Review Article Nonalcoholic Fatty Liver Disease (nafld) - a Disease of New Era

Non-alcoholic fatty liver disease (NAFLD) is the term used to describe the alcohol-like liver injury that occurs in the absence of alcohol abuse (alcohol consumption of over 20 g/day excludes the condition). It includes a range of histological abnormalities including simple steatosis or fatty liver, non-alcoholic steatohepatitis (NASH) and NAFLD induced cirrhosis. Its increasing prevalence in western countries, the diagnostic difficulties by noninvasive tests, and the possibility of progression to advanced fibrosis and even cirrhosis make NASH a challenge for physicians. NASH is frequently associated with type 2 diabetes and the metabolic syndrome, and several genetic and acquired factors are involved in its pathogenesis. Insulin resistance plays a central role in the development of a steatotic liver, which becomes vulnerable to additional injuries. Several cyclic mechanisms leading to self-enhancement of insulin resistance and hepatic accumulation of fat have been recently identified. Excess intracellular fatty acids, oxidant stress, tumor necrosis factor, and mitochondrial dysfunction are causes of hepatocellular injury, thereby leading to disease progression and to the establishment of NASH. Intestinal bacterial overgrowth also plays a role, by increasing production of endogenous ethanol and proinflammatory cytokines. Therapeutic strategies aimed at modulating insulin resistance, managing risk factors, including reduction of weight normalizing lipoprotein metabolism, and down regulating inflammatory mediators with probiotics have promising potential. 1. Assistant Professor of Medicine, BSMMU. 2. Assistant Professor of Pharmacology, Pioneer Dental College. 3. Junior Consultant, Shibpur Health complex, Narsingdhi. 4. Associate Professor of Medicine, BSMMU. 5. Professor & Chairman, Department of Medicine, BSMMU. Introduction NAFLD comprises a spectrum of liver disease characterized from simple fatty liver (macrovascular fatty change), to nonalcoholic steatohepatitis (NASH), and to cirrhosis in absence of alcohol consumption in amounts considered detrimental to the liver1. In 1980, Dr. J. Ludwig from the Mayo Clinic in Rochester, Minnesota was the first to coin the term NASH. Synonyms of NASH are pseudoalcoholic hepatitis, alcohol-like hepatitis, fatty liver hepatitis, steatonecrosis, and diabetic hepatitis. Cryptogenic cirrhosis is a common cause of liverrelated morbidity and mortality in USA. NAFLD is now recognized as the most common cause of cryptogenic cirrhosis2. NAFLD affects 10 to 24% of general population in various countries. The prevalence increases to 57.5%3 to 74%4 in obese persons. NAFLD affects 2.6% of children and 22.5% to 52.8% of obese children5. The prevalence of T2 Diabetes Mellitus varied between 10 to 75% and the prevalence of hyperlipidemia varied between 20 to 92 %6. Staging / spectrum of NAFLD NAFLD begins with fatty liver, progressing through NASH, and ending with cirrhosis. Fatty liver (steatosis), a harmless condition, is characterized by accumulation of fat in the liver cells without inflammation or scarring. Fatty liver is defined as fat, largely triglyceride exceeding 5% of the liver weight. When the fat content in the liver is 10%, fat begins to appear in many hepatocytes, and exceeds 30% of the weight; almost all of the hepatocytes contain a large drop of fat. It can be roughly estimated by how much of the acinus has fat laden hepatocytes; the involvement is characterized as mild for the pervienular third only, moderate for two-thirds, and severe for the entire acinus7. Only a fraction of patients with simple fatty liver will develop NASH, which involves fat accumulation J MEDICINE 2007; 8 : 17-27