Nonalcoholic fatty liver disease (NAFLD) is an emergent problem around the world, affecting various people in every age. Nonalcoholic fatty liver disease is the accumulation of fats in the liver. It represents a continuum of conditions characterized histologically by chiefly macro-vesicular heptic steatosis. NAFLD occurs to many individuals who are non-alcoholics. Accumulation of fats in the body may occur because of obesity, diabetes and other conditions. This condition is capable of growing to liver inflammation, scarring, and eventually cause liver failure. NAFLD is a nonalcoholic steatohepatitithis. Presently, nonalcoholic fatty liver disease is the fastest-rising sign for liver transplant. This paper, thus, provides a research about nonalcoholic fatty liver disease.
History of Discovery of NAFLD
The relationship of fibrosis in obese subjects and macrovesicular steatosis of liver with inflammatory changes have been known for several decades. According to several reports, it was largely ignored as a clinical entity. However, documentation of the development of liver failure in a number of patients because of surgical jejunoileal bypass for morbid obesity. It was easy to distinguish alcoholic hepatitis from mascular steatosis, ballooning degeneration, fibrosis, Mallory bodies, and hepatocyte necrosis. In most of the obese patients, hepatic lesions were considered to have neither undergone weight loss surgery nor abused alcohol. This led to the introduction of the term “non-alcoholic steatohepatitis” (NASH) to describe histologic finding in individuals who did not consume alcohol. Other synonyms that are used presently to describe this condition include fatty liver hepatitis, nonalcoholic steatonecrosis, and nonalcoholic fatty hepatitis.
A complete diagnosis of fatty liver disease ought to define the grades of the disease, etiology, and the histology. Traditionally, the definition of most fatty liver disorders, are either as alcoholic or as non-alcoholic. It is essential to note that NAFLD also incorporates NASH since it is associated with various etiological processes. This might be because NAFLD varies in regards to a given etiology. In terms of etiology, the use of term “nonalcoholic” in describing fatty liver disorder renders the condition heterogeneous. This renders the condition in a difficult situation to describe and unsatisfactory to study in various aspects. In short, there is no consensus as to how to classify fatty liver diseases.
Diagnosis of Fatty Liver Disease and Steatohepatitis by Histological Process
The main histologic feature of NAFLD is usually the presence of macrovesicular fatty changes in hepatocytes accomoanied by displacement of the nucleus to the edge of the cell. It is presently appreciated that various patients, only some of the features like Mallory bodies, ballooning disintegration, Rappaport zone III perisinusodal fibrosis, and principally lobular neutrophilic inflammation may be present. However, Mallory bodies are less present in NASH as compared to alcoholic steatohepatitis.
Symptoms of NAFLD
Just like many other types of chronic heart diseases, most patients suffering from NAFLD in cross-sectional studies are asymptomatic. The liver disease appears during either regular medical / laboratory check-ups or workup conditions such as diabetes, morbid obesity, or hypertension. In numerous asymptomatic subjects, elevated levels of serum alanine aminotrasferase (ALT) are usually discovered when a hepatic panel is ordered to monitor such patients under treatment with antihyperlipidemic drugs. Elevated levels of ALT or sonographic evidence of fatty liver is occasionally noticed during workup of assumed gallstone syndrome (Elizabeth et al 49). Elevation of ALT is usually caused by NAFLD, which is a heterogeneous disorder. The heterogeneity is formed by the variability in the definitions of the term “steatohepatitis” as well as diverse clinical association. The persistent elevation of ALT is noticed once hepatitis C that causes chronic liver diseases has been excluded. Symptoms of NAFLD are usually nonspecific when they occur. Another common symptom that does not usually correlate well with the severity of the histologic lesion is fatigue. Subjects may also experience discomfort on the right upper quadrant. This discomfort is typically a vague, nondescript aching character. Most patients experience symptoms indicative of serious liver disease. Such indicative symptoms may cause nausea, pruritus, and anorexia. Decompensated cirrhosis is indicated by symptoms such as the development of anasrca, variceal hemorrhage, ascites, or symptoms of hepatic encephalopathy. After some period when subject suffers, jaundice occurs because of non-alcoholic steatohepatitis (NASH), which is also indicative of advanced liver disease.
Physical signs of NAFLD
On physical examination of NAFLD, obesity is the common abnormality and it is usually present ranging from 30% to 100%. It is noteworthy that there are no pathognomonic signs of NASH. Hepatomegaly is the most common finding of liver disease, which has been reported on various subjects. However, a very small number of patients have stigmata of persistent liver malady. Amongst all the known stigmata, the presence of palmar erithema and spider nevi are very common in most subjects. Only patients with advanced cirrhosis experience asterixis, edema, signs of portal hypertension, and jaundice. As the liver disease becomes more advanced, muscle wasting may occur, but it is usually underestimated due to edema and pre-existing obesity.
Treatment of NAFLD
Takada G. et al (239) explains that before treating any condition, it is important to understand the natural history, safety of the therapeutic options, cost, and relative efficacy of the condition. As mentioned earlier, NASH is capable of progressing to cirrhosis, particularly, in the presence of bridging fibrosis. Also, the individuals with fat and ballooning integration and perisinusoidal fibrosis are likely at a greater risk for succession. Older people, particularly those with diabetes and severe obesity are at higher risk of being infected. Therefore, when considering a therapeutic option for any patient, it is important to keep the above factors in perspective. When this condition is not treated, therapeutic measures are usually directed towards correction of the risk factors for NASH. These risk factors include lessening deliverance of acids that are full of fat to the liver, insulin resistance, increased usage of drugs that have likely hepatoprotective result.
Treatment of Risk Factors
Various reports indicate that weight loss improves liver histology by a small margin. However, very few clinical trials approve weight control as a treatment measure for NAFLD. Overweight individuals with elevated aminotrasferase levels, weight control by at least 10% indicates correct aminotransferase activities that decrease hepatomegaly. Few studies confirm that obese subjects with NAFLD need to work on ways of losing weight because of wonderful benefits associated with loss of weight on cardiovascular risk profile. According to the National Heart, Lung, and Blood Institute (NHLBI) and National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) clinical guidelines for obesity management affirms that weight loss can only work for few adult subjects. Subjects with BMI are greater than 95th percentile or greater than 85th percentile and have obesity complication should be evaluated and treated. In the above mentioned category of patients, it is worth excluding endocrine and genetic disorders related to obesity.
Considerably, weight loss causes improvement in insulin sensitivity and cardiovascular risk profile. Very rapid weight loss may cause deterioration of steatohepatitis and impetuous liver failure. For liver dysfunction, it is important to monitor rapid weight loss monthly in patients with NAFLD. Another way of ensuring that there is considerable weight loss in patients with NAFLD, diet is an important element. Intake of saturated fats in the body can worsen insulin resistance whereas; dietary fiber improves insulin resistance.
b)Pharmacologic Management of Insulin Resistance
Given the fact that NASH relates to reduced insulin-mediated restraint of lypolysis, the denominator in this particular instance is insulin resistance. As a result, high serum-free oily acid uptake and corrosion is usually present in subjects with NASH. Moreover, the increased delivery of delivery of fatty acids may affect the process of insulin resistance.
Orlistat and sibutramine are some of the medications that are used for weight loss. For example orlistat inhibits pancreatic and gastric lipase, agents that are capable of absorbing long chain fatty acids and cholesterol. Orlistat reduces the absorption of fats to about 30%. However, unabsorbed fats are usually excreted in the stool. This treatment helps in reducing systolic blood pressure, fasting serum insulin, and reducing glucose levels. Even though this drug indicates encouraging results, randomized control trials of anti-obesity agents both have long and short-term effects. In addition, bariatric surgery is also prudent in improving conditions associated with NAFLD in morbidity obese patients. Bariatric surgery is remarkably important since patients lose and sustain weight loss through it.
It is evident that various genetically and environmentally responsive factors are likely to cause NAFLD and its simple development to NASH. The ‘two-hit-model,’ which is currently accepted, explains the pathogenesis of NAFLD/NASH. In that sense, it proposes that accumulation of fats in hepatocytes is prerequisite for second hit that is likely to induce inflammation and fibrosis. Accumulation of fats in the liver results in insulin resistance and continuous impairment of fatty acid metabolism, adipose tissue, and skeleton muscles. Dysfunction in several oxidation pathways within the hepatocyte leads to overproduction of reactive oxygen species (ROS) that is likely to result in lipids buildup, fibrogenesis, and swelling. There are significant risk factors associated with NAFLD/NASH. One of the risk factors is an increased MBI, which increases the chances of having liver fibrosis in children. In adults, visceral obesity is the most influential as compared to the total fat mass in predicting fatty liver disease. This is because visceral fat delivers free fatty acids (FFAs) that are also associated with insulin resistance that is a critical factor in pathogenesis of NAFLD. In most instances, peripheral insulin resistance promotes high circulating FFAs and also increased delivery of FFAs in the liver. Finally, the net result can therefore lead to a decreased secretion of Triglyceride from the liver as net accumulation of triglyceride in microcytic vacuoles as indicated in the diagram below.
Nonalcoholic fatty liver disease (NAFLD) is the major cause of liver-related morbidity globally. It is usually related to the presence of insulin resistance in the body of the subjects. According to the above research, there is considerable evidence that nonalcoholic fatty liver disease can progress to cirrhosis and finally liver failure. It is essential for physicians to check the presence NAFLD in individuals who are diabetic and overweight. It is worth noting that an established treatment of NAFLD is lacking. He further confirms that much of treatment measures are usually aimed at optimizing body weight in a controlled manner. Pharmacologists must therefore exercise the duty of defining pathogenesis of NAFLD come up with apt management measures.