scholarly journals Alkoholos májbetegség: a genetikai-epigenetikai tényezők szerepe és az absztinencia hatása

2019 ◽  
Vol 160 (14) ◽  
pp. 524-532 ◽  
Author(s):  
Alajos Pár ◽  
Gabriella Pár
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Environmental Factors ◽  
Alcoholic Liver Disease ◽  
Liver Toxicity ◽  
Hepatitis Virus ◽  
Alcoholic Cirrhosis ◽  
Protective Role ◽  
Micro Rna ◽  
Alcoholic Fatty Liver

Abstract: The pathogenesis of alcoholic liver disease depends not only on the toxic effects of alcohol, but also on the complex interaction of host’s and environmental factors. Thus, the genetic pre-disposition, co-morbidities and behavioral factors all play a role in the individual variations in the disease outcomes. On the other hand, the essential part of the therapeutic strategy is the complete withdrawal of the harmful etiological agent. The present paper is devoted to overview the genetics, the environmental factors and the effects of abstinence in alcoholic liver disease. Genetic variants in two enzymes involved in the metabolism of ethanol, alcohol-dehydrogenase ADH1B *2 and aldehyde-dehydrogenase ALDH2 *2 through increasing the blood level of acetaldehyde, may play a “protective” role against alcoholism. The P450 CYP2E1 *5 c2, an inducible microsomal oxidase, upregulated by ethanol and by formation of acetaldehyde and reactive oxygen species, increases liver toxicity. Three novel gene polymorphisms – such as the patatin-like phospholipase domain-containing 3 (PNPLA3 I148M C>G), the transmembrane 6 superfamily member 2 (TM6SF2 E167K), and the membrane-bound O-acyltransferase domain-containing 7 (MB0AT7 rs641738 C>T) – have been proven as risk factors of steatosis, fibrosis and even hepatocellular carcinoma in both alcoholic and non-alcoholic fatty liver disease patients. Alcohol-induced epigenetic effects, reversible but inheritable gene expression alterations – as histon modulations, DNA methylation and micro-RNA-s – are of importance in the pathogenesis as well, and in the future, they may serve as diagnostic markers and therapeutic targets. Women are at greater risk of developing alcoholic cirrhosis, furthermore, malnutrition, obesity, diabetes, smoking, and hepatitis virus infections are also risk factors. Alcoholic liver disease should be regarded as a preventable disease. Several clinical studies revealed that abstinence may result in the regression of steatohepatitis and fibrosis, compensation of cirrhosis, improving disease outcome and increasing survival even in patients with advanced stages. Early diagnosis and multidisciplinary interventions are highly required to achieve long-term abstinence and to prevent alcoholic cirrhosis. Orv Hetil. 2019; 160(14): 524–532.

scholarly journals Alcoholic Liver Disease: Current Mechanistic Aspects with Focus on Their Clinical Relevance

Biomedicines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 68 ◽  
Author(s):  
Rolf Teschke
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Experimental Studies ◽  
Alcoholic Cirrhosis ◽  
Sufficient Evidence ◽  
Liver Sinusoidal Endothelial Cells ◽  
Alcoholic Fatty Liver ◽  
Gut Leakage ◽  
Parenchymal Cells

The spectrum of alcoholic liver disease (ALD) is broad and includes alcoholic fatty liver, alcoholic steatohepatitis, alcoholic hepatitis, alcoholic fibrosis, alcoholic cirrhosis, and alcoholic hepatocellular carcinoma, best explained as a five-hit sequelae of injurious steps. ALD is not primarily the result of malnutrition as assumed for many decades but due to the ingested alcohol and its metabolic consequences although malnutrition may marginally contribute to disease aggravation. Ethanol is metabolized in the liver to the heavily reactive acetaldehyde via the alcohol dehydrogenase (ADH) and the cytochrome P450 isoform 2E1 of the microsomal ethanol-oxidizing system (MEOS). The resulting disturbances modify not only the liver parenchymal cells but also non-parenchymal cells such as Kupffer cells (KCs), hepatic stellate cells (HSCs), and liver sinusoidal endothelial cells (LSECs). These are activated by acetaldehyde, reactive oxygen species (ROS), and endotoxins, which are produced from bacteria in the gut and reach the liver due to gut leakage. A variety of intrahepatic signaling pathways and innate or acquired immune reactions are under discussion contributing to the pathogenesis of ALD via the five injurious hits responsible for disease aggravation. As some of the mechanistic steps are based on studies with in vitro cell systems or animal models, respective proposals for humans may be considered as tentative. However, sufficient evidence is provided for clinical risk factors that include the amount of alcohol used daily for more than a decade, gender differences with higher susceptibility of women, genetic predisposition, and preexisting liver disease. In essence, efforts within the last years were devoted to shed more light in the pathogenesis of ALD, much has been achieved but issues remain to what extent results obtained from experimental studies can be transferred to humans.

scholarly journals Non-alcoholic fatty liver disease in polycystic ovary syndrome women

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Young Bin Won ◽  
Seok Kyo Seo ◽  
Bo Hyon Yun ◽  
SiHyun Cho ◽  
Young Sik Choi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Fatty Liver ◽  
Liver Enzyme ◽  
Fatty Liver Disease ◽  
Polycystic Ovary ◽  
Insulin Level ◽  
University Hospital ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractTo evaluate risk factors leading to non-alcoholic fatty liver disease (NAFLD) occurrence in polycystic ovarian syndrome (PCOS) women. A retrospective cohort study of a total of 586 women diagnosed with PCOS aged 13–35 years at the gynecology department at a university hospital was done to evaluate PCOS phenotype, metabolic syndrome (MetS) diagnosis, body composition, insulin sensitivity, sex hormones, lipid profile, liver function, and transient elastography (TE). In PCOS women with NAFLD compared to those without, MetS diagnosis (Hazard ratio [HR] 5.6, 95% Confidence interval [CI] 2.2–14.4, p < 0.01) and hyperandrogenism (HA) (HR 4.4, 95% CI 1.4–13.4, p = 0.01) were risk factors significantly associated with subsequent NAFLD occurrence, whereas 2-h insulin level in 75 g glucose tolerance test (GTT) (HR 1.2, 95% CI 0.5–2.5, p = 0.70) and body mass index (BMI) > 25 kg/m2 (HR 2.2, 95% CI 0.6–8.0, p = 0.24) was not. Among NAFLD patients who underwent TE, a higher number of MetS components indicated a worse degree of fibrosis and steatosis. MetS diagnosis and HA at PCOS diagnosis were risk factors associated with NAFLD, while 2-h insulin level in 75 g GTT and obesity were not. Although elevated aspartate aminotransferase levels were significant for NAFLD risk, liver enzyme elevations may not be present until late liver damage. Further prospective studies of PCOS women with MetS or HA are warranted to determine whether patients without liver enzyme elevations should undergo preemptive liver examinations.

scholarly journals Health-related quality of life in Chinese population with non-alcoholic fatty liver disease: a national multicenter survey

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rui Huang ◽  
Jian-Gao Fan ◽  
Jun-Ping Shi ◽  
Yi-Min Mao ◽  
Bing-Yuan Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Alcoholic Fatty Liver ◽  
Related Quality ◽  
Health Related ◽  
Independent Risk Factors ◽  
Alcoholic Fatty Liver Disease

Abstract Background Health Related Quality of Life (HRQL) is a multi-dimensional construct that can comprehensively evaluate the patient’s health status, including physical, emotional, mental and social well-being. In this study, we aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on HRQL in a Chinese population. Methods In this national multicenter cross-sectional survey, patients with NAFLD were enrolled. Chronic Liver Disease Questionnaire (CLDQ)-NAFLD was used to qualify HRQL. Univariate and multivariate analysis were used to identify independent risk factors of HRQL. Results A total of 5181 patients with NAFLD from 90 centers were enrolled in this study (mean age, 43.8 ± 13.3 years; male, 65.8%). The overall CLDQ score was 5.66 ± 0.89. Multivariate logistic regression analysis showed that body mass index (BMI: HR, 1.642; 95% CI, 1.330–2.026), alanine transaminase (ALT: HR, 1.006; 95% CI, 1.001–1.011), triglyceride (HR, 1.184; 95% CI, 1.074–1.305), disease severity (HR, 3.203; 95% CI, 1.418–7.232) and cardiovascular disease (HR, 4.305; 95% CI, 2.074–8.939) were independent risk factors for overall CLDQ score. In the logistic analyses of individual domain, BMI and triglyceride were independent risk factors of all domains. ALT, disease severity, diabetes, depression and cardiovascular disease were influencing factors for the CLDQ score of several domains. Conclusions This national multicenter cross-sectional survey in China indicated that the HRQL in patients with NAFLD was impaired. HRQL was found to be significantly associated with sociodemographic and clinical factors. Attention should be paid to the optimally managing care of patients with NAFLD to improve their HRQL.

scholarly journals Implementation of a care bundle improves the management of patients with non-alcoholic fatty liver disease

2021 ◽  
pp. flgastro-2020-101480
Author(s):  
Laura Jane Neilson ◽  
Louise Macdougall ◽  
Phey Shen Lee ◽  
Timothy Hardy ◽  
David Beaton ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Metabolic Risk Factors ◽  
Care Bundle ◽  
Metabolic Risk ◽  
Lifestyle Advice ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is common and is associated with liver-related and cardiovascular-related morbidity. Our aims were: (1) to review the current management of patients with NAFLD attending hospital clinics in North East England (NEE) and assess the variability in care; (2) develop a NAFLD ‘care bundle’ to standardise care; (3) to assess the impact of implementation of the NAFLD care bundle.MethodsA retrospective review was conducted to determine baseline management of patients with NAFLD attending seven hospitals in NEE. A care bundle for the management of NAFLD was developed including important recommendations from international guidelines. Impact of implementation of the bundle was evaluated prospectively in a single centre.ResultsBaseline management was assessed in 147 patients attending gastroenterology, hepatology and a specialist NAFLD clinic. Overall, there was significant variability in the lifestyle advice given and management of metabolic risk factors, with patients attending an NAFLD clinic significantly more likely to achieve >10% body weight loss and have metabolic risk factors addressed. Following introduction of the NAFLD bundle 50 patients were evaluated. Use of the bundle was associated with significantly better documentation and implementation of most aspects of patient management including management of metabolic risk factors, documented lifestyle advice and provision of NAFLD-specific patient advice booklets.ConclusionThe introduction of an outpatient ‘care bundle’ led to significant improvements in the assessment and management of patients with NAFLD in the NEE and could help improve and standardise care if used more widely.

11. Risk factors for development of diabetes mellitus in non-alcoholic fatty liver disease (NAFLD) patients

2018 ◽  
Vol 8 ◽  
pp. S39-S40
Author(s):  
Shivaram Prasad Singh ◽  
Saroj Kanta Sahu ◽  
Prasanta Kumar Parida ◽  
Sambit Kumar Behera ◽  
Suryakanta Parida ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Antidiabetic Drugs in NAFLD: The Accomplishment of Two Goals at Once?

2018 ◽  
Vol 11 (4) ◽  
pp. 121 ◽  
Author(s):  
Matteo Tacelli ◽  
Ciro Celsa ◽  
Bianca Magro ◽  
Aurora Giannetti ◽  
Grazia Pennisi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Meta Analysis ◽  
Pancreatic Beta Cell ◽  
Protective Role ◽  
Antidiabetic Drugs ◽  
Alcoholic Fatty Liver ◽  
Compensated Cirrhosis ◽  
Ppar Γ ◽  
Insulin Use

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in Western countries, accounting for 20–30% of general population and reaching a prevalence of 55% in patients with type 2 diabetes mellitus (T2DM). Insulin resistance plays a key role in pathogenic mechanisms of NAFLD. Many drugs have been tested but no medications have yet been approved. Antidiabetic drugs could have a role in the progression reduction of the disease. The aim of this review is to summarize evidence on efficacy and safety of antidiabetic drugs in patients with NAFLD. Metformin, a biguanide, is the most frequently used drug in the treatment of T2DM. To date 15 randomized controlled trials (RCTs) and four meta-analysis on the use of metformin in NAFLD are available. No significant improvement in histological liver fibrosis was shown, but it can be useful in the treatment of co-factors of NAFLD, like body weight, transaminase or cholesterol levels, and HbA1c levels. A possible protective role in various types of cancer has been reported for Metformin. Thiazolidinediones modulate insulin sensitivity by the activation of PPAR-γ. The RCTs and the meta-analysis available about the role of these drugs in NAFLD show an improvement in ballooning, lobular inflammation, and perhaps fibrosis, but some side effects, in particular cardiovascular, were showed. GLP-1 analogues stimulate insulin secretion by pancreatic beta cell and inhibit glucagon release; Liraglutide is the most used drug in this class and significantly improves steatosis, hepatocyte ballooning and transaminase levels. Scanty data about the role of DPP-4 and SGLT inhibitors were published. No data about insulin effects on NAFLD are available but it was showed a possible association between insulin use and the development of solid neoplasms, in particular HCC. In conclusion, antidiabetic drugs seem to be promising drugs, because they are able to treat both NAFLD manifestations and diabetes, preventing worsening of hepatic damage, but data are still conflicting. All antidiabetic drugs can be safely used in patients with compensated cirrhosis, while insulin is the preferred drug in decompensated Child C cirrhosis.

scholarly journals Genetic and Life Style Risk Factors for Recurrent Non-alcoholic Fatty Liver Disease Following Liver Transplantation

2022 ◽  
Vol 8 ◽  
Author(s):  
Speranta Iacob ◽  
Susanne Beckebaum ◽  
Razvan Iacob ◽  
Cristian Gheorghe ◽  
Vito Cicinnati ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Fatty Liver ◽  
Life Style ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Recurrent Nash ◽  
Alcoholic Fatty Liver Disease

Recurrent or de novo non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) following liver transplantation (LT) is a frequent event being increasingly recognized over the last decade, but the influence of recurrent NASH on graft and patient outcomes is not yet established. Taking into consideration the long term survival of liver transplanted patients and long term complications with associated morbidity and mortality, it is important to define and minimize risk factors for recurrent NAFLD/NASH. Metabolic syndrome, obesity, dyslipidemia, diabetes mellitus are life style risk factors that can be potentially modified by various interventions and thus, decrease the risk of recurrent NAFLD/NASH. On the other hand, genetic factors like recipient and/or donor PNPLA3, TM6SF2, GCKR, MBOAT7 or ADIPOQ gene polymorphisms proved to be risk factors for recurrent NASH. Personalized interventions to influence the different metabolic disorders occurring after LT in order to minimize the risks, as well as genetic screening of donors and recipients should be performed pre-LT in order to achieve diagnosis and treatment as early as possible.

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