(A) Comprehensive internal medicine treatment
Principle: At present, there is a lack of specific drugs and means for the medical treatment of liver failure. In principle, we emphasize early diagnosis and early treatment, and take corresponding comprehensive treatment measures for different causes and actively prevent and treat various complications.
1.General supportive treatment
(1) Bed rest, reduce physical exertion, reduce the burden on the liver.
(2) Strengthen the monitoring of the disease.
(3) High-carbohydrate, low-fat and moderate protein diet; for those who do not eat enough, provide sufficient fluids and vitamins intravenously daily to ensure a total calorie intake of more than 6272 k (1500 kcal) per day.
(4) Actively correct hypoproteinemia, supplement albumin or fresh plasma, and supplement coagulation factors as appropriate.
(5) Pay attention to the correction of water, electrolyte and acid-base balance disorders, especially to correct hyponatremia, hypochlorhydria, hypokalemia and alkalosis.
(6) Pay attention to disinfection and isolation, strengthen oral care, and prevent the occurrence of intra-hospital infection.
2.Treatment for etiology and pathogenesis
(1) Treatment for the cause or specific treatment
① For patients with HBV DNA positive liver failure, nucleoside analogues such as lamivudine, adefovir, entecavir, etc. can be used as early as appropriate on the basis of informed consent. However, attention should be paid to the possibility of viral mutation during subsequent treatment and exacerbation of the disease after drug discontinuation.
② For drug-related liver failure, drugs that may cause liver damage should be discontinued first; for acetaminophen poisoning, N acetylcysteine (NAC) should be given, preferably by oral activated charcoal plus NAC intravenous drip before the onset of liver failure.
(3) Mushroom poisoning can be treated with silymarin or penicillin G according to the clinical experience in Europe and America.
(2) Immunomodulatory therapy
There are still different opinions on the application of adrenocorticotropic hormone in the treatment of hepatic failure. Non-viral infectious liver failure, such as autoimmune liver disease and acute alcoholism (severe alcoholic hepatitis) are indications. Other causes of hepatic failure in the early stages may be used if the disease progresses rapidly without serious complications such as infection and bleeding.
To regulate the immune function of the organism in patients with liver failure and to reduce complications such as infection, immunomodulators such as thymosin alpha may be used as appropriate.
(3) Hepatocyte growth promotion therapy can be used to reduce hepatocyte necrosis and promote hepatocyte regeneration by using hepatocyte growth promoters and prostaglandin E1 (PEG1) liposomes, as appropriate, but the efficacy needs to be further confirmed.
(4) Other treatments can be applied to intestinal microecological regulators, lactulose or lactitol to reduce intestinal bacteria or endotoxemia; and treatment with drugs to improve microcirculation and antioxidants, such as NAC and reduced glutathione, as appropriate.
3.Prevent and control complications
(1) Hepatic encephalopathy.
① Removal of causative factors, such as severe infection, bleeding and electrolyte disturbance (HI).
② Restrict protein diet.
(③ Apply lactulose or lactitol, orally or by high enema, to acidify the intestine, promote ammonia excretion and reduce absorption of toxins of intestinal origin.
④ Selecting ammonia-lowering drugs such as arginine, ornithine monomenclonine, as appropriate, depending on the patient’s electrolyte and acid-base balance.
⑤ Use branched-chain amino acids or a mixture of branched-chain amino acids and arginine as appropriate to correct amino acid imbalance.
(6) Artificial liver support therapy.
(2) Cerebral edema.
(1) if there is increased intracranial pressure, give hypertonic dehydrating agents, such as 20% mannitol or glycerol fructose, but use with caution in patients with hepatorenal syndrome; (2) loop diuretics, usually furosemide, can be used alternately with osmotic dehydrating agents; (3) artificial liver support therapy
(3) Hepatorenal syndrome.
① high-dose loop diuretic shock, furosemide can be pumped continuously; ② limit the amount of fluid intake, the total 24-h intake should not exceed the volume of urine plus 500-700 ml; ③ the inadequate renal perfusion pressure can apply albumin expansion or add terlipressin and other drugs, but patients with acute liver failure should be cautious with terlipressin, so as not to increase cerebral edema due to increased cerebral blood flow; ④ artificial liver support therapy.
(4) Infection.
① Patients with liver failure are prone to co-infection, commonly due to low immune function, imbalance of intestinal microecology, reduced intestinal mucosal barrier and more invasive operations; ② Common infections in patients with liver failure include spontaneous peritonitis, pulmonary infection and sepsis; ③ Common pathogens of infection are gram-negative bacilli such as Escherichia coli, staphylococci, Streptococcus pneumoniae, anaerobes, enterococci Bacteria and fungi such as Pseudomonas; ④ Once an infection occurs, it should first be used empirically, with strong antibiotics or a combination of antibiotics, while micro-ecological regulators can be added. As far as possible, pathogen isolation and drug sensitivity test should be conducted before applying antibiotics, and the medication should be adjusted according to the drug sensitivity results. Also pay attention to the prevention and control of secondary infection.
(5) Bleeding.
① For patients with portal hypertensive bleeding, in order to reduce portal pressure, growth inhibitor analogues are preferred, and posterior pituitary hormone (or combined application of nitrates) can also be used; hemostasis can be stopped by compression with a three-lumen tube; or hemostasis can be stopped by endoscopic sclerotherapy injection or ligature treatment; if conservative medical treatment is ineffective, emergency surgery can be performed. For patients with diffuse intravascular coagulation, fresh plasma, prothrombinogen complex and fibrinogen can be given to supplement coagulation factors, platelets can be transfused if platelets are significantly reduced, small doses of low molecular heparin or normal heparin can be given as appropriate, and anti-fibrinolytic drugs such as tranexamic acid or hemostatic aromatic acid can be applied to those with evidence of hyperfibrinolysis.
(B) Artificial liver support therapy
1.Treatment mechanism and method
Artificial liver is a treatment method to remove various harmful substances, replenish essential substances, improve the internal environment and temporarily replace part of the function of the failing liver through mechanical, physicochemical or biological devices outside the body, which can create conditions for hepatocyte regeneration and liver function recovery or wait for the opportunity to carry out liver transplantation. There are three types of artificial liver support systems: non-biological, biological and hybrid. The non-biological type of artificial liver has been widely used in clinical practice and has been proven to be effective. The currently used non-biologic artificial liver methods include plasma exchange (PE), hemoperfusion (HP), plasma bilirubin absorption (PBA), hemofihration (HF), hemodialysis (HD), and hemodialysis. hemodialysis (HD), albumin dialysis (AD), plas-madiafiltration (PDF), and continuous blood purification (CBP). etc. Since the principles of various artificial livers are different, different methods should be chosen individually or in combination according to the patient’s specific situation: PE combined with CBP, HF or PDF in case of cerebral edema or renal failure; PBA or PE in case of hyperbilirubinemia; HD or AD (HI) in case of water and electrolyte disorders. Attention should be paid to the standardization of the operation of artificial liver therapy. Biological and mixed biological artificial liver not only has detoxification function, but also has some synthetic and metabolic functions, which is the direction of artificial liver development and is now in the clinical research stage.
2.Indications
(1) Early and middle stage of liver failure caused by various reasons, patients with PTA between 20% and 40% and platelets > 50×109/L are suitable; patients with advanced liver failure can also be treated, but complications are common and should be treated with caution; those who do not meet the diagnostic criteria of liver failure but have the tendency of liver failure can also be considered for early intervention.
(2) Patients with advanced liver failure waiting for a donor before liver transplantation, rejection reaction after liver transplantation, and non-functional stage of transplanted liver.
3. Relative contraindications
(1) Those with severe active bleeding or diffuse intravascular coagulation.
(2) Those who are highly allergic to blood products or drugs used in the treatment process such as plasma, heparin and fisetin.
(3) Those with circulatory failure (4) Those with non-stable stages of cardiac or cerebral infarction.
(5)Late stage of pregnancy.
4.Complications
Complications of artificial liver therapy include allergic reaction, hypotension, secondary infection, bleeding, imbalance syndrome, hemolysis, air embolism, water, electrolyte and acid-base balance disorders, etc. With the development of artificial liver technology, the incidence of complications is gradually decreasing, and once they occur, they can be treated accordingly according to the specific situation.
(iii) Liver transplantation
Liver transplantation is the most effective treatment for advanced liver failure.
1. Indications
(1) Intermediate and advanced liver failure due to various causes. The effect of active internal medicine and artificial liver treatment is not good.
(2) Various types of end-stage cirrhosis.
2.Contraindications
(1) Absolute contraindications
(1) Systemic infection that is difficult to control; (2) Malignant tumor outside the liver that is difficult to cure; (3) Alcoholism or drug abuse that is difficult to quit; (4) Serious organic lesions of the heart, brain, lungs and other important organs; (5) Psychiatric disease that is difficult to control.
(2) Relative contraindications
(1) Age over 65 years old; (2) Malignant tumor of liver with portal vein trunk cancer thrombosis or metastasis; (3) Combination of diabetes mellitus, cardiomyopathy and other diseases with poor prognosis; (4) Serious infection such as sepsis due to biliary tract infection; (5) Human immunodeficiency virus (HIV) infection; (6) Obvious anatomical abnormalities such as portal vein thrombosis.
3. Prevention and treatment of hepatitis virus reinfection in transplanted liver
(1) HBV reinfection HBV reinfection prevention program is the use of nucleoside antivirals such as lamivudine, adefovir or entecavir for more than 1 month before surgery, and the application of high potency hepatitis B immunoglobulin with nucleoside antivirals for a longer period of time during and after surgery.
(2) HCV reinfection At present, there is no effective prevention method for hepatitis recurrence after liver transplantation in HCV-infected patients. Combined antiviral therapy with alpha interferon and ribavirin can be given after transplantation as appropriate.