1. Introduction Over the past decades, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) have been the leading causes of liver disease in Western countries. While the incidence of other chronic liver diseases has remained stable or even declined over the past two decades, the incidence of NAFLD has doubled. Recent data have demonstrated that the prevalence of NAFLD and NASH in the Middle East, the Far East, Africa, the Caribbean, and Latin America is similar to that in Western countries. NAFLD is a state of excessive triglyceride accumulation (steatosis), of which NASH is a subgroup, and is characterized by hepatocellular injury, inflammation, and excessive fat accumulation. there is little histologic difference between NASH and alcoholic steatohepatitis. purely steatoinflammatory disease is not associated with a significant short-term increase in morbidity (morbidity and mortality), but the progression to NASH increases the risk of cirrhosis, liver failure, and hepatocellular cancer. However, progression to NASH increases the risk of cirrhosis, liver failure, and hepatocellular carcinoma. The exact pathogenesis of NASH has not been elucidated and varies in almost every patient. Although pathogenesis is most associated with insulin resistance, obesity, and the metabolic syndrome, not all patients with these conditions have NAFLD and/or NASH, and not all patients with NAFLD and/or NASH experience these conditions.NASH can also lead to cirrhosis, liver failure, and hepatocellular carcinoma. Note: There are no definitive treatments with evidence-based clinical guidelines, and data from prospective randomized double-blind controlled studies are not yet available to support guideline development. Given the limited resources in different regions, this global guideline aims to provide the best clinical pathways for diagnosis and treatment from experts around the world. Epidemiology NASH is an increasingly prevalent chronic liver disease worldwide and is closely related to diabetes and obesity (with similar prevalence rates). The global obese population is estimated to be 1.46 billion. In the United States, nearly 6 million adults may progress to NASH, of which approximately 600,000 progress to NASH-related cirrhosis. There are also significant cultural and regional differences in the prevalence of obesity. In most Western countries, women, in particular, are favored to be thin and have a small percentage of body fat. In other countries, however, obesity is a symbol of attractiveness and success. In the United States, obesity is particularly prevalent among low-income people, mainly due to a high dependence on a high-fat, calorie-rich fast-food diet (junk food). However, in many poor countries, obesity rates are highest among the well-educated and affluent (Table 1). 3.Diagnostic strategies for NASH NASH is the most severe histologic manifestation of NAFLD and is defined as an enrichment of fat in the liver of more than 5% of the liver weight. The diagnostic and staging criteria for NASH are still controversial. Insulin resistance associated with obesity is central in the pathogenesis of NAFLD. In addition, peroxic stress and cytokines, which are important pathogenic factors, combine to contribute to the progression of steatosis and liver damage in genetically susceptible individuals. The disease can persist asymptomatically for many years or progress to cirrhosis and hepatocellular carcinoma. NASH and liver enzyme testing should be considered in the presence of the following conditions: hypertension, type 2 diabetes, sleep apnea, positive family history, non-black ethnicity, obesity, high blood cholesterol, and an inactive lifestyle (Figures 1-3).The diagnostic grading of patients with NAFLD and/or NASH is shown in Table 2. NOTE: There are no noninvasive tests available to rule out other possible underlying diseases or for disease staging (prognosis). It should be noted that NAFLD and/or NASH is a diagnosis of exclusion, and liver biopsy is commonly used to establish the diagnosis, stage the disease, rule out other liver diseases, and decide on invasive treatment. 4. MANAGEMENT 4.1 Treatment Options for NASH 4.1.1 Treatment of Metabolic Status Appropriate control of risk factors such as diabetes mellitus, hyperlipidemia, and cardiovascular risk factors is recommended. Studies have shown that histologic improvement in NASH can be obtained with atorvastatin and pravastatin. NAFLD patients with dyslipidemia may be treated with statins. Patients with underlying liver disease did not show any other statin drug toxicity. Severe hepatocellular toxicity due to statins is virtually nonexistent. Note: There are no approved drugs based on solid evidence for the treatment of NAFLD and/or NASH. 4.1.2 Improve insulin sensitivity: reduce body mass The decisive measure in the approach to reversing the progression of NAFLD and/or NASH is lifestyle change. 4.1.3 Diet Based on the patient’s age and gender, the goal is to reduce body mass by 5-10% and to reduce normal dietary calorie intake by 25% (approximately 2500 calories/d). Appropriately tight calorie control (along with adjustments in nutrient composition) is more effective than a very low calorie diet. Attention should be paid to the role of low-calorie diets and the recommendations regarding food groups, avoiding fructose and trans fats in soft drinks and fast foods, and increasing omega-3/omega-6 polyunsaturated fatty acids in the diet. However, patients may have difficulty adhering to it, and many experience rebound in body mass once they give it up. 4.1.4 Exercise Exercise (to 60% ~70% of the upper age-based heart rate limit) should be encouraged 3 ~4 times per week. The effects of dietary and exercise modifications should be monitored after 6 months. If ineffective, additional treatment options (e.g., medications) may be considered. 4.1.5 Bariatric Surgery May be beneficial in morbidly obese patients. Again, it is emphasized that surgery should be considered early and is not possible if the patient has pre-existing cirrhosis. A limited number of studies have shown that liver disease, metabolic syndrome and insulin resistance can be significantly improved in patients after successful bariatric surgery. Drugs for insulin resistance such as thiazolidinediones and metformin, although approved for diabetes, are not approved for NAFLD/NASH and should be considered for use empirically in the clinic (more information can be obtained from the literature and used after careful discussion). 4.2 Antioxidant and Antifibrotic Drugs Antioxidant and antifibrotic drugs (e.g., vitamin E and hexoketone cotinine) are not yet approved for use in NAFLD/NASH.There are only relatively limited research data (no double-blind controlled trials) to support their use, and therefore they should only be considered for empirical use. The therapeutic classification is shown in Table 3. 5. CONCLUSION NAFLD and NASH remain an important public health problem, and are equally prevalent in rich and poor countries. Screening for NASH and progressive liver disease in the general population is not supported by effective evidence. A diagnosis of NASH should be considered in all patients with relevant risk factors. Not all patients with risk factors will develop NAFLD and/or NASH, and not all patients with NASH have typical associated risk factors. Not every patient with fatty liver disease requires invasive human therapy. All patients should modify their diet and engage in exercise. Liver biopsies should be planned for those patients with NASH and/or other risk factors for liver disease. Patients with NASH-related risk factors or NASH should first be treated with diet and exercise. Vitamin E or hexacosanol can be used in these patients. Empirical treatment should be considered only for patients who have not lost 5% to 10% of their body mass after 6 to 12 months of correct lifestyle modification. Bariatric surgery should be considered in patients who have failed all of these approaches and should precede progression to cirrhosis. Liver transplantation is effective in patients who meet criteria for liver failure; however, NASH can recur after transplantation and morbidly obese patients may refuse surgery. NAFLD and NASH are also growing problems in pediatric patients, including those younger than 10 years of age. In conclusion, NAFLD and NASH are diagnoses of exclusion and require careful consideration of other diseases. Just as NASH cannot be diagnosed on its own based on clinical data, histopathology does not accurately differentiate between alcoholic and nonalcoholic, although it can demonstrate the presence of steatohepatitis lesions.