Liver failure

　　Liver failure can be caused by various reasons, the most common being various viral hepatitis and some side effects of drugs.

　　1. Various types of viral hepatitis such as hepatitis A, B, C, D, and E. It can also be caused by mixed or superimposed infection of two or more types of hepatitis viruses.

　　2. Medications such as antipyretics and analgesics like acetaminophen, analgin, and aspirin; antituberculosis drugs like rifampin and rifabutin; and other drugs such as halothane, methyldopa, antimonials, arsenic, sulfonamides, etc.

　　3. Poisoning such as mushroom poisoning, smelly rice powder poisoning, carbon tetrachloride poisoning, etc.

　　4. Hypoxic liver injury such as liver congestion and hypoxia caused by persistent heart failure or shock.

　　5. Other complications such as acute Wilson's disease, etc. Chronic liver failure: It often occurs in the process of chronic severe hepatitis and various types of liver cirrhosis, etc.

　　During the extreme stage of liver failure, the main manifestation is hepatic encephalopathy, and complications may occur, such as:

　　1. Cerebral edema When there are ankle clonus and positive pyramidal tract signs, there is already cerebral edema, or there are conjunctival edema, dilated and fixed pupils, slow and irregular breathing, and papilledema, all indicating the presence of cerebral edema.

　　2. Coagulation dysfunction and bleeding Bleeding sites are commonly found in the skin, gingiva, nasal mucosa, conjunctiva, and gastric mucosa, etc.

　　3. Infection Respiratory tract infections are the most common, followed by urinary tract infections, which are mostly caused by Gram-negative bacilli, Gram-positive cocci, and can also be caused by anaerobic bacteria and fungal infections.

　　4. Renal failure In FHF, renal dysfunction reaches 70%, and acute tubular necrosis accounts for half of the cases. There may be high urine sodium, isotonic urine, and tubular necrosis. It is related to factors such as liver cell necrosis, endotoxemia, inappropriate use of diuretics, gastrointestinal bleeding leading to hypovolemia and hypotension. There are reports that renal failure is the leading cause of death in FHF, which deserves attention.

　　5. Disruption of electrolyte and acid-base balance Hyponatremia, hypocalcemia, hypomagnesemia, hypokalemia, respiratory alkalosis, metabolic alkalosis, and metabolic acidosis, etc.

　　6. Other symptoms include hypoglycemia, hypoxemia, pulmonary edema, arrhythmia, portal hypertension, and acute pancreatitis, etc.

　　The clinical manifestations of liver failure are divided into two stages: the early stage and the late stage. The clinical manifestations in each stage are different.

　　Early symptoms

　　Some systemic symptoms may appear in the early stage of liver failure.

　　1. Jaundice is commonly known as yellow disease, caused by elevated bilirubin in serum, resulting in yellowing of the skin, mucous membranes, and sclera.

　　(1) If the total bilirubin is greater than 171μmol/L within a short period after the onset of jaundice, and accompanied by other severe liver dysfunction symptoms such as bleeding tendency, prolonged prothrombin time, and elevated ALT, it indicates abnormal liver function. If only severe jaundice is present without other serious liver dysfunction, it indicates intrahepatic cholestasis;

　　(2) The duration of jaundice is long, the general rule of the rise and fall of jaundice is deepening, persistence, and regression in three stages. If the jaundice does not subside after 2 to 3 weeks, it indicates a severe condition.

　　(3) There is no improvement in the condition after the appearance of jaundice, which is generally the acute jaundice type of hepatitis. When jaundice appears, appetite gradually improves, and nausea and vomiting decrease. If there is no improvement in symptoms for one week after the appearance of jaundice, one should be vigilant for severe hepatitis.

　　2. Persistent low fever, there may be low fever at the beginning of the disease, and the body temperature decreases to normal after jaundice appears. If there is a persistent low fever with jaundice, it indicates the necrosis of liver cells or endotoxemia.

　　3. General symptoms of fatigue, lassitude, anorexia, and in severe cases, even unable to manage daily life.

　　4. Marked and frequent gastrointestinal symptoms, such as frequent nausea and vomiting, belching, marked abdominal distension, disappearance of bowel sounds, and intestinal paralysis.

　　5. Bleeding tendency, such as skin ecchymosis, purpura, epistaxis, gingival bleeding, and a few cases of upper gastrointestinal bleeding, indicating coagulation dysfunction and liver failure.

　　6. Ascites due to the long half-life of albumin (about 2 weeks), generally low albuminemia appears 2 to 3 weeks after the disease, and ascites are common in patients with a course of more than 2 to 8 weeks.

　　7. Character change, such as from originally cheerful to suddenly depressed, or vice versa. The sleep rhythm is reversed, language is repetitive, unable to构思, disorientation, eccentric behavior, urinating anywhere, etc., are all signs of hepatic encephalopathy. Subsequently, there is disturbance of consciousness, and enter hepatic coma.

　　8. Progressive liver shrinkage, liver odor, flapping tremors, increased muscle tone, positive corticospinal tract signs, clonus, and other symptoms indicate severe liver damage.

　　9. Heart rate acceleration and hypotension are related to endotoxemia or internal hemorrhage.

　　10. Cerebral edema and pulmonary edema may be related to inappropriate large amounts of fluid replacement and hypoxia, which are prone to cause cerebral hernia and respiratory failure.

　　II. Late symptoms

　　During the extreme stage of the disease, the main manifestation is hepatic encephalopathy, followed by the following symptoms, and the transitional stage between them is not easily separated.

　　1. Cerebral edema, when there are clonus, positive corticospinal tract signs, there is already cerebral edema, or conjunctival edema, dilated and fixed pupils, slow and irregular breathing, and papilledema, all indicating the symptoms of cerebral edema.

　　2. Coagulation dysfunction and hemorrhage, the bleeding sites are commonly found in the skin, gingiva, nasal mucosa, conjunctiva, and gastric mucosa, etc. The cause of bleeding is:

　　(1) Abnormal platelet quality and quantity, in FHF, platelets are smaller than normal, electron microscopy can show vacuoles, pseudopods, and blurred cell membranes. Platelets are normal without hepatic encephalopathy. Platelet reduction may occur due to bone marrow suppression, splenic hyperfunction, and consumption by intravascular coagulation.

　　(2) Deficiency in coagulation factor synthesis, all coagulation factors in the plasma are reduced, especially Factor VII, which is synthesized outside the liver, leading to an increase. The prothrombin time is significantly prolonged.

　　(3) DIC accompanied by secondary local fibrinolysis, the plasma levels of plasmin and its activators are both decreased, while the products of fibrin/fibrinogen degradation increase.

　　3. Infection is most common through respiratory tract infection, other cases may develop urinary tract infection, mostly caused by Gram-negative bacilli, Gram-positive cocci, and may also involve anaerobic bacteria and fungal infections.

　　4. Renal Failure Renal dysfunction reaches 70% in FHF, with acute tubular necrosis accounting for half. There are high urine sodium, isotonic urine, and tubular necrosis. It is related to factors such as liver cell necrosis, endotoxemia, inappropriate use of diuretics, gastrointestinal bleeding leading to hypovolemia and hypotension.

　　5. Electrolyte and Acid-Base Balance Disorders Low sodium, low calcium, low magnesium, low potassium, respiratory alkalosis, hypochloremic alkalosis, and metabolic acidosis.

　　6. Other complications such as hypoglycemia, hypoxemia, pulmonary edema, arrhythmia, portal hypertension, and acute pancreatitis. Severe complications such as hepatorenal syndrome and shock may occur.

　　The mortality rate of acute liver failure is relatively high, and efforts should be made to prevent its occurrence. Clinically, what can be done is to pay attention to the adverse effects on the liver when taking medication. For example, when treating tuberculosis with rifampicin, isoniazid, or pyrazinamide, blood transaminases and bilirubin should be checked. If changes in liver function are detected, the medication should be changed promptly. For patients undergoing major surgical procedures, attention should be paid to the patient's liver function before surgery, especially for those with pre-existing liver cirrhosis, hepatitis, jaundice, hypoalbuminemia, and other conditions. Adequate preparation is required. Anesthesia should avoid hepatotoxic drugs. During the operation and postoperative period, it is necessary to prevent hypoxia, hypotension, or shock, infection, and other factors to avoid damage to liver cells; postoperatively, liver function should be monitored continuously according to the condition, maintaining good respiration and circulation, anti-infection, and maintaining nutritional metabolism, which has a positive effect on the liver.

　　The most important clinical examination for liver function damage is the prothrombin time test, which is one of the most valuable indicators reflecting the severity of damage and is helpful for early diagnosis. This test requires strict implementation and should be performed by experienced personnel to ensure accuracy. It is manifested by a significant prolongation of the prothrombin time. Clinically, other examination methods should be combined to make a definitive diagnosis.

　　1. Cholesteryl Esterase Measurement

　　This enzyme is synthesized by liver cells, so in severe liver damage, the serum cholesteryl esterase level is significantly reduced.

　　2. Bile Enzyme Separation Phenomenon

　　Bilirubin levels gradually increase while ALT levels decrease. 80% of ALT is present in the cytoplasm of liver cells. When liver cells are damaged, the permeability of the cell membrane changes, and ALT leaks into the blood. Early ALT levels may increase, but as the condition worsens, the enzyme is exhausted at a certain stage, and with its short half-life, the serum ALT level decreases, indicating a poor prognosis.

　　3. Dynamic Observation of AST/ALT Ratio

　　Measurement within 10 days after the onset of the disease has certain significance for predicting the condition and prognosis. ALT is mainly present in the cytoplasm of liver cells, while AST is mostly located in the mitochondria, with a normal AST/ALT ratio of 0.6. When liver cells are severely damaged, AST is excreted from the mitochondria, and the ratio exceeds 1.

　　4. Amino Acid (AA) Measurement

　　Including total urine amino acid levels and serum tyrosine analysis. Since almost all amino acids are metabolized in the liver and synthesized by liver cells into the human body's essential proteins. When severe liver damage occurs, amino acids (AA) cannot be utilized, leading to AA metabolic disorders and imbalances.

　　Maintain a regular diet and do not overeat. Liver disease patients or those with abnormal liver function should pay attention to dietary taboos: crabs, animal internal organs, a variety of seafood (such as yellow croaker, cuttlefish, etc.) should not be eaten, and high-fat, high-cholesterol foods should not be taken arbitrarily. Foods that are nutritious and suitable for liver disease patients include freshwater fish, soy products, and vegetables and fruits.

　　Try to reduce unnecessary extra food, control the dietary calories between 1800 to 2200 kcal, and eat to eight parts full at each meal. These are the principles we should follow.

　　Six principles of liver-protecting diet

　　1. Maintain a balanced diet, with staple food as the main part, eat more vegetables and fruits;

　　2. Do not eat unclean food, especially moldy peanuts and unfermented sauerkraut;

　　3. Eat less animal oil and fatty meat;

　　4. Do not drink excessively, and do not drink on an empty stomach, as drinking on an empty stomach is more likely to absorb acetaldehyde.

　　5. When eating barbecue, do not eat food that comes into direct contact with the charcoal fire, as it contains more carcinogens than electric barbecue and iron plate barbecue.

　　6. Canned food is prone to microbial contamination, which can harm the liver. It is appropriate to supplement B vitamins and minerals, such as cereal foods.

　　Early detection and treatment of liver function failure have the possibility of recovery, but a considerable number of patients have poor prognosis. Patients should lie in bed absolutely, avoid and remove the causes of hepatic coma, prevent and control infection, timely treat hemorrhage, strengthen symptomatic supportive therapy. Those who have the condition should consider liver transplantation surgery.

　　One, etiology treatment

　　1. Patients with HBV, HCV, HDV co-infection, hepatitis virus, or those with a slow progression of the disease in the early stage can be treated with antiviral drugs such as interferon.

　　2. Patients with onset caused by medication should discontinue the medication.

　　Two, immune regulation:It is appropriate to use immunoenhancers such as thymic peptides, but it is not advisable to use adrenal cortical hormones and immunosuppressants.

　　Usage: 6 to 20mg per day added to 250 to 500ml of 10% glucose solution, infused slowly intravenously once a day, 30 days as one course of treatment, skin test should be done before medication.

　　Three, glucagon-insulin therapy (GI therapy):The principle is to resist liver cell necrosis and promote liver cell regeneration.

　　Usage: Insulin-like growth factor 1mg, insulin 10U added to 500ml of 10% glucose solution, infused slowly intravenously, 1 to 2 times a day, combined with preparations mainly containing branched-chain amino acids, with good efficacy. Generally, 2 to 4 weeks is one course of treatment.

　　Four, treatment of hepatic encephalopathy

　　1. 14-amino acid 800, 6-amino acid 520: The former is suitable for liver cirrhosis and hepatic encephalopathy. Both contain branched-chain amino acids and do not contain aromatic amino acids.

　　Usage: 6-amino acid 520, 250ml each time, twice a day, infused slowly intravenously after串联with an equal amount of 10% glucose solution and 500mg of L-acetylglutamic acid, reduce the dose by half when consciousness returns to normal, until completely清醒, the course of treatment is 5 to 7 days. After that, 14-amino acid 800 is used to consolidate the efficacy. Note that Sohamine or Freamine, a compound amino acid, contains a high amount of tyrosine, phenylalanine, and methionine, which may trigger hepatic encephalopathy.

　　2. Levodopa and Carbidopa: This drug should not be used with Vitamin B6, as Vitamin B6 has dopa decarboxylase activity, which causes levodopa to decarboxylate, reducing dopamine concentration in the brain and losing its effect, making the efficacy not very ideal.

　　Usage: 100mg of levodopa, 10mg of carbidopa added to 500ml of 10% glucose solution, administered by slow intravenous infusion, once or twice a day. The combination of the two drugs can reduce the side effects of levodopa.

　　3. Control the production of ammonia

　　(1) Cleansing enema: Use 30ml of vinegar and 1000ml of normal saline for enema, or normal saline enema, twice a day. After enema, use 30ml of 50% lactulose and 100mg of neomycin in 100ml of normal saline for retention enema.

　　(2) Oral metronidazole or ampicillin.

　　(3) Lactulose therapy: Use 30-50ml of 50% lactulose, taken three times a day, orally (nasogastric feeding can be used for coma patients), preferably after meals, until two bowel movements of paste-like feces are achieved each day. This method can acidify the intestinal environment, reduce blood ammonia, and eliminate endotoxemia.

　　Five, treatment of complications

　　1. Cerebral edema: Prevention is more important than treatment for cerebral edema. When there is hyperreflexia of the patellar reflex, clonus of the ankle, or positive corticospinal tract sign, the effect is better.

　　(1) Diuretic: 20% mannitol or 25% inositol, 250ml each time, administered by rapid pressure intravenous infusion, which must be completed within 20-30 minutes. Subsequently, use it once every 4-6 hours, and add Furosemide between two diuretic sessions if necessary. If consciousness improves, the dosage can be halved, but the interval should not be extended to avoid rebound. Sorbitol has a slightly lower diuretic effect than mannitol, but does not cause hematuria as a side effect. It is safer to use sorbitol for severe hepatitis patients with encephalopathy.

　　(2) Dexamethasone: 10mg of dexamethasone is added to an appropriate amount of 10% glucose solution for intravenous bolus injection, followed by the use of 5mg in combination with a diuretic every 4-6 hours, for 2-3 days consecutively.

　　2. Prevention and treatment of hemorrhage

　　(1) To supplement coagulation factors, use thrombin complex (PPSB) containing II, V, VII, and IX coagulation factors, with an effective dosage of 10U/kg per day.

　　(2) H-2 receptor blockers: These drugs are mainly metabolized in the liver and kidneys. There have been reports that Cimetidine can cause liver damage as a side effect, so Ranitidine (Ranitidine) is used, with a dosage of 150mg, once a day at night. It has few side effects, good efficacy, and can prevent gastric hemorrhage.

　　(3) To reduce portal vein pressure, use Propranolol, with the dosage adjusted to slow down the heart rate by 25%. When used in combination with H-2 receptor blockers, the dosage can be reduced.

　　(4) Thrombin dosage is 2000-10000U per time, once every 4-6 hours, or once every 1-2 hours at the shortest interval. This method has satisfactory hemostatic effect on gastric mucosal erosion and bleeding, and渗血. When bleeding stops, the dosage can be reduced or the interval between taking the medicine can be extended.

　　3. Prevention and treatment of infection

　　(1) Strengthen oral and skin care, strictly implement disinfection and isolation, sterile operation, purify indoor air, and prevent respiratory tract infection.

　　(2) For endotoxemia, hydroxymethylpenicillin or Lactobacillus probiotics can be used to inhibit intestinal bacteria.

　　(3) For bacterial infections, it is necessary to select antibiotics that are non-toxic to the liver and kidneys, such as ampicillin, amoxicillin, kanamycin, and cephalosporins.

　　4. Renal Failure: This disease has a high mortality rate, and prevention is more important than treatment.

　　1. Control the intake of fluids and avoid using drugs that damage the kidneys.

　　2. Early use of osmotic diuretics, drugs to improve microcirculation, and prevention of hyperkalemia, etc. Hemodialysis and peritoneal dialysis have no significant therapeutic effect on this disease.

　　Six, Prevention and treatment of acid-base balance disorders of electrolytes:Adjust the treatment plan according to blood gas analysis and electrolyte changes over time.

　　1. Metabolic alkalosis, respiratory alkalosis combined with metabolic acidosis, metabolic acidosis, and other conditions.

　　2. Hyponatremia, hypocalcemia, hypomagnesia, hypokalemia, and other conditions.

　　Seven, Hepatocyte Growth Factor Therapy (HGF):

　　1. According to multi-center cooperative research reports in China, the addition of HGF or prostaglandin E1 on the basis of comprehensive therapy, or the combination of traditional Chinese and Western medicine in the treatment of fulminant liver failure and hepatic encephalopathy, has significantly reduced the mortality rate compared with the past, which may be related to early diagnosis, strengthening comprehensive support therapy and nursing.

　　2. In recent years, many reported cases of liver disease have shown varying degrees of increase in serum HGF, and the activation of HGF receptor and cmet gene (cancer gene proto-oncogene) are related. Therefore, before the wide application of HGF, it is necessary to understand the benefits and drawbacks of giving high-dose exogenous HGF and the possible activation of proto-oncogenes, which requires further in-depth study.

　　The survival rate of fulminant liver failure varies depending on the patient's condition and etiology:

　　(1) The survival rate can reach 50% for young patients with acetaminophen poisoning or hepatitis A.

　　(2) The survival rate of patients over 40 years old and hepatitis caused by certain drugs may be less than 10%.

　　(3) The mortality rate after orthotopic liver transplantation has dropped to 20% to 30%, and the one-year survival rate has reached 55% to 80%.

　　Since liver transplantation can effectively save the lives of patients, liver transplantation should be performed in a timely manner for patients with poor prognosis, and the indicators for poor prognosis are the indications for liver transplantation.