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1. Introduction
Nonalcoholic fatty liver disease (NAFLD) is reported to be the most common liverdisease, increasing in prevalence in Western countries as well as in Japan because of the raising prevalence of obesity [1, 2]. NAFLD shows a wide disease spectrum ranging from simple steatosis to steatohepatitis and finally to cirrhosis. Approximately 3% of the patients who have NAFLD will develop cirrhosis [3]. The main pathophysiological problem in NAFLD patients is insulin resistance. Thus, there is a clear association between NAFLD and metabolic syndrome which induces type 2 diabetes mellitus (DM), obesity, hypertension, and dyslipidemia [4]. Improvement of insulin resistance and sensitivity has therapeutic effect in preventing the progression of NAFLD because the accumulation of triglycerides in hepatocytes is considered to be the first step in the current two-hit theory of the pathophysiological development of NAFLD [5]. Several studies indicated that improving insulin resistance and sensitivity would reduce fatty liver change and might prevent the second step of hepatocytes injury due to oxidative stress [6–8].
Glucagon like peptide-1 (GLP-1) is a naturally existing incretin hormone with a potent blood-glucose reducing action only during hyperglycemia because it induces insulin secretion and reduces glucagon secretion in a glucose-dependent mechanism [9]. In addition, GLP-1 prolongs gastric emptying and induces satiety, leading to decreased energy intake and body weight [10, 11]. Therefore, GLP-1 has a great potential among type 2 DM patients. However, its half-life is extremely short because GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4) [9]. Liraglutide, one of the GLP-1 analogues, has 97% aminoacid sequence identity to native human GLP-1 and an acyl side-chain attachment, which makes it bind to albumin. These small structural differences prolong the half-life of GLP-1 to 13 hours, making it possible for once daily administration [12]. Several studies showed that liraglutide was well tolerated, improved glycaemic control with a low risk of hypoglycemia, improved functions of beta-cell, and was associated with body weight reduction [13]. The receptors of GLP-1 analogue also exist in human hepatocytes and administration of GLP-1 analogue reported to directly reduce liver steatosis and fibrosis in