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This article reports studies of the biological activity of polysaccharides from aqueous and alkaline fractions isolated from the seed coats of the common horse chestnut (Aesculus hippocastanum L.). The polysaccharides studied here were found to belong to class V, essentially non-toxic substances, as the LD50 was greater than 2000 mg/kg. Studies of hepatoprotective activity in mice showed that intragastric administration of polysaccharides at a dose of 25 mg/kg gave a total coefficient of hepatoprotective activity, in terms of survival, life expectancy, liver weight coefficient, and body weight, of 0.931. The polysaccharides of the aqueous fraction used at a dose of 25 mg/kg had high hepatoprotective activity, while the same dose of polysaccharides from the alkaline fraction had moderate hepatoprotective activity. While liver enzyme (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP)) activities increased significantly in the control group of animals as compared with intact animals, by factors of 1.5 and 2.0, levels in the experimental groups approached normal i.e., test substances significantly reduced the activities of markers of cytolytic syndrome (ALT, AST) and cholestasis (AP). [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) can be considered in cases of acute hepatitis by the exclusion of any disease-related causes. For several decades, anabolic steroids have been considered not only as drugs for treatment of diseases such as hypogonadism, sarcopenia, hypotrophy in cancer patients, aplastic anemia, etc., but also as risk factor for acute liver failure, that can lead to liver cancer, and even sudden death. Anabolic steroids are known to be increa­singly used not only for legitimate medical uses, but also for enhance physical performance and promote muscle growth for ideal body shape. The article presents a clinical case of acute drug-induced hepatitis after 2 months of using stanozolol, a synthetic testosterone derivative, in a 25-year-old previously healthy man. Thorough etiological investigations ruled out other causes of DILI. The man was treated at the in-patient department and discharged with improvement, but it took several months for the disappearance of hepatic cytolytic and cholestatic changes. Clinicians should be aware of the risk for toxic drug-induced hepatitis in male bodybuilders and collect a thorough history of the patient’s intake of nutritional supplements that may contain androgen derivatives.

The review article discusses modern aspects of drug-induced liver injury (DILI) in patients with tuberculosis who are receiving etiotropic therapy. The main mechanisms of DILI, including toxic and idiosyncratic types, are described, as well as their pathogenetic, biochemical, and epidemiological differences. DILI can manifest as various clinicomorphological forms of liver damage, such as steatosis and steatohepatitis, acute and chronic hepatitis, mitochondrial cytopathy, cholestasis, sclerosing cholangitis, vascular injury, and others. The main diagnostic method for DILI is the detection of liver enzymes — transaminases and alkaline phosphatase — based on the degree of elevation and their ratio, which identify two main types of liver injury — hepatocellular and cholestatic — as well as a mixed variant. The article provides a scoring assessment of liver damage in a patient receiving chemotherapy to classify it as drug-induced liver injury.

Background. The article reflects the clinical significance of the early diagnosis of toxic hepatitis in patients who have undergone a new coronavirus infection with the determination of clinical and laboratory predictors of the response to therapy. A dynamic analysis of the effectiveness of toxic hepatitis therapy in patients of three experimental groups and a control group is presented. Aim. The aim of the present study is to increase the effectiveness of the treatment of toxic hepatitis in patients who have undergone COVID-19. Materials and methods. On the basis of the newly created infection centers of the Central Clinical Hospital RZhD-Medicine and Vishnevsky 3-rd Central Military Clinical Hospital 996 patients with COVID-19, who had clinical and laboratory signs of toxic liver damage (cytolytic and/or cholestatic syndromes) against the background of COVID-19 therapy. Results. On the 14th day from the start of therapy in group 3, there was a significant decrease in the clinical manifestations of jaundice in 163 (72.8%) patients, on the 21st day of treatment, this symptom was stopped in all patients. In groups 1 and 2, the decrease in clinical manifestations of jaundice was significantly lower 122 (55.2%) and 134 (58.8%); p0.05. At the end of therapy, no manifestations of jaundice were observed in all experimental groups, while in the control group, symptom reduction was achieved only in 47 (14.5%) patients. Conclusion. The use of drugs with hepatoprotective effect in the form of monotherapy in groups 1 (UDCA) and 2 (ademethionine) showed a low therapeutic effect with positive dynamics of clinical and laboratory indicators of toxic hepatitis activity. The use of combined treatment in group 3 (UDCA and ademethionine) demonstrated the maximum therapeutic effect, pronounced positive dynamics in the form of normalization of clinical and laboratory indicators of toxic hepatitis activity.

Occupational exposure to dimethylacetamide (DMAc) has been reported to cause toxic hepatitis. Sixty spandex workers were included in this study to research the clinical manifestations and expression of cytokines and lymphocytes in DMAc-induced toxic hepatitis. Chinese drugs (reduced glutathione and Hugan tablets) were used to treat them. The manifestations including jaundice, asthenia, appetite, nausea, emesis, abdominal distension, yellow urine, and dizziness were scored. The percentages of patients rated as 0–3, 4–6, 7–9, and 10–12 points were 33.3%, 43.3%, 21.7%, and 1.7%, respectively, before treatment, and all patients showed 0–3 points after the treatment. The ultrasonic and CT imaging revealed diffuse intrahepatic hypodensity, intrahepatic calcification, signs of liver injury, and splenomegaly, which improved after therapy. Blood analysis showed that ALT, AST, TBIL, IL-6, IL-10, TNF-α, IFN-γ, CD3+%, and CD4+/CD8+ statistically decreased after drug treatment. Correlation analysis demonstrated positive linear correlations between ALT and TBIL, AST and TBIL, IL-10 and ATL, IL-10 and AST, IL-10 and TBIL, IFN-γ and IL-6, IFN-γ and TNF-α, and CD3+% and ALT. Pro-inflammatory cytokines and lymphocytes in DMAc-induced toxic hepatitis reflected an active immune state that decreased after treatment. IL-10 may inhibit the immune response in this disease, as a protective mechanism. [ABSTRACT FROM AUTHOR]

Background: Carbon tetrachloride (CCl4) as an organic solvent causes symptoms of acute and chronic liver injury, including necrosis, fat changes, liver cancer, and cirrhosis. Lepidium sativum contains flavonoids, alkaloids, and antioxidant components. Objectives: This study aims to investigate the hepatic protection of L. Sativum Extract (LSE) on CCl4-induced hepatotoxicity in mice. Methods: A total of 25 male mice were randomly divided into five groups (n=5): control (olive oil), CCl4, and 3 LSE groups. Except for the control group, all the mice received CCl4 (50%, 0.5 mL/kg) intraperitoneally twice a week for 4 weeks. The mice in the LSE groups were treated daily with LSE (200, 400, and 600 mg/kg) via IP injection. The animals were sacrificed 24 h after the last dose, and liver function parameters, such as Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Glutathione (GSH) were determined. Furthermore, 0.1 g of liver tissue was removed for histochemical analysis. Results: Significant differences were observed in GSH, ALP, AST, and ALT levels between the CCI4 and the control groups. Compared to the CCl4 group, LSE treatment significantly decreased plasma ALT (P

Fever is a defensive and adaptive reaction of the body that develops in response to the action of pathogenic stimuli. It often accompanies various infectious, autoimmune, oncohematological and other diseases. Due to the frequent significant deterioration of children's general health, the occurrence of fever in children gives rise to concern not only in parents, but also in pediatricians. According to temperature level, fever can be classified into different categories: subfebrile - 37.1 to 37.9 °C, moderate -38 to 39 °C, febrile - 39.1 to 41 °C and hyperthermic - above 41 °C. By clinical manifestation distinguish benign, or rose, and malignant, or white, fever. The need to use antipyretic drugs depends not only on the hight of the body temperature elevation, but also on the patient's general health. The clinical guidelines state that the use of acetylsalicylic acid, nimesulide and met-amizole to lower the body temperature in children is not recommended, due to high risk of adverse reactions. Ibuprofen and paracetamol are the drugs of choice to lower body temperature in children both in Russia and abroad. Over 120 comparative studies of these two drug formulations have shown their close efficacy, but ibuprofen is most preferred for the treatment of fever and pain. In order to lower body temperature, parents can uncontrollably use antipyretic drugs in various combinations and incorrect dosages, which leads to severe toxic effects. The article presents a clinical case of Reye's syndrome in a 10-year-old girl, which is most likely associated with the use of aspirin as an antipyretic.

Background: N,N-dimethylformamide (DMF) is a colorless, odorless and volatile liquid that is miscible with water and most organic liquids and is used in various industrial applications. Exposure to DMF is mainly through the dermal and respiratory systems. After exposure to DMF, it is mainly metabolized in the liver and the metabolites are excreted by the kidneys. Acute or chronic occupational exposure to this solvent is hepatotoxic and may cause poisoning.(1) We aimed to present the intensive care management of a patient who developed acute hepatitis after serious occupational dimethylformamide exposure. Case: A 22-year-old male patient applied to the emergency department with complaints of nausea, vomiting, diarrhea and fever after exposure to dimethylformamide at work. The patient was admitted to the intensive care unit with the diagnosis of acute toxic hepatitis. The patient had no history of additional disease or previous hepatitis. Hepatobiliary ultrasound was performed in the patient with high liver function tests, and hepatitis markers were negative. Viral infection-associated and alcoholic hepatitis were ruled out. In the intensive care unit, hepatotoxic agents were avoided and n acetyl cysteine and symptomatic supportive treatment were given. At the end of the 6-day follow-up, the patient was discharged, whose symptoms improved and liver function tests decreased. Discussion: Occupational exposure limits for dimethylformamide is 10 ppm or 30 mg/m3 as an 8-hour time-weighted average (TWA) according to Occupational Safety and Health Administration (OSHA) and American Conference of Governmental Industrial Hygienists (ACGIH).(2,3) In recent years, poisoning cases associated with occupational exposure to DMF have been reported. Findings of this toxic solvent exposure are nonspecific, they can be confused with many diseases in terms of differential diagnosis. There is no specific antidote to DMF, treatment is supportive. Conclusion: The use of DMF in the industrial field is increasing day by day and cases of acute and chronic poisoning related to occupational exposure are reported. The target organ is the liver, and especially severe hepatotoxicity should be monitored in the intensive care unit. [ABSTRACT FROM AUTHOR]

The liver is a crucial organ in metabolism, and some substances can induce toxic hepatitis with high morbidity and mortality. Chemical and drug-induced liver disease is a diagnostic and therapeutic challenge since it requires extension studies to rule out other entities. We present the case of a 51-year-old female patient without underlying comorbidities, admitted due to symptoms of two-day evolution consisting of progressive jaundice, diarrheal episodes without acholia, or any other additional manifestation. Her condition was caused by the intake of nimesulide, two tablets a day for two days, for pain secondary to a mandibular cyst diagnosed in previous days. During her admission to the emergency room, the patient described chronic consumption of Herbalife® products daily for four years. She presented with elevated transaminases, prolonged prothrombin time (PT), and direct hyperbilirubinemia. Infectious and immunological diseases were ruled out. We decided to start antibiotic and vitamin K coverage. Finally, and by exclusion, a liver biopsy suggested an inflammatory process compatible with drug-induced hepatitis. The woman evolved favorably when the medication and dietary supplement were discontinued. In conclusion, this case constitutes an initial point in advancing research into hepatotoxicity by shared mechanisms of various substances simultaneously, such as what happened to the patient with the parallel use of Herbalife® and nimesulide. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) can be considered in cases of acute hepatitis by the exclusion of any disease-related causes. For several decades, anabolic steroids have been considered not only as drugs for treatment of diseases such as hypogonadism, sarcopenia, hypotrophy in cancer patients, aplastic anemia, etc., but also as risk factor for acute liver failure, that can lead to liver cancer, and even sudden death. Anabolic steroids are known to be increasingly used not only for legitimate medical uses, but also for enhance physical performance and promote muscle growth for ideal body shape. The article presents a clinical case of acute drug-induced hepatitis after 2 months of using stanozolol, a synthetic testosterone derivative, in a 25-year-old previously healthy man. Thorough etiological investigations ruled out other causes of DILI. The man was treated at the in-patient department and discharged with improvement, but it took several months for the disappearance of hepatic cytolytic and cholestatic changes. Clinicians should be aware of the risk for toxic drug-induced hepatitis in male bodybuilders and collect a thorough history of the patient’s intake of nutritional supplements that may contain androgen derivatives. [ABSTRACT FROM AUTHOR]

The paper describes an in-depth in vitro and in vivo comparative study of hepatoprotective properties of some "doubled" derivatives of 4,6-dimethyl-1,2-dihydro-1-(2-hydroxyethyl)pyrimidin-2-one (the drug xymedon 1), in which the moieties of 1 are linked by ester bridges with different numbers of methylene groups (succinate (2a), adipate (2b), and suberate (2c)). The effect of "doubled" derivatives of compound 1 on the cell cycle of Chang Liver cell line was determined. The hepatoprotective properties of compounds 2a and 2b were studied in vivo in Wistar rats. Compounds 2a—c were found to restore the proliferative activity of Chang Liver cells in the presence of the d-galactosamine toxicant. Compounds 2a and 2b were effective over the widest concentration range and were more active than 2c. Compound 2b was most effective, causing a maximum increase in the percentage of cells in the G2/M phase of the cell cycle, in the concentration range from 62.5 to 250 µmol L−1, similarly to compound 1. According to in vivo studies, "doubled" derivatives 2a and 2b had less pronounced hepatoprotective properties than parent compound 1: an effect similar to that of 1 was attained at doses exceeding the minimum effective dose of xymedon (0.24 mg kg−1) by factors 7.5 and 2.7, respectively. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease is an important cause of global liver disease characterized by diffuse hepatocytes with hepatocellular ballooning, intrahepatic inflammation and progressive fibrosis. A relevant task is the study of the relationship between content of free fatty acids and serum cytokine profile in patients with chronic diffuse liver diseases. A total of 74 people with chronic diffuse liver diseases were examined, including 32 patients with non-alcoholic fatty liver disease, 22 patients with alcoholic liver disease, 20 patients with toxic hepatitis. Chromatographic examination of free fatty acids (FFA) in blood serum was carried out using a Chromatek-Crystal 5000 gas chromatography system. Patients with chronic diffuse liver diseases had a significant increase in the level of unsaturated free fatty acids (USFA) in cases of toxic hepatitis (by 2.92 times, P > 0.05) and a decrease in the level of saturated free fatty acids (SFA) in cases of non-alcoholic fatty liver disease (by 1.52 times, P > 0.05) compared with the control group; the balance between omega-6 and omega-3 PUFA significantly changed due to increase in linoleic acid in patients with alcoholic liver disease and toxic hepatitis (by 1.91 and 2.11 times, respectively) and arachidonic acid in patients with toxic hepatitis (by 1.78 times). The level of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α) were determined. In patients suffering chronic diffuse liver diseases there were multidirectional changes in the composition of free fatty acids of blood serum: a significant increase in the level of USFA, levels ІL-6 in toxic hepatitis; a decrease in the level of SFA, levels ІL-6 and TNF-α during non-alcoholic fatty liver disease; increased TNF-α production, ІL-6 during alcoholic liver disease compared with the control group. Significant change occurred in the balance between omega-6 and omega-3 PUFA due to increase in linoleic acid in cases of alcoholic liver disease and toxic hepatitis and arachidonic acid in cases of toxic hepatitis. The revealed correlations support the hypothesis that inflammation and lipotoxicity of FFA of blood serum contribute to the development and progression of structural changes in the liver. However, the pathomechanism of lipid metabolism and cytokine regulation with different etiological factors have their own characteristics, which should be taken into account when treating patients of these groups. Prospects for further research: these parameters may be used for serologic biomarkers of liver disease and development and implementation of the ratio between FFA and cytokines for the differential diagnosis of chronic diffuse liver disease in medical practice.

According to the World Health Organization, diseases of the gastrointestinal tract rank third place after cardiovascular disease and cancer and more than 2 billion people suffer from hepatic diseases and toxic hepatitis is one of them. Given the complexity of differentiation and confirmation of iatrogenic toxic hepatitis and broad spectrum of possible medication side effects, there is a real problem with precise statistics of hepatic drug lesions. This study aims to improve the possibility of diagnosing liver fibrosis in patients with normal weight and overweight and determine and study the relationship between the level of polyfunctional cytokine TGF-β1 with BMI. We examined 44 patients with a history of breast cancer of I-II degree according to the TNM classification (TNM-8 system, 2016) without malignancy and who belonged to the III clinical group (persons with proven malignant tumors who have completed radical treatment and are in remission) aged 35 to 79 years. Patients were divided into two main groups. The first group included patients without signs of toxic liver disease and the second group represented patients with signs of toxic hepatitis. In addition to biochemical analysis, the subjects were examined to determine the FibroTest index to verify the fibrosis stage. Additionally, the FIB-4 index was calculated. This study found that FIB-4 and fibrotest may be sensitive and reliable methods for liver fibrosis screening in patients after cancer chemotherapy. The presence of excess body weight may be an important factor in predicting the development of severe fibrosis in such patients. The level of profibrogenic cytokine TGF-β1 may be an additional predictor of fibrosis progression. [ABSTRACT FROM AUTHOR]

The influence of extra genital pathology on the reproductive function of female rats and the structural and functional development of the immune system of the offspring was researched. More pronounced violations of reproductive function were found in females with chronic toxic hepatitis (CTH) than in autoimmune enterocolitis (AIE). The appearance of prenatal mortality in females, an increase in mortality of rat pups on days 1-3 after birth, a lag in the development of offspring, in the form of a decrease in growth and weight indicators, the mass of internal organs of rat pups, were also more pronounced in the group with CTG. Deeper structural and functional changes in early postnatal ontogenesis associated with a lag in the development of the thymus, spleen, mesenteric lymph nodes and Peyer's patches before the transition of rat pups to mixed and definitive nutrition is also characteristic of the offspring of CTG females. [ABSTRACT FROM AUTHOR]

The aim. Study the degree of absorption, assimilation, and excretion of calcium in rats with chronic toxic hepatitis. Materials and methods. The studies were carried out on 1 month old Wistar rats. Toxic hepatitis in the experimental group was reproduced by intraperitoneal injection of hydrazine sulfate at a dose of 50 mg / kg twice a week. Studies of the absorption of substances in rats were carried out under thiopental anesthesia according to the Tyri method after 3 months of pathology modelling. In the intestinal contents, the amount of unabsorbed calcium and amino acids was determined. To determine the amount of assimilated and excreted calcium metabolic chambers were used for daily collection of urine, faeces and food residues, in which the calcium content was determined (average for three days per animal). After removing the rats from the experiment, the level of calcium in the blood serum was determined, in the bone tissue -- the degree of its resorption by the activity of acid phosphatase and the content of calcium. Results and discussion. Toxic hepatitis reduced calcium absorption by 34.5 % in the small intestine of rats and did not have a significant effect on amino acids, the inhibition of absorption of which in hepatitis was only 5.5 %. The excretion of calcium in the urine of rats with toxic hepatitis was reduced by 1.8 times, and with faeces, on the contrary, increased by 1.5 times. As a result, calcium absorption in rats with hepatitis decreased by 24.2 %. Decreased absorption of calcium, and its increased excretion in the faeces, led to a decrease in the level of this element in the blood of animals with hepatitis by 14.7 %. Our studies found bone destruction in rats with hepatitis: an increase in bone acid phosphatase activity by 65.3 % and a decrease in calcium levels by 15.5 %. Conclusion. The triggering mechanism for the development of hepatic osteodystrophy is the inhibition of calcium absorption in the small intestine of rats with hepatitis, consequently - a decrease in its absorption and level in the blood, which ultimately leads to the activation of bone resorption. The established patterns will form the basis of the pathogenetic scheme for the prevention of hepatic osteodystrophy [ABSTRACT FROM AUTHOR]

INTRODUCTION: Toxic hepatitis is a dose-dependent or idiosyncratic liver disease accompanied by acute or chronic liver injury that induced by the ingestion of drugs or other substances. It even could be mortal, sometimes. Toxic hepatitis is common due to Heliz grass which is consumed frequently in Eastern and Southeastern Anatolia of our country. We aim to present toxic hepatitis due to Heliz consumption for the first time in the literature, in this study. METHODS: The data of 30 patient, hospitalized and followed-up and treated in gastroenterology department of our hospital, and who had a history of Heliz grass consumption in the last 1 day between 2014-2018 were compiled and analyzed. RESULTS: Liver function tests of the patients were elevated. Hepatitis markers were negative in viral serology except one patient. Examinations for autoimmune liver disease, brucellosis and celiac examinations were normal. Ten patients were referred to the transplant center because of the need for transplantation. None of these patients required transplantation at follow-up. All were discharged with healing. DISCUSSION AND CONCLUSION: Heliz, well known in Turkey's eastern and southeastern Anatolia, is a plant used in various dishes, making cheese with herbs and making pickles. Although it is thought that this plant has various benefits among the public, its hepatotoxicity-producing effect has not yet entered the literature. We believe that Heliz hepatotoxicity will be included in the differential diagnosis in patients with toxic hepatitis.

Many drugs with different mechanisms of action and indications available on the market today are capable of inducing hepatotoxicity. Drug-induced liver injury (DILI) has been a treatment challenge nowadays as it was in the past. We searched Medline (via PubMed), CENTRAL, Science Citation Index Expanded, clinical trials registries and databases of DILI and hepatotoxicity up to 2021 for novel therapies for the management of adult patients with DILI based on the combination of three main search terms: 1) treatment, 2) novel, and 3) drug-induced liver injury. The mechanism of action of novel therapies, the potential of their benefit in clinical settings, and adverse drug reactions related to novel therapies were extracted. Cochrane Risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment approach was involved in the assessment of the certainty of the evidence for primary outcomes of included studies. One thousand three hundred seventy-two articles were identified. Twenty-eight articles were included in the final analysis. Eight randomized controlled trials (RCTs) were detected and for six the available data were sufficient for analysis. In abstract form only we found six studies which were also anaylzed. Investigated agents included: bicyclol, calmangafodipir, cytisin amidophospate, fomepizole, livina-polyherbal preparation, magnesium isoglycyrrhizinate (MgIG), picroliv, plasma exchange, radix Paeoniae Rubra, and S-adenosylmethionine. The primary outcomes of included trials mainly included laboratory markers improvement. Based on the moderate-certainty evidence, more patients treated with MgIG experienced alanine aminotransferase (ALT) normalization compared to placebo. Low-certainty evidence suggests that bicyclol treatment leads to a reduction of ALT levels compared to phosphatidylcholine. For the remaining eight interventions, the certainty of the evidence for primary outcomes was assessed as very low and we are very uncertain in any estimate of effect. More effort should be involved to investigate the novel treatment of DILI. Well-designed RCTs with appropriate sample sizes, comparable groups and precise, not only surrogate outcomes are urgently welcome. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease is an important cause of global liver disease characterized by diffuse hepatocytes with hepatocellular ballooning, intrahepatic inflammation and progressive fibrosis. A relevant task is the study of the relationship between content of free fatty acids and serum cytokine profile in patients with chronic diffuse liver diseases. A total of 74 people with chronic diffuse liver diseases were examined, including 32 patients with non-alcoholic fatty liver disease, 22 patients with alcoholic liver disease, 20 patients with toxic hepatitis. Chromatographic examination of free fatty acids (FFA) in blood serum was carried out using a Chromatek-Crystal 5000 gas chromatography system. Patients with chronic diffuse liver diseases had a significant increase in the level of unsaturated free fatty acids (USFA) in cases of toxic hepatitis (by 2.92 times, P > 0.05) and a decrease in the level of saturated free fatty acids (SFA) in cases of nonalcoholic fatty liver disease (by 1.52 times, P > 0.05) compared with the control group; the balance between omega-6 and omega-3 PUFA significantly changed due to increase in linoleic acid in patients with alcoholic liver disease and toxic hepatitis (by 1.91 and 2.11 times, respectively) and arachidonic acid in patients with toxic hepatitis (by 1.78 times). The level of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α) were determined. In patients suffering chronic diffuse liver diseases there were multidirectional changes in the composition of free fatty acids of blood serum: a significant increase in the level of USFA, levels ІL-6 in toxic hepatitis; a decrease in the level of SFA, levels ІL-6 and TNF-α during non-alcoholic fatty liver disease; increased TNF-α production, ІL-6 during alcoholic liver disease compared with the control group. Significant change occurred in the balance between omega-6 and omega-3 PUFA due to increase in linoleic acid in cases of alcoholic liver disease and toxic hepatitis and arachidonic acid in cases of toxic hepatitis. The revealed correlations support the hypothesis that inflammation and lipotoxicity of FFA of blood serum contribute to the development and progression of structural changes in the liver. However, the pathomechanism of lipid metabolism and cytokine regulation with different etiological factors have their own characteristics, which should be taken into account when treating patients of these groups. Prospects for further research: these parameters may be used for serologic biomarkers of liver disease and development and implementation of the ratio between FFA and cytokines for the differential diagnosis of chronic diffuse liver disease in medical practice. [ABSTRACT FROM AUTHOR]

We analyzed changes in activities of enzymes of phases I and II of xenobiotic biotransformation and parameters of NO metabolism in liver microsomes of rats with toxic CCl4-induced hepatitis after a 14-day course of sesquiterpene lactones from Artemisia leucodes (10 mg/kg). It was found that toxic hepatitis was associated with significant inhibition of NADPH-cytochrome c-reductase, benzo(a)pyrene hydroxylase, and NADPH-diaphorase, reduced cytochrome P-450 content, and enhanced induction of nitrate/nitrite reductase with accumulation of NO metabolites in the liver. Administration of sesquiterpene lactones stimulated activity of the studied components of the cytochrome P-450 system and promoted recovery of the NOergic system components; the effects were most pronounced in 7 and 14 days after treatment. [ABSTRACT FROM AUTHOR]

Many drugs with different mechanisms of action and indications available on the market today are capable of inducing hepatotoxicity. Drug-induced liver injury (DILI) has been a treatment challenge nowadays as it was in the past. We searched Medline (via PubMed), CENTRAL, Science Citation Index Expanded, clinical trials registries and databases of DILI and hepatotoxicity up to 2021 for novel therapies for the management of adult patients with DILI based on the combination of three main search terms: 1) treatment, 2) novel, and 3) drug-induced liver injury. The mechanism of action of novel therapies, the potential of their benefit in clinical settings, and adverse drug reactions related to novel therapies were extracted. Cochrane Risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment approach was involved in the assessment of the certainty of the evidence for primary outcomes of included studies. One thousand three hundred seventy-two articles were identified. Twenty-eight articles were included in the final analysis. Eight randomized controlled trials (RCTs) were detected and for six the available data were sufficient for analysis. In abstract form only we found six studies which were also anaylzed. Investigated agents included: bicyclol, calmangafodipir, cytisin amidophospate, fomepizole, livina-polyherbal preparation, magnesium isoglycyrrhizinate (MgIG), picroliv, plasma exchange, radix Paeoniae Rubra, and S-adenosylmethionine. The primary outcomes of included trials mainly included laboratory markers improvement. Based on the moderate-certainty evidence, more patients treated with MgIG experienced alanine aminotransferase (ALT) normalization compared to placebo. Low-certainty evidence suggests that bicyclol treatment leads to a reduction of ALT levels compared to phosphatidylcholine. For the remaining eight interventions, the certainty of the evidence for primary outcomes was assessed as very low and we are very uncertain in any estimate of effect. More effort should be involved to investigate the novel treatment of DILI. Well-designed RCTs with appropriate sample sizes, comparable groups and precise, not only surrogate outcomes are urgently welcome.

Introduction: Very little artificial intelligence (AI) work has been performed to investigate acetaminophen-associated hepatotoxicity. The objective of this study was to develop an AI algorithm for analyzing weighted features for toxic hepatitis after acetaminophen poisoning. Methods: The medical records of 187 patients with acetaminophen poisoning treated at Chang Gung Memorial Hospital were reviewed. Patients were sorted into two groups according to their status of toxic hepatitis. A total of 40 clinical and laboratory features recorded on the first day of admission were selected for algorithm development. The random forest classifier (RFC) and logistic regression (LR) were used for artificial intelligence algorithm development. Results: The RFC-based AI model achieved the following results: accuracy = 92.5 ± 2.6%; sensitivity = 100%; specificity = 60%; precision = 92.3 ± 3.4%; and F1 = 96.0 ± 1.8%. The area under the receiver operating characteristic curve (AUROC) was approximately 0.98. The LR-based AI model achieved the following results: accuracy = 92.00 ± 2.9%; sensitivity = 100%; specificity = 20%; precision = 92.8 ± 3.4%; recall = 98.8 ± 3.4%; and F1 = 95.6 ± 1.5%. The AUROC was approximately 0.68. The weighted features were calculated, and the 10 most important weighted features for toxic hepatitis were aspartate aminotransferase (ALT), prothrombin time, alanine aminotransferase (AST), time to hospital, platelet count, lymphocyte count, albumin, total bilirubin, body temperature and acetaminophen level. Conclusion: The top five weighted features for acetaminophen-associated toxic hepatitis were ALT, prothrombin time, AST, time to hospital and platelet count. [ABSTRACT FROM AUTHOR]

Background and Aim: Though rodenticidal hepatotoxicity is reported from India, there is no systematic study to assess its magnitude. This study aimed to assess exposure to rodenticide as a risk factor for acute hepatotoxicity in Tamil Nadu, India. Methods: We retrospectively analyzed acute hepatotoxicity caused by ingestion of hepatotoxin or potentially hepatotoxic drug overdose across 15 hospitals in 6 districts of Tamil Nadu from 1 January 2019 to 30 June 2019. Study exclusion criteria were idiosyncratic drug-induced liver injury and chronic liver diseases. Results: Of the 702 patients, 685 gave history of consuming rodenticide; hepatotoxicity in the other patients resulted from paracetamol overdose (n=10) and due to other drugs (n=7); 97% patients had a suicidal intent. Of 671 patients with complete data, ratio of number of patients with hepatotoxicity due to rodenticide to paracetamol overdose was 450:6 (i.e. 75:1). The 451 rodenticidal hepatotoxicity patients (255 males, 75% were 15–34 years old) underwent conservative management (n=396), plasma exchange (n=54) and plasma exchange followed by liver transplant (n=1); 159 patients (35%) had poor outcome (131 died, 28 discharged in moribund state). Based on our observations, we estimate a case burden of 1584 rodenticidal hepatotoxicity patients (95% CI: 265–6119) with poor outcome in 554 patients in Tamil Nadu from January 2019 to June 2019. Population attributable risk for rodenticide as cause of hepatotoxicity was 22.7%. Conclusion: Rodenticide ingestion was an important cause of acute hepatotoxicity in Tamil Nadu. Most patients were young and one-third had poor outcome. Public health interventions are needed to address this. [ABSTRACT FROM AUTHOR]

The aim. Study the degree of absorption, assimilation, and excretion of calcium in rats with chronic toxic hepatitis. Materials and methods. The studies were carried out on 1 month old Wistar rats. Toxic hepatitis in the experimental group was reproduced by intraperitoneal injection of hydrazine sulfate at a dose of 50 mg/kg twice a week. Studies of the absorption of substances in rats were carried out under thiopental anesthesia according to the Tyri method after 3 months of pathology modelling. In the intestinal contents, the amount of unabsorbed calcium and amino acids was determined. To determine the amount of assimilated and excreted calcium metabolic chambers were used for daily collection of urine, faeces and food residues, in which the calcium content was determined (average for three days per animal). After removing the rats from the experiment, the level of calcium in the blood serum was determined, in the bone tissue -- the degree of its resorption by the activity of acid phosphatase and the content of calcium. Results and discussion. Toxic hepatitis reduced calcium absorption by 34.5 % in the small intestine of rats and did not have a significant effect on amino acids, the inhibition of absorption of which in hepatitis was only 5.5 %. The excretion of calcium in the urine of rats with toxic hepatitis was reduced by 1.8 times, and with faeces, on the contrary, increased by 1.5 times. As a result, calcium absorption in rats with hepatitis decreased by 24.2 %. Decreased absorption of calcium, and its increased excretion in the faeces, led to a decrease in the level of this element in the blood of animals with hepatitis by 14.7 %. Our studies found bone destruction in rats with hepatitis: an increase in bone acid phosphatase activity by 65.3 % and a decrease in calcium levels by 15.5 %. Conclusion. The triggering mechanism for the development of hepatic osteodystrophy is the inhibition of calcium absorption in the small intestine of rats with hepatitis, consequently -- a decrease in its absorption and level in the blood, which ultimately leads to the activation of bone resorption. The established patterns will form the basis of the pathogenetic scheme for the prevention of hepatic osteodystrophy [ABSTRACT FROM AUTHOR]

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Objective: The aim of this study was to determine the effect of HIV-1 genetic variants and drug resistance-associated mutations (DRM) on the development of hepatotoxicity. Design and participants: This was a longitudinal study of 81 newly diagnosed HIV-infected individuals in five HIV Treatment clinics in the Northwest Region (NWR) of Cameroon from February 2016 to November 2016. Methodology: Eighty-one antiretroviral drug-naïve patients were recruited into the study and followed-up for 6 months. Blood samples were collected prior to ART initiation and 180 days (D180) later. Serum levels of aminotransferases were analyzed by enzymatic methods. The HIV-1 protease and reverse transcriptase sequences were obtained using an in-house protocol and DRMs were identified using the Stanford HIVDR interpretation program, and HIV-1 subtypes by phylogeny. Results: The mean age of the study participants was 36.5 years. Of these, 37(45.7%) patients showed hepatotoxicity at D180. There were four pure subtypes and five recombinant types with CRF02_AG (74.1%) being the predominant genetic variants. The prevalence of hepatotoxicity was highest among individuals infected with HIV-1 CRF02_AG (70.3%). The prevalence of DRM was 11.1% (9/81). Hepatotoxicity was significantly (p =0.04) higher 77.8% (7/9) among patients with resistant virus. Conclusion: Data from this study reveals a high level of hepatotoxicity among patients with DRM probably as a result of persistent viral replication. These findings highlight the need to conduct routinely DRM surveillance among patients with hepatotoxicity in order to improve patient management and care. [ABSTRACT FROM AUTHOR]

Introduction: Drug-induced liver injury is an increasingly prevalent consequence of the diversification of available therapeutic weapons, mostly idiosyncratic and with several possible mechanisms and patterns of specific damage for each drug. Carvedilol, a widely used non-selective alpha and beta blocker leads, in very rare cases, to injury of the bile ducts by toxic metabolites, resulting in a mixed-pattern hepatitis with possible progression to chronic cholestatic syndrome and cirrhosis. The authors report the second known case of this important toxicity. Clinical Case: An 83-year-old woman was admitted to the Internal Medicine ward for etiological clarification of a mixed-pattern hepatitis. Clinical history was unremarkable and structural, infectious, and autoimmune causes were excluded by blood tests and imaging exams, ultimately leading to the diagnosis of toxic hepatitis that was further confirmed by liver biopsy with morphologic findings of mixed-pattern liver injury. Carvedilol, started 6 months before, was deemed the causal agent since it was the only drug with a clinically, temporally, analytically, and histologically compatible pattern. The withdrawal of the drug resulted in slow reversal of the referred abnormalities. Conclusion: In very rare cases, carvedilol can cause important liver toxicity as a chronic cholestatic syndrome which can evolve to cirrhosis. It should be taken in consideration as causal agent in similar cases and stopped immediately upon suspicion, as the timely withdrawal results in reversion of the pathological findings.

Abstract Background Exposure to sustained high concentrations of HCFC-123 is known to be hepatotoxic. We report two simultaneous cases of toxic hepatitis related to exposure to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123), a common refrigerant, at a Korean fire extinguisher manufacturing facility. Case presentation Patients A and B were men aged 21 and 22 years, respectively, with no notable medical histories. They had recently started working for a manufacturer of fire extinguishers. During the third week of their employment, they visited the emergency center of a general hospital due to fever, lack of appetite, and general weakness. At the time of their visit, they were suspected as having hepatitis due to elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin levels and were hospitalized. However, as their condition did not improve, they were moved to a tertiary general hospital. After conservative treatment, one patient improved but the other died from acute hepatic failure. Assessments of the work environment showed that the short-term exposure levels of HCFC-123 for valve assembly processes were as high as 193.4 ppm. A transjugular liver biopsy was performed in patient A; the results indicated drug/toxin-induced liver injury (DILI). Given the lack of a medical history and the occupational exposure to high levels of HCFC-123, a hepatotoxic agent, the toxic hepatitis of the workers was likely related to HCFC-123 exposure. Conclusions Work environment assessments have not included this agent. To the best of our knowledge, we are the first to report a case of death related to HCFC-123-induced liver damage. Our findings suggest that exposure standards and limits for HCFC-123 must be developed in Korea; work environments will have to be improved based on such standards.

Today, antithyroid drugs are widely used in the treatment of hyperthyroidism. Elevated creatine kinase and liver injury (hepatitis) caused by methimazole are some of rare side effects. Elevation of creatine kinase (CK) should be monitored due to the risk of rhabdomyolysis development. Also, drug-induced liver injury can be seen. In this article, we report a patient who received methimazole 2 months ago for hyperthyroidism, but then began to have complaints like muscle pain, jaundice (icterus) in the eyes along with itching and dark urine, and found out to have elevated CK as well as liver enzymes induced by liver injury, thus showed rapid recovery upon N-acetylcysteine treatment. [ABSTRACT FROM AUTHOR]

Introduction. Sometimes we find cases of elevated transaminases with an unclear etiology. A detailed history is useful and can uncover hidden causes. We report here two cases of herbal-induced liver injury with severe hypertransaminasemia caused by ingestion of Chelidonium majus L (celandine), considered an alternative therapeutic. Case description. Case No. 1: A 64-year-old female patient presented to the emergency department for jaundice. The patient reported using celandine capsules for one month to treat her gallstones. The diagnosis was herb-induced liver injury (HILI), gallstones, and choledocolithiasis. Transaminases were over 1000 UI/l. After discontinuing the use of celandine and receiving intravenous treatment consisting of amino acids and phospholipids, the patient's condition improved. Following this, they were referred for endoscopic extraction of common bile duct stones and cholecystectomy. Case no. 2: A 66-year-old female patient presented to our medical department for investigation of increased liver function tests that were incidentally detected while evaluating musculoskeletal pain. After a directed questionnaire, she reported consuming celandine tea regularly for "health promotion." Transaminases normalized after intravenous therapy with amino acids and phospholipids. Discussion. As more and more people use herbal substances as alternative therapies, it is important to expect an increase in cases with unexplained elevated liver function tests. Celandine is one of the most aggressive herbs, and physicians should clearly ask about its use in cases of unexplained liver injury. Conclusion. Celandine is an herb used as an alternative therapy with high liver toxicity. Patients with unexplained liver injuries should be asked about the consumption of this herb. [ABSTRACT FROM AUTHOR]

Studies on the role of immunity mechanisms in the emergence and maintenance of inflammatory and destructive processes in the liver under toxic hepatitis and nutrient deficiency are topical. The aim of research – to study the quantitative content and functional activity of leukocytes under the conditions of acetaminophen-induced hepatitis on the background of nutritional protein deficiency. The most pronounced changes in cell-mediated immunity are observed in protein-deficient animals with toxic hepatitis. The pronounced defects of both specific and non-specific cellular immunity were manifested by the leukocytosis, increase number of segmented neutrophils in blood serum against decrease their phagocytic index and phagocytic number, reduction of total lymphocyte number, and simultaneously lowering of T- and B-lymphocytes was established under the conditions of acetaminophen-induced hepatotoxicity on the background of protein deficiency. Installed changes indicate the defective formation of functional immunity state which can manifest by decrease the body’s ability to carry out the reaction of cellular and humoral immunity. Research results may be used for the rationale of therapeutic approaches to the elimination and correction of the consequences of immunological status disturbances under the conditions of acetaminophen-induced hepatitis, aggravated by the alimentary protein deprivation.

Background. In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department.Material and methods. We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia.Results. We analyzed 273 patients – 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values.Conclusion. Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.

Copyright of Journal of Tepecik Education & Research Hospital / İzmir Tepecik Eğitim ve Araştırma Hastanesi Dergisi is the property of Logos Medical Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The purpose of this study is to identify hepatoprotective properties of melanins from aqueous extracts of Inonotus obliquus distinguished by microwave modes used in extraction in both in vitro and in vivo studies. In vitro tests were used in studies of the effect of Chaga mushroom melanins on the vitality of cells of a normal human hepatocyte line Chang Liver, as well as their hepatoprotective effect and influence on the cell cycle. The hepatoprotective effect was studied in the context of the influence of the toxicant d-galactosamine, at a concentration of 150 mM. The results show that the melanin of the aqueous extract of Chaga, obtained in the process of microwave-assisted extraction at 180 W, at concentrations of 10−5 and 10−3 g/l, displays a hepatoprotective effect, as it increases the vitality of cells under the toxic influence of d-galactosamine by 2–2.5 times. In vivo tests were used in studies of the hepatoprotective properties of the melanin of the aqueous extract of Chaga obtained in the process of microwave-assisted extraction at 180 W on white male Sprague Dawley rats. The melanin was administered to rats for 14 days at a dose of 100 mg/kg. Toxic damage was inflicted on the liver using carbon tetrachloride on days 5 to 12 of administering the melanin; the liver was studied and the blood biochemical parameters were determined on day 15. It was shown that melanin produces a hepatoprotective effect which is expressed in the minimization of liver injury signs such as steatosis, necrosis, fat accumulation, and normalization of the total and unconjugated bilirubin, total protein, serum cholinesterase, and gamma-glutamyl transpeptidase levels. [ABSTRACT FROM AUTHOR]

Many categories of drugs can induce hepatotoxicity, so improving the prediction of toxic drugs is important. In vitro models using human hepatocytes are more accurate than in vivo animal models. Good in vitro models require an abundance of metabolic enzyme activities and normal cellular polarity. However, none of the in vitro models can completely simulate hepatocytes in the human body. There are two ways to overcome this limitation: enhancing the metabolic function of hepatocytes and changing the cultural environment. In this review, we summarize the current state of research, including the main characteristics of in vitro models and their limitations, as well as improved technology and developmental prospects. We hope that this review provides some new ideas for hepatotoxicity research. In vitro models using human hepatocytes are more accurate than in vivo models. Good in vitro models require an abundance of metabolic enzyme activities and cellular polarity. However, none of the in vitro models can simulate an in vivo environment. To overcome this limitation, there are two methods, enhancing the metabolic function of hepatocytes and changing the cultural environment. In this review, we summarize the current state of research, including the main characteristics of in vitro models and their limitations, as well as improved technology and developmental prospects. [ABSTRACT FROM AUTHOR]

Humoral and cellular factors of natural resistance in different blood vessels for experimental CCl4-hepatitis have been studied. Sharp decrease of all factors have been detected with prevailing suppression of cellular link in lever veins and gradual increase of lysozime by 14 days which supposes the use of corresponding immunoprotectors in post-desintoxication period.