Pathogenesis
The pathogenesis of alcoholic liver disease has not been fully elucidated and may be related to the following factors.
1, liver alcohol metabolite damage
(1) Chemical damage by acetaldehyde.
(2) Altered redox reactions.
(3) Oxygen stress and lipid peroxidation.
(4) Mitochondrial damage.
(5) Iron loading.
2. Inflammatory (immune) mechanisms
(1) Abnormal increase in TNFα mRNA, intercellular adhesion molecule-1, IL-8, IL-6, TGF-β cytokines;
(2) Activation of kwashiorkor cells and endotoxemia;
(3) Immune response: hepatocyte proteins and acetaldehyde and hydroxyethyl groups form adducts to stimulate the body to produce antibodies causing cellular immune response.
(3) Hypoxia: Hepatocytes around the central vein are prone to hypoxia, forming secondary damage.
4, nutritional mechanism Secondary malnutrition, so that protein, vitamin and mineral deficiencies, such as lack of choline or polyunsaturated lecithin can lead to hepatic steatosis and liver fibrosis.
5. Increased degree of hepatocyte apoptosis.
Diagnostic criteria
I. Clinical diagnostic criteria for alcoholic liver disease
1. A history of long-term alcohol consumption, generally more than 5 years, equivalent to 40 g/d of ethanol (20 g/d for women), or a history of heavy drinking (> 80 g/d) within 2 weeks. Ethanol amount conversion formula: g = drinking volume (ml) × alcohol content (%) × 0.8 (specific gravity of ethanol).
2, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ a glutamate transketolase (GGT) decreased significantly after the prohibition of alcohol, and basically returned to normal within 4 weeks. The enlarged liver shrank significantly within 1 week and returned to normal within 4 weeks.
3. When diagnosing, attention should be paid to whether HBV or HCV infection is combined, except for liver injury caused by metabolic abnormalities and drugs, etc.
For those who fail to meet the above conditions, histological diagnostic evidence should be obtained. The following items can be used for diagnostic reference: AST/ALT>2 increased serum sugar-deficient transferrin, increased mean red blood cell volume, positive alcoholic hepatocyte membrane antibody, serum glutamate dehydrogenase/ornithine carbamoyltransferase> 0.6, and increased liver volume >720 cm3 per square meter of body surface area as measured by early CT. Alcoholic liver disease can occur even if the amount of alcohol consumed is <40 g/d.
II. Clinical diagnosis of alcoholic liver disease
For those who meet the clinical diagnostic criteria of alcoholic liver disease, the clinical typing diagnosis is as follows.
1.Light alcoholic liver disease: those who have a history of long-term alcohol consumption, but the liver function test is basically normal, and the liver histological performance is consistent with light alcoholic liver disease.
2.Alcoholic fatty liver: those with fatty liver-specific manifestations on imaging diagnosis (CT or B ultrasound) or confirmed by pathology.
3.Alcoholic hepatitis: without biopsy, three or more of the following diagnostic bases and additional items should be met. Diagnostic basis.
(1) Increased alcohol consumption may serve as a trigger for the onset or deterioration of the disease;
(2) Elevated AST-based serum transaminases;
(3) Elevated serum bilirubin (34.2 umol/L). Additional items.
(1) Abdominal pain;
(2) Fever;
(3) Increased peripheral blood leukocytes;
(4) Increased ALT >2.0 ULN; (5) Increased GGT >2.0 ULN (Note: ULN is the upper limit of normal).
Severe alcoholic hepatitis may be combined with hepatic encephalopathy and reduced prothrombin activity (<40%) and other manifestations of liver failure.
4.Alcoholic cirrhosis: those with clinical manifestations of cirrhosis should be distinguished as compensated and decompensated in the diagnosis.
Three, imaging diagnosis
1.Alcoholic fatty liver including diffuse fatty liver and restricted fatty liver. Ultrasound: diffuse fatty liver. The liver is generally enlarged, with smooth envelope, and the liver parenchyma is echogenically enhanced and diffusely fine-dotted as a bright liver. Intrahepatic echogenic intensity decreases with depth (acoustic attenuation phenomenon), and intrahepatic vascular echogenicity is diminished or poorly displayed. Restricted fatty liver is divided into two types.
(1) Lobular segmental type: The liver parenchyma shows patchy echogenic enhancement areas, often bounded by lobe segments or distributed along the long axis of portal vein branches, with clear borders and no occupancy effect.
(CT: diffuse fatty liver: decreased density of liver parenchyma, CT ratio of liver/spleen <0.7, intrahepatic vessels show higher density than liver parenchyma. Limited fatty liver: confined hypodense areas with indistinct boundaries, which can also be seen as isodense areas with normal liver parenchyma. After enhancement scan, the lesion area has no significant enhancement effect and is less obvious than normal liver tissue. MRI: In severe fatty infiltration, high signal is produced in T1 T2 weighting. In diffuse fatty liver, the T1-weighted signal is brighter in the forward phase, and in the inverse phase, the fatty area is shown to be significantly low signal.
2. Alcoholic cirrhosis Ultrasound.
(1) It is small nodular cirrhosis with corrugated liver surface and diffusely enhanced intrahepatic echogenicity. The intrahepatic vessels are reduced or poorly displayed.
(2) Signs of portal hypertension, widening of the main trunk of portal vein >13 mm, with formation of collateral circulation, such as opening of umbilical vein, dilatation of left gastric vein >4 mm. also shows splenomegaly and ascites.
CT.
(1) Disproportionate liver lobes with enlargement of the lateral segment of the left liver lobe and caudate lobe. The surface of the liver was uneven with blunt margins and widened hepatic fissures. Regenerative nodules are seen in the liver parenchyma.
(2) Portal hypertension: splenomegaly, splenic vein and portal vein varices. Lateral circulation formation, short gastric vein, gastric coronary vein and esophageal vein varices.
(3) Dynamic CT shows that the time of peak intensification and delay in the alcoholic cirrhosis group is significantly longer than that in the non-alcoholic cirrhosis group.MRI: wavy liver surface, enlargement of the lateral segment and caudate lobe of the left liver, narrowing of the right lobe and medial segment of the left lobe, and widening of the hepatic fissure. Splenomegaly and ascites could be seen. Regenerative nodules were shown in the liver parenchyma.
Treatment
Treatment of alcoholic liver disease consists of.
① Reducing the severity of alcoholic liver disease;
② Stopping or reversing liver fibrosis;
③ Improving pre-existing secondary malnutrition;
④ Treatment of alcoholic cirrhosis.
Treatment needs to be adjusted for risk factors that affect mortality. The risk factor discriminant function (DF) is DF=4.6×[prothrombin time (sec) – normal control + bilirubin (mg/dL)]. Most treatment trials have been limited to patients with DF ≥ 32 and/or the presence of hepatic encephalopathy, while in patients with less severe disease, treatment has focused on abstinence from alcohol.
Acamprosate and naltrexone can reduce the number of days of drinking in patients with ALD and improve the abstinence rate. Class C patients.
2. Glucocorticoids are only indicated in a few heavy cases without cirrhosis. Contraindications are combined bacterial infection, gastrointestinal bleeding, renal insufficiency, etc.
3.Hexketone cocaine: phosphodiesterase inhibitor, which can improve the degenerative stress of red blood cells and inhibit the release of tumor necrosis factor α (TNFα).
4, anti-TNF therapy: anti-TNFα monoclonal antibody – infliximab or etanercept is a p75 soluble TNF receptor (neutralize TNF). The efficacy needs to be further studied.
5. Colchicine Colchicine inhibits leukocyte migration, reduces toxic liver injury and anti-fibrotic effects. Its application value needs to be further researched.
6.Insulin and glucagon can be tried in alcoholic liver disease, but blood glucose should be tested during the treatment to prevent fatal hypoglycemia.
7.Propylthiouracil Propylthiouracil can inhibit the high metabolic state of the body and reduce the oxygen consumption of hepatocytes, which may be effective for alcoholic liver disease.
8.Malotilate can inhibit CYP2E1 and treat ALD.
9.Antioxidants Reduced glutathione, taurine, carotenoids, vitamins A and E, evening primrose, selenium organic compounds, etc., can reduce oxygen stress damage and lipid peroxidation-induced liver fibrosis and release the toxicity of exogenous toxic substances. However, the effect on alcoholic liver disease is unknown.
10.Polyunsaturated lecithin/phosphatidylcholine Phospholipids can reduce alcohol-induced mitochondrial dysfunction, and polyunsaturated lecithin may play an anti-fibrotic role by increasing hepatic collagen degradation.
11.Anti-endotoxic agents Polymyxin B and neomycin, which can inhibit intestinal flora, reduce endotoxemia, reduce Kupffer cell activation, and thus improve liver function, resulting in a decrease in liver pathology scores.
12.S-adenosylmethionine S-adenosylmethionine can partially correct and reduce liver injury in alcoholic liver disease, mainly improving mitochondrial damage, with no effect on hepatic steatosis and liver fibers.
13.Nutritional support and nutritional therapy Giving saturated fatty acid rich can reduce or stop the occurrence of fatty liver and liver fibrosis.
14.Lipid-lowering drugs Niacin, elastase and phenoxyacetic acid class of Antomin, benzobet and other lipid-lowering drugs have potential hepatotoxicity, reduce glucose tolerance and raise blood uric acid and other adverse effects, and have no improvement effect on intrahepatic fat deposition or make it worse.
15, calcium channel blockers ALD when the activation of Kupffer cells depends on the calcium ion transport across the cell membrane. Calcium channel blockers such as nimodipine and aminoacetic acid can interfere with calcium channel activation and reduce alcoholic liver injury in rats.
16.Chinese herbal medicines to inhibit liver fibrosis Chinese herbal medicines such as peach kernel, Salvia miltiorrhiza, Radix Angelicae Sinensis, Hanfangjiaosu, He Shou Wu, Shan Biao, Turmeric, Constituent Seeds, Sichuan Peony, Zelenia, Huang Cen, Huang Jing, Rhubarb, etc. have the effects of improving liver microcirculation, preventing hepatocyte degeneration and necrosis, reducing collagen fiber production or enhancing collagenase activity, which can be used in the treatment of liver fibrosis in alcoholic hepatitis.
17.Liver transplantation Liver transplantation should be considered for patients with severe alcoholic cirrhosis (Child Class C). Patients are required to abstain from alcohol for more than six months prior to liver transplantation.
18.Other treatment Various complications may occur in the late stage of alcoholic cirrhosis, such as hepatic encephalopathy, hepatorenal syndrome, ascites, portal hypertension, ruptured esophageal varices and bleeding, etc. The treatment is similar to that of other causes of cirrhosis.