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Novelties in the pathophysiology and management of portal hypertension: new treatments on the horizon

  • Special Issue - Portal Hypertension
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Portal hypertension (PH) is responsible for the most severe complications of cirrhosis and leading cause of death and liver transplantation. The standard pharmacological treatment available for PH currently consists of the use of a non-selective beta-blocker. However, a significant proportion of patients do not respond to pharmacological treatment. This has led to the development of identifiable targets for the discovery of new horizons in PH treatment. Recently, there has been significant progress in understanding the mechanism behind PH, which is a product of increased hepatic vascular resistance including structural changes and functional change due to endothelial dysfunction. Moreover, increased portal inflow is the outcome of dilation of splanchnic vessels and hyperdynamic circulation. Here, challenges in formulating potential pharmacological treatment as well as current potential targets for PH will be reviewed. During the past decades, there have been many efforts to explore new techniques to stimulate liver regeneration in addition to pharmacological treatment. The bone marrow (BM) stem cells which differentiate into mature hepatocytes are thought to contribute to liver regeneration and have been found to demonstrate great potential as regenerative medicine in different therapeutic applications. Based on these insights, we explore the current and potential novel therapeutic uses of BM stem cell therapy in PH.

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Abbreviations

ARB:

Angiotensin-II receptor blockade

BH4:

Tetrahydrobiopterin

BM:

Bone marrow

BM-MSC:

Bone marrow-derived mesenchymal stem/stromal cells

COX:

Cyclooxygenase

eNOS:

Endothelial NO synthase

FXR:

Farnesoid X receptor

HCC:

Hepatocellular carcinoma

HSC:

Hematopoietic stem cells

HStCs:

Hepatic stellate cells

HVR:

Hepatic vascular resistance

HVPG:

Hepatic venous pressure gradient

JAK2:

Janus-kinase-2

LOXL2:

Lysyloxidase-like-2

MSC:

Mesenchymal stem/stromal cells

NO:

Nitric oxide

NSBB:

Non-selective beta-blocker

OCA:

Obeticholic acid

PDE-5:

Phosphodiesterase-5

PDGF:

Platelet-derived growth factor

PH:

Portal hypertension

RAAS:

Renin–angiotensin–aldosterone system

RCT:

Randomized control trial

rMnSOD:

Recombinant human manganese superoxide dismutase

SOD:

Superoxide dismutase

TGF:

Transforming growth factor receptor

TXA2:

Thromboxane A2

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea

    Seong Hee Kang, Moon Young Kim & Soon Koo Baik

  2. Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea

    Moon Young Kim & Soon Koo Baik

  3. Institute of Evidence Based Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea

    Soon Koo Baik

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  1. Seong Hee Kang
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Soon Koo Baik has received research grants of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and the Ministry of Health & Welfare, Republic of Korea (HI15C2364). Moon Young Kim declares that he has no conflict of interest. Seong Hee Kang declares that she has no conflict of interest.

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Kang, S.H., Kim, M.Y. & Baik, S.K. Novelties in the pathophysiology and management of portal hypertension: new treatments on the horizon. Hepatol Int 12 (Suppl 1), 112–121 (2018). https://doi.org/10.1007/s12072-017-9806-1

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