Alcoholic liver disease

　　1. Etiology

　　About 80% to 90% of alcohol is metabolized in the liver. It is oxidized to acetaldehyde by the catalytic action of alcohol dehydrogenase in the cytoplasm of liver cells, which is then converted to acetic acid by acetaldehyde dehydrogenase, and finally forms carbon dioxide. A large number of hydrogen ions are released during the oxidation of ethanol and combine with coenzyme I. Coenzyme I is reduced to the reduced form of coenzyme I, which increases its ratio to coenzyme I, causing changes in the oxidation-reduction reactions of the cell, leading to altered metabolism of substances dependent on reduced form of coenzyme I/coenzyme I, and becoming the basis for metabolic disorders and disease.

　　At the same time, acetaldehyde has a direct toxic effect on liver cells. As a highly reactive compound, it can interfere with various functions of liver cells, such as affecting the production of ATP by mitochondria, protein biosynthesis and secretion, damaging microtubules to impair the excretion of proteins and fats, and accumulating them within liver cells, causing cell osmotic swelling and even collapse.

　　When alcohol is oxidized, it produces a large amount of reduced form of coenzyme I, which becomes a raw material for the synthesis of fatty acids, thereby promoting fat synthesis. Acetaldehyde and a large amount of reduced form of coenzyme I can inhibit the function of mitochondria, causing obstacles in the oxidation of fatty acids and leading to the formation of fatty liver.

　　Alcohol-induced hyperlactatemia increases proline levels by stimulating the activity of proline hydroxylase and inhibiting proline oxidation, leading to increased liver collagen formation and accelerating the process of liver cirrhosis. It is believed that hyperlactatemia and hyperprolinemia can be used as markers for the development of liver fibrosis in alcoholic liver disease.

　　Second, pathogenesis

　　Recent studies have shown the pathogenesis of alcoholic fatty liver:

　　1. Excessive entry of free fatty acids into the blood.

　　2. Increased synthesis of fatty acids in the liver.

　　3. Reduced oxidation of fatty acids in the liver.

　　4. Excessive synthesis of triglycerides.

　　5. Impaired release of lipoproteins from liver cells.

　　Currently, it is believed that the direct toxic effect of alcohol on liver cells is the main cause of fatty liver.

　　Recent studies have shown that the pathogenesis of alcoholic hepatitis involves immune factors and is of great significance. Currently, it is believed that the enlarged liver cells cannot excrete microfilaments (filaments) and accumulate them within the liver cells to form alcoholic hyaline bodies, which then cause the production of antibodies against hyaline bodies. Autoimmune liver antigens and isolated alcoholic hyaline bodies can stimulate the transformation and migration inhibitory factor (MIF) activity of patient lymphocytes.

　　Alcoholic liver cirrhosis can be detected for natural DNA antibodies with autoimmune characteristics and IgG and IgA antibodies produced by liver cells. These antibodies can be adsorbed by liver extracts.

　　Recent studies have shown that alcohol and acetaldehyde can change the antigenicity of the liver cell membrane, not directly acting on the liver cell membrane due to the toxicity of acetaldehyde.

　　1. Liver cirrhosis manifestations, such as: mild fatigue, abdominal distension, mild splenomegaly, mild jaundice, liver palms, and spider angiomas. Imaging, biochemistry, or blood tests may show dysfunction of liver cell synthesis or portal hypertension (such as splenic hypersplenism and esophageal varices).

　　2. There is also malnutrition, anemia, neuritis, muscle atrophy, parotid swelling, testicular atrophy, and changes in serum biochemical indicators.

　　1. Fatty liver

　　A single drinking session close to intoxication can cause liver steatosis within a few hours. Most of these patients are of moderate obesity, with symptoms that are insidious and resemble the gastrointestinal symptoms of hepatitis, such as pain in the liver area, discomfort in the upper abdomen, and abdominal pain. A few have jaundice, edema, vitamin deficiency, liver enlargement, soft palpation, smooth edges, with a sense of elasticity or tenderness. Splenomegaly is less common. Due to liver cell swelling and central vein sclerosis or venous thrombosis around the central vein, portal hypertension may occur, leading to the occurrence of ascites, but without sclerosis. Severe cases may die due to hypoglycemia or fat embolism.

　　2. Alcoholic hepatitis

　　Severe gastrointestinal symptoms may include nausea, vomiting, decreased appetite, fatigue, weight loss, and worsening pain in the liver area. In severe cases, it may present as acute fulminant hepatitis or liver failure.

　　3. Alcoholic liver cirrhosis

　　In Western and European countries, alcoholic liver cirrhosis accounts for 50% to 90% of all liver cirrhosis, while it is still rare in China, usually appearing around the age of 50. 80% of patients have a history of drinking in large quantities for 5 to 10 years. In addition to general symptoms of liver cirrhosis, there are also symptoms such as malnutrition, anemia, spider angiomas, liver palms, neuritis, muscle atrophy, parotid swelling, gynecomastia, and testicular atrophy, which are more common than post-hepatitis liver cirrhosis. Dupuytren's contracture, glossitis, and when parotid swelling occurs, it may be accompanied by pancreatitis. Early liver enlargement, late liver shrinkage, and less common splenomegaly than post-hepatitis liver cirrhosis. Ascites appears earlier, often accompanied by peptic ulcer disease.

　　First-level prevention

　　Not drinking alcoholic beverages is the fundamental measure to prevent alcoholic liver disease. In real life, it is impossible to completely achieve this. Therefore, the next best thing is to try to drink as little as possible of spirits. Timely supplementation of high-protein, high-vitamin diet after drinking, and taking alcohol detoxification drugs such as Pueraria root.

　　Second, Secondary prevention

　　For patients with a large amount of drinking and/or long-term drinking, regular liver function tests should be conducted, and liver biopsy may be performed when necessary to detect alcoholic liver disease early and determine the extent of its development. At present, there is a lack of specific and sensitive indicators for the diagnosis of alcoholic liver disease, which needs further research. Early treatment of alcoholic liver disease includes:

　　1, Lifetime abstinence from alcohol.

　　2, High-protein, high-vitamin diet, especially B vitamins, vitamins A, C, K, etc., should be taken in large amounts of folic acid.

　　3, There are reports that corticosteroids are effective for fatty liver and active alcoholic hepatitis, but there are also reports that the effectiveness cannot be confirmed.

　　Propylthiouracil has been tried, but the effectiveness cannot be determined.

　　First, Laboratory examination

　　1, Blood count, anemia may occur, and liver cirrhosis is often accompanied by decreased white blood cells and platelets.

　　2, Glutamic-oxaloacetic transaminase (AST) and alanine aminotransferase (ALT), increased in alcoholic hepatitis and active alcoholic cirrhosis, but AST increases significantly, ALT increases slightly, and the ratio of AST/ALT greater than 2 is diagnostic of the aforementioned two diseases.

　　3, Gamma-glutamyl transferase (γ-GTP), distributed in the cytoplasm of liver cells and the endothelium of capillary bile ducts, increases more sensitively when alcohol damages the liver cell mitochondria.

　　4, In the amino acid profile, α-aminobutyric acid and leucine increase proportionally.

　　5, Abnormal indocyanine green retention test is an early indicator of alcoholic liver disease.

　　6, Specificity in serum, positive for alcoholic hyaline bodies, antigen-antibody positive; in severe cases, both antigen and antibody are positive; in the recovery period, antigen is negative, and antibody remains positive for a short time; if antigen-antibody is positive, it indicates disease progression. Serum IgA increases, and there is hypozincemia, hyperzincuria, so renal zinc clearance rate is helpful for etiological diagnosis during liver disease.

　　7, Elevated blood triglycerides and cholesterol levels help in the diagnosis of fatty liver, decreased albumin, increased globulin, and prolonged prothrombin time help in the diagnosis of liver cirrhosis.

　　Second, Imaging examination

　　1, B-ultrasound examination

　　(1) Fatty liver: shows increased liver volume, uniform and consistent fine echoes in the parenchyma, with dense fine light spots and beam attenuation enhancement, known as 'bright liver'.

　　(2) In alcoholic cirrhosis, there is splenic enlargement, enhanced liver parenchyma echo, relatively enlarged caudate lobe, and significantly larger diameter of splenic vein and portal vein than normal (the former is normal 1.0cm, the latter is 1.5cm).

　　2, CT examination

　　(1) Fatty liver: characterized by the whole liver, liver lobes, or local areas with lower density than the spleen, with normal liver areas and spleen showing significant enhancement during contrast-enhanced scan, contrasting more distinctly with the low-density areas of fatty liver.

　　(2) Liver cirrhosis: characterized by widened hepatic fissures, abnormal proportions of liver lobes, relatively enlarged caudate lobe, liver deformation, spleen enlargement, more than 5肋 units.

　　3, Liver biopsy

　　It can determine whether there is fatty liver, alcoholic hepatitis, cirrhosis, and can be distinguished from other viral hepatitis by histological examination.

　　(1) Fatty liver: The main liver lesions are more than 1/3 of the liver lobules (more than 1/3 of all liver cells) fatty, which can be diagnosed.

　　(2) Alcoholic hepatitis: Its tissue characteristics include alcoholic hyaline bodies (Mallory bodies), accompanied by necrosis of cells with neutrophil infiltration; balloon-like transformation of liver cells.

　　(3) Alcoholic cirrhosis: The typical cirrhosis presents as small nodular, the nodules do not contain portal tracts and central veins, the sizes of the nodules are similar, and they are surrounded by fibrous septa. The diameter of the nodules is often less than 3mm, generally not more than 1cm, and can form large nodules or postnecrotic cirrhosis with the evolution of pathology.

　　1, Angelica sinensis, Curcuma aromatica, and hawthorn drink

　　Angelica sinensis and Curcuma aromatica each 12 grams, hawthorn and orange cake each 25 grams. Boil the above four ingredients together with water to extract the juice. Take it in 2-3 doses.

　　2, Atractylodes macrocephala and jujube

　　Atractylodes macrocephala, Plantago asiatica, and Curcuma aromatica each 12 grams, jujube 120 grams. Wrap Atractylodes macrocephala, Plantago asiatica, and Curcuma aromatica in gauze, boil them with jujube, try to make the jujube absorb the medicine liquid, remove the dregs and eat the jujube.

　　3, Angelica sinensis, Curcuma aromatica, and hawthorn drink

　　Angelica sinensis and Curcuma aromatica each 12 grams, hawthorn and orange cake each 25 grams. Boil the above four ingredients together with water to extract the juice. Take it in 2-3 doses.

　　4, Safflower, hawthorn, and orange peel drink

　　Safflower 10 grams, hawthorn 50 grams, orange peel 12 grams. Boil the above three ingredients in water.

　　First, treatment

　　There is no specific therapy, and supportive therapy is the main approach.

　　1, After about 10 days of abstinence from alcohol, the fat in the liver can be significantly improved, and some patients with abnormal liver function have a good response after abstinence from alcohol.

　　2, When liver function is abnormal, rest should be taken, and a diet high in protein and high in calories and low in fat should be consumed.

　　3, Choline and methionine are helpful for the recovery of liver function. Supplementation with vitamins B1, B6, B12, folic acid, zinc, etc., can restore the activity of suppressed liver cells, stimulate nucleic acid synthesis and cell regeneration, and zinc can promote enzyme activity and improve the metabolism of alcohol. It can also treat night blindness that is ineffective to vitamin A.

　　4, Huanjide is a compound preparation of phospholipids and various B vitamins, which promotes the regeneration of liver cell membrane tissue, accelerates liver fat metabolism, synthesizes proteins, and has detoxifying function. Oral administration: 2 tablets, 3 times a day. If intravenous infusion is required, it should be decided according to the patient's condition. There are no significant side effects.

　　5, The compound preparation of liver and gallbladder, composed of p-methylbenzyl alcohol and niacin ester-5α-naphthoic acid, promotes bile secretion, protects the liver, anti-inflammatory, and can inhibit the destructive effect of liver cells during alcohol intoxication. Side effects are mild, and some may experience mild diarrhea.

　　6, TAD's active ingredient is glutathione. TAD is a reduced form of glutathione, in which the sulfhydryl group (—SH) combines with numerous toxic chemicals and other metabolic substances to exert a detoxifying effect. It can be used for alcohol intoxication, drug intoxication, and other chemical intoxications. Dosage: 300-600mg intramuscular injection, once a day, or 300-600mg added to a small bottle, 1-2 times a day, depending on the condition. However, do not place it in a glucose solution bottle for intravenous infusion to prevent oxidation and失效. Side effects: occasional rash, which disappears after discontinuation of the drug.

　　7. Adenosine, a lipolytic drug, can reduce the increase of triglycerides in the liver after acute alcohol damage, stimulate the oxidation of fatty acids by mitochondria. A large amount of ATP (which can be decomposed into adenosine) also has the same effect. Clofibrate (Clofibrate) can reduce the synthesis of triglycerides and undergo enzyme-induced oxidation of long-chain fatty acids.

　　8. Alcohol-induced liver disease, due to vigorous metabolism and hypoxia, Canadian authors reported that short-term treatment with propylthiouracil, 300mg per day, has a liver-protecting effect. It can reduce the mortality rate of alcoholic liver disease. The cumulative mortality rate is 0.13%, and the control group is 0.2%. It can be used for severe alcoholic liver disease and liver cirrhosis.

　　9. Coenzyme I injection can reduce the increase of γ-GTP in half a year after treatment for half a month, and improve the redox action of liver cells. Male hormones can promote protein synthesis, and adrenal cortical hormones can inhibit collagen formation and immune response.

　　10. Anti-hepatic fibrosis, refer to the treatment of liver cirrhosis:

　　(1) D-penicillamine can inhibit the cross-linking of collagen molecules, reduce collagen production, but does not improve liver function and survival rate.

　　(2) Colchicine can inhibit the collagen transport of intracellular microtubules and can also reduce blood lactic acid and proline, improving clinical indicators.

　　II. Prognosis

　　Fatty liver can be completely recovered after abstinence from alcohol, and the mortality rate of acute alcoholic hepatitis is about 40% to 50%. After 3 years of follow-up, 50% of abstainers have non-active alcoholic hepatitis, and a small part develops into liver cirrhosis. 25% of liver cirrhosis patients can be completely recovered, which is better than liver cirrhosis caused by other reasons. The 5-year survival rate after 5 years of abstinence is 51.3% to 63%, and the 10-year survival rate is 25.1%. The 5-year survival rate without abstinence is 40%, the incidence of upper gastrointestinal bleeding is 59%, jaundice is 47.9%, and the incidence of ascites is also high, thereby increasing mortality. The causes of death include gastrointestinal bleeding, hepatic encephalopathy, infection, and liver cancer. It is noteworthy that the incidence of liver cell carcinoma in abstainers is relatively increased, because after abstinence, the patient's life is often prolonged; the inhibitory effect of alcohol on liver cell regeneration is released, and canceration occurs during the process of liver cell regeneration.