Impaired Liver Function Research Articles

A novel mutation in the ATP7B gene causing hepatolenticular degeneration in a Chinese family: A case report.

Hepatolenticular degeneration (Wilson disease) is an autosomal recessive monogenic disorder caused by mutations in the ATPase copper transporting beta (ATP7B) gene located on human chromosome 13. This gene encodes a copper-transporting P-type ATPase (ATP7B). Recent studies have revealed that the ATP7B gene is predominantly affected by a few hotspot mutations, with the His1069Gln mutation in exon 14 accounting for 50 to 80% of cases. In China, the Arg778Leu mutation in exon 8 is the most prevalent. However, the discovery of novel mutant genes persists. A 56-year-old Chinese female was referred to our hospital with a liver injury and cirrhosis. Her parents, 2 younger brothers, and children exhibited no signs of liver function impairment. Whole-exome sequencing was conducted on the proband's genomic DNA, and Sanger sequencing was performed on 6 family members for first-generation verification. We identified a novel c.3715G > T (p.Val1239Phe) variant mutation in the ATP7B gene in the patient. The ATP7B c.3715G > T (p.Val1239Phe) variant is predicted to impact the copper transport P-type ATPase. When combined with another mutant gene to form a compound heterozygous mutation, it can lead to hepatolenticular degeneration. This discovery broadens the range of pathogenic genes in the ATP7B gene.

Clinical Value of Liquid Biopsy in Patients with FGFR2 Fusion-Positive Cholangiocarcinoma During Targeted Therapy.

FGFR2 fusions occur in 10% to 15% of patients with intrahepatic cholangiocarcinoma (iCCA), potentially benefiting from FGFR inhibitors (FGFRi). We aimed to assess the feasibility of detecting FGFR2 fusions in plasma and explore plasma biomarkers for managing FGFRi treatment. We conducted a retrospective study in 18 patients with iCCA and known FGFR2 fusions previously identified in tissue samples from prior FGFRi treatment. Both tissue and synchronous plasma samples were analyzed using a custom hybrid capture gene panel with next-generation sequencing (VHIO-iCCA panel) and validated against commercial vendor results. Longitudinal plasma analysis during FGFRi was performed. Subsequently, we explored the correlation between plasma biomarkers, liver enzymes, tumor volume, and clinical outcomes. Sixteen patients (88.9%) were positive for FGFR2 fusion events in plasma. Remarkably, the analysis of plasma suggests that lower levels of ctDNA are linked to clinical benefits from targeted therapy and result in improved progression-free survival and overall survival. Higher concentrations of cell-free DNA before FGFRi treatment were linked to worse overall survival, correlating with impaired liver function and indicating compromised cell-free DNA removal by the liver. Additionally, increased ctDNA or the emergence of resistance mutations allowed earlier detection of disease progression compared with standard radiologic imaging methods. VHIO-iCCA demonstrated accurate detection of FGFR2 fusions in plasma. The integration of information from various plasma biomarkers holds the potential to predict clinical outcomes and identify treatment failure prior to radiologic progression, offering valuable guidance for the clinical management of patients with iCCA.

The deubiquitinase OTUD1 stabilizes NRF2 to alleviate hepatic ischemia/reperfusion injury

Hepatic ischemia/reperfusion (I/R) injury is an important cause of liver function impairment following liver surgery. The ubiquitin-proteasome system (UPS) plays a crucial role in protein quality control and has substantial impact on the hepatic I/R process. Although OTU deubiquitinase 1 (OTUD1) is involved in diverse biological processes, its specific functional implications in hepatic I/R are not yet fully understood. This study demonstrates that OTUD1 alleviates oxidative stress, apoptosis, and inflammation induced by hepatic I/R injury. Mechanistically, OTUD1 deubiquitinates and activates nuclear factor erythroid 2-related factor 2 (NRF2) through its catalytic site cysteine 320 residue and ETGE motif, thereby attenuating hepatic I/R injury. Additionally, administration of a short peptide containing the ETGE motif significantly mitigates hepatic I/R injury in mice. Overall, our study elucidates the mechanism and role of OTUD1 in ameliorating hepatic I/R injury, providing a theoretical basis for potential treatment using ETGE-peptide.

Clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia and cytomegalovirus DNA detected in bronchoalveolar lavage fluid.

This study aimed to investigate the clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia (CAP) and concomitant cytomegalovirus (CMV) infection. This cross-sectional study enrolled consecutive pediatric patients admitted with CAP who tested positive for CMV DNA in bronchoalveolar lavage fluid (BALF). Flexible fiberoptic bronchoscopy was performed when routine treatment for CAP proved ineffective. The study participants were further stratified into two groups based on CMV serological test results: recent CMV infection group and CMV replication group. Clinical characteristics were compared between these two groups. Among 124 patients aged 1-11 months included in this study, 80 (64.5%) patients were categorized as having recent CMV infection, and 44 (35.5%) tested positive for CMV replication. Co-infection with other pathogens was detected more frequently in the CMV replication group (n = 29, 65.9%) than in the recent CMV infection group (n = 35, 43.7%; P = 0.018). Patients with recent CMV infection were younger and exhibited higher levels of alanine transaminase (ALT) and aspartate aminotransferase compared to those with CMV replication (all P < 0.05). Multivariable regression analysis showed age was independently associated with recent CMV infection (odds ratio [OR], 0.707; 95% confidence interval [CI], 0.586-0.853; P < 0.001). Notably, receiver operating characteristic curve analysis showed that a CMV PCR level of 3,840 copies/ml in blood samples had a sensitivity of 34.7% and specificity of 90.0% for diagnosis of recent CMV infection with an area under the curve (AUC) of 0.625 (95% CI: 0.513-0.736, P = 0.048). A CMV PCR level of 6,375 copies/ml in urine samples had a sensitivity of 77.1% and specificity of 61.5% for diagnosis of recent CMV infection with an AUC of 0.695 (95% CI: 0.531-0.858, P = 0.04). Furthermore, multivariate linear regression analysis revealed that the blood CMV DNA copy number was associated with ALT (B = 0.001; P < 0.001). The CMV DNA copy numbers in blood and urine could serve as discriminatory markers between recent CMV infection and CMV replication. Measuring CMV DNA levels in blood may be an effective method for monitoring liver function impairment in pediatric patients presenting with CAP and concurrent CMV infection.

The activity of glutathione reductase under impaired liver function and regulation by the Krebs cycle intermediates of the catalytic action of the enzyme isolated by chromatographic methods

The aim of the study was to determine the activity of glutathione reductase (GR, EC 1.6.4.2) in the blood serum of patients with alcoholic hepatitis (AH) and in the blood serum and livers of rats with experimental toxic hepatitis (ETH), as well as to develop a scheme for the purification of the enzyme from the liver of experimental animals using chromatographic methods. In the experiment, we used the blood serum of apparently healthy individuals with normal indices of general and biochemical blood tests (control group of patients), people diagnosed with alcoholic hepatitis (AH), as well as the serum and livers of rats in the control group and rats with ETG. The pathological state in experimental animals was modelled by oral administration of carbon tetrachloride, an organ-specific toxin with hepatotropic effect, as a 33% solution in paraffin oil at the rate of 64 µl of toxin per 100 g of animal weight. The animals were slaughtered on the 4th day after administration of the toxic agent. The control animals were injected with the corresponding aliquot of paraffin oil. The activity of GR was determined spectrophotometrically using a spectrophotometer SF-46 at a wavelength of 340 nm. The total amount of protein was determined by the Lowry method. To study the regulatory properties of the enzyme, it was purified from the livers of the control rats and those with induced toxic hepatitis using the protein separation by ammonium sulphate, as well as gel filtration through Sephadex G-25 and ion-exchange chromatography on DEAE-cellulose. As a result, we obtained 54.5 and 49.1 times purified GR enzyme preparations from the livers of the control rats and animals with ETG. We determined that in the process of ion-exchange chromatography using a column with DEAE-cellulose, the enzyme from the livers of the studied groups of animals was desorbed as a single peak at a KCl concentration of 100 mM. Using the obtained enzyme preparations, we detected differences in the regulation of GR activity under the action of Krebs cycle intermediates. They are obviously associated with conformational modifications of the enzyme molecules under oxidative stress developing during pathology.

Advanced Techniques for Liver Fibrosis Detection: Spectral Photoacoustic Imaging and Superpixel Photoacoustic Unmixing Analysis for Collagen Tracking.

Liver fibrosis, a major global health issue, is marked by excessive collagen deposition that impairs liver function. Noninvasive methods for the direct visualization of collagen content are crucial for the early detection and monitoring of fibrosis progression. This study investigates the potential of spectral photoacoustic imaging (sPAI) to monitor collagen development in liver fibrosis. Utilizing a novel data-driven superpixel photoacoustic unmixing (SPAX) framework, we aimed to distinguish collagen presence and evaluate its correlation with fibrosis progression. We employed an established diethylnitrosamine (DEN) model in rats to study liver fibrosis over various time points. Our results revealed a significant correlation between increased collagen photoacoustic signal intensity and advanced fibrosis stages. Collagen abundance maps displayed dynamic changes throughout fibrosis progression. These findings underscore the potential of sPAI for the noninvasive monitoring of collagen dynamics and fibrosis severity assessment. This research advances the development of noninvasive diagnostic tools and personalized management strategies for liver fibrosis.

Evolution of liver function during immune checkpoint inhibitor treatment for hepatocellular carcinoma.

Deterioration of liver function is a leading cause of death in patients with advanced hepatocellular carcinoma (HCC). We evaluated the impact of immune checkpoint inhibitor (ICI)-treatment on liver function and outcomes. HCC patients receiving ICIs or sorafenib between 04/2003 and 05/2024 were included. Liver function (assessed by Child-Pugh score [CPS]) was evaluated at the start of ICI-treatment (baseline, BL) and 3 and 6months thereafter. A ≥1 point change in CPS was defined as deterioration (-) or improvement (+), while equal CPS points were defined as stable (=). Overall, 182 ICI-treated patients (66.8±11.8years; cirrhosis: n=134, 74%) were included. At BL, median CPS was 5 (IQR: 5-6; CPS-A: 147, 81%). After 3months, liver function improved/stabilized in 102 (56%) and deteriorated in 61 (34%) patients, while 19 (10%) patients deceased/had missing follow-up (d/noFU). Comparable results were observed at 6months (+/=: n=82, 45%; -: n=55, 30%; d/noFU: n=45, 25%). In contrast, 54 (34%) and 33 (21%) out of 160 sorafenib patients achieved improvement/stabilization at 3 and 6months, respectively. Radiological response was linked to CPS improvement/stabilization at 6months (responders vs. non-responders, 73% vs. 50%; p=0.007). CPS improvement/stabilization at 6months was associated with better overall survival following landmark analysis (6months: +/=: 28.4 [95% CI: 18.7-38.1] versus -: 14.2 [95% CI: 10.3-18.2] months; p<0.001). Of 35 ICI-patients with CPS-B at BL, improvement/stabilization occurred in 16 (46%) patients, while 19 (54%) patients deteriorated/d/noFU at 3months. Comparable results were observed at 6months (CPS +/=: 14, 40%, -: 8, 23%). Importantly, 6/35 (17%) and 9/35 (26%) patients improved from CPS-B to CPS-A at 3 and 6months. Radiological response to ICI-treatment was associated with stabilization or improvement in liver function, which correlated with improved survival, even in patients with Child-Pugh class B at baseline.

Liver fibrosis as a predictor of liver failure and outcome following ALPPS among patients with primary liver cancer

The influence of liver fibrosis on the rate of liver regeneration and complications following ALPPS has yet to be fully understood. This study aimed to scrutinize the effects of liver fibrosis on the postoperative complications, and prognosis subsequent to ALPPS. Clinical data were collected from patients with primary liver cancer who underwent ALPPS at Peking Union Medical College Hospital between May 2014 and October 2022. The degree of liver fibrosis was assessed using haematoxylin–eosin staining and Sirius red staining. This study encompassed thirty patients who underwent ALPPS for primary liver cancer, and there were 23 patients with hepatocellular carcinoma, 5 with cholangiocarcinoma, and 2 with combined hepatocellular-cholangiocarcinoma. The impact of severe liver fibrosis on the rate of liver regeneration was not statistically significant (P = 0.892). All patients with severe complications belonged to the severe liver fibrosis group. Severe liver fibrosis exhibited a significant association with 90 days mortality (P = 0.014) and overall survival (P = 0.012). Severe liver fibrosis emerges as a crucial risk factor for liver failure and perioperative mortality following the second step of ALPPS. Preoperative liver function impairment is an important predictive factor for postoperative liver failure.

The Efficiency of Volumetry in Graft Weight Assessment in Living Donor Liver Transplant

Abstract Background Liver transplantation is the treatment of choice for end-stage hepatic diseases. The most important factor responsible for the success of the transplant is the size of the graft and the remnant liver volume in the donor. A small graft may not meet the metabolic demands of the recipient resulting in impaired liver functions such as hyperbilirubinemia, prolonged prothrombin time (PT), ascites and portal hypertension. Patient and Methods This comparative study was conducted on manual contrast enhanced hepatic CT scans of 40 potential living liver donors (29) male and (11) female Age range from (18 to 50 ) in Ain shams specialized hospital and some private centers during the period from May 2021 till July 2022. The potential donors were investigated using 16 channel multi-detector row CT scanner (Alexion; Toshiba medical systems). All potential donors underwent 1st step laboratory investigations to enter the 2nd step investigations for living donor liver transplantation operations. All potential donors were of average weight and physically fit for operation with no history of any medical diseases. Results We correlated the results of CT volumetry of right lobe graft weight with the intra-operative weight of liver graft in patients undergoing Living Donor Liver Transplantation(LDLT). CT Volumetry is an efficient and a reliable tool for assessing potential donors undergoing liver transplant, and this information is essential for donor selection and pre operative surgical planning as well as it ensure that the liver remnant volume is at least 30 % which guarantee the safety of the donor. Conclusion The size of the right lobe graft for LDLT can be precisely calculated from pre-operative CT Volumetry with confidence and accuracy up to 95%.

Correlation between Acute Liver Injury and Disease Severity in Hospitalized Egyptian Patients with Covid-19

Abstract Background COVID-19 pandemic has brought new health threats and challenges to the world. However, the scientific progress over the last months has shed more light on several key questions concerning COVID-19-associated complications. Aim of the Work The aim of this study is to correlate acute liver injury in Covid-19 hospitalized patients with the severity of the disease. Patients and Methods This was a cross-sectional study that was conducted on 110 patients at Ain Shams University hospitals including Ain-Shams Quarantine field hospital, Ain Shams University Quarantine hospital in Al-Obour, and Quarantine ICU of Demerdash through twenty months. Results In total, 110 patients with positive SARS-CoV-2 PCR test were included in this study. The study population was mostly males with 58.2% and median age of the population was 65 years old. As regards to the morbidity status of the study population, 67.3% of the patient died due to disease severity, while 32.7% showed recovery. There was statistical significant relation between liver injury in terms of elevation of (AST-ALP-GGT-Bilirubin) and the increase in oxygen demand. As regards to the inflammatory markers, they significantly correlated with liver injury. Conclusion This study concluded that impaired liver function constitute a common finding in COVID-19 patients. Deterioration of liver function worsens the prognosis and prolongs duration of hospitalization. Thus, critically ill Covid-19 patients should be monitored closely to manage any possible complications.

Microwave ablation followed by cTACE in 5-cm HCC lesions: does a single-session approach affect liver function?

PurposeMicrowave ablation (MWA) and conventional transarterial chemoembolization (cTACE) are locoregional treatments commonly performed in very early, early and intermediate stages of hepatocellular carcinoma (HCC). Despite combined locoregional approaches have shown encouraging results in obtaining complete tumor necrosis, their application in a single session is poorly described.Our aim was to evaluate the safety and efficacy of single-session MWA and cTACE treatment in 5-cm HCCs and its influence on liver function.Materials and methodsAll 5-cm HCCs treated by MWA and cTACE performed in a single-session in our Interventional Radiology unit between January 2020 and December 2022 were retrospectively recorded and analyzed. Patients with poor or missing pre- and post-treatment imaging were excluded. Technical success, clinical success, and complications rate were examined as primary endpoints. Pre- and post-treatment liver function laboratory parameters were also evaluated.ResultsA total of 15 lesions (mean lesion diameter, 5.0 ± 1.4 cm) in 15 patients (11 men; mean age, 67.1 ± 8.9 years) were retrospectively evaluated. Technical and clinical success were 100% and 73%, respectively. Four (27%) cases of partial response and no cases of progressive or stable disease were recorded. AST and ALT values have found to be significantly higher in post-treatment laboratory tests. No other significant differences between pre- and post-treatment laboratory values were registered. AST and ALT pre- and post-treatment higher differences (ΔAST and ΔALT) were significantly associated with a lower clinical success rate.ConclusionMWA and cTACE single-session approach is safe and effective for 5-cm HCCs, without significant liver function impairment. A post-treatment increase in AST and ALT values may be a predictor for clinical failure.

Liver autotransplantation and atrial reconstruction on a patient with multiorgan alveolar echinococcosis: a case report

BackgroundAlveolar echinococcosis (AE) primarily affects the liver and potentially spreads to other organs. Managing recurrent AE poses significant challenges, especially when it involves critical structures and multiple major organs.Case presentationWe present a case of a 59-year-old female with recurrent AE affecting the liver, heart, and lungs following two previous hepatectomies, the hepatic lesions persisted, adhering to major veins, and imaging revealed additional diaphragmatic, cardiac, and pulmonary involvement. The ex vivo liver resection and autotransplantation (ELRA), first in human combined with right atrium (RA) reconstruction were performed utilizing cardiopulmonary bypass, and repairs of the pericardium and diaphragm. This approach aimed to offer a potentially curative solution for lesions previously considered inoperable without requiring a donor organ or immunosuppressants. The patient encountered multiple serious complications, including atrial fibrillation, deteriorated liver function, severe pulmonary infection, respiratory failure, and acute kidney injury (AKI). These complications necessitated intensive intraoperative and postoperative care, emphasizing the need for a comprehensive management strategy in such complicated high-risk surgeries.ConclusionsThe multidisciplinary collaboration in this case proved effective and yielded significant therapeutic outcomes for a rare case of advanced hepatic, cardiac, and pulmonary AE. The combined approach of ELRA and RA reconstruction under extracorporeal circulation demonstrated distinct advantages of ELRA in treating complex HAE. Meanwhile, assessing diaphragm function during the perioperative period, especially in patients at high risk of developing pulmonary complications and undergoing diaphragmectomy is vital to promote optimal postoperative recovery. For multi-resistant infection, it is imperative to take all possible measures to mitigate the risk of AKI if vancomycin administration is deemed necessary.

No lipiodol, no beads-another transcatheter arterial chemoembolization (TACE) with fine cisplatin powder and porous gelatin particles for TACE-naïve, multifocal, up-to-seven out hepatocellular carcinoma.

The Japanese Interventional oncology group (JIVROSG) showed the efficacy and safety of nonselective transarterial chemoembolization (TACE) with fine cisplatin powder (diamminedichloroplatinum; DDP-H) (65 mg/m2) and porous gelatin particles (DDP-H TACE) without lipiodol for extensive multifocal hepatocellular carcinoma (HCC). However, there are no studies on this method following the JIVROSG study. Therefore, we aimed to evaluate the efficacy of this new DDP-H TACE and its effect on liver function. We retrospectively reviewed the medical records of TACE-naïve patients with multifocal HCC (Child-Pugh class A, up-to-seven out, no prior history of systemic therapy) who underwent whole-liver DDP-H TACE between January 2006 and December 2019. Sixty patients were included in this study. The median age of the patients was 71 (range, 35-88) years. The median maximum size of tumors was 26 (range, 8-184) mm; 86.7% of patients met the up-to-11 criteria out. The overall survival duration was 30.3 months. At the time of initial evaluation (median, 45 days), the overall response rate was 65.0%; the disease control rate was 86.7% based on the modified response evaluation criteria in solid tumors guideline. Although nine patients' liver function had deteriorated to Child-Pugh class B at initial evaluation, six of them recovered to Child-Pugh class A. Only three patients (5%) showed permanently impaired liver function. Whole-liver DDP-H TACE without lipiodol or beads effectively reduced tumors and preserved liver function.

Modified SMILE (mSMILE) is active in the treatment of pediatric Epstein-Barr virus-associated natural killer/T-cell lymphoma: a single center experience, case series.

The Epstein-Barr virus-associated natural killer (NK) and T-cell lymphoma (EBV + NK/T cell lymphoma) is a severe illness mainly affecting children and young adults, often resulting in a poor prognosis. To date, there is no consensus on an established treatment strategy. This study aims to evaluate the efficacy and safety of the mSMILE (modified steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen in treating EBV+ NK/T-cell lymphoma and to provide insights into potential treatment outcomes. In this study, we conducted a retrospective analysis of the clinical data and treatment outcomes for patients with EBV + NK/T cell lymphoma treated at Children's Hospital of Nanjing Medical University between July 2017 and January 2022. These patients received at least two cycles of the mSMILE chemotherapy, in which a single dose of pegaspargase was substituted for 7 doses of L-asparaginase per cycle. Eight patients were included in the study: one with extranodal NK/T-cell lymphoma, one with primary nodal NK/T-cell lymphoma, and six with Systemic EBV+ NK/T cell lymphoma of childhood. The results showed that five patients achieved complete remission, two achieved partial remission, and one showed progressive disease, resulting in a complete remission rate of 62.5% and an overall response rate of 87.5%. The 3-year overall survival (OS) and event-free survival (EFS) rates were 87.5% and 75%, respectively. The most common adverse reactions associated with chemotherapy were hematologic toxicities of stages III to IV. Nonhematologic adverse reactions mainly included impaired liver function, infections, and oral mucositis, which were resolved with aggressive anti-infective therapy. Based on our clinical experience, the mSMILE appears to be a safe and effective treatment option for EBV + NK/T-cell lymphoma, meriting further investigation in late-phase clinical trials.

Nano-drug-based Targeted Therapy Alleviates Ferroptosis-induced Liver Toxicity

Abstract: Iron is an essential inorganic element for an organism, with several metabolic activities. The glycoproteins ferritin and transferrin, which assist in carrying iron to various body parts, are used to store iron. In terms of iron uptake, storage, and excretion, equilibrium should be preserved. Ferroptosis is an iron-dependent form of cell death with traits like lipid peroxidation buildup and ROS generation. It is distinct from other forms of cell death visually and biochemically. Many cancer cells block ferroptosis by controlling different cell survival pathways. Compared to healthy, normal cells, cancer cells are more dependent on iron. A subgroup of tumor cells known as cancer stem cells has stem-like characteristics. These are in charge of metastasis and recurrence. The liver plays a significant part in the body's detoxifying process and is the primary iron storage organ. Numerous liver disorders are frequently accompanied by excessive iron accumulation. Due to excessive iron deposits, the liver is more vulnerable to oxidative damage, which can occasionally result in liver failure. Chemotherapy, which involves administering several medications to treat cancer, may be hazardous to the body's other cells. The ferroptosis condition and high iron accumulation can potentially impair liver function. A tailored drug delivery method may ameliorate the impact of excessive iron accumulation and favorably correlate with liver damage, consequently enhancing liver function.

Chronic Toxic Effects of Chocolate Brown HT Dye on Hepatorenal Functions In Vivo

Background: Synthetic colors are prevalent in modern food processing, with Chocolate Brown HT (E155) being widely used to meet the demand for chocolate colors. This study examined the long-term health effects of E155 on both male and female subjects. Methods: Six treatment groups received E155 in low to high dosages (200, 400, and 600 mg/kg body weight) for 40 weeks, while control groups consumed a normal diet. After the feeding period, biochemical and histological evaluations were conducted alongside regular physical observations. Results: The female high-dose (FHD) group exhibited the most significant decrease in body weight. Body Mass Index (BMI) dropped notably in females at moderate (FMD) and high doses (FHD). Serum levels of cholesterol, LDL, and triglycerides increased dose-dependently, with males being more susceptible. Elevated SGPT and SGOT levels indicated liver function impairment due to E155. Both genders showed centrilobular necrosis and fibrosis at high doses, with immune cell invasion even at low doses. Serum creatinine levels, especially in males, were significantly elevated. Females experienced severe injuries, including arteriolar hyalinosis at low doses and IgA nephropathy in the FHD group. Conclusion: The findings underscore serious public health concerns regarding the long-term intake of E155, which can cause significant hepatic and renal damage, particularly in females. This highlights the need for regulatory review and potential restrictions on the use of E155 in food products.

Hemostatic Status of Neonates with Perinatal Hypoxia, Studied via NATEM in Cord Blood Samples.

Perinatal hypoxia may result in coagulation dysfunction. Diminished blood flow or oxygen to the fetus/neonate during the perinatal period can cause bone marrow and liver function impairment, leading to thrombocytopenia, impaired synthesis of clotting and fibrinolytic factors, and increased destruction of platelets in the small blood vessels. The goal of the present study was to evaluate the hemostatic status of newborns with perinatal hypoxia via the non-activated thromboelastometry (NATEM) assay in cord blood samples. 134 hypoxic neonates born in our maternity unit over a 1.5-year period were enrolled in this observational cohort study, and 189 healthy neonates served as the control group. Participation in the study was voluntary and parents signed informed consent prior to recruitment. Demographic and clinical data were recorded on admission, and the NATEM method was performed on cord blood samples. The following NATEM values were evaluated: clotting time (CT), alpha angle (α-angle), clot formation time (CFT), clot amplitude at 5 and 10 min. (A5, A10), maximum clot firmness (MCF), clot lysis index at 60 min. after CT (LI60), and maximum clot elasticity (MCE). Statistical analysis was conducted utilizing the SAS for Windows 9.4 software platform. Neonates with perinatal hypoxia exhibited decreased fibrinolytic potential in comparison to healthy neonates, as indicated by increased LI60, and this difference was statistically significant (LΙ60: 94 (92-96) Vs 93 (91-95), p value = 0.0001). There were no statistically significant differences noted among the remaining NATEM variables. Our findings indicate decreased fibrinolytic potential in hypoxic neonates in comparison to healthy neonates, suggesting that NATEM could serve as an effective tool for promptly identifying hemostasis dysfunction in this group of neonates.

The Modified Albumin–Bilirubin (ALBI) Grade Reflect the Fate of Limb Prognosis in Patients with Chronic Limb-Threatening Ischemia

ObjectiveTo examine the influence of liver function on patients with chronic limb-threatening ischemia (CLTI), we classified patients with CLTI after revascularization according to their modified ALBI grades. MethodsWe retrospectively analyzed single-center data of patients who underwent revascularization for CLTI between 2015 and 2020. Patients were classified with modified albumin–bilirubin (ALBI) grades 1, 2a, and 2b & 3 according to the ALBI score, which was calculated based on serum albumin and total bilirubin levels. The endpoints were the two-year amputation-free survival (AFS) and one-year wound healing rates. ResultsWe included 190 limbs in 148 patients, and 50, 54, and 86 cases were assigned as grade 1, 2a, and 2b & 3, respectively. The two-year AFS rates for the grade 1, 2a, and 2b & 3 groups were 79 ± 6%, 66% ± 7%, and 45 ± 6%, respectively (P < 0.01). One-year cumulative wound healing rates for grade 1, 2a, and 2b & 3 groups were 68 ± 7%, 69% ± 6%, and 48% ± 5%, respectively (P = 0.01). Multivariate Cox proportional hazard analyses identified age (≥75 years), dependent ambulatory status, and modified ALBI grades 2b & 3 compared with grades 1 and 2a as significant independent predictors of AFS. The dependent ambulatory status and WIfI stage 4 were significant negative predictors of wound healing. ConclusionsMany patients with CLTI had high modified ALBI grades and impaired liver function classified as modified ALBI grade 2b or 3 is a robust negative predictor of amputation-free survival.

FUNCTIONAL CHANGES IN THE HEPATOBILIARY SYSTEM IN PATIENTS WITH CHRONIC CORONARY SYNDROME DURING ANTIFUNGAL THERAPY

Modern medicine is faced with the global challenge of multimorbidity. It is a combination of various visceral diseases, which affect the development and manifestation of the underlying disease. In elderly patients, pathologies are often combined with cardiovascular diseases, such as coronary artery disease. Coronary artery disease is usually treated with several drugs or their combinations, such as antianginal, antithrombotic, lipid-lowering, and cardiac metabolic drugs. However, these drugs are metabolized in the liver and may have a direct effect on it. Besides, combined treatment of two pathologies has a pronounced negative effect on the liver. The purpose of the study was to examine functional changes in the liver while treating patients with onychomycosis and coronary artery disease. Materials and Methods. The study involved 68 people who consulted a dermatologist due to toenail changes. All patients were divided into 2 groups: patients with stable coronary artery disease (20 middle-aged and 14 elderly ones) and patients without coronary artery disease (24 middle-aged and 10 elderly ones). in both groups underwent systemic antifungal therapy (terbinafine, 250 mg once a day). Patients with stable coronary artery disease underwent the following therapy: antiplatelet agent (acetylsalicylic acid), HMG-CoA inhibitor (atorvastatin, 40 mg), beta-blocker (82 % of patients, bisoprolol) and ACE inhibitor (enalapril or lisinopril). The effectiveness of therapy was assessed according to the dynamics of clinical manifestations and the results of mycological nail tests. Control microscopic tests of the material from the nails were carried out three times after clinical recovery with a 3-month interval. Conclusion. When treated with antifungal drugs, patients demonstrated elevated liver enzymes. This is because the hepatobiliary system, which is already under high stress during the coronary artery disease treatment, also processes antifungal drugs. Therefore, it is necessary to take into account liver state when prescribing antifungal drugs. It is important to develop an algorithm for onychomycosis diagnosis and treatment in patients with coronary artery disease in order to prevent polypharmacy and impaired liver function.

HDAC6 inhibitor ACY-1215 protects from nonalcoholic fatty liver disease via inhibiting CD14/TLR4/MyD88/MAPK/NFκB signal pathway

Background & aimsNonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic steatosis, for which there is currently no effective treatment. ACY-1215 is a selective inhibitor of histone deacetylation 6, which has shown therapeutic potential in many tumors, as well as acute liver injury. However, no research about ACY-1215 on NAFLD has been published. Therefore, our study aims to explore the role and mechanism of ACY-1215 in the experimental model of NAFLD, to propose a new treatment strategy for NAFLD. MethodsWe established cell and animal models of NAFLD and verified the effect of ACY-1215 on NAFLD. The mechanism of ACY-1215 on NAFLD was preliminarily explored through TMT relative quantitative proteomics, and then we verify the mechanism discovered in the experimental model of NAFLD. ResultsACY-1215 can reduce lipid aggregation, IL-1β, and TNF α mRNA levels in liver cells in vitro. ACY-1215 can reduce the weight gain and steatosis in the liver of the NAFLD mouse model, alleviate the deterioration of liver function, and reduce IL-1βs and TNF α mRNA levels in hepatocytes. TMT relative quantitative proteomics found that ACY-1215 decreased the expression of CD14 in hepatocytes. It was found that ACY-1215 can inhibit the activation level of CD14/TLR4/MyD88/MAPK/NFκB pathway in the NAFLD experimental model. ConclusionsACY-1215 has a protective effect on the cellular model of NAFLD induced by fatty acids and lipopolysaccharide, as well as the C57BL/6J mouse model induced by a high-fat diet. ACY-1215 may play a protective role by inhibiting CD14/TLR4/MyD88/MAPK/NFκB signal pathway.