Reviews & Analysis

Pancreatic ductal adenocarcinoma (PDAC) is thought to develop through the stepwise accumulation of cancer gene mutations. A new study suggests that 16% of PDACs exhibit genetic rearrangements that simultaneously altered two or more cancer driver genes. These findings challenge the current models of PDAC development, but arguably remain compatible with a stepwise tumour progression.

Patients with ulcerative colitis in clinical remission are increasingly undergoing colonoscopies to determine endoscopic remission. However, the histological evaluation of biopsy samples provides additional criteria to predict which patients are most likely to undergo relapse, so what is the ideal therapeutic end point for patients with ulcerative colitis?

Long-standing IBD is associated with an increased risk of neoplasia. Chromoendoscopy was proven to be the most sensitive modality for dysplasia detection in several clinical trials, but a new study has now shown it to be an effective screening strategy in a routine clinical setting, further warranting its implementation into real-world practice.

In a new study, Younossi et al. poignantly depict the daunting and enormous prevalence of NAFLD and its associated clinical and economic burden in the USA and four countries in Europe. The astronomical health-care costs will increase as the prevalence of NAFLD increases. All stakeholders are called to action.

Zinc is essential for biological processes in both mammalian hosts and their microbial symbionts. Sequestration of zinc is a strategy used by mammals to protect against bacterial pathogens. A new study has demonstrated that zinc supplementation increased susceptibility and worsened disease in a mouse model of Clostridium difficile infection.

The gastrointestinal safety of incretin-based therapies is controversial. Two new studies find no effect of GLP-1 receptor agonists on acute pancreatitis risk, but increased risk of bile duct and gallbladder disease. However, no retrospective epidemiological studies can provide definitive answers, and nausea, vomiting and diarrhoea remain the most clinically relevant adverse effects of these drugs, compromising long-term adherence.

A new study has advanced our knowledge on the pathogenesis of noncoeliac wheat sensitivity (NCWS), implicating the activation of innate immunity markers and immunological mechanisms at the basis of NCWS. However, limitations in the design of studies performed in this field will need addressing to help identify the root cause of NCWS.

The first phase of chronic hepatitis B, the immune tolerance phase, is traditionally considered to be a quiescent stage of disease. Emerging data now suggests the contrary, with immunological, pathological and virological evidence supporting an underlying active disease, signifying the need to consider earlier treatment commencement.

Unexpected data from new studies show that direct-acting antiviral agents might promote tumour occurrence in patients with cirrhosis, or recurrence in patients with presumed cure of hepatocellular carcinoma. In view of the potential clinical implications, this controversy calls for a thorough and expeditious consideration of the hypothetical oncogenic activity of novel HCV drugs.

Converging studies have shown that the gut microbiota composition and activity possibly contribute to shape host metabolism. A new study deeply analysed metabolic parameters in humans with obesity after short-term antibiotic exposure; the conclusion calls into doubt some direct and simple associations found between the gut microbiota and metabolic disorders

Although a colonoscopy for the evaluation of IBD and the surveillance of colitis-associated neoplasia should be performed at the time of the diagnosis of primary sclerosing cholangitis (PSC), the results from a new study suggest that screening for PSC with magnetic resonance cholangiography in patients with long-term IBD might be needed.

A recent study reports that being overweight in late adolescence is associated with an increased risk of liver-related morbidity and mortality later in life. These findings give further strength to the concerns for the deleterious effects of childhood obesity on liver health. Early prevention by screening and lifestyle modification should be advised by health policies.

Maternal obesity has been linked to neurodevelopmental disorders in offspring but the underlying mechanisms are unclear. Buffington and colleagues now provide causal evidence linking maternal diet, gut microbiota and the central nervous system, highlighting key components of gut–brain signalling and indicating that a probiotic might relieve behavioural abnormalities.

Since the recognition of reflux oesophagitis as a disease entity, scientists and clinicians have commonly assumed that the first step in its pathogenesis was a loss of superficial epithelial cells, brought about by caustic acid injury. However, new data suggests that it is time to reconsider this concept.

Symptom-based diagnostic criteria have been criticized for being overly complex and performing modestly in differentiating organic from functional gastrointestinal diseases. The new Rome IV criteria now supersede Rome III. In general, these minor amendments are unlikely to lead to substantial improvement in accuracy and use in routine clinical care. Is a different approach required in future?

The global burden of malnutrition (undernutrition, micronutrient deficiencies or obesity) is considerable and associated with risk of excess mortality and long-term adverse outcomes. Concerted action to achieve agreed global nutrition targets is proposed for the next decade, which must be coupled with the political will to address the root causes of malnutrition and implement evidence-based strategies.

Obesity is a risk factor for several noncommunicable diseases, but some individuals with obesity remain metabolically healthy throughout life; whether these individuals are at risk of developing NAFLD is uncertain. In a new study, Chang et al. showed a statistically significant, graded relationship between BMI and NAFLD in metabolically healthy individuals.

Elucidating the entire complexity of biological functions in the liver is vital to understand its key role in the progression of complex diseases. A new mouse study integrates complementary '–omics' data across various environmental states using the liver as a platform for multiomics analysis and identifies new mechanisms in hepatic mitochondrial function.

A new study reports that activation of neutrophils leads to the release of neutrophil extracellular traps (NETs) and coagulation, which then promote development of a tumorigenic microenvironment in the small intestine. These findings provide novel insights into the role of neutrophils in cancer and suggest enticing directions for future research.

A recent study reports on drug clearance in newborn babies after in utero exposure to anti-TNF antibodies, infliximab and adalimumab. As women with IBD are increasingly exposed to these drugs due to changing treatment paradigms and earlier diagnosis, this commentary explores these clinically important results.