A Comprehensive Overview of Fatty Liver Disease: In-Depth Analysis from Serious Complications and Pathological Evolution to the Triggering Factors

Acute fatty liver of pregnancy is a relatively rare pregnancy-related disease. Its incidence rate in recent years is 1/7000–16000. Due to timely diagnosis and treatment, maternal mortality has decreased to 10%–18%, and perinatal mortality to 15%–23%. It mostly occurs between 28 and 40 weeks of gestation, commonly around 35 weeks. There are now numerous reports of this disease occurring in mid-pregnancy (22 weeks) and postpartum. Primiparous women, twins, and male fetuses are more susceptible. The disease has a rapid onset and progression, ultimately leading to death from multiple organ failure, primarily due to severe liver dysfunction. The fetus often dies due to placental fibrosis and multifocal infarction, resulting in placental insufficiency. Patients with fatty liver often have hepatosplenomegaly. The spleen is also an important immune organ; splenomegaly leads to hypersplenism, and abnormal spleen function inhibits cellular immunity. Furthermore, fatty degeneration of hepatocytes reduces detoxification function, easily causing the retention of endotoxins and exotoxins in the body, which are toxic.

Reye's syndrome, also known as visceral fatty degeneration encephalopathy, is most prominently characterized by a yellowish liver exterior and elevated triglyceride levels within the liver. Microscopic examination reveals uniform foamy cytoplasm in hepatocytes accompanied by microvesicular fat droplet deposition. Pathological changes primarily include diffuse cerebral edema and severe hepatic steatosis, resulting in an enlarged, firm liver. Significant cerebral symptoms are present, including seizures, progressive altered consciousness, and even coma. The mortality rate is as high as 70%–80%. Immediate treatment is crucial upon diagnosis to prevent disability and death.

Based on the pathological evolution of fatty liver, it can be divided into three stages: early, middle, and late. Early stage: Simple fatty liver without hepatocyte necrosis and inflammatory response. Simple fatty liver refers to hepatocyte steatosis alone. Generally, clinical symptoms and signs are not obvious; liver function indicators are normal or slightly elevated; blood lipid indicators are normal or slightly elevated; and ultrasound shows mild to moderate changes. Middle stage: Fatty hepatitis accompanied by intralobular and portal inflammation and fibrosis. Fatty hepatitis refers to hepatocyte steatosis accompanied by degeneration, necrosis, and inflammatory cell infiltration, which may be accompanied by Mallorv bodies, pericentral venous fibrosis, and perihepatocyte fibrosis. Clinical symptoms and signs of fatty hepatitis are more obvious, including fatigue, shortness of breath, anorexia, discomfort in the liver area, hepatosplenomegaly, etc.; liver function is significantly abnormal; and ultrasound shows moderate changes. Late stage: Fatty cirrhosis. Fatty cirrhosis is a severe fibrosis and pseudolobule formation secondary to fatty liver. Fatty liver cirrhosis presents with obvious clinical symptoms and signs, including hepatic discoloration, spider angiomas, and hepatosplenomegaly. The liver is relatively hard, the tongue is dark purple with petechiae, varicose veins are present under the tongue, liver function is abnormal, portal and splenic veins are widened, coagulation mechanisms are abnormal, esophageal varices are present, and ultrasound often shows a "bright liver".

Fatty liver is classified into mild, moderate, and severe degrees. Mild fatty liver: Contains 5%–10% fat, or 1/3–2/3 of hepatocytes per unit area show steatosis. Ultrasound shows increased near-field echogenicity, with minimal far-field echogenicity attenuation; intrahepatic tubular structures are still visible. Often asymptomatic, some patients only experience fatigue. Since most patients with mild fatty liver are obese, it is even more difficult to detect mild symptoms, and it is often discovered incidentally during a physical examination. The optimal time for treatment of mild fatty liver is during this period. Moderate fatty liver: Contains 10–25% fat, or more than 2/3 of hepatocytes show steatosis. Ultrasound shows increased anterior-field echogenicity, decreased posterior-field echogenicity, and blurred intrahepatic tubular structures. It presents with symptoms similar to chronic hepatitis, such as loss of appetite, fatigue, nausea, vomiting, weight loss, and dull pain in the liver area or right upper quadrant. It also often presents with changes of peripheral neuritis, such as glossitis, angular cheilitis, skin ecchymosis, numbness in the limbs, and abnormal sensation in the limbs. A few patients may also have gastrointestinal bleeding, gingival bleeding, epistaxis, splenomegaly, and palmar erythema.

Based on the degree of pathological changes in liver tissue, fatty liver can be broadly classified into four types: 1. Simple fatty liver: The liver lesion only manifests as fatty degeneration of hepatocytes. Based on the extent of hepatocyte steatosis, fatty liver is divided into diffuse fatty liver, focal fatty liver, and diffuse fatty liver with normal hepatic islands. Simple fatty liver is the early stage of the disease; if detected early and treated promptly, it can be completely cured. 2. Steatohepatitis: This refers to hepatocyte inflammation occurring on the basis of hepatocyte steatosis. Based on etiology, steatohepatitis can be divided into two main categories: alcoholic hepatitis and non-alcoholic steatohepatitis. The histological changes of both are basically similar, both showing ballooning degeneration of hepatocytes and mixed inflammatory cell infiltration, mainly neutrophils, within the lobules, on the basis of hepatic steatosis. Fatty liver is very common among alcoholics, while alcoholic hepatitis only occurs in some severely alcoholic individuals. The incidence of alcoholic fatty liver and alcoholic hepatitis is much higher in Europeans and Americans than in people of East Asian descent. 3. Fatty liver fibrosis. Fatty liver disease refers to fibrosis around hepatocytes. The degree of fibrosis is related to the persistence of the causative factors and the severity of fatty liver. Clinically, both alcoholic and non-alcoholic fatty liver disease can induce liver fibrosis, eventually leading to cirrhosis and liver failure. It is generally believed that fatty liver develops from simple fatty liver to steatohepatitis, then to fibrosis, and finally to cirrhosis. However, there are exceptions; for example, alcoholic fatty liver can directly develop into liver fibrosis and cirrhosis without going through steatohepatitis. 4. Fatty Cirrhosis. Fatty cirrhosis is the result of fatty liver disease progressing to a late stage. Long-term accumulation of large amounts of fat in hepatocytes affects their blood and oxygen supply and metabolism, causing hepatocyte swelling, inflammatory infiltration, and degeneration and necrosis. Once fibrosis occurs in the liver, it becomes cirrhosis, greatly increasing the risk of liver cancer. Patients with fatty liver should be wary of cirrhosis. The following conditions should raise suspicion of early cirrhosis: unexplained splenomegaly; unexplained gynecomastia in men; and recurrent abnormalities in liver function or transaminase levels.

Fatty liver can be divided into two main categories: acute and chronic. 1. Acute Fatty Liver. Acute fatty liver generally refers to acute fatty liver during pregnancy. This disease has a sudden onset and rapidly changing course. Clinical manifestations are similar to acute severe hepatitis, often including fatigue, nausea, vomiting, and varying degrees of jaundice, and may even lead to altered consciousness and grand mal seizures. Death often occurs within a short period. This disease mostly occurs between 28 and 40 weeks of gestation, and is most common in primiparous women around 35 weeks of gestation. It is more likely to occur in twins and male fetuses with gestational hypertension. 2. Chronic Fatty Liver. Chronic fatty liver is what is commonly referred to as fatty liver. It is relatively common, with a slow and insidious onset and a long course. Early on, there are no obvious clinical symptoms; it is usually discovered incidentally during an ultrasound examination. Some patients may experience loss of appetite, nausea, fatigue, pain in the liver area, abdominal distension, and a feeling of fullness and pressure in the right upper quadrant. In middle-aged and elderly people, the metabolic function gradually declines, making them prone to fat accumulation and increasing the likelihood of fatty liver. If you get sick, early treatment leads to a better prognosis. Generally, you can return to a normal life after 2 to 3 months of treatment.

Based on the causes, fatty liver is divided into two main categories: alcoholic fatty liver and non-alcoholic fatty liver. Non-alcoholic fatty liver refers to fatty liver caused by daily alcohol consumption of less than 20g. Alcoholic fatty liver is further divided into simple alcoholic fatty liver and mixed fatty liver, with mixed fatty liver referring to simple alcoholic fatty liver. According to liver biopsies of long-term heavy drinkers, 75%–95% of alcoholic fatty liver cases show fatty infiltration. Medically, alcohol consumption is defined as follows: if a fatty liver patient has a history of alcohol consumption for more than five years, equivalent to an intake of more than 40g of alcohol per day for men and more than 20g of alcohol per day for women; or has a history of heavy drinking within two weeks, equivalent to an intake of more than 80g of alcohol per day, then they can be classified as having alcoholic fatty liver. Simply put, if you habitually drink more than 100ml of 50° alcohol daily, you are highly susceptible to developing alcoholic fatty liver.