Alcoholic liver disease: Treatment

The excess consumption of alcohol is associated with alcoholic liver diseases(ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation.

Current concepts and controversies in the treatment of alcoholic hepatitis

The treatment of alcoholic hepatitis remains one of the most debated topics in medicine and a field of continued research. In this review, we discuss the evolution of scoring systems, including the recent development of the Glasgow alcoholic hepatitis score, role of liver biopsy and current treatment interventions. Studies of treatment interventions with glucocorticoids, pentoxifylline, infliximab, s-adenosyl-methionine, and colchicine are reviewed with discussion on quality. Glucocorticoids currently remain the mainstay of treatment for severe alcoholic hepatitis.

Combination drug treatment in patients with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis, a benign condition, and non-alcoholic steatohepatitis, a condition that beyond TG accumulation also includes necroinflammation and fibrosis. An association between NAFLD and cardiovascular disease (CVD) has been recently suggested. NAFLD patients usually have an increased CVD risk profile. NAFLD is also associated with metabolic syndrome (MetS) and is considered as the hepatic component of MetS by some authors. Currently, the only established treatment of NAFLD is gradual weight loss. However, multifactorial treatment of NAFLD risk factors may be needed to reduce the increased CVD risk of NALFD patients. Drug combinations that include antiobesity drugs (such as orlistat and sibutramine) and target CVD risk factors may be a good approach to NAFLD patients. Our group has investigated the orlistat-fenofibrate combination treatment in obese patients with MetS and the orlistatezetimibe and sibutramine-antihypertensive combination treatment in obese patients with hyperlipidaemia with promising results in CVD risk factor reduction and improvement of liver function tests. Small studies give promising results but double-blind, randomized trials examining the effects of such multifactorial treatment in hard CVD endpoints in NAFLD patients are missing.

Treatment options for alcoholic and non-alcoholic fatty liver disease: A review

Alcoholic liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma.Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver(simple steatosis),a small percentage develops progressive liver disease.Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available.The treatment for ALD remains as it was 50 years ago:abstinence,nutritional support and corticosteroids(or pentoxifylline as an alternative if steroids are contraindicated).As for NAFLD,the treatment modality is mainly directed toward weight loss and co-morbidity management.Therefore,new pathophysiology directed therapies are urgently needed.However,the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy.Hence,a combination therapy towards multiple targets would eventually be required.In this review,we delineate the treatment options in ALD and NAFLD,including various new targeted therapies that are currently under investigation.We hope that soon we will be having an effective multi-therapeutic regimen for each disease.

Microbiota-based treatments in alcoholic liver disease

Gut microbiota plays a key role in the pathogenesis of alcoholic liver disease(ALD). Consumption of alcohol leads to increased gut permeability, small intestinal bacterial overgrowth, and enteric dysbiosis. These factors contribute to the increased translocation of microbial products to the liver via the portal tract. Subsequently, bacterial endotoxins such as lipopolysaccharide, in association with the Toll-like receptor 4 signaling pathway, induce a gamut of damaging immune responses in the hepatic milieu. Because of the close association between deleterious inflammation and ALD-induced microbiota imbalance, therapeutic approaches that seek to reestablish gut homeostasis should be considered in the treatment of alcoholic patients. To this end, a number of preliminary studies on probiotics have confirmed their effectiveness in suppressing proinflammatory cytokines and improving liver function in the context of ALD. In addition, there have been few studies linking the administration of prebiotics and antibiotics with reduction of alcoholinduced liver damage. Because these preliminary results are promising, large-scale randomized studies are warranted to elucidate the impact of these microbiotabased treatments on the gut flora and associated immune responses, in addition to exploring questions about optimal delivery. Finally, fecal microbiota transplant has been shown to be an effective method of modulating gut microbiota and deserve further investigation as a potential therapeutic option for ALD.

Alcoholic hepatitis: A comprehensive review of pathogenesis and treatment

Alcoholic hepatitis(AH)is an acute hepatic inflammation associated with significant morbidity and mortality.Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism,inflammation and innate immunity.Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH;such as Child-Turcotte-Pugh score,the Maddrey discriminant function,the Lille Model,the model for end stage liver disease scores,and the Glasgow alcoholic hepatitis score.At present,Corticosteroids or pentoxifylline are the current pharmacologic treatment options;though the outcomes from the therapies are poor.Liver trans-plantation as the treatment of alcoholic hepatitis remains controversial,and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option.Because of the limitations in the therapeutic options,it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH.

Non-alcoholic fatty liver disease and diabetes: From physiopathological interplay to diagnosis and treatment

Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2diabetes are at a particularly high risk for developing the progressive forms of NAFLD,non-alcoholic steatohepatitis and associated advanced liver fibrosis.Moreover,diabetes is an independent risk factor for NAFLD progression,and for hepatocellular carcinoma development and liver-related mortality in prospective studies.Notwithstanding,patients with NAFLD have an elevated prevalence of prediabetes.Recent studies have shown that NAFLD presence predicts the development of type2 diabetes.Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients.The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods,although histopathological evaluation is still considered the gold standard diagnostic method.An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking.We sought to outline the published data including epidemiology,pathogenesis,diagnosis and treatment of NAFLD in diabetic patients,in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.

Work as An Effective Intervention Strategy and Rehabilitation Treatment Program for People Who Abuse Drugs And Alcohol

Despite years of interventions in the United States, substance abuse continues to be a major national problem in our society. For individuals affected, it can constitute a major disability and a decrease in quality of life. Current American societal expectations are that individuals who identify!they are involved in substance abuse will go to treatment, eventually recover, get off public assistance straightaway, and return to work. Most rehabilitation professionals also maintain the same expectations. The reality is that efforts of prevention do not appear to diminish the number of people with substance abuse. Traditional treatment appears to have minimal, if any, influence upon the cessation of substance abuse, and traditional vocational rehabilitation practices appear unsuited for the unique problems and types of symptoms experienced by substance abusers. Creative, yet sound, alternatives that combine effective treatment strategies and non-traditional vocational rehabilitation methods need to be exqlored and tested for effectiveness, and applied.

Proteasome inhibitor treatment in alcoholic liver disease

Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally located in the cytoplasm and in the mitochondria, which does not only injure liver cells, but also other vital organs, such as the heart and the brain. Therefore, there is a need for better treatment to enhance the antioxidant response elements. To date, there is no established treatment to attenuate high levels of oxidative stress in the liver of alcoholic patients. To block this oxidative stress, proteasome inhibitor treatment has been found to significantly enhance the antioxidant response elements of hepatocytes exposed to ethanol. Recent studies have shown in an experimental model of alcoholic liver disease that proteasome inhibitor treatment at low dose has cytoprotective effects against ethanol-induced oxidative stress and liver steatosis. The beneficial effects of proteasome inhibitor treatment against oxidative stress occurred because antioxidant response elements (glutathione peroxidase 2, superoxide dismutase 2, glutathione synthetase, glutathione reductase, and GCLC) were upregulated when rats fed alcohol were treated with a low dose of PS-341 (Bortezomib, Velcade  ). This is animportant finding because proteasome inhibitor treatment up-regulated reactive oxygen species removal and glutathione recycling enzymes, while ethanol feeding alone down-regulated these antioxidant elements. For the first time, it was shown that proteasome inhibition by a highly specific and reversible inhibitor is different from the chronic ethanol feeding-induced proteasome inhibition. As previously shown by our group, chronic ethanol feeding causes a complex dysfunction in the ubiquitin proteasome pathway, which affects the proteasome system, as well as the ubiquitination system. The beneficial effects of proteasome inhibitor treatment in alcoholic liver disease are related to proteasome inhibitor reversibility and the rebound of proteasome activity 72 h post PS-341 administration.

Non-alcoholic fatty liver disease: What has changed in the treatment since the beginning?

Non-alcoholic fatty liver disease(NAFLD) is an umbrella term to describe the entire spectrum of this common liver disease. In patients with NAFLD, especially those with non-alcoholic steatohepatitis(NASH), most often have one or more components of the metabolic syndrome, but this is not universal. Although most patients with NAFLD share many clinical features, only a subset of patients develops significant liver inflammation and progressive fibrosis. On the other hand, not all patients with NASH exhibit insulin resistance. NASH can be seen in patients who are lean and have no identifiable risk factors. Many clinical studies have tried numerous drugs and alternative medicine, however, investigators have failed to identify a safe and effective therapy for patients with NASH. As summarized, the heterogeneity of pathogenic pathways in individual patients with NASH may warrant the development of an individualized treatment according to the underlying pathogenic pathway. The differentiation of pathogenetic targets may require the development of diagnostic and prognostic biomarkers, and the identification of genetic susceptibilities. At present, evidence-based medicine provides only a few options including life-style modifications targeting weight loss, pioglitazone and vitamin E in non-diabetic patients with biopsy-proven NASH.

Focus on alcoholic liver disease:From nosography to treatment

Abusive alcohol intake currently ranks as a major cause of liver disease, and is associated with significant mortality worldwide. Alcoholic liver disease(ALD) generically defines liver abnormalities ranging from liver steatosis to the end-stages of disease such as liver cirrhosis. Information regarding the precise incidence and prevalence of ALD is still limited by a lack of large population-based studies and by the absence of large systematic reviews of all epidemiological data available. However, existing collected data show an overall increase in the number of alcohol abusers and alcoholrelated liver disease. The burden exerted on medical systems worldwide is significant, with hospitalization and management costs rising constantly over the years. A great number of all cirrhosis-related deaths in Europe and a significant percentage worldwide areassociated with alcohol consumption. The main possible risk factors for ALD are the amount and duration of alcohol abuse, patterns of drinking and the type of alcoholic beverage consumed. However, ALD does not progress to cirrhosis in all patients, therefore a series of additional factors are implicated. Even though insufficiently studied, genetic factors are generally regarded as highly important, and the presence of comorbidities and dietary habits seem to play a role in disease onset and progression. This lack of clear pathophysiological data further translates in the absence of definite treatment for ALD and shall prove challenging in the coming years. In this article, we aimed to briefly review epidemiologic data on the burden of ALD, risk factors, clinical and nosographic as well as therapeutic aspects of this disease. Without attempting to be exhaustive, this short topic highlight emphasizes each point and may serve as a general guidance tool in the complicated literature related to ALD.

General aspects of the treatment of alcoholic hepatitis

General measures for treating patients with alcoholic hepatitis(AH) are similar irrespective of the disease severity.Alcohol abstinence is the cornerstone of treatment and can be achieved with appropriate social support,Alcoholics Anonymous and sometimes pharmacological therapy.Alcohol withdrawal should be anticipated and treatment initiated to prevent this complication.Treatment for complications of cirrhosis should be as for any other patient with cirrhosis.AH patients are particularly prone to infections and malnutrition.These should be identified and treated appropriately using broad spectrum antibiotics and nutritional support respectively.

PVDF/PVA共混膜的制备及其在去除污水COD中的应用

以聚乙烯醇(PVA)、聚偏氟乙烯(PVDF)为原料,聚乙烯吡咯烷酮为溶剂,制备了PVDF/PVA共混膜。将该膜应用于膜生物反应器处理污水,测试化学需氧量(COD)去除率和膜的使用性能。结果表明:膜的水通量随PVA加入量的增加而逐渐增加,在牵伸比为1.7时,膜的水通量达到最大值;平板膜用清水清洗后,膜的水通量恢复率较高,膜的运行周期经第一次清洗后下降了18 h,经第二次和第三次清洗后,膜的运行周期基本稳定在6~8 h,COD去除率高于90%,表明该膜具有良好的使用性能。

非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是一种与胰岛素抵抗和代谢综合征相关的慢性肝脏疾病。随着全球肥胖和糖尿病患者的增加,NAFLD的发病率也在逐年上升,成为全球范围内一个重要的公共卫生问题。NAFLD患者常会出现乏力、腹胀、右上腹不适或疼痛等症状,严重时可出现肝硬化、肝细胞癌等,这时会出现呕血、黑便、血便等症状,对患者的身体健康和生命质量产生严重的影响。因此,及时的诊断和治疗对改善NAFLD患者预后至关重要。本文将从NAFLD的发病机制、病理生理、流行病学特点、临床表现、诊断和治疗等方面进行综述。

PNPLA3 rs738409 underlies treatment response in nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)has now become the leading cause of chronic liver disease with its growing incidence worldwide.Patatin-like phospholipase domain-containing protein 3(PNPLA3)rs738409 C>G reflects one of the critical genetic factors that confers high-risk to NAFLD.However,the role of PNPLA3 polymorphism in NAFLD treatment remains uncertain.Here,the present review reveals that NAFLD patients with G-allele at PNPLA3 rs738409(PNPLA3 148M variant)are sensitive to therapies of lifestyle modification,dipeptidyl peptidase-4 inhibitors,and bariatric surgery.They exhibit much significant reduction of liver fat content,in concurrence with weigh loss and abolished insulin resistance,as compared to those of C-allele carriers.In contrast,patients bearing PNPLA3 rs738409 C-allele(PNPLA3 148I variant),instead of G-allele,demonstrate greater beneficial effects by omega-3 poly-unsaturated fatty acids and statin intervention.Improved adipose tissue-liver interaction and decrease in intrahepatic triglyceride efflux may contribute to the PNPLA3 rs738409related diversities in therapeutic efficacy.Therefore,PNPLA3 rs738409 underlies the response to a variety of treatments,which warrants a personalized,precise medicine in NAFLD on the basis of genotype stratification.

AMP依赖的蛋白激酶调节脂质积累治疗非酒精性脂肪肝病的治疗研究进展

非酒精性脂肪肝病(non-Alcoholic fatty liver disease, NAFLD)作为慢性肝病最主要的患病原因,已经对全球的公共健康卫生与医疗带来了巨大挑战。由于NAFLD的发病机制尚不明确,脂质积累在NAFLD疾病发展中起到关键作用。AMP依赖的蛋白激酶(AMPK)作为脂质代谢调节关键分子,能够改善NAFLD所造成的脂质积累。本文阐述了AMPK相关分子改善脂质积累并治疗NAFLD的具体作用机制,同时列举了目前AMPK相关实验和治疗研究的药物。证明了AMPK相关药物用于改善脂肪积累、治疗NAFLD的潜力,为后续对于AMPK相关治疗NAFLD药物的研究提供了思路与参考。

玉米发酵酒精废水处理工艺的选择

人类与自然之间的关系是紧密而复杂的,我们赖以生存的空气和水资源,如果环境受到污染,将会对人类的生存构成威胁。因此,我国各地的酒精企业纷纷采取措施,加强对玉米发酵酒精废水的处理,以防止酒精废水处理的不合格所带来的环境污染。本文将深入探讨玉米发酵酒精废水的处理技术,并提出有效的科学处理措施。

化合物治疗非酒精性脂肪肝病相关肝细胞癌的研究进展

目前非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)已成为全球健康的严重威胁,将成为肝细胞癌(hepatocellular carcinoma,HCC)的主要诱导因素,并最终导致NAFLD相关的HCC的发生。但目前为止,其具体分子机制仍不完全清楚。现越来越多的研究关注着化合物在NAFLD和NAFLD相关的HCC中的应用。因此本文在简要回顾了NAFLD相关HCC发病和进展可能机制的最新研究基础上,进行总结和整理化合物对NAFLD相关肝细胞癌治疗的最新进展,并将这部分药物分为以下五种作用机制:抗炎、抗氧化、调节脂质代谢、调节肠道菌群和抑制肝纤维化,以期为今后NAFLD相关HCC的治疗和预防提供有价值的信息。

非酒精性脂肪肝的诱发机制及中药治疗研究进展

非酒精性脂肪肝病(NAFLD)是最常见的肝病之一,如不及时诊治,可逐渐发展为肝纤维化、肝硬化甚至肝癌。因此,阐明NAFLD的诱发机制,有助于从根本上了解NAFLD,为治疗NAFLD提供理论依据。本文简述了NAFLD的诱发机制以及中药的治疗研究现状,认为中药的多成分虽然能够多靶点作用于NAFLD,改善NAFLD,但中药及其有效成分发挥作用的具体机制尚未完全清楚,仍需进一步研究,以期为NAFLD的治疗提供新思路和研究方向,并为今后该领域的中药深入研究提供参考。

代谢相关脂肪性肝病发病机理及治疗的研究进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是一种以肝内脂质沉积为特征的慢性肝病,目前已更名为代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)。近年来MAFLD发病率逐步提升,对医疗系统的负担持续增加,在治疗方面尚无特效药物。本研究通过查阅相关文献,概述了影响MAFLD发病的相关机制,归纳了MAFLD治疗方法的当前进展,为临床治疗MAFLD提供理论基础。