scholarly journals Liver Fibrosis and MAFLD: From Molecular Aspects to Novel Pharmacological Strategies

2021 ◽  
Vol 8 ◽  
Author(s):  
Weiyi Qu ◽  
Tengfei Ma ◽  
Jingjing Cai ◽  
Xiaojing Zhang ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Large Scale ◽  
Alcoholic Fatty Liver ◽  
Disease Definition ◽  
Significant Burden ◽  
Molecular Aspects ◽  
Druggable Targets

Metabolic-associated fatty liver disease (MAFLD) is a new disease definition, and this nomenclature MAFLD was proposed to renovate its former name, non-alcoholic fatty liver disease (NAFLD). MAFLD/NAFLD have shared and predominate causes from nutrition overload to persistent liver damage and eventually lead to the development of liver fibrosis and cirrhosis. Unfortunately, there is an absence of effective treatments to reverse MAFLD/NAFLD-associated fibrosis. Due to the significant burden of MAFLD/NAFLD and its complications, there are active investigations on the development of novel targets and pharmacotherapeutics for treating this disease. In this review, we cover recent discoveries in new targets and molecules for antifibrotic treatment, which target pathways intertwined with the fibrogenesis process, including lipid metabolism, inflammation, cell apoptosis, oxidative stress, and extracellular matrix formation. Although marked advances have been made in the development of antifibrotic therapeutics, none of the treatments have achieved the endpoints evaluated by liver biopsy or without significant side effects in a large-scale trial. In addition to the discovery of new druggable targets and pharmacotherapeutics, personalized medication, and combinatorial therapies targeting multiple profibrotic pathways could be promising in achieving successful antifibrotic interventions in patients with MAFLD/NAFLD.

scholarly journals Hepatic Unsaturated Fatty Acids Are Linked to Lower Degree of Fibrosis in Non-alcoholic Fatty Liver Disease

2022 ◽  
Vol 8 ◽  
Author(s):  
Michael Fridén ◽  
Fredrik Rosqvist ◽  
Håkan Ahlström ◽  
Heiko G. Niessen ◽  
Christian Schultheis ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Large Scale ◽  
Unsaturated Fatty Acids ◽  
Vaccenic Acid ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background: The hepatic lipidome of patients with early stages of non-alcoholic fatty liver disease (NAFLD) has been fairly well-explored. However, studies on more progressive forms of NAFLD, i.e., liver fibrosis, are limited.Materials and methods: Liver fatty acids were determined in cholesteryl esters (CE), phospholipids (PL), and triacylglycerols (TAG) by gas chromatography. Cross-sectional associations between fatty acids and biopsy-proven NAFLD fibrosis (n = 60) were assessed using multivariable logistic regression models. Stages of fibrosis were dichotomized into none-mild (F0–1) or significant fibrosis (F2–4). Models were adjusted for body-mass index (BMI), age and patatin-like phospholipase domain-containing protein 3 (PNPLA3 rs738409) (I148M) genotype. A secondary analysis examined whether associations from the primary analysis could be confirmed in the corresponding plasma lipid fractions.Results: PL behenic acid (22:0) was directly associated [OR (95% CI): 1.86 (1.00, 3.45)] whereas PL docosahexaenoic acid (22:6n-3) [OR (95% CI): 0.45 (0.23, 0.89)], TAG oleic acid (18:1n-9) [OR (95% CI): 0.52 (0.28, 0.95)] and 18:1n-9 and vaccenic acid (18:1n-7) (18:1) [OR (95% CI): 0.52 (0.28, 0.96)] were inversely associated with liver fibrosis. In plasma, TAG 18:1n-9 [OR (95% CI): 0.55 (0.31, 0.99)], TAG 18:1 [OR (95% CI): 0.54 (0.30, 0.97)] and PL 22:0 [OR (95% CI): 0.46 (0.25, 0.86)] were inversely associated with liver fibrosis.Conclusion: Higher TAG 18:1n-9 levels were linked to lower fibrosis in both liver and plasma, possibly reflecting an altered fatty acid metabolism. Whether PL 22:6n-3 has a protective role, together with a potentially adverse effect of hepatic 22:0, on liver fibrosis warrants large-scale studies.

Liver fibrosis: noninvasive assessment using supersonic shear imaging and FIB4 index in patients with non-alcoholic fatty liver disease

Choonpa Igaku ◽  
2020 ◽  
Vol 47 (6) ◽  
pp. 241-248
Author(s):  
Hirohito TAKEUCHI ◽  
Katsutoshi SUGIMOTO ◽  
Hisashi OSHIRO ◽  
Kunio IWATSUKA ◽  
Shin KONO ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Supersonic Shear Imaging ◽  
Noninvasive Assessment ◽  
Alcoholic Fatty Liver Disease

Early kidney dysfunction in non-alcoholic fatty liver disease - is transient elastography useful as a screening method?

2021 ◽  
Author(s):  
Marta Freitas ◽  
Vítor Macedo Silva ◽  
Sofia Xavier ◽  
Joana Magalhes ◽  
Carla Marinho ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Transient Elastography ◽  
Screening Method ◽  
Kidney Dysfunction ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Significant Liver Fibrosis

Introduction: Increasing evidence suggests an association between metabolic associated fatty liver disease (MAFLD) and chronic kidney disease (CKD). Timely prediction of early kidney dysfunction (EKD) is thus essential in this population, although a screening method is not stablished. We aimed to evaluate the role of transient elastography (TE) in predicting EKD in patients with MAFLD. Methods: Prospective cohort study that included patients with MAFLD scheduled for evaluation, between May/2019 and January/2020. Demographic, clinical and laboratory data, and TE parameters were obtained. EKD was defined as microalbuminuria (urinary albumin-to-creatinine ratio 30-300mg/g) and estimated glomerular filtration rate≥60mL/min/1.73m2. Significant liver fibrosis was defined as liver stiffness measurement (LSM)≥8.2kPa. Results: Included 45 patients with MALFD, 53.3% female gender, mean age of 53.5±10.9years. EKD was found in 17.8% of patients. MAFLD patients with EKD were significantly more obese (body mass index≥30) (75.0% vs 32.4%,p=0.045) and had significantly higher LSM (8.5±4.1 vs 5.8±2.2kPa,p=0.01). After adjustment of potential confounders for EKD the presence of liver fibrosis, remained a significant predictor of EKD, being associated with a 14.3-fold increased risk of EKD (p=0.04). The optimal cutoff value of LSM to predict EKD was 6.1kPa (sensitivity:85.7%; specificity:67.6%). Conclusion: Significant liver fibrosis is associated with a significant increased risk of EKD in patients with MAFLD, regardless of other comorbidities. Higher levels of LSM, particularly >6.1kPa, alert for timely identification of EKD and associated comorbidities, as well as their control, in order to prevent the development of CKD in the long term.

Epidemiological survey of hemoglobin A1c and liver fibrosis in a general population with non‐alcoholic fatty liver disease

2018 ◽  
Vol 49 (3) ◽  
pp. 296-303 ◽  
Author(s):  
Kenichi Tanaka ◽  
Hirokazu Takahashi ◽  
Hideyuki Hyogo ◽  
Masafumi Ono ◽  
Noriko Oza ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
General Population ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Hemoglobin A1c ◽  
Epidemiological Survey ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

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

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.

scholarly journals Impact of Long-Term Supplementation with Fish Oil in Individuals with Non-Alcoholic Fatty Liver Disease: A Double Blind Randomized Placebo Controlled Clinical Trial

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3372
Author(s):  
Kátia Cansanção ◽  
Marta Citelli ◽  
Nathalie Carvalho Leite ◽  
María-Carmen López de las Hazas ◽  
Alberto Dávalos ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fish Oil ◽  
Fatty Liver Disease ◽  
Double Blind ◽  
Alcoholic Fatty Liver ◽  
Pufa Supplementation ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease affecting up to 25% of the population worldwide. n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) have been associated with improved clinical parameters of NAFLD. Our purpose was to conduct a pilot study to evaluate the effects of n-3 PUFA supplementation in a randomized, double-blind, placebo-controlled clinical study performed on NAFLD individuals diagnosed by ultrasound. Patients received n-3 PUFA (n = 13) or placebo (n = 11) supplementation for six months. Circulating miR-122 expression (determined by quantitative real time-polymerase chain reaction (qRT-PCR), liver fibrosis (FibroScan®), red blood cells (RBC) fatty acids (gas chromatography), and biochemical tests were performed at baseline and after intervention. After the intervention, in the n-3 PUFA group, docosahexaenoic acid (DHA) and omega index increased significantly in RBC (p = 0.022 and p = 0.012, respectively), in addition to a significant reduction in alkaline phosphatase (ALP) (p = 0.002) and liver fibrosis (p = 0.039). However, there was no change in the expression of circulating miR-122 in both groups. Our results showed that omega-3 PUFA were incorporated in erythrocytes after six months of fish oil supplementary intake, and that n-3 PUFA were effective in reducing ALP and liver fibrosis without altering the expression of circulating miR-122 in individuals with NAFLD.

scholarly journals Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats

2020 ◽  
Vol 21 (9) ◽  
pp. 3308 ◽  
Author(s):  
Carla Cremonese ◽  
Robert Schierwagen ◽  
Frank Erhard Uschner ◽  
Sandra Torres ◽  
Olaf Tyc ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Western Diet ◽  
Suitable Model ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially, the development of fibrosis and portal hypertension in NAFLD patients requires treatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-β1 (TGF-β1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1β (IL1β) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. As expected, WD induced obesity and liver fibrosis as confirmed by Sirius Red and Oil Red O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increased during feeding of WD, indicating infiltration of macrophages into the liver, even though this increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin–angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity.

scholarly journals Network Modeling Approaches and Applications to Unravelling Non-Alcoholic Fatty Liver Disease

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 966 ◽  
Author(s):  
Blencowe ◽  
Karunanayake ◽  
Wier ◽  
Hsu ◽  
Yang
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Diagnostic Biomarkers ◽  
Pathogenic Genes ◽  
Novel Biomarkers ◽  
Network Approaches ◽  
Druggable Targets ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a progressive condition of the liver encompassing a range of pathologies including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Research into this disease is imperative due to its rapid growth in prevalence, economic burden, and current lack of FDA approved therapies. NAFLD involves a highly complex etiology that calls for multi-tissue multi-omics network approaches to uncover the pathogenic genes and processes, diagnostic biomarkers, and potential therapeutic strategies. In this review, we first present a basic overview of disease pathogenesis, risk factors, and remaining knowledge gaps, followed by discussions of the need and concepts of multi-tissue multi-omics approaches, various network methodologies and application examples in NAFLD research. We highlight the findings that have been uncovered thus far including novel biomarkers, genes, and biological pathways involved in different stages of NAFLD, molecular connections between NAFLD and its comorbidities, mechanisms underpinning sex differences, and druggable targets. Lastly, we outline the future directions of implementing network approaches to further improve our understanding of NAFLD in order to guide diagnosis and therapeutics.

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