Efficacy Observation Of Combined Application Of Metformin And UDCA In Treatment Of NAFLD

BackgroundNon-alcoholic fatty liver disease(NAFLD) refers to a clinical syndrome which is characterized by fatty degeneration and lipid accumulation of liver cells, but is unrelated to a history of excessive alcohol consumption. It consists of non-alcoholic simple fatty liver(NAFL), non-alcoholic steatohepatitis(NASH), and hepatic cirrhosis and cancer associated. As the development of society and change of life style, the morbidity of NAFLD is increasing year by year. In our country, NAFLD has become the second bigger liver disease inferior only to viral hepatitis. NAFLD is a metabolic disease which is closely related with insulin resistance(IR) and genetic susceptibility. As a part of metabolic syndrome, NAFLD can not only destroy liver function, but also promote the advance of cardiovascnlar and cerebrovascular diseases and reduce the life expectancy, for it is one of the most important dangerous factors of metabolic disorders and arteriosclerotic cardiovascular and cerebtovascular diseases. The pathogenesis of NAFLD is complex, and what is now widely accepted is the "Two Hits" theory. The first hit is fatty degeneration and lipid accumulation of liver cells induced by insulin resistance, and the second hit refers to the inflammation and necrosis of liver cells caused by oxidative stress and lipid peroxidation on the basis of the first hit. Up to now, drug therapy has been an important treatment, as with etiological treatment, deal with primary diseases, improvement of life style, and so on. Our research is to observe the effect of combined application of two drugs, metformin and ursodeoxycholic acid(UDCA), in treatment of NAFLD. ObjectiveWe tried to find the curative effect of combined application of metformin and UDCA in treatment of NAFLD, and analyse the pharmacological mechanisms of the two drugs.MethodsWe had chosen96patients with moderate or severe NAFLD from the outpatients and inpatients of Qianfoshan Hospital attached to Shandong University from2009to2011, according to the diagnostic criteria of NAFLD established by Fatty Liver and Alcoholic Liver Disease Study Group of the Chinese Liver Disease Association in2006. According to whether they were fat, the patients were divided into two groups. There were61patients in the obesity group, and35patients in the non-obesity group. Before the theropy, the height and weight of each patient had to be measured, and the body mass index(BMI) had to be calculated. Their blood was collected and the results of liver function and blood lipid test were record, which were represented respectively by alanine aminotransferase(ALT) and triglyceride(TG). Everyone participated in the research was inspected by B ultrasound or CT, and got a score according to the level of fatty degeneration of liver. Individuals with no fatty degeneration of liver got0point, mild ones got1point, moderate ones got2points, and severe ones got3points. Patients of the obesity group were given metformin0.5g bid and UDCA250mg bid, while those of non-obesity group were given metformin0.25g qd/bid and UDCA250mg bid. All the individuals were told to do proper exercises and control their diets. The patients measured their weight once a month, and make sure the body weight loss was less than3kg in the first month, and less than1.5kg per month in the follows. Liver function and blood lipid were tested every three months, as well as the level of fatty degeneration of liver inspected by B ultrasound or CT. Dosage of drugs could be adjusted according to the results, and the follow-up visit lasted for one year.ResultsAfter treatment of one year, clinical symptoms of both groups significantly improved. Compared with those before the treatment, BMI、ALT and TG level of patients of obesity group decreased significantly, as well as their scores of fatty liver. As for the non-obesity group, ALT level and the scores of fatty liver decreased significantly, while their BMI and TG level seemed not significantly different from that before the treatment.ConclusionOur research showed that combined application of metformin and UDCA was effective and safe for NAFLD. It was obvious that the liver function and the level of fatty degeneration of liver of all the patients improved. The therapy could also decreased BMI and blood lipid level of fat patients significantly, while might have little influence on those of the ones who were not obese.