Acute liver failure in children

Acute hepatic insufficiency in children (ARF) is a rapidly developing disorder of the synthetic function of the liver, characterized by pronounced coagulopathy and hepatic encephalopathy. The absence of a history of liver disease is a necessary condition for the diagnosis of acute hepatic insufficiency. There is a decrease in PTI or an increase in prothrombin time, as well as a decrease in the V concentration of the clotting factor by more than 50% of the norm in combination with any stage of hepatic encephalopathy lasting less than 26 weeks.

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

Diagnosis of subfulminant hepatic insufficiency is established with the development of hepatic failure, not accompanied by hepatic encephalopathy for 26 weeks.

In a number of cases, acute hepatic failure occurs against a background of a previously undiagnosed liver disease. For example, ARF may be the first symptom of Wilson's disease or a1-antitrypsin deficiency. If the previous diseases are detected, the term "acute liver failure" is not used (since the duration of the disease exceeds 26 weeks). However, it is sometimes impossible to establish the fact of a chronic liver disease. The exception is patients with Wilson's disease, against which hepatitis B virus infection occurs or the development of autoimmune hepatitis. These diseases are the immediate causes of non-prolonged hepatic insufficiency (less than 26 weeks).

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

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

ICD-10 code

К 72 0 Acute and subacute liver failure.

K 72 9 Liver failure, unspecified.

Epidemiology of acute liver failure

The prevalence of acute hepatic insufficiency is relatively low. As studies have shown, in the US, about 2000 cases are diagnosed annually. Data on the incidence of Russian arthritis in the literature are absent. The mortality from acute hepatic insufficiency averages 3-4 people per year per 1 million of the population and depends on many factors, primarily on the etiology and age of the patient. Venerable hepatitis B and hepatitis-delta are considered to be the most prognostically unfavorable causes of ARF development, as well as age (under 10 and over 40).

[1], [2], [3], [4], [5]

What causes acute renal failure?

Viral and medicinal hepatitis are the main causes of the development of acute hepatic insufficiency. According to data obtained in the US, in more than half of cases, ARI occurs due to drug damage to the liver. In 42% of cases, the development of OPN is caused by an overdose of paracetamol. In Europe, the first place among the causes of OPN is also an overdose of paracetamol. In developing countries, viral hepatitis B and delta prevail among diseases causing arthritis (in the form of co-infection or superinfection). Other viral hepatitis less often cause the development of arterial hypertension. Approximately in 15% of patients the cause of acute hepatic insufficiency can not be established.

Causes of Acute Hepatic Insufficiency

Viruses of hepatitis A, B (+5), C, E, G7	Violation of the synthesis of bile acids
Cytomegalovirus	Galactosemia
Herpes simplex virus	Fructoseemia
Epstein-Barr virus	Tyrosinemia
Paramyxovirus	Neonatal hemochromatosis
Adenovirus	Wilson's disease
Medications and toxins	Deficiency of a-1-antitrypsin
Dose-dependent	Neoplastic
Acetaminophen	Lymphoma
CCI4	Metastases in the liver for breast or lung cancer, melanoma
Poisoning with fungi of the genus Amanita	Related to pregnancy
Yellow phosphorus	Acute fatty liver of pregnant women
Toxin Bacillus cereus	HELLP syndrome (hemolysis, elevated indicators of functional liver tests, decrease in the number of platelets)
Idiosyncratic	Other reasons
Halothane	Badda-Chiari Syndrome
Isoniazid	Venous-occlusive disease
Rifampicin	Autoimmune Hepatitis
Vapyrroic acid	Ischemic shock liver
Disulfiram	Heatstroke
Nonsteroidal anti-inflammatory drugs	Reaction of rejection after liver transplantation
Nortriptyline	Cryptogenic
Reye's syndrome (salicylic acid)
Herbal Medicine
Other

Symptoms of Acute Hepatic Insufficiency

The main clinical symptoms of acute liver failure are jaundice (not always diagnosed) and pain in the right upper quadrant. The liver is not enlarged upon examination. Characteristic of the development of ascites and its combination in severe cases with peripheral edema and ansarca. On the surface of the skin, hematomas are sometimes found. Often, bleeding from the mucous membranes of the gastrointestinal tract is noted, while in patients a tarry stool (melena) or vomiting with blood is observed. Determine the varying degrees of severity of encephalopathy and elevated ICP. When cerebral edema occurs, systemic hypertension, hyperventilation, altered pupillary reflexes, muscular rigidity, and in severe cases - to the decerebration coma are noted.

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

When poisoning with fungi, severe pains in the abdomen and watery diarrhea occur, occurring 6-24 hours after ingestion of fungi and lasting for several days (usually from 1 to 4 days) PE occurs in 2-4 days.

Diagnosis of acute liver failure

[6], [7]

Laboratory research

• Thrombocytopenia.
• Change in indicators reflecting the synthetic function of the liver. Decrease in the concentration of albumin and cholesterol, V factor of blood clotting and fibrinogen, decrease in AChE activity, decrease of PTI (or lengthening of prothrombin time).
• Significant increase in the activity of transaminases ALT and ACT. In case of an overdose of paracetamol, ACT activity may exceed 10 000 U / l (the norm is up to 40 U / l). Increase in activity of AP is not always recorded.
• Increase in the concentration of bilirubin and ammonia in the blood serum.
• Hypoglycemia.
• Increase in lactate in serum.
• Increase in the concentration of creatinine and urea in the blood serum (with the development of hepatorenal syndrome).

Instrumental Diagnosis of Acute Hepatic Insufficiency

With ultrasound and Doppler studies, nonspecific changes are observed in the depletion of the vascular pattern, disturbance of the portal blood flow of various degrees, and free fluid in the abdominal cavity. The liver is small in size.

When a liver biopsy specimen is histologically examined, necrosis of hepatocytes is noted, 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 on the background of hypocoagulation. This study is carried out only if liver transplantation is necessary or in case of autopsy.

Treatment of acute liver failure

The basis for the treatment of acute liver failure is the measures aimed at eliminating etiological factors (when they are detected), and posidrome therapy, which allows to correct complications.

When poisoning with paracetamol, gastric lavage is performed through a wide probe. When a tablet is detected in washing waters, enterosorbents (for example, activated charcoal) are prescribed. In the absence of a tablet in washing waters, it is recommended to administer acetylcysteine at a dose of 140 mg / kg (simultaneously through a nasogastric tube) and then prescribe 70 mg / kg orally every 4 hours for three days. Acetylcysteine produces the greatest effect when applied in the first 36 hours after paracetamol poisoning.

The most frequently poisoning is caused by fungi of the genus Amatia and Galerina. Fungi of the genus Amatia contain a-amanitine, which has a toxic effect by irreversible inhibition of the RNA polymerase. Therapy of this condition includes the use of silibinin [inside at a dose of 20-50 mg / (kilogram)) and penicillin G [intravenously at a dose of 1 mg / (kilogram) or 1,800,000 units / kgg). The action of silibinin is based on its ability to inhibit the capture of a-amanitine by hepatocytes and to increase antioxidant activity. This drug produces the maximum effect within the first 48 hours after poisoning. Penicillin G helps reduce the concentration of a-amanitine in bile by interrupting the hepatic-intestinal circulation of the toxin.

Measures to be taken when an acute liver failure of any etiology is detected:

• Provide adequate oxygenation. Additional oxygen is supplied, and if necessary, ventilation.
• Correction of metabolic disorders, electrolytes and CBS.
• Monitoring of hemodynamic parameters.
• Control of ICP.
• Parenteral administration of glucose to correct hypoglycemia.
• The introduction of mannitol to reduce ICP.
• Parenteral administration of proton pump inhibitors or histamine type II receptor blockers to prevent gastrointestinal bleeding.

Treatment of complications of acute liver failure

Liver encephalopathy

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

Edema of the brain

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

[8], [9], [10], [11], [12], [13], [14], [15]

Hypocoagulation

Introduce FFP [intravenously drip in a dose of 10 ml / (kilogram)) and vikasol [intramuscularly or intravenously at a dose of 1 mg / (kilogram)]. With insufficient effectiveness of the drugs, clotting factors are used (Feiba TIM-4 Immuno-coagulation factors II, VII, IX and X in the combination 75-100 IU / kg). For the prevention of gastrointestinal hemorrhages against the background of hypocoagulation, parenteral administration of proton pump inhibitors or histamine receptor blockers of the second type (for example, a 1-2mg Dkgsut squamatel) in 2-3 doses but not more than 300 mg / day is performed.

Hepatorenal Syndrome

Treatment measures include the replacement of bcc with hypovolemia (infusion of 5% glucose solution), dopamine administration [at a dose of 2-4 μg / (kghh)], and if the drugs are ineffective, HD is administered. It is also recommended to use veno-venous hemofiltration.

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

If the conservative treatment is ineffective and there are no contraindications, it is recommended to perform liver transplantation. Determination of indications for liver transplantation is an extremely difficult task. Even with severe forms of acute hepatic insufficiency, there is a possibility of recovery. On the other hand, at any time there may be irreversible changes in other organs, including the brain, which are considered contraindications to liver transplantation.

With the development of acute hepatic insufficiency, spontaneous recovery occurs rarely in patients with significantly reduced hepatic function (low albumin concentration, expressed coagulopathy), high bilirubin level, low ALT activity, and also for 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 various studies):

• An increase in the concentration of bilirubin is more than 299 μmol / l.
• Prothrombin time increase (more than 62 s).
• The decrease in ALT activity is 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 is less than two years.

Prevention of acute hepatic impairment

Prevention requires treatment and prevention of liver disease, which can cause acute liver failure, avoid the use of potentially hepatotoxic substances, drug overdose, including paracetamol.

What prognosis does acute hepatic insufficiency have?

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

• Hypoglycemia (less than 2.5 mmol / l).
• Increase in the concentration of creatinine (more than 200 mmol / l).
• The presence of metabolic acidosis (pH less than 7.3).
• Increase in prothrombin time (more than 100 s).
• PE of the III degree.

The presence of these violations in children indicates an increase in the likelihood of death, and also indicates a worsening of the prognosis.

Unfavorable prognostic factors in the development of acute liver failure:

• Increase in prothrombin time (more than 100 s).
• Reduction of the V factor of blood clotting (less than 20-30%).
• Prolonged jaundice (more than 7 days).
• Age (younger than 11 and older than 40 years).

Acute hepatic insufficiency due to hepatitis A or after paracetamol poisoning is characterized by a good prognosis.

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