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Drug-induced liver injury (DILI) is a relevant issue in clinical practice and is still a diagnosis of exclusion. Despite the low incidence in the general population, DILI is the cause of most cases of acute hepatic injury and has a mortality rate of up to 50%. Despite many reports in the medical literature about the DILI mechanisms, a clear causal relationship between them, drugs, and risk factors has not been established. Current clinical practice is based on a combination of a thorough study of a history of risk factors, the timing of drug and dietary supplements' administration, and the analysis of laboratory and instrumental tests. It aligns with the international criteria of the Rousell Uclaf Causality Assessment Method (RUCAM), which is considered one of the main diagnostic algorithms for DILI. The article addresses current DILI classification, risk factors, diagnostic algorithms, causalities, clinical evaluation, promising liver function biomarkers, and specific treatment.

Аim: to describe clinical cases of Wilson – Konovalov disease in pediatric patients.Key points. The first clinical case demonstrates the manifestation of Wilson – Konovalov disease with unexplained mild elevation of aminotransferases at the age of 6 years. Despite the persistent hyperenzymemia, no additional laboratory tests were prescribed. At the age of 10, the patient showed signs of liver failure and neurological symptoms. Laboratory and instrumental examination enabled to diagnose Wilson – Konovalov disease at the stage of liver cirrhosis. The diagnosis was confirmed at the Federal medical center. The diagnosis was delayed and made 4 years after the hyperenzymemia was first revealed. The relief of clinical signs was observed after the orthotopic transplantation of the right lobe of the liver from a living related donor. The patient was under surveillance for 10 years after the transplantation.The second clinical case shows another variant of the course of the Wilson – Konovalov disease manifested as an acute hepatitis. To clarify the etiology of the disease, the patient was hospitalized. In 2 weeks, the patient developed symptoms of acute liver failure, progressive hemorrhagic syndrome, acute hepatic encephalopathy. Death from fulminant hepatitis occurred in 3 weeks after the disease onset after the disease onset.Conclusion. Healthcare workers should be aware of clinical signs of Wilson – Konovalov disease. Screening for the disease is recommended for children with an unexplained increase of liver transaminases, acute liver failure, chronic hepatitis and liver cirrhosis.

Introduction. Wilson's disease represents one of the genetic diseases that has lifelong treatment, which significantly improved the quality of life for patients and reduced the disabling complications associated with the lack of an early diagnosis. Material and methods. A structured search was performed in PubMed and HINARI, using English search terms: "Wilson's disease", "acute liver failure", "cirrhosis", "acute Wilsonian hepatitis", "hepatic manifestation", "chronic liver disease", "asymptomatic Wilson's disease", and "active chronic hepatitis". Results. Wilson's disease can occur at any age and can mimic the presence of other chronic liver diseases. The hepatic expression is highly variable, ranging from asymptomatic presentation to severe liver diseases, such as decompensated cirrhosis and acute liver failure. Any patient with transaminitis and abnormal parameters of cooper metabolism should be comprehensively and carefully evaluated to identify Wilson's disease early and to prevent misdiagnosis or unnecessary therapies. Confirmation of the diagnosis should not exclude the co-existence of other liver diseases. Conclusions. The use of validated and adapted scores for Wilson's disease may facilitate diagnosis, but they cannot be used in acute liver failure. Considering that WD presents itself with great phenotypic diversity and can evolve under the mask of other pathologies, it is necessary to carry out a careful differential diagnosis.

The aim of the study: to evaluate the efficacy of extracorporeal liver support systems in patients with acute liver failure of various etiologies.Material and methods. The study included 117 patients with acute liver failure of various etiologies. The main group consisted of 71 patients who received complex intensive therapy, including MARS-therapy and hemodiafiltration. The comparison group included 46 patients who received albumin dialysis (24 patients) and hemodiafiltration (22 patients) alone. The mean age of the patients was 34±5.6 years, the majority (56.4%) were men. Dynamic assessment of patients' severity was performed using Sequential Organ Failure Assessment (SOFA) and Model for End-Stage Liver Disease (MELD) scales.Results. A more significant reduction of SOFA and MELD scores was noted as early as by day 10 of intensive therapy in the main group with sequential use of extracorporeal liver detoxification methods — to 2.7±0.2 vs. 8.3±0.5 points (P=0.021) on SOFA and to 16.7±0.4 vs. 23.4±1.4 points (P=0.023) MELD scales. The use of a comprehensive approach to extracorporeal detoxification in acute decompensated liver failure increased the regression rate of multiple organ failure from 51.2 to 74.6% and reduced mortality from 47.8 to 25.4% (χ2=6.266; df=1; P=0.013). At the same time, the cumulative proportion of survivors depending on the type of complication within 30 days was 88.4% in the main group and 69.0% in the comparison group (χ2=4.164; df=1; P=0.042).Conclusion. A comprehensive approach to extracorporeal detoxification is highly effective, providing a more significant reduction of SOFA and MELD scores, increasing the proportion of regression of multiple organ dysfunction and reducing mortality.

Introduction. Paracetamol is the most commonly used drug across Western Europe and North America. There is no such trend of using Paracetamol in the Republic of Moldova, thus overdose cases are extremely rare. The mechanisms leading to overdose episodes might induce hepatotoxicity. Clinical case. This present article reports a case of acute liver failure induced by Paracetamol overdose. A 46-year-old man presented to the Medpark International Hospital. He was administered Paracetamol 1000 mg, approximately every 4 hours for 2 days, and 1000 mg twice a day for another 2 days, after an intense physical exertion, followed by muscle fever with myalgia and low-grade fever (37.4 °C) The reason for asking the medical care were pronounced fatigue, nausea, loss of appetite, night sweats, and frequent urination. Conclusion. Eventually, the case was successfully resolved due to N-acetyl-cysteine, administered according to the established treatment scheme, as well as the adjuvant therapy.

Extensive liver resection (ELR), performed in a number of surgical operations, refers to a critical injury, which necessitates the improvement of methods of therapy of acute post-resection liver failure.Aim: to compare the effectiveness of stimulation of regenerative processes in the liver residue after ELR (60–70%) by intraperitoneal administration of lysed aspirate bone marrow cells (BMCs) and total RNA (tRNA) isolated from BMCs.Materials and methods. This work was performed on 175 rats-male Wistar breed 250–300 g, on 75 of which under the inhalation anesthesia it was reproduced the model of the ELR in three groups of experiments: group 1 – control (administration of isotonic solution after ELR), group 2 – in 3–5 hours after ELR the tRNA from BMCs was intraperitoneally injected at a dose of 30 μg/100 g, group 3 – in 3–5 hours after ELR BMCs was administered intraperitoneally at a dose of 30–35 × 106 cells per rat. Comparative studies of the restorative processes in the liver after the ELR in the three groups were carried out by dynamic control of the mitotic activity of hepatocytes in the liver residue, cytolytic enzymes, total bilirubin and total serum protein, as well as the liver residue (mass) weight.Results. The tRNA from BMCs and BMCs in the indicated doses prevent the risk of the development of lethal outcomes, and also contribute to an earlier (by 10–14 days) normalization of the functional indices of hepatic homeostasis. However, the tRNA from BMCs, compared with BMCs, has a stronger stimulating effect on the recovery processes: it promotes earlier intensification of mitotic activity of hepatocytes and provides a higher rate of recovery of liver mass.Conclusion. For the induction of recovery processes in the liver residue after ELR, the preference should be given to the tRNA from BMCs.

This article summarizes data on etiology, epidemiology and clinical presentation of acute liver failure. The review provides statistics on the incidence rates of acute liver failure in patients with different underlying diseases, describes the most common complications and the main treatment approaches. The purpose of this review is to raise awareness of acute liver failure among physicians.

Uterine fibroids are the most common pelvic tumor formation in women and the most common indication for hysterectomy. The effectiveness of long-term intermittent use of ulipristal acetate (UA) in patients with uterine myoma has been proven earlier. In May 2018, the ability of UA to cause a drug-induced liver injury (drug-induced liver injury, DILI) was disproved, and the European Commission approved a positive decision. According to the conclusion Expertise of the Pharmacovigilance Risk Assessment Committee (Pharmacovigilance Risk Assessment Committee - PRAC) the benefit/risk ratio remains favorable. Published recommendations are aimed at reducing the risk of liver damage. UA remains the 1st line of treatment for most myomas.

Acetaminophen (AAP) is one of the most common and widely used antipyretic drugs, but its overdose is the leading cause of fulminant hepatic insufficiency in the world. Mechanisms of liver damage at the use of toxic doses of AAP are caused by the transformation of the isoform of cytochrome P450 (CYP2E1, CYP2A6) into a reactive metabolite, N-acetyl-parabenzoquinonimine (NAPQI), which plays a major role in hepatotoxicity. Another mechanism of hepatotoxicity includes the formation of peroxynitrite – a toxic free radical produced in the mitochondria, which causes oxidative damage. In addition to liver damage in case of acetaminophen poisoning, nephrotoxic effect can occur. Potential mechanisms of nephrotoxicity in overdose of AAP are presented, caused by cytochrome P450, as well as prostaglandin synthetase and enzyme N-deacetylase are described. In the clinical case described by us, the development of fulminant hepatic insufficiency against the background of acetaminophen administration led to the development of a coma along with the kidney damage, however, a stable positive dynamics, was achieved during treatment. In the catamnesis 2.5 years later, there were no signs of fibrosis or cirrhosis of the liver.

Aim. A comparative analysis of the functional efficacy of biomedical cell products (BMCP) for the regeneration of damaged liver based on biopolymer scaffolded porous and hydrogel matrices was performed on the experimental model of acute liver failure. Materials and methods. Matrices allowed for clinical use were employed for BMCP in the form of a sponge made from biopolymer nanostructured composite material (BNCM) based on a highly purified bacterial copolymers of poly (β-hydroxybutyrate-co-β-oxyvalerate) and polyethylene glycol and a hydrogel matrix from biopolymer microheterogeneous collagen-containing hydrogel (BMCH). Cellular component of BMCP was represented by liver cells and multipotent mesenchymal bone marrow stem cells. The functional efficacy of BMCP for the regeneration of damaged liver was evaluated on the experimental model of acute liver failure in Wistar rats (n = 40) via biochemical, morphological, and immunohistochemical methods. Results. When BMCP was implanted to regenerate the damaged liver on the basis of the scaffolded BNCM or hydrogel BMCH matrices, the lethality in rats with acute liver failure was absent; while in control it was 66.6%. Restoration of the activity of cytolytic enzyme levels and protein-synthetic liver function began on day 9 after modeling acute liver failure, in contrast to the control group, where recovery occurred only by days 18–21. Both matrices maintained the viability and functional activity of liver cells up to 90 days with the formation of blood vessels in BMCP. The obtained data confirm that scaffolded BNCM matrix and hydrogel BMCH matrix retain for a long time (up to 90 days) the vital activity of the adherent cells in the BMCP composition, which allows using them to correct acute liver failure. At the same time, hydrogel matrix due to the presence of bioactive components contributes to the creation of the best conditions for adhesion and cell activity which accelerate the regeneration processes in the damaged liver compared to BMCP on scaffolded matrix. Conclusion. A statistically significant difference was found between the functional efficacy of the BMCP studied based on BNCM and BMCH matrices. BMCP based on hydrogel BMCH matrix was more effective for the regeneration of damaged liver.

Information on etiology, epidemiology and clinical manifestations of acute liver failure is systemized. The review provides statistics on the frequency of its occurrence in different nosological manifestations, describes the most frequent developed complications and the main approaches to therapy. Aim: to raise awareness of acute liver failure among physicians.

Currently, the world is marked rise in the number of patients with liver disease. Approximately 100,000 patients hepatitis complicated by acute liver failure, with mortality in this disease reaches 70-90 % despite the use of modern methods of treatment Currently, there are more than 20 concepts of this disease. In 15-20 % of cases the cause of acute liver failure can not be established. Most clinicians believe that the pathogenesis of liver failure is a strong humoral and hyperimmune response, resulting in massive necrosis of liver cells. Diagnosis of liver failure based on anamnesis, clinical, biochemical and electroencephalographic changes. Traditional conservative therapy of acute liver failure in the first place based on the measures taken to address the etiological factor. Transplantation is an effective measure in acute liver failure. In the world there are a sufficient number of prognostic scales, criteria and risk factors of acute liver failure. Each of them has its own characteristics, but a unified system of prognostic estimation of arrester.

Drug-induced liver injury (DILI) is a relevant issue in clinical practice and is still a diagnosis of exclusion. Despite the low incidence in the general population, DILI is the cause of most cases of acute hepatic injury and has a mortality rate of up to 50%. Despite many reports in the medical literature about the DILI mechanisms, a clear causal relationship between them, drugs, and risk factors has not been established. Current clinical practice is based on a combination of a thorough study of a history of risk factors, the timing of drug and dietary supplements' administration, and the analysis of laboratory and instrumental tests. It aligns with the international criteria of the Rousell Uclaf Causality Assessment Method (RUCAM), which is considered one of the main diagnostic algorithms for DILI. The article addresses current DILI classification, risk factors, diagnostic algorithms, causalities, clinical evaluation, promising liver function biomarkers, and specific treatment.