Acute liver failure (ALF) refers to a clinical syndrome often triggered by factors such as drugs, hepatotoxic substances, viruses, or alcohol. It is characterized by a sudden deterioration in liver function, manifesting as consciousness disturbances and coagulation dysfunction. It is more common in young and middle-aged individuals, progresses rapidly, and is associated with a high mortality rate.
Etiology and Pathogenesis
The primary cause of liver failure is hepatitis B virus (HBV), with acute-on-chronic (subacute) liver failure being the most common presentation. Other common causes include drug-induced liver injury, viral hepatitis, autoimmune liver diseases, and ischemic liver injury caused by shock or hypotension. However, approximately 15% of cases have an unknown etiology.
The pathogenesis involves immune-inflammatory damage mediated by endotoxins and cytokines, hepatic microcirculatory disturbances, apoptosis, inhibition of hepatocyte regeneration, and the loss of liver energy metabolism and detoxification functions. These processes lead to multi-organ failure, which further accelerates mortality in liver failure patients.
Histopathology
Histopathological findings include hepatocyte necrosis affecting 2/3 or more of the liver parenchyma, submassive necrosis (involving approximately 1/2-1/3 of the liver parenchyma), or bridging necrosis (extensive confluent necrosis disrupting the structural integrity of the liver parenchyma). The surviving hepatocytes show severe degeneration, and the hepatic sinusoidal reticulin framework is collapsed or partially collapsed.
Physical Examination and Laboratory Tests
Physical Examination
Mental status should be assessed to determine the presence and grading of hepatic encephalopathy. Signs of chronic liver disease should also be evaluated.
Laboratory Tests
Laboratory tests include:
- General tests: Complete blood count, arterial blood gas analysis, and arterial blood lactate.
- Coagulation function: Prothrombin time (PT) and international normalized ratio (INR).
- Blood biochemistry: Liver and kidney function, blood glucose, and electrolytes.
- Viral hepatitis serology.
- Autoimmune markers.
Clinical Diagnosis
Acute liver failure is diagnosed in cases with acute onset, the development of grade 2 or higher hepatic encephalopathy within two weeks, and the presence of the following features:
- Extreme fatigue, along with significant anorexia, abdominal distension, nausea, emesis, or other severe gastrointestinal symptoms.
- Progressive worsening of jaundice over a short period, with total bilirubin (TB) levels often ≥171 μmol/L and the presence of a dissociation between enzyme and bilirubin levels.
- Marked bleeding tendencies, with plasma prothrombin activity (PTA) ≤40% (or INR ≥1.5), after excluding other causes.
- Progressive liver shrinkage.
Differential Diagnosis
Biliary Obstruction and Severe Biliary Infections
These conditions typically present with deep jaundice but only mild liver dysfunction. ALT elevation is less pronounced, and patients often exhibit fever, abdominal pain, and hepatomegaly.
Cholestatic Hepatitis
Deep jaundice may lead to misdiagnosis as liver failure. However, gastrointestinal symptoms are mild, serum ALT and PT prolongation are not significant, and patients often experience noticeable pruritus and pale stools. Hepatic encephalopathy, bleeding, and ascites are rare.
Hepatic Encephalopathy
It should be distinguished from coma caused by other conditions.
Treatment
Etiological Treatment
For cases of acute liver failure (ALF) with a clear etiology, etiological treatment is necessary. ALF caused by acetaminophen (APAP) overdose can be treated with N-acetylcysteine (NAC). For ALF due to mushroom poisoning, penicillin and silibinin may be used. In cases of drug-induced liver injury (DILI), discontinuation of the offending drug is required. Patients with viral hepatitis may benefit from antiviral therapy, while autoimmune hepatitis can be managed with glucocorticoids. For acute fatty liver of pregnancy, termination of pregnancy is necessary.
Standard Treatment
Medical Monitoring
Most ALF patients experience varying degrees of circulatory dysfunction, cerebral edema, and intracranial hypertension, which significantly increase mortality. Intensive critical care monitoring and support are essential alongside etiological treatment.
Supportive Therapy
Supportive measures are crucial for improving the prognosis of ALF and include the following:
- Absolute bed rest to minimize physical exertion and reduce liver burden.
- Provision of a high-glucose, low-fat, and low-protein diet, along with adequate supplementation of vitamins, trace elements, and branched-chain amino acids.
- Administration of fresh plasma and human albumin to improve microcirculation, prevent or alleviate cerebral edema and ascites, and address coagulation dysfunction using cryoprecipitate.
- Correction of electrolyte imbalances and acid-base disturbances.
Management of Cerebral Edema and Hepatic Encephalopathy
Cerebral edema and intracranial hypertension are severe complications of ALF and may result in fatal brain herniation. Excessive fluid administration should be avoided. For patients with intracranial hypertension, treatments such as mannitol, hypertonic saline, barbiturates, and hypothermia therapy may be employed. Glucocorticoids are not recommended for controlling intracranial hypertension in ALF patients.
Infection Control
Early identification of potential bacterial or fungal infections is critical, and anti-infective therapy should be initiated promptly based on microbiological findings.
Prevention and Management of Bleeding
Proton pump inhibitors (PPIs) may be used short-term to prevent stress ulcer bleeding. Platelet transfusion should only be considered in cases of active bleeding or prior to invasive procedures.
Correction of Metabolic Disorders
Nutritional status and electrolyte levels should be closely monitored, with timely correction of metabolic disturbances. Adequate parenteral or enteral nutrition should be provided as needed.
Artificial Liver Support
Artificial liver support systems are an effective treatment option for ALF. These systems use extracorporeal mechanical, physical, and biological devices to remove harmful substances, supply essential compounds, and improve the internal environment. This approach temporarily replaces some liver functions, providing time for hepatocyte regeneration and liver function recovery or allowing time for liver transplantation.
Liver Transplantation
Liver transplantation is an effective treatment for ALF and should be performed at an appropriate time.
Prognosis
The etiology of ALF is one of the most critical prognostic factors. ALF caused by acetaminophen overdose, hepatitis A, shock, or pregnancy-related conditions has a post-transplant survival rate of over 50%, while ALF from other causes has a post-transplant survival rate of less than 25%. Prognosis is also influenced by factors such as gender, age, liver condition at admission, clinical and biochemical status, the severity of hepatic encephalopathy during the peak deterioration phase, prothrombin time, INR, renal function, bilirubin levels, serum sodium, and arterial blood pH.