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Taras Nykula, professor, ph.d. of medicine, full professor
Elina Manzhalii, assistant, candidate of medicine, associate professor
Borys Nykula, doctor of medicine
Bogomolets National Medical University, Ukraine
Championship participant: the National Research Analytics Championship - "Ukraine";
the Open European-Asian Research Analytics Championship;
Introduction. Damages of the hepatobiliary system are one of the most common diseases of our time [1-10, 13, 14]. One of the most important causes of morbidity and mortality in patients with HCV infection is cirrhosis. In patients with chronic liver disease, there is mixed protein-energy malnutrition [11, 12, 15]. Modified food intake from 4 to 7 times a day, provided once per evening, improves nitrogen use and recycling of substrates. With the development of acute liver failure and development of coma, the introduction of protein must be drastically limited - 20 g / day. After knocking complications, its number increases every 2 days for 10 g until a tolerant dose is achieved. Plant proteins have certain benefits, since they contain fewer methionine and provide binding and excretion of nitrogen. In patients with cirrhosis, self-catering is insufficient for maintaining normal power.
An important component ofthe treatment of liver failure is parenteral nutrition, which provides adequate supply of plastic materials, energy resources, electrolytes, trace elements and vitamins. The need for parenteral nutrition is associated with catabolic orientation exchange in liver cirrhosis. Severity of the catabolic reaction is directly proportional to the severity of the disease. In hepatocellular insufficiency, the body should receive only amino acids with branched side chains (isoleucine, leucine and valine) and low concentrations of aromatic amino acids (phenylalanine, tyrosine, tryptophane). As a result of impaired metabolism, the latter can be converted into false neurotransmitters - tyramine, octopamine, phenylethylamine.
There aretotal parenteral nutrition (conducted through a central vein) and additional parenteral nutrition (through a peripheral vein; up to 2 weeks). Parenteral nutrition should be conducted against a background of continuous monitoring of the electrolyte composition of blood, water balance, glucose level, blood urea nitrogen and serum triglycerides. The criterion of adequacy of parenteral nutrition is a positive nitrogen balance.
Unlike known solutions for parenteral nutrition used for hepatic failure treatment, Aminoplasmal Hepa - 10% (AH) contains 20 amino acids (essential – 8; replacement – 12), the high part of which are branched chain amino acids (isoleucine, leucine and valine) and low concentrations of aromatic amino acids (phenylalanine and tyrosine), which provides a better adaptation to amino acid and protein metabolism in patients with cirrhosis.
AH-solution of amino acids - solution for infusion is indicated for parenteral nutrition patients with severe hepatic impairment, contributes to the body with amino acids, used for the prevention and treatment of liver failure, hepatic encephalopathy. Contraindications to its use are: violation of amino acid non-hepatic state of nature, acidosis, hyperhydration and hypokalemia.
Maximum injection rate of AH is 20 drops, which equals 1 ml or 0.1 g AA/kg/h, with the daily dose of up to 2 g / kg of body weight. The rate of injection is increased 1.5 times when injected concurrently with fats and carbohydrates. With the injection of 1 ml / kg per day, and of 5 g / kg per day of glucose, positive effect occurs after an average of 8 hours. The injections are intravenous, through a central or peripheral venous catheter / needle (osmolarity of 875 mOsm / l).
Purpose. To examine the clinical effectiveness of AH in patients with cirrhosis of the hepatic-cellular failure, according to clinical, laboratory and instrumental methods.
Material and methods. The study involved 26 patients (men - 17, women - 9, the average age - 43,5 ± 5,7 years) for decompensated cirrhosis during acute illness. Among the patients - 18 (69.23%) patients with cirrhosis HCV etiology, 8 (44.4%) were found to be associated with liver toxicity associated with concomitant alcoholism or drug addiction, and 8 (30.77%) - with alcoholic cirrhosis. Liver function evaluated using Child-Pugh score: first stage – in 2 (7.69%), second - in 9 (34.62%), third - in 15 (57.69%). According to the criteria established by West Haven, there were discovered 1, 2 and 3 degrees of hepatic encephalopathy. The diagnosis of cirrhosis was established in 3.9 ± 0.5 year following the detection of viral etiology chronic hepatitis B, and when combined with a toxic lesion - in 3,4 ± 1,5 years. By social status - 21 people (80.77%) were classified as unemployed persons and pensioners and the disabled. The background cirrhotic liver disease had coexisting disease - gastrointestinal tract - in 22 (84.62%), urogenital system - in 7 (26.92%), endocrine - in 5 (19.23%), nervous system - 4 (15.39%).
Patients were divided into two groups according to the therapy performed. The core group included 14 patients who received parenteral nutrition AH; the control group imcluded 12 patients who were on standard therapy without AH (diet therapy, corticosteroids, vitamins). Basic therapy included the cessation of exposure to toxic agents, administration of lactulose drugs and rifaximin.
To verify the diagnosis and monitoring of treatment, patients underwent general clinical examination methods, ultrasound of the abdomen, sonography of the heart and blood vessels, measuring the diameter of the portal vein, the volume of blood circulation in it and splenic artery pulse calculation of the index in the splenic artery. When collecting anamnesis, we paid attention to acute viral infection, blood transfusion, the possibility of an overdose of drugs, poisoning, shock, and illness in the family. We determined the nutritional status of patients, the presence of chronic alcohol intoxication, and the effects of other toxic agents. We assessed indicators of the functional state of the liver: the content of serum total protein, albumin, protein fractions, total, direct and indirect bilirubin, total cholesterol, the activity of alanine and aspartate aminotransferase (ALT, AST), gamma-glutamyl transpeptidase, alkaline phosphatase, serum tests for hepatitis A, B, C, D, and E. To assess the severity of PE criteria, we used West Haven (WH).
We assessed the patients' diet by statistical data of chemical composition of day most typical for a specific patient's diet prescribed by interview. Heart rate was calculated, blood pressure was measured.
Results. Clinical characteristics of patients based on a study of the complaints, history, defining the objective situation, the interpretation of these additional studies. Statistical analysis of the data from studies performed using computer programs Microsoft Excel 7.0, the standard version of SPSS 9.0 (US).
Asthenic-vegetative syndrome was observed in 20 patients (76.92%), diarrhea - in 22 (84.61%), abdominal pain - 16 (61.53%), swelling and ascitic - in 12 (46.15%), cholestatic – in 13 (50.00%), hemorrhage (hemorrhage at injection site, nosebleeds) – in 4 (15.38%). In patients with cirrhosis of alcoholic origin (as the last stage of alcoholic liver disease), encephalopathic signs dominated (mental and emotional lability, heartache, inversion of sleep - sleepy during the day and insomniac at night). Headache troubled 22 patients (84.61%), pain in the heart area - 11 (42.30%), dizziness in the head - 8 (30.76%), disruption of the heart - 19 (73.07%). Unlike true hepatocellular insufficiency accompanied by encephalopathy, a rapid weakening of neuropsychiatric symptoms was found in drug addicts due to the termination of the drugs. In 24 patients (92.31%) there occurred ascites, splenomegaly of varying degrees, expanding of veins of the lower third of the esophagus and cardia; in 16 (61.53%) - jaundice. 16 patients (61.54%) complained of sleep disturbance, 14 (53.84%) - disturbances of appetite, 11 (42.31%) - nausea, 7 (26.92%) - vomiting, 16 (61.54% ) - itching.
After the first AH introduction, progression of liver failure was limited to stages I-II encephalopathy, decrease of prothrombin index within 43-51%, a slight increase hemorrhage, jaundice with bilirubin 200-290 mmol / L and susceptibility to hypoglycemia. The phenomena of liver failure persisted for a long time.
Under the influence of three-week treatment of patients with liver cirrhosis, symptoms of asthenic-vegetative, cytolytic, cholestatic syndromes disappeared or significantly disappeared or significantly reduced, severity of encephalopathy decreased. After treatment with AH, in patients expression of cytolytic syndrome, a syndrome of immune inflammation and cholestasis, coagulopathy decreased.
Dynamics of biochemical parameters in patients with cirrhosis of the liver under the influence AH can be presented using the following scheme; performance before and after treatment (p ± mp):
- totalbilirubin (umol/L): 242.4 ± 12.9 and 72.7 ± 19.5 (P<0.05);
- bilirubindirect (umol/L): 78.6 ± 6.9 and 22.6 ± 4.5 (P<0.05);
- bilirubinindirect (umol / L): 22.9 ± 2.3 and 15.8 ± 1.5 (P<0.05);
- ALT (umol / h • L): 1.22 ± 0.29 and 0.69 ± 0.18 (P<0.05);
-AST (umol / h • L): 1.20 ± 0.22 and 0.54 ± 0.16 (P<0.05);
- Alkalinephosphatase (N / mol • L): 3220 ± 106 and 2007 ± 104 (P<0.05).
Discussion. Therapeutic effect of hepatitis AH can be explained primarily by an increase in amino acid composition of the preparation, which help normalize blood plasma Fisher ratio: the ratio of branched amino acids (leucine + isoleucine + valine) and aromatic amino acids (phenylalanine + tyrazyn). It is known that, in patients with hepatic insufficiency, content of branched amino acids in plasma decreased and aromatic - increased. The degree of this imbalance depends on the severity of encephalopathy. The literature suggests that AH eliminates the imbalance between the ratio of branched and aromatic amino acids and brings the Fisher ratio in the plasma of patients with liver cirrhosis to 3, which moves hepatic encephalopathy in a lighter stage. AH reduces ammonia levels.
Conclusions. Thus, our data, consonant with literature data, shows that the adapted solution AH can reduce the manifestations of hepatocellular insufficiency in patients with cirrhosis of the liver, its use is pathogenetically substantiated and improves the effectiveness of treatment and quality of life for patients.