The impact of non-alcoholic fatty liver disease fibrosis score on cardiac prognosis in patients with chronic heart failure

Non-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level (F0F1 vs. F3F4). A non-targeted metabolomics strategy was applied. We analyzed 52 pairs of human HCC and adjacent non-tumoral tissues which included 26 HCC developed in severe fibrosis or cirrhosis (F3F4) and 26 in no or mild fibrosis (F0F1). Tissue extracts were analyzed using 1H-Nuclear Magnetic Resonance spectroscopy. An optimization evolutionary method based on genetic algorithm was used to identify discriminant metabolites. We identified 34 metabolites differentiating the two groups of NAFLD-HCC according to fibrosis level, allowing us to propose two metabolomics phenotypes of NAFLD-HCC. We showed that HCC-F0F1 mainly overexpressed choline derivatives and glutamine, whereas HCC-F3F4 were characterized by a decreased content of monounsaturated fatty acids (FA), an increase of saturated FA and an accumulation of branched amino acids. Comparing HCC-F0F1 and HCC-F3F4, differential expression levels of glucose, choline derivatives and phosphoethanolamine, monounsaturated FA, triacylglycerides were identified as specific signatures. Our metabolomics analysis of HCC tissues revealed for the first time two phenotypes of HCC developed in NAFLD according to fibrosis level. This study highlighted the impact of the underlying liver disease on metabolic reprogramming of the tumor.

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RIPK3 acts as a lipid metabolism regulator contributing to inflammation and carcinogenesis in non-alcoholic fatty liver disease

Gut ◽

10.1136/gutjnl-2020-321767 ◽

2020 ◽

pp. gutjnl-2020-321767

Author(s):

Marta B Afonso ◽

Pedro M Rodrigues ◽

Miguel Mateus-Pinheiro ◽

André L Simão ◽

Maria M Gaspar ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Body Weight Gain ◽

Control Diet ◽

Peroxisome Proliferator ◽

Functional Link ◽

Alcoholic Fatty Liver ◽

The Impact ◽

Alcoholic Fatty Liver Disease

ObjectiveReceptor-interacting protein kinase 3 (RIPK3) is a key player in necroptosis execution and an emerging metabolic regulator, whose contribution to non-alcoholic fatty liver disease (NAFLD) is controversial. We aimed to clarify the impact of RIPK3 signalling in the pathogenesis of human and experimental NAFLD.DesignRIPK3 levels were evaluated in two large independent cohorts of patients with biopsy proven NAFLD diagnosis and correlated with clinical and biochemical parameters. Wild-type (WT) or Ripk3-deficient (Ripk3−/−) mice were fed a choline-deficient L-amino acid-defined diet (CDAA) or an isocaloric control diet for 32 and 66 weeks.ResultsRIPK3 increased in patients with non-alcoholic steatohepatitis (NASH) in both cohorts, correlating with hepatic inflammation and fibrosis. Accordingly, Ripk3 deficiency ameliorated CDAA-induced inflammation and fibrosis in mice at both 32 and 66 weeks. WT mice on the CDAA diet for 66 weeks developed preneoplastic nodules and displayed increased hepatocellular proliferation, which were reduced in Ripk3−/− mice. Furthermore, Ripk3 deficiency hampered tumourigenesis. Intriguingly, Ripk3−/− mice displayed increased body weight gain, while lipidomics showed that deletion of Ripk3 shifted hepatic lipid profiles. Peroxisome proliferator-activated receptor γ (PPARγ) was increased in Ripk3−/− mice and negatively correlated with hepatic RIPK3 in patients with NAFLD. Mechanistic studies established a functional link between RIPK3 and PPARγ in controlling fat deposition and fibrosis.ConclusionHepatic RIPK3 correlates with NAFLD severity in humans and mice, playing a key role in managing liver metabolism, damage, inflammation, fibrosis and carcinogenesis. Targeting RIPK3 and its intricate signalling arises as a novel promising approach to treat NASH and arrest disease progression.

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The impact of non-alcoholic fatty liver disease and metabolic syndrome on the progression of coronary artery calcification

Scientific Reports ◽

10.1038/s41598-018-30465-y ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 6

Author(s):

Yun Kyung Cho ◽

Yu Mi Kang ◽

Jee Hee Yoo ◽

Jiwoo Lee ◽

Seung Eun Lee ◽

...

Keyword(s):

Metabolic Syndrome ◽

Liver Disease ◽

Coronary Artery ◽

Fatty Liver ◽

Coronary Artery Calcification ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

The Impact ◽

Alcoholic Fatty Liver Disease

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Correlation Between Point Shear Wave Elastography and Liver Function Tests as A Predictor of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

10.53350/pjmhs211571936 ◽

2021 ◽

Vol 15 (7) ◽

pp. 1936-1939

Author(s):

Shahla Mohammed Saeed Rasul ◽

Ali Khalaf Salim ◽

Hiwa Abubakr Hussein

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Liver Function ◽

Fatty Liver ◽

Shear Wave ◽

Fatty Liver Disease ◽

Liver Function Tests ◽

Fibrosis Score ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Background: Nowadays, generating shear waves and simulation of the liver tissue is done using point shear-wave elastographic (pSWE) techniques which uess acoustic radiation force impulse (ARFI). Objective: This study aimed to evaluate the correlation between pSWE and liver function tests (LFTs) to predict liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Materials and methods: It was a cross sectional study conducted in an Ultrasound Clinic in Suleymaniya city. The duration of the study was from 1st of November, 2018 to 30th of June, 2019 which conducted on 50 NAFLD patients. After confirming NAFLD diagnosis, the patients were referred to Ultrasound Clinic to go under pSWE test. Results: The data showed that the mean PSWE of NAFLD patient was 4.12±0.87 Kpa; and 18% of them had high PSWE (> 4.6). Elastography fibrosis score was distributed to F0 (82%), F1 (6%), F2 (8%) and F3 (4%). There was a significant association between high APRI and high Aspartate Aminotransferase/Alanine Aminotransferase(AST/ALT) ratio (p=0.04). There was also a highly significant association between elastography fibrosis score and APRI fibrosis score among NAFLD patients (p<0.001). Conclusion: This study showed that the pSWE is a valuable noninvasive diagnostic technique for predicting liver fibrosis among NAFLD patients and there is significant correlation between APRI and pSWE scores. Keywords: Non-alcoholic fatty liver disease, Point shears wave elastography, Liver fibrosis.

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Abstract 12917: Prognostic Value of the Combination of Model for End-stage Liver Disease Excluding Inr Score and Non-alcoholic Fatty Liver Disease Fibrosis Score in Patients Admitted for Acute Heart Failure

Circulation ◽

10.1161/circ.142.suppl_3.12917 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Masatsugu Kawahira ◽

Takahisa Yamada ◽

Tetsuya Watanabe ◽

Takashi Morita ◽

Yoshio Furukawa ◽

...

Keyword(s):

Heart Failure ◽

Liver Disease ◽

Liver Fibrosis ◽

Ejection Fraction ◽

Fatty Liver Disease ◽

Fibrosis Score ◽

Alcoholic Fatty Liver ◽

End Stage Liver Disease ◽

End Stage ◽

Alcoholic Fatty Liver Disease

Background: Cardiohepatic interactions have been a focus of attention in heart failure(HF), and the model for end-stage liver disease excluding INR (MELD-XI) has been shown to be useful for prediction of poor outcome in patients (pts) with acute decompensated heart failure (ADHF). Furthermore, it has been reported that liver stiffness predicts adverse prognosis in pts with HF. Liver fibrosis is assessed by non-invasive fibrosis markers such as Fibrosis-4 (FIB4) index, non-alcoholic fatty liver disease fibrosis score (NFS) and aminotransferase to platelet ratio index (APRI). Recently, a new group of HF pts with mid-range ejection fraction (HFmrEF) has been defined, separated from reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, there is little information available on the comparison of prognostic significance of MELD-XI and liver fibrosis scores in ADHF pts, relating to LVEF. Methods: We prospectively studied 466 consecutive ADHF pts (HFrEF (LVEF≦40%): n=164, HFmrEF (40<LVEF<50): n=104 and HFpEF (LVEF≧50%): n=198). At the discharge, we calculated MELD-XI, FIB4 index , NFS, and APRI. The endpoint was all cause death (ACD). Results: During a follow-up period of 2.8±1.5 years, 143 pts had ACD. At multivariate Cox analysis, MELD-XI and FIB4 index was independently associated with ACD irrespective of LVEF. The pts with both greater MELD-XI ([HFrEF]≥25.8, [HFmrEF]≥33.2, [HFpEF]≥30.1) and greater FIB4 index ([HFrEF]≥2.58, [HFmrEF]≥2.58, [HFpEF]≥2.22) had a significantly increased risk of ACD than those with either and none of them in all three groups. Conclusions: The combination of MELD-XI and FIB4 index might be useful for stratifying pts at risk for ACD in ADHF pts with irrespective of LVEF.

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