The lymphatic system: A new frontier in hepatology

Iwakiri, Yasuko

doi:10.1002/hep.28650

Cited by 22 publications

(33 citation statements)

References 10 publications

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“…(2) He also indicated that the study of the lymphatic vascular system is overlooked partly because of lack of established techniques for studying the lymphatic vasculature. (1) We support the information provided by Iwakiri; however, we believe that the lymphatic vascular system may be analyzed by means of modern magnetic resonance (MR) techniques. Noncontrast heavily T 2weighted three-dimensional MR imaging, which was introduced in the early 1990s, is a completely noninvasive imaging technique that can accurately depict the morphological characteristics of the biliary and pancreatic ducts.…”

Section: To the Editorsupporting

confidence: 76%

“…We read with great interest the article by Iwakiri in the September 2016 issue of HEPATOLOGY emphasizing the role of the lymphatic system in liver physiology. (1) He indicated that the liver is the largest lymphproducing organ of the body and that production of lymph markedly increases in cirrhosis with portal hypertension with likely implication of the lymphatic system in ascites formation. (2) He also indicated that the study of the lymphatic vascular system is overlooked partly because of lack of established techniques for studying the lymphatic vasculature.…”

Section: To the Editormentioning

confidence: 99%

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MR lymphography of hepatic lymphatic system

Arrivé

Mouhadi

2017

Hepatology

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and LSM by TE) would not be applicable, whereas the other proposed model, platelet-to-spleen ratio (PSR; which includes platelet count and the bipolar diameter of the spleen, first proposed by Dr. Giannini and colleagues) would be always applicable, given that spleen diameter can be measured in 100% of the cases. Indeed, one of the aims of the ANTICIPATE study was to provide different noninvasive tools to predict varices needing treatment, so that in case of failure or unavailability of one tool, an alternative tool could be used. This was done having in mind that the availability of LSM by TE is very limited in some areas of the world. The main conclusion of our study was that "LSPS, a combination of LSM by TE-platelet count, or PSR could be used to identify a relevant subset of patients with compensated cirrhosis and Child-Pugh A with a very low probability of VNT (<5%) in which endoscopy could be avoided." Therefore, we think we sufficiently addressed this concern in our report.The second issue raised by Drs. Giannini and Savarino was that the results of our study should be corrected in an "intention-to-test" analysis, taking into account the technical failures. This is especially important when using traditional measurements of diagnostic performance, such as sensitivity, specificity, and positive and negative predictive values. The approach that we followed in our study was, however, different. We used risk prediction modeling to assign a probability of the target condition for each value of the noninvasive predictor. The model (or its nomogram) can be used if the predictors are available and cannot be used if they are not. The performance statistics of the model only apply to the group of patients in which the model can be applied. Our approach therefore overcomes the question of how to factor technical failures on diagnostic accuracy parameters. The only value reported in our study that could be impacted by the rate of technical failures would be the percentage of endoscopies that would be avoided by a certain noninvasive test. Because our study was a blend of prospective and retrospective data, we cannot provide an exact applicability figure for our models. In a theoretical worst-case scenario of 20% unreliable results/technical failures of LSM by TE, the number of endoscopies saved would decrease from 30% to 24%.

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Section: To the Editorsupporting

confidence: 76%

Section: To the Editormentioning

confidence: 99%

MR lymphography of hepatic lymphatic system

Arrivé

Mouhadi

2017

Hepatology

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“…The role of lymphatic vessels in the liver is largely unknown. However, an increase in lymphatic vessels has been reported in liver fibrosis, idiopathic portal hypertension, and hepatocellular carcinoma (HCC), suggesting their involvement in these pathological conditions [129][130][131].…”

Section: Lymphatic Vascular Systemmentioning

confidence: 99%

Biology of portal hypertension

McConnell

Iwakiri

2017

Hepatol Int

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Portal hypertension develops as a result of increased intrahepatic vascular resistance often caused by chronic liver disease that leads to structural distortion by fibrosis, microvascular thrombosis, dysfunction of liver sinusoidal endothelial cells (LSECs), and hepatic stellate cell (HSC) activation. While the basic mechanisms of LSEC and HSC dysregulation have been extensively studied, the role of microvascular thrombosis and platelet function in the pathogenesis of portal hypertension remains to be clearly characterized. As a secondary event, portal hypertension results in splanchnic and systemic arterial vasodilation, leading to the development of a hyperdynamic circulatory syndrome and subsequently to clinically devastating complications including gastroesophageal varices and variceal hemorrhage, hepatic encephalopathy from the formation of portosystemic shunts, ascites, and renal failure due to the hepatorenal syndrome. This review article discusses: (1) mechanisms of sinusoidal portal hypertension, focusing on HSC and LSEC biology, pathological angiogenesis, and the role of microvascular thrombosis and platelets, (2) the mesenteric vasculature in portal hypertension, and (3) future directions for vascular biology research in portal hypertension.

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“…As such, the lymphatic vascular system in the liver is a large open area for investigation 160 , which will significantly advance our understanding of liver physiology and pathophysiology and in turn contribute to the development of new therapeutic strategies for many liver diseases.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and Lymphangiogenesis

Tanaka

Iwakiri

2016

Cellular and Molecular Gastroenterology and Hepatology

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102

119

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The lymphatic vascular system has been minimally explored in the liver despite its essential functions including maintenance of tissue fluid homeostasis. The discovery of specific markers for lymphatic endothelial cells has advanced the study of lymphatics by methods including imaging, cell isolation, and transgenic animal models and has resulted in rapid progress in lymphatic vascular research during the last decade. These studies have yielded concrete evidence that lymphatic vessel dysfunction plays an important role in the pathogenesis of many diseases. This article reviews the current knowledge of the structure, function, and markers of the hepatic lymphatic vascular system as well as factors associated with hepatic lymphangiogenesis and compares liver lymphatics with those in other tissues.

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The lymphatic system: A new frontier in hepatology

Cited by 22 publications

References 10 publications

MR lymphography of hepatic lymphatic system

MR lymphography of hepatic lymphatic system

Biology of portal hypertension

The Hepatic Lymphatic Vascular System: Structure, Function, Markers, and Lymphangiogenesis

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