Endothelial Dysfunction as a Predictor of Portal Hypertension Syndrome at the Early Stages

T.V. Romaniuk, I.Ya. Dzyubanovsky


Worldwide we observe an increase of portal hypertension syndrome frequency. Hypertension within the portal system in case of cirrhosis and diffuse liver affection are the major risk factors of esophageal varices bleeding in approximately 90 % of patients with cirrhosis. This also makes bleedings the most common complication of portal hypertension.
The initiating factor of portal hypertension development is endothelial dysfunction — an imbalance of vasoconstrictors and vasodilators in portal system. At the initial stage of portal hypertension endothelin-1 plays the main role in vasoconstriction. Nitric oxide is a second important regulator of visceral blood flow. Nitric oxide is a potent vasodilator, an antagonist of endothelin-1.
However today dynamics of endocrine regulators plasma concentration and their role in the development of portal hypertension syndrome is not studied enough.
Purpose. Investigation of endothelin-1 and nitric oxide concentrations at different stages of portal hypertension syndrome.
Material and Methods. Endothelial dysfunction is evaluated through the measuring of endothelin-1 and nitric oxide plasma concentration. The study was conducted in 3 groups of the patients: group I (n = 38) — patients with cirrhosis without clinical manifestations of portal hypertension, group II (n = 42) — patients with cirrhosis and symptomatic portal hypertension (esophageal varices and/or cardial varices, splenomegaly, ascites), group III (n = 34) — patients with complicated portal hypertension caused by liver cirrhosis (bleeding of esophageal varices and/or cardial varices, hypersplenism). The control group (n = 30) — physically healthy people of 23–37 years.
Results and Discussion. All patients of all groups showed a three-times increase of ET-1 in plasma. This fact indicates that the increase of endothelin-1 is the initiating element in the portal hypetension syndrome. The level of endothelin-1 in the second and third groups showed a further increase of its level. In the second group the increase was almost 476 %, and in the third group — 635 %. Further increase in endothelin-1 plays an important role in the portal hypertension development and in the occurrence of its complications, such as: esophageal varices bleeding, bleeding of the secondary haemorrhoids, etc.
In patients of all groups level of nitric oxide metabolites was within the physiological norm. However, in the II group the level of nitric oxide metabolites was increased: nitrite anion 255.74 %, nitrate anion 341.41 % and their total level — 300.62 %. In the third group we observed that the level of nitrite anion increased in 472.01 %, nitrate anion — 679.96 %, and their overall level — 591.70 %. This means, that progressive increase of nitric oxide metabolites in plasma due to excessive endothelial nitroxid-production function causes decompensation of portal blood flow and the appearance of complications.
Conclusions. All patients with chronic diffuse liver disease have elevated levels of endothelin-1, which makes them a risk category of portal hypertension syndrome. Alternatively, these patients already have indirectly confirmed portal hypertension that is not clinically evident. Thus, measurement of endothelin-1 can serve as a reliable diagnostic criterion for early diagnosis of portal hypertension syndrome during the preclinical stage.
A particular pathognomonic point of portal hypertension pathophysiological mechanism is the endothelial nitroxid-production hyperproduction that begins the «vice circle» of portal hypertension and development of hyperdynamic circulatory status. The increase of nitric oxide metabolites is the clinical criterion of these disorders and obligate predictor of portal hypertension complications.


portal hypertension syndrome; endothelial dysfunction; diagnostic criteria


Гарбузенко Д.В. Кровотечения из варикозно расширенных вен пищевода и желудка у больных циррозом печени: патогенез, профилактика, лечение. — Челябинск : Издательский дом «Восточные Ворота», 2004. — 63 c.

Гарбузенко Д.В. Патофизиологические механизмы и новые направления терапии портальной гипертензии при циррозе печени / Д.В. Гарбузенко // Клинические перспективы гастроэнтерологии, гепатологии. — 2010. — № 6. — С. 11-20.

Кошевой А.П. Комбинированные операции при варикозном расширении вен пищевода и желудка / А.П. Кошевой, Д.Н. Чирков, O.A. Шелко // Актуальные проблемы хирургической гепатологии : XVII международный конгресс 13–14 мая 2010 г. : тезисы докл. — Уфа, 2010. — С. 75-76.

Colle I. Splanchnic hemodynamic changes in portal hypertension / I. Colle, A.M. Geerts, C. van Steenkiste // Anat. Rec. — 2008. — Vol. 291, № 6. — P. 699-713.

Iacob S. MELD exceptions and new predictive score of death on long waiting lists for liver transplantation / S. Iacob, L. Gheorghe, R. Iacob // Chirurgia (Bucur). — 2009. — Vol. 104, № 3. — P. 267-273.

Kinoshita K. Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats / K. Kinoshita, Y. Iimuro, K. Otogawa et al. // Gut. — 2007. — Vol. 56, № 5. — P. 706-714.

Stauber R. E. Evaluation of indocyanine green clearance and model for end-stage liver disease for estimation of short-term prognosis in decompensated cirrhosis / R.E. Stauber et al. // Liver Int. — 2009. — Vol. 29, № 10. — P. 1516-1520.

Triantos C.K., Burroughs A.K. Prevention of the development of varices and first portal hypertensive bleeding episode / C.K. Triantos, A.K. Burroughs // Best. Pract. Res. Clin. Gastroenterol. — 2007. — № 21. — Р. 31-42.

Van Landeghem L. Carbon monoxide produced by intrasinusoidally located haem-oxygenase-1 regulates the vascular tone in cirrhotic rat liver / L. Van Landeghem, W. Laleman, I. van der Elst // Liver Int. — 2009. — Vol. 29, № 5. — P. 650-660.

DOI: https://doi.org/10.22141/1997-2938.2.21.2013.87500


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