What Are the Causes of Liver Failure?

As one of the important organs of the human body, the liver is also called a "processing plant" because it has functions such as synthesis, detoxification, metabolism, secretion, biological transformation, and immune defense. When severe damage is caused by a variety of factors (such as viruses, alcohol, drugs, etc.), a large number of hepatocytes will be necrotic, leading to severe impairment or decompensation of the above functions, and then coagulation mechanism disorders and jaundice, liver encephalopathy, ascites The main manifestation is a group of clinical syndromes, called liver failure. The main symptoms are extreme fatigue, decreased appetite, abdominal distension, nausea, vomiting, and changes in consciousness. Due to the rapid progress of the disease, the difficulty of treatment, the cost of medical treatment is expensive, and the overall prognosis is poor.

Meng Qinghua

(Chief physician)

Department of Hepatology, Beijing Youan Hospital

Western Medicine Name: Liver failure
Affiliated Department: Internal Medicine-Gastroenterology

Disease site: liver
The main symptoms: Jaundice, ascites, fatigue, low fever
Main cause: Virus, alcohol, drugs

Classification of liver failure diseases

According to the histopathological characteristics and the rate of disease progression, liver failure is divided into four categories: acute liver failure (ALF), subacute liver failure (SALF), and chronic acute (subacute) liver failure (acute-on-chronic liver failure (ACLF) and chronic liver failure (CLF). See the following table for specific definitions.

name	definition
Acute liver failure	Urgent onset, liver failure characterized by hepatic encephalopathy above degree within 2 weeks of onset
Subacute liver failure	Onset is more acute, clinical manifestations of liver failure occur within 15-26 weeks
Chronic acute (subacute) liver failure	Acute or subacute liver decompensation based on chronic liver disease
Chronic liver failure	On the basis of liver cirrhosis, chronic liver decompensation mainly due to ascites or portal hypertension, coagulopathy, and hepatic encephalopathy caused by progressive liver function decline

Causes of liver failure

At present in China, the main cause of liver failure is still the hepatitis virus (mainly hepatitis B virus, accounting for about 80-85%), followed by drugs or hepatotoxic substances (such as alcohol, chemical agents, etc.); Drugs are the main cause of acute and subacute liver failure, and alcohol often causes chronic liver failure. In addition, acute fatty liver of pregnancy, autoimmune liver disease, and parasitic infections can also cause liver failure.

The etiology of liver failure in children is uncommon and genetic metabolic diseases (including hepatolenticular degeneration, galactosemia, tyrosinemia, Reye syndrome, neonatal hemochromatosis, 1-antitrypsin deficiency, etc.) . Zhu Shishu and other analysis of 120 children with liver failure, the unknown cause of the infant group and the group over the age of 1 year were the first, with 40.6% and 30.7% respectively.

The cause of liver failure can be a single factor, such as infection with a certain hepatitis virus, alcoholism, taking a drug, etc., or a combination of factors, such as overlapping infection with other viruses and chronic alcoholism based on chronic hepatitis Based on the merger of viral infections. ^[1-2]

Pathophysiology of liver failure

Histopathological examination is of great value in the diagnosis, classification and prognosis of liver failure. Liver failure (except chronic liver failure) is mainly manifested by different degrees of hepatocyte necrosis and residual hepatocyte regeneration. The location and extent of necrosis vary according to the etiology and duration of the disease. In addition to the uneven distribution of hepatocyte necrosis, chronic liver failure is mainly diffuse liver fibrosis and abnormal nodule formation. ^[3]

Pathogenesis of liver failure

The pathogenesis of liver failure is very complex, and multiple factors can affect each other. The specific mechanism is not very clear. At present, the mechanisms that cause liver failure mainly include two aspects: one is the direct damage to liver cells by various factors, such as direct damage to liver cells by drugs and viruses, causing liver cells to different degrees of necrosis; the other is immune Mechanisms, such as immune damage mediated by cytokines or endotoxins.

Clinical manifestations of liver failure

Liver failure disease symptoms

Extreme weakness, severe gastrointestinal symptoms (abdominal pain, bloating, nausea, loss of appetite, vomiting), progressive deepening of yellow skin and mucous membranes, progressive deepening of urine color, severe coagulation dysfunction (cutaneous mucosal bleeding, nosebleeds, bleeding gums, digestion Tract hemorrhage, urethral hemorrhage, etc.) are the main common clinical features, and may also have low fever, corresponding manifestations of various complications, etc. The specific clinical manifestations are different due to different classifications of liver failure.

(1) Acute liver failure: acute onset, hepatic encephalopathy of degree or above (expressed as personality change, abnormal behavior, mental confusion, blurred consciousness, sleep disturbance, decreased orientation and comprehension, etc.) within 2 weeks. Beijing Youan Hospital summarized the data of 50 patients with acute liver failure: 88% of patients with high fatigue, 80% of patients with severe loss of appetite, 76% of patients with nausea and vomiting, and 84% of patients with abdominal distension. Among the patients, 78% were young adults under 40 years old. Because of her previous health and tolerance to the disease, she can continue to work or work in the early stages of the disease. In addition, insufficient understanding of the disease is also one of the reasons for the exacerbation and rapid deterioration of the disease.

(2) Subacute liver failure: the onset is relatively rapid, and the duration of onset is 15 to 26 weeks. In addition to the symptoms and signs the same characteristics as acute liver failure, jaundice deepens rapidly. Due to the prolonged course of the disease, the incidence of various complications Increase, such as: ascites, abdominal infections, hepatic encephalopathy, etc., patients will experience abdominal distension, edema, and disturbance of consciousness. Diagnosis is also divided into ascites or encephalopathy.

(3) Chronic acute (subacute) liver failure: previous chronic liver disease manifestations, acute or subacute liver decompensation in the short term, and clinical symptoms are heavier than the onset of acute hepatitis.

(4) Chronic liver failure: On the basis of liver cirrhosis, progressive decline in liver function and decompensation, coagulation dysfunction, ascites, gastrointestinal bleeding, hepatic encephalopathy and other complications.

Liver failure disease hazards:

Ge Zongcheng et al reported that the fatality rate of liver failure was 73.9%, among which the fatality rates of acute liver failure, subacute liver failure, and chronic liver failure were 87.8%, 69.3%, and 66.5%, respectively. The worse the coagulation function, the higher the fatality rate.

Diagnosis of liver failure

Auxiliary examination of liver failure :

Based on the above-mentioned classification of liver failure and the characteristics of various types of liver failure, the following related examinations need to be completed at the time of clinical consultation, and individualized examinations must be performed in accordance with the specific conditions of the patient.

project	content	significance
Whole blood cell analysis	WBC, Hemoglobin, Platelet, WBC Classification	Find out if there is hypersplenism and infection
Urine routine	Specific gravity, pH value, urobilinogen, urinary bilirubin, etc.	Indirect evaluation of the type of jaundice; preliminary judgment of the body's metabolic status
Stool routine + occult blood	Stool characteristics, cells and occult blood	Understand the presence of gastrointestinal bleeding
liver function	ALT, AST, TBIL, ALB, CHE, CHO, PALB	Understand the degree of liver damage and the ability of the liver to consolidate reserves
Blood biochemistry and blood sugar	K, Na, Cl, Bun, Cr, Glu	Learn about electrolytes, kidney function and blood glucose levels
Blood gas analysis	PH, PCO2, PO2, HCO3, etc.	Understand the body's acid-base balance
Blood ammonia	Blood NH3	Combined physical examination to assess the presence of hepatic encephalopathy
Coagulation term	PT, PTA, INR, etc.	PT, PTA, INR, etc.
Hepatitis virus marker	HAV-Ab, Hepatitis B five, HCV-Ab, HDV-AbHEV-Ab, other virus markers (CMV, EBV antibodies)	Understand the specific virus types that cause liver failure, such as HBV or HCV positive, then conduct further quantitative virus testing to assess the degree of virus replication
Serum alpha-fetoprotein	AFP	Indirect evaluation of disease prognosis
Ultrasound or CT, NMR	Abdominal organs BUS or CT, MRI	Assess liver size, degree of injury, and inner diameter of blood vessels and bile ducts, while excluding malignant obstructive lesions
Electronic gastroscopy or upper gastrointestinal angiography	Gastroscopy or barium meal	Understand esophageal varices and gastric mucosa, especially those with a history of chronic liver disease and long-term alcohol abuse

Differential diagnosis of liver failure :

The "Hepatic Failure Diagnosis and Treatment Guide" issued by the Liver Failure and Artificial Liver Group of the Infectious Diseases Branch of the Chinese Medical Association in 2006 and the Liver Failure and Artificial Liver Group of the Chinese Medical Association Hepatology Branch is applicable to various etiologies (virus, drugs, alcohol, etc. ) Liver failure caused by diagnostic criteria:

(1) Acute liver failure: acute onset, hepatoencephalopathy of degree or above occurs within 2 weeks, jaundice can be less than 10 times the upper limit of normal value, and jaundice progressively deepens in a short period; examination or ultrasound indicates progressive liver shrinkage.

(2) Subacute liver failure: the onset is relatively rapid, the onset period is 15 to 26 weeks, jaundice rapidly deepens, and the requirement is 10 times greater than the upper limit of normal value or a daily increase of 17.1umol / L.

(3) Chronic acute (subacute) liver failure: On the basis of chronic liver disease, the above-mentioned acute (subacute) liver decompensation manifests in the short term, and the test is TBIL 171umol / L, and PTA 40%.

(4) Chronic liver failure: On the basis of cirrhosis, progressive liver function decline and decompensation. The main points of diagnosis are: with ascites or other portal hypertension (reduced blood, gastrointestinal bleeding, etc.); hepatic encephalopathy; serum total bilirubin increased (can be less than 10 times the upper limit of normal value), albumin Significantly reduced; Must have coagulopathy, PTA 40%.

Liver failure treatment

At present, there is no specific and effective treatment for the clinical treatment of liver failure, and comprehensive treatment is emphasized, including basic medical treatment, artificial liver support treatment and liver transplantation treatment.

Liver failure medication

(1) Principles of basic medical treatment: early diagnosis, early treatment, appropriate comprehensive treatment for different causes, and active prevention and treatment of various complications to win time for liver cell regeneration.

General supportive treatment: bed rest, strict disinfection and isolation, ensuring daily energy and fluid supply, maintaining internal environment stability, dynamically monitoring changes in liver function, blood biochemistry, and coagulation terms.

Treatment for the cause and pathogenesis:

a. Etiology treatment: For patients with liver failure who are positive for HBV markers and HBV DNA, use nucleoside analogs such as lamivudine, telbivudine, and entecavir, as appropriate, on the basis of informed consent. Clinical studies have shown that: Active and effective antiviral therapy can inhibit viral replication, can curb the inflammatory process of liver failure in the near future, can inhibit the onset of inflammation in the long run, delay liver fibrosis, and reduce the incidence of liver cancer; however, attention should be paid to virus mutations and subsequent disease progression in subsequent treatment Possible. For liver failure caused by drugs or alcohol, promptly stop suspicious drugs and strictly abstain from alcohol.

b Hormonal therapy: Studies have shown that glucocorticoids have a significant effect on reducing the mortality of acute liver failure (especially alcoholic liver failure), but the application of glucocorticoids to patients with chronic acute liver failure caused by HBV is controversial. Zhou Xianshan et al. Through a randomized study of 63 patients with early chronic severe hepatitis B / ACLF found that the application of glucocorticoids (dexamethasone 10mg / day × 7 days) on the basis of antiviral therapy, and then gradually reduced the total course of treatment 7 weeks) can effectively improve clinical symptoms, total bilirubin and prothrombin activity, while not increasing the incidence of complications such as abdominal infections and gastrointestinal bleeding. We used 30 patients with HBV-ACLF as the treatment group and applied methylprednisolone in the previous group, and 26 patients in the control group. The results suggest that hormones can improve the prognosis of patients.

c. Nutrition support and hepatocyte regeneration promotion treatment: In order to reduce hepatocyte necrosis and promote liver cell regeneration, drugs such as hepatotrophin and prostaglandin El (PEG1) liposome can be used as appropriate, but the efficacy needs to be further confirmed. What needs to be emphasized here is that nutrition support treatment, providing the necessary amount and balanced nutritional substrate is the key to liver regeneration and reducing mortality. Our recent studies suggest that patients with liver failure not only have a low metabolic state but also have a high chance of survival. It is sufficient to ensure basic metabolic requirements during the critical period of the disease. Excessive glucose input and excessive energy are not conducive to the disease. Rehabilitation. In addition, nutritional intake through the gastrointestinal tract is recommended at any stage of the disease, and insufficient parts are given intravenously.

d Intestinal protection and other: Intestinal mucosal barrier function is closely related to the incidence of spontaneous peritonitis in patients with liver failure. More importantly, 80% of secreted IgA comes from intestinal chorionic epithelial cells, and the body's immune status It is closely related to the patient's prognosis, so protecting the gut is essential. We emphasize that regular nutrition is an important measure to protect the intestines and nourish the intestines. In addition, oral intestinal probiotics, lactulose, etc. are beneficial to maintain the intestinal environment; antioxidants are selected as appropriate, such as: reduced glutathione, polyene phosphatidylcholine that repairs liver cell membranes, and adenosine that alleviates cholestasis Methionine and other medications.

Active prevention and treatment of various complications: According to the characteristics of the causes, pathogenesis and clinical manifestations of various complications, select targeted prevention and treatment methods. ^[4-5]

Liver failure surgery

(2) Artificial liver support treatment: There are many types. At present, the most commonly used clinical practice is plasma exchange. The principle is to replace the plasma of patients with liver failure with fresh plasma to eliminate harmful substances, supplement essential substances in the body, and improve the internal environment. Role, temporarily replacing part of the function of the failed liver, creating conditions for liver cell regeneration and liver function recovery or waiting for opportunities for liver transplantation. Artificial liver treatment is also a part of comprehensive medical treatment. Choosing suitable indications and the application of internal environment adjustment drugs after plasma exchange can enhance the value of artificial liver treatment and save blood for the country.

(3) Liver transplantation treatment: Liver transplantation is an indispensable part of the integrated (integrated) treatment of liver failure by internal medicine-artificial liver-liver transplantation. In recent years, experience in the application of rejection drugs in addition to transplantation surgery, postoperative antiviral treatment and There have been major academic advances in preventing recurrence of tumors, but they are limited due to liver shortages and high costs. For intermediate and advanced liver failure caused by various reasons, those with acute liver failure who are still irreversible after active medical treatment and artificial liver treatment should consider liver transplantation as soon as possible. ^[6]

Prognosis of liver failure disease

The prognosis of liver failure depends on the "competition" between the degree of hepatocyte necrosis and the ability to regenerate. If a large number of hepatocytes regenerate more than necrosis, the disease gradually recovers. Otherwise, the condition worsens and the prognosis is poor. However, due to the diversity and individual differences of inducement, etiology, clinical type, course, complications, and clinical intervention measures of liver failure, there is no unified assessment index for prognosis. Currently recognized prothrombin time activity percentage (PTA), prothrombin time internationalization ratio, and serum creatinine are correlated with the prognosis of liver failure. In addition, some studies have also suggested that serum alpha-fetoprotein (AFP), serum sodium, lactate levels, arterial blood ammonia, and phosphate are related to the prognosis of liver failure. ^[7]

Liver failure diet note

Due to the loss of appetite in patients with liver failure accompanied by obvious gastrointestinal symptoms, absorption and indigestion are more common. In addition, the metabolism of the three major nutrients of sugar, fat, and protein is disturbed during liver failure, and the status of malnutrition is particularly prominent. In the treatment of patients with failure, we have found that reasonable and effective nutritional support can meet the body's energy needs, promote liver cell regeneration, improve liver function, improve the body's immunity and resistance to infection and toxins, reduce the incidence of complications, and improve disease prognosis Is often more important than medicine.

Through resting energy metabolism measurements and dietary records of patients with different liver failure, we found that patients with liver failure generally suffer from insufficient dietary nutrition intake and three major nutrient metabolism imbalances in the body, combining the clinical types of patients with liver failure and the characteristics of different complications. The diet should pay attention to the following points:

(1) The diet of patients with liver failure should avoid foods that are hard, spicy, hot, and fast food. The food should be light, fresh, digestible, and mainly liquid and semi-liquid diets; strictly limit the intake of tobacco and alcohol;

(2) In the early stage of the disease, intravenous nutrition is mainly used, supplemented by oral administration. During the recovery period, oral nutrition is mainly used, supplemented by intravenous administration. Some critically ill patients can perform nutritional infusion through the nasal duodenal nutrition tube. If there is no diabetes, You can choose how to eat less and eat more;

(3) In the case of intravenous nutrition support treatment, the nutrient solution should include a comprehensive supplement of glucose, medium and long-chain fatty milk, amino acids, and multivitamins, electrolytes, and trace elements. It is advisable to continue slow intravenous infusion;

(4) Ensure a total daily calorie intake of 1500 kcal (depending on the severity of the disease). For patients with hepatic encephalopathy, the intake of protein should be limited and amino acid preparations can be taken;

(5) In addition to eating during the day, the need for a meal before bedtime (200-300 kcal) is emphasized. Studies have shown that a meal before bedtime (mainly 50 grams of carbohydrates) helps improve the body's "hungry state". Ultimately improve the patient's body metabolism;

(6) For patients with a large amount of ascites or edema, the intake of salt and water should be appropriately controlled. The daily sodium salt intake is 500-800mg (1.2-2.0g of sodium chloride), and the water intake is limited to about 1000ml. If there is severe hyponatremia, it should be adjusted under the guidance of a doctor.

(7) Yogurt contains more lactic acid bacteria, which can inhibit the reproduction of harmful bacteria in the intestine, and can promote the absorption of calcium, phosphorus, and iron. It is recommended to take it between meals. ^[8-9]

Liver failure disease prevention

The prevention of liver failure first emphasizes the prevention of the cause:

(1) For patients with chronic hepatitis virus infection, liver function and hepatitis B virus replication status should be checked regularly every year, abnormal liver function should be found, and effective treatment measures should be taken in time under the guidance of specialists. , Chronic hepatitis patients should be hospitalized in time as soon as jaundice occurs, be alert for liver failure;

(2) Patients who have been treated with oral antiviral drugs must not stop the drug without authorization. Once the drug is discontinued, it will cause a large number of virus replication and the immune response will cause acute liver failure. It is necessary to regularly review liver function and hepatitis B virus quantification, etc., to understand whether there is a mutation in the virus, and to adjust the treatment plan in time if it appears. Withdrawal standards should be implemented in accordance with the guidelines;

(3) For alcoholics, it is necessary to abstain from alcohol, but also to abstain from alcohol;

(4) The use of drugs should be cautious, and the traditional Chinese medicine of common drug-induced liver failure cannot be ignored, and the idea of "harmlessness of traditional Chinese medicine" should be eliminated.

Liver failure complications

Ge Zongcheng retrospectively analyzed the incidence of complications of acute liver failure, subacute liver failure, and chronic liver failure among 437 patients with liver failure. The incidences of hepatic encephalopathy were 70.7%, 41.3%, and 37.3%, respectively. It was 51.2%, 58.6%, and 88%. The incidence of electrolyte disorders was 65.8%, 54.8%, and 81.5%, the incidence of cerebral edema was 70.7%, 35.6%, and 14.7%. The incidence of hepatorenal syndrome was 21.9%, 18.3%, 17.5%, the incidence of spontaneous peritonitis was 12.2%, 22.1%, 52.7%, the incidence of cerebral hernia was 17.1%, 8.6%, 6.5%, and the incidence of upper gastrointestinal bleeding was 12.2% , 14.4%, 30.5%. ^[10]

(1) Hepatic encephalopathy: Hepatic encephalopathy can cause neurological disorders of varying degrees due to comprehensive liver function disorders, which are mainly manifested as disturbances of consciousness, behavioral disorders, and coma, which can eventually lead to death.

(2) Water and electrolyte acid-base imbalance: due to severe gastrointestinal symptoms and the use of diuretics, low sodium, low potassium, hyperkalemia, and acid-base disorders may occur.

(3) Renal insufficiency: Due to insufficient circulating blood volume, endotoxin and other effects, functional renal insufficiency can be caused. If it is not corrected in time, it can lead to organic renal insufficiency and eventually renal failure.

(4) Severe nosocomial infections: due to the patient's low immune function, intestinal microecological imbalance, reduced intestinal mucosal barrier effect, and more aggressive operations, etc., various nosocomial infections can be combined during the hospitalization to aggravate the disease, including various fungi and Bacteria and so on.

(5) Various bleeding caused by impaired coagulation and energy supply: such as nosebleeds, mucosal ecchymosis and even internal bleeding.

(6) blood glucose metabolism abnormalities: due to poor appetite and liver metabolic disorders of glucose, severe hypoglycemia may occur.