Biochemical Parameters Of Liver Function Research Articles

Integrated plasma metabolomics and lipidomics profiling highlights distinctive signature of hepatocellular carcinoma in HCV patients

BackgroundEarly diagnosis of hepatocellular carcinoma (HCC) is essential towards the improvement of prognosis and patient survival. Circulating markers such as α-fetoprotein (AFP) and micro-RNAs represent useful tools but still have limitations. Identifying new markers can be fundamental to improve both diagnosis and prognosis. In this approach, we harness the potential of metabolomics and lipidomics to uncover potential signatures of HCC.MethodsA combined untargeted metabolomics and lipidomics plasma profiling of 102 HCV-positive patients was performed by HILIC and RP-UHPLC coupled to Mass Spectrometry. Biochemical parameters of liver function (AST, ALT, GGT) and liver cancer biomarkers (AFP, CA19.9 e CEA) were evaluated by standard assays.ResultsHCC was characterized by an elevation of short and long-chain acylcarnitines, asymmetric dimethylarginine, methylguanine, isoleucylproline and a global reduction of lysophosphatidylcholines. A supervised PLS-DA model showed that the predictive accuracy for HCC class of metabolomics and lipidomics was superior to AFP for the test set (100.00% and 94.40% vs 55.00%). Additionally, the model was applied to HCC patients with AFP values < 20 ng/mL, and, by using only the top 20 variables selected by VIP scores achieved an Area Under Curve (AUC) performance of 0.94.ConclusionThese exploratory findings highlight how metabo-lipidomics enables the distinction of HCC from chronic HCV conditions. The identified biomarkers have high diagnostic potential and could represent a viable tool to support and assist in HCC diagnosis, including AFP-negative patients.Graphical abstract

Cytochrome P450 3A4 activity and genetic variants as predictors of liver failure in patients with obstructive jaundice

Liver failure in patients with obstructive jaundice is a significant contributor to mortality within this patient cohort. The exact mechanism and triggers of this occurrence are yet to be fully understood. With this in mind, our study aimed to assess the correlation between the urinary 6 β-OHC/C ratio and various biochemical parameters of liver function. Furthermore, we conducted genotyping of CYP3A4*22 (rs35599367), CYP3A5*3 (rs776746) polymorphic markers to investigate the potential effects of their variants on the probability of liver failure in obstructive jaundice. Our study included 75 patients diagnosed with severe obstructive jaundice. All test subjects underwent functional liver tests, and control blood tests were administered on the seventh day following biliary decompression. Patients were categorized into two groups: group 1 - patients without liver failure (n = 60) and group 2 - patients with liver failure (n = 15). Laboratory indexes such as 6 β –OHC concentration and 6 β- OHC/cortisol ratio can serve as significant predictors of liver failure in patients with moderate and severe degree obstructive jaundice after biliary decompression. Based on the study of “wild” and polymorphic variants of CYP3A4*22 (CC and CT) and polymorphism of CYP3A5*3A6986G (GG, GA, AA), it was discovered that liver failure in the CYP3A4*22 variant may be associated with the CC genotype, and in the CYP3A5*3 variant - with the GA genotype. Hence, the determination of 6β- OHC concentration and 6β- OHC/C ratio, as well as the analysis of polymorphic and “wild” variants of CYP3A4*22 (CC and CT) and CYP3A5*3 polymorphism A6986G (GG, GA, AA), may play a crucial role in predicting liver failure in patients with obstructive jaundice.

Could real-time sonoelastography-measured placental strain ratio (PSR) value be a soft marker for the diagnosis of intrahepatic cholestasis of pregnancy?: A case-control study and short reviews.

Diagnosis of intrahepatic cholestasis of pregnancy (ICP) is often decided upon with typical pruritus supported by elevated serum bile acid levels. However, there is confusion regarding the absolute reference range for serum bile acid . To confirm the utility of Placental Strain Ratio (PSR) measurement as a marker for the diagnosis of ICP and to reveal the extent to which it is correlated with serum bile acid concentration. A case-control study was conducted. The case group included 29 patients who were admitted to our hospital in the second or third trimester of pregnancy with typical itching and were clinically diagnosed with ICP with >10 mmol/L serum bile acid. The first 45 pregnant women were assigned to a control group. Real-time tissue elastography software was used for ultrasound assessment of all pregnant placentas. Software was used to estimate the SR values. Biochemical liver function parameters, hemograms, serum bile acid levels, and SR values were compared between these groups. PSR was found to predict the development of cholestasis with poor discrimination (area under the curve [AUC] = 0.524; 95% CI = 0.399-0.646). The optimal threshold value with the best sensitivity and specificity rates was calculated to be 0.46 PSR. ICP developed significantly more frequently in the low PSR group than in the high PSR group (60% vs 29.3%, P = .05, odds ratios [OR] = 0.276, 95% CI = 0.069-1.105). No correlation was found between the PSR and bile acid levels (rho = -0.029, P = .816). PSR values can support the diagnosis of ICP, predict serum bile acid levels, and can be used as soft markers.

Upregulated microRNA-450b-5p represses the development of acute liver failure via modulation of liver function, inflammatory response, and hepatocyte apoptosis.

It has been evidenced that microRNAs (miRs) exert crucial effects on acute liver failure (ALF), while the detailed function of miR-450b-5p in ALF progression remained obscure. The purpose of this research was to unravel the regulatory mechanism of miR-450b-5p in ALF via modulating Mouse Double Minute 2 protein (MDM2). ALF was induced in mice by intraperitoneal injection of d-galactosamine ( d-GalN) and lipopolysaccharide (LPS). Adenoviruses containing overexpressed miR-450b-5p, MDM2 shRNA, and overexpressed MDM2 sequences were utilized to manipulate miR-450b-5p and MDM2 expression in the liver before the mice were treated with d-GalN/LPS-induced ALF. Subsequently, miR-450b-5p and MDM2 expression levels in liver tissues of ALF mice were examined. Serum biochemical parameters of liver function were tested, serum inflammatory factors were assessed, and the histopathological changes and hepatocyte apoptosis in liver tissues were observed. The relation between miR-450b-5p and MDM2 was verified. In ALF mice, miR-450b-5p was low-expressed while MDM2 was high-expressed. The upregulation of miR-450b-5p or downregulation of MDM2 could alleviate liver function, mitigate the serum inflammatory response and pathological changes in liver tissues, as well as inhibit the apoptosis of hepatocytes. MiR-450b-5p targeted MDM2. MDM2 overexpression reversed the repressive effects of elevated miR-450b-5p on ALF. The upregulated miR-450b-5p blocks the progression of ALF via targeting MDM2. This study contributes to affording novel therapeutic targets for ALF treatment.

Metabolic support of antiviral therapy in patients with COVID-19

Remaxol was evaluated as a means of hepatotropic support for patients with COVID-19 receiving antiviral therapy. Patients were observed in two groups of 30 people each and received intravenous infusions of Remaxol (400.0 ml) or “active placebo” (400.0 ml. 0.9% sodium chloride) for 10 days. In these groups of patients, an analysis was made of the dynamics of clinical parameters and laboratory tests that characterize the functionality of the liver. The results of the analysis made it possible to state that the use of the corrector of cellular and energy metabolism metabolism Remaxol as a hepatoprotector in complex therapy contributes to favorable clinical dynamics, stabilization of biochemical parameters of liver function and allows completing the course of etiotropic therapy in all patients.Good tolerability of the drug “Remaxol” and the absence of pronounced side effects were noted. The course of Remaxol made it possible to carry out therapy with antiviral agents without dose adjustment and duration of treatment.

Liver Functions in Type 2 Diabetes Individuals after Pfizer Vaccination in Iraqi Patients

Coronavirus is a highly contagious disease, especially in diabetes mellitus type 2. It remains the main cause of death despite the availability of a vaccine. Coronavirus is transmitted via droplets from the nose, mouth, or throat. The study evaluates the biochemical parameters of liver function in patients suffering from type 2 diabetes and the correlation between D-dimer level and platelet count after a second dose of the Pfizer vaccine (14–21) days after vaccination. A study was carried out in al Suwayrah hospital, which included 300 patients aged 20 to 70 years old. one hundred were excluded from this study. A physician diagnosed with Type-2 diabetes mellitus (the ADA) (the American Diabetes Association, 2021) was involved in this study from December 2021 to March 2022. results showed that AST and ALT were normal, while ALP was higher in diabetics compared to controls (ALP was higher in both groups of diabetics vaccinated and non-vaccinated with Pfizer vaccine compared to controls). correlation with no significant effect on platelet count and D-dimer. The current research concludes that there is no effect of the Pfizer vaccine on a biochemical parameter of the liver.

Apoptotic bone marrow-derived mononuclear cells accelerate liver regeneration after extended resection

Objective: to compare the efficiency of regenerative processes in the liver using apoptotic bone marrow-derived mononuclear cells (BMMCs) and intact BMMCs from healthy animals on an extended liver resection (ELR) model.Materials and methods. Male Wistar rats (n = 77) with an ELR model (70–75%) were divided into 3 groups: group 1 (control with a single intraperitoneal injection of saline), group 2 (single intraperitoneal injection of unsorted intact BMMCs at a dose of 30–35 × 106, and group 3 (single intraperitoneal injection of apoptotic BMMCs at the same dose). Restoration of biochemical parameters of liver function and mass, as well as the emerging microstructural changes in hepatocytes in histological preparations, were monitored by assessing hepatocyte mitotic activity (MA) during the first 7–10 days after ELR.Results. It was found that in groups 2 and 3, as compared with group 1, there was no death after ELR modeling, and that the biochemical parameters of liver function normalized more rapidly (at days 10–14). Hepatocyte MA in group 3 sharply increased as early as on day 1, and mitotic index (MI) averaged 14‰, reaching 20.9‰ in some experiments; MI in the control group remained at the baseline by this time, while in group 2, MI was only 3.2‰. In group 3, liver mass recovered more rapidly after ELR to baseline values already at days 8–10, whereas the recovery was at day 12–14 and day 17–20 in group 2 and group 1, respectively. It was suggested that the more pronounced increase in the efficiency of regenerative processes in the liver after ELR in group 3 after using apoptotic BMMCs was due to the release from these cells of a large spectrum of formed paracrine factors, including various classes of RNA molecules involved in the regeneration process.Conclusion. Apoptotic BMMNCs have a more effective adaptive and regulatory potential than intact BMMCs because reorganizations are rapidly formed in the damaged liver cells, providing an early and more powerful activation of the targeted regenerative program.

Celecoxib-mediated attenuation of non-alcoholic steatohepatitis is potentially relevant to redistributing the expression of adiponectin receptors in rats

Pharmacological inhibition of cyclooxygenase-2 (COX-2) activity ameliorated the severity of non-alcoholic steatohepatitis (NASH) rats. It is not completely understood that the role of COX-2 inhibitor celecoxib on adiponectin receptors (Adipo-R1/R2) expression in different tissues in NASH rats. Sprague-Dawley male NASH rats induced by a high-fat diet (HFD) were administrated with or without celecoxib for 8 weeks. Biochemical parameters of liver function, glucose, and lipid metabolism, and the levels of adiponectin, tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2) in the serum or liver were collected according to the standard protocols. The mRNA and protein levels of Adipo-R1, Adipo-R2, and COX-2 in the liver, muscle, and visceral fat were performed by quantitative real-time polymerase chain reaction (q-PCR) and Western blot analysis, respectively. The results showed that celecoxib ameliorated the various clinical indicators and pathological characteristics in the NASH rats, including body weight, liver function, liver index, and redox activities in serum and hepatic samples. The serum concentrations of adiponectin and TNF-α and PGE2 were negatively correlated. As expected, these ameliorative effects of celecoxib were associated with the gene and protein levels up-regulation of Adipo-R1, Adipo-R2 in the liver and visceral fat tissues, and seeming to be compensatory down-regulation expression in muscle tissues (P <0.05). Additionally, COX-2 protein expression was negatively correlated with serum adiponectin levels, protein expression of adiponectin receptors from the liver and visceral fat, conversely, positively correlated with those from the muscle. Our current study demonstrate that celecoxib might effectively alleviate NASH rats in a unique manner closely relevant to redistributing the expression of adiponectin receptors in the liver, visceral fat, and muscle. However, the precise molecular mechanism needs further study.

Anamnestic and biochemical predictors of obstetric and perinatal complications in intrahepatic cholestasis of pregnancy

Objective. To determine the anamnestic and biochemical predictors of obstetric and perinatal complications in women with intrahepatic cholestasis of pregnancy (ICP).Materials and methods. 59 women with ICP and 30 pregnant women included into the comparison group were examined. The characteristics of the reproductive history, anamnesis of the disease, complaints, biochemical parameters of liver function (syndromes of cholestasis and hepatocyte cytolysis, function of protein synthesis), features of the course and treatment of ICP were studied.Results. The main predictors of preterm birth in the women with ICP were: age (P(U)=0.027), multiple pregnancy (OR=17.5, p=0.033); alkaline phosphatase (ALP) blood level &gt; 499 U/l (AUC=0.801; p=0.008); De Ritis Ratio value ≤ 0.49 (AUC=0.757; p=0.005). The main prognostic markers for meconium staining of amniotic fluid (MSAF) in the patients with ICP were: ICP in previous pregnancies (OR=7.1; p=0.029); serum bile acid concentration &gt; 14 μmol/l (AUC=0.718; p=0.043); total bilirubin blood level &gt; 13 μmol/l (AUC=0.773; p=0.007); ALP activity &gt; 484 U/l (AUC=0.728; p=0.033); blood creatinine concentration ≤ 60 μmol/l (AUC=0.930; p=0.0001) in asymptomatic course. The development of respiratory disorders in children born to women with asymptomatic ICP was associated with a total protein concentration in the blood of 78 g/l or less (AUC=0.852; p=0.0001).Conclusion. The anamnesis of the disease and the determination of the levels of the biochemical parameters of liver function allows predicting obstetric and perinatal complications in ICP.

Stress Induced Hyperbilirubinemia; Biochemical Changes in Some Neonates

Cases of neonatal jaundice due to Hyperbilirubinemia abound with some resulting in mortality especially arising from complications in Ceaserean Section. We studied biochemical patterns of some enzymes, hormones and other parameters in 1 - 4 days old neonates. Using spectrophotometnc and radioimmunoassay techniques we measured biochemical liver function parameters bilirubin, transaminases and gammaglutamyltransferase. Hormonal evaluation included cortisol, glucagon and adrenocortical hormone. Using SPSS version 23, paired sample test at 95% confidence intervals of difference shows 2 tail significance for bilirubin, transaminase; giucagon, cortisol and ACTH. Paired sample correlation also showed strong negative pattern with days. We conclude that the interplay of nervous system and self-regulating influence of stress hormones coupled with an immature liver triggers the formation of excess bilirubin.

Effectiveness of Saffron against Hepatotoxicity Caused by Silver Nanoparticles in Vivo

Adverse effects of silver nanoparticles (Ag-NPs) on health remain a concern. This research study was performed to appreciate the activity of saffron plant (SAF) upon Ag-NPs-induced hepatotoxicity. Eighteen male rats were consumed, separated into three groups of equal numbers. The animals of the group (CON) were not dosed with either treatment, while the animals of the group (Ag-NPs) were treated with Ag-NPs orally. In the latter group (Ag-NPs + SAF) intoxicated rats with Ag-NPs were provided with SAF. The experiment lasted seven days. The study found that dosing with Ag-NPs led to a considerable elevates in serum levels of biochemical parameters of liver function and hepatic oxidative stress, while significantly diminished glutathione activity. But the combined use of SAF extract improved the disturbed hepatic parameters. It was concluded that SAF could efficaciously mitigate Ag-NPs-induced liver toxicity in vivo. More investigations are needed to determine the exact mechanisms behind affront’s ability to protect the liver. Keywords: Silver nanoparticles, biochemical parameters, hepatotoxicity.

Amygdalin potentiates the anti-cancer effect of Sorafenib on Ehrlich ascites carcinoma and ameliorates the associated liver damage

The burden of cancer diseases is increasing every year, therefore, the demands to figure out novel drugs that can retain antitumor properties have been raised. This study aimed to investigate the anti-tumor properties of amygdalin (Amy) against Ehrlich ascites carcinoma (EAC) bearing mice and its protective properties against liver damage. Amy and the standard anticancer drug Sorafenib (Sor) were given alone or in combination to Swiss albino female mice that had been injected with EAC cells. Biochemical parameters of liver function (AST, ALT, GGT, total protein, albumin), tumor volume, oxidative stress [malondialdehyde, (MDA)] and antioxidative [superoxide dismutase (SOD), and reduced glutathione (GSH)] markers were measured. The hepatic expression of the antioxidant-related gene [nuclear factor erythroid-2-related factor 2 (Nrf2)], the migration-related gene [matrix metalloprotease 9 (MMP9)], and the angiogenesis-related gene [vascular endothelial growth factor (VEGF)] were evaluated by qPCR. The results revealed that EAC-bearing mice treated with Amy and/or Sor showed a decrease in the tumor burden and hepatic damage as evidenced by (1) decreased tumor volume, number of viable tumor cells; (2) increased number of dead tumor cells; (3) restored the liver function parameters; (4) reduced hepatic MDA levels; (5) enhanced hepatic GSH and SOD levels; (6) upregulated expression of Nrf2; (7) downregulated expression of MMP9 and VEGF, and (8) improved hepatic structure. Among all treatments, mice co-treated with Amy (orally) and Sor (intraperitoneally) showed the best effect. With these results, we concluded that the Amy improved the antitumor effect of Sor and had a protective role on liver damage induced by EAC in mice.

Predictors of residual hepatic reserve and hepatic decompensation in cirrhotic patients after ablated hepatocellular carcinoma treated by DDAs or systemic therapy

BackgroundTherapeutic interventions for hepatocellular carcinoma (HCC) particularly in patients with advanced liver disease may lead to more aggravation of clinical and biochemical parameters of liver functions. We aimed to assess the utilization of easily applied variables which evaluate residual hepatic reserve to predict liability for complications and hepatic decompensation in cirrhotic patients with ablated HCC particularly when these patients were exposed to specific medical treatment such as DAAs and systemic therapy for HCC such as sorafenib.This study included 3 groups with HCC. Group 1: patients with ablated HCC and Child-Turcotte-Pugh (CTP) class A, who received Sofosbuvir (SOF)-based treatment (n = 250), group 2: HCC patients CTP (A), managed with sorafenib after transarterial chemoembolization (TACE) (n = 250) and group 3 as a control group of non-cirrhotic patients (n = 176). Evaluation for all patients was done by routine laboratory investigations including liver and kidney functions, complete blood count, platelet indices and plasma ammonia, upper gastrointestinal (GI) endoscopy and estimation of liver volume by ultrasound and liver stiffness (LS) by Fibroscan.ResultsUnfavorable outcome and increased incidence of complications during DAAs were independently associated with severity of thrombocytopenia (p = 0.001) at a cut-off 78,000/μl, LS > 20 kPa (p = 0.001), liver volume < 500 ml (p = 0.002), and gamma globulin levels > 4 gm/dl (p = 0.004).In the sorafenib group, unfavorable outcome and complications were independently associated with PDW/MPV ratio > 2.74 (p = 0.001), level of ammonia > 87 μg/dl (p = 0.001), LS > 25 kPa (p = 0.001), and liver volume < 490 ml (p = 0.001).ConclusionNon-invasive parameters of residual hepatic reserve are promising tools to guide therapy and avoid further complications in patients with liver cirrhosis and ablated HCC.

Crosstalk Between Plasma Cytokines, Inflammation, and Liver Damage as a New Strategy to Monitoring NAFLD Progression.

Cytokines are involved in the immunopathogenesis of nonalcoholic fatty liver disease (NAFLD), but the relationship between them and clinical parameters of NAFLD progression is still unknown. Using flow cytometry, we evaluated the plasma levels of IL-1β, IL-6, IL-12, TNF and IL-10 and their association with clinical and biochemical parameters of liver function during simple steatosis (NAFL) and nonalcoholic steatohepatitis (NASH) in biopsy-proven patients. The NASH patients showed higher levels of IL-6 associated with a lower IL-10/IL-6 ratio. Besides heatmaps were similar in the NAFL and NASH groups, the same did not occur in signature curves, the NASH patients were high producers to IL-12 and IL-6 while the NAFL patients were not high producers of any cytokines evaluated. Integrative biomarker network analysis revealed that cytokines are differently correlated with clinical parameters, while IL-12, IL-10 presented moderate and negative correlations with glycemic and lipid profile in the NAFL group. The NASH group IL-12 and TNF revealed stronger and positive correlations with transient elastography parameters and NAFLD liver fibrosis score. These data suggest that IL-6 and IL-10 might act in chronic inflammation and insulin resistance whereas IL-12 and TNF may be involved in promoting liver damage and NAFLD progression. Plasma concentration analysis of these molecules and their association with clinical parameters can be used as new biomarkers to monitoring NAFLD progression and to reflect NASH development.

Mechanisms of hepatic steatosis formation in adolescent boys with hypoandrogenism

There has been an increase the prevalence of andrological diseases in all age groups in recent decades, including those with comorbid conditions such as pathology of the cardiovascular system and liver, which are manifestations of metabolic syndrome.Research aim: to investigate the relationship between formation of hepatic steatosis and hypoandrogenism (HA) in adolescent boys.Materials and methods. The study involved 42 adolescent boys aged 14–18 years with laboratory confirmed HA in whom total testosterone levels were less than 12.0 nmol/l. Sex hormones, gonadotropins, insulin levels, biochemical parameters of liver function, the state of free radical oxidation and antioxidant protection were determined in patients. Based on ultrasound examination adolescents with HA were divided into 2 groups: group 1 – 15 adolescents with signs of liver steatosis; group 2 – 27 adolescents with normal ultrasound parameters of a liver. The control group consisted of 38 boys of the same age with normal indicators of physical and sexual development without signs of pathology of the hepatobiliary system. Results. Individual assessment of sexual development allowed to diagnose I degree of delayed sexual development in 44.7%, II degree in 38.3% and III degree in 17.0% of adolescents. HA negatively affects the physical development of most boys (78.7%), due to short stature (40.0%), weight deficiency (20.0%) and overweight (18.7%). Factor analysis allowed to build a factor model of hepatic steatosis formation in adolescents with delayed sexual development and HA, which describes 76.0% of the sample and consists of five factors. Conclusion. Atherogenic changes of the lipid profile, androgen deficiency, insulin resistance, activation of cytolytic processes in the liver and oxidative stress formation due to a decrease in the effectiveness of antioxidant protection are important in the pathogenesis of hepatic steatosis in boys with HA. A factor model of the hepatic steatosis development in adolescent boys with HA gives grounds for the development of therapeutic and preventive measures in adolescent boys with HA and comorbid liver pathology.

Hepatic Injury in Neonates with Perinatal Asphyxia.

Background: Perinatal asphyxia (PA) is a major cause of morbidity and mortality in which dramatic transient impairment in liver functions occurs in some patients. Objectives: We aimed to evaluate the state of the liver in cases of Perinatal asphyxia and to assess the severity of hepatic impairment in relation to different grades of HIE. Patients and Methods: This case-control study was conducted on 100 full-term newborns with perinatal asphyxia (Group I) and 50 healthy neonates served as controls (Group II). All biochemical parameters of liver function were measured on the 1st, 3rd, and 10th day after birth. These parameters include serum alanine transferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total protein, serum albumin, serum bilirubin (total and direct), and international normalized ratio (INR), in both cases and controls. Results: Among babies with PA, 25 (25%) had an Apgar score of 0 to 3 (severe PA), 43 (43%) had an Apgar score of 4 to 5 (moderate PA) and 32 (32%) had an Apgar score of 6 to 7 (mild PA) at 5 minutes of life. HIE was found in 39% among cases of PA and the remaining 61% were normal. Among babies with PA and HIE; 25.7% had stage I, 41% had stage II and 33.3% had stage III. Impaired liver function was reported in 48% of asphyxiated babies. On the first day of life, ALT, AST, ALP, LDH, PT, and INR were significantly higher in Group I compared to Group II. However, total protein and serum albumin were significantly lower in Group I compared to Group II. ALT and AST showed a positive correlation with the severity of HIE. On the third day of life, LDH rises as the stage of HIE progressed from stage 0 to stage 3. The difference in LDH among most stages of HIE was statistically significant. Conclusion: Liver enzymes can be used as an easy early diagnostic marker to differentiate between babies with asphyxia and those without asphyxia. Also, liver enzymes can be used for the detection of the severity of PA.

JILBER’S SYNDROME: CLINICAL AND PHARMACOLOGICAL ASPECTS. Review

Relevance. At present, the metabolism of drugs in patients with Gilbert's syndrome will be actively studied, as it may be associated with both the risk of dose-dependent adverse reactions and treatment ineffectiveness.&#x0D; Objective: to summarize the information of various authors on the peculiarities of the use of drugs in patients with Gilbert's syndrome.&#x0D; Methods. Analysis of scientific publications in the international electronic scientometric database PubMed by keywords. Search depth - 10 years (2010-2019).&#x0D; Results. Gilbert’s syndrome is observed in 3-10% of the population and is characterized by an isolated increase of bilirubin in the blood to moderate values without changes in other biochemical parameters of liver function and without damage to its structure. Gilbert's syndrome is inherited autosomal recessively and is mainly due to the presence of an additional dinucleotide thymine-adenine (TA) in the promoter region A(TA)6TAA gene encoding the enzyme UGT1A1. Elongation of the promoter sequence reduces the formation of UGT1A1. Invariant A(TA)7TAA, the level of enzyme production can be reduced to 80% of the norm in hetero- and up to 20% in homozygotes, respectively. Gilbert’s syndrome is manifested by increased levels of indirect bilirubin in the blood, jaundice of the skin and mucous, abdominal pain, as well as dyspepsia, and asthenovegetative syndrome. Intermittent icteric sclera and skin occur against the background of exogenous and endogenous factors such as starvation, dehydration, infectious diseases, emotional and physical stress, hemolysis, menstruation, alcohol consumption, hormonal contraception, etc., usually at a bilirubin concentration exceeding 40-45 μmol/l. Complications of hyperbilirubinemia with Gilbert’s syndrome include the development of gallstone disease, including in children and adolescents. Gilbert’s syndrome is associated with impaired metabolism of some drugs – aglucones. These include anabolic steroids, glucocorticoids, androgens, rifampicin, cimetidine, chloramphenicol, streptomycin, sodium salicylate, ampicillin, caffeine, Ethinyl estradiol, paracetamol, ibuprofen, The clinical feature of Gilbert’s syndrome is the appearance or aggravation of jaundice associated with the use of such drugs. In conditions of UGT1 deficiency, drugs compete with bilirubin for the enzyme, which leads to an increase of indirect bilirubin in the serum. Therefore, to prevent liver damage, it is necessary to assess the risk and benefit of drug treatment of patients with Gilbert’s syndrome in each case.&#x0D; Conclusions. Gilbert’s syndrome is a common pathological condition and therefore it is important to diagnose it as early as possible. Given that the use of aglucones in patients with Gilbert's syndrome may cause the development of drug-induced liver damage, it is necessary to assess the risk and benefit of drug treatment of patients with Gilbert’s syndrome in each case.

Activation of regenerative processes in the liver when using cell-bone marrow total RNA

Objective: to study the cellular mechanisms of activation of regenerative processes in the liver when using total RNA (tRNA) of bone marrow cells (BMCs) based on an extended liver resection (ELR) model. Materials and methods. Male Wistar rats (n = 80) with ELR model (70%) were divided into 2 groups: group 1 (control group) had a single saline injection, while group 2 (experimental group) received a single tRNA injection at a 30 μg/100 g dose of animal weight. The biochemical parameters of liver function and weight were monitored over time. Also monitored were microstructural changes in hepatocytes 48 hours after ELR by examining mitotic activity, caspase-9 expression and morphometric parameters. Results. It was found that in group 2, in comparison to group 1, there was faster normalization of biochemical parameters (by 10–14 days), a higher mitotic index of hepatocytes (23.45‰ versus 5.37‰), and initially sharper decrease and then faster recovery of liver mass (by 10–12 days versus 18–20 days). Both groups showed almost total expression of caspase-9, including in mitotically splitting hepatocytes. Group 1 demonstrated decreased values of morphometric parameters of single and binuclear cells, decreased number of binucleated hepatocytes and increased total density of hepatocytes as compared to the intact liver. Intraperitoneal administration of tRNA increased morphometric parameters of mononuclear hepatocytes, did not affect their number, but increased the area of the nuclei of binuclear hepatocytes as compared to the control group. Conclusion. The proven capability of cell-bone marrow total RNA to simultaneously support apoptosis in liver cells after ELR and induce mitotic activity indicates that tRNA can switch activated apoptosis to cell proliferation at the early phase of the regenerative process. This effect may be due to the presence of regulatory RNA molecules in tRNA, including numerous non-coding RNAs.

Autotaxin: An Early Warning Biomarker for Acute-on-chronic Liver Failure.

Background and Aims: Recent accumulating evidence indicates the biological actions of autotaxin (ATX) in liver disease. However, the relationship between ATX and liver failure has not been reported. The present study aimed to examine alterations of serum ATX in acute-on-chronic liver failure (ACLF) and evaluate whether serum ATX could be useful as an early warning biomarker of ACLF.Methods: Serum ATX was measured in 50 patients with hepatitis B-related ACLF, 14 patients with alcohol-related ACLF, 11 patients with hepatitis B-related pre-ACLF, 11 patients with alcohol-related Child-Pugh A cirrhosis, 39 patients with hepatitis B-related Child-Pugh A cirrhosis, 26 patients with chronic hepatitis B, and 38 healthy volunteers by enzyme-linked immunosorbent assay.Results: Serum ATX level was significantly higher in the pre-ACLF group than in the Child-Pugh A cirrhosis and chronic hepatitis B groups but lower than in the ACLF group; furthermore, patients with pre-ACLF deteriorated to ACLF had significantly higher serum ATX levels than pre-ACLF patients that did not progress to ACLF. Serum ATX levels were significantly higher among male ACLF patients with preclinical infection, spontaneous bacterial peritonitis or pneumonia, as compared to patients with ACLF but no spontaneous bacterial peritonitis or pneumonia. Serum ATX levels were well correlated with serum biochemical parameters of liver function and model for end-stage liver disease score. Serum ATX ≥ 584.1 ng/mL was a poor prognostic factor for ACLF (hazard ratio of 4.750, 95% confidence interval of 1.106-20.392, p=0.036).Conclusions: Serum ATX level may be a useful early warning biomarker for ACLF.

Antioxidant and in vivo hepatoprotective effects of Gardenia gummifera L.f. fruit methanol extract

BackgroundGardenia gummifera L.f. (Family: Rubeacea) is used in indigenous system of medicine to cure many diseases. To authenticate the traditional medicinal claim investigation has been under taken to evaluate the antioxidant and hepatoprotective activities of Gardenia gummifera L.f. fruit methanol extract (GFME).MethodGFME was evaluated using various antioxidant assays, including DPPH and Nitric oxide radical scavenging assays. The protective effects of GFME were studied in carbon tetrachloride reduced biochemical markers of hepatic injury such as serum glutamyl oxaloacetate transaminase (SGOT), serum glutamyl pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total protein (TP), total bilirubin (TB) and direct bilirubin (DB) and in silico studies were carried out to screen the GFME phytocompounds.ResultsThe extract showed significant antioxidant activity in DPPH and Nitric oxide radical scavenging with IC50 value of 131.11 and 175.95 respectively. Quantitative phytochemical assay determines the presence of alkaloids 69.1 μg/1 mg and phenolics 76.5 μg/1 mg. GC-MS analysis of aromatic extract resulted in 36 compounds. Among them, compounds 2, 3-Dihydro-3,5-dihydroxy-6-methyl-4 h-pyran-4-one, 2-furancarboxaldehyde 5-(hydroxymethyl) and Quinic acid are the major ones. The fruit methanol extract showed significant in vivo hepatoprotective activity by altering the levels of liver function biochemical parameters such as SGOT, SGPT, ALP, TP, TB and DB. Histology of the liver section also confirms the hepatoprotective activity of GFME. Molecular docking of GC-MS profiled phytocompounds with the target protein TGF-β1and PPARα also confirmed the therapeutic effect with good hydrogen bonding and hydrophobic interactions.ConclusionThus the present study clearly strengthened the traditional medicinal claim of the plant Gardenia gummifera L.f. possessing the hepatoprotective drug.