Clinics in Liver Disease RSS feed: Current Issue. This quarterly periodical devotes each issue to a single topic in liver disease. Comprehensive, state-of-the-art coverage provides current, practical information on the diagnosis and treatment of conditions affecting the liver and biliary tract. Issues incorporate new and experimental therapies that have resulted from the multitude of advances in hepatology research. At a time when hepatology is changing rapidly, Clinics in Liver Disease serves as a compelling and current reference to update readers between editions of hepatology and gastroenterology books. http://www.liver.theclinics.com/?rss=yesElsevier Inc.en © 2009 Published by Elsevier Inc. All rights reserved. Clinics in Liver Disease1089-3261134November 2009 © 2009 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.liver.theclinics.com/article/PIIS1089326109000713/abstract?rss=yesContents10.1016/S1089-3261(09)00071-3Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8viixhttp://www.liver.theclinics.com/article/PIIS1089326109000725/abstract?rss=yesForthcoming issues10.1016/S1089-3261(09)00072-5Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8xixihttp://www.liver.theclinics.com/article/PIIS1089326109000658/abstract?rss=yes Our understanding of nonalcoholic fatty liver disease (NAFLD) has grown exponentially in the past 29 years since Ludwig and colleagues first described the histologic lesions that comprise a subset of NAFLD known as nonalcoholic steatohepatitis (NASH). A recent PubMed search using the term “nonalcoholic fatty liver disease” generated 1475 articles published since 1980, of which 1405 were published since the year 2000. Concern for this liver disease is validated, as NAFLD is becoming, if it has not already become, the number one chronic liver disease in this country and in many others around the world. As the prevalence of obesity and diabetes, both of which are characterized by impairment in insulin signaling, continues to rise, so will the prevalence of NAFLD. We as health care providers are now faced with an epidemic.PrefaceStephen A. Harrison10.1016/j.cld.2009.08.001Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8xiiixivhttp://www.liver.theclinics.com/article/PIIS1089326109000579/abstract?rss=yesNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition in many parts of the world. This article describes the epidemiology and natural history of this disorder. It also describes current diagnostic and treatment methods and describes future implications NAFLD may have.Epidemiology and Natural History of Non-Alcoholic SteatohepatitisCurtis K. Argo, Stephen H. Caldwell10.1016/j.cld.2009.07.005Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8511531http://www.liver.theclinics.com/article/PIIS1089326109000609/abstract?rss=yesCurrent imaging methodologies can detect steatosis with increasing accuracy but cannot detect inflammation or pre-cirrhotic fibrosis or remodeling of the liver parenchyma. Imaging also cannot assess types or localization of hepatic steatosis. With the increased use of rodents to study NAFLD/NASH, careful analysis or reading highlights the fact that liver tissue evaluations reported in many of the popular animal models of NAFLD/NASH often do not imitate many of the significant aspects of the human disease, despite similar terminology applied by investigators. This review will focus on the findings in human disease.Histopathology of Non-Alcoholic Fatty Liver DiseaseElizabeth M. Brunt10.1016/j.cld.2009.07.008Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8533544http://www.liver.theclinics.com/article/PIIS1089326109000610/abstract?rss=yesIt is well established that the development of NAFLD and NASH are closely linked to an excess flow of free fatty acids (FFA) arising from dysfunctional/insulin resistant adipose tissue causing ectopic fat deposition in many organs. In the liver, when chronic lipid supply surpasses the metabolic ability to adapt it will induce hepatocellular damage as FFA are redirected into harmful pathways of non-oxidative metabolism with intracellular accumulation of toxic lipid-derived metabolites. Multiple mechanisms have been implicated including mitochondrial dysfunction, endoplasmic reticulum stress, and activation of multiple inflammatory pathways. Understanding the role of insulin resistance and lipotoxicity in NASH as part of a broader metabolic disorder is likely to assist practitioners in the successful management of these challenging patients.Role of Insulin Resistance and Lipotoxicity in Non-Alcoholic SteatohepatitisKenneth Cusi10.1016/j.cld.2009.07.009Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8545563http://www.liver.theclinics.com/article/PIIS1089326109000555/abstract?rss=yesNon-alcoholic fatty liver disease (NAFLD), one of the commonest causes of chronic liver disease in the United States, represents several overlapping clinicopathological states, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Although dysregulated lipid accumulation occurs across the spectrum of NAFLD, features of liver cell injury, such as hepatocyte ballooning, cytoskeletal changes (Mallory-Denk bodies), and hepatocyte apoptosis, occur predominantly in NASH and distinguish NASH from simple steatosis. Indeed, NASH is a more serious form of liver damage because cirrhosis and hepatocellular carcinoma are potential outcomes of NASH. Meanwhile, cirrhosis and hepatocellular carcinoma rarely occur in individuals with simple steatosis. Hepatic injury and apoptosis that occur in adults are often dysregulated and accompanied by the accumulation of immune cells, which produce cytokines and growth factors that drive chronic inflammation and may result in fibrosis. This article summarizes the process of apoptosis and roles of putative cytokines in progressive NAFLD.Apoptosis and Cytokines in Non-Alcoholic SteatohepatitisWing-Kin Syn, Steve S. Choi, Anna Mae Diehl10.1016/j.cld.2009.07.003Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8565580http://www.liver.theclinics.com/article/PIIS1089326109000567/abstract?rss=yesThe endoplasmic reticulum (ER) is the key cellular organelle involved in protein homoeostasis. The unfolded protein response (UPR) is a fundamental cellular process triggered by ER stress because of lack of ATP or primary ER dysfunction. The UPR is activated and dysregulated in non-alcoholic fatty liver disease (NAFLD). The UPR has been shown to be involved in both normal physiologic functions and the cellular response to a host of pathologic states. This article reviews the pathways by which the UPR unfolds and its potential role in the development and progression of NAFLD.Endoplasmic Reticulum Stress and the Unfolded Protein ResponseAshwani Kapoor, Arun J. Sanyal10.1016/j.cld.2009.07.004Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8581590http://www.liver.theclinics.com/article/PIIS1089326109000634/abstract?rss=yesNon-alcoholic fatty liver disease is the most common cause of chronic liver disease in the United States. The development of non-alcoholic steatohepatitis increases the risk for cirrhosis and its complications. The gold standard for diagnosis is liver biopsy, the costs and risks of which make it impractical. Some demographic factors, blood tests, and imaging studies can be used to predict a higher risk of steatohepatitis or advanced fibrosis, but are of limited sensitivity and specificity. More accurate predictors and scoring systems would allow identifying who would benefit most from liver biopsy and monitor disease progression and response to therapy.Predictors of Steatohepatitis and Advanced Fibrosis in Non-Alcoholic Fatty Liver DiseaseMangesh Pagadala, Claudia O. Zein, Arthur J. McCullough10.1016/j.cld.2009.07.011Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8591606http://www.liver.theclinics.com/article/PIIS1089326109000543/abstract?rss=yesNo imaging modality has yet been proven to reliably differentiate simple hepatic steatosis from steatohepatitis. This review focuses on the predominant non-nuclear imaging modalities available to clinicians at the present time. The key feature of the techniques outlined in this review that demonstrate the most interesting results have one thing in common: imaging is not performed in a passive manner but is undertaken as a method to investigate functional differences between simple hepatic steatosis and steatohepatitis based upon the current working model for pathogenesis and progression. The purpose of this article is to review the strengths and weakness of current clinical and experimental imaging modalities for noninvasive detection of NAFLD, with an emphasis on NASH.New Imaging Techniques for Non-Alcoholic SteatohepatitisJeffrey D. Browning10.1016/j.cld.2009.07.002Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8607619http://www.liver.theclinics.com/article/PIIS1089326109000622/abstract?rss=yesNon-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis are common complications of overnutrition and obesity. In the setting of worsening epidemics of obesity in developed and developing countries, the global prevalence and impact of NAFLD seems likely to increase. The large number of patients at risk will translate into major challenges for the liver transplant community, affecting donors and recipients. The comorbidities and hepatic effects of obesity and NAFLD present important new challenges in the management of donors and recipients. This article addresses some of these challenges.Fatty Liver and Liver TransplantationEdith Koehler, Kymberly Watt, Michael Charlton10.1016/j.cld.2009.07.010Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8621630http://www.liver.theclinics.com/article/PIIS1089326109000592/abstract?rss=yesPrimary liver cancer is the fifth most common malignancy worldwide and the third leading cause of cancer mortality. Non-alcoholic fatty liver disease is the most common cause of chronic liver disease in the United States encompassing a spectrum of entities marked by hepatic steatosis in the absence of significant alcohol consumption. Although simple steatosis follows a generally benign course, the more aggressive form, non-alcoholic steatohepatitis, can progress to cirrhosis and result in complications including hepatocellular carcinoma. A significant number of cases of hepatocellular carcinoma remain cryptogenic without known underlying chronic liver disease. It is increasingly recognized that non-alcoholic steatohepatitis likely accounts for a substantial portion of cryptogenic hepatocellular carcinoma.NASH and HCCJohn M. Page, Stephen A. Harrison10.1016/j.cld.2009.07.007Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8631647http://www.liver.theclinics.com/article/PIIS1089326109000580/abstract?rss=yesThis article reviews the rationale and data behind recommending lifestyle changes to prevent and reverse NASH, focusing specifically on changes that lead to increased physical activity in sedentary patients, changes in dietary habits, and decreased calorie consumption to achieve gradual and sustained weight loss in those who are overweight or obese. In a culture that values avoiding even minimal exertion these are not easy changes to make. Ultimately, the success of care providers in helping patients to recognize and overcome these barriers depends on a patient's motivation, but clinicians can be more persuasive and able to bolster this motivation when armed with a conviction based on data that establish this to be the best course of action for patients with NASH.Lifestyle Modification as the Primary Treatment of NASHBrent A. Neuschwander-Tetri10.1016/j.cld.2009.07.006Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8649665http://www.liver.theclinics.com/article/PIIS1089326109000531/abstract?rss=yesSpecific therapy for non-alcoholic steatohepatitis (NASH) is needed because of the potential severity of this liver disease. NASH is a recognized cause of cryptogenic cirrhosis and, increasingly, of hepatocellular carcinoma. Therefore, there is an unmet medical need for the therapy of NASH. This article discusses this therapy, with particular emphasis on pharmacologic therapy.Pharmacologic Therapy of Non-Alcoholic SteatohepatitisVlad Ratziu, Shira Zelber-Sagi10.1016/j.cld.2009.07.001Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8667688http://www.liver.theclinics.com/article/PIIS1089326109000646/abstract?rss=yesAs the worldwide obesity epidemic continues to increase, the prevalence of non-alcoholic fatty liver disease (NAFLD) and specifically non-alcoholic steatohepatitis (NASH) will become increasingly prominent. NASH will surpass chronic hepatitis C infection as the primary indication for orthotopic liver transplantation in the near future. With the evolution of surgical techniques, bariatric surgery is currently recognized as the most effective method for achieving sustained weight loss and reversing numerous comorbidities in severely obese individuals. This review focuses on the potential risks and benefits of bariatric surgery in subjects with NAFLD and explores its role in the management of NASH in the obese patient.Non-Alcoholic Fatty Liver Disease: Is Bariatric Surgery the Answer?Anjana A. Pillai, Mary E. Rinella10.1016/j.cld.2009.07.012Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8689710http://www.liver.theclinics.com/article/PIIS1089326109000737/abstract?rss=yesIndex10.1016/S1089-3261(09)00073-7Clinics in Liver Disease 13, 4 (2009)2009-11-01Clinics in Liver Disease2009-11-01134S1089-3261(09)X0004-8711719