OVERVIEW
Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive intracellular fat deposition in the hepatocytes due to non-alcoholic and other well-defined liver-damaging factors, and acquired metabolic stress liver injury closely related to insulin resistance and genetic susceptibility. It includes simple fatty liver (SFL), non-alcoholic steatohepatitis (NASH) and its associated cirrhosis. With the epidemiological trend of globalization of obesity and its associated metabolic syndrome, non-alcoholic fatty liver disease has now become an important cause of chronic liver disease in developed countries such as Europe and the United States and affluent regions of China, with the prevalence of NAFLD in the general adult population ranging from 10% to 30%, of which 10% to 20% is NASH, with the latter’s cirrhosis incidence within 10 years as high as 25%.
In addition to directly contributing to decompensated cirrhosis, hepatocellular carcinoma and transplanted liver recurrence, NAFLD can also affect the progression of other chronic liver diseases and participate in the pathogenesis of type 2 diabetes mellitus and atherosclerosis. Metabolic syndrome-associated malignancies, atherosclerotic cardiovascular disease, and cirrhosis are important factors affecting the quality of life and life expectancy of patients with nonalcoholic fatty liver disease. For this reason, nonalcoholic fatty liver disease is a new challenge in contemporary medicine, and the risk to human health from nonalcoholic fatty liver disease will continue to increase in the near future.
Etiology
Non-alcoholic fatty liver disease (NAFLD) is categorized into two main groups: primary and secondary, with the former being related to insulin resistance and genetic susceptibility, and the latter being due to some specific causes. Excessive weight gain and overweight due to overnutrition, fatty liver associated with metabolic syndrome such as obesity, diabetes mellitus, hyperlipidemia, and cryptogenic fatty liver are primary NAFLD, while fatty liver due to malnutrition, total parenteral nutrition, dramatic weight loss after bariatric surgery, and drug/environmental and industrial toxicity are secondary NAFLD.
Pathology
According to the degree of pathological changes and whether the diseased liver tissue is accompanied by inflammation and fibrosis, NAFLD can be classified into: simple fatty liver, NASH, NASH-associated cirrhosis.
1. Simple fatty liver
Based on the range of hepatocellular steatosis occupying the amount of liver tissue specimen obtained, it is classified into 4 degrees (F0～4): F0<5% hepatocellular steatosis; F1 5%～30% hepatocellular steatosis; F2 30%～50% hepatocellular steatosis; F3 50%～75% hepatocellular steatosis; F4 75% or more hepatocellular steatosis.
2. Non-alcoholic steatohepatitis
It refers to hepatocellular inflammation that occurs on the basis of hepatocellular steatosis. The degree of fatty liver is categorized into 4 degrees (F0～4); the degree of inflammation is categorized into 3 grades (G0～3)
3. Cirrhosis associated with non-alcoholic steatohepatitis
Complete destruction of hepatic lobular structure, replaced by pseudolobule formation and extensive fibrosis, roughly small nodular cirrhosis. Depending on whether the fibrous septum has interfacial hepatitis, it is divided into active and quiescent.
Symptoms
1. Most patients with fatty liver do not have conscious symptoms, some patients may have non-specific symptoms and signs such as fatigue, dyspepsia, vague pain in the liver area and hepatosplenomegaly.
2. There may be overweight and/or visceral obesity, increased fasting glucose, dyslipidemia, hypertension and other metabolic syndrome-related symptoms.
Examination
1. Ultrasound diagnosis
(1) Diffuse enhancement of near-field echoes in the hepatic region (stronger than that of kidneys and spleen), with gradual attenuation of far-field echoes.
(2) Intrahepatic ductal structures are poorly visualized.
(3) The liver is mildly to moderately enlarged, with rounded edge angles.
(4) Color Doppler flow imaging suggests that the intrahepatic blood flow signal is reduced or not easily displayed, but the intrahepatic vascular course is normal.
(5) The echoes of the right lobe of the liver and the transverse septum are not clear or incomplete.
Those who have item 1 and one of items 2 to 4 above are regarded as mild fatty liver; those who have item 1 and two of items 2 to 4 above are regarded as moderate fatty liver; those who have item 1, two of items 2 to 4 and item 5 above are regarded as severe fatty liver.
2.CT diagnosis
Diffuse decreased liver density, liver/spleen CT ratio ≤1.0 but greater than 0.7 is considered mild; liver/spleen CT ratio ≤0.7 but greater than 0.5 is considered moderate; liver/spleen CT ratio ≤0.5 is considered severe.
3. Liver biopsy by liver puncture.
Diagnosis
The diagnosis of non-alcoholic fatty liver disease requires the following 3 conditions:
1. No history of alcohol consumption or consumption of alcohol containing less than 140g of ethanol per week (<70g for women).
2. Exclusion of viral hepatitis, drug-induced liver disease, total parenteral nutrition, hepatomegaly, and other specific diseases that can lead to fatty liver.
3. Liver biopsy histologic changes meet the pathological diagnostic criteria for fatty liver disease.
Differential diagnosis
Alcoholic liver disease, chronic hepatitis C, autoimmune liver disease, hepatomegaly, and other specific diseases that may lead to fatty liver; medications (tamoxifen, amiodarone, methotrexate, glucocorticosteroids), total parenteral nutrition, inflammatory bowel disease, hypothyroidism, Cushing’s syndrome, beta-lipoprotein deficiency, and the association with congenital insulin resistance syndrome should be excluded.
Treatment
1. Basic treatment
Formulate reasonable energy intake and dietary structure adjustment, moderate aerobic exercise, correct bad lifestyle and behavior.
2. Avoid aggravating liver damage
Prevent rapid weight loss, drug abuse and other factors that may induce worsening of liver disease.
3. Weight loss
All patients with overweight, visceral obesity and rapid short-term weight gain in non-alcoholic fatty liver disease need to control their weight and reduce waist circumference through lifestyle changes.
4. Insulin sensitizer
For patients with type 2 diabetes mellitus, impaired glucose tolerance, increased fasting blood glucose and visceral obesity, metformin and thiazolidinediones may be considered with a view to improving insulin resistance and controlling blood glucose.
5. Lipid-lowering drugs
If dyslipidemia is still mixed hyperlipidemia or hyperlipidemia combined with more than 2 risk factors after basic treatment and application of weight-loss and hypoglycemic drugs for more than 3-6 months, it is necessary to consider the addition of lipid-lowering drugs such as beta, statin or probucol.
6. Drugs for liver disease
For non-alcoholic fatty liver disease with abnormal liver function, metabolic syndrome, those who are still ineffective after 3-6 months of basic treatment, and those whose liver biopsy confirms that they have NASH and the course of the disease is chronic and progressive, drugs against liver disease can be used as adjuvant therapy to fight against oxidation, inflammation, and fibrosis, and they can be reasonably selected according to the performance of the drugs, as well as the degree of activity of the disease and the stage of the disease, such as polyenophospholipid phthalic acid, vitamin E, silymarin, and ursodeoxycholic acid. Polyenophosphatidylcholine, vitamin E, silymarin and ursodeoxycholic acid can be used according to the performance of the drugs and the disease activity and stage.
Prognosis
The vast majority of non-alcoholic fatty liver disease has a good prognosis, and the prognosis is relatively good if the liver histology progresses slowly or even becomes static. In some patients, even if steatohepatitis and hepatic fibrosis have already occurred, if timely diagnosis and treatment can be made, the changes in liver histology can still be reversed, and it is rare for fat cysts to rupture and cause fat embolism and death. A minority of patients with steatohepatitis progress to cirrhosis, and once cirrhosis occurs, the prognosis is poor. In the majority of patients with fatty liver, weight and blood glucose control, lipid lowering, and liver histologic reversal can sometimes be achieved with non-pharmacological measures such as dietary modification and moderate aerobic exercise.