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Portal Hypertension in NASH: Is It Different from Other Aetiologies?

  • Portal Hypertension (J Gonzalez-Abraldes and E Tsochatzis, Section Editors)
  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

In non-alcoholic fatty liver disease (NAFLD), an increased portal pressure is observed before signs of cirrhosis or even inflammation or fibrosis are histologically present. This review describes the differences between the mechanisms of cirrhotic portal hypertension (PHT) and PHT in non-cirrhotic NAFLD.

Recent Findings

The increased portal pressure in NAFLD is primarily a result of an increased intrahepatic vascular resistance. Vasodilation is decreased by endothelial dysfunction and the sensitivity to vasoconstrictors is increased. Furthermore, the activation of hepatic stellate cells and the presence of microvascular thrombosis could also be involved in the pathogenesis of PHT in NAFLD.

Summary

Although the increased portal pressure in early NAFLD is not considered clinically significant PHT, it might play a role in the pathophysiology of NAFLD. Due to the increased intrahepatic vascular resistance, the hepatic blood flow is impaired and hence the oxygen delivery is decreased, potentially triggering transition to steatohepatitis. The underlying mechanisms of these alterations therefore represent promising targets for pharmacological treatment.

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Abbreviations

ACh:

Acetylcholine

CBDL:

Common bile duct ligation

COX:

Cyclooxygenase

eNOS:

Endothelial nitric oxide synthase

ET:

Endothelin

HABR:

Hepatic arterial buffer response

HSC:

Hepatic stellate cell

HVPG:

Hepatic venous pressure gradient

HFD:

High-fat diet

H2S:

Hydrogen sulphide

HIF:

Hypoxia-inducible factor

IHVR:

Intrahepatic vascular resistance

LT:

Leukotriene

MCD:

Methionine-choline-deficient diet

NO:

Nitric oxide

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

OSA:

Obstructive sleep apnoea

PGF:

Placental growth factor

PHT:

Portal hypertension

PGI2:

Prostacyclin

ROS:

Reactive oxygen species

TX:

Thromboxane

TXAS:

Thromboxane synthase

TNF-α:

Tumour necrosis factor α

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Laboratory of Experimental Medicine and Paediatrics (LEMP), University of Antwerp, Wilrijk, Antwerp, Belgium

    Sven M. Francque, W. J. Kwanten & D. van der Graaff

  2. Department of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, B-2650, Edegem, Belgium

    Sven M. Francque, W. J. Kwanten & D. van der Graaff

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Denise van der Graaff and Wilhelmus Kwanten each declare no potential conflicts of interest.

Sven Francque received funding from the Fund for Scientific Research (FWO) Flanders (1802154N). The funder had no role in preparation of the manuscript.

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Francque, S.M., Kwanten, W.J. & van der Graaff, D. Portal Hypertension in NASH: Is It Different from Other Aetiologies?. Curr Hepatology Rep 18, 134–143 (2019). https://doi.org/10.1007/s11901-019-00459-z

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