I. Definition and etiology of liver failure
(A) Definition
Liver failure is a group of clinical syndromes caused by severe liver damage caused by various factors, resulting in severe impairment or loss of compensation of its synthesis, detoxification, excretion and biotransformation functions, with the main manifestations of impaired coagulation mechanisms and jaundice, hepatic encephalopathy, ascites, etc.
(II) Etiology
The main cause of liver failure in China is hepatitis virus (mainly hepatitis B virus), followed by drugs and hepatotoxic substances (such as ethanol, chemical agents, etc.). In Europe and the United States, drugs are the main cause of acute and subacute liver failure; alcoholic liver damage often leads to chronic liver failure [2]. Liver failure in children is also seen in genetic metabolic diseases (Table 3).
II. Classification and diagnosis of liver failure
(I) Classification
Based on the pathological histological features and the rate of progression, liver failure can be classified into four categories (Table 4): acute liver failure. Acute liver failure is characterized by an acute onset, with liver failure syndrome characterized by hepatic encephalopathy of degree II or higher within 2 weeks of onset; subacute liver failure has a more acute onset, with liver failure syndrome occurring within 15 d to 26 weeks of onset; slow plus acute (subacute) liver failure is an acute loss of liver function based on chronic liver disease; chronic liver failure is based on cirrhosis with progressive decompensation of liver function leading to ascites or portal hypertension, coagulation dysfunction and hepatic encephalopathy as the main manifestations of chronic liver failure [3-7].
(II) Staging
According to the severity of clinical manifestations, subacute liver failure and slow plus acute (subacute) liver failure can be divided into early, intermediate and late stages [8].
1, Early stage
(1) Extreme malaise with severe gastrointestinal symptoms such as marked anorexia, vomiting and abdominal distention.
(2) Progressive deepening of jaundice (total serum bilirubin ≥ 171 μmol/L or a daily rise of 1 μmol/L).
(3) Bleeding tendency with 30% < prothrombin activity ≤ 40%.
(4) No hepatic encephalopathy or significant ascites.
2. Intermediate stage.
On the basis of the early manifestations of liver failure, the disease further develops and one of the following two items appears
(1) The appearance of hepatic encephalopathy below grade II and/or obvious ascites.
(2) Significant bleeding tendency (bleeding spots or petechiae), and 20% < PTA ≤ 30%.
3. Advanced stage.
On the basis of the manifestation of the middle stage of liver failure, the condition is further aggravated and one of the following three items appears
(1) There are refractory complications, such as hepatorenal syndrome, upper gastrointestinal hemorrhage, severe infections and electrolyte disturbances that are difficult to correct.
(2) The presence of hepatic encephalopathy of grade III or higher.
(3) Severe bleeding tendency (petechiae at the injection site, etc.) with PTA ≤ 20%.
(C) Diagnosis
1.Clinical diagnosis.
The clinical diagnosis of liver failure needs to be determined based on a comprehensive analysis of medical history, clinical manifestations and auxiliary examinations.
(1) Acute liver failure: those with acute onset and hepatic encephalopathy of degree II or higher (classified according to the classification of degree IV [9]) within 2 weeks and with the following manifestations.
(i) Extreme weakness with severe gastrointestinal symptoms such as marked anorexia, abdominal distension, nausea and vomiting.
(ii) Progressive deepening of jaundice in a short period of time.
③Significant bleeding tendency with PTA ≤ 40%, and other causes are excluded.
④Progressive shrinkage of the liver.
(2) Subacute liver failure: those with more acute onset and the following manifestations in 15d to 26 weeks.
(①Extreme weakness with obvious GI symptoms.
(② Rapid deepening of jaundice with total serum bilirubin greater than 10 times the upper limit of normal or a daily rise of ≥17, 1 μmol/L.
(3) Significantly prolonged prothrombin time, PTA ≤ 40% and exclude other causes.
(3) Slow plus acute (subacute) liver failure: the main clinical manifestation of acute liver function loss in a short period of time on the basis of chronic liver disease.
(4) Chronic liver failure: on the basis of cirrhosis, progressive decompensation and loss of liver function.
The main points of diagnosis are.
(1) There is ascites or other manifestations of portal hypertension.
②Hepatic encephalopathy may be present.
③Total serum bilirubin is elevated and albumin is significantly decreased.
④There is coagulation dysfunction with PTA ≤ 40%.
2. Histopathological manifestations.
Histopathological examination is of great value in the diagnosis, classification and prognosis determination of liver failure, but due to the severely reduced coagulation function in patients with liver failure, performing liver puncture has certain risks, and special attention should be paid in clinical work. In liver failure (except in chronic liver failure), extensive hepatocellular necrosis can be observed on liver histology, with the site and extent of necrosis varying depending on the etiology and course of the disease. According to the extent and degree of necrosis, it can be divided into massive necrosis (necrosis of more than 2/3 of the liver parenchyma), submassive necrosis (about 1/2 to 2/3 of the liver parenchyma), fusion necrosis (necrosis of adjacent patches of hepatocytes) and bridging necrosis (more extensive fusion necrosis with destruction of the parenchymal structure).
In liver tissues of different stages of liver failure, one-time or multiple lesions with varying degrees of old and new hepatocyte necrosis may be observed. Currently, there is no consensus on the correlation between the etiology, classification and staging of liver failure and hepatic histological changes. Given that liver failure due to hepatitis B virus (HBV) infection is the most common in China, this Guideline introduces the typical pathological manifestations of various types of liver failure, taking liver failure due to HBV infection as an example.
(1) Acute liver failure: hepatocytes show one-time necrosis, with necrosis area ≥ 2/3 of the liver parenchyma; or submassive necrosis, or bridging necrosis, with severe degeneration of surviving hepatocytes and non-collapse or incomplete collapse of the hepatic sinusoidal reticular scaffold.
(2) Subacute liver failure: submassive necrosis or bridging necrosis with varying degrees of old and new liver tissue; collapse of reticular fibers in older necrotic areas or collagen fiber deposition; varying degrees of regeneration of residual hepatocytes with fine and small bile duct hyperplasia and cholestasis.
(3) Slow plus acute (subacute) liver failure: on the basis of the pathological damage of chronic liver disease, new necrotic lesions of varying degrees of hepatocytes occur.
(4) Chronic liver failure: mainly diffuse liver fibrosis as well as abnormal nodule formation, which may be accompanied by unevenly distributed hepatocyte necrosis.
3. Diagnostic format of liver failure.
Liver failure is not an independent clinical diagnosis, but a functional judgment. In clinical practice, a complete diagnosis should include etiology, clinical type and staging, and it is recommended to be written according to the following format