Endoscopic ultrasound-guided tissue acquisition for focal liver lesions in patients with a history of multiple primary malignant neoplasms.

Objective: This study aimed to investigate the usefulness of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing focal liver lesions in patients with a history of multiple primary malignant neoplasms. Methods: Among patients who underwent EUS-TA for focal liver lesions between 2016 and 2022, those with a history of multiple malignant neoplasms were included. A histologically confirmed malignant tumor within the past 5 years before EUS-TA was defined as a history of malignant neoplasm. The primary outcomes were diagnostic ability and adverse events of EUS-TA. Results: This study included 16 patients (median age, 73 [33-90] years), the median tumor size was 32 (6-51) mm, 14 had a history of double malignant neoplasms, whereas two had triple malignant neoplasms. Malignant neoplasms were detected histologically or cytologically in all cases. Immunohistochemistry was performed in 75% (12/16), and the final diagnosis of EUS-TA was metastatic liver tumor in 12 patients, and primary malignant liver tumor in four patients. The primary site could be identified in 11 of 12 metastatic tumor cases. The diagnostic yield of EUS-TA was 100% (16/16) for differentiating benign and malignant tumors and 94% (15/16) for confirming the histological type including the primary site of metastatic lesions. No adverse events were associated with the procedure. Conclusion: EUS-TA is a useful diagnostic modality for focal liver lesions in patients with a history of multiple malignant neoplasms, allowing for the differential diagnosis of primary and metastatic tumors and identification of the primary site of metastatic lesions.

The role of neutrophil extracellular traps in ß-methylamino L-alanine-induced liver injury in mice.

The non-protein amino acid ß-N-methylamino-L-alanine (BMAA), produced by cyanobacteria, has been recognized as a neurotoxin. L-serine as an antagonist of BMAA can effectively alleviate BMAA-induced neurotoxicity. Although BMAA has long been emphasized as a neurotoxin, with the emergence of BMAA detected in a variety of algae in freshwater around the world and its clear biological enrichment effect, it is particularly important to study the non-neurotoxic adverse effects of BMAA. However, there is only limited evidence to support the ability of BMAA to cause oxidative damage in the liver. The exact molecular mechanism of BMAA-induced liver injury is still unclear. The formation of neutrophil extracellular traps (NETs) is a 'double-edged sword' for the organism, excessive formation of NETs is associated with inflammatory diseases of the liver. Our results innovatively confirmed that BMAA was able to cause the formation of NETs in the liver during the liver injury. The possible mechanism may associated with the regulation of ERK/p38 and cGAS/STING signaling pathways. The massive formation of NETs was able to exacerbate the BMAA-induced oxidative stress and release of inflammatory factors in the mice liver. And the removal of NETs could alleviate this injury. This article will bring a new laboratory evidence for BMAA-induced non-neurotoxicity and immunotoxicity.

Generation of Olfactory Compounds in Cat Food Attractants: Chicken Liver-Derived Protein Hydrolysates and Their Contribution to Enhancing Palatability.

The present study investigated the impact of four chicken liver protein hydrolysate-based cat food attractants on palatability. Aroma compounds were analyzed in these attractants, which were subsequently sprayed onto four different types of cat foods. Results revealed that CF4 exhibited the highest intake ratio and the first choice ratio, followed by CF2 sample. Orthogonal partial least-squares discriminant analysis (OPLS-DA) demonstrated significant differences among 50 volatile compounds identified from the four cat foods. Using variable importance in projection (VIP) values, we selected 17 key flavor compounds responsible for distinguishing between the four cat foods. Peptides with a molecular mass <180 Da showed correlation with nonanoic acid and cedrol, while those >3000 Da correlated with hexanoic acid ethyl ester. Regression coefficients (RCs) calculated from partial least-squares regression (PLSR) results showed positive correlations between compound content and palatability for six compounds, whereas negative correlations were observed for ten compounds. Validation experiments confirmed that nonanal, 2-propylpyridine, and 3-octen-2-one enhanced palatability and correlated with peptides ranging from 180 to 500 Da; conversely, nonanoic acid ethyl ester and 3-methyl-pentanoic acid reduced palatability and correlated with peptides ranging from 1000 to 3000 Da.

Current application and future perspective of CRISPR/cas9 gene editing system mediated immune checkpoint for liver cancer treatment.

Liver cancer, which is well-known to us as one of human most prevalent malignancies across the globe, poses a significant risk to live condition and life safety of individuals in every region of the planet. It has been shown that immune checkpoint treatment may enhance survival benefits and make a significant contribution to patient prognosis, which makes it a promising and popular therapeutic option for treating liver cancer at the current time. However, there are only a very few numbers of patients who can benefit from the treatment and there also exist adverse events such as toxic effects and so on, which is still required further research and discussion. Fortunately, the clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) provides a potential strategy for immunotherapy and immune checkpoint therapy of liver cancer. In this review, we focus on elucidating the fundamentals of the recently developed CRISPR/Cas9 technology as well as the present-day landscape of immune checkpoint treatment which pertains to liver cancer. What's more, we aim to explore the molecular mechanism of immune checkpoint treatment in liver cancer based on CRISPR/Cas9 technology. At last, its encouraging and powerful potential in the future application of the clinic is discussed, along with the issues that already exist and the difficulties that must be overcome. To sum up, our ultimate goal is to create a fresh knowledge that we can utilize this new CRISPR/Cas9 technology for the current popular immune checkpoint therapy to overcome the treatment issues of liver cancer.

Methane gas in breath test is associated with non-alcoholic fatty liver disease.

Although the associations between a patient's body mass index (BMI) and metabolic diseases, as well as their breath test results, have been studied, the relationship between breath hydrogen/methane levels and metabolic diseases needs to be further clarified. We aimed to investigate how the composition of exhaled breath gases relates to metabolic disorders, such as diabetes mellitus, dyslipidemia, hypertension, and nonalcoholic fatty liver disease (NAFLD), and their key risk factors. An analysis was performed using the medical records, including the lactulose breath test (LBT) data of patients who visited the Ajou University Medical Center, Suwon, Republic of Korea, between January 2016 and December 2021. The patients were grouped according to four different criteria for LBT hydrogen and methane levels. Of 441 patients, 325 (72.1%) had positive results for methane only (hydrogen < 20 parts per million [ppm] and methane ⩾ 3 ppm). BMIs and NAFLD prevalence were higher in patients with only methane positivity than in patients with hydrogen and methane positivity (hydrogen ⩾ 20 ppm and methane ⩾ 3 ppm). According to a multivariate analysis, the odds ratio of only methane positivity was 2.002 (95% confidence interval [CI]: 1.244-3.221,P= 0.004) for NAFLD. Our results demonstrate that breath methane positivity is related to NAFLD and suggest that increased methane gas on the breath tests has the potential to be an easily measurable biomarker for NAFLD diagnosis.

Liver click dECM hydrogels for engineering hepatic microenvironments.

Decellularized extracellular matrix (dECM) hydrogels provide tissue-specific microenvironments which accommodate physiological cellular phenotypes in 3D in vitro cell cultures. However, their formation hinges on collagen fibrillogenesis, a complex process which limits regulation of physicochemical properties. Hence, achieving reproducible results with dECM hydrogels poses as a challenge. Here, we demonstrate that thiolation of solubilized liver dECM enables rapid formation of covalently crosslinked hydrogels via Michael-type addition, allowing for precise control over mechanical properties and superior organotypic biological activity. Investigation of various decellularization methodologies revealed that treatment of liver tissue with Triton X-100 and ammonium hydroxide resulted in near complete DNA removal with significant retention of the native liver proteome. Chemical functionalization of pepsin-solubilized liver dECMs via 1-ethyl-3(3-dimethylamino)propyl carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling of l-Cysteine created thiolated liver dECM (dECM-SH), which rapidly reacted with 4-arm polyethylene glycol (PEG)-maleimide to form optically clear hydrogels under controlled conditions. Importantly, Young's moduli could be precisely tuned between 1 - 7 kPa by varying polymer concentrations, enabling close replication of healthy and fibrotic liver conditions in in vitro cell cultures. Click dECM-SH hydrogels were cytocompatible, supported growth of HepG2 and HepaRG liver cells, and promoted liver-specific functional phenotypes as evidenced by increased metabolic activity, as well CYP1A2 and CYP3A4 activity and excretory function when compared to monolayer culture and collagen-based hydrogels. Our findings demonstrate that click-functionalized dECM hydrogels offer a highly controlled, reproducible alternative to conventional tissue-derived hydrogels for in vitro cell culture applications. STATEMENT OF SIGNIFICANCE: Traditional dECM hydrogels face challenges in reproducibility and mechanical property control due to variable crosslinking processes. We introduce a click hydrogel based on porcine liver decellularized extracellular matrix (dECM) that circumnavigates these challenges. After optimizing liver decellularization for ECM retention, we integrated thiol-functionalized liver dECM with polyethylene-glycol derivatives through Michael-type addition click chemistry, enabling rapid, room-temperature gelation. This offers enhanced control over the hydrogel's mechanical and biochemical properties. The resultant click dECM hydrogels mimic the liver's natural ECM and exhibit greater mechanical tunability and handling ease, facilitating their application in high-throughput and industrial settings. Moreover, these hydrogels significantly improve the function of HepaRG-derived hepatocytes in 3D culture, presenting an advancement for liver tissue cell culture models for drug testing applications.

Disruption of the peripheral biological clock may play a role in sleep deprivation-induced dysregulation of lipid metabolism in both the daytime and nighttime phases.

STUDY OBJECTIVES: This study aimed to examine the effect of sleep deprivation (SD) on lipid metabolism or lipid metabolism regulation in the liver and white adipose tissue (WAT) during the light and dark phases and explored the possible mechanisms underlying the diurnal effect of SD on lipid metabolism associated with clock genes. METHODS: Male C57BL/6J mice aged 2 months were deprived of sleep daily for 20 h for ten consecutive days with weakly forced locomotion. The body weights and food consumption levels of the SD and control mice were recorded, and the mice were then sacrificed at ZT (zeitgeber time) 2 and ZT 14. The peripheral clock genes, enzymes involved in fat synthesis and catabolism in the WAT, and melatonin signalling pathway-mediated lipid metabolism in the liver were assessed. Untargeted metabolomics and tandem mass tag (TMT) proteomics were used to identify differential lipid metabolism pathways in the liver. RESULTS: Bodyweight gain and daily food consumption were dramatically elevated after SD. Profound disruptions in the diurnal regulation of the hepatic peripheral clock and enzymes involved in fat synthesis and catabolism in the WAT were observed, with a strong emphasis on hepatic lipid metabolic pathways, while melatonin signalling pathway-mediated lipid metabolism exhibited moderate changes. CONCLUSIONS: In mice, ten consecutive days of SD increased body weight gain and daily food consumption. In addition, SD profoundly disrupted lipid metabolism in the WAT and liver during the light and dark periods. These diurnal changes may be related to disorders of the peripheral biological clock.

Analysis of factors related to recanalization of portal vein thrombosis in liver cirrhosis: a retrospective cohort study.

BACKGROUND: Portal vein thrombosis (PVT) is a common complication of liver cirrhosis, yet there are fewer studies about predictors of PVT recanalization. We aimed to further explore the predictors of recanalization in cirrhotic PVT to facilitate accurate prediction of patients' clinical status and timely initiation of appropriate treatment and interventions. To further investigate the benefits and risks of anticoagulant therapy in cirrhotic PVT patients. METHODS: A retrospective cohort study of patients with cirrhotic PVT in our hospital between January 2016 and December 2022, The primary endpoint was to analyze predictors of PVT recanalization by COX regression. Others included bleeding rate, liver function, and mortality. RESULTS: This study included a total of 82 patients, with 30 in the recanalization group and 52 in the non-recanalization group. Anticoagulation therapy was the only independent protective factor for portal vein thrombosis recanalization and the independent risk factors included massive ascites, history of splenectomy, Child-Pugh B/C class, and main trunk width of the portal vein. Anticoagulation therapy was associated with a significantly higher rate of PVT recanalization (75.9% vs. 20%, log-rank P < 0.001) and a lower rate of PVT progression (6.9% vs. 54.7%, log-rank P = 0.002). There was no significant difference between different anticoagulation regimens for PVT recanalization. Anticoagulation therapy did not increase the incidence of bleeding complications(P = 0.407). At the end of the study follow-up, Child-Pugh classification, MELD score, and albumin level were better in the anticoagulation group than in the non-anticoagulation group. There was no significant difference in 2-year survival between the two groups. CONCLUSION: Anticoagulation, massive ascites, history of splenectomy, Child-Pugh B/C class, and main portal vein width were associated with portal vein thrombosis recanalization. Anticoagulation may increase the rate of PVT recanalization and decrease the rate of PVT progression without increasing the rate of bleeding. Anticoagulation may be beneficial in improving liver function in patients with PVT in cirrhosis.

Skeletal muscle quality predicts overall survival in advanced liver hepatocellular carcinoma treated with SIRT and sorafenib: A subanalysis of the SORAMIC trial.

BACKGROUND AND AIMS: Our purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC. METHODS: This is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index ≥25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis. RESULTS: In the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04. CONCLUSIONS: Myosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS. IMPACT AND IMPLICATIONS: Associations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC.

Liver Transplantation Profile Among Teenagers in the United States.

PURPOSE: Indications for liver transplantation (LT) vary across age groups. We identified predictors of outcomes for teenage LT waitlisted candidates and recipients in the United States from 2008 to 2022. METHODS: The Scientific Registry of Transplant Recipients 2008-2022 provided data (clinical, sociodemographic, indications for LT, outcomes) for all teenagers (13-19 years) waitlisted for LT in the United States. Sociodemographic and clinical characteristics, including primary listing diagnoses, were evaluated and compared by age group (13-16 vs. 17-19 years) among waitlisted teenage candidates. RESULTS: There were 2,813 teenage LT candidates listed between 2008 and 2022. The most common LT indication was acute liver disease (23.5%), followed by biliary atresia or hypoplasia (11.9%), autoimmune hepatitis (11.1%), and primary sclerosing cholangitis (9.7%). In contrast, chronic viral hepatitis, metabolic dysfunction-associated steatotic liver disease, and alcohol-related liver disease (the most common indications in adults) did not exceed 1% each; 2.8% had hepatocellular carcinoma. Excluding the two most recent years, 67.2% of candidates received a transplant; mean time to transplant was 217.0 days (standard deviation 371.6). Independent predictors of receiving a transplant were a more recent calendar year, younger age, higher model for end-stage liver disease score, and an acute liver disease diagnosis (all p < .05). Among the LT group, 3-year survival was 90%, with an improving survival trend. Higher post-transplant mortality was associated with earlier years of transplantation, older age, having Medicaid, being retransplanted, and having hepatocellular carcinoma (adjusted hazard ratios >1, all p < .05). DISCUSSION: Indications for LT among US teenagers are different from adults or younger children. There is a trend toward improved post-transplant outcomes.

Therapeutic Effect of Melatonin on CCl4-Induced Fibrotic Liver Model by Modulating Oxidative Stress, Inflammation, and TGF-ß1 Signaling Pathway in Pinealectomized Rats.

The study aimed to determine the CCl4-induced liver fibrosis model in pinealectomized rats and biochemically, immunohistochemically, and histopathologically investigate the therapeutic effect of melatonin on liver fibrosis. The surgical procedure for pinealectomy was performed at the beginning of the study, and the sham and pinealectomized rats were administered CCl4 dissolved in corn oil (1:1) alone every other day to induce liver fibrosis or together with melatonin (10 mg/kg) therapy for 15 days. Melatonin is an essential therapeutic agent and offers an alternative therapeutic strategy in CCl4-induced liver fibrosis by suppressing inflammation, oxidative stress, and the TGF-ß1 signaling pathway. Treatment with melatonin ameliorated CCl4-induced liver fibrosis by restoring hepatocellular damage and reducing plasma AST, ALT, and ALP values. Melatonin increases the activity of SOD and CAT, which are important enzymes for antioxidant defence, and raises GSH levels, which further enhances antioxidant function. Also, melatonin reduced hepatic inflammation (IL-6 and IL-1ß) and oxidative stress indices. Moreover, histopathological changes and immunohistochemical expression of TGF-ß1 were restored following melatonin supplementation in the CCl4-induced liver fibrosis model in pinealectomized rats. Our study shows that melatonin supplementation has a beneficial effect in protecting the liver fibrosis induced by CCl4 in pinealectomized rats.

A contemporary view on vascular resections and reconstruction during hepatectomies.

Oncological hepatic surgery carries the possibility to perform vascular reconstructions for advanced tumours with vessel invasion since surgery often represents the only potentially curative approach for these tumours. An extended review was conducted in an attempt to understand and clarify the latest trends in hepatectomies with vascular resections. We searched bibliographic databases including PubMed, Scopus, references from bibliographies and Cochrane Library. Information and outcomes from worldwide clinical trials were collected from qualified institutions performing hepatectomies with vascular resection and reconstruction. Careful patient selection and thorough preoperative imaging remain crucial for correct and safe surgical planning. A literature analysis shows that vascular resections carry different indications in different diseases. Despite significant advances made in imaging techniques and technical skills, reports of hepatectomies with vascular resections are still associated with high postoperative morbidity and mortality. The trend of complex liver resection with vascular resection is constantly on the increase, but more profound knowledge as well as further trials are required. Recent technological developments in multiple fields could surely provide novel approaches and enhance a new era of digital imaging and intelligent hepatic surgery.

Modulation of PI3K/AKT/mTOR signaling pathway in the ovine liver and duodenum during early pregnancy.

The liver and intestine play a critical role in nutrient absorption, storage, and metabolism. The aim of this study was to evaluate expression pattern of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) signaling pathway that included PI3K, AKT1, mTOR, FoxO1, SREBP-1, PPARα, PTEN and FXR in the maternal liver and duodenum. Ovine livers and duodenums were sampled at day 16 of the estrous cycle, and at days 13, 16 and 25 of gestation, and RT-qPCR, western blot and immunohistochemistry analysis were used to detect mRNA and protein expression. The results showed that expression of PI3K, AKT1, p-mTOR, FoxO1, SREBP-1 and PTEN upregulated in the maternal liver, and PPARα upregulated in the duodenum. However, expression of FoxO1, SREBP-1 and PTEN in the duodenum downregulated during early pregnancy. In addition, expression levels of SREBP-1, PTEN and PPARα in the maternal liver, and PI3K in the duodenum peaked at day 13 of pregnancy. In addition, expression levels of PI3K, p-mTOR and FoxO1 in the liver, and AKT1 and p-mTOR in the duodenum peaked at day 16 of pregnancy. Nevertheless, expression levels of FXR both in the maternal liver duodenum downregulated at days 13 and 16 of pregnancy. In conclusion, early pregnancy regulated expression pattern of PI3K/AKT/mTOR signaling pathway in the ovine liver and duodenum in a pregnancy stage-specific and tissue-specific manner, which may be necessary for the adaptations in maternal hepatic nutrient metabolism and intestinal nutrient absorption early pregnancy.

Nimodipine ameliorates liver fibrosis via reshaping liver immune microenvironment in TAA-induced in mice.

Nimodipine, a calcium antagonist, exert beneficial neurovascular protective effects in clinic. Recently, Calcium channel blockers (CCBs) was reported to protect against liver fibrosis in mice, while the exact effects of Nimodipine on liver injury and hepatic fibrosis remain unclear. In this study, we assessed the effect of nimodipine in Thioacetamide (TAA)-induced liver fibrosis mouse model. Then, the collagen deposition and liver inflammation were assessed by HE straining. Also, the frequency and phenotype of NK cells, CD4+T and CD8+T cells and MDSC in liver and spleen were analyzed using flow cytometry. Furthermore, activation and apoptosis of primary Hepatic stellate cells (HSCs) and HSC line LX2 were detected using α-SMA staining and TUNEL assay, respectively. We found that nimodipine administration significantly attenuated liver inflammation and fibrosis. And the increase of the numbers of hepatic NK and NKT cells, a reversed CD4+/CD8+T ratio, and reduced the numbers of MDSC were observed after nimodipine treatment. Furthermore, nimodipine administration significantly decreased α-SMA expression in liver tissues, and increased TUNEL staining adjacent to hepatic stellate cells. Nimodipine also reduced the proliferation of LX2, and significantly promoted high level of apoptosis in vitro. Moreover, nimodipine downregulated Bcl-2 and Bcl-xl, simultaneously increased expression of JNK, p-JNK, and Caspase-3. Together, nimodipine mediated suppression of growth and fibrogenesis of HSCs may warrant its potential use in the treatment of liver fibrosis.

Multiple indicators of gut dysbiosis predict all-cause and cause-specific mortality in solid organ transplant recipients.

OBJECTIVE: Gut microbiome composition is associated with multiple diseases, but relatively little is known about its relationship with long-term outcome measures. While gut dysbiosis has been linked to mortality risk in the general population, the relationship with overall survival in specific diseases has not been extensively studied. In the current study, we present results from an in-depth analysis of the relationship between gut dysbiosis and all-cause and cause-specific mortality in the setting of solid organ transplant recipients (SOTR). DESIGN: We analysed 1337 metagenomes derived from faecal samples of 766 kidney, 334 liver, 170 lung and 67 heart transplant recipients part of the TransplantLines Biobank and Cohort-a prospective cohort study including extensive phenotype data with 6.5 years of follow-up. To analyze gut dysbiosis, we included an additional 8208 metagenomes from the general population of the same geographical area (northern Netherlands). Multivariable Cox regression and a machine learning algorithm were used to analyse the association between multiple indicators of gut dysbiosis, including individual species abundances, and all-cause and cause-specific mortality. RESULTS: We identified two patterns representing overall microbiome community variation that were associated with both all-cause and cause-specific mortality. The gut microbiome distance between each transplantation recipient to the average of the general population was associated with all-cause mortality and death from infection, malignancy and cardiovascular disease. A multivariable Cox regression on individual species abundances identified 23 bacterial species that were associated with all-cause mortality, and by applying a machine learning algorithm, we identified a balance (a type of log-ratio) consisting of 19 out of the 23 species that were associated with all-cause mortality. CONCLUSION: Gut dysbiosis is consistently associated with mortality in SOTR. Our results support the observations that gut dysbiosis is associated with long-term survival. Since our data do not allow us to infer causality, more preclinical research is needed to understand mechanisms before we can determine whether gut microbiome-directed therapies may be designed to improve long-term outcomes.

Parkinsonism in liver diseases or dysfunction.

Parkinsonism in liver diseases or dysfunction, mainly including neurological manifestations in hereditary liver diseases and neurological complications of advanced liver diseases, occur in isolation or in combination with other movement disorders, and progress along disease course. Prominent akinetic-rigidity syndrome, various onset and progression, poor levodopa response and metabolism abnormalities reflected by serum biomarkers and neuroimaging, make this atypical parkinsonism recognizable and notable in clinical practice. Different susceptibility of brain areas, especially in basal ganglia, to manganese, iron, copper, ammonia overload, together with subsequent oxidative stress, neurotransmitter alterations, disturbed glia-neuron homeostasis and eventually neurotoxicity, contribute to parkinsonism under the circumstances of insufficient liver clearance ability. These mechanisms are interrelated and may interact collectively, adding to the complexity of clinical manifestations and treatment responses. This review summarizes shared clinical features of parkinsonism in liver diseases or dysfunction, depicts their underlying mechanisms and suggests practical flowchart for differential diagnosis.

Systemic immune-inflammation index mediates the association between metabolic dysfunction-associated fatty liver disease and sub-clinical carotid atherosclerosis: a mediation analysis.

Background: Limited research has been conducted to quantitatively assess the impact of systemic inflammation in metabolic dysfunction-associated fatty liver disease (MAFLD) and sub-clinical carotid atherosclerosis (SCAS). The systemic immune-inflammation index (SII), which integrates inflammatory cells, has emerged as a reliable measure of local immune response and systemic inflammation Therefore, this study aims to assess the mediating role of SII in the association between MAFLD and SCAS in type 2 diabetes mellitus (T2DM). Method: This study prospectively recruited 830 participants with T2DM from two centers. Unenhanced abdominal CT scans were conducted to evaluate MAFLD, while B-mode carotid ultrasonography was performed to assess SCAS. Weighted binomial logistic regression analysis and restricted cubic splines (RCS) analyses were employed to analyze the association between the SII and the risk of MAFLD and SCAS. Mediation analysis was further carried out to explore the potential mediating effect of the SII on the association between MAFLD and SCAS. Results: The prevalence of both MAFLD and SCAS significantly increased as the SII quartiles increased (P<0.05). MAFLD emerged as an independent factor for SCAS risk across three adjusted models, exhibiting odds ratios of 2.15 (95%CI: 1.31-3.53, P < 0.001). Additionally, increased SII quartiles and Ln (SII) displayed positive associations with the risk of MAFLD and SCAS (P < 0.05). Furthermore, a significant dose-response relationship was observed (P for trend <0.001). The RCS analyses revealed a linear correlation of Ln (SII) with SCAS and MAFLD risk (P for nonlinearity<0.05). Importantly, SII and ln (SII) acted as the mediators in the association between MAFLD and SCAS following adjustments for shared risk factors, demonstrating a proportion-mediated effect of 7.8% and 10.9%. Conclusion: SII was independently correlated with MAFLD and SCAS risk, while also acting as a mediator in the relationship between MAFLD and SCAS.

What is the crux of successful living-donor liver transplantation for recipients aged 70 and beyond?

Aim: There is limited evidence regarding the feasibility of living-donor liver transplantation (LDLT) for patients aged over 70. The aims of this study were to assess postoperative outcomes in elderly recipients and to ascertain the potential feasibility and acceptability of LDLT. Methods: Data were collected from 762 recipients, including 26 in the elderly group (aged ≥70) and 736 in the younger group (aged <70), and reviewed even by propensity score matching (PSM). Results: No significant differences were observed in the frequency of postoperative complications between the two groups. Additionally, both groups exhibited a comparable 30-day mortality rate after LDLT (3.9% in both) and similar hospital stays (36 days vs. 40 days). The 1-, 3-, and 5-year graft survival rates in the elderly group were 92.0%, which was comparable to those in the younger group (p = 0.517), as confirmed by PSM. Notably, all donors for elderly patients were the children of the recipients, with an average age of 41.6 years, and grafts from donors aged ≥50 years were not utilized, signifying the use of high-quality grafts. Our inclusion criterion for elderly recipients was strictly defined as an ECOG-PS score of 0-2, which played a pivotal role in achieving favorable postoperative outcomes. Conclusion: LDLT can be performed safely for elderly patients aged 70 years or older, provided they have a preserved PS and receive high-quality grafts from younger donors, inevitably all children of elderly recipients. This approach yields acceptable long-term outcomes. Consequently, age alone should not serve as an absolute contraindication for LDLT.

New trends in surgery for colorectal liver metastasis.

By presenting the most up-to-date findings and incorporating the latest evidence, this article seeks to present a comprehensive guide for navigating the complexities inherent in the management of colorectal liver metastasis. It aims to serve as a valuable resource offering clinicians and healthcare professionals an understanding of the diverse modalities and approaches available for treating this challenging and multifaceted disease. In an era of rapidly evolving medical knowledge, this article examines the latest insights to make informed decisions in the realm of colorectal liver metastasis management. The article does not only highlight the up-to-date knowledge but also provides the evidence for existing therapeutic strategies. This practical tool provides evidence-based recommendations to clinicians, thereby contributing to the ongoing advancement of effective treatment strategies for this challenging disease.

Advantages of laparoscopic segmentectomy of the liver using ICG fluorescent navigation by the negative staining method: A comparison with open procedure.

Aim: Laparoscopic segmentectomy (LS) using indocyanine green (ICG) fluorescence navigation with negative staining method has potential for performing accurate and safe anatomical excision. This study aimed to evaluate the significance of LS using ICG fluorescence navigation compared with open segmentectomy (OS). Methods: Eighty-seven patients who underwent anatomical segmentectomies were evaluated for OS (n = 44) and LS (n = 43). The Glissonean pedicle approach was performed using either extra- or intrahepatic method, depending on the location of segment in LS. After clamping pedicle, negative staining method was performed. Liver transection was done along intersegmental plane visualizing by overlay mode of ICG camera. Surgical outcomes were compared between two groups. Correlation between predicted resecting liver volume (PRLV) calculated using volumetry and actual resected liver volume (ARLV) was assessed in two groups. Results: Patients who underwent LS showed better outcomes in operative time, blood loss, and length of hospital stay. There were significantly fewer Grade II and Grade III or higher postoperative complications in LS group. Both values of AST (p < 0.001) and ALT (p < 0.001) on postoperative day 1 were significantly lower in LS group than in OS group. PRLV and ARLV were more strongly correlated in LS (r = 0.896) than in OS (r = 0.773). The difference between PRLV and ARLV was significantly lower in LS group than in OS group (p = 0.022), and this trend was particularly noticeable in posterosuperior segment (p = 0.008) than in anterolateral segment (p = 0.811). Conclusion: LS using ICG navigation allows precise resection and may contribute to safer short-term outcomes than OS, particularly in posterosuperior segment.