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Review
. 2015 Apr;62(1 Suppl):S121-30.
doi: 10.1016/j.jhep.2015.01.003.

Evolution in the understanding of the pathophysiological basis of portal hypertension: How changes in paradigm are leading to successful new treatments

Jaume Bosch  1 , Roberto J Groszmann  2 , Vijay H Shah  3
Affiliations
Review

Evolution in the understanding of the pathophysiological basis of portal hypertension: How changes in paradigm are leading to successful new treatments

Jaume Bosch et al. J Hepatol. 2015 Apr.

Abstract

Among the common complication of cirrhosis portal hypertension witnessed a major improvement of prognosis during the past decades. Principally due to the introduction of rational treatments based on new pathophysiological paradigms (concepts of thought) developed in the 1980s. The best example being the use of non-selective beta-blockers and of vasopressin analogs, somatostatin, and its analogs. Further refinement in the knowledge of the molecular mechanisms involved in the regulation of both the splanchnic and hepatic circulation has led to the emergence of new treatments, which are based on evidence that show not only structural but also vasoactive components increase the hepatic vascular resistance, as well as of angiogenesis. This knowledge and future improvements will most likely result in more effective treatment of portal hypertension and effective prevention of its complications in early stages.

Keywords: Endothelial dysfunction; Hepatic stellate cells; Hyperdynamic syndrome; Liver sinusoidal endothelial cells; Portal pressure; Splanchnic vasodilation.

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Figures

Fig. 1
Fig. 1. Schematic representation of the historical evolution of the understanding of portal hypertension (PH) and how changes in paradigms have led to the introduction of successful new therapies
The figure also shows new therapies under evaluation.
Fig. 2
Fig. 2. Newer molecular paradigms in the sinusoids in cirrhosis
Boxed area is a higher magnification cartoon depiction of potential molecular events within the sinusoids during cirrhosis. The cartoon shows crosstalk between sinusoidal endothelial cells (SEC), macrophage (M), and hepatic stellate cells (HSC). Selected signal pathways under active investigation are depicted including innate immunity through toll like receptors (TLR), traditional inflammatory molecules, angiocrine signals, and matrix such as fibronectin. Potential effects of thrombus are also shown.
See this image and copyright information in PMC

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