Preparation of bovine liver candidate reference material

The bovine liver candidate reference material specially for micro analytical techniques was prepared. The preparation process including material collection, dried, pulverize, sieve, homogenization and preliminary test was described in detail. The more effective grinding methods were established to achieve the median particle size of 22μm.

Advancements in Liver Tumor Detection:A Comprehensive Review of Various Deep Learning Models

Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment planning.Liver Tumors(LTs)vary significantly in size,shape,and location,and can present with tissues of similar intensities,making automatically segmenting and classifying LTs from abdominal tomography images crucial and challenging.This review examines recent advancements in Liver Segmentation(LS)and Tumor Segmentation(TS)algorithms,highlighting their strengths and limitations regarding precision,automation,and resilience.Performance metrics are utilized to assess key detection algorithms and analytical methods,emphasizing their effectiveness and relevance in clinical contexts.The review also addresses ongoing challenges in liver tumor segmentation and identification,such as managing high variability in patient data and ensuring robustness across different imaging conditions.It suggests directions for future research,with insights into technological advancements that can enhance surgical planning and diagnostic accuracy by comparing popular methods.This paper contributes to a comprehensive understanding of current liver tumor detection techniques,provides a roadmap for future innovations,and improves diagnostic and therapeutic outcomes for liver cancer by integrating recent progress with remaining challenges.

Elafibranor, a dual PPARα and PPARδ agonist, reduces alcoholassociated liver disease: Lessons from a mouse model

Metabolic dysfunction-associated steatotic liver disease(MASLD)is a highly prevalent liver pathology in need of novel pharmacological treatments to complement lifestyle-based interventions.Nuclear receptor agonists have been under scrutiny as potential pharmacological targets and as of today,resmetirom,a thyroid hormone receptor b agonist,is the only approved agent.The dual PPARαandδagonist elafibranor has also undergone extensive clinical testing,which reached the phase III clinical trial but failed to demonstrate a beneficial effect on MASLD.As alcohol-associated liver disease and MASLD can be interconnected,whether elafibranor might be affective against liver disease caused by alcohol consumption is worth investigating.Writing recently in the World Journal of Gastroenterology,Koizumi et al reported using a mouse model of alcoholassociated liver disease and found that hepatic steatosis,liver fibrosis,and hepatocyte apoptosis were alleviated by administration of elafibranor.Although preclinical in nature,these data support the potential beneficial action of elafibranor in alcohol-induced MASLD,warranting the testing of this molecule in patients with steatotic liver disease caused by alcohol consumption.

High metabolic dysfunction-associated steatotic liver disease prevalence in type 2 diabetes: Urgent need for integrated screening and lifestyle intervention

This letter discusses the recent study by Mukherjee et al,which identifies a significant prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)among newly diagnosed type 2 diabetes mellitus(T2DM)patients in Bihar,India,and underscores the pressing need for integrated MASLD mana-gement within T2DM care.With 72.3%of the study cohort affected by MASLD,implementing routine liver function tests and ultrasound screenings is recom-mended as a standard practice in diabetes care,especially in regions with high prevalence rates.The study also advocates for dietary and lifestyle modifications,particularly the reduction of saturated fats,to slow MASLD progression.Patient education on monitoring body mass index and waist circumference,coupled with the integration of these metrics into digital health records,could enhance patient involvement and support proactive health management.Moreover,the letter emphasizes the advantages of developing a region-specific MASLD risk model that incorporates local dietary patterns and socioeconomic factors.Continued research into genetic and environmental determinants of MASLD remains es-sential for advancing our understanding of its etiology and informing targeted public health strategies.

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

A Comparison of Gamma Irradiation Response Models of Bovine Blood, Liver and Kidney Tissues at Radiofrequency

This study is aimed at identifying gamma irradiated response of bovine blood, liver and kidney tissues at radiofrequency. For this purpose, impedence meter (Booton 7200) working in conjunction with signal generators (Loadster, SG416013 and Harris G857993) and improvised parallel plate dielectric cells constructed in line with the method of Laogun et al., (2005) were used to obtain the dielectric spread parameter gamma radiation α, of blood, liver and kidney tissues exposed to gamma irradiation dose range of 1.0 - 85.0 Gy. The dielectric spread parameter α gives the extent of damage induced in an irradiated tissue. Results of this work revealed that at 0 - 50 MHz frequency range, Kidney tissues displayed higher sensitive, followed Liver tissues and lasted the bovine blood between 0 - 60 Gy but reversed for blood and liver at 85 Gy. At 0 - 100 kHz frequency range liver tissue is more venerable to radiation injuries between gamma irradiation dose range of 0 - 20 Gy while between 43 - 85 Gy the Kidney’s sensitivity is the highest followed by blood and liver tissues. This implies that the liver tissues are less liable to radiation injuries at radiofrequency. A comparison of the linear, exponential and polynomial models using Akaike Information Criteria (AIC) revealed that linear models were the most suitable models for describing the effect of gamma radiation on the dielectric dispersion properties of bovine tissues at low and high radiofrequencies. This implies that the response of the investigated tissues increases linearly with gamma irradiation dose.

Role of surgical resection for non-colorectal non-neuroendocrine liver metastases

It is widely accepted that the indications for hepatectomy in colorectal cancer liver metastases and liver metastases of neuro-endocrine tumors result in relatively better prognoses, whereas, the indications and prognoses of hepatectomy for non-colorectal non-neuroendocrine liver metastases(NCNNLM) remain controversial owing to the limited number of cases and the heterogeneity of the primary diseases. There have been many publications on NCNNLM; however, its background heterogeneity makes it difficult to reach a specific conclusion. This heterogeneous disease group should be discussed in the order from its general to specific aspect. The present review paper describes the general prognosis and risk factors associated with NCNNLM while specifically focusing on the liver metastases of each primary disease. A multidisciplinary approach that takes into consideration appropriate timing for hepatectomy combined with chemotherapy may prolong survival and/or contribute to the improvement of the quality of life while giving respite from systemic chemotherapy.

Advancements in liver retraction techniques for laparoscopic gastrectomy

Traditionally,liver retraction for laparoscopic gastrectomy is done via manual methods,such as the placement of retractors through the accessory ports and using a Nathanson retractor.However,these techniques often posed issues including extra abdominal incisions,risk of liver injury or ischaemia,and the potential for compromised visualization.Over the years,the development of innovative liver retraction techniques has significantly improved the safety and efficacy of laparoscopic gastrectomy and similar other hiatal procedures.This editorial will comment on the article by Lin et al,and compare this to the other liver retractor techniques available for surgeons and highlight the pros and cons of each technique of liver retraction.

Prediction of posthepatectomy liver failure in patients withhepatocellular carcinoma through ultrasound elastography

In this article,we comment on the article by Cheng et al published in recently.Posthepatectomy liver failure(PHLF)remains a leading cause of hepatectomyrelated mortality and can be evaluated according to liver reserve function.Liver stiffness(LS)measured by ultrasonic elastography and spleen area demonstrate a strong correlation with hepatic proliferation,fibrosis,and portal vein congestion,thus indirectly reflecting liver reserve function.This article highlights a meticulous study aimed at investigating the potential of two-dimensional shear wave elastography in assessing LS,as well as its integration with spleen area,surgical factors,and laboratory indicators,for predicting the risk of PHLF in hepatocellular carcinoma patients.In this article,we discussed the non-invasive elastography modality by ultrasound and magnetic resonance imaging to assess LS.Based on literature data,we subsequently suggested that several risk factors may contribute to PHLF,including excessive intrahepatic neutrophil accumulation,the formation of neutrophil extracellular traps,end-stage liver disease scores,and albumin-bilirubin scores.Therefore,a more comprehensive study incor-porating detailed information requires further investigation.

Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease:A crosssectional study

BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.

Hepatitis B virus infection and metabolic dysfunction associated steatotic liver disease:Rising pandemic with complex interaction

Due to sedentary lifestyle and rising prevalence of obesity,patients with general population and those who are infected with chronic hepatitis B are found to have metabolic dysfunction associated steatotic liver disease(MASLD).Both chronic hepatitis B virus(HBV)infection and MASLD can damage hepatocytes in their own way,but concomitant HBV-MASLD has its own clinical implications.Cherry on top is the presence of diabetes mellitus,hypertension or obesity which added more chances of unfavorable outcomes in these patients.In this article,we co-mment on the article by Wang et al published in the recent issue.This article provides a comprehensive overview of the complex interaction between HBV-MASLD,HBV alone and MASLD alone patients.We discuss key findings from recent studies,including the promising outcomes observed in patients with concurrent HBV and MASLD,warrants further research.The insights presented here offer renewed understanding of this complex interaction.

Elafibranor:A promising treatment for alcoholic liver disease,metabolic-associated fatty liver disease,and cholestatic liver disease

Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.

Adenosine triphosphate-binding pocket inhibitor for mixed lineage kinase domain-like protein attenuated alcoholic liver disease via necroptosis-independent pathway

BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.

Screening for metabolic dysfunction-associated fatty liver disease:Time to discard the emperor’s clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Predicting liver function after hemihepatectomy in patients with hepatocellular carcinoma using different modalities

In response to Dr.Yue et al's study on prognostic factors for post-hemihep-atectomy outcomes in hepatocellular carcinoma(HCC)patients,this critical review identifies methodological limitations and proposes enhancements for future research.While the study identifies liver stiffness measure and standard residual liver volume as potential predictors,concerns regarding small sample size,reliance on biochemical markers for safety assessment,and inadequate ad-justment for confounding variables are raised.Recommendations for rigorous methodology,including robust statistical analysis,consideration of confounding factors,and selection of outcome measures with clinical components,are proposed to strengthen prognostic assessments.Furthermore,validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hem-ihepatectomy.

Pediatric and adult liver transplantation in Bahrain: The experiences in a country with no available liver transplant facilities

BACKGROUND Liver transplantation(LT)is a life-saving procedure for patients with end-stage liver disease and has become the standard and most effective treatment method for these patients.There are many indications for LT that vary between countries and settings.The outcome of LT depends on the available facilities and surgical expertise,as well as the types of liver graft donors available.AIM To assess the clinical characteristics of patients from Bahrain who underwent LT overseas,and analyze factors affecting their survival.METHODS In this retrospective cohort study,we reviewed the medical records and overseas committee registry information of all pediatric and adult patients who were sent overseas to undergo LT by the Pediatric and Medical Departments of Salmaniya Medical Complex and Bahrain Defence Force Hospital via the Overseas Treatment Office,Ministry of Health,Kingdom of Bahrain,between 1997 and 2023.Demographic data,LT indication,donor-recipient relationship,overseas LT center,graft type,post-LT medications,and LT complications,were collected.Outcomes measured included the overall and 5-year LT survival rate.Fisher’s exact,Pearsonχ2,and Mann-Whitney U tests were used to compare the pediatric and the adults’group in terms of clinical characteristics,donor-recipient relationship,medication,complications,and outcome.Survival analysis was estimated via the Kaplan-Meier’s method.Univariate and multivariate analyses were used to detect predictors of survival.RESULTS Of the 208 eligible patients,170(81.7%)were sent overseas to undergo LT while 38(18.3%)remained on the waiting list.Of the 170 patients,167(80.3%)underwent LT and were included in the study.The majority of the patients were Bahraini(91.0%),and most were males(57.5%).One-hundred-and-twenty(71.8%)were adults and 47(28.3%)were children.The median age at transplant was 50.0[interquartile range(IQR):14.9–58.4]years.The main indication for pediatric LT was biliary atresia(31.9%),while that of adult LT was hepatitis C-related cirrhosis(35.0%).Six(3.6%)patients required re-transplantation.Most patients received a living-related liver graft(82%).Pediatric patients received more living and related grafts than adults(P=0.038 and P=0.041,respectively),while adult patients received more cadaveric and unrelated grafts.Most patients required long-term immunosuppressive therapy after LT(94.7%),of which tacrolimus was the most prescribed(84.0%),followed by prednisolone(50.7%),which was prescribed more frequently for pediatric patients(P=0.001).Most patients developed complications(62.4%)with infectious episodes being the most common(38.9%),followed by biliary stricture(19.5%).Tonsilitis and sepsis(n=12,8.1%for each)were the most frequent infections.Pediatric patients experienced higher rates of infection,rejection,and early poor graft function than adult patients(P<0.001,P=0.003,and P=0.025,respectively).The median follow-up time was 6.5(IQR:2.6–10.6)years.The overall survival rate was 84.4%,the 5-year survival rate,86.2%,and the mortality rate,15.6%.Younger patients had significantly better odds of survival(P=0.019)and patients who survived had significantly longer follow-up periods(P<0.001).CONCLUSION Patients with end-stage liver disease in Bahrain shared characteristics with those from other countries.Since LT facilities are not available,an overseas LT has offered them great hope.

Endoscopic ultrasound-guided tissue acquisition for the diagnosis of focal liver lesion

In patients with liver tumors,the histopathology examination can assist in diagnosis,staging,prognosis,and therapeutic management strategy.Endoscopic ultrasound(EUS)-guided tissue acquisition using fine needle aspiration(FNA)or more newly fine needle biopsy(FNB)is a well-developed technique in order to evaluate and differentiate the liver masses.The goal of the EUS-FNA or EUS-FNB is to provide an accurate sample for a histopathology examination.Therefore,malignant tumors such as hepatocarcinoma,cholangiocarcinoma and liver metastasis or benign tumors such as liver adenoma,focal hyperplastic nodular tumors and cystic lesions can be accurately diagnosed using EUS-guided tissue acquisition.EUS-FNB using 19 or 22 Ga needle provide longer samples and a higher diagnostic accuracy in patients with liver masses when compared with EUS-FNA.Few data are available on the diagnostic accuracy of EUS-FNB when compared with percutaneously,ultrasound,computer tomography or transjugulary-guided liver biopsies.This review will discuss the EUS-guided tissue acquisition options in patients with liver tumors and its efficacy and safety in providing accurate samples.The results of the last studies comparing EUS-guided liver biopsy with other conventional techniques are presented.The EUS-guided tissue acquisition using FNB can be a suitable technique in suspected liver lesions in order to provide an accurate histopathology diagnosis,especially for those who require endoscopy.

Delivering Care

Gertrude Nyathi walks calmly into Zimbabwe’s Mahusekwa Hospital for antenatal care in Mashonaland,where she is expected to give birth in the next five months.In a country where medical facilities are obsolete,patients flock to seek medical care at the Chinese-aided hospital,seen by many as a game changer in Marondera district.

Major liver resections,perioperative issues and posthepatectomy liver failure:A comprehensive update for the anesthesiologist

Significant advances in surgical techniques and relevant medium-and long-term outcomes over the past two decades have led to a substantial expansion in the indications for major liver resections.To support these outstanding results and to reduce perioperative complications,anesthesiologists must address and master key perioperative issues(preoperative assessment,proactive intraoperative anesthesia strategies,and implementation of the Enhanced Recovery After Surgery approach).Intensive care unit monitoring immediately following liver surgery remains a subject of active and often unresolved debate.Among postoperative complications,posthepatectomy liver failure(PHLF)occurs in different grades of severity(A-C)and frequency(9%-30%),and it is the main cause of 90-d postoperative mortality.PHLF,recently redefined with pragmatic clinical criteria and perioperative scores,can be predicted,prevented,or anticipated.This review highlights:(1)The systemic consequences of surgical manipulations anesthesiologistsmust respond to or prevent,to positively impact PHLF(a proactive approach);and(2)the maximal intensivetreatment of PHLF,including artificial options,mainly based,so far,on Acute Liver Failure treatment(s),to buytime waiting for the recovery of the native liver or,when appropriate and in very selected cases,toward livertransplant.Such a clinical context requires a strong commitment to surgeons,anesthesiologists,and intensivists towork together,for a fruitful collaboration in a mandatory clinical continuum.

Reducing invasiveness in liver surgery-where is the limit?

In this article,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology Surgery.Most prominent advancements in liver surgery in the last two decades are related to refinements in surgical technique(extraglissonean approach)and advancements in surgical technology(laparoscopy and robotics).In this article,authors present both these aspects:Laparoscopic segmentectomy using extraglissonean approach.Furthermore,they describe segmental resections of all 8 segments which is the main novelty that can be observed in the article.By now,extraglissonean approach was thoroughly described mainly in hepatectomies or lateral sectionectomies.Various“hilar gates”are defined which allows safe liver resection by ligating Glissonean pedicles first which is then followed by parenchymal resection.We here focus on past,present and future perspectives of extraglissonean approach and laparoscopic liver resections and comment the value of the presented article.