The Global Nonalcoholic Fatty Liver Disease Epidemic: What a Radiologist Needs to Know

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disorders from a benign steatosis to hepatocellular carcinoma (HCC). Metabolic syndrome, mainly obesity, plays an important role, both as an independent risk factor and in the pathogenesis of NAFLD. With the progressive epidemics of obesity and diabetes mellitus, the prevalence of NAFLD and its associated complications is expected to increase dramatically. Therapeutic strategies for treating NAFLD and metabolic syndrome, particularly obesity, are continuously being refined. Their goal is the prevention of NAFLD by the management of risk factors, prevention of progression of the disease, as well as management of complications, ultimately preventing morbidity and mortality. Optimal management of NAFLD and metabolic syndrome requires a multidisciplinary collaboration between the government as well as the health system including the nutritionist, primary care physician, radiologist, hepatologist, oncologist, and transplant surgeon. An awareness of the clinical presentation, risk factors, pathogenesis, diagnosis, and management is of paramount importance to a radiologist, both from the clinical perspective as well as from the imaging standpoint. With expertise in imaging modalities as well as minimally invasive percutaneous endovascular therapies, radiologists play an essential role in the comprehensive management, which is highlighted in this article, with cases from our practice. We also briefly discuss transarterial embolization of the left gastric artery (LGA), a novel method that promises to have an enormous potential in the minimally invasive management of obesity, with details of a case from our practice.

[1]  D. Marzio,et al.  Concepts and Treatment Approaches in Nonalcoholic Fatty Liver Disease , 2014 .

[2]  L. Hebbard,et al.  Non alcoholic steatohepatitis a precursor for hepatocellular carcinoma development. , 2014, World journal of gastroenterology.

[3]  B. Cha,et al.  Pathogenesis and therapeutic approaches for non-alcoholic fatty liver disease. , 2014, World journal of hepatology.

[4]  A. Gunn,et al.  A Preliminary Observation of Weight Loss Following Left Gastric Artery Embolization in Humans , 2014, Journal of obesity.

[5]  S. Park,et al.  Radiologic evaluation of nonalcoholic fatty liver disease. , 2014, World journal of gastroenterology.

[6]  Chao-Long Chen,et al.  Interventional radiology in living donor liver transplant. , 2014, World journal of gastroenterology.

[7]  K. Flegal,et al.  Prevalence of childhood and adult obesity in the United States, 2011-2012. , 2014, JAMA.

[8]  Q. Anstee,et al.  Non-alcoholic fatty liver disease: a practical approach to treatment , 2014, Frontline Gastroenterology.

[9]  Laurent Castera,et al.  Noninvasive evaluation of NAFLD , 2013, Nature Reviews Gastroenterology &Hepatology.

[10]  W. Wassef,et al.  Bariatric procedures: an update on techniques, outcomes and complications , 2013, Current opinion in gastroenterology.

[11]  V. Wong,et al.  Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a randomized controlled trial. , 2013, Journal of hepatology.

[12]  G. Tarantino,et al.  What about non-alcoholic fatty liver disease as a new criterion to define metabolic syndrome? , 2013, World journal of gastroenterology.

[13]  A. Gamst,et al.  Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis. , 2013, Radiology.

[14]  N. Kipshidze,et al.  FIRST–IN–MAN STUDY OF LEFT GASTRIC ARTERY EMBOLIZATION FOR WEIGHT LOSS , 2013 .

[15]  S. Stinnett,et al.  Bariatric embolization for suppression of the hunger hormone ghrelin in a porcine model. , 2013, Radiology.

[16]  M. Davies,et al.  Transjugular intrahepatic portosystemic shunts in liver transplant recipients: technical analysis and clinical outcome. , 2013, AJR. American journal of roentgenology.

[17]  H. Cotrim,et al.  Sonographic hepatorenal ratio: A noninvasive method to diagnose nonalcoholic steatosis , 2013, Journal of clinical ultrasound : JCU.

[18]  Y. Hiasa,et al.  Real‐time tissue elastography for evaluation of hepatic fibrosis and portal hypertension in nonalcoholic fatty liver diseases , 2012, Hepatology.

[19]  D. Torres,et al.  Treatment of nonalcoholic fatty liver disease: Role of dietary modification and exercise , 2012, Clinical liver disease.

[20]  M. Tschöp,et al.  Anti-obesity drugs: past, present and future , 2012, Disease Models & Mechanisms.

[21]  B. Neuschwander‐Tetri,et al.  Dietary trans-Fatty Acid Induced NASH is Normalized Following Loss of trans-Fatty Acids from Hepatic Lipid Pools , 2012, Lipids.

[22]  P. O'Neil,et al.  Randomized Placebo‐Controlled Clinical Trial of Lorcaserin for Weight Loss in Type 2 Diabetes Mellitus: The BLOOM‐DM Study , 2012, Obesity.

[23]  K. Cusi,et al.  The Diagnosis and Management of Non-alcoholic Fatty Liver Disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association , 2012, The American Journal of Gastroenterology.

[24]  A. Tsung,et al.  Outcomes of curative treatment for hepatocellular cancer in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease , 2012, Hepatology.

[25]  E. Finkelstein,et al.  Obesity and severe obesity forecasts through 2030. , 2012, American journal of preventive medicine.

[26]  Namkug Kim,et al.  Hepatic Fat Quantification: A Prospective Comparison of Magnetic Resonance Spectroscopy and Analysis Methods for Chemical-Shift Gradient Echo Magnetic Resonance Imaging With Histologic Assessment as the Reference Standard , 2012, Investigative radiology.

[27]  K. Rioux,et al.  The potential role of prebiotic fibre for treatment and management of non‐alcoholic fatty liver disease and associated obesity and insulin resistance , 2012, Liver international : official journal of the International Association for the Study of the Liver.

[28]  V. Wong,et al.  Diagnosis of liver fibrosis and cirrhosis using liver stiffness measurement: comparison between M and XL probe of FibroScan®. , 2012, Journal of hepatology.

[29]  Giovanni Simonetti,et al.  Liver elasticity in NASH patients evaluated with real-time elastography (RTE). , 2012, Ultrasound in medicine & biology.

[30]  G. Teng,et al.  Ghrelin Suppression and Fat Loss after Left Gastric Artery Embolization in Canine Model , 2012, CardioVascular and Interventional Radiology.

[31]  R. Levine,et al.  A phase 2, randomized, double‐blind, placebo‐controlled study of GS‐9450 in subjects with nonalcoholic steatohepatitis , 2012, Hepatology.

[32]  A. Pollett,et al.  Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients , 2012, Hepatology.

[33]  G. Nguyen,et al.  Increased perioperative mortality following bariatric surgery among patients with cirrhosis. , 2011, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[34]  S. Reeder,et al.  Quantitative assessment of liver fat with magnetic resonance imaging and spectroscopy , 2011, Journal of magnetic resonance imaging : JMRI.

[35]  J. Heimbach,et al.  Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. , 2011, Gastroenterology.

[36]  Ned C. Rouze,et al.  Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease. , 2011, Journal of hepatology.

[37]  A. Baranova,et al.  Systematic review: the epidemiology and natural history of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis in adults , 2011, Alimentary pharmacology & therapeutics.

[38]  P. Hayes,et al.  A case‐controlled study of the safety and efficacy of transjugular intrahepatic portosystemic shunts after liver transplantation , 2011, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[39]  R. Ehman,et al.  Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography. , 2011, Radiology.

[40]  S. Park,et al.  Biopsy-proven nonsteatotic liver in adults: estimation of reference range for difference in attenuation between the liver and the spleen at nonenhanced CT. , 2011, Radiology.

[41]  J. Bruix,et al.  Management of hepatocellular carcinoma: An update , 2011, Hepatology.

[42]  A. Fodor,et al.  Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. , 2011, Gastroenterology.

[43]  C. Lee,et al.  Association Between Body Composition and Pulmonary Function in Elderly People: The Korean Longitudinal Study on Health and Aging , 2011, Obesity.

[44]  P. Newsome,et al.  Systematic review: the diagnosis and staging of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis , 2010, Alimentary pharmacology & therapeutics.

[45]  J. DeLany,et al.  Effects of diet and physical activity interventions on weight loss and cardiometabolic risk factors in severely obese adults: a randomized trial. , 2010, JAMA.

[46]  S. Møller EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. , 2010, Journal of hepatology.

[47]  R. Ehman,et al.  Magnetic resonance elastography: A review , 2010, Clinical anatomy.

[48]  B. Neuschwander‐Tetri,et al.  Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. , 2010, The New England journal of medicine.

[49]  Manal M. Hassan,et al.  Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma , 2010, Cancer.

[50]  Seong Ho Park,et al.  Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. , 2010, Journal of hepatology.

[51]  G. Klintmalm,et al.  Nonalcoholic fatty liver disease after liver transplantation for cryptogenic cirrhosis or nonalcoholic fatty liver disease , 2010, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[52]  D. Tiniakos,et al.  Serum markers of hepatocyte apoptosis: Current terminology and predictability in clinical practice , 2010, Hepatology.

[53]  T. Barrientos-Gutiérrez,et al.  Bariatric surgery for non-alcoholic steatohepatitis in obese patients. , 2010, The Cochrane database of systematic reviews.

[54]  P. Fontes,et al.  Recurrent disease following liver transplantation for nonalcoholic steatohepatitis cirrhosis , 2009, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[55]  H. Tilg,et al.  Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. , 2009, Journal of hepatology.

[56]  E. Finkelstein,et al.  Annual medical spending attributable to obesity: payer-and service-specific estimates. , 2009, Health affairs.

[57]  K. Imanaka,et al.  Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis , 2009, Journal of Gastroenterology.

[58]  F. Pattou,et al.  Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. , 2009, Gastroenterology.

[59]  Zamir Halpern,et al.  Diagnostic value of a computerized hepatorenal index for sonographic quantification of liver steatosis. , 2009, AJR. American journal of roentgenology.

[60]  Thomas Wadden,et al.  When prevention fails: obesity treatment strategies. , 2009, The American journal of medicine.

[61]  L. Mogoantă,et al.  Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis. , 2009, World journal of gastroenterology.

[62]  G. Pacini,et al.  Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of fatty liver. , 2009, The American journal of clinical nutrition.

[63]  K. Kasturi,et al.  Effect of bariatric surgery on nonalcoholic fatty liver disease: systematic review and meta-analysis. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[64]  A. Diehl,et al.  Mechanisms of disease progression in nonalcoholic fatty liver disease. , 2008, Seminars in liver disease.

[65]  F. Marra,et al.  Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis , 2008, Hepatology.

[66]  Johan Auwerx,et al.  Targeting bile-acid signalling for metabolic diseases , 2008, Nature Reviews Drug Discovery.

[67]  G. Davis,et al.  Hepatocellular Carcinoma: Management of an Increasingly Common Problem , 2008, Proceedings.

[68]  J. Mancero,et al.  Liver transplantation for subacute hepatocellular failure due to massive steatohepatitis after bariatric surgery , 2008, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[69]  H. Kirikoshi,et al.  Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD). , 2008, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[70]  I. Guha,et al.  Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: Validating the European Liver Fibrosis Panel and exploring simple markers , 2007, Hepatology.

[71]  P. Everest The Enterobacteria, 2nd Edition , 2007, Gut.

[72]  J. German,et al.  Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. , 2007, The American journal of clinical nutrition.

[73]  S. Park,et al.  Unenhanced CT for assessment of macrovesicular hepatic steatosis in living liver donors: comparison of visual grading with liver attenuation index. , 2007, Radiology.

[74]  B. Barnett,et al.  Catheter-directed gastric artery chemical embolization for modulation of systemic ghrelin levels in a porcine model: initial experience. , 2007, Radiology.

[75]  Xiaohong Joe Zhou,et al.  Measurement of liver fat content using selective saturation at 3.0 T , 2007, Journal of Magnetic Resonance Imaging.

[76]  P. Puvanachandra,et al.  Hepatology outpatient service provision in secondary care: a study of liver disease incidence and resource costs. , 2007, Clinical medicine.

[77]  A. Halpern,et al.  Effects of bariatric surgery on nonalcoholic fatty liver disease: Preliminary findings after 2 years , 2007, Journal of gastroenterology and hepatology.

[78]  Z. Younossi,et al.  Epidemiology and natural history of NAFLD and NASH. , 2007, Clinics in liver disease.

[79]  J. George,et al.  Fibrosis in genotype 3 chronic hepatitis C and nonalcoholic fatty liver disease: Role of insulin resistance and hepatic steatosis , 2006, Hepatology.

[80]  T. Saibara,et al.  7. 非アルコール性脂肪肝炎 (NASH) の診断と治療 , 2006 .

[81]  Sang Won Lee,et al.  Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. , 2006, Radiology.

[82]  Benjamin M Yeh,et al.  Accuracy of liver fat quantification at MR imaging: comparison of out-of-phase gradient-echo and fat-saturated fast spin-echo techniques--initial experience. , 2005, Radiology.

[83]  G. Bedogni,et al.  Prevalence of and risk factors for nonalcoholic fatty liver disease: The Dionysos nutrition and liver study , 2005, Hepatology.

[84]  P. Giral,et al.  Sampling variability of liver biopsy in nonalcoholic fatty liver disease. , 2005, Gastroenterology.

[85]  O. Cummings,et al.  Design and validation of a histological scoring system for nonalcoholic fatty liver disease , 2005, Hepatology.

[86]  S. Olshansky,et al.  A potential decline in life expectancy in the United States in the 21st century. , 2005, The New England journal of medicine.

[87]  Claude Bouchard,et al.  Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. , 2004, The New England journal of medicine.

[88]  A. Gressner,et al.  Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. , 2004, Clinical chemistry.

[89]  S. Grundy,et al.  Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[90]  D. Schoenfeld,et al.  Measurement of free testosterone in normal women and women with androgen deficiency: comparison of methods. , 2004, The Journal of clinical endocrinology and metabolism.

[91]  H. El‐Serag,et al.  Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. , 2004, Gastroenterology.

[92]  P. Hayashi,et al.  Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis , 2003, American Journal of Gastroenterology.

[93]  R. Ross Advances in the application of imaging methods in applied and clinical physiology , 2003, Acta Diabetologica.

[94]  U. Settmacher,et al.  Diagnosis and treatment of arterial steal syndromes in liver transplant recipients , 2003, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[95]  Michael J Thun,et al.  Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. , 2003, The New England journal of medicine.

[96]  D. Allison,et al.  Years of life lost due to obesity. , 2003, JAMA.

[97]  C. Wai,et al.  Pitfalls in interpreting liver biopsy results: The story of the blind men and the elephant , 2002, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[98]  Erick M Remer,et al.  The utility of radiological imaging in nonalcoholic fatty liver disease. , 2002, Gastroenterology.

[99]  E. Dellinger,et al.  Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. , 2002, The New England journal of medicine.

[100]  R. Batterham,et al.  Ghrelin causes hyperphagia and obesity in rats. , 2001, Diabetes.

[101]  Margaret S. Wu,et al.  Role of AMP-activated protein kinase in mechanism of metformin action. , 2001, The Journal of clinical investigation.

[102]  L. Bianchi,et al.  Liver biopsy in elevated liver functions tests? An old question revisited. , 2001, Journal of hepatology.

[103]  P. Thuluvath,et al.  Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: A case‐control study , 2000, Hepatology.

[104]  H. Adami,et al.  Role of diabetes mellitus in the etiology of hepatocellular carcinoma. , 2000, Journal of the National Cancer Institute.

[105]  M. Kirsch Re: Daniel et al.: liver biopsy without clear indication or informed consent. , 2000 .

[106]  H. Cortez‐Pinto,et al.  Non-alcoholic fatty liver: another feature of the metabolic syndrome? , 1999, Clinical nutrition.

[107]  C. Day,et al.  Steatohepatitis: a tale of two "hits"? , 1998, Gastroenterology.

[108]  M Linet,et al.  Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. , 1997, Journal of the National Cancer Institute.

[109]  H. Adami,et al.  Excess risk of primary liver cancer in patients with diabetes mellitus. , 1996, Journal of the National Cancer Institute.

[110]  R. Groszmann,et al.  American association for the study of liver diseases , 1992 .

[111]  M. Dumont,et al.  European Association for the Study of the Liver , 1971 .

[112]  M. Kroh,et al.  Bariatric surgery in patients with liver cirrhosis. , 2013, Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery.

[113]  T. Abribat,et al.  Clinical perspectives for ghrelin-derived therapeutic products. , 2013, Endocrine development.

[114]  Joel Z Stengel,et al.  Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. , 2011, Gastroenterology.

[115]  H. Cotrim,et al.  Liver: Does bariatric surgery reduce the severity of NAFLD? , 2010, Nature Reviews Gastroenterology &Hepatology.

[116]  Riitta Parkkola,et al.  Nonalcoholic fatty liver disease: rapid evaluation of liver fat content with in-phase and out-of-phase MR imaging. , 2009, Radiology.

[117]  Tetsuji Sato,et al.  The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. , 2006, Annals of internal medicine.

[118]  D. Katz Competing dietary claims for weight loss: finding the forest through truculent trees. , 2005, Annual review of public health.

[119]  David A. Sass,et al.  Nonalcoholic Fatty Liver Disease: A Clinical Review , 2005, Digestive Diseases and Sciences.

[120]  S. Woods,et al.  Gastrointestinal hormones and food intake. , 2005, Gastroenterology.

[121]  M. Kirsch Re: Daniel et al.: liver biopsy without clear indication or informed consent , 2000, American Journal of Gastroenterology.

[122]  Leonard H. Epstein,et al.  Overweight, obesity, and health risk. , 2000, Archives of internal medicine.

[123]  H. Cortez‐Pinto,et al.  Non-alcoholic fatty liver: another feature of the metabolic syndrome? , 1999, Clinical nutrition.

[124]  T. Wadden,et al.  Treatment of obesity by very low calorie diet, behavior therapy, and their combination: a five-year perspective. , 1989, International journal of obesity.