Acute liver failure in children

Acute liver failure in children (ALF) is a rapidly developing disorder of the synthetic function of the liver, characterized by severe coagulopathy and hepatic encephalopathy. The absence of a history of liver disease is a prerequisite for the diagnosis of acute liver failure. A decrease in PTI or an increase in prothrombin time, as well as a decrease in the concentration of blood coagulation factor V by more than 50% of the norm in combination with any stage of hepatic encephalopathy lasting less than 26 weeks are noted.

The term "fulminant liver failure" was first introduced by Trey and Davidson in 1970 to define a clinical syndrome characterized by acute onset, coagulopathy, and hepatic encephalopathy occurring within 8 weeks of onset.

The diagnosis of subfulminant liver failure is established when liver failure develops without hepatic encephalopathy within 26 weeks.

In some cases, acute liver failure occurs against the background of a previously undiagnosed liver disease. For example, acute liver failure may be the first symptom of Wilson's disease or alpha-1 antitrypsin deficiency. If previous diseases are detected, the term "acute liver failure" is not used (since the duration of the disease exceeds 26 weeks). However, sometimes it is impossible to establish the fact of chronic liver disease. The exception is patients with Wilson's disease, against the background of which infection with the hepatitis B virus or the development of autoimmune hepatitis occurs. These diseases are the immediate causes of short-term liver failure (less than 26 weeks).

Concepts used in relation to the time of onset of hepatic encephalopathy after detection of jaundice:

• Hyperacute liver failure (less than 7 days).
• Acute liver failure (8 to 28 days).
• Subacute liver failure (4 to 12 weeks).

ICD-10 code

K 72 0 Acute and subacute liver failure.

K 72 9 Liver failure, unspecified.

Epidemiology of acute liver failure

The prevalence of acute liver failure is relatively low. As studies have shown, about 2,000 cases are diagnosed in the United States annually. There are no data on the incidence of acute liver failure in Russians in the literature. Mortality from acute liver failure averages 3-4 people per year per 1 million population and depends on many factors, primarily on the etiology and age of the patient. The most prognostically unfavorable causes of acute liver failure are viral hepatitis B and hepatitis delta, as well as age (younger than 10 and older than 40 years).

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What causes acute renal failure?

Viral and drug-induced hepatitis are the main causes of acute liver failure. According to data obtained in the USA, in more than half of cases, ARF occurs due to drug-induced liver damage. In 42% of cases, ARF is caused by an overdose of paracetamol. In Europe, the first place among the causes of ARF is also occupied by an overdose of paracetamol. In developing countries, viral hepatitis B and delta (as a coinfection or superinfection) prevail among diseases causing ARF. Other viral hepatitis causes ARF less often. In approximately 15% of patients, the cause of acute liver failure cannot be determined.

Causes of Acute Liver Failure

Hepatitis viruses A, B (+5), C, E, G7	Bile acid synthesis disorder
Cytomegalovirus	Galactosemia
Herpes simplex virus	Fructosemia
Epstein-Barr virus	Tyrosinemia
Paramyxovirus	Neonatal hemochromatosis
Adenovirus	Wilson's disease
Drugs and toxins	α-1-antitrypsin deficiency
Dose dependent	Neoplastic
Acetaminophen	Lymphoma
CCI4	Liver metastases from breast or lung cancer, melanoma
Amanita mushroom poisoning	Pregnancy related
Yellow phosphorus	Acute fatty liver of pregnancy
Bacillus cereus toxin	HELLP syndrome (hemolysis, elevated liver function tests, decreased platelet count)
Idiosyncratic	Other reasons
Halothane	Budd-Chiari syndrome
Isoniazid	Veno-occlusive disease
Rifampicin	Autoimmune hepatitis
Vapproic acid	Ischemic shock liver
Disulfiram	Heat stroke
Nonsteroidal anti-inflammatory drugs	Rejection reaction after liver transplantation
Nortriptyline	Cryptogenic
Reye's syndrome (salicylic acid)
Herbal medicine
Other

Symptoms of Acute Liver Failure

The main clinical symptoms of acute liver failure are jaundice (not always diagnosed) and pain in the right hypochondrium. The liver is not enlarged on examination. The development of ascites and its combination in severe cases with peripheral edema and anasarca are characteristic. Hematomas are sometimes found on the surface of the skin. Bleeding from the mucous membranes of the gastrointestinal tract is often noted, while patients have tarry stools (melena) or vomiting with blood. Encephalopathy of varying severity and increased intracranial pressure are determined. When cerebral edema occurs, systemic hypertension, hyperventilation, altered pupillary reflexes, muscle rigidity are noted, and in severe cases, decerebrate coma.

After taking large doses of paracetamol, anorexia develops during the first day, the patient is bothered by nausea and vomiting (they later disappear). Then the symptoms of acute liver failure described above are detected.

In mushroom poisoning, severe abdominal pain and watery diarrhea are observed, occurring 6-24 hours after eating mushrooms and continuing for several days (usually from 1 to 4 days). After 2-4 days, PE occurs.

Diagnosis of acute liver failure

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Laboratory research

• Thrombocytopenia.
• Changes in indicators reflecting the synthetic function of the liver. Decreased concentration of albumin and cholesterol, blood coagulation factor V and fibrinogen, decreased activity of AChE, decreased PTI (or prolongation of prothrombin time).
• Significant increase in the activity of transaminases ALT and AST. In case of paracetamol overdose, AST activity may exceed 10,000 U/l (normal - up to 40 U/l). Increased activity of alkaline phosphatase is not always recorded.
• Increased concentration of bilirubin and ammonia in the blood serum.
• Hypoglycemia.
• Increased serum lactate levels.
• Increased concentration of creatinine and urea in the blood serum (with the development of hepatorenal syndrome).

Instrumental diagnostics of acute liver failure

Ultrasound and Doppler examination reveal non-specific changes: depletion of the vascular pattern, portal blood flow disorders of varying degrees, and free fluid in the abdominal cavity. The liver is small in size.

Histological examination of liver biopsy reveals necrosis of hepatocytes, which in most cases does not allow to establish the cause of the disease. In acute liver failure, puncture biopsy is not performed due to the high probability of bleeding due to hypocoagulation. This study is performed only if liver transplantation is necessary or during autopsy.

Treatment of acute liver failure

The basis of treatment for acute liver failure consists of measures aimed at eliminating etiological factors (if detected) and syndrome-based therapy, which allows for the correction of complications.

In cases of paracetamol poisoning, gastric lavage is performed through a wide tube. If a tablet is found in the lavage water, enterosorbents (for example, activated carbon) are prescribed. If there is no tablet in the lavage water, it is recommended to administer acetylcysteine at a dose of 140 mg/kg (at one time through a nasogastric tube), and then prescribe 70 mg/kg orally every 4 hours for three days. Acetylcysteine produces the greatest effect when used in the first 36 hours after paracetamol poisoning.

The most common causes of poisoning are mushrooms of the genus Amatia and Galerina. Mushrooms of the genus Amatia contain a-amanitin, which has a toxic effect by irreversibly inhibiting RNA polymerase. Therapy for this condition includes the use of silibinin [orally at a dose of 20-50 mg / (kg x day)] and penicillin G [intravenously at a dose of 1 mg / (kg x day) or 1,800,000 IU / (kg x day)]. The action of silibinin is based on its ability to prevent the capture of a-amanitin by hepatocytes and increase antioxidant activity. This drug produces a maximum effect during the first 48 hours after poisoning. Penicillin G helps to reduce the concentration of a-amanitin in bile by interrupting the enterohepatic circulation of the toxin.

Measures taken upon detection of acute liver failure of any etiology:

• Ensuring adequate oxygenation. Provide additional oxygen and, if necessary, mechanical ventilation.
• Correction of metabolic disorders, electrolytes and acid-base balance.
• Monitoring of hemodynamic parameters.
• Control of intracranial pressure.
• Parenteral administration of glucose to correct hypoglycemia.
• Administration of mannitol to reduce ICP.
• Parenteral administration of proton pump inhibitors or histamine II receptor blockers to prevent gastrointestinal bleeding.

Treatment of complications of acute liver failure

Hepatic encephalopathy

To correct PE, it is necessary to limit protein intake with food and prescribe lactulose at a dose of 3-10 g/day orally (for children under one year - 3 g/day, from 1 to 6 years - 3-7 g/day, 7-14 years - 7-10 mg/day).

Cerebral edema

General measures include ensuring rest and a certain position of the head (at an angle of 100 degrees to the horizontal surface), prevention of arterial hypotension and hypoxemia. Specific therapy consists of prescribing mannitol at a dose of 0.4 g / kg every hour (intravenous bolus) until normalization of ICP. It should be noted that the use of this drug is ineffective in renal failure and hyperosmolarity of the blood serum. In the development of hepatic coma, hyperventilation often has a positive effect. In the treatment of cerebral edema caused by acute liver failure, the administration of glucocorticoid drugs is inappropriate (due to the lack of effect).

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Hypocoagulation

FFP is administered [intravenously by drip at a dose of 10 ml/(kg x day)] and vicasol [intramuscularly or intravenously at a dose of 1 mg/(kg x day)]. If the drugs are insufficiently effective, blood clotting factors are used (Feiba TIM-4 Immuno - blood clotting factors II, VII, IX and X in combination 75-100 IU/kg). To prevent gastrointestinal bleeding against the background of hypocoagulation, parenteral administration of proton pump inhibitors or histamine type II receptor blockers is performed [for example, quamatel at 1-2 mg/(kg x day) in 2-3 doses, but not more than 300 mg/day].

Hepatorenal syndrome

Treatment measures include replenishment of the BCC in case of hypovolemia (infusion of 5% glucose solution), administration of dopamine [at a dose of 2-4 mcg/(kg h)], and if the drugs are ineffective, HD is performed. It is also recommended to use venovenous hemofiltration.

The development of sepsis is an indication for the use of antibacterial drugs. The drugs are prescribed taking into account the sensitivity of the cultured microflora. The use of antibiotics is combined with passive immunization with pentaglobin. Newborns are prescribed 250 mg/kg, infants - 1.7 ml/(kg h) intravenously by drip. Older children and adults are recommended to administer 0.4 ml/(kg h) until a total dose of 100 ml is reached, then continuous infusion of pentaglobin4 is carried out over the next 72 hours [at 0.2 ml/(kg h), increasing the rate of administration to 15 ml/(kg h)].

If conservative treatment is ineffective and there are no contraindications, liver transplantation is recommended. Determining indications for liver transplantation is an extremely difficult task. Even with severe forms of acute liver failure, there is a chance of recovery. On the other hand, irreversible changes in other organs, including the brain, may occur at any time, which are considered a contraindication to liver transplantation.

In the development of acute liver failure, spontaneous recovery rarely occurs in patients with significantly reduced synthetic function of the liver (low albumin concentration, severe coagulopathy), high bilirubin levels, low ALT activity, as well as with a longer period between the onset of the disease and the appearance of signs of encephalopathy.

Criteria for determining indications for liver transplantation in the development of acute liver failure (according to data from various studies):

• Increased bilirubin concentration over 299 µmol/l.
• Increased prothrombin time (more than 62 s).
• ALT activity decreased to less than 1288 U/L.
• Leukocytosis (more than 9 thousand).
• The duration of the disease before the development of PE is more than 10.5 days.
• Age under two years.

Prevention of acute liver failure

Prevention involves treatment and prevention of liver diseases that can cause acute liver failure, avoiding the use of potentially hepatotoxic substances, drug overdose, including paracetamol.

What is the prognosis for acute liver failure?

In case of paracetamol overdose, additional criteria for assessing the severity of the patient's condition are used:

• Hypoglycemia (less than 2.5 mmol/l).
• Increased creatinine concentration (more than 200 mmol/l).
• Presence of metabolic acidosis (pH less than 7.3).
• Increased prothrombin time (more than 100 s).
• PE grade III.

The presence of these disorders in children indicates an increased likelihood of death and also indicates a worsening prognosis.

Unfavorable prognostic factors in the development of acute liver failure:

• Increased prothrombin time (more than 100 s).
• Decreased levels of blood coagulation factor V (less than 20-30%).
• Prolonged jaundice (more than 7 days).
• Age (under 11 and over 40 years old).

Acute liver failure due to hepatitis A or after paracetamol poisoning has a good prognosis.

The survival rate of the organ after liver transplantation performed in acute liver failure is usually not very high (compared to surgery for chronic liver disease). According to the literature, the survival rate of patients after emergency transplantation during the first year is 66%, and 59% within five years. After operations performed for chronic liver failure, depending on the diagnosis, an increase in survival is recorded to 82-90% in the first year and to 71-86% within five years.