tissue–liver axis in liver disease pathogenesis and outcomes.

NAFLD is growing in prevalence worldwide, and has emerged as a leading cause of end-stage liver disease in many countries. In this Review, the authors describe the global epidemiology of NAFLD, discuss associated risk factors and outline challenges for screening and management.

Proton-pump inhibitors (PPIs) are widely used for gastric acid suppression in a number of gastric-acid-related diseases, including GERD. However, in recent years, increasing evidence of adverse events has been reported, raising concerns with clinicians and patients. This Review provides an update on the complications and risks of PPI use.

Various mechanisms eliciting symptoms in GERD and its most common phenotypic presentation, nonerosive reflux disease (NERD), have been suspected and investigated. One study now suggests that superficial nerves in the oesophageal epithelium might have a key role in the pathogenesis of NERD and could represent a potential target for topical therapies.

KRAS oncogene mutations are commonly encountered in pancreatic ductal adenocarcinoma, driving tumour initiation, proliferation, progression and metastasis. Human exosomes engineered to deliver small interfering RNA silencing KRAS^G12D are highly efficient at specifically targeting pancreatic cancer cells to dramatically reduce RAS activation, cancer cell proliferation and metastatic processes.

IBD is associated with markedly reduced intestinal mucosal oxygen levels. In this Review, the authors discuss the role of mucosal hypoxia and hypoxia-induced signalling in IBD and identify potential targets for therapies, focusing on the cell-specific functions of hypoxia-inducible factors, prolyl hydroxylases and nuclear factor-κB.

Direct-acting antiviral agents (DAAs) are highly effective treatments for HCV, but are not always accessible to people who inject drugs (PWID). Here, Grebely and colleagues outline the epidemiology of HCV in PWID, discuss current data on DAA outcomes in this population and highlight steps required to broaden access to HCV therapy with the eventual goal of HCV elimination.

IBD is a complex disease characterized by multiple interacting pathogenic components. In this Perspectives, the authors advocate studying the 'IBD interactome' to build a molecular network of IBD, and discuss new concepts and tools to implement an unbiased systems approach that could facilitate development of novel therapies.

Endocrine (such as diabetes) and exocrine (such as pancreatitis) disorders of the pancreas have a substantial burden worldwide. This Review explores the potential of regenerative medicine and cell-based approaches to restore both endocrine and exocrine pancreatic function, describing insights into cell replacement, implantation and reprogramming.

Perianal fistulizing Crohn's disease has a major negative effect on a patient's quality of life and is a predictor of poor long-term outcome. Here, the authors provide an up-to-date overview on the pathogenesis and diagnosis of fistulizing Crohn's disease, as well as therapeutic strategies.

Clinicians face a rapidly evolving set of challenges and opportunities for generating insights into the health of patients from microbiome analysis. Here, the authors summarize the major decision points confronting new entrants to the field or for those designing new projects in microbiome research.

A large-scale comprehensive analysis of hepatocellular carcinoma (HCC) based on the integration of six distinct data platforms has pinpointed novel oncogenic processes and prognostic subgroups. These findings confirm previously identified molecular subclasses and fuel the need for a clear strategy of precision medicine in HCC.

In a new report, adolescents with genotype 2 or 3 HCV infection who were given sofosbuvir and ribavirin showed a near 100% sustained virologic response. This study is the beginning of a new wave of treatments for paediatric HCV infection, forming part of a global strategy to eradicate viral hepatitis.

A new study reveals an involvement of SLC22A3 in the development of familial oesophageal squamous cell carcinoma (ESCC). Reduced expression of SLC22A3 is detected not only in ESCC tumours but also in non-tumour tissues of patients with familial ESCC. Interestingly, adenosine-to-inosine editing of SLC22A3 mRNA is proposed to drive early tumour invasion and metastasis, by inhibiting SLC22A3 expression.

Changes in the composition and metabolic function of the gut microbiota have been linked to IBD, but a direct causal association has yet to be established in humans. This Review discusses the evidence supporting dysbiosis in the gut microbiota in Crohn's disease and ulcerative colitis, exploring evidence from animal models and the translation to human disease.

Owing to its unique composition and influence on numerous biological processes, the extracellular matrix (ECM) is an ideal therapeutic substrate for tissue repair. In this Review, the authors provide an overview of ECM bioscaffolds derived from gastrointestinal tissues, and discuss advances in regenerative medicine using these scaffolds for the reconstruction of functional gastrointestinal tissues.

Combating the obesity epidemic necessitates a range of effective therapies. In this Review, Dixon and Lee explore the medical devices developed to bridge the gap between conservative lifestyle and pharmacotherapy interventions and disruptive surgical approaches, focusing on mechanisms of action, efficacy and safety.

Biosimilar monoclonal antibodies are now being accepted in clinical practice by IBD specialists. However, switching patients already undergoing originator biologic treatment to biosimilars has been debated due to lack of controlled studies. The NOR-SWITCH study now provides novel clinical evidence in switching from originator to biosimilar in patients with IBD.

Increasing evidence suggests that the gut microbiota are important modulators of chronic liver disease progression and the development of hepatocellular carcinoma. In this Review, Yu and Schwabe discuss the mechanisms by which the gut microbiota promote hepatocarcinogenesis, and explore therapeutic interventions with clinical potential.