Current Opinion in Gastroenterology最新文献

Purpose of review: Current treatment options for cholangiopathies are severely limited and there is thus a critical need to identify and develop therapies. This review discusses the role of integrins in biliary injury and fibrosis and their potential as therapeutic targets.

Recent findings: There are a diverse set of roles that integrins play in biliary injury and fibrosis. Some integrins activate TGF-β signaling or are involved in sensing of the extracellular matrix, making them attractive targets for biliary fibrosis. In recent work, autoantibodies to α v β 6 were identified in patients with PSC, supporting the relevance of this integrin in the disease. In addition, a role for α 2 β 1 in cyst formation was identified in a mouse model of polycystic liver disease. Leukocyte integrins (e.g. α E β 7 and α 4 β 7 ) contribute to lymphocyte trafficking, making them potential targets for biliary inflammation; however, this has not yet translated to the clinic.

Summary: While all members of the same family of proteins, integrins have diverse roles in the pathogenesis of biliary disease. Targeting one or multiple of these integrins may slow or halt the progression of biliary injury and fibrosis by simultaneously impacting different pathologic cells and processes.

Purpose of review: This review addresses the newest findings on micronutrient status and protein-energy malnutrition in the increasingly aging global population; understanding the nutritional challenges they face is vital for healthcare, well being, and public health.

Recent findings: The review examines deficiencies in macro- and micronutrients among nonhospitalized, free-living older adults, revealing significant associated health consequences, including frailty, cognitive decline, and reduced quality of life. Deficiencies in fat-soluble vitamins such as A, D, and E, are common in older populations, emphasizing the need for close monitoring for status of these. Furthermore, water-soluble vitamin deficiencies, especially vitamins B12 and C are also common, and pose health risks, including neurological disorders and cognitive decline. Iron and iodine deficiencies contribute to anemia, and neurocognitive disorders. Finally, protein-energy malnutrition is common in older adults living in high-resource countries and may occur concomitant with depletion of one or more micronutrients.

Summary: Addressing specific nutritional deficiencies is fundamental to enhancing the wellbeing and quality of life for free-living older adults. Protein-energy malnutrition, impacting over 25% of those aged 65 and above, results in a range of health issues, including poor wound healing, susceptibility to infections, anemia, and delayed convalescence. These concerns are aggravated by inadequate energy, macronutrient, and micronutrient intake, affecting muscle strength and overall health. Future research should focus on tailored appropriate monitoring of at-risk individuals, specific nutritional interventions, and dietary strategies to mitigate these issues and improve health outcomes among older adults.

Purpose of review: To delineate common and uncommon dietary and nutritional deficiencies in individuals with chronic heavy alcohol use and alcohol use disorder and to highlight important advances in the nutrition field in patients ranging from those with alcohol use disorder (AUD) and no liver disease to those with decompensated alcohol-associated liver disease (ALD).

Recent findings: Patients with AUD may have nutritional deficiencies, especially isolated nutrient deficiencies, such as thiamine or zinc deficiencies. This should not be surprising, as alcohol is a major source of "empty calories." It is devoid of critical macronutrients, such as protein, and micronutrients including important vitamins and minerals. Patients with AUD frequently drink much more than often appreciated (10-20 drinks a day). Patients with AUD and early ALD often begin to develop more apparent nutritional deficiencies. Healthcare providers need to be aware of the presenting features of individual nutrient deficiencies, such as thiamine deficiency, and to provide prompt treatment. In patients with more advanced liver disease, malnutrition correlates with severity of liver disease. It is important to understand the value of nutritional support throughout the spectrum of AUD.

Summary: We review nutritional deficiencies in the spectrum of patients with AUD and ALD and highlight new information and recommendations.

Purpose of review: The purpose of this review is to summarize commonly encountered nutritional deficiencies in children and their implications. Considering data suggesting that the majority of children with the United States consume unhealthy diets, the growing interest in the consumption of limiting diets, as well as the insidious clinical presentation of nutritional deficiencies, this is a timely and highly relevant review.

Recent findings: The underlying socioeconomic and medical circumstances that predispose to nutritional deficiencies in the Western world are covered. The high index of suspicion required to recognize nutritional deficiencies and the limitations of available testing are also discussed. Finally, the need for the development of accurate nutritional biomarkers is presented as a future research priority.

Summary: Nutritional deficiencies are not uncommon, even in high resource countries. Clinicians should remain vigilant and include nutritional deficiencies in the differential diagnoses of patients presenting with nonspecific symptoms.

Purpose of review: Primary sclerosing cholangitis is a chronic cholestatic liver disease for which no pharmacological treatment options are available. It is an immune-mediated disease and macrophages have been implicated in disease pathogenesis. However, which specific macrophage populations contribute to disease, and how we can apply this as therapeutic strategy is still unclear.

Recent findings: Recent studies have shown that fibrous tissue is characterized by osteopontin-positive macrophages, including in patients with primary sclerosing cholangitis. Experimental models indicate that intracellular osteopontin in macrophages confers protection, while secreted osteopontin contributes to disease. Serum osteopontin is increased in different liver diseases, including primary sclerosing cholangitis, and might thus serve as therapeutic target.

Summary: Although several studies report on the role of osteopontin in liver disease, only a minority of the studies have focused on isoform-specific functions, and the importance of the cellular source of secreted osteopontin. Future studies investigating these aspects, and how this can be translated to therapies for primary sclerosing cholangitis, and other chronic liver diseases, are required.

Purpose of review: In the pathophysiological context of cholangiopathies and more broadly of hepatopathies, while it is conceptually clear that the maintenance of inter-cholangiocyte and inter-hepatocyte tight junction integrity would be crucial for liver protection, only scarce studies have been devoted to this topic. Indeed, in the liver, alteration of tight junctions, the intercellular adhesion complexes that control paracellular permeability would result in leaky bile ducts and bile canaliculi, allowing bile reflux towards hepatic parenchyma, contributing to injury during the disease process.

Recent findings: Last decades have provided a great deal of information regarding both tight junction structural organization and signaling pathways related to tight junctions, providing clues about potential intervention to modulate paracellular permeability during cholangiopathies pathogenesis. Interestingly, several liver diseases have been reported to be associated with abnormal expression of one or several tight junction proteins. However, the question remains unanswered if these alterations would be primarily involved in the disease pathogenesis or if they would occur secondarily in the pathological course.

Summary: In this review, we provide an overview of tight junction disruptions described in various biliary diseases that should pave the way for defining new therapeutic targets in this field.

Purpose of review: This review discusses evidence regarding progenitor populations of the biliary tree in the tissue regeneration and homeostasis, and the pathobiology of cholangiopathies and malignancies.

Recent findings: In embryogenesis biliary multipotent progenitor subpopulation contributes cells not only to the pancreas and gall bladder but also to the liver. Cells equipped with a constellation of markers suggestive of the primitive endodermal phenotype exist in the peribiliary glands, the bile duct glands, of the intra- and extrahepatic bile ducts. These cells are able to be isolated and cultured easily, which demonstrates the persistence of a stable phenotype during in vitro expansion, the ability to self-renew in vitro, and the ability to differentiate between hepatocyte and biliary and pancreatic islet fates.

Summary: In normal human livers, stem/progenitors cells are mostly restricted in two distinct niches, which are the bile ductules/canals of Hering and the peribiliary glands (PBGs) present inside the wall of large intrahepatic bile ducts. The existence of a network of stem/progenitor cell niches within the liver and along the entire biliary tree inform a patho-biological-based translational approach to biliary diseases and cholangiocarcinoma since it poses the basis to understand biliary regeneration after extensive or chronic injuries and progression to fibrosis and cancer.