Alcoholic Liver Disease in Asia, Europe, and North America

Liangpunsakul, Suthat; Haber, Paul S.; McCaughan, Geoffrey W.

doi:10.1053/j.gastro.2016.02.043

Cited by 148 publications

(142 citation statements)

References 100 publications

(141 reference statements)

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“…Excessive alcohol consumption is a leading cause of chronic liver diseases worldwide 1 and causes a broad spectrum of liver disorders ranging from simple steatosis to severe forms of liver injury including steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma 2, 3 . Over the last five decades, investigators have been actively exploring animal models for alcoholic liver disease (ALD), studying its pathogenesis and searching for therapeutic drugs for the treatment of ALD.…”

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confidence: 99%

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

et al. 2017

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Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models that have been useful for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals. All of these models recapitulate some features of the different stages of ALD and have been widely used by many investigators to study the pathogenesis of ALD and test therapeutic drugs/components. However, these models are somewhat variable, depending on mouse genetic background, ethanol dose, and animal facility environment. This review focuses on these models and discusses these variations and some methods to improve the feeding protocol. The pathogenesis, clinical relevance, and translational studies of these models are also discussed.

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confidence: 99%

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

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“…In the liver, excessive alcohol use can lead to a broad spectrum of liver disorders, ranging from simple steatosis to severe forms of liver injury including steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma 2 . The underlying mechanisms of alcohol-induced liver injury are complex, involving the derangement in hepatic lipid metabolism, innate immune responses, as well as epigenetic regulation 33–35 – all these processes are also under control by lncRNAs 17, 24, 26 .…”

Section: Discussionmentioning

confidence: 99%

“…ALD consists of a spectrum of pathological changes ranging from alcoholic steatosis to fibrosis and cirrhosis 2 . Alcohol-induced steatosis occurs in most if not all patients who consume alcohol excessively, but can be reversed with abstinence 3 .…”

Section: Introductionmentioning

confidence: 99%

LncRNA AK054921 and AK128652 are potential serum biomarkers and predictors of patient survival with alcoholic cirrhosis

Yang

Ross

Zhao

et al. 2017

Hepatology Communications

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Background Alcoholic liver disease (ALD) is one of the leading causes of chronic liver disease. Recent studies have demonstrated the roles of long noncoding RNAs (lncRNAs) in the pathogenesis of several disease processes. However, the roles of lncRNAs in patients with ALD remain unexplored. Methods Global profiling for human lncRNAs from peripheral blood RNA was performed in a well characterized cohort of healthy controls (HC, n=4), excessive drinkers without liver diseases (ED, n=4), and those with alcoholic cirrhosis with different severities (AC, n=12). The expression of unique lncRNA signatures were validated in a separate cohort of HC (n=17), ED (n=19), AC (n=48), and human liver tissues with ALD (n=19). Results Detailed analysis of plasma lncRNAs in AC subjects with different severities compared to HC identified 244 commonly up-regulated lncRNAs and 181 commonly down-regulated lncRNAs. We further validated top 20 most differentially up- and down-regulated lncRNAs in ED and AC as compared to HC and also determined the expression of selected lncRNAs in human liver tissues with or without AC. Among those lncRNAs, AK128652 and AK054921 were two of the most abundantly expressed lncRNAs in normal human plasma and liver, and their levels were significantly elevated in AC. The prognostic significance of AK128652 and AK054921 was determined in 48 subjects with AC; who were prospectively followed for 520 days. The expression of AK128652 and AK054921 was inversely associated with survival in patients with AC. Conclusions LncRNAs AK054921 and AK128652 are potential biomarkers to predict the progression to ALD in those with excessive alcohol consumption and are predictors of survival with patients with alcoholic cirrhosis.

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“…8 Simple fatty liver, which is defined as the accumulation of fat (triglycerides, phospholipids, and cholesterol esters) in hepatocytes, is usually a self-limited condition that can resolve in those who remain abstinent for ∼4-6 weeks. 9 However, alcoholic steatosis, which was once considered benign, is now recognized as a condition that may lead to advanced liver disease or cirrhosis.…”

Section: Alcohol and Liver Disease Alcoholic Liver Diseasementioning

confidence: 99%

Management of Alcohol Misuse in Patients with Liver Diseases

Peng

Patel

McGee

et al. 2017

Journal of Investigative Medicine

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Excessive alcohol use not only causes alcoholic liver disease (ALD) but also increases the risk of liver-related mortality in patients who already have other chronic liver diseases. Screening for alcohol misuse or alcohol use disorder (AUD) among patients with underlying liver disease is essential. This clinical review covers what is known about ALD, the impact of alcohol in patients with underlying liver diseases, current management of alcohol misuse and AUD, and the management of alcohol misuse and AUD specifically in patients with liver diseases. Several treatment options for alcohol misuse and AUD exist such as psychosocial intervention and behavioral and pharmacological therapies. The strategies used in the treatment of alcohol misuse and AUD are still applicable in those who consume alcohol and have underlying liver disease. However, certain medications still need to be carefully used due to potentially worsening already compromised liver function. Screening of ongoing alcohol use in subjects with liver disease is important, and prompt intervention is needed to prevent the associated morbidity and mortality from the detrimental effects of continued alcohol use on underlying liver disease. Considering alcoholism is a complex disease, probably a multidisciplinary approach combining psychotherapy and comprehensive medical care will be the most effective. Future research could focus on identifying additional treatment options for addressing the psychotherapy component since the self-determination and will to quit drinking alcohol can play such a crucial role in promoting abstinence.

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Alcoholic Liver Disease in Asia, Europe, and North America

Cited by 148 publications

References 100 publications

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

LncRNA AK054921 and AK128652 are potential serum biomarkers and predictors of patient survival with alcoholic cirrhosis

Management of Alcohol Misuse in Patients with Liver Diseases

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