Coeliac disease is a systemic disorder characterized by immune-mediated enteropathy, which is caused by gluten ingestion in genetically susceptible individuals. The clinical presentation of coeliac disease is highly variable and ranges from malabsorption through solely extra-intestinal manifestations to asymptomatic. As a result, the majority of patients with coeliac disease remain undiagnosed, misdiagnosed or experience a substantial delay in diagnosis. Coeliac disease is diagnosed by a combination of serological findings of disease-related antibodies and histological evidence of villous abnormalities in duodenal biopsy samples. However, variability in histological grading and in the diagnostic performance of some commercially available serological tests remains unacceptably high and confirmatory assays are not readily available in many parts of the world. Currently, the only effective treatment for coeliac disease is a lifelong, strict, gluten-free diet. However, many barriers impede patients' adherence to this diet, including lack of widespread availability, high cost, cross-contamination and its overall restrictive nature. Routine follow-up is necessary to ensure adherence to a gluten-free diet but considerable variation is evident in follow-up protocols and the optimal disease management strategy is not clear. However, these challenges in the diagnosis and management of coeliac disease suggest opportunities for future research.
A number of environmental factors have been associated with the development of IBD. Alteration of the gut microbiota, or dysbiosis, is closely linked to initiation or progression of IBD, but whether dysbiosis is a primary or secondary event is unclear. Nevertheless, early-life events such as birth, breastfeeding and exposure to antibiotics, as well as later childhood events, are considered potential risk factors for IBD. Air pollution, a consequence of the progressive contamination of the environment by countless compounds, is another factor associated with IBD, as particulate matter or other components can alter the host's mucosal defences and trigger immune responses. Hypoxia associated with high altitude is also a factor under investigation as a potential new trigger of IBD flares. A key issue is how to translate environmental factors into mechanisms of IBD, and systems biology is increasingly recognized as a strategic tool to unravel the molecular alterations leading to IBD. Environmental factors add a substantial level of complexity to the understanding of IBD pathogenesis but also promote the fundamental notion that complex diseases such as IBD require complex therapies that go well beyond the current single-agent treatment approach. This Review describes the current conceptualization, evidence, progress and direction surrounding the association of environmental factors with IBD.
Globally, nearly half of deaths from cirrhosis and chronic liver diseases (CLD) and three-quarters of deaths from hepatocellular carcinoma (HCC) occur in the Asia-Pacific region. Chronic hepatitis B is responsible for the vast majority of liver-related deaths in the region. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common form of CLD, affecting an estimated 30% of the adult population. Compared with people of European descent, people from the Asia-Pacific region carry more genetic variants associated with MASLD and its progression. Alcohol is a fast-growing cause of CLD and HCC in Asia as a result of the rising per-capita consumption of alcohol. Drug-induced liver injury is under-recognized and probably has a high prevalence in this region. The epidemiological and outcome data of acute-on-chronic liver failure are heterogeneous, and non-unified definitions across regions contribute to this heterogeneity. CLDs are severely underdiagnosed, and effective treatments and vaccinations are underutilized. In this Review, we highlight trends in the burden of CLD and HCC in the Asia-Pacific region and discuss the rapidly changing aetiologies of liver disease. We examine the multiple gaps in the care cascade and propose mitigating strategies and future directions.