I. Epidemiology
Alcohol is long recognized as an addictive substance. According to the WHO report, alcohol consumption is associated with 64 diseases and injuries, and diseases caused by alcohol consumption are mainly focused on tumors, cardiovascular and circulatory diseases, digestive system (including liver) diseases, traffic injuries, accidental injuries, intentional injuries, etc. The Lancet magazine published the 2010 global total burden of disease ranking, showing that in the 20 years from 1990 to 2010, among all In the 20 years from 1990 to 2010, alcohol consumption has rapidly climbed from the sixth to the third place among all disease risk factors, after hypertension and smoking. Alcohol use is responsible for 4.9 million deaths annually, accounting for 5.5% of all disability-adjusted life years (DALYs) worldwide. Alcohol use is ranked first in the total burden of disease for the 15-49 age group and third in the total burden of disease for people over 50 years of age worldwide.
The latest statistics show that the lifetime prevalence of adult alcohol use disorders is already as high as 16% globally, and the prevalence is higher in Eastern European countries. rehm et al. also reported that the number of deaths worldwide due to alcoholic cirrhosis was 493,300 in 2010, and the number of disability adjusted life years due to alcohol use related disorders is climbing rapidly worldwide.
II. Alcohol use disorders
Based on the above severe epidemiological trends, there is an urgent need to establish a standardized diagnosis and treatment system for alcohol use disorder (AUD) and alcohol-related somatic co-morbidities to provide timely and effective treatment for patients. Although the Diagnostic and Statistical Classification Manual of Mental Disorders, Fourth Edition (DSM-IV) makes a clear distinction between alcohol abuse and alcohol dependence, defining the former as problematic drinking without compulsive use, tolerance changes, and withdrawal symptoms, while the latter is clearly defined as a group of syndromes: including compulsive use, with or without tolerance changes, and withdrawal symptoms. However, in the most recent Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), the distinction between the two is abolished and alcohol use disorder (AUD) is used consistently as a continuous, uniform spectrum of mental, behavioral, and somatic symptoms with varying degrees of severity. The DSM-V currently has 11 diagnostic criteria for AUD, and these entries are divided into subgroups: impaired control (entries 1 through 4), impaired social functioning (entries 5 through 7), risky drinking (entries 8 through 9), and criteria for pharmacological dimensions (entries 10 through 11), as detailed in Table 1. AUD is defined as problem drinking within the last 12 months that results in The following 11 criteria were met for AUD: a clear clinically significant impairment or distress in physical and social functioning within the last 12 months.
Table 1. Diagnostic and Statistical Classification of Mental Disorders (DSM-5) Alcohol Use Disorder Diagnostic Criteria
Another thing that clinicians need to recognize is that chronic excessive alcohol intake can lead to a range of clinically characteristic impairments, including enlarged parotid glands, skeletal muscle atrophy, dystrophy, and symmetrical peripheral neuropathy. Extrahepatic damage also includes alcoholic cardiomyopathy, chronic pancreatitis and pancreatic secretion disorders, and alcoholic encephalopathy, and can lead to complex psychiatric disorders and a variety of somatic co-morbidities. In addition to the clinically characteristic damage described above, alcohol damage to the liver is something that needs to be taken very seriously and is mostly one of the major causes of disability or death in patients. Alcoholic liver injury includes a series of processes such as hepatic steatosis, hepatitis, liver fibrosis and cirrhosis.
Three, alcoholic liver disease
(a) Pathogenesis: Alcohol Liver Disease (ALD) has become one of the physical damages that often co-morbid with alcohol use disorder and seriously endangers the health of alcohol addicts. Numerous studies have shown that microRNAs are involved in the process of alcoholic liver injury. mishra et al. found that downregulation of metallo-matrix proteinase 9 (MMP-9) prevented alcohol-induced liver injury in mice, suggesting that MMP-9 is involved in the pathogenesis of ALD. In addition, signal transducer and activator of transcription-3 (STAT3), a member of the signal transducer and activator of transcription family, is involved in acute inflammatory response, anti-apoptosis and cell proliferation, and its mechanism may be activated by IL-6 and then enters the nucleus to initiate transcription of various genes and thus trigger various biological effects. It was demonstrated that the amount and activity of STAT3 protein in alcoholic cirrhotic tissues are lower than those in healthy liver; the decreased ability of STAT3 protein to bind DNA may be related to its inhibitor Pias3 protein, and related studies also demonstrated the upregulation of Pias3 protein expression in alcoholic cirrhotic liver tissues. The above may be the molecular biological mechanisms of alcoholic liver disease.
(II) Clinical classification, diagnosis and severity assessment
Alcoholic liver disease should include alcoholic fatty liver, alcoholic hepatitis, alcoholic liver fibrosis, and alcoholic cirrhosis. Among them, alcoholic fatty liver is usually asymptomatic and easily returns to normal after quitting alcohol. 20% of patients who have developed alcoholic fatty liver and still do not stop drinking alcohol will develop liver fibrosis and cirrhosis.
Alcoholic liver disease can be diagnosed if three or more of the following diagnostic criteria and additional items are met. (See Table 2 for detailed diagnostic criteria and additional items)
Table 2. Diagnostic criteria for alcoholic liver disease
In addition, liver biopsy is a confirmatory method of diagnosis, but is not usually used. Pathological findings show ballooning and hyaline changes in hepatocytes, with Mallory vesicles visible in the cytoplasm; sometimes giant mitochondria, intrahepatocellular siltation, small bile duct hyperplasia and iron granules deposition are seen; neutrophilic leukocyte infiltration is present in the foci of inflammatory necrosis. Apoptotic vesicles are easily seen, and necrosis can be fused.
Alcoholic fatty liver can also present with the reactions of alcoholic hepatitis and hepatocellular damage. Acute severe alcohol hepatitis (SAH) is one of the common and important life-threatening causes of liver failure and was once referred to as acute liver failure in chronic alcoholics. However, because the disease often occurs on the basis of fatty liver or cirrhosis caused by long-term excessive alcohol consumption, or in patients who drink heavily in a short period of time, it is characterized by rapid onset of fever, jaundice, ascites, and multi-organ dysfunction such as hepatic encephalopathy, pneumonia, acute renal failure, and upper gastrointestinal bleeding, and is therefore called acute severe alcohol hepatitis. In fact, there may be weeks to months of subacute development before the onset of significant hepatitis symptoms.
Some of the more commonly used indicators to evaluate SAH include.
1. the Child-Pugh (CTP) score, which includes factors such as prothrombin time (PT), total bilirubin (T-Bil), albumin (Alb) and the degree of hepatic encephalopathy and ascites, and is still a good system for evaluating liver function.
2. Model for End-Stage Liver Disease (MELD) score, which includes PT, creatinine (Cr) and T-Bil, without subjective indicators, and can predict the occurrence of hepatorenal syndrome, which is better than CTP score.
3, Maddrey Discriminant Function (MDF) score, which was obtained from the clinical trial of hormone therapy for alcoholic hepatitis [MDF=4.6×(PT-normal control)+ T-Bil (mg/dL)], if the patient develops hepatic encephalopathy, MDF≥32, short-term mortality exceeds 50%.
Since the evaluation methods are biased, it is necessary to select the appropriate evaluation criteria and treatment methods according to the different stages (fatty liver or cirrhosis) and degrees of alcoholic liver disease in patients. Most scholars believe that a CTP >8, MELD score >11, and MDF ≥32 indicate a poor prognosis for the patient.
IV. Comprehensive treatment
Complete abstinence from alcohol is the most important and basic measure in all treatments. However, the treatment of alcohol withdrawal requires comprehensive cooperation between psychiatry and gastroenterology, neurology and infectious diseases.