Iron oxide nanoparticles have become increasingly significant in the biomedical field due to their exceptional magnetic properties and biocompatibility. However, understanding their in vivo metabolism and transformation is crucial due to the potential biological effects they may induce. This study investigates the metabolic pathways of PEGylated ultrasmall iron oxide nanoparticles (PUSIONPs) in vivo, particularly under varying iron statuses and dosages. Employing a comprehensive analytical approach─including magnetic resonance imaging, elemental analysis, histological assessments, hematological analysis, and Western blot analysis─the biodistribution and transformation of PUSIONPs were mapped. The findings reveal significant differences in the metabolic fate of PUSIONPs between iron-sufficient and iron-deficient conditions, underscoring the pivotal role of iron homeostasis in regulating PUSIONPs biodegradation. In iron-deficient states, degradation and transformation were markedly accelerated, with the released iron rapidly incorporated into hemoglobin. Additionally, the liver and spleen exhibited different PUSIONPs metabolism rates due to their distinct physiological roles: the spleen, primarily responsible for iron recycling, facilitated faster degradation, while the liver, serving as an iron storage organ, showed slower degradation. Under iron deficiency, most degradation products were directed toward hemoglobin synthesis, whereas under normal conditions, the liver gradually metabolized the degradation products, and the spleen retained higher iron levels. Moreover, PUSIONPs degradation demonstrated dose dependency, with higher doses slowing degradation and reducing the utilization rate by the iron-deficient body. Comprehensive safety evaluations confirmed that PUSIONPs exhibit excellent biocompatibility across all doses, with no significant safety concerns. Compared to the clinically used intravenous iron supplement iron sucrose, PUSIONPs also demonstrated superior bioavailability and more effective iron supplementation. These findings provide critical insights into the interaction between iron oxide nanoparticles and iron metabolism, offering a foundation for future research and the broader application of PUSIONPs in biomedical contexts.

Hepatocellular carcinoma (HCC) is a malignant disease with high incidence and mortality worldwide. This study focuses on the TP53 target protein to investigate the potential therapeutic effect of tetrahydrocurcumin (THC) on HCC and its mechanism of action. The research hypothesis is that THC can inhibit the proliferation, migration, and invasion of HCC cells, and promote their apoptosis by regulating the TP53 target protein.

To explore the mechanism by which THC inhibits HCC cell proliferation via the TP53 signaling pathway.

Potential targets of THC and HCC were identified from multiple databases. The core targets were subjected to analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, and visualization processing, using the online platform Metascape to identify the key molecules and signaling pathways involved in the action of THC against HCC. The molecular mechanisms of action of THC against TP53 in the inhibition of HCC cells were verified using cell counting kit-8, Transwell, apoptosis, and western blotting assays.

Molecular docking results showed that THC had a high score for the TP53 target protein. In vitro experiments indicated that THC effectively inhibited the proliferation and migration of HCC cells, and affected the expression levels of TP53, MDM2, cyclin B, Bax, Bcl-2, caspase-9, and caspase-3.

THC induces the apoptosis of HCC cells through the TP53 signaling pathway, thereby inhibiting their proliferation and migration.

To investigate whether multiphase hepatic CT can predict liver function measured with indocyanine-green-retention test (ICG-R15) and identify patients with severe liver dysfunction contraindicating major hepatectomy, defined as ICG-R15 ≥ 20%, compared to technetium-99m-galactosyl serum albumin (99mTc-GSA) scintigraphy.

This retrospective study included 118 patients (84 men, mean age, 69.4 ± 11.3 years) who underwent ICG-R15, 99mTc-GSA, and multi-phase CT including early portal-venous-phase and 3-min delayed-phase. CT-derived extracellular volume fraction (ECV), iodine washout rate (IWR), liver and spleen volumes normalized by body-surface-area (LV/BSA and SpV/BSA, respectively), and 99mTc-GSA-derived blood clearance index (HH15) and liver receptor index (LHL15) were quantified. Each parameter was compared between ICG-R15 ≥ 20% (n = 22) and ICG-R15 < 20% (n = 96) groups. Correlations with ICG-R15 were analyzed. The diagnostic performance to predict ICG-R15 ≥ 20% was assessed with areas under the receiver operating characteristic curve (AUC). Multivariable logistic regression analysis was used to identify independent CT predictors, and combined performance was determined.

In the ICG-R15 ≥ 20% group, IWR (p < 0.001), LV/BSA (p = 0.026), LHL15 (p < 0.001) were lower and ECV (p = 0.001), SpV/BSA (p = 0.005), and HH15 (p < 0.001) were higher compared to ICG-R15 < 20% group. ICG-R15 showed positive correlations with ECV (r = 0.355), SpV/BSA (r = 0.248), and HH15 (r = 0.385), while negative correlations with IWR (r = -0.523), LV/BSA (r = -0.123, not statistically significant), and LHL15 (r = -0.504). The AUC of ECV, IWR, LV/BSA, SpV/BSA, HH15, and LHL15 were 0.719, 0.845, 0.653, 0.694, 0.844, and 0.878, respectively. IWR, SpV/BSA, and LV/BSA were independent predictors, with a combined AUC of 0.924.

IWR predicted liver function better than ECV and hepatosplenic volumetry. The combined IWR and volumetry yielded an accurate prediction of severe liver dysfunction.

Question Despite the widespread use of multiphase CT in patients with hepatobiliary diseases, its potential role in assessing liver function has been scarcely evaluated. Findings Iodine washout rate (IWR), liver volume indexed by body surface area, and spleen volume indexed by body surface area were independent predictors for severe liver dysfunction. Clinical relevance Combined IWR and hepatosplenic volumetry on routine hepatic CT may help assess hepatic function for optimizing treatment strategies and predicting patient prognosis.

Normothermic machine perfusion (NMP) enables pretransplantation assessment of donor liver viability to increase donor liver utilization. However, unambiguous objective criteria to determine integrated liver function during NMP to decide upon acceptance are still lacking. This study investigates whether the indocyanine green (ICG) elimination test can be applied to assess liver function during NMP.

Donor livers underwent dual-hypothermic oxygenated machine perfusion and NMP. The ICG elimination test was improved during an optimization phase (n = 10) and tested against current functional perfusion parameters and posttransplantation outcomes in clinically perfused livers (n = 32).

The ICG plasma disappearance rate (PDR) during NMP was dependent on perfusion blood flow and liver weight. The corrected PDR (NMP-PDR) was correlated to the hepatic extraction rate ( R  = 0.923; P  > 0.001) and ATP content in liver biopsies at 2 h of NMP ( R  = 0.692; P  = 0.027). In the clinical phase, the length of the functional warm ischemia time in the donation process was inversely correlated to the NMP-PDR ( P  = 0.042). Both individual acceptance criteria (lactate clearance, ability of self-regulate pH, Δbicarbonate, and ΔpH) and overall hepatocellular and cholangiocellular acceptance criteria were correlated to the NMP-PDR. The NMP-PDR was higher in the cohort accepted for transplantation (n = 18; 18.1%/L·kg [14.0% to 22.7%/L·kg]) than in the nontransplanted cohort (n = 14; 11.8%/L·kg [8.8% to 12.9%/L·kg]; P  < 0.0001). Furthermore, the NMP-PDR correlated with the liver graft assessment following transplantation at 7 d score posttransplantation ( R  = -0.551; P  = 0.027).

We demonstrate that the NMP-PDR correlates with both liver function during NMP and short-term posttransplantation outcomes. This simple objective test has the potential to increase donor liver utilization rate, while preventing hepatocellular dysfunction posttransplantation.

Organic anion transporting polypeptides (OATPs) are membrane proteins that mediate the uptake of a wide range of substrates across the plasma membrane of various cells and tissues. They are classified into 6 subfamilies, OATP1 through OATP6. Humans contain 12 OATPs encoded by 11 solute carrier of organic anion transporting polypeptide (SLCO) genes: OATP1A2, OATP1B1, OATP1B3, the splice variant OATP1B3-1B7, OATP1C1, OATP2A1, OATP2B1, OATP3A1, OATP4A1, OATP4C1, OATP5A1, and OATP6A1. Most of these proteins are expressed in epithelial cells, where they mediate the uptake of structurally unrelated organic anions, cations, and even neutral compounds into the cytoplasm. The best-characterized members are OATP1B1 and OATP1B3, which have an important role in drug metabolism by mediating drug uptake into the liver and are involved in drug-drug interactions. In this review, we aimed to (1) provide a historical perspective on the identification of OATPs and their nomenclature and discuss their phylogenic relationships and molecular characteristics; (2) review the current knowledge of the broad substrate specificity and their role in drug disposition and drug-drug interactions, with a special emphasis on human hepatic OATPs; (3) summarize the different experimental systems that are used to study the function of OATPs and discuss their advantages and disadvantages; (4) review the available experimental 3-dimensional structures and examine how they can help elucidate the transport mechanisms of OATPs; and (5) finally, summarize the current knowledge of the regulation of OATP expression, discuss clinically important single-nucleotide polymorphisms, and outline challenges of physiologically based pharmacokinetic modeling and in vitro to in vivo extrapolation. SIGNIFICANCE STATEMENT: Organic anion transporting polypeptides (OATPs) are a family of 12 uptake transporters in the solute carrier superfamily. Several members, particularly the liver-expressed OATP1B1 and OATP1B3, are important drug transporters. They mediate the uptake of several endobiotics and xenobiotics, including statins and numerous other drugs, into hepatocytes, and their inhibition by other drugs or reduced expression due to single-nucleotide polymorphisms can lead to adverse drug effects. Their recently solved 3-dimensional structures should help to elucidate their transport mechanisms and broad substrate specificities.

Tuberculosis (TB) continues to pose a significant threat to global public health. Enhancing patient prognosis is essential for alleviating the disease burden.

This study aims to evaluate TB prognosis by incorporating treatment discontinuation into the assessment framework, expanding beyond mortality and drug resistance.

Seven feature selection methods and twelve machine learning algorithms were utilized to analyze admission test data from TB patients, identifying predictive features and building prognostic models. SHapley Additive exPlanations (SHAP) were applied to evaluate feature importance in top-performing models.

Analysis of 1,086 TB cases showed that a K-Nearest Neighbor classifier with Mutual Information feature selection achieved an area under the receiver operation curve (AUC) of 0.87 (95% CI: 0.83-0.92). Key predictors of treatment failure included elevated levels of 5'-nucleotidase, uric acid, globulin, creatinine, cystatin C, and aspartate transaminase. SHAP analysis highlighted 5'-nucleotidase, uric acid, and globulin as having the most significant influence on predicting treatment discontinuation.

Our model provides valuable insights into TB outcomes based on initial patient tests, potentially guiding prevention and control strategies. Elevated biomarker levels before therapy are associated with increased risk of treatment discontinuation, indicating their potential as early warning indicators.

Alkaline phosphatase (ALP) is a ubiquitously expressed dephosphorylating enzyme and its level in blood is widely used as a diagnosis marker of liver damage or bone disorders in human patients. ALP is also considered as an anti-inflammatory protein due to its ability to dephosphorylate and inactivate inflammation-triggering molecules such as lipopolysaccharide (LPS). Placental alkaline phosphatase (ALPP) is one of tissue-specific ALP isozymes expressed mostly during pregnancy, however it was found to be differentially upregulated in certain hepatocellular carcinomas by us recently. In addition, ALPP has been identified as a reliable biomarker of diverse germ cell tumors. Nevertheless, little is known of its immune modulatory role in vivo. In this study, we generated ALPP transgenic mice and tested these mice in the LPS-induced sepsis and male-to-female skin graft rejection models. Our results showed that ALPP transgenic mice are more susceptible to intraperitoneal injection of LPS in comparison to control animals. In addition, female ALPP transgenic mice were better at delaying the rejection of male skin grafts. In an in vitro phagocytosis experiment, addition of exogenous ALPP compromised the phagocytic ability of THP-1 monocytic cells. These results indicate that excess ALPP plays a role in modulating both innate and adaptive immune functions.

To study the feasibility of hepatobiliary scintigraphy (HBS) to improve selection and planning of patients with hepatocellular carcinoma (HCC) treated with holmium-166 (166Ho)-microspheres radioembolization.

Thirty-one patients with HCC were included and treated with 166Ho- radioembolization as part of a prospective phase 2 study. Twenty-seven patients were eligible for analysis, 67% had a cirrhotic liver morphology on imaging, 70% had multifocal disease and 51% had bilobar disease. None of the patients had clinical signs of liver decompensation (Child Pugh ≤ B7, median MELD 9 or ALBI - 2.55). Global and regional hepatic function was based on manual delineation of HBS using 200 MBq 99mTc-mebrofenine, acquired during screening and approximately three months after 166Ho-radioembolization, referred to as liver clearance rate (LCR). In line with LCR at baseline, a significant correlation was found between LCR and lab results, including bilirubin, albumin, ALT, MELD-score, and ALBI-score (p < 0.05) during follow-up. HBS showed a significant decrease in median LCR (-16%; p = 0.0017) and volume (-17%; p = 0.0027) in the treated liver, without a significant increase in the non-treated liver. Median relative change in overall LCR in non-cirrhotics was 0% (range - 23-33%), in cirrhotics - 10% (range - 40 - 19%; p = 0.40).

HBS showed that hepatic function and volume significantly decreased in parts of the liver treated with 166Ho-microspheres radioembolization in patients with HCC. Cirrhotic patients do not seem to have the capacity to increase hepatic function in the treated part of the liver.

Registry name: Clinicaltrials.gov.

NCT03379844. Date of registration: 21 November 2017. Trial URL: https://clinicaltrials.gov/study/NCT03379844?cond=hcc&term=hepar primary&rank=1#study-overview .

Routine liver function tests capture information about the metabolic and inflammatory condition of the liver, but we lack sensitive biomarkers of early hepatocyte stress. In humans, soluble CD46 (sCD46) levels in blood were recently identified as an accurate biomarker of hepatic steatosis. Here, we explore the diagnostic utility of sCD46 in other liver diseases.

We developed, optimised and validated an ELISA that facilitates measurements of human sCD46 in plasma, serum and culture supernatants. Then, we analysed mechanisms that lead to the release of sCD46 and identified its role in various hepatic stress conditions.

We discovered that prostaglandin E2 (PGE2) drives upregulation of matrix metalloproteinase (MMP)-1 in fat-loaded hepatocytes, leading to proteolytic shedding of CD46. We further found that sCD46 release was increased by viral, toxic and hypoxic stresses.

sCD46 appears to be a promising biomarker with potential applications in the detection of early liver diseases or monitoring therapeutic responses, which could complement established diagnostic algorithms because sCD46 release is uniquely responsive to hepatocyte stress.

Multiple and complicated hepatolithiasis can be associated with decompensated cirrhosis. Endoscopic retrograde cholangiopancreatography is unavailable for multiple and complicated hepatolithiasis, and the mainstay for decompensated cirrhosis is liver transplantation. However, due to the ethical factors and the complexity of operation, liver transplantation cannot be widely operated. This study aimed to evaluate percutaneous transhepatic cholangioscopy in the extraction of stones and the recompensation of cirrhosis in patients with hepatolithiasis associated with decompensated cirrhosis.

Between January 2021 and February 2024, we retrospectively reviewed the clinical data of 21 patients with multiple and complicated hepatolithiasis associated with decompensated cirrhosis. Before PTCS, the 21 patients were all assessed by the Model for End-stage Liver Disease as having indications for liver transplantation. One-step PTCS (n = 19) and two-step PTCS (n = 2) were used to remove the stones.

The technical success rate was 100%, and most stones were cleared 90.48% (19/21). After 3 months of PTCS, MELD score of the patients had significantly decreased (10.81 ± 3.31 vs. 17.24 ± 3.40, p < 0.05), and it was lowest at 6 months after the operation (9.94 ± 4.31). After a median follow-up period of 18 months (up to 40 months), the stone recurrence rate was 28.57% (6/21), 13 patients survived without liver transplantation, three patients underwent liver transplantation and survived, and five patients died of liver failure or cancer (mortality rate 23.81%).

PTCS can significantly improve patients' liver function in hepatolithiasis associated with decompensated cirrhosis.

To explore the value of T1 mapping-based whole-liver histogram analysis on gadoxetic acid-enhanced MRI for predicting post-hepatectomy liver failure (PHLF).

Consecutive patients from March 2016 to March 2018 who underwent gadoxetic acid-enhanced MRI in our hospital were retrospectively analyzed, and 37 patients were enrolled. Whole-liver T1 mapping-based histogram analysis was performed. The indocyanine green (ICG) clearance tests were performed, and albumin-bilirubin (ALBI) scores were calculated. Univariate and multivariate binary logistic analyses were performed to identify independent predictors for PHLF. Diagnostic performance was evaluated with ROC analysis. Histogram-extracted parameters were also associated with the ICG test and ALBI scoring system.

In enrolled 37 patients (age 57.19 ± 12.28 years), 28 were male. 35.1% (13/37) of patients developed PHLF. For univariate analysis, pre-contrast T1 relaxation time (T1pre) mean, T1pre 95th percentile, the standard deviation (SD) of T1 relaxation time in hepatobiliary phase (T1HBP SD), T1HBP 95th percentile, T1HBP kurtosis, and ICG percentage retained at 15 min (ICG-R15) showed significant differences between the PHLF and non-PHLF groups (all p < 0.05), whereas the ALBI scores showed no significant differences between the two groups (p = 0.937). Multivariate analysis showed that a higher T1HBP 95th percentile was the independent predictor for PHLF (p < 0.05; odds ratio (OR) = 1.014). In addition, most of the histogram-extracted parameters showed significant correlations to the ICG test.

T1 mapping-based whole-liver histogram analysis on gadoxetic acid-enhanced MRI is valuable for PHLF prediction and risk stratification, which outperformed the ICG clearance test and ALBI scoring system.

Question What is the value of T1 mapping-based whole-liver histogram analysis on gadoxetic acid-enhanced MRI for PHLF? Findings The histogram parameters extracted from gadoxetic acid-enhanced T1 mapping manifested potential for grading liver function preoperatively. Clinical relevance T1 mapping-based whole-liver histogram analysis on gadoxetic acid-enhanced MRI can serve as a convenient one-station radiological tool to help identify potential PHLF risks within the preoperative clinical decision-making framework.

The Resection And Partial Liver Transplantation with Delayed total hepatectomy (RAPID) procedure involves left hepatectomy with orthotopic implantation of a left lobe and right portal vein ligation. This technique induces volumetric graft increase, allowing for a right completion hepatectomy within 15 days. Notably, there is a lack of data on the hemodynamics of small-for-size grafts exposed to portal overflow without triggering small-for-size syndrome.

A prospective single-center protocol included 8 living donors and 8 RAPID noncirrhotic recipients. Comprehensive clinical and biological data were collected, accompanied by intraoperative arterial and portal flow and pressure measurements. Early kinetic growth rate (eKGR%) and graft function were assessed using computed tomography and 99Tc-mebrofenin scintigraphy on postoperative days 7 and 14. Findings were compared with retrospective data from 13 left living donor liver transplantation (LDLT) recipients.

The median Graft-body weight ratio was 0.41% (interquartile range: 0.34-0.49), markedly lower than in LDLT. However, there was no significant difference in eKGR between RAPID and LDLT grafts. Sequential analysis revealed variable eKGR per day: 10.6% (7.8-13.2) in the first week and 7.6% (6-9.1) in the second week posttransplantation. Indexed portal flow (indexed portal vein flow) was significantly higher in RAPID compared with left LDLT ( P = 0.01). No hemodynamic parameters were found to correlate with regeneration speed. We modulated portal flow in 2 out of 8 cases.

This study presents the first report of hemodynamic and volumetric data for the RAPID technique. Despite initial graft volumes falling below conventional LDLT recommendations, the study highlights acceptable clinical outcomes.

Cyanobacterial blooms have emerged as a significant environmental issue worldwide in recent decades. However, the toxic effects of microcystin-LR (MC-LR) on aquatic organisms, such as frogs, have remained poorly understood. In this study, frogs (Pelophylax nigromaculatus) were exposed to environmentally relevant concentrations of MC-LR (0, 1, and 10 μg/L) for 21 days. Subsequently, we assessed the impact of MC-LR on the histomorphology of the frogs' livers and conducted a global MS-based nontarget metabolomics analysis, followed by the determination of substances involved in lipid metabolism. Results showed that MC-LR significantly induced histological alterations in the frogs' hepatopancreas. Over 200 differentially expressed metabolites were identified, primarily enriched in lipid metabolism. Biochemical analysis further confirmed that MC-LR exposure led to a disorder in lipid metabolism in the frogs. This study laid the groundwork for a mechanistic understanding of MC-LR toxicity in frogs and potentially other aquatic organisms.

Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a potential prognostic parameter in different tumour types. The aim was to investigate whether established liver scores can establish the prognosis of CM. Methods: According to established methods, the APRI, the MELD score, the MELD-Na score and the De Ritis ratio were calculated from the laboratory values at the time of the initial diagnosis. Survival was compared with the Kaplan-Meier curve and tested with log-rank tests. Risk factors associated with cutaneous melanoma-specific survival (CMSS) and progression-free survival (PFS) were assessed by using the Cox proportional hazards regression model. To determine the diagnostic accuracy, we performed a time-dependent ROC analysis. Results: A total of 423 patients were included, including 141 patients in AJCC stage (2017) I (33.3%), 82 in stage II (19.4%), 128 in stage III (30.3%) and 72 in stage IV (17%). Median time until melanoma-specific death was 99 months (IQR: 37-126). In addition, 37.6% of patients relapsed with a median time to relapse of 88 months (IQR: 17.5-126). In all stages, tumour thickness and ulceration were independent markers for predicting CMSS and PFS (p < 0.05). The multivariable analysis with all stages showed no significant association with CM outcome for liver scores (p > 0.05). The subgroup analysis revealed that the APRI (≥0.2241) was associated with CMSS and PFS in melanoma stages I and II, independently of tumour thickness, age and ulceration (HR 2.57, 95% CI 1.14-5.75; HR 2.94, 95% CI 1.42-6.09, respectively). Conclusions: The 20-year prognosis of AJCC stage I and II CM was dependent on tumour thickness and the APRI. High tumour thickness and an APRI ≥ 0.2241 at the initial diagnosis were associated with a worse prognosis. Future studies should investigate the independent prognostic value of the APRI in low-stage CM. Furthermore, the APRI score could be a potential biomarker for nomograms.

To investigate the effect of urinary PAHs on MAFLD.

The study included 3,136 adults from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2016. Among them, 1,056 participants were diagnosed with MAFLD and were designated as the case group. The analysis of the relationship between monohydroxy metabolites of seven PAHs in urine and MAFLD was carried out using logistic regression and Bayesian kernel regression (BKMR) models.

In single-pollutant models, the concentration of 2-hydroxynaphthalene (2-OHNAP) was positively correlated with MAFLD (OR = 1.47, 95% CI 1.18, 1.84), whereas 3-hydroxyfluorene (3-OHFLU) and 1-hydroxypyrene (1-OHPYR) demonstrated a negative correlation with MAFLD (OR = 0.59, 95% CI 0.48 0.73; OR = 0.70, 95% CI 0.55, 0.89). Conversely, in multi-pollutant models, 2-OHNAP, 2-hydroxyfluorene (2-OHFLU), 2-hydroxyphenanthrene, and 3-hydroxyphenanthrene (2&3-OHPHE) displayed positive correlations with MAFLD (OR = 6.17, 95% CI 3.15, 12.07; OR = 2.59, 95% CI 1.37, 4.89). However, 3-OHFLU and 1-OHPYR continued to exhibit negative correlations with MAFLD (OR = 0.09, 95% CI 0.05, 0.15; OR = 0.62, 95% CI 0.43, 0.88). Notably, the BKMR analysis mixtures approach did not indicate a significant joint effect of multiple PAHs on MAFLD, but identified interactions between 3-OHFLU and 2-OHFLU, 1-OHPYR and 2-OHFLU, and 1-OHPYR and 3-OHFLU.

No significant association was found between mixed PAHs exposure and the risk of MAFLD. However, interactions were observed between 3-OHFLU and 2-OHFLU. Both 2-OHFLU and 2&3-OHPHE exposure are significant risk factors for MAFLD, whereas 3-OHFLU is a key protective factor for the disease.

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and colitis. It is recognized as one of the most significant hospital-acquired infections. Although CDI can develop severe complications and spores of Clostridioides difficile can be transmitted by the fecal-oral route, CDI is occasionally overlooked in clinical settings. Thus, it is necessary to monitor high CDI risk groups, particularly those undergoing antibiotic treatment, to prevent complications and spread. We developed and validated a deep learning-based model to predict the occurrence of CDI within 28 days after starting antibiotic treatment using longitudinal electronic health records. For each patient, timelines of vital signs and laboratory tests with a 35-day monitoring period and a patient information vector consisting of age, sex, comorbidities, and medications were constructed. Our model achieved the prediction performance with an area under the receiver operating characteristic curve of 0.952 (95% CI: 0.932-0.973) in internal validation and 0.972 (95% CI: 0.968-0.975) in external validation. Platelet count and body temperature emerged as the most important features. The risk score, the output value of the model, exhibited a consistent increase in the CDI group, while the risk score in the non-CDI group either maintained its initial value or decreased. Using our CDI prediction model, high-risk patients requiring symptom monitoring can be identified. This could help reduce the underdiagnosis of CDI, thereby decreasing transmission and preventing complications.

Fermented mare's milk (koumiss), a traditional Central Asian dairy product derived from fermented mare's milk, is renowned for its unique sour taste and texture. It has long been consumed by nomadic tribes for its nutritional and medicinal benefits. This study aimed to comprehensively analyze the protective effects of koumiss against alcohol-induced harm across behavioral, hematological, gastrointestinal, hepatic, and reproductive dimensions using a mouse model. Optimal intoxicating doses of alcohol and koumiss doses were determined, and their effects were explored through sleep tests and blood indicator measurements. Pretreatment with koumiss delayed inebriation, accelerated sobering, and reduced mortality in mice, mitigating alcohol's impact on blood ethanol levels and various physiological parameters. Histopathological and molecular analyses further confirmed koumiss's protective role against alcohol-induced damage in the liver, stomach, small intestine, and reproductive system. Transcriptomic studies on reproductive damage indicated that koumiss exerts its benefits by influencing mitochondrial and ribosomal functions and also shows promise in mitigating alcohol's effects on the reproductive system. In summary, koumiss emerges as a potential natural agent for protection against alcohol-induced harm, opening avenues for future research in this field.

2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) is a major compound in Cleistocalyx nervosum seed extract (CSE), which has been reported to have various biological activities, including anti-cancer activity. Therefore, this study attempted to evaluate whether DMC is a chemopreventive compound in CSE. Moreover, the preventive mechanisms of CSE and DMC in the DEN-induced early stages of hepatocarcinogenesis in rats were investigated. Male Wistar rats were intraperitoneally injected with DEN 50 mg/kg bw once a week for 8 weeks. Rats received CSE and DMC orally throughout the experiment. The number of glutathione S-transferase placental form (GST-P)-positive foci in the liver was measured. Furthermore, the preventive mechanisms of CSE and DMC on DEN-induced HCC, including cell proliferation and apoptosis, were investigated. Administering CSE at a dosage of 400 mg/kg bw and DMC at a dosage of 10 mg/kg bw significantly decreased the number and size of GST-P-positive foci and GST-P expression. In addition, DMC inhibited the development of preneoplastic lesions by decreasing cell proliferation and causing cell apoptosis; however, CSE inhibited the development of preneoplastic lesions by inducing cell apoptosis. In conclusion, DMC exhibited a cancer chemopreventive effect on the early stages of hepatocarcinogenesis by increasing cell apoptosis and reducing cell proliferation.

This study aimed to develop a prognostic nomogram for predicting the recurrence-free survival (RFS) of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with low preoperative platelet-albumin-bilirubin (PALBI) scores after transarterial chemoembolization (TACE) combined with local ablation treatment.

We gathered clinical data from 632 HBV-related HCC patients who received the combination treatment at Beijing You'an Hospital, affiliated with Capital Medical University, from January 2014 to January 2020. The patients were divided into two groups based on their PALBI scores: low PALBI group (n=247) and high PALBI group (n=385). The low PALBI group was then divided into two cohorts: training cohort (n=172) and validation cohort (n=75). We utilized eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox analysis to pinpoint the risk factors for RFS. Then, we developed a nomogram based on the screened factors and assessed its risk stratification capabilities and predictive performance.

The study finally identified age, aspartate aminotransferase (AST), and prothrombin time activity (PTA) as key predictors. The three variables were included to develop the nomogram for predicting the 1-, 3-, and 5-year RFS of HCC patients. We confirmed the nomogram's ability to effectively discern high and low risk patients, as evidenced by Kaplan-Meier curves. We further corroborated the excellent discrimination, consistency, and clinical utility of the nomogram through assessments using the C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA).

Our study successfully constructed a robust nomogram, effectively predicting 1-, 3-, and 5-year RFS for HBV-related HCC patients with low preoperative PALBI scores after TACE combined with local ablation therapy.

Determination of the functional liver mass is important in a variety of clinical settings including liver surgery and transplantation. [99mTc]Tc-diethylenetriamine-pentaacetic acid galactosyl human serum albumin (99mTc-GSA) is a radiotracer targeting the asialoglycoprotein receptor (ASGR) and is routinely used in Japan for this purpose. Here we describe the development and evaluation of [68Ga]Ga-NODAGA-TriGalactan a low molecular weight PET-tracer targeting this structure.

For synthesis TRIS as branching unit and NODAGA as chelator for labelling with [68Ga]Ga are included. Three galactose moieties are conjugated via a click chemistry approach resulting in the desired labelling precursor.68Ga-labelling could be accomplished in high radiochemical yield and purity. [68Ga]Ga-NODAGA-TriGalactan is very hydrophilic and revealed high plasma stability and low plasma protein binding. Fluorescence imaging showed binding on ASGR-positive organoids and the IC50-value was in the nanomolar range. Most importantly, both biodistribution as well as animal imaging studies using normal mice demonstrated high liver uptake with rapid elimination from all other organs leading to even higher liver-to-background ratios as found for 99mTc-GSA.

[68Ga]Ga-NODAGA-TriGalactan shows high in vitro stability and selectively binds to the ASGR allowing imaging of the functional liver mass with high contrast. Thus, our first generation compound resulted already in an alternative to 99mTc-GSA for imaging the functional liver reserve and might allow the broader use of this imaging technique.

A recently discovered risk factor for chronic liver disease is ambient fine particulate matter (PM2.5). Our research aims to elucidate the effects of PM2.5 on liver injury and the potential molecular mechanisms.

A population-based longitudinal study involving 102,918 participants from 15 Chinese cities, using linear mixed-effect models, found that abnormal alterations in liver function were significantly associated with long-term exposure to PM2.5. The serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, direct bilirubin, and triglyceride increased by 2.05%, 2.04%, 0.58%, 2.99%, and 1.46% with each 10 µg/m3 increase in PM2.5. In contrast, the serum levels of total protein, albumin, and prealbumin decreased by 0.27%, 0.48%, and 2.42%, respectively. Mice underwent chronic inhalation exposure to PM2.5 experienced hepatic inflammation, steatosis and fibrosis. In vitro experiments found that hepatocytes experienced an inflammatory response and lipid metabolic dysregulation due to PM2.5, which also activated hepatic stellate cells. The down-regulation and mis-localization of polarity protein Par3 mediated PM2.5-induced liver injury.

PM2.5 exposure induced liver injury, mainly characterized by steatosis and fibrosis. The down-regulation and mis-localization of Par3 were important mechanisms of liver injury induced by PM2.5.

The liver has the unique capacity to regenerate, and up to 70% of the liver can be removed without detrimental consequences to the organism. Liver regeneration is a complex process involving multiple signaling networks and organs. Liver regeneration proceeds through three phases: the initiation phase, the growth phase, and the termination phase. Termination of liver regeneration occurs when the liver reaches a liver-to-body weight that is required for homeostasis, the so-called "hepatostat." The initiation and growth phases have been the subject of many studies. The molecular pathways that govern the termination phase, however, remain to be fully elucidated. This review summarizes the pathways and molecules that signal the cessation of liver regrowth after partial hepatectomy and answers the question, "What factors drive the hepatostat?" SIGNIFICANCE STATEMENT: Unraveling the pathways underlying the cessation of liver regeneration enables the identification of druggable targets that will allow us to gain pharmacological control over liver regeneration. For these purposes, it would be useful to understand why the regenerative capacity of the liver is hampered under certain pathological circumstances so as to artificially modulate the regenerative processes (e.g., by blocking the cessation pathways) to improve clinical outcomes and safeguard the patient's life.

Apart from hypoxic hepatitis (HH), the hepatic consequences of out-of-hospital cardiac arrest (OHCA) have been little studied. This cohort study aimed to investigate the characteristics of liver dysfunction resulting from OHCA and its association with outcomes.

Among the conventional static liver function tests used to define acute liver failure (ALF), we determined which one correlated more closely with the reference indocyanine green (ICG) clearance test in a series of OHCA patients from the CYRUS trial (NCT01595958). Subsequently, we assessed whether ALF, in addition to HH (i.e., acute liver injury), was an independent risk factor for death in a large cohort of OHCA patients admitted to two intensive care units between 2007 and 2017.

ICG clearance, available for 22 patients, was impaired in 17 (77.3%) cases. Prothrombin time (PT) ratio was the only static liver function test that correlated significantly (r = -0.66, p < 0.01) with ICG clearance and was therefore used to define ALF, with the usual cutoff of < 50%. Of the 418 patients included in the analysis (sex ratio: 1.4; median age: 64 [53-75] years; non-shockable rhythm: 73%), 67 (16.0%) presented with ALF, and 61 (14.6%) had HH at admission. On day 28, 337 (80.6%) patients died. Following multivariate analysis, ALF at admission, OHCA occurring at home, absence of bystander, non-cardiac cause of OHCA, low-flow duration ≥ 20 min, and SOFA score excluding liver subscore at admission were independently associated with day 28 mortality.

ALF occurred frequently after OHCA and, unlike HH, was independently associated with day 28 mortality.

Ageratina adenophora (A. adenophora) is an invasive plant that is harmful to animals. The plants toxic effects on the liver have been studied in detail, however, the inflammation aspects of the hepatotoxicity are rarely discussed in literature. Therefore, in this study, we investigated the level of inflammation and the associated changes in liver metabolism caused by A. adenophora ingestion. Goat were fed with A. adenophora powder which accounts for 40% of the forage for 90 d. After the feeding period, the liver tissues were collected and the level of inflammation was detected using H & E staining and the changes in metabolites by LC-MS/MS. The results indicated that A. adenophora changes the liver metabolites, The test group shown 153 different metabolites in liver of which 71 were upregulated and 82 down regulated. We also found two differential metabolic pathways: neuroactive ligand-receptor interaction and pyrimidine metabolism. The changes in the pathway suggested an association with inflammation and with pathological processes such as oxidative stress and apoptosis. In addition, we observed an increase in the levels of serum liver function indexes (AST and ALT), indicating the liver injury. Furthermore, inflammatory cell infiltration and cell degeneration were observed in histopathological sections. In conclusion, this study reveals that A. adenophora causes chronic inflammation and upregulate metabolites related to inflammation in the liver. The study complements the research content of A. adenophora hepatotoxicity and provides a basis for further research by analyzing changes in the liver metabolites.

Polycyclic aromatic hydrocarbon (PAH) exposure has been associated with adverse health effects, and accumulating evidence suggests that PAH exposure may impair liver function. However, the underlying mechanisms linking PAH exposure and liver function impairment remain unclear. This study aimed to explore the association between PAH exposure and liver function biomarkers, and the mediating effects of inflammation and oxidative stress. The cross-sectional study included 155 adults and their urinary PAH metabolites (OH-PAHs) were determined, and eight liver function biomarkers were measured in paired serum samples. A comprehensive statistical analysis investigated the linear, non-linear, individual, and joint effects of the association between urinary OH-PAHs and liver function biomarkers. The results indicated significant positive associations between urinary OH-PAH concentrations and liver function biomarker levels, suggesting that PAH exposure may adversely affect liver function. 2-hydroxyfluorene was identified as the individual metabolite contributing significantly to elevated gamma-glutamyl transferase levels. Further stratification by gender revealed that this association is more pronounced in males. Moreover, we observed significant mediation effects of the oxidative stress biomarker 8-hydroxy-2'-deoxyguanosine and the inflammatory biomarkers C-reactive protein and white blood cell count on this association. The physiological responses triggered by PAH exposure are mediated by inflammation, which serves as a link between oxidative stress, cellular injury, and elevated liver enzyme levels. The results demonstrated that increased inflammation and oxidative stress mediated the association between increased urinary OH-PAHs and elevated liver function biomarkers. The results contribute to a better understanding of the potential mechanisms underlying PAH exposure's hepatotoxic effects.

Liver resection and liver transplantation are the mainstay of treatment for patients with hepatocellular carcinoma. Patient comorbidities, tumor resectability, and perioperative morbidity and mortality risk, specifically of post-hepatectomy liver failure, are determining factors when deciding between liver resection and liver transplantation in patients who do not have an obvious contraindication to either treatment. Liver resection is preferred in patients without cirrhosis, and it may be a reasonable choice in patient with cirrhosis but preserved liver function and no portal hypertension if the size and function of the future liver remnant are appropriate, especially if organ availability is scarce.

Compared with corn, wheat contains higher crude protein, amino acids concentration. However, wheat contains a mass of anti-nutritional factors, resulting in increased of the digesta viscosity and impaired the intestinal function in ruminant.

This study aimed to investigate the effects of substitution of different amounts of wheat for corn on hepatic metabolism in the Tibetan lamb.

Ninety Tibetan lambs (Body weight = 12.37 ± 0.92 kg) were randomly assigned to three groups: 0% wheat diet (Control), 10% wheat diet (Low group), and 15% wheat diet (High group). The feeding trial lasted for 130 d, including a 10 d adaption period. Hepatic gene expression profiling was performed via RNA sequencing after the conclusion of the feeding trials.

Results showed that greater level of glutathione peroxidase levels in L group compared with those of the C and H groups (P < 0.05). The immune indexes, including interleukin-1β (IL-1β), immunoglobulin A (IgA), and IgM were also elevated in L group compared with the other groups (P < 0.05). Compared with H group, the hepatocytes were arranged radially, and hepatic plates anastomosed with each other to form a labyrinth-like structure in L group. Transcriptomic analysis showed 872 differentially expressed genes (DEG) between H and L group, of which 755 were down-regulated and 117 were up-regulated. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, 32 pathways were significantly enriched (Q-value < 0.05), such as the cAMP signaling pathway, Th1 and Th2 cell differentiation, leukocyte transendothelial migration, platelet activation and adipocytokine signaling pathway. Additionally, the expression of comment DEGs were verified via quantitative reverse-transcription polymerase chain reaction.

In summary, our findings suggest that wheat can be supplemented up to 10% in Tibetan sheep, contributing to improve the hepatic oxidative stress, immune response and lipid metabolism through regulating the expression of related genes.

Drug-induced liver injury is the most common cause of acute liver failure. Off-Target effect "hepatotoxicity "frequently detected during clinical examination of patients on anti-Tb medication particularly isoniazid (INH), and rifampin (RMP). However, there is no any treatment option against isoniazid and rifampicin induced hepatotoxicity. It is, therefore, necessary to search for effective affordable and safe drugs from medicinal plants for the prevention of liver toxicity caused by isoniazid and rifampicin. The aim the current study is to evaluate hepatoprotective effect of hydro methanol extract from Otostegia integrifolia leaves in isoniazid and rifampicin-induced hepatotoxicity in Swiss albino mice.

O. integrifolia leaves powder was macerated in hydromethanol and thirty Swiss albino mice 29.0-40.6 g were grouped in to five groups. Group I were given 20 ml/kg distilled water, group II were given 100 mg INH and 150 mg RIF per kg body weight. Group III, group IV, and group V were given 200 mg extract, 400 mg extract, and 100 mg of N-acetyl cysteine respectively per kg 1hr before induction with 100 mg INH plus 150 mg RIF per kg. The treatments were followed for 14 days. On the 15th day, all mice were anaesthetized with diethyl ether; blood samples were collected for the assessment liver enzyme and function test.

Group II mice's serum ALT, AST and total bilirubin levels were significantly increased and serum total protein and albumin levels were significantly decreased as compared with group I mice. The groups of mice treated with O. integrifolia at a dose of 400 mg/kg and N-acetyl cysteine AST, ALT and total bilirubin level were significantly decreased; and total protein and albumin levels were significantly (P < 0.05) increased as compared with group II. The liver index of the group IV showed decreased (P < 0.05) as compared to the group II.

Evidence from our study revealed that the hydromethanol extract of O. integrifolia has a hepatoprotective effect against isoniazid and rifampicin-induced hepatotoxicity in Swiss Albino mice. This protective effect of O. integrifolia extract may be based on its metal ion reducing power, free radical scavenging activity, and anti-inflammatory activity and could be used as a potential therapeutic option.

The liver plays a key role in glucose homeostasis. Serum liver enzyme levels, including alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transferase (GGT), are reportedly predictive of the risk of type 2 diabetes (T2D). However, the link between the liver enzyme profile and metabolic derangements in T2D, particularly the secretion of both insulin and glucagon, is not clear. This study evaluated its relationships with glycemia, insulin and glucagon both during fasting and after an oral glucose load or a mixed meal in T2D. 15 healthy and 43 T2D subjects ingested a 75 g glucose drink. 86 T2D subjects consumed a mixed meal. Venous blood was sampled for measurements of blood glucose and plasma insulin, C-peptide and glucagon. Blood glucose, plasma insulin, C-peptide and glucagon concentrations, both fasting and after oral glucose, correlated directly with ALT, while fewer and weaker correlations were observed with GGT or AST. Subgroup analysis in T2D subjects ascertained that plasma insulin, C-peptide and glucagon concentrations after oral glucose were higher with increasing ALT. Similar findings were observed in the T2D subjects who received a mixed meal. In conclusion, serum liver enzyme profile, particularly ALT, reflects dysregulated fasting and nutrient-stimulated plasma insulin and glucagon concentrations in T2D.

Understanding the impact of altered hepatic uptake and/or efflux on the hepatobiliary disposition of the imaging agents [99mTc]Mebrofenin (MEB) and [153Gd]Gadobenate dimeglumine (BOPTA) is important for proper estimation of liver function.

A multi-compartmental pharmacokinetic (PK) model describing MEB and BOPTA disposition in isolated perfused rat livers (IPRLs) was developed. The PK model was simultaneously fit to MEB and BOPTA concentration-time data in the extracellular space, hepatocytes, bile canaliculi, and sinusoidal efflux in livers from healthy rats, and to BOPTA concentration-time data in rats pretreated with monocrotaline (MCT).

The model adequately described MEB and BOPTA disposition in each compartment. The hepatocyte uptake clearance was much higher for MEB (55.3 mL/min) than BOPTA (6.67 mL/min), whereas the sinusoidal efflux clearance for MEB (0.000831 mL/min) was lower than BOPTA (0.0127 mL/min). The clearance from hepatocytes to bile (CLbc) for MEB (0.658 mL/min) was similar to BOPTA (0.642 mL/min) in healthy rat livers. The BOPTA CLbc was reduced in livers from MCT-pretreated rats (0.496 mL/min), while the sinusoidal efflux clearance was increased (0.0644 mL/min).

A PK model developed to characterize MEB and BOPTA disposition in IPRLs was used to quantify changes in the hepatobiliary disposition of BOPTA caused by MCT pretreatment of rats to induce liver toxicity. This PK model could be applied to simulate changes in the hepatobiliary disposition of these imaging agents in rats in response to altered hepatocyte uptake or efflux associated with disease, toxicity, or drug-drug interactions.

Liver resection is an effective therapeutic option for patients with hepatocellular carcinoma. However, posthepatectomy liver failure (PHLF) remains a major cause of hepatectomy-related mortality, and the accurate prediction of PHLF based on preoperative assessment of liver functional reserve is a critical issue. The definition of PHLF proposed by the International Study Group for Liver Surgery has gained acceptance as a standard grading criterion. Liver function can be estimated using a variety of parameters, including routine blood biochemical examinations, clinical scoring systems, dynamic liver function tests, liver stiffness and fibrosis markers, and imaging studies. The Child-Pugh score and model for end-stage liver disease scores are conventionally used for estimating liver decompensation, although the alternatively developed albumin-bilirubin score shows superior performance for predicting hepatic dysfunction. Indocyanine green clearance, a dynamic liver function test mostly used in Japan and other Asian countries, serves as a quantitative estimation of liver function reserve and helps determine indications for surgical procedures according to the estimated risk of PHLF. In an attempt to improve predictive accuracy, specific evaluation of liver fibrosis and portal hypertension has gained popularity, including liver stiffness measurements using ultrasonography or magnetic resonance elastography, as well as noninvasive fibrosis markers. Imaging modalities, including Tc-99m-labeled galactosyl serum albumin scintigraphy and gadolinium-enhanced magnetic resonance imaging, are used for preoperative evaluation in combination with liver volume. This review aims to provide an overview of the usefulness of current options for the preoperative assessment of liver function in predicting PHLF.

Little is known about the correlation between perioperative concentrations of inflammatory biomarkers and postoperative complications. This study explored whether the plasma concentrations and perioperative changes of procalcitonin (PCT), C reactive protein (CRP) and high-sensitivity CRP (hsCRP) could predict the risk of postoperative morbidity in elderly patients undergoing elective non-cardiac surgery.

A nested case-control study.

A tertiary hospital in China.

A total of 498 patients aged ≥65 years from a prospective cohort who underwent elective non-cardiac surgery between June 2020 and April 2021.

The primary outcomes were the efficacy of plasma concentrations of PCT, CRP and hsCRP in predicting the risk of Clavien-Dindo Classification (CDC) ≥grade 3 and major complications. The major complications included mortality, an intensive care unit stay length >24 hour, cardiovascular events, acute kidney injury, postoperative cognitive dysfunction and infections.

For major complications, the area under the curve (AUC) (95% CI) of PCT-24 hours, PCT change and PCT change rate were 0.750 (0.698 to 0.803), 0.740 (0.686 to 0.795) and 0.711 (0.651 to 0.771), respectively. The AUC (95% CI) of CRP-24 hours, CRP change, CRP change rate and hsCRP baseline were 0.835 (0.789 to 0.881), 0.818 (0.770 to 0.867), 0.691 (0.625 to 0.756) and 0.616 (0.554 to 0.678), respectively. For complications ≥CDC grade 3, the AUC (95% CI) of PCT-24 hours, PCT change and PCT change rate were 0.662 (0.543 to 0.780), 0.643 (0.514 to 0.772) and 0.627 (0.494 to 0.761), respectively. The AUC (95% CI) of CRP-24 hours and hsCRP baseline were 0.649 (0.527 to 0.771) and 0.639 (0.530 to 0.748), respectively.

PCT-24 hours, CRP-24 hours, the change of perioperative PCT and CRP were valuable predictors of major complications occurring within 30 days after non-cardiac surgery in the elderly.

China Clinical Trial Registry: ChiCTR1900026223.

To evaluate the value of four indices of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced (Gd-EOB-DTPA) magnetic resonance as a potential imaging marker of liver functional reserve.

PubMed/Medline, Embase, Cochrane Library, and Web of Science were searched for studies concerning the relationship between Gd-EOB-DTPA-enhanced MRI and liver functional reserve estimated by ICG-R15, Pooled correlation coefficient (r) and 95% confidence intervals (CIs) were calculated, Meanwhile, Sensitivity and subgroup analyses were performed along with Egger's test for the estimation of publication bias and potential heterogeneity.

14 publications with 1285 patients were included. The pooled r between relative liver enhancement (RLE), reduction rate of T1 relaxation time of the liver (rrT1), liver-to-spleen ratio (LSR), liver-to-muscle ratio (LMR), and ICG-R15 were -0.49 (95% CI, -0.56 to -0.41, p < 0.05), -0.47 (95% CI, -0.57 to -0.36, p < 0.05), -0.45 (95% CI, -0.55 to -0.34, p < 0.05), -0.50 (95% CI, -0.61 to -0.38, p < 0.05). moderate heterogeneity was observed between studies on rrT1, LSR, LMR, and ICG-R15 (p ≤ 0.05), but no significant heterogeneity was observed between RLE and ICG-R15. Further analysis shows that there was a notable heterogeneity between subgroup analysis of LSR and ICG-R15 stratified by years of publication, as well as rrT1 and LMR stratified by total patients and study design, the distribution funnel plots and the results of Egger's test showed no evidence of publication bias.

RLE, LSR, LMR, and rrT1 all correlated significantly with ICG-R15-estimated hepatic functional reserve. The four indices represent a promising imaging biomarker in the prediction of liver functional reserve.

The aim of this joint EANM/SNMMI/IHPBA procedure guideline is to provide general information and specific recommendations and considerations on the use of [99mTc]Tc-mebrofenin hepatobiliary scintigraphy (HBS) in the quantitative assessment and risk analysis before surgical intervention, selective internal radiation therapy (SIRT) or before and after liver regenerative procedures. Although the gold standard to estimate future liver remnant (FLR) function remains volumetry, the increasing interest in HBS and the continuous request for implementation in major liver centers worldwide, demands standardization.

This guideline concentrates on the endorsement of a standardized protocol for HBS elaborates on the clinical indications and implications, considerations, clinical appliance, cut-off values, interactions, acquisition, post-processing analysis and interpretation. Referral to the practical guidelines for additional post-processing manual instructions is provided.

The increasing interest of major liver centers worldwide in HBS requires guidance for implementation. Standardization facilitates applicability of HBS and promotes global implementation. Inclusion of HBS in standard care is not meant as substitute for volumetry, but rather to complement risk evaluation by identifying suspected and unsuspected high-risk patients prone to develop post-hepatectomy liver failure (PHLF) and post-SIRT liver failure.

Liver function reserve (LFR) is the sum of remnant functional hepatic cells after liver injury. In the pathologic process of liver fibrosis (LF), LFR is impaired. LFR assessment can help determine the safe scope of liver resection or drug regimen and predict prognosis of patients with liver disease. Here, we used a photoacoustic imaging (PAI) system to assess LF and LFR in rabbit models. We performed PAI, ultrasound elastography and biopsy for 21 rabbits developing none (n = 6) and LF (n = 15). In vivo indocyanine green (ICG) measurements by PAI showed that LF group presented a significantly attenuated ICG clearance compared to control group, indicating LFR impairment of LF. Another finding was a significantly higher collagen photoacoustic signal intensity value was observed in LF both in vivo and in vitro. Our findings demonstrated that PAI was potentially effective to evaluate LFR and collagen accumulation of LF.

In the context of liver surgery, predicting postoperative liver dysfunction is essential. This study explored the potential of preoperative liver function assessment by MRI for predicting postoperative liver dysfunction and compared these results with the established indocyanine green (ICG) clearance test. This prospective study included patients undergoing liver resection with preoperative MRI planning. Liver function was quantified using T1 relaxometry and correlated with established liver function scores. The analysis revealed an improved model for predicting postoperative liver dysfunction, exhibiting an accuracy (ACC) of 0.79, surpassing the 0.70 of the preoperative ICG test, alongside a higher area under the curve (0.75). Notably, the proposed model also successfully predicted all cases of liver failure and showed potential in predicting liver synthesis dysfunction (ACC 0.78). This model showed promise in patient survival rates with a Hazard ratio of 0.87, underscoring its potential as a valuable tool for preoperative evaluation. The findings imply that MRI-based assessment of liver function can provide significant benefits in the early identification and management of patients at risk for postoperative liver dysfunction.

Annona muricata is a common plant used in Africa and South America to manage various types of disease. However, there is insufficient toxicological information or published standard available regarding repeated dose animal toxicity data. As part of the safety assessment, we exposed Sprague Dawley rats to an acute oral toxicity of A. muricata. The intent of the current study was to use advanced proton nuclear magnetic resonance (1H NMR) in serum and urinary metabolomics evaluation techniques to provide the in vivo acute toxicological profile of A. muricata leaf ethanol extract in accordance with the Organization for Economic Co-operation and Development's (OECD) 423 guidelines. A single 2000 mg/kg dose of A. muricata leaf ethanol extract was administered to Sprague Dawley rats over an observational period of 14 days. The toxicity evaluation (physical and behavior observation, body weight, renal function test, liver function test and 1H NMR analysis) showed no abnormal toxicity. Histopathological analysis manifested mild changes, i.e., the treated kidney manifested mild hypercellularity of mesangial cells and mild red blood cell congestion. In addition, there was mild hemorrhage into tissue with scattered inflammatory cells and mild dilated central vein with fibrosis in the liver. However, the changes were very mild and not significant which correlate with other analyses conducted in this study (biochemical test and 1H NMR metabolomic analysis). On the other hand, urinary 1H NMR analysis collected on day 15 revealed high similarity on the metabolite variations for both untreated and treated groups. Importantly, the outcomes suggest that A. muricata leaf ethanol extract can be safely consumed at a dose of 2000 mg/kg and the LD50 must be more than 2000 mg/kg.

A 76-year-old man with hepatocellular carcinoma was referred for liver radioembolization. Given a prior left hemihepatectomy, it was clinically important to consider potentially irradiated healthy liver at planning. Thus, at the SPECT/CT imaging of the scout dose 166 Ho-microparticles before injected superselectively in the right hepatic artery, 99m Tc-mebrofenin was injected intravenously, and functional volumetry SPECT was performed simultaneously. Based on the 2 image sets, the nonirradiated healthy liver was calculated as 1589 mL (functional liver reserve of 85.5% on 99m Tc-mebrofenin SPECT). Posttreatment dosimetry calculations showed optimal normal tissue and tumor absorbed doses, and the patient is clinically well after 3 months.

Liver-to-spleen signal intensity ratio (LSR) is evaluated by magnetic resonance imaging (MRI) in the hepatobiliary phase and has been reported as a useful radiological assessment of regional liver function. However, LSR is a passive (non-time-associated) assessment of liver function, not a dynamic (time-associated) assessment. Moreover, LSR shows limitations such as a dose bias of contrast medium and a timing bias of imaging. Previous studies have reported the advantages of time-associated liver functional assessment as a precise assessment of liver function. For instance, the indocyanine green (ICG) disappearance rate, which is calculated from serum ICG concentrations at multiple time points, reflects a precise preoperative liver function for predicting post-hepatectomy liver failure without the dose bias of ICG or the timing bias of blood sampling. The aim of this study was to develop a novel time-associated radiological liver functional assessment and verify its correlation with traditional liver functional parameters.

A total of 279 pancreatic cancer patients were evaluated to clarify fundamental time-associated changes to LSR in normal liver. We defined the time-associated radiological assessment of liver function, calculated using information on LSR from four time points, as the "LSR increasing rate" (LSRi). We then investigated correlations between LSRi and previous liver functional parameters. Furthermore, we evaluated how timing bias and protocol bias affect LSRi.

Significant correlations were observed between LSRi and previous liver functional parameters such as total bilirubin, Child-Pugh grade, and albumin-bilirubin grade (P < 0.001 each). Moreover, considerably high correlations were observed between LSRi calculated using four time points and that calculated using three time points (r > 0.973 each), indicating that the timing bias of imaging was minimal.

This study propose a novel time-associated radiological assessment, and revealed that the LSRi correlated significantly with traditional liver functional parameters. Changes in LSR over time may provide a superior preoperative assessment of regional liver function that is better for predicting post-hepatectomy liver failure than LSR using the hepatobiliary phase alone.

Liver regeneration has been studied for many decades, and the mechanisms underlying regeneration of normal liver following resection are well described. However, no less relevant is the study of mechanisms that disrupt the process of liver regeneration. First of all, a violation of liver regeneration can occur in the presence of concomitant hepatic pathology, which is a key factor reducing the liver's regenerative potential. Understanding these mechanisms could enable the rational targeting of specific therapies to either reduce the factors inhibiting regeneration or to directly stimulate liver regeneration. This review describes the known mechanisms of normal liver regeneration and factors that reduce its regenerative potential, primarily at the level of hepatocyte metabolism, in the presence of concomitant hepatic pathology. We also briefly discuss promising strategies for stimulating liver regeneration and those concerning methods for assessing the regenerative potential of the liver, especially intraoperatively.