scholarly journals Alcoholic Liver Disease: Alcohol Metabolism, Cascade of Molecular Mechanisms, Cellular Targets, and Clinical Aspects

Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 106 ◽  
Author(s):  
Rolf Teschke
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Alcoholic Liver Disease ◽  
Molecular Mechanisms ◽  
Lipid Peroxides ◽  
Sirtuin 1 ◽  
Clinical Aspects ◽  
Alkoxyl Radical ◽  
Alcoholic Fatty Liver ◽  
Cyp 2E1

Alcoholic liver disease is the result of cascade events, which clinically first lead to alcoholic fatty liver, and then mostly via alcoholic steatohepatitis or alcoholic hepatitis potentially to cirrhosis and hepatocellular carcinoma. Pathogenetic events are linked to the metabolism of ethanol and acetaldehyde as its first oxidation product generated via hepatic alcohol dehydrogenase (ADH) and the microsomal ethanol-oxidizing system (MEOS), which depends on cytochrome P450 2E1 (CYP 2E1), and is inducible by chronic alcohol use. MEOS induction accelerates the metabolism of ethanol to acetaldehyde that facilitates organ injury including the liver, and it produces via CYP 2E1 many reactive oxygen species (ROS) such as ethoxy radical, hydroxyethyl radical, acetyl radical, singlet radical, superoxide radical, hydrogen peroxide, hydroxyl radical, alkoxyl radical, and peroxyl radical. These attack hepatocytes, Kupffer cells, stellate cells, and liver sinusoidal endothelial cells, and their signaling mediators such as interleukins, interferons, and growth factors, help to initiate liver injury including fibrosis and cirrhosis in susceptible individuals with specific risk factors. Through CYP 2E1-dependent ROS, more evidence is emerging that alcohol generates lipid peroxides and modifies the intestinal microbiome, thereby stimulating actions of endotoxins produced by intestinal bacteria; lipid peroxides and endotoxins are potential causes that are involved in alcoholic liver injury. Alcohol modifies SIRT1 (Sirtuin-1; derived from Silent mating type Information Regulation) and SIRT2, and most importantly, the innate and adapted immune systems, which may explain the individual differences of injury susceptibility. Metabolic pathways are also influenced by circadian rhythms, specific conditions known from living organisms including plants. Open for discussion is a 5-hit working hypothesis, attempting to define key elements involved in injury progression. In essence, although abundant biochemical mechanisms are proposed for the initiation and perpetuation of liver injury, patients with an alcohol problem benefit from permanent alcohol abstinence alone.

scholarly journals Streptococcus, the Predominant Bacterium to Predict the Severity of Liver Injury in Alcoholic Liver Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaodan Zhong ◽  
Ping Cui ◽  
Junjun Jiang ◽  
Chuanyi Ning ◽  
Bingyu Liang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Gut Microbiota ◽  
Alcoholic Liver Disease ◽  
Early Stage ◽  
Characteristic Curve ◽  
Hepatic Function ◽  
Rrna Gene ◽  
Alcoholic Fatty Liver ◽  
Predominant Bacterium

BackgroundNew evidence implies that the imbalance of gut microbiota is associated with the progression of alcoholic liver disease (ALD) and that the composition of gut microbiota is altered in ALD patients. However, the predominant bacterium in patients involved in the progress of ALD has not been identified. The purpose of this study is to investigate the predominant bacterium in the early and end-stages of ALD as well as the relationship between the bacterium and the degree of liver injury.MethodsWe enrolled 21 alcoholic fatty liver (AFL) patients, 17 alcoholic liver cirrhosis (ALC) patients and 27 healthy controls, and sequenced the 16S rRNA gene of their fecal microbiota. The gut microbiota composition and its relationship with the indicators of clinical hepatic function were assessed using canonical correspondence analysis (CCA), spearman correlation heatmap and multivariate association with linear (MaAsLin) Models.ResultsThe composition and structure of gut microbiota changed greatly in different stages of ALD, and the degree of disorder was aggravated with the progression of ALD, even in the early stage. Moreover, the relative abundance of Streptococcus was highly enriched only in patients with ALC (P <0.001), and positively correlated with AST level (P = 0.029). The abundance of Streptococcus distinguished the liver injury of ALC patients from the controls with an area under the receiver-operating characteristic curve (AUC) of 0.877 (P < 0.001).ConclusionsThese findings indicate that the imbalance of gut microbiota exists at the early and end-stages of ALD, and the degree of disorder is aggravated with the progression of ALD. Streptococcus, as the predominant bacterium, may be a microbiological marker to evaluate the severity of liver injury in ALD patients.

scholarly journals Ademetionine in patients with liver disease: a review

2019 ◽  
Vol 7 (6) ◽  
pp. 2482 ◽  
Author(s):  
Sanjiv Saigal ◽  
Dharmesh Kapoor ◽  
Dyotona Sen Roy
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Alcoholic Liver Disease ◽  
Biochemical Markers ◽  
Fatty Liver Disease ◽  
Signs And Symptoms ◽  
Drug Induced ◽  
Alcoholic Fatty Liver ◽  
Drug Induced Liver Injury ◽  
Alcoholic Fatty Liver Disease

The aim of the present review is to have an in-depth analysis of the published scientific literature relating to the clinical use of ademetionine in various etiologies of liver disease. Literature search was performed using electronic databases like Pubmed/Medline/others to identify studies on ademetionine in patients with intrahepatic cholestasis, alcoholic liver disease, non-alcoholic fatty liver disease, drug induced liver injury and viral hepatitis. Ademetionine has been studied in various etiologies of liver disease with varying dosing and durations. In patients with chronic and alcoholic liver disease, ademetionine was found to be beneficial in improving liver enzyme levels, increasing glutathione levels, improving signs and symptoms of fatigue, pruritus and jaundice. Positive effects of ademetionine therapy have also been documented in multiple studies in patients with non-alcoholic fatty liver disease, with improvements observed in triglyceride, total cholesterol, alanine transaminase and asprtate transaminase levels and ultrasound grading of fatty change. In patients with drug induced liver injury, improvements were observed in liver biochemical markers and symptoms such as pruritus, fatigue and jaundice. Ademetionine has also been studied in patients with viral hepatitis with improvement in laboratory markers and signs and symptoms. Published data suggest that there is clinical evidence to substantiate the use of ademetionine across indications. Its use has resulted in sustained improvement in biochemical markers; signs and symptoms of liver disease has been observed in both acute and chronic liver disease. Further data is warranted through clinical studies to focus on specific end points of therapy areas, in existing and new indications.

Protective effects of fucoidan against ethanol-induced liver injury through maintaining mitochondria function and mitophagy balance in rats.

2021 ◽  
Author(s):  
Huichao Zhao ◽  
Shuang Liu ◽  
Hui Zhao ◽  
Meilan Xue ◽  
Huaqi Zhang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Alcoholic Liver Disease ◽  
Therapeutic Strategy ◽  
Hepatic Lesion ◽  
Protective Effects ◽  
Regulatory Effects

For alcoholic liver disease (ALD), mitophagy was reported as a promising therapeutic strategy to alleviate the hepatic lesion elicited by ethanol. This study was to investigate the regulatory effects of...

A polysaccharide of PFP-1 from Pleurotus geesteranus attenuates alcoholic liver diseases via Nrf2 and NF-κB signaling pathways

2021 ◽  
Author(s):  
Xinling Song ◽  
Wenxue Sun ◽  
Wenxin Cai ◽  
Le Jia ◽  
Jianjun Zhang
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Liver Injury ◽  
Signaling Pathways ◽  
Alcoholic Liver Disease ◽  
Fruiting Body ◽  
Liver Diseases ◽  
Alcoholic Liver Diseases

A polysaccharide named as PFP-1 was isolated from Pleurotus geesteranus fruiting body, and the potential investigations on ameliorating oxidative stress and liver injury against alcoholic liver disease (ALD) were processed...

scholarly journals Caspase-Cleaved Keratin 18 Measurements Identified Ongoing Liver Injury after Bariatric Surgery

2021 ◽  
Vol 10 (6) ◽  
pp. 1233
Author(s):  
Felix Hempel ◽  
Martin Roderfeld ◽  
Lucas John Müntnich ◽  
Jens Albrecht ◽  
Ziya Oruc ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Liver Disease ◽  
Liver Injury ◽  
Response To Treatment ◽  
Morbidly Obese ◽  
Alcoholic Fatty Liver ◽  
Laboratory Parameters ◽  
Nafld Fibrosis Score ◽  
Keratin 18 ◽  
One Year

Bariatric surgery has emerged as an effective treatment option in morbidly obese patients with non-alcoholic fatty liver disease (NAFLD). However, worsening or new onset of non-alcoholic steatohepatitis (NASH) and fibrosis have been observed. Caspase-cleaved keratin 18 (ccK18) has been established as a marker of hepatocyte apoptosis, a key event in NASH development. Thus, ccK18 measurements might be feasible to monitor bariatric surgery patients. Clinical data and laboratory parameters were collected from 39 patients undergoing laparoscopic Roux-en-Y gastric bypass at six timepoints, prior to surgery until one year after the procedure. ccK18 levels were measured and a high-throughput analysis of serum adipokines and cytokines was carried out. Half of the cohort’s patients (20/39) presented with ccK18 levels indicative of progressed liver disease. 21% had a NAFLD-fibrosis score greater than 0.676, suggesting significant fibrosis. One year after surgery, a mean weight loss of 36.87% was achieved. Six and twelve months after surgery, ccK18 fragments were significantly reduced compared to preoperative levels (p < 0.001). Yet nine patients did not show a decline in ccK18 levels ≥ 10% within one year postoperatively, which was considered a response to treatment. While no significant differences in laboratory parameters or ccK18 could be observed, they presented with a greater expression of leptin and fibrinogen before surgery. Consecutive ccK18 measurements monitored the resolution of NAFLD and identified non-responders to bariatric surgery with ongoing liver injury. Further studies are needed to elicit the pathological mechanisms in non-responders and study the potential of adipokines as prognostic markers.

High resolution metabolomics technology reveals widespread pathway changes of alcoholic liver disease

2016 ◽  
Vol 12 (1) ◽  
pp. 262-273 ◽  
Author(s):  
Aihua Zhang ◽  
Guangli Yan ◽  
Xiaohang Zhou ◽  
Yangyang Wang ◽  
Ying Han ◽  
...  
Keyword(s):  
Liver Disease ◽  
High Resolution ◽  
Alcoholic Liver Disease ◽  
Molecular Mechanisms ◽  
High Resolution Metabolomics

The current study provides insights into the molecular mechanisms of ALD from widespread pathway changes.

Molecular mechanisms of non-alcoholic fatty liver disease development

2021 ◽  
Vol 24 (4) ◽  
pp. 120
Author(s):  
T.S. Sall ◽  
E.S. Shcherbakova ◽  
S.I. Sitkin ◽  
T.Ya. Vakhitov ◽  
I.G. Bakulin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Disease Development ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Serum adipokine levels predictive of liver injury in non-alcoholic fatty liver disease

2009 ◽  
Vol 29 (9) ◽  
pp. 1431-1438 ◽  
Author(s):  
Maud Lemoine ◽  
Vlad Ratziu ◽  
Minji Kim ◽  
Mustapha Maachi ◽  
Dominique Wendum ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Is liver fat detrimental to vessels?: intersections in the pathogenesis of NAFLD and atherosclerosis

2008 ◽  
Vol 115 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Paola Loria ◽  
Amedeo Lonardo ◽  
Giovanni Targher
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Liver Fat ◽  
Cvd Risk ◽  
Alcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Major Player

NAFLD (non-alcoholic fatty liver disease) encompasses the spectrum of fatty liver disease in insulin-resistant individuals who often display T2DM (Type 2 diabetes mellitus) and obesity. The present review highlights the pathophysiological basis and clinical evidence for a possible causal linkage between NAFLD and CVD (cardiovascular disease). The role of traditional and non-traditional CVD risk factors in the pathophysiology of NAFLD is considered in the first part of the review, with the basic science shared by atherogenesis and hepatic steatogenesis discussed in depth in the second part. In conclusion, NAFLD is not an innocent bystander, but a major player in the development and progression of CVD. NAFLD and CVD also share similar molecular mechanisms and targeted treatment strategies. On the research side, studies should focus on interventions aimed at restoring energy homoeostasis in lipotoxic tissues and at improving hepatic (micro)vascular blood supply.

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