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

ABSTRACT: 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.

SUBMITTER: Boyer-Diaz Z

PROVIDER: S-EPMC6835927 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Boyer-Diaz Zoe Z Domingo Joan Carles JC De Gregorio Estefanía E Manicardi Nicolò N Aristu-Zabalza Peio P Cordobilla Begoña B Abad-Jordà Laia L Ortega-Ribera Martí M Fernández-Iglesias Anabel A Marí Montserrat M Bosch Jaime J Gracia-Sancho Jordi J

Nutrients 20191003 10

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) phenoty ...[more]

PMID: 31623374

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Project description:BackgroundLiver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) is influenced by liver fibrosis and hepatic perfusion pressure. VCTE-based controlled attenuation parameter (CAP) is a noninvasive marker for hepatic steatosis (HS).AimsTo investigate the diagnostic performance of CAP in patients with advanced chronic liver disease (ACLD)/portal hypertension (PHT: hepatic venous pressure gradient (HVPG) ≥ 6 mmHg).MethodsEighty-eight patients with LS ≥ 10 kPa and/or HVPG ≥ 6 mmHg who underwent simultaneous liver biopsy, CAP, and HVPG measurement were included. HS was histologically graded according to the modified Brunt classification.ResultsPatient characteristics: Mean MELD:11 (standard derivation [SD] ± 4), median HVPG:16 (interquartile range [IQR]10-19) mmHg, median LS:27.4 (IQR 16.2-48.9) kPa, and mean CAP:221 (SD ± 75) dB/m. According to histology, 47 (53.4%) patients had no HS (S0), 28 (31.8%) had S1, 11 (12.5%) had S2, and 2 (2.3%) had S3. The area under the receiver operating characteristic curve (AUROC) of CAP for diagnosing any HS (S0 vs. ≥ S1) was 0.692 (95% confidence interval [95% CI] 0.582-0.802) in the overall cohort, 0.830 (95% CI 0.637-1.0) in patients with HVPG < 10 mmHg, and 0.629 (95% CI 0.497-0.761) in patients with clinically significant portal hypertension (CSPH; HVPG ≥ 10 mmHg; n = 69). Using the established cutoff for any HS (248 dB/m), the sensitivity/specificity of CAP was only 48.8%/76.6%, respectively. In contrast, the AUROC and sensitivity/specificity (cutoff 268 dB/m) for diagnosing HS ≥ S2 were 0.842 (95% CI 0.747-0.936) and 84.6%/81.3%, respectively. CAP correlated with the percentage of steatotic hepatocytes (Spearman's ρ = 0.402; p ≤ 0.001) and showed a weak correlation with liver stiffness (ρ = 0.225; p = 0.035).ConclusionsThe diagnostic performance of CAP for any HS seems to be limited in patients with ACLD, if CSPH is present.

Dataset Information

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

Publications

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

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