Elevated Plasma IL-6 Associates with Increased Risk of Advanced Fibrosis and Cholangiocarcinoma in Individuals Infected by Opisthorchis viverrini

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and increasing risk of advanced fibrosis and bile duct cancer; for example, in age and sex adjusted analyses, individuals with the highest quartiles of plasma IL-6 had a 19 times greater risk of developing advanced periductal fibrosis and a 150 times greater risk of developing of bile duct cancer than individuals with no detectable level of plasma IL-6. Finally, we show that a single plasma IL-6 measurement has excellent positive predictive value for the detection of both advanced bile duct fibrosis and bile duct cancer in regions with high O. viverrini transmission. These data support our hypothesis that common mechanisms drive bile duct fibrosis and bile duct tumorogenesis from chronic O. viverrini infection. Our study also adds a unique aspect to the literature on circulating levels of IL-6 as an immune marker of hepatobiliary pathology by showing that high levels of circulating IL-6 in plasma are not related to infection with O. viverrini, but to the development of the advanced and often lethal pathologies resulting from chronic O. viverrini infection

The legal determinants of health: harnessing the power of law for global health and sustainable development

Health risks in the 21st century are beyond the control of any government in any country. In an era of globalisation, promoting public health and equity requires cooperation and coordination both within and among states. Law can be a powerful tool for advancing global health, yet it remains substantially underutilised and poorly understood. Working in partnership, public health lawyers and health professionals can become champions for evidence-based laws to ensure the public's health and safety. This Lancet Commission articulates the crucial role of law in achieving global health with justice, through legal instruments, legal capacities, and institutional reforms, as well as a firm commitment to the rule of law. The Commission's aim is to enhance the global health community's understanding of law, regulation, and the rule of law as effective tools to advance population health and equity. The term law throughout is used to mean legal instruments such as statutes, treaties, and regulations that express public policy, as well as the public institutions (eg, courts, legislatures, and agencies) responsible for creating, implementing, and interpreting the law. By establishing the rules and frameworks that shape social and economic interactions, laws exert a powerful force on all the social determinants of health. Well designed laws can help build strong health systems, ensure safe and nutritious foods, evaluate and approve safe and effective drugs and vaccines, create healthier and safer workplaces, and improve the built and natural environments. However, laws that are poorly designed, implemented, or enforced can harm marginalised populations and entrench stigma and discrimination. This Commission brings together global leaders in the fields of health, law, and governance. We make the case for better, more strategic linkages between health and law, and the professionals who work in both fields. We begin by providing a short explanation of legal terms and concepts, and the actors and institutions that govern health. Our report is structured around four legal determinants of health, each of which powerfully affects health outcomes. We use the term legal determinants of health because it demonstrates the power of law to address the underlying social and economic causes of injury and disease. These four legal determinants show how law can substantially influence health and equity. We do not endeavour a systematic review of law in global health, but rather to advocate for, and demonstrate, the crucial value of law in advancing global health with justice. Finally, drawing on identified areas for reform, as well as principles of good governance and the right to health, we offer seven concrete recommendations for action.</p