Assessment Of Liver Function Research Articles

Arsenic trioxide preconditioning attenuates hepatic ischemia- reperfusion injury in mice: Role of ERK/AKT and autophagy.

Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by Green fluorescent protein-monomeric Red fluorescent protein-LC3 (GFP-mRFP-LC3)staining and transmission electron microscope. A low dose of ATO (0.75μmol/L in vitro and 1mg/kg in vivo)significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitrostudies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.

A hypocaloric protein-rich diet before metabolic surgery improves liver function in patients with obesity and diabetes

PurposeObesity and type 2 diabetes (T2DM) are major risk factors for hepatic steatosis. Diet or bariatric surgery can reduce liver volume, fat content, and inflammation. However, little is known about their effects on liver function, as evaluated here using the LiMAx test.MethodsIn the MetaSurg study (RCT on the effects of different Roux-en-Y gastric bypass (RYGB) limb lengths on diabetes remission in patients with BMI ≥ 27 to ≤ 60 kg/m2 and T2DM; trial registration: DRKS00007810, German Clinical Trials Register Freiburg), 24 consecutive patients underwent liver function (LiMAx) and imaging assessments (MRI, transient elastography; TE) before and after diet and surgery. Two weeks before surgery, the patients received a hypocaloric protein-rich diet.ResultsNine of 18 patients had a pathologic LiMAx value (≤ 315 µg/kg/h) at baseline. After two weeks of diet, LiMAx values improved (p = 0.01, paired t test, n = 15). LiMAx values further recovered six months after RYGB (p = 0.01, paired t test, n = 15), which was accompanied by decreased liver volumes (p = 0.005, paired t test, n = 10), proton density fat fraction (p = 0.003, paired t test, n = 12), and TE measurements (p = 0.032, paired t test, n = 14). The need for medical diabetes treatment decreased from 100 to 35%.ConclusionLiver function improved after a two-week hypocaloric protein-rich diet and metabolic surgery in patients with obesity and T2DM. These data suggest that a two-week diet for this group of patients prior to abdominal surgery could improve a presumably impaired liver function.

Associations of Essential and Non-Essential Trace Elements' Levels in the Blood, Serum, and Urine in Women with Premature Ovarian Insufficiency.

Premature ovarian insufficiency (POI) is poorly understood, with causes identified in only 25% of cases. Emerging evidence suggests links between trace elements (TEs) and POI. This study is the first to compare concentrations of manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) across urine, serum, and whole blood in women with POI compared to healthy controls (HC), aiming to explore their distribution and potential associations with POI. This cross-sectional-case-control study enrolled 81 participants (40 POI patients and 41 healthy controls) at the University Medical Centre Ljubljana, Slovenia. Blood and urine samples were collected to quantify basic biochemical parameters using standard clinical chemistry methods and concentrations of Mn, Cu, Zn, Se, Mo, As, Cd, Hg, and Pb using inductively coupled plasma-mass spectrometry (ICP-MS). Participants also completed questionnaires on socio-demographics, medical history, lifestyle, and nutrition. Data was analyzed using the Mann-Whitney U test, Student's t-tests, Fisher exact test, logistic regression models adjusted on body mass index (BMI), age, hematocrit, and Kendall's tau correlation. Women with POI had significantly higher BMI and red blood cell (RBC) indices, including hemoglobin, hematocrit, and red cell distribution width (RDW), compared to controls. A larger proportion of POI patients resided in rural agricultural areas. Liver and kidney function assessments showed no significant differences between the groups. Adjusted models revealed that POI patients had significantly lower urinary levels of Cu, Zn, Se, Mo, Cd, Hg, and Pb than controls, while whole blood Mn levels were higher. Serum Cu levels were significantly elevated in POI patients, whereas Pb, Cd, and Hg were lower. No significant differences were observed for As. Correlation analysis showed several strong to moderate associations among TEs across biofluids, but only weak correlations were found between TEs and demographic or biochemical factors. This study suggests potential associations between TEs and POI in women. Notably, most TEs (Zn, Se, Cu, Mo, Cd, Hg, Pb) were significantly lower in the urine of the POI group, while Cu, Cd, Hg, and Pb showed significant differences in both urine and serum.

Development and Validation of a Predictive Model for Liver Failure After Transarterial Chemoembolization Using Gadoxetic Acid-Enhanced MRI and Functional Liver Imaging Score.

Post-transarterial chemoembolization liver failure (PTLF) is a potentially fatal complication of transarterial chemoembolization (TACE). Accurate preoperative prediction of PTLF is crucial for improving patient outcomes. This study aimed to develop and validate a prediction model based on the functional liver imaging score (FLIS) to assess the risk of PTLF. A total of 156 patients underwent Gadoxetic acid-enhanced MRI within four weeks before TACE. Two radiologists, unaware of the clinical data, independently assessed FLIS on hepatobiliary phase images to quantitatively assess liver function. Univariate and multivariate logistic regression analyses identified independent predictors of PTLF. A nomogram was developed and subjected to internal validation through bootstrap resampling of 1000 samples. The model's performance was conducted through the area under the curve (AUC), Hosmer-Lemeshow test, calibration curves, and decision curve analysis (DCA). P<0.05 was considered statistically significant. PTLF occurred in 37.2% of patients (58/156). Significant differences were observed in factors such as portal vein thrombosis, albumin, aspartate transaminase, international normalized ratio (INR), model for end-stage liver diseasescoring, albumin-bilirubinscore, and FLIS. Multivariate analysis showed FLIS, portal vein thrombosis, and INR as independent predictors. The model achieved an AUC of 0.759, with 87.8% specificity and 56.9% sensitivity, and demonstrated good calibration (χ² = 7.101, P=0.526). Calibration curves and DCA confirmed its clinical utility. This FLIS-based prediction model performs well in predicting PTLF, potentially serving as a practical clinical tool.

Current Role of Intraoperative Ultrasonography in Hepatectomy

Introduction: In the past decade, hepatectomy was associated with a high mortality rate due to insufficient surgical techniques, excessive intraoperative blood loss, errors in assessing liver function reserves, and various postoperative complications. Intraoperative ultrasonography (IOUS) offers real-time insights into the tumor’s quantity, size, location, and the vascular structure of the portal and hepatic veins. It assists the surgeon in identifying resection planes, contributing to improved surgical outcomes. This study aims to evaluate the current role of IOUS in hepatectomy. Methods: A descriptive cross-sectional study was conducted at Kathmandu Medical College Teaching Hospital, Nepal, from March 2022 to March 2024. Twenty-three patients undergoing various hepatectomy procedures, primarily for colorectal liver metastasis and hepatocellular carcinoma, were included. Intraoperative IOUS complemented preoperative triphasic CT scans and. data analysis was performed using SPSS Statistics version 16. Results: Out of 23 patients, 14 (60.8%) patients underwent segmentectomy, five (21.7%) right hemihepatectomy, two (8.6%) left hemihepatectomy, one (4.3%) left lateral sectionectomy and one (4.3%) right posterior sectionectomy. In seven patients (30.4%), IOUS provided additional information beyond what was seen on triphasic CT, resulting in a change in the surgical approach for four of them (17%). In all four patients, the change in surgical approach was proved to be correct based on the histological results. Notably, IOUS facilitated detailed anatomical mapping in 43% of cases, aiding in precise tumor localization relative to critical vascular structures. Conclusions: IOUS provides information on the hepatic anatomy in addition to supporting the final decision regarding which portion to resect. It is a safe technique that ensures favorable oncologic outcomes, especially in ultrasoundguided parenchyma-sparing surgeries for colorectal liver metastases.

Liver function and Alzheimer's brain pathologies: A longitudinal study: Liver and Alzheimer's pathologies.

The neuropathological links underlying the association between changes in liver function and AD have not yet been clearly elucidated. We aimed to examine the relationship between liver function markers and longitudinal changes in Alzheimer's disease (AD) core pathologies. Data from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a longitudinal cohort study initiated in 2014, were utilized. Community and memory clinic setting. Three hundred forty-seven older adults. Participants underwent baseline and 2-year follow-up evaluations, including liver function assessments and various brain imaging techniques, such as amyloid and tau PET, FDG-PET, and MRI). Liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin] were examined as exposure variables. Higher baseline ALT levels were associated with a greater increase in beta-amyloid deposition over 2 years [β = 0.166, Bonferroni-corrected P (PB) = 0.012], while lower total bilirubin levels were associated with a greater increase in tau deposition over the same period (β = -0.570, PB < 0.001). In contrast, AST alone showed no significant association with changes of AD pathologies. The findings suggest a possible link between lower liver function and the accumulation of core AD pathologies in the brain. These results also support the possibility that the liver-brain axis could be a potential target for therapeutic or preventive strategies against AD.

Overall Survival and the Impact of Albumin-bilirubin Grade in Patients with Advanced Hepatocellular Carcinoma: Data from a Tertiary Care Hospital in a Lower-middle-income Country.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Most patients are diagnosed at an advanced stage, limiting their treatment options. The traditional assessment of liver function using the Child-Pugh score has limitations due to its subjectivity. The albumin-bilirubin (ALBI) grade delivers a more precise evaluation of liver function. This study examines overall survival (OS) in advanced HCC patients treated with first-line systemic therapy and the impact of ALBI grading on these outcomes. A total of 104 patients with advanced HCC treated between January 2017 and December 2023 with one of the three first-line therapy options: Sorafenib, lenvatinib or atezolizumab/bevacizumab were retrospectively analyzed. The Kaplan-Meier method was utilized to examine the survival results, and the log-rank test was employed to evaluate the variations in survival among ALBI grades and therapy types. Cox proportional hazards regression examined the impact of ALBI grading and other covariates on OS, with a significance threshold of p < 0.05 for the multivariable model. The median age of HCC patients was 58.5 years, with 70% males, and a primary etiology of hepatitis C (43%). The median OS and time to progression (TTP) in this cohort were 9 months and 3.25 months. In ALBI grade I patients, the OS was 21 months, while in grade II or III patients, it was just 5 months. Treatment-related side effects necessitated dose reductions in over 84% of patients. Albumin-bilirubin grade, Child-Pugh class, and treatment modifications due to adverse effects were significant predictors of survival. Lenvatinib appears to have better survival outcomes compared to other options. The albumin-bilirubin grading is a useful method for evaluating liver function and forecasting survival rates for individuals with HCC. Our findings support the use of ALBI grading in clinical decision-making for advanced HCC. Naviwala MSS, Tariq M, Ahmed F, et al. Overall Survival and the Impact of Albumin-bilirubin Grade in Patients with Advanced Hepatocellular Carcinoma: Data from a Tertiary Care Hospital in a Lower-middle-income Country. Euroasian J Hepato-Gastroenterol 2024;14(2):251-257.

Alpinetin Exhibits Antioxidant and Anti-Inflammatory Effects in C57BL/6 Mice with Alcoholic Liver Disease Induced by the Lieber-DeCarli Ethanol Liquid Diet.

Alcohol-associated liver disease (ALD) is a common non-communicable chronic liver disease characterized by a spectrum of conditions ranging from steatosis and alcohol-associated steatohepatitis (AH) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of ALD involves a complex interplay of various molecular, biochemical, genetic, epigenetic, and environmental factors. While the mechanisms are well studied, therapeutic options remain limited. Alpinetin, a natural flavonoid with antioxidant and anti-inflammatory properties, has shown potential hepatoprotective effects, though its efficacy in ALD remains unexplored. This study investigated the hepatoprotective effects of alpinetin using a Lieber-DeCarli ethanol liquid diet model of ALD in C57BL/6 mice. Mice were divided into three groups: the control group, the ethanol group, and the ethanol group treated with alpinetin. Serum activity of ALT, AST, γ-GT, and ALP was measured to assess liver function, along with antioxidative and oxidative/nitrosative stress markers in liver tissue. Pro-inflammatory cytokines and endoplasmic reticulum (ER) stress parameters in liver tissue were also evaluated. Histological assessment of disease activity was performed using the SALVE grading and staging system. Treatment with alpinetin significantly reduced serum levels of ALT, AST, γ-GT, and oxidative/nitrosative stress markers while increasing antioxidative markers. The levels of pro-inflammatory cytokines and ER stress parameters were significantly decreased. Histological analysis demonstrated reduced steatosis, hepatocyte ballooning, and inflammation. These findings suggest that alpinetin holds promise as a potential therapeutic agent for managing ALD.

The protective effect of the vagus nerve-α7nAChR-IL-22 pathway on acute liver injury.

Acute liver injury is a common pathological feature of various clinical diseases, and prolonged liver damage can lead to fibrosis and even liver failure. Studies have reported that the vagus nerve can repair liver injury through the regulation of the cholinergic anti-inflammatory pathway. However, there is limited research on the regulation of interleukin-22 and its role in liver injury. This study aimed to investigate the regulatory effect of vagus nerve receptor α7nAChR on interleukin-22 and whether this regulatory axis can protect against liver injury. Rats and the human liver cell line L-02 were treated with carbon tetrachloride to simulate acute liver injury. The experimental groups were divided as follows: control group, model group, model + PNU282987 group, model + MLA group, and MLA group. After the intervention, blood samples, liver tissues, and cells were collected to assess liver function (AST, ALT), inflammation (TNF-α, IL-6,), α7nAChR and interleukin-22 concentrations, apoptosis levels (Bax, BCL-2), and proliferation markers (Ki-67, PCNA) using quantitative real time PCR, Western blot, immunohistochemistry and ELISA. The results indicated that carbon tetrachloride intervention led to compensatory increases in interleukin-22 while inhibition of α7nAChR decreased interleukin-22 concentrations and exacerbated the injury marked by high levels of AST, ALT and TNF-α,IL-6. Exogenous administration of a vagus nerve agonist alleviated liver injury and was accompanied by an increase in interleukin-22 levels. In rescue experiments, simultaneous inhibition of vagus nerve receptors and administration of exogenous interleukin-22 reduced liver injury and significantly enhanced liver regeneration. Conversely, activation of vagus nerve receptors while inhibiting interleukin-22 aggravated liver injury. This study confirms that vagus nerve receptor α7nAChR can promote liver regeneration and protect against carbon tetrachloride-induced liver injury by regulating interleukin-22.

Comparative performance of prognostic models in predicting mortality in cirrhotic patients with spontaneous bacterial peritonitis

BACKGROUND: Prognostic models are widely used to predict mortality and management outcomes in liver cirrhosis patients with spontaneous bacterial peritonitis (SBP). However, it remains unclear whether these prognostic models can be applied to SBP. OBJECTIVES: To determine the predictive value of prognostic models, including Child-Turcotte-Pugh (CTP), Model for End-stage Liver Disease score- Sodium (MELD-Na), Albumin to Bilirubin (ALBI), and Neutrophil-to-Lymphocyte Ratio (NLR) in cirrhotic patients with SBP. METHODS: Seventy-four hospitalized cirrhotic patients with SBP were selected. Diagnosis was based on clinical, biochemical, ultrasonographic, and ascitic fluid analysis. CTP, MELD-Na, ALBI, and NLR scores at admission were calculated. The area under the ROC curve (AUC) was used to measure accuracy. Sensitivity and specificity were calculated for the optimal cut-off points. RESULTS: Our results revealed that patients who died had higher scores in NLR (MD: 7.51; 95% CI: 1.46–13.56; p: 0.0150), MELD-Na (MD: 10.09; 95% CI: 6.91–13.27; p: 0.0000), CTP (MD: 2.57; 95% CI: 1.82–3.32; p: 0.0000), and ALBI (MD: 0.47; 95% CI: 0.22–0.73; p: 0.0000) compared to survivors. Among these scores, the highest AUC in univariate logistic regression analysis were CTP, MELD-Na, NLR, and ALBI with 0.87, 0.82, 0.73, and 0.72, respectively. CONCLUSION: The combination of CTP and MELD-Na scores was superior to ALBI and NLR prognostic models. These can be used to assess liver function and prognosis in cirrhotic patients with SBP.

Influence of Cinnamon Supplementation on Liver Enzymes in Male Rabbits

The liver, a vital organ in the body, plays a central role in managing the metabolism of both internal and external substances. It is crucial for drug processing and detoxification; however, it is vulnerable to damage from foreign chemicals, alcohol intake, poor nutrition, environmental pollutants, illnesses, and various medications. Besides being commonly used as a spice, the inner bark of cinnamon (Cinnamomum zeylanicum L.) has gained popularity for its applications in disease prevention and treatment. Current evidence has indicated potential health benefits associated with cinnamon intake; however, its effects on liver function remain unclear. Therefore, this systematic review and meta-analysis aimed to investigate the effects of cinnamon supplementation on liver enzymes in male rabbits. Relevant studies were identified through a comprehensive search of PubMed/Medline, Scopus, Web of Science, Cochrane Library, and Embase databases up to September 2023. Ten male New Zealand White rabbits were randomly divided into two groups: (1) a control group, and (2) a group treated with cinnamon at a dose of 200 mg/kg body weight. Blood samples and liver homogenates were used to assess liver function markers in both serum and liver tissue. The results showed that cinnamon treatment led to a significant (P&lt;0.05) reduction in the activity of blood plasma and liver enzymes "LDH", "AST", and "ALT", while "ALP" and "AcP" levels significantly (P&lt;0.05) increased compared to the control group. Further high-quality studies are necessary, especially in populations with abnormal liver enzyme levels, to more definitively establish the clinical efficacy of cinnamon on liver function.

Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?

Primary biliary cholangitis (PBC) is an autoimmune liver disease. During the diagnostic process, the patient's autoimmune antibodies are routinely examined. Approximately 20% of PBC patients have positive anti-centromere antibody (ACA). We evaluated the clinical characteristics of ACA-positive and ACA-negative PBC patients to explain the differences in disease progression between these two groups. Retrospective data from 961 PBC patients at Beijing Youan Hospital from 2010 to 2019 were gathered and separated into two groups based on ACA positivity. We collected and evaluated clinical laboratory indices, gastroscopy findings, and liver function assessments. In addition, 60 liver biopsies were available for comparison between the 2 groups. Pathologists staged the histological findings using the Ludwig staging criteria and Nakanuma staging and grading. Immunohistochemical staining was also performed on liver biopsies to examine the expression of cytokeratin 7 (CK7) in the tissue. A synthesis of clinical indicators in the large cohort showed that alanine transaminase, aspartate aminotransferase, total bilirubin, IgG, white blood cell, and platelet were significantly lower in the ACA-positive group, indicating that the overall status of liver injury was more moderate in the ACA-positive group. Additionally, ACA-positive patients in the non-cirrhotic group were more likely to present with gastroesophageal varices related to portal hypertension. Finally, analysis of pathologic findings showed that parameters were mostly comparable in the two groups, but CK7 differed and was more significantly lower in the ACA-positive group in albumin-bilirubin grade 2 and 3 patients. In summary, we characterized and compared the clinical features of ACA-positive and ACA-negative PBC patients, corroborating previous studies on the relationship between ACA positivity and portal hypertension cross-sectionally. It suggested that gastroesophageal varices might happen in the earlier course of PBC natural progression in the ACA-positive group.

Pre-infection liver function is associated with all-cause mortality among hemodialysis patients with SARS-CoV-2 Omicron variant infection

Background There is ample evidence to suggest that patients infected with SARS-CoV-2 Omicron variant may experience liver dysfunction. However, the impact of pre-infection liver function on postinfection mortality rates remains inadequately researched. Methods Data from 847 hemodialysis (HD) patients, diagnosed with Omicron across six HD centers between December 2022 and February 2023, were analyzed. Initial liver function assessments were conducted, following which patients were monitored for mortality outcomes. The stepwise multivariable Cox regression analysis and receiver operating characteristic (ROC) curves were utilized to identify the predictors of mortality. Results From the total, 98 patients (11.6%) succumbed, with a majority (80/98) within a month postinfection. The deceased patients were observed to be mostly older males with an increased prevalence of diabetes and tumors, signifying higher AST and C-reactive protein levels. These patients also exhibited lower hemoglobin, albumin, and prealbumin levels. An elevated AST [per 1 IU increment; HR 1.04 (95% CI 1–1.04), p = 0.026], AST/ALT ratio [per 1 increment; HR 1.52 (95% CI 1.27–2.36), p = 0.004], and reduced prealbumin [per 10 mg/L increment; HR 0.93 (95% CI 0.9–0.96), p < 0.001] were discovered to be independent indicators of an increased mortality risk. Notably, AST, AST/ALT ratio, and prealbumin proved significant predictors of mortality (AUC values were 0.59, 0.65, and 0.79 respectively). Conclusions This study underscores that pre-infection liver function, specifically AST, AST/ALT ratio, and prealbumin levels, substantially influence the mortality rates in HD patients following Omicron infection. Therefore, careful consideration of these liver function parameters could guide superior patient management strategies and potentially decrease mortality rates within this at-risk population.

HPB SO64 - Outcomes of liver resection for hepatocellular cancer with or without liver functional assessment using Tc 99m Mebrofenate SPECT-CT, portal pressures: A comparative study

Abstract Background Presence of background liver disease increases the post operative morbidity and mortality among patients undergoing liver resection for hepatocellular carcinoma (HCC). These patients need evaluation of background liver function and portal hypertension, in addition to the conventional risk assessment. The current study aims to look at the outcomes of liver resections performed for HCC cases comparing cohorts with conventional risk assessment (CA) and those with functional assessment (FA) of background liver. Method A retrospective study including all liver resections for HCC cases performed in our tertiary care hepatobiliary unit between 2013 and 2022 (10 years) was conducted. A pathway for liver functional assessment using Tc 99m Mebrofenate SPECT-CT, and portal pressures (cut-off values of 2.79/min/m2 and 10mmHg, respectively) was included in the departmental protocol in December 2018. Data on demographics, underlying degree of liver cirrhosis, types of liver resection and post-operative outcomes including post-hepatectomy liver failure (PHLF) were collected and reported using descriptive statistics. Results 200 liver resections, performed for HCC between 2013 and 2022, were divided into a conventional (126 patients) and functional (74 patients) assessment groups. Median age (68 years) was similar. Background liver cirrhosis was present in 27 (21%) vs 19 (26%) cases, and major resections were performed in 47 (37%) and 10 (13%) cases in the CA and FA groups respectively. In the CA group, 90-day mortality was 7% (compared to FA group (1%) (p=0.26). None of the patients in FA group was found to have PHLF whereas 3 patients each had PHLF grade B and C in the conventional group. Conclusion Formal functional assessment of the background liver by evaluating the function of future liver remnant and presence of portal hypertension helps in selection of patients for appropriate surgical treatment options and improve the post-operative outcomes.

Impact of IL-8 on survival after TARE in HCC: a comprehensive investigation and external validation from the SORAMIC trial.

In the treatment of hepatocellular carcinoma (HCC) with transarterial radioembolization (TARE), identifying reliable biomarkers for predicting survival outcomes remains a critical challenge. We aimed to address this gap by investigating the significance of serum cytokines associated with inflammation as potential biomarkers for the selection of patients for TARE. Our retrospective study involved 161 patients diagnosed with HCC who underwent Y90 radioembolization at our medical center between 2010 and 2020. Serum samples from a subset of 78 patients were retrospectively analyzed to determine the concentrations of pro-inflammatory cytokines. The results from the prospective SORAMIC trial were used for independent validation. With a median overall survival of 36 weeks (range 4-436), our study showed the strongest correlation between 12-week survival and IL-8 levels before treatment (p < 0.001), while other relevant interleukins, interferon-α2, INF-γ, TNF-α and MCP-1 were not associated with survival. IL-8 levels below the cut-off of 190 pg/mL were significantly associated with increased 12-week and 24-week survival, with hazard ratios of 19.01 (95% CI: 2.29-157.89) and 2.57 (95% CI: 1.05-6.31), respectively (p = 0.006 and p = 0.039, respectively). In the adjusted multivariate analysis, the 190 pg/mL cut-off for IL-8 remained independently associated with 12- (p = 0.011) and 24-week survival (p = 0.039). Similarly, the SORAMIC population showed a strong association between IL-8 levels and 36-week survival (p = 0.03). Our study emphasizes the pivotal role of IL-8 as a valuable parameter, demonstrating its potential for predicting treatment outcomes and assessing liver function in patients with HCC undergoing TARE. The robustness of these findings warrants further validation.

The influence of the combination of methanolic extract Scurrula atropurpurea (Blume) and Dendrophthoe pentandra on rat liver function and structure

Background. Tea mistletoe (Scurrula atropurpurea (Blume)) and mango mistletoe (Dendrophthoe pentandra) have been known as a potential medicine for several diseases.Objective: to investigate the effect of the combination of methanolic extract Scurrula atropurpurea (Blume) and Dendrophthoe pentandra (MESA-DP) on rat liver function and structure using serological and histopathological analysis.Material and methods. This study was experimental during 28 days using 20 rats divided into four groups (Group 1 as a control, while Groups 2, 3, and 4 were given MESA-DP at doses 250, 500, and 1,000 mg/kg of body weight, respectively). The liver histopathological structure was observed using hematoxylin-eosin staining. The liver function assessment included total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total protein, albumin, globulin, cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels. Data were analyzed using a one-way ANOVA analysis (ANalysis Of VAriance) and performed via SPSS Statistics 17.0 (IBM, USA).Results. The administration of MESA-DP did not show significant differences at all doses for the liver rat function in total bilirubin, SGOT, SGPT, albumin, cholesterol and triglycerides (p&gt;0.05), while globulin, total protein, HDL and LDL showed significant results (p&lt;0.05). The liver histopathological structure showed the number of pyknotic, karyorrhectic and karyolytic cells in rats after MESA-DP administration compared to controls, which grew with increasing dose.Conclusion. The liver function in rats after being exposed to MESA-DP was not affected in terms of total bilirubin, SGOT, SGPT, albumin, cholesterol, and triglyceride levels. However, using MESA-DP increased the necrotic liver cells. It may be beneficial for the liver health of experimental animals taking into account the correct dosage.

New criteria for preoperative liver function assessment with safety margins to avoid postoperative mortality during liver resection for hilar cholangiocarcinoma

BackgroundDespite recent medical advancements, surgery for hilar cholangiocarcinoma is associated with high complication and mortality rates. This may be partly attributed to the absence of established preoperative liver evaluation criteria for safe surgery. This study aimed to propose a reliable indicator for safe and well-planned management of major hepatectomy with extrahepatic bile duct resection. MethodsWe included 150 patients who underwent major hepatectomy with extrahepatic bile duct resection between 2013 and 2021 in Japan. The risk factors for post-hepatectomy liver failure (PHLF) were retrospectively analyzed. ResultsPHLF was observed in 24 (16.0 %) patients who underwent major hepatectomy with extrahepatic bile duct resection. In the multivariate analysis, the identified risk factors for PHLF were the ratio of future remnant liver volume to total liver volume (FRLV/TLV) ≤ 42 % and indocyanine green clearance fraction of the future remnant liver (ICGK-F) ≤ 0.07. Patients with these two factors were significantly associated with PHLF compared with those with either one or none of the risk factors (60.0 % vs 15.1 % and 8.1 %, respectively). ConclusionThe combinational use of ICGK-F and FRLV/TLV is useful for preoperative liver function assessment with a safety margin to avoid PHLF and postoperative mortality in hepatectomy for hilar cholangiocarcinoma.

Prognostic value of albumin-bilirubin score in patients with chronic heart failure

Abstract Background Liver dysfunction is one of the common comorbidities, and associated with worse clinical outcomes in patients with chronic heart failure (CHF). Recently, the albumin-bilirubin (ALBI) score has been developed as an effective and convenient scoring system for assessing liver function. However, the prognostic significance of the ALBI score in patients with CHF remained to be clarified. Purpose We sought to investigate the clinical significance of ALBI score on outcome prediction in patients with CHF. Methods We prospectively examined 1567 symptomatic CHF patients (median age 74, inter quartile range [IQR] 64-82 years, mean left ventricular ejection fraction [LVEF] 49 ± 15.9 %, median N-terminal pro-brain natriuretic peptide [NT-pro BNP] 801 [IQR 372-1820] pg/ml) in a multicentre registry with 27 Japanese sites between January 2020 and December 2023. The ALBI score was calculated according to the following formula: log10 total bilirubin (mg/dl) × 0.06 + albumin (g/dL) × 10 × (-0.085). Studied patients were divided into three groups according to the ALBI grade; ALBI score ≤ -2.60 (Grade1, n = 691), -2.60 &amp;lt; ALBI score ≤ -1.39 (Grade 2, n = 864), ALBI score &amp;gt; -1.39 (Grade3, n = 12). Primary outcome of interest was a composite of all-cause death and hospitalisation due to worsening heart failure. Results Patient with higher ALBI grade had higher age, New York Heart Association functional class, NT-pro BNP level, prevalence of atrial fibrillation and chronic obstructive pulmonary disease, and lower body mass index, systolic blood pressure, haemoglobin level, serum albumin level and estimated glomerular filtration rate compared to those with lower ALBI grade. LVEF was comparable between the groups. During a median follow-up period of 537 (IQR 285-701) days, the primary outcome occurred in 267 patients (17%). Higher ALBI grade were significantly related to increased incidence of the primary outcome (P for trend &amp;lt; 0.001) (Figure 1). Multivariable Cox regressions showed that a higher ALBI score was independently associated with higher risk of the primary outcome (hazard ratio 2.8, 95% confidential interval (CI) 2.08-3.77, P &amp;lt; 0.001), even after adjustment for the MAGGIC score as an established risk prediction model, NT-pro BNP, aspartate aminotransferase, and platelet counts. Furthermore, addition of the ALBI score to the MAGGIC score significantly increased c-index from 0.70 (95% CI 0.66-0.74) to 0.73 (95% CI 0.69-0.76) (P &amp;lt; 0.001) (Figure 2). The net reclassification improvement afforded by the ALBI score was 26% for the primary outcome (P&amp;lt;0.001). Conclusions Liver dysfunction assessed by the ALBI score was independently associated with worse clinical outcomes in patients with CHF. Moreover, addition of the score to the existing risk prediction model significantly increased the ability of outcome prediction, suggesting beneficial clinical application of the ALBI score in patients with CHF.

Pharmacological Screening of Hepatoprotective Activity of Vanillylacetone in Paracetamol Induced Hepatotoxic Rats

Paracetamol is often used as a pain reliever and fever reducer. However, when taken in excessive amounts or used repeatedly, it may result in adverse consequences, such as liver damage. The current study aims to assess the hepatoprotective effects of Vanillylacetone against paracetamol-induced hepatotoxicity in rats, at a dosage of 2g/kg body weight administered orally. A dose of 100 mg/kg of Silymarin was administered orally as a standard reference. On the eleventh day, animals were euthanized and blood samples were collected to assess liver function using liver profile tests including ALT, AST, bilirubin, and total protein levels. The result was also validated by the histopathological examination of liver tissue samples. The administration of 400 mg vanillylacetone per kilogram of body weight per day to group-V rats resulted in a notable reduction in the levels of AST, ALT, direct and total bilirubin, and a considerable rise in total protein levels compared to group-II rats. The hepatoprotective effects of a daily dose of 400 mg vanillylacetone per kilogram were found to be similar to those of a daily dose of 100 mg silymarin per kilogram. Administration of vanillylacetone has effectively restored the aberrant levels of biochemical markers to almost normal levels, with the degree of improvement being depending on the dosage. The current investigation demonstrates that vanillylacetone provides substantial protection against hepatocellular damage generated by paracetamol.

Impact of Etiology on Efficacy Outcomes with Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Retrospective Analysis in Asia-Pacific.

Atezolizumab-bevacizumab is a standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). Given the diversity in HCC etiology and its potential impact on the tumor microenvironment, understanding how different liver disease etiologies affect treatment efficacy is important. We assessed the influence of liver disease etiology on the efficacy of atezolizumab-bevacizumab and evaluated changes in liver function during treatment with atezolizumab-bevacizumab. This study included 390 patients with uHCC treated with first-line atezolizumab-bevacizumab from Asan Medical Center, South Korea, and National Cancer Centre Singapore, Singapore from July 2016 to March 2023. Patients were classified to viral, metabolic dysfunction-associated liver disease (MASLD) and nonviral/non-MASLD groups. Albumin-bilirubin (ALBI) scores were recorded at baseline and every two cycles up to cycle six and at the time of disease progression. The majority of patients presented with viral etiologies (74.1%), and 17.2% had MASLD. Across etiological groups (viral versus MASLD versus nonviral/non-MASLD) no significant differences in objective response rate (23.2% versus 29.9% versus 23.5%, respectively; p = 0.515), progression-free survival (median 5.4 versus 7.7 versus 6.0 months; p = 0.320), and overall survival (18.1 versus 18.9 versus 14.4 months; p = 0.400) were observed. Among the patients with disease progression, ALBI scores at the time of progression were significantly higher than at baseline. Subsequent therapy was administered significantly less often to patients with ALBI grade 3 at disease progression compared with those with ALBI grades 1 or 2 (48.4% versus 78.8%, p = 0.002) CONCLUSIONS: Atezolizumab-bevacizumab demonstrates consistent efficacy regardless of HCC etiology, supporting its use as a first-line treatment across diverse patient populations. Liver function assessments remain crucial for managing therapy and predicting outcomes.