Oxidative Stress in Chronic Liver Disease and Portal Hypertension: Potential of DHA as Nutraceutical

Chronic liver disease constitutes a growing public health issue worldwide, with no safe and effective enough treatment clinical scenarios. The present review provides an overview of the current knowledge regarding advanced chronic liver disease (ACLD), focusing on the major contributors of its pathophysiology: inflammation, oxidative stress, fibrosis and portal hypertension. We present the benefits of supplementation with docosahexaenoic acid triglycerides (TG-DHA) in other health areas as demonstrated experimentally, and explore its potential as a novel nutraceutical approach for the treatment of ACLD and portal hypertension based on published pre-clinical data.

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A Nutraceutical Rich in Docosahexaenoic Acid Improves Portal Hypertension in a Preclinical Model of Advanced Chronic Liver Disease

Nutrients ◽

10.3390/nu11102358 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2358 ◽

Cited By ~ 9

Author(s):

Boyer-Diaz ◽

Domingo ◽

de Gregorio ◽

Manicardi ◽

Aristu-Zabalza ◽

...

Keyword(s):

Oxidative Stress ◽

Portal Hypertension ◽

Liver Disease ◽

Docosahexaenoic Acid ◽

Chronic Liver Disease ◽

Stellate Cell ◽

Preclinical Study ◽

Chronic Liver ◽

Preclinical Model ◽

And Oxidative Stress

Inflammation and oxidative stress play a key role in the pathophysiology of advanced chronic liver disease (ACLD) and portal hypertension (PH). Considering the current lack of effective treatments, we evaluated an anti-inflammatory and antioxidant nutraceutical rich in docosahexaenoic acid (DHA) as a possible therapy for ACLD. We investigated the effects of two-week DHA supplementation (500 mg/kg) on hepatic fatty acids, PH, oxidative stress, inflammation, and hepatic stellate cell (HSC) phenotype in rats with ACLD. Additionally, the effects of DHA were evaluated in murine macrophages and human HSC. In contrast to vehicle-treated animals, cirrhotic rats receiving DHA reestablished a healthy hepatic fatty acid profile, which was associated with an improvement in PH. The mechanisms underlying this hemodynamic improvement included a reduction in oxidative stress and inflammation, as well as a marked HSC deactivation, confirmed in human HSC. Experiments with cultured macrophages showed that treatment with DHA protects against pro-inflammatory insults. The present preclinical study demonstrates that a nutraceutical rich in DHA significantly improves PH in chronic liver disease mainly by suppressing inflammation and oxidative stress-driven HSC activation, encouraging its evaluation as a new treatment for PH and cirrhosis.

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FRI-110-A nutraceutical supplement rich in docosahexaenoic acid improves portal hypertension in a pre-clinical model of chronic liver disease

Journal of Hepatology ◽

10.1016/s0618-8278(19)30855-2 ◽

2019 ◽

Vol 70 (1) ◽

pp. e435-e436

Author(s):

Zoe Boyer-Diaz ◽

Nicolo Manicardi ◽

Peio Aristu ◽

Laia Abad ◽

Begoña Cordobilla ◽

...

Keyword(s):

Portal Hypertension ◽

Liver Disease ◽

Docosahexaenoic Acid ◽

Chronic Liver Disease ◽

Chronic Liver ◽

Clinical Model

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Limited diagnostic performance of controlled attenuation parameter for assessing hepatic steatosis in patients with advanced chronic liver disease and portal hypertension

10.1055/s-0038-1654646 ◽

2018 ◽

Author(s):

G Semmler ◽

J Stift ◽

B Scheiner ◽

R Paternostro ◽

P Schwabl ◽

...

Keyword(s):

Portal Hypertension ◽

Liver Disease ◽

Chronic Liver Disease ◽

Hepatic Steatosis ◽

Diagnostic Performance ◽

Chronic Liver ◽

Controlled Attenuation Parameter ◽

Attenuation Parameter

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Results of liver and spleen endoscopic ultrasonographic elastography predict portal hypertension secondary to chronic liver disease

Endoscopy International Open ◽

10.1055/a-1233-1934 ◽

2020 ◽

Vol 08 (11) ◽

pp. E1623-E1632

Author(s):

Carlos Robles-Medranda ◽

Roberto Oleas ◽

Miguel Puga-Tejada ◽

Manuel Valero ◽

Raquel Del Valle ◽

...

Keyword(s):

Liver Cirrhosis ◽

Portal Hypertension ◽

Liver Disease ◽

Chronic Liver Disease ◽

Predictive Value ◽

Strain Ratio ◽

Chronic Liver ◽

Spleen Stiffness ◽

Eus Elastography ◽

Sensitivity Specificity

Abstract Background and study aims Assessment of endoscopic ultrasonography (EUS)-elastography of the liver and spleen may identify patients with portal hypertension secondary to chronic liver disease. We aimed to evaluate use of EUS-elastography of the liver and spleen in identification of portal hypertension in patients with chronic liver disease. Patients and methods This was a single-center, diagnostic cohort study. Consecutive patients with liver cirrhosis and portal hypertension underwent EUS-elastography of the liver and spleen. Patients without a history of liver disease were enrolled as controls. The primary outcome was diagnostic yield of liver and spleen stiffness measurement via EUS-elastography in prediction of portal hypertension secondary to chronic liver cirrhosis. Cutoff values were defined through Youden’s index. Overall accuracy was calculated for parameters with an area under the receiver operating characteristic (AUROC) curve ≥ 80 %. Results Among the 61 patients included, 32 had cirrhosis of the liver. Liver and spleen stiffness was measured by the strain ratio and strain histogram, with sensitivity/(1 − specificity) AUROC values ≥ 80 %. For identification of patients with cirrhosis and portal hypertension, the liver strain ratio (SR) had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 84.3 %, 82.8 %, 84.4 %, and 82.8 %, respectively; the liver strain histogram (SH) had values of 87.5 %, 69.0 %, 75.7 %, and 83.3 %, respectively. EUS elastography of the spleen via the SR reached a sensitivity, specificity, PPV, and NPV of 87.5 %, 69.0 %, 75.7 %, and 83.3 %, respectively, whereas the values of SH were 56.3 %, 89.7 %, 85.7 %, and 65.0 %, respectively. Conclusion Endoscopic ultrasonographic elastography of the liver and spleen is useful for diagnosis of portal hypertension in patients with cirrhosis.

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Relationship between Tetrahydrobiopterin and Portal Hypertension in Patients with Chronic Liver Disease

Journal of Korean Medical Science ◽

10.3346/jkms.2014.29.3.392 ◽

2014 ◽

Vol 29 (3) ◽

pp. 392 ◽

Cited By ~ 6

Author(s):

Won Ki Hong ◽

Kwang Yong Shim ◽

Soon Koo Baik ◽

Moon Young Kim ◽

Mee Yon Cho ◽

...

Keyword(s):

Portal Hypertension ◽

Liver Disease ◽

Chronic Liver Disease ◽

Chronic Liver

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Use of noninvasive markers of portal hypertension and timing of screening endoscopy for gastroesophageal varices in patients with chronic liver disease

Hepatology ◽

10.1002/hep.26652 ◽

2013 ◽

Vol 59 (2) ◽

pp. 729-731 ◽

Cited By ~ 19

Author(s):

Annalisa Berzigotti ◽

Jaime Bosch ◽

Thomas D. Boyer

Keyword(s):

Portal Hypertension ◽

Liver Disease ◽

Chronic Liver Disease ◽

Chronic Liver ◽

Gastroesophageal Varices ◽

Screening Endoscopy ◽

Noninvasive Markers

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Identifying Compensated Advanced Chronic Liver Disease: When (Not) to Start Screening for Varices and Clinically Significant Portal Hypertension

Portal Hypertension VI ◽

10.1007/978-3-319-23018-4_5 ◽

2016 ◽

pp. 39-49 ◽

Cited By ~ 7

Author(s):

Salvador Augustin ◽

Mónica Pons ◽

Begoña Santos ◽

Meritxell Ventura ◽

Joan Genescà

Keyword(s):

Portal Hypertension ◽

Liver Disease ◽

Chronic Liver Disease ◽

Chronic Liver ◽

Clinically Significant

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Portal Angiogenesis in Chronic Liver Disease Patients Correlates with Portal Pressure and Collateral Formation

Digestive Diseases ◽

10.1159/000500115 ◽

2019 ◽

Vol 37 (6) ◽

pp. 498-508 ◽

Cited By ~ 1

Author(s):

Carolina A. Serrano ◽

Simon C. Ling ◽

Sofia Verdaguer ◽

Miguel León ◽

Nicolás Jarufe ◽

...

Keyword(s):

Liver Transplantation ◽

Portal Hypertension ◽

Liver Disease ◽

Chronic Liver Disease ◽

Venous Pressure ◽

Portal Pressure ◽

Peripheral Circulation ◽

Chronic Liver ◽

Noninvasive Markers ◽

Collateral Formation

Background/Aims: One hallmark of chronic liver disease in patients with portal hypertension is the formation of portal-systemic collaterals in which angiogenesis has a fundamental role. We studied patients with chronic liver disease undergoing liver transplantation to correlate levels of circulating angiogenic factors in portal and peripheral circulation with portal pressure and portal-systemic collaterals. Methods: Sixteen patients who underwent liver transplantation were enrolled. During transplant surgery, we determined portal venous pressure and portal-systemic collateral formation. We determined angiogenics mediator levels in systemic and portal plasma. Peripheral plasma from healthy donors was measured as controls. Results: Vascular endothelial growth factor (VEGF)-R1 and 2, Ang-1 and 2, Tie2, FGF- 1 and 2, CD163, PDGFR-β, PDGFsRα, PDGF-AB and BB, CD163, TGF-β VASH-1 levels were significantly different in the controls in comparison to cases. Significantly decreased portal venous levels of Ang-1, FGF-1, PDGF-AB/BB, and CC were observed in patients with higher portal pressure. Peripheral VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation. While peripheral VEGF-R1 was higher in patients with severe collateral formation. For portal circulation, VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation Conclusions: Angiogenesis factors correlated with portal pressure and collateral formation and different patterns of circulating angiogenesis mediators were found in peripheral and portal blood of patients with chronic liver disease. These results support the importance of angiogenic pathways in cirrhosis and portal hypertension and highlight areas for further study to identify clinically useful noninvasive markers of portal pressure and collateral formation.

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Liver Stiffness Assessed by Ultrasound Shear Wave Elastography from General Electric Accurately Predicts Clinically Significant Portal Hypertension in Patients with Advanced Chronic Liver Disease

Ultraschall in der Medizin - European Journal of Ultrasound ◽

10.1055/a-0965-0745 ◽

2019 ◽

Vol 41 (05) ◽

pp. 526-533

Author(s):

Horia Stefanescu ◽

Corina Rusu ◽

Monica Lupsor-Platon ◽

Oana Nicoara Farcau ◽

Petra Fischer ◽

...

Keyword(s):

Portal Hypertension ◽

Liver Disease ◽

Diagnostic Accuracy ◽

Chronic Liver Disease ◽

Shear Wave ◽

Liver Stiffness ◽

Shear Wave Elastography ◽

Chronic Liver ◽

General Electric ◽

Clinically Significant

Abstract Purpose Clinically significant portal hypertension (CSPH) is responsible for most of the complications in patients with cirrhosis. Liver stiffness (LS) measurement by vibration-controlled transient elastography (VCTE) is currently used to evaluate CSPH. Bi-dimensional shear wave elastography from General Electric (2D-SWE.GE) has not yet been validated for the diagnosis of PHT. Our aims were to test whether 2D-SWE.GE-LS is able to evaluate CSPH, to determine the reliability criteria of the method and to compare its accuracy with that of VCTE-LS in this clinical setting. Materials and Methods Patients with chronic liver disease referred to hepatic catheterization (HVPG) were consecutively enrolled. HVPG and LS by both VCTE and 2D-SWE.GE were performed on the same day. The diagnostic performance of each LS method was compared against HVPG and between each other. Results 2D-SWE.GE-LS was possible in 123/127 (96.90 %) patients. The ability to record at least 5 LS measurements by 2D-SWE.GE and IQR < 30 % were the only features associated with reliable results. 2D-SWE.GE-LS was highly correlated with HVPG (r = 0.704; p < 0.0001), especially if HVPG < 10 mmHg and was significantly higher in patients with CSPH (15.52 vs. 8.14 kPa; p < 0.0001). For a cut-off value of 11.3 kPa, the AUROC of 2D-SWE.GE-LS to detect CSPH was 0.91, which was not inferior to VCTE-LS (0.92; p = 0.79). The diagnostic accuracy of LS by 2D-SWE.GE-LS to detect CSPH was similar with the one of VCTE-LS (83.74 % vs. 85.37 %; p = 0.238). The diagnostic accuracy was not enhanced by using different cut-off values which enhanced the sensitivity or the specificity. However, in the subgroup of compensated patients with alcoholic liver disease, 2D-SWE.GE-LS classified CSPH better than VCTE-LS (93.33 % vs. 85.71 %, p = 0.039). Conclusion 2D-SWE.GE-LS has good accuracy, not inferior to VCTE-LS, for the diagnosis of CSPH.

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