Predictors of Improvement of Nonalcoholic Fatty Liver Disease in Morbidly Obese Patients Undergoing Bariatric Surgery(II)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver biochemistry tests in the world. NAFLD is a spectrum of chronic liver disease, ranging from simple steatosis, non-alcoholic steatohepatitis (NASH) to cirrhosis. NAFLD, the hepatic manifestation of the metabolic syndrome, is associated with central obesity, insulin resistance, hypertension, and hypertriglyceridemia. The prevalence rate of NAFLD has been reported to be 30–40% in men and 15–20% in women, up to 70% of people with type 2 diabetes mellitus (T2DM) and even surpassing 74% to 90% of morbidly obese patients with body mass index (BMI) higher than 35 kg/m2. For morbidly obese patients (BMI > 40 kg/m2 or BMI between 35 and 40 kg/m2 with comorbidities), weight loss through lifestyle modification may be difficult, and bariatric surgery (BS) is recommended for long-term maintenance of weight loss. In terms of liver injury, several studies have identified the benefits of bariatric surgery on NAFLD, based on liver biochemistry, steatosis, inflammation, fibrosis. However, unsuccessful weight loss has been reported in 10–30% of patients who have undergone BS. It is important to identify specific characteristics that can predict weight outcomes in morbidly obesity patients evaluated during a surgical weight loss program. Several studies indicate that age, gender, BMI, waist circumference, HbA1c, triglycerides, adipokines and the type of operation have been associated with weight outcomes. Transient elastography (FibroScan) appears to be a noninvasive, reproducible, and reliable method for predicting liver fibrosis. A new transient elastography probe (XL) for liver stiffness measurement has been proposed to overcome these limitations for patients who are overweight or obese. However, the diagnostic accuracy of LSM by transient elastography in morbidly obese patients underwent bariatric surgery remain to be validated. Current estimates are that approximately 25-30% of people with NAFLD develop NASH and development of hepatic fibrosis occurs in 40–50% of patients with NASH. Although the major risk factors for hepatic fat and hepatic fibrosis development in NAFLD are well established (e.g., age >50 years, obesity, insulin resistance, T2DM, hypertension, hyperlipidemia, metabolic syndrome, and the patatin-like phospholipase domain-containing 3 (PNPLA3) I148M polymorphism), the pathological mechanisms by which each of these risk factors cause NAFLD progression are less well understood. The Gene Expression Omnibus (GEO) is a database repository of sequence- and array-based data. We would use the keywords“bariatric surgery",“diabetes",“nonalcoholic fatty liver disease” to search the GEO repository. We would select differentially expressed genes between the NAFLD and no NAFLD groups, the DM and no DM groups which exhibited a 1.5-fold change and a P value of <0.05 to investigate NAFLD and DM overlapping gene signature. The primary aims of this prospective cohort study would evaluate the predictive factors of successful weight reduction, NAFLD and NASH improvement in a large cohort of morbidly obese patients undergoing bariatric surgery. Secondarily, the diagnostic accuracy of noninvasive serum markers, Doppler ultrasonography and transient elastography would be validated. Thirdly, we would conduct gene expression analyses to elucidate biological pathways underlying NAFLD phenotypes in this unique cohort.