1.Introduction
In the past decades, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepati-tis (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 decreased in the past 20 years, the incidence of NAFLD has doubled. Recent data demonstrate that the prevalence of NAFLD and NASH in the Middle East, Far East, Africa, 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 that presents with hepatocellular injury, inflammation, and excessive fat accumulation; there is little histological difference between NASH and alcoholic steatohepatitis. 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 metabolic syndrome, not all patients in these states have NAFLD and/or NASH, nor do all patients with NAFLD and/or NASH experience these states. nash can also lead to cirrhosis, liver failure, and hepatocellular carcinoma.
Note: There are no conclusive treatments with evidence-based clinical guidelines and no data from prospective randomized double-blind controlled studies to support guideline development. Given the limited resources available in different regions, this global guideline aims to provide the best clinical pathway for diagnosis and treatment from global experts.
2. 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. Nearly 6 million adults in the United States can progress to NASH, with approximately 600,000 progressing to NASH-related cirrhosis. Also, there are significant cultural and regional differences in the prevalence of obesity.
In most Western countries, women in particular prefer a slimmer and less fatty figure. However, in other countries, obesity is a symbol of attractiveness and success. In the United States, obesity is particularly prevalent among low-income people, mainly because of a high reliance on a high-fat and calorie fast-food diet (junk food). But in many poor countries, but is well educated affluent people obesity rate is the highest.
3.Diagnostic strategy of NASH
NASH is the most serious histological manifestation of NAFLD, which is defined as fat enrichment in the liver exceeding 5% of the weight of the liver. The diagnosis and staging criteria of NASH are still controversial.
Insulin resistance associated with obesity is central in the pathogenesis of NAFLD. In addition, peroxisomal stress and cytokines, which are important causative factors, also contribute to the progression of steatosis and liver damage in genetically susceptible individuals.
The disease can persist asymptomatic for many years or progress to cirrhosis and hepatocellular carcinoma. NASH and testing for liver enzymes should be considered in the presence of: hypertension, type 2 diabetes, sleep apnea, positive family history, non-black race, obesity, hyperlipidemia, and a physically inactive lifestyle. There are no non-invasive 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 determine the diagnosis, disease staging, exclude other liver diseases, and determine invasive treatment or not.
4. Treatment options for NASH
Treatment of metabolic status
Appropriate control of risk factors such as diabetes mellitus, hyperlipidemia and cardiovascular disease is recommended. Studies have shown that histological improvement of NASH can be obtained with atorvastatin and pravastatin. Patients with NAFLD with dyslipidemia can be treated with statins. Patients with underlying liver disease did not show any other statin toxicity. Serious hepatocellular toxicity due to statins is almost absent.
Note: There are no approved drugs based on solid evidence for the treatment of NAFLD and/or NASH.
Improving insulin sensitivity: reducing body mass
The decisive measure in the approach to reverse the progression of NAFLD and/or NASH is lifestyle change.
Diet
Depending on the patient’s age and gender, the goal is to reduce body mass by 5-10%, while reducing normal dietary caloric intake by 25% (approximately 2500 cal/d). Appropriate tight control of calories (with adjustment of nutrient composition) is more effective than a very low calorie diet. The role of low-calorie diets and recommendations for food groups should be noted, avoiding fructose and trans fats in soft drinks and fast foods, and increasing the amount of omega-3/omega-6 polyunsaturated fatty acids in the diet. However, it may be difficult for patients to adhere to the diet, and many patients experience a rebound in body mass once they give up.
Exercise
Exercise should be encouraged 3 to 4 times per week (up to 60% to 70% of the upper age-based heart rate). The effectiveness of diet and exercise modifications should be monitored after 6 months. If ineffective, additional treatment options (e.g., medications) may be considered.
Bariatric surgery
May be beneficial for morbidly obese patients. Again, surgery should be considered early and is not possible if the patient has pre-existing cirrhosis. Limited studies have shown significant improvement in liver disease, metabolic syndrome, and insulin resistance after successful bariatric surgery.
Drugs for insulin resistance such as thiazolidinedione and metformin, although approved for diabetes, are not approved for NAFLD/NASH and should be considered clinically based on experience (more information can be obtained from the literature and used after careful discussion).
Antioxidant and antifibrotic drugs
Antioxidant and antifibrotic agents (e.g., vitamin E and capsaicin) are not approved for use in NAFLD/NASH. only relatively limited research data (no double-blind controlled trials) support their use, and therefore they should only be considered empirically. Treatment grading is shown in Table 3.
5. Summary
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 valid evidence.
The diagnosis of NASH should be considered in all patients with associated risk factors. Not all patients with risk factors will develop NAFLD and/or NASH, and not all patients with NASH are associated with typical associated risk factors.
Not every patient with fatty liver needs invasive human treatment.
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 be treated with diet and exercise first. Vitamin E or capsaicin may be used in these patients. Empirical treatment should only be considered 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 the above and should be done before progression to cirrhosis.
Liver transplantation in patients who meet the criteria for liver failure is effective; however, NASH can recur after transplantation and morbidly obese patients may refuse surgery.
NAFLD and NASH are also a growing problem in pediatric patients (including those younger than 10 years of age).
In conclusion, NAFLD and NASH are exclusionary diagnoses that require careful consideration of other diseases. Just as NASH cannot be diagnosed clinically based on clinical data alone, histopathology, while demonstrating the presence of steatohepatitis lesions, does not accurately differentiate between alcoholic and non-alcoholic.